Malignant chondroblastoma. Report of two cases and reviw of the literature.


Ultrastructure of a cardiac myxoma.

Ultrastructure of a cardiac myxoma.


The human hypophysis in anencephaly. II. Ultrastructure of the pars intermedia.


Postnatal mumps virus infection. Associated with endocardial fibroelastosis.


Medullary thyroid carcinoma and parathyroid hyperplasia in rats.


Myocardial lesions following open heart surgery.


Thymic agenesis. Report of a case.

Thymic agenesis. Report of a case.


Adenine nucleotides and magnesium ions in relation to control of mammalian cerebral-cortex hexokinase. 1. The kinetics of inhibition of brain soluble cytoplasmic hexokinase by ADP were examined in relation to variations in the concentrations of Mg(2+) and ATP. The type of inhibition observed was dependent on the Mg(2+)/ATP ratio. 2. ADP at Mg(2+)/ATP ratios 2:1 exhibited inhibition of the ;mixed' type; at Mg(2+)/ATP ratios 1:1 the inhibition appeared to be competitive with regard to ATP. 3. Inhibition by free ATP was observed when the Mg(2+)/ATP ratio was less than 1:1. The inhibition was also of the ;mixed' type with respect to MgATP(2-). 4. The inhibitions due to ADP and to free ATP were not additive. The results suggested that there may be up to four sites in the soluble enzyme: for glucose, glucose 6-phosphate, ADP and MgATP(2-). 5. The ;free' non-particulate intracellular Mg(2+) concentration was measured and concluded to be about 1.5mm. 6. The concentrations in vivo of Mg(2+) and ATP likely to be accessible to a cytoplasmic enzyme are suggested to be below those that yield maximum hexokinase rates in vitro. The enzymic rates were measured at relevant suboptimum concentrations of Mg(2+) and ATP in the presence of ADP. Calculations that included non-competitive inhibition due to glucose 6-phosphate (56-65% at 0.25mm) resulted in net rates very similar to the measured rates for overall glycolysis. This system may therefore provide a basis for effective control of cerebral hexokinase.


Inhibition by oestrogen of collagen breakdown in the involuting rat uterus. 1. Both the post-partum involution of the rat uterus and the rapid breakdown of collagen that accompanies it are extensively inhibited by oestrogenic hormones. In the normal rat, 85% of the uterine collagen is degraded within 4 days after parturition; in rats treated with 100mug. of 17beta-oestradiol/day, only 35% of uterine collagen is broken down in the same period. 2. Similar effects are produced by diethylstilboestrol if the dose is increased tenfold. 3. Collagen breakdown is inhibited to a greater extent than is the loss of wet weight by oestradiol but not by diethylstilboestrol. 4. The oestrogens appear to act by blocking the breakdown of collagen. There is a greatly decreased concentration of free hydroxyproline in the uterus of treated animals. 5. Acid hydrolase concentrations (beta-glucuronidase, beta-galactosidase, cathepsin D and acid phosphatase) in the uterus are decreased by oestrogen treatment compared with controls, but the total amounts of these enzymes in the uterus are somewhat elevated. Oestrogens do not appear to inhibit collagen breakdown by altering the concentration and total amount of acid hydrolases.


Rates of ketone-body formation in the perfused rat liver. 1. The rates of formation of acetoacetate and beta-hydroxybutyrate by the isolated perfused rat liver were measured under various conditions. 2. The rates found after addition of butyrate, octanoate, oleate and linoleate were about 100mumoles/hr./g. wet wt. in the liver of starved rats. These rates are much higher than those found with rat liver slices. 3. The differences between the rates given by slices and by the perfused organ were much higher with the long-chain than with short-chain fatty acids. The increments caused by oleate and linoleate were 12 and 16 times as large in the perfused organ as in the slices, whereas the increments caused by butyrate and octanoate were about four times as large. 4. The rates of ketogenesis in the unsupplemented perfused liver of well-fed rats, and the increments caused by the addition of fatty acids, were about half of those in the liver from starved rats. 5. The value of the [beta-hydroxybutyrate]/[acetoacetate] ratio of the medium was raised by octanoate, oleate and linoleate. 6. Carnitine did not significantly accelerate ketogenesis from fatty acids. 7. Oleate formed up to 82% of the expected yield of ketone bodies. 8. In the liver of alloxan-diabetic rats the endogenous rates of ketogenesis were raised, in some cases as high as in the liver from starved rats, after addition of oleate. 9. On addition of either beta-hydroxybutyrate or acetoacetate to the perfusion medium the liver gradually adjusted the [beta-hydroxybutyrate]/[acetoacetate] ratio towards the normal range. 10. The [beta-hydroxybutyrate]/[acetoacetate] ratio of the medium was about 0.4 when slices were incubated, but near the physiological value of 2 when the liver was perfused. 11. The experiments demonstrate that for the study of ketogenesis slices are in many ways grossly inferior to the perfused liver.


Effects of magnesium, manganese and adenosine triphosphate ions on pyruvate carboxylase from baker's yeast. 1. Pyruvate carboxylase from baker's yeast acts with either MgATP(2-) or MnATP(2-) as substrate. The optimum pH for the enzyme reaction is 8.0 with MgATP(2-) and 7.0 with MnATP(2-). 2. When the reaction velocity is plotted against MgATP(2-) (or MnATP(2-)) concentration slightly sigmoid curves are obtained, either in the presence or in the absence of acetyl-CoA (an allosteric activator). In the presence of excess of free Mg(2+) (or Mn(2+)) the curves turn into hyperbolae, whereas in the presence of excess of free ATP(4-) the apparent sigmoidicity of the curves increases. 3. The sigmoidicity of the plots of v against MgATP(2-) (or MnATP(2-)) concentration can be explained by the inhibitory effect of free ATP(4-), the concentration of which, in the experimental conditions employed, is significant and varies according to the total concentration of the ATP-magnesium chloride (or ATP-manganese chloride) mixture. Free ATP(4-) behaves as a negative modifier of yeast pyruvate carboxylase. 4. The effect of high concentrations of Mg(2+) (or Mn(2+)) on the kinetics of yeast pyruvate carboxylase can be explained as a deinhibition with respect to ATP(4-), instead of a direct enzyme activation. 5. At pH6.5 manganese chloride is more effective than magnesium chloride as enzyme activator even in the presence of a great excess (16-fold) of the latter. This is consistent with a significant contribution of the MnATP(2-) complex to the activity of yeast pyruvate carboxylase, in medium conditions resembling those existing inside the yeast cell (pH6.25-6.75; 12mm-magnesium chloride and 0.75mm-manganese chloride). 6. The physiological significance of the enzyme inhibition by free ATP(4-) is doubtful since the Mg(2+) and Mn(2+) concentrations reported to exist inside the yeast cell are sufficient to decrease ATP(4-) concentrations to ineffective values.


Relationship between intracellular amino acids and protein synthesis in the extensor digitorum longus muscle of rats. 1. The incorporation into protein, and the accumulation into the free amino acid pools, of radioactive l-leucine and glycine was studied in rat extensor digitorum longus muscle. 2. The tissue was incubated first with (14)C-labelled and then with (3)H-labelled amino acid. 3. The experimental results were consistent with a model based on the premise that the amino acids in protein were incorporated directly from the extracellular pool.


An early effect of oestradiol-17-beta on the permeability of rat uterus to ribonucleic acid precursors.


Human small-intestinal beta-galactosidases. Separation and characterization of one lactase and one hetero beta-galactosidase. 1. Two beta-galactosidases from human small-intestinal mucosa were separated by gel-filtration chromatography and the properties of the two enzymes were studied. Lactose and four hetero beta-galactosides were used as substrates. 2. One of the enzymes was particle-bound and could be partially solubilized with papain. Of the substrates hydrolysed by this enzyme, lactose was hydrolysed most rapidly. This enzyme is thus essentially a disaccharidase and is named lactase. It is presumably identical with the ;lactase 1' described earlier. 3. The other enzyme was mainly soluble and hydrolysed all artificial substrates used, whereas no lactase activity could be detected. This enzyme has therefore been designated hetero beta-galactosidase. 4. p-Chloromercuribenzoate (0.1mm) inhibited the hetero beta-galactosidase completely but did not influence the activity of the lactase. Tris was a competitive inhibitor of both enzymes. 5. The residual lactase activity in the mucosa of lactose-intolerant patients may be exerted by a small amount of remaining lactase as such, or possibly by a third enzyme with a more acid pH optimum.


The effect of 3-deoxy-3-fluoro-d-glucose on Saccharomyces cerevisiae.


N-Monoacetylspermidine as a normal constituent of urine.


Phosphate-induced loss of citric acid cycle intermediates from rat-liver mitochondria.


The emission of infrared radiation from human skin--implications for clinical thermography.


Pregnancy tests over the counter.

Pregnancy tests over the counter.


Creatinine clearance in renal disease. A reappraisal. To determine the validity of endogenous creatinine clearance as a measure of glomerular filtration rate in patients with renal disease 308 simultaneous determinations of inulin clearance and endogenous creatinine clearance were reviewed and analysed. The ratio of creatinine clearance/inulin clearance increased progressively with the decline in inulin clearance, while the finding of a normal endogenous creatinine clearance masked a definite but mild decrease of glomerular filtration rate in 42% of the patients and a moderate decrease of glomerular filtration rate in 23%. This indicates that with declining glomerular filtration rates the endogenous creatinine clearance progressively overestimates actual glomerular filtration rates. Hence a single determination of creatinine clearance can be misleading as a screening measurement of glomerular filtration rate.


Immunological studies in tropical splenomegaly syndrome in Uganda. An immunological evaluation carried out in eight patients with the tropical splenomegaly syndrome showed no evidence of impairment in cellular or humoral immunity, though raised levels of macroglobulins were noted in four patients. Hence gross immunological deficiency cannot be associated with the intense lymphoreticular proliferation observed in this disorder.


Hiatus hernia and reflux esophagitis.

Hiatus hernia and reflux esophagitis.


Blood glucose and insulin relationships in the human mother and fetus before onset of labour. The effects of a maternal intravenous glucose load on the fetal plasma levels of glucose and insulin have been studied in 11 patients before the onset of labour. Within five minutes the fetal plasma glucose concentration rose significantly, indicating a rapid transfer of glucose across the placenta. Following this, the rate of fall in fetal plasma glucose closely reflected that in the mother.Serial fetal insulin estimations carried out in 8 of the 11 subjects following maternal glucose showed an early rise in fetal insulin in four and a delayed rise in one; in the remaining three there was no definite change.It is concluded that the blood glucose level of the fetus is controlled by that of the mother, but that the fetal pancreas at term may respond to hyperglycaemia by the secretion of insulin.


Angiographic studies of Quinton-Scribner arteriovenous cannulae. An analysis of 86 angiographic studies of Quinton-Scribner shunts has shown that these may be very useful in determining the cause and helping in the management of poorly functioning cannulae in patients on regular haemodialysis treatment.


Impact of community-orientated psychiatry on marriage and fertility of psychotic women. A large representative sample of psychotic women of reproductive age was selected from patients admitted to a London mental hospital during 1955-63 and followed up during the years of developing community care. Before first admission the probability of marriage of schizophrenics was three-quarters of that of corresponding normal women, and after admission it was just over one-third of normal. Fertility of schizophrenics was slightly reduced both before and after illness, and much of this reduction remains due to their being in hospital. The probability of marriage and fertility of women suffering from severe affective disorders was very similar to that found in the corresponding general population. Despite a lessening of differentials between patients and normal women since the impact of community care the probability of marriage of schizophrenics with abnormal personalities is still significantly reduced.


Beriberi heart disease in London.

Beriberi heart disease in London. Haemodynamic measurements before and after treatment are described in two patients with beriberi heart disease. The first patient had severe disease with a cardiac output of 17.3 litres per minute, which had returned to normal a month later. The second patient had moderate disease with a cardiac output of 7.4 litres per minute; a fall in this and a rise in systemic vascular resistance was found one and two hours after the intravenous injection of aneurine hydrochloride. The plasma pyruvate concentration was raised in the first patient but only slightly so in the second, in whom the pyruvate metabolism test was abnormal. The haemodynamic studies in both cases were of considerable help in making the diagnosis. The diagnosis of beriberi should be considered in any patient with heart disease who has a history of alcoholism, especially as prompt vitamin treatment is curative.


All that sweetens is not sugar.

All that sweetens is not sugar.


Sudden death after exertion in apparently healthy boy.


Attack on cholera.

Attack on cholera.


Little strokes.

Little strokes.


Visiting nurse--analysis of one year's work.


Depressive changes after fluphenazine treatment.


Tropical splenomegaly syndrome.

Tropical splenomegaly syndrome.


The team.

The team.


Achalasia of the oesophagus.

Achalasia of the oesophagus.


Fibrinolytic enzyme system.

Fibrinolytic enzyme system.


Oral contraceptives and thromboembolic disease.


Awareness during anaesthesia.

Awareness during anaesthesia.


Premedication for hypotensive anaesthesia.


Hypotensive reaction after propanidid and atropine.


Accidental inhalation of talcum powder.

Accidental inhalation of talcum powder.


Hyperaldosteronism.

Hyperaldosteronism.


Necropsy after exhumation.

Necropsy after exhumation.


Smoking at school.

Smoking at school.


Nitrogen metabolism of Picea glauca. IV. Metabolism of uniformly labelled 14-C-L-arginine, [carbamyl-14C]-L-citrulline, and [1,2,3,4-14C]-gamma-guanidinobutyric acid during diurnal changes in the soluble and protein nitrogen associated with the onset of expansion of spruce buds.


Bovine hepatic carboxylesterases: chromatographic fractionation, gel filtration, and molecular weight estimation.


Metabolism of 75Se-selenite by human whole blood in vitro.


Disc electrophoresis of snake venoms. I. A qualitative comparison of the protein patterns from the species of Crotalidae and Elapidae.


Trauma rounds at the Montreal General Hospital.


Human freedom and mental illness.

Human freedom and mental illness.


Cardiovascular effects of thyroxine.

Cardiovascular effects of thyroxine.


Chromosomal rearrangements in Plantago insularis Eastw.


Progressive muscular dystrophy. Hemodynamic, angiographic, and pathologic study of a patient with myocardial involvement.


Pyridoxal kinase in the human placenta and foetus through gestation.


Influence of proteolysis inhibitors on the formation of the anaemization factor released following interaction of hypersensitive lymph node cells with antigen in vitro.


Effect of salivary gland extirpation on the carcinogenesis of rat stomach by 4-nitroquinoline 1-oxide.


Effect of prednisolone on gastric function and structure in man.


Effect of the vagus nerve and salicylate administration on the permeability characteristics of the rat gastric mucosal barrier.


Effect of exclusion, acidification, and excision of the duodenum on gastric acid secretion and the production of pentagastrin-induced peptic ulcers in cats.


Stroke: U.S. & Japan. Electroencephalographic investigations.


Effect of hypokalemia on the reductive amination of alpha-ketoglutarate by mitochondria from normal and cirrhotic rat liver.


Aminoacid constitution of two gastrins isolated from Zollinger-Ellison tumour tissue. Two peptides which are potent stimulants of gastric acid secretion are isolated from Zollinger-Ellison tumour tissue. They have aminoacid constitutions identical with those of human gastrin types I and II as isolated from human antral mucosa, and they are present in similar proportions. Their electrophoretic and chromatographic behaviour corresponds to that of human gastrins. Evidence is presented in respect of the one isolated in greater amount that its aminoacid sequence is probably identical with that of human gastrin type I.


X-ray diffraction studies of the composition of gallstones from English and Australian patients. The crystalline composition of two collections of gallstones from patients in England and Australia have been determined by the x-ray powder diffraction technique. Twelve substances have been identified including a form of cholesterol which hitherto has not been reported. The weighted percentage composition averaged over each collection shows that cholesterol is the major constituent of the Australian stones and cholesterol and cholesterol monohydrate the major constituents of the English calculi. The cholesterol is possibly a decomposition product of the monohydrate. The calcium carbonates-calcite, aragonite, and vaterite-constitute most of the remainder of the calculi. Although their percentage composition is much smaller than that of the cholesterols, they are nevertheless present in a high proportion of stones. Small traces of apatite, whitlockite, sodium chloride, calcium stearate and palmitic acid (or other long-chain compounds having closely related spacings) have been found. Small spheroids scattered throughout some stones appear to be mainly calcium stearate, although the total quantity available is too small and too impure for a definite identification.


Erythrocyte transaminase activity in infantile malnutrition: in vivo and in vitro response to vitamin B6.


Congenital non-haemolytic jaundice in a four-year-old girl without disease of the central nervous system.


Red cell transfusion in infected infants at altitude. Experimental basis IV for "substitutive-inhibitory" transfusions.


Immunoallergic lung purpura treated with azathioprine and with splenectomy and azathioprine.


Chromatography of food preservatives on polyamide layers and columns.


The use of triphenyltetrazolium chloride for the quantitive analysis of sugars and sugar derivatives reported in glycoproteins.


Chromatographic separation of lysergic acid amide and isolysergic acid amide in morning glory seeds.


A thin-layer chromatographic separation of some closely related 6-fluoro-16-alpha-hydroxycorticosteroids.


Miniature excitatory junction potentials in the somatic muscle of the earthworm, Pheretima communissima, in sodium free solution.


Sensory and motor interaction in the locomotor reflexes of crabs.


An investigation of the electrogenic sodium pump in snail neurones, using the constant-field theory.


A technique for discriminating direction of propagation of action potentials recorded from an intact mixed nerve.


Meaningfulness and pronounceability in the coding of visually presented verbal materials.


A kinetic study of the growth of Aspergillus nidulans and other fungi.


Genetic transformation in Rhizobium.

Genetic transformation in Rhizobium.


Congenital inclusion body hemolytic anemia: study of a family.


Antigenic relationships among strains of Mycoplasma mycoides var. mycoides, M. capri and M. laidlawii revealed by complement-fixation tests.


Dispersal of Streptomycetes in air.

Dispersal of Streptomycetes in air.


The nature of the in vivo sodium and chloride uptake mechanisms through the epithelium against sodium and of bicarbonate against chloride. The Chilean frog, Calyptocephallela gayi, placed in dilute NaCl solutions may pump Na(+) and Cl(-) at very different rates depending on the kind of bath solutions in which it was preadapted. Furthermore, Na(+) and Cl(-) may be absorbed from solutions in which the accompanying coion, such as sulfate and choline, respectively, is impermeant. In all these cases it is obligatory to postulate the existence of two ionic exchange mechanisms, Cl(-) and Na(+), being exchanged against endogenous anions and cations, respectively. It has been determined that Na(+) is exchanged against endogenous H(+) and that Cl(-) is exchanged against HCO(3) (-). In animals pumping Na(+) and Cl(-) from dilute NaCl solutions Na(+) or Cl(-) uptake may be selectively inhibited, while the flux of the accompanying ion remains unchanged. This is considered to be an additional proof that both Na(+) and Cl(-) fluxes are always independent. The role of the ionic exchange mechanisms in the direct regulation of the Na(+) and Cl(-) levels in the internal medium is discussed as well as their relationship in the regulation of the acid-base equilibrium; other physioecological considerations have been treated.


Injuries of the ossicular chain.

Injuries of the ossicular chain.


Quantification of right-to-left transpulmonary shunts in man.


Synthesis and pharmacological activity of alkylaminoalkyl esters and amides of 2-hydroxy- (or alkoxy-) 3-methoxybenzoic acid.


Psychosedative agents. N-(4-phenyl-1-piperazinylalkyl)-substituted cyclic imides.


A simple method of reducing airborne bacterial contamination.


Non-haemolytic group B streptococcus.

Non-haemolytic group B streptococcus.


A sample collection warning device for gel chromatography.


An automated chromatography applicator giving discrete application spots with up to two-ml. amounts.


A compact block storage system.

A compact block storage system.


A commercially available, low-priced, thermostatically-controlled, low-temperature water bath.


Lesions induced in rats by injections of 4-nitroquinoline-1-oxide.


Hemodynamic consequences of respiratory insufficiency following trauma.


Description of a self-adherent stethoscope.


A clinical assessment of glybenclamide (HB 419, "Daonil"), a hypoglycaemic sulphonylurea.


Adult hypertrophic pyloric stenosis.

Adult hypertrophic pyloric stenosis.


The EEG in the traumatic encephalopathy of boxers.


Dual simultaneous interviews: a research approach with the psychotic patient.


Conversion hysteria in Appalachia.

Conversion hysteria in Appalachia.


The effects of prenatal x-irradiation of the rat on postnatal growth and mortality.


Orthopaedics, physiotherapy and chiropractic.


Yet another sulphonylurea for late-onset diabetics.


The effect of Co60 irradiation on bone in dogs. I. Mature bone.


The effect of Co60 irradiation of bone in dogs. II. Growing bone.


Water intake and urine output in relation to the survival of x-irradiated rats.


Digital computation in radiotherapy. Analysis of techniques for tele-radiation of the bladder.


The effect of local irradiation of the gonads of infantile and adult male rats on the survival and regeneration of reproductive organs.


Effect of Co60 internal irradiation on the liver of the Indian catfish, Heteropneutes fossilis Bloch.


CNDO-2 calculations on the acidities of alkanes and saturated alcohols and the basicities of methylamines.


Desquamative alveolar disease (desquamative interstitial pneumonia): case report.


Microanatomy of glomic tissue of the pulmonary trunk.


Thrombohemorrhagic lesions induced by temporary ischemia.


Platelet adhesion and throms formation on vascular catheters in dogs.


Vertebra plana due to histiocytosis X: serial studies.


Concentra. A new overhead unit for roentgenography in the operation theatre.


Spinal cord tolerance to roentgen contrast med particularly during aortography with temporary occlusion of the aorta. An experimental investigation in dogs.


Gastric ulceration following cobalt teletherapy. Estimation of the tolerance dose.


Myometrial blood flow studies in carcinoma of the corpus uteri. A preliminary report on the clearance method using xenon 133.


Retention of cobalt in experimentally induced kidney disease. Studies of 60Co in irradiated and sublimate-poisoned mouse kidney.


Radiation-induced release of catecholamines from perfused bovine adrenal gland.


Hypotensive drug therapy in the management of hypertension.


Anomalous pulmonary venous drainage associated with mitral valve disease.


The long-term prognosis for patients resuscitated after cardiac arrest. A follow-up study.


The natural history of atrioventricular conduction defects in acute myocardial infarction.


Diagnostic value of the first heart sound in children with atrial septal defect.


The first heart sound in atrial septal defect.


Ventricular dynamics in Bantu cardiomyopathy.


The coronary attack: concepts on its etiology and hemodynamic management.


A comparison of the hemodynamic effects of ventricular and sequential A-V pacing in patients with heart block.


Continuous radioelectrocardiographic monitoring of football and basketball coaches during games.


Determination of left ventricular wall thickness by angiocardiography.


Relation of hemodynamics to height and weight percentiles in children with ventricular septal defects.


Single ventricle with normal relationship of the great vessels and pulmonic stenosis. A case report of an adult with the "Holmes heart".


Pseudotruncus arteriosus. Report of the oldest surviving patient.


Crural hypertension in abdominal aortic coarctation.


The nature of intercoronary arterial flow in the normal heart.


Clinical pathologic conference.

Clinical pathologic conference.


Cardiopulmonary resuscitation. I.

Cardiopulmonary resuscitation. I.


Posthyperventilation apnea and the criteria of brain damage and death.


Is there an "ideal" cardiac pacing rate?


Re-evaluation of septal activation in the human heart.


Familial dissecting aneurysm complicating Marfan's syndrome.


A note on the detection of linkage of a possible X-linked locus to a known X-linked locus.


Sex-linked congenital deafness.

Sex-linked congenital deafness.


Purification and some properties of the three common genetic types of haptoglovins and the hemoglobin-haptoglobin complexes.


Random association of human acrocentric chromosomes.


A pseudocholinesterase variant (E Cynthiana) associated with elevated plasma enzyme activity.


Factor analysis of reasons retardates are referred to an institution.


Verbal expressivity as an index of adaptive behavior.


A school study of group counseling with educable retarded adolescents.


The attention of retardates and normals in distraction and non-distraction condtions.


Incidence of stuttering and other speech disorders among the retarded.


Intelligence and the factorial structure of person perception.


Short-term memory and rehearsal in educable subnormals.


Békésy audiometry with the retarded.

Békésy audiometry with the retarded.


The Vineland and Cain-Levine: a correlational study and program evaluation.


Cognitive and motivational factors in concept switching among the retarded.


Discrimination learning and learning set with institutionalized retarded children.


Paired associate learning performance as a function of meaningfulness and response times.


Motivational differences: cultural-familial retardates vs. normal subjects on expectancy for failure.


Aversive stimulation as applied to discrimination learning in mentally retarded children.


Response learning and the paired-associate performance of mental retardates.


Comparative constructional praxis performance of organically impaired and cultural-familial mental retardates.


Sensory-motor training of the profoundly retarded.


Correlation between urinary estriol excretion and fetal acidosis in high-risk pregnancies.


Treatment of Candida albicans septicemia.


Adenine nucleotide metabolism in stored human platelets.


Microbodies in experimentally altered cells. V. Histochemical and cytochemical studies on the livers of rats and acatalasemic (Csb) mice treated with CPIB.


Alterations of platelet ultrastructure in patients with carcinoid syndrome.


The development of the hepatic megalocytosis of chronic pyrrolizidine alkaloid poisoning.


Skeletal muscle hypertrophy after heavy exercise in rats with surgically reduced muscle function.


Glomerular changes induced by extrarenal foci of inflammation and by polymorphonuclear cell lysates.


Repetitive trauma in the genesis of cervical spondylosis.


"Death" from lightning and the possibility of living again.


Microbiology as a field of science and application.


Translocation between both members of chromosome pair number 15 causing recurrent abortions.


Peptidase D (prolidase) variants in man.


Congenital malformations; a detailed study of 2500 liveborn infants.


Further data on the adenosine deaminase (ADA) polymprphism and a report of a new phenotype.


Long arm measurements of chromosomes 4 and 5 with special reference to the cri du chat syndrome.


A discussion of Weinberg's rule on the zygosity of twins.


Consanguineous marriages and calculation of the genetic load.


Birth weight and birth order.

Birth weight and birth order.


Stillbirth and birth order.

Stillbirth and birth order.


Traumatic tattoo due to silver salt.

Traumatic tattoo due to silver salt.


Cicatricial pemphigoid.

Cicatricial pemphigoid.


Symptomatic pitted keratolysis.

Symptomatic pitted keratolysis.


Perforating folliculitis.

Perforating folliculitis.


Sebaceous nevus and keratoacanthoma.

Sebaceous nevus and keratoacanthoma.


Lichen amyloidosus.

Lichen amyloidosus.


Progesterone.

Progesterone.


Shell nail syndrome.

Shell nail syndrome.


Pemphigus vulgaris.

Pemphigus vulgaris.


Vertical dermatology.

Vertical dermatology.


Steroids.

Steroids.


Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum.


Chronic varicelliform parapsoriasis and hyperparathyroidism.


Cold urticaria.

Cold urticaria.


Methotrexate.

Methotrexate.


A case of (and for) syphilis maligna and negative serology.


Infantile digital fibroma.

Infantile digital fibroma.


Lupus erythematosus and calcinosis cutis.


Hemochromatosis and the skin.

Hemochromatosis and the skin.


Muciparous metaplasia and primary mucoepidermoid skin tumors.


Chronic erythema nodosum.

Chronic erythema nodosum.


Collodion baby. Report of a case.

Collodion baby. Report of a case.


Accentuation of ichthyosis vulgaris in denervated skin.


Darier's disease with mucous membrane involvement. A case report.


Sporotrichoid cutaneous infection with Mycobacterium kansasii.


Sturge-Weber syndrome associated with multiple myeloma.


Perifollicular fibroma.

Perifollicular fibroma.


Treatment of pemphigus vulgaris with methotrexate.


Warts and ultrasound.

Warts and ultrasound.


Tylosis palmaris et plantaris. Its occurrence with internal malignancy.


Human louse infestation. Treatment with Carbacide.


Early effects of ultraviolet light on DNA synthesis in human skin in vivo.


Pathogenesis of trichomycosis axillaris.


Site of action of methotrexate in psoriasis.


Cytogenetic evaluation of methotrexate-treated psoriatic patients.


Surgical eradication of familial benign chronic pemphigus from the axillae. Report of a case.


Topical application of mafenide acetate. Its association with erythema multiforme and cutaneous reactions.


Papular dermatitis herpetiformis in childhood.


Pruritus and acquired anhidrosis. Two unusual cases.


Radiation angiokeratoma following grenz radiation.


Developmental arteriovenous malformation with secondary angiodermatitis. Report of a case.


Keratoacanthoma. Association with basal and squamous cell carcinoma.


Clinical appearance of a balloon cell nevus.


Sarcoidal reactions in tattoos.

Sarcoidal reactions in tattoos.


Urticaria of nine year's duration cleared following dental extraction. A case report.


New tool for dermabrasion.

New tool for dermabrasion.


Histology and cytochemistry of human skin. 3. The eyelid.


Skin ultrastructure in Hand-Schüller-Christian disease. Report on abnormal Langerhans' cells.


Are deans really necessary?

Are deans really necessary?


Lichen planus limited to the nails.

Lichen planus limited to the nails.


Subcorneal pustular dermatosis.

Subcorneal pustular dermatosis.


Erthropoietic protoporphyria.

Erthropoietic protoporphyria.


Porphyria cutanea tarda treated with chloroquine phosphate.


Salicylanilide photosensitivity.

Salicylanilide photosensitivity.


Dermatomyositis in a child.

Dermatomyositis in a child.


Tuberculosis verrucosa cutis. (Prosector's wart).


Porokeratosis of Mibelli.

Porokeratosis of Mibelli.


Arsenical keratoses.

Arsenical keratoses.


Chromoblastomycosis.

Chromoblastomycosis.


Cutaneous sporotrichosis.

Cutaneous sporotrichosis.


Familial chronic pemphigus.

Familial chronic pemphigus.


Carbon monoxide poisoning.

Carbon monoxide poisoning.


Intramolecular cross-link of chick skin collagen.


Mechanism of alkali cation transport in bulk membranes using macrotetrolide antibiotics.


Biosynthesis of glucohydrolase I, a glycoenzyme from Aspergillus niger.


Effect of 4-pentenoic acid on coenzyme A metabolites in rat liver.


In vitro interaction of 1-anilino 8 naphthalene sulfonate with excitable membranes isolated from the electric organ of Electrophorus electricus.


tRNA-dependent translational control of in vitro hemoglobin synthesis.


Uncoupling and charge transfer in submitochondrial particles.


Proton magnetic resonance evidence for methionine-iron coordination in mammalian-type ferrocytochrome c.


Ternary complex formation of 1,2-propanediol dehydratase, cobamide coenzyme and substrate analogue.


The N- and C-terminal amino acid sequences of cobratoxin from Formosan cobra venom.


Chemiluminescence elicitation from an O2 and-or HOOH complex of the riboflavin-copper(I)-chelate.


Incorporation of mannose into mouse brain lipid.


Qualitative and quantitative patterns of gangliosides in extraneural tissues.


Isolation of placental and liver "mitochondrial" fractions which support steroid 11-beta-hydroxylation.


Thermodynamics of binding lysolecithin to serum albumin.


Triglyceride breakdown in rat liver. The demonstration of three different lipases.


Retroconversion of docosahexaenoic acid in the rat.


Alkoxylipids. V. The isomeric monounsaturated substituents of neutral alkoxylipids and triglycerides of ratfish liver.


Effect of orotic acid on the lipid and acid-soluble nucleotide concentrations in avian liver.


Lipids associated with pancreatic lipase during purification.


Studies on the mechanisms of estrogen biosynthesis. VII. 2-beta-hydroxylation of estr-4-ene-3,17-dione in human placenta, in vitro.


The influence of follicle-stimulating hormone on testicular phospholipids.


Cytochrome photooxidation at liqud nitrogen temperatures in photosynthetic bacteria.


Comparison of inosine and glucose as a substrate for energy metabolism in isolated rat-thymus nuclei.


Enhancement of the dark reconstitution of photosynthetic reaction center 2 by nigericin and CCCP.


Re-evaluation of cytochrome c concentrations in rat organs using a new method for cytochrome c.


Ferredoxin from the photosynthetic bacterium, Chlorobium thiosulfatophilum. A link to ferredoxins from nonphotosynthetic bacteria.


Low potential titration of the fluorescence yield changes in photosynthetic bacteria.


A new interpretation of the evidence for a first-order thermal reaction in the production of oxygen by Chlorella pyrenoidosa.


The effect of mineral deficiency and leaf age on the nitrogen and chlorophyll content of spinach chloroplasts.


Correlation of electrical and permeability properties of ion-selective membranes. The linear phenomenological equations giving particle and practical fluxes of a single electrolyte across an ion-selective membrane are stated and interrelated. It is shown that the experimental measurements commonly made in biological and synthetic membrane studies may be used, with minor modification, to obtain the phenomenological transport coefficients and their concentration dependences. It is demonstrated that the electrical properties of a homogeneous membrane may be obtained as functions of the bathing solution concentration by combining fluxes measured under open and short circuit. Attention is paid to the use of radiotracers when measuring ionic fluxes. To obtain all the phenomenological coefficients at least one measurement must be made under a pressure gradient. The experimental difficulties in such measurements are discussed and the merits and demerits of various experiments considered. The problems of measuring potentials and concentrations at the low pressure face of a supported membrane make several mathematically simple approaches experimentally unattractive. The best methods appear to be either the measurement of a succession of "apparent osmotic pressures" under concentration differences sufficiently small that the membrane does not require support or the study of "reverse osmosis". Sets of equations are given which enable the phenomenological coefficients to be evaluated from convenient experiments. With a stable homogeneous membrane nine coefficients may be obtained thus enabling either the applicability of the reciprocal relations or the applicability of linear theory under the conditions of the experiments to be tested. For a discontinuous system the six independent coefficients may be obtained from experiments in a single membrane cell.


Concentration dependence of permeability coefficient to an electrolyte component across bovine lens capsule in vitro. Theoretical and experimental studies have been made on permeability coefficients to various kinds of electrolyte across lens capsules that are dissected from bovine eyes and that are found to be positively fixed charged membranes from our experiments of membrane potentials. The differential permeability coefficient, P(m), is defined as J(s) = P(m)(C(2) - C(1)), where J(s) is the flux of an electrolyte component in moles per sec across unit area of the lens capsule that separates two aqueous solutions of the same electrolyte at different concentrations, C(2) and C(1). Various types of strong electrolytes were studied; KCl, NaCl, Cacl(2), MgSO(4), MgCl(2) and LaCl(3). It was found that at C(2)/C(1) = constant, P(m) decreases to zero as C(2) decreases and P(m) increases to a limiting value, (P(m))(infinity), that is characteristic for the system of the salt used and the membrane as C(2) increases, despite of electrolytes. We assumed in theory that single ion activity coefficients of co-ion and gegen-ion are ideal, that the systems studied are in electric neutrality, that the fixed charge density of the membrane is independent of concentrations C(2), and that Donnan equilibrium holds between the bulk solution and membrane surface. Although the concentration-dependent changes of P(m) were quantitatively different depending on the type of electrolyte used, general agreement between theory and experiment was obtained over a wide range of concentrations except for the case of very dilute solutions.


Calculations of pulsatile flow across bifurcations in distensible tubes. A simple method is given for extending across junctions the numerical methods previously used to study fluid flow in nonuniform, nonbranching, distensible tubes. Calculations with this method suggest that the ratio of downstream to upstream cross-sectional areas and the pressure wave velocity ratio in mammals are optimal for energy transfer across the junction.


Inhibition of pyrimidine dimer formation in DNA by cationic molecules: role of energy transfer. In addition to the acridine dyes, acridine orange and proflavine, we find that three other cationic molecules which bind to DNA-ethidium bromide, chloroquine, and methyl green-inhibit the production of cyclobutyl pyrimidine dimers by ultraviolet radiation. Intercalation is not necessary for dimer inhibition. The long range nature of the inhibition implies that energy transfer is responsible. The transfer is between the lowest excited singlet state of DNA and the acceptor singlet, and seems to involve the Förster mechanism.


Conformation of dipeptides.

Conformation of dipeptides.


Infrared spectrum of a DNA-RNA hybrid.

Infrared spectrum of a DNA-RNA hybrid.


The effects of arousal on the amplitude of evoked potentials.


Dielectric properties of hemoglobin and myoglobin. I. Influence of solvent and particle size on the dielectric dispersion.


The effect of lateral geniculate lesions on phasic electrical activity of the cortex during desynchronized sleep in the cat.


Observations on the lamination of the lateral geniculate body in some primates.


Autoradiographic investigation of the distribution of [14C]GABA in tissues of normal and aminooxyacetic acid-treated mice.


Infrared spectrometry of locus coeruleus and substantia nigra pigments in human brain.


Effect of reserpine on the turnover of glutamate, glutamine, aspartate and GABA labeled with [1-14C]acetate in caudate nucleus, thalamus and sensorimotor cortex(cat).


DNA, RNA, and cholesterol increases in cerebrum and cerebellum during development of human fetus.


Brain transplantation in salamanders: an approach to memory transfer.


The effects of forebrain commissurotomies on the rate of learning a dark-light discrimination by cats.


An abnormal retinogeniculate projection in Siamese cats.


Aggregates of irregular axoplasmic tubules in early Wallerian degeneration of guinea pig optic nerve.


Is there a cortico-nigral tract? A comment based on experimental electron microscopic observations in the cat.


Effect of low frequency caudate stimulation on the EEG of epileptic neocortex.


Subcortical origin of rabbit hypnosis.

Subcortical origin of rabbit hypnosis.


Activity in efferent sympathetic nerves evoked by stimulation of the hypoglossal nerve.


Glycine, strychnine, picrotoxin and spinal inhibition.


GABA-picrotoxin interaction in the mammalian central nervous system.


Effect of cations on the association of L-glutamic acid decarboxylase with some subcellular fractions of mouse brain.


Esterase activity in purified myelin preparations from beef brain.


Cross-cultural use of the perceptual maze test.


Stored fascia lata for ophthalmic surgery.


Cryofixation with vitreous excision. A suggestion for the management of some cases of traumatic retinal detachment.


The effects of single instillations of isoproterenol on intraocular pressure in man.


Cerebro-vascular studies in chronic simple glaucoma.


Radiographic evaluation of orbital blow-out fracture.


The penetration of steroids into the rabbit's vitreous, choroid and retina following retrobulbar injection. I.


Medial wall fracture of the orbit.

Medial wall fracture of the orbit.


Fluorescein angiography as a source of artefact in the investigation of hypertension.


Guidelines in low vision prescriptions.

Guidelines in low vision prescriptions.


Bilateral retinal detachment accompanying renal insufficiency secondary to obstructive uropathy.


New eye research laboratories. Department of Ophthalmology, McGill University.


Nocturnal enuresis: studies in bladder function in normal children and enuretics.


Dietary protein and pesticide toxicity: with particular reference to endrin.


Reaction of unmarried girls to pregnancy.


Paradox within paradox.

Paradox within paradox.


Trauma rounds at the Montreal General Hospital. Subtrochanteric fracture (delayed union). (Case P17).


Dissecting aneurysm of the superior mesenteric artery.


Mortality rates of smokers.

Mortality rates of smokers.


The value of chest radiography in the localization of central venous pressure catheters.


The methylation of transfer RNA in vitro by extracts of normal and malignant tissue.


Metabolism of steroids by transplantable mouse interstitial cell tumor.


Mechanism of inhibition of DNA synthesis of sarcoma 180 cells by liver extract.


Fine structure of a transplanted chemically induced nonlymphoid thymoma.


Rat virus-mediated suppression of leukemia induction by Moloney virus in rats.


Lactate dehydrogenase subunits in normal and neoplastic tissues of the rat.


Effect of antilymphocytic and antithymocytic sera on the development of mouse lymphoma.


The action of phleomycin on meiotic cells.


Comparison of tumor radioactivity after the administration of either 125I- or 3H-labeled 5-iodo-2'-deoxyuridine.


Reduced tumor-producing capacity of mycoplasma-modified lines of FL human amnion cells in the cheek pouch of cortisonized hamsters.


Protective influence of cardiac denervation against arrhythmias of myocardial infarction.


Fine structure of developing and adult intercalated discs in rat heart.


The interaction of sympathetic stimulation and blockade on the calcium uptake of the sarcoplasmic reticulum.


Persistence of contractile behaviour in acutely ischaemic myocardium.


The influence of changes in pH of the perfusion fluid on the occurrence of the calcium paradox in the isolated rat heart.


Pressure-flow studies in man during pulsus alternans.


The effects of lower body negative pressure on hand blood flow.


The haemodynamics of cardiac tamponade and blood volume overload in dogs.


Distribution rates of coronary inflow and outflow in the post-mortem canine heart.


The circulatory effects of isoproterenol, acetylstrophanthidin, and volume loading in acute pericardial tamponade.


The circulatory effects of the Valsalva manoeuvre during anaesthesia and thoracotomy.


Venous distensibility in essential hypertension.


Effect of ethanol ingestion on the myocardial capillaries of mice.


Electrocardiographic studies of cardiac orthotopic allotransplantation. 1. The normal puppy.


The in vivo "quantum" synthesis of reserve waxes in seeds o Murraya koenigii (lknii.) Spreng.


Stimulatory effect of insect-metamorphosing steroids from ferns on protein synthesis in mouse liver.


Studies on digitalis glycosides. 28. The structure of digiprogenin. (3).


Total synthesis of dl-anisomycin.

Total synthesis of dl-anisomycin.


Studies on digitalis glycosides. XXIX. The structure of digiprogenin. (4). Partial synthesis of dihydro-alpha-digiprogenin acetate.


Antibiological actions of 2-amino-1,4-naphthoquinone imine.


Studies on pharmaceutical suspension. IV. Flocculation of dispersed phase and structural viscosity.


Disintegration of the aspirin tablets containing potato starch and microcrystalline cellulose in various concentrations.


Studies on digitalis glycosides. XXX. Digitoxin acetates. (1).


Studies on pyrimidinylpyrazoles. IV. Pharmacological activities of 1-(4-methoxy-6-methyl-2-pyrimidinyl)-3-methyl-5-methoxypyrazole and its related compounds.


Modification of conceptual style preference by differential reinforcement.


Myocardial contractile response to norepinephrine, isoproterenol, and calcium chloride in hyperthyroid guinea pigs.


Effect of altering P-R interval on the amplitude of the first heart sound in the anesthetized dog.


Positive and negative inotropic responses of the atria and ventricles to vagosympathetic stimulation in the isovolumic canine heart.


Black identity and the helping person.

Black identity and the helping person.


Capacitance responses and fluid exchange in the cat liver during stimulation of the hepatic nerves.


Comprehensive child psychiatry through a team approach.


A hotline telephone service for young people in crisis.


Turnover and synthesis of norepinephrine in experimental hypertension in rats.


Paradoxical effect of vagus nerve stimulation on heart rate in dogs.


Effects of beta-receptor blockade on the systemic and coronary hemodynamic response to an increasing ventricular rate in the unanesthetized dog.


Simultaneous measurements of radii and wall thickness of microvessels in the anesthetized rat.


Combining social casework and group work methods in a children's hospital.


Acclimatization to decompression sickness: a study of passive relaxation in several tissues.


Pressure, flow and volume changes during exercise within pulmonary vascular bed in patients after pneumonectomy.


The deep-breath-venoconstriction reflex.


A school guidance class for emotionally disturbed children.


Working with families of delinquent boys.


The effect of inhibition of lipolysis on blood concentrations of 3-hydroxybutyrate and acetoacetate.


The effect of nephrectomy on the metabolism of labelled parathyroid hormone.


The effect of adrenal steroids on stool composition, as revealed by in vivo dialysis of faeces.


The effects of oligomycin and 2,4-dinitrophenol on the mechanical performance and metabolism of the perfused rat heart.


The effect of peritoneal dialysis upon the amino acids and other nitrogenous compounds in the blood and dialysates from patients with renal failure.


Intracellular concentrations of water and of the principal electrolytes determined by analysis of isolated human leucocytes.


Relation of plasma phosphate concentration to renal tubular reabsorption of phosphate.


Glucose tolerance and insulin sensitivity.


Thyroid function studies using resin uptake of radioactive thyronines from serum and total thyroxine assay; the free thyroxine index.


The incorporation of (14C)acetate into the plasma cholesterol and the turnover of the plasma cholesteryl esters in familial hypercholesterolaemia.


The role of circulating catecholamines in arterial baroceptor reflexes in the dog and in man.


The effect of salicylate on pyrogen-induced fever in man.


Renal sodium handling and responsiveness of plasma renin levels in hypertension.


Effect of packing and resuspension on the osmotic fragility and rate of autohaemolysis of incubated red blood cells.


The distribution of a cardiotonic factor, splenitransin, in mammalian tissues.


Isosmotic intracellular regulation as a mechanism of volume control in crab muscle fibers.


Isolation and partial characterization of transferiin in the sea lamprey, Petromyzon marinus.


Microelectrode records from a cockroach thoracic ganglion: synaptic potentials and temporal patterns of spike activity.


An electrophoretic study of protein extracted in distilled water and in saline solution from the eye lens nucleus of the squid, Nototodarus hawaiiensis (Berry).


Biosynthesis of UDP-sugars from 32P-labelled precursors in various biological materials.


Vitamin E concentrations in the serum of various experimental animals.


Lymphedema, pleural effusions and yellow nails: associated immunologic deficiency.


Inhaled argon boluses in man.

Inhaled argon boluses in man.


Serial studies of factors influencing airway dynamics during recovery from acute asthma attacks.


Circulatory and respiratory responses to postural changes in the hemorrhagic dog.


Autonomic control of cardiac pacemaker activity and atrioventricular transmission.


Respiratory gas exchange in normal men breathing 0.9 per cent oxygen in helium at 31.3 Ata.


Optimum current duration for capacitor-discharge defibrillation of canine ventricles.


Peripheral involvement in thermoregulatory response to an imposed heat debt in man.


Inhibition of sweating by atropine before and after acclimatization to heat.


Erythropoiesis in response to blood loss in man.


Hindlimb blood flow and oxygen usage in hemorrhagic shock.


Hemoconcentration at altitude.

Hemoconcentration at altitude.


Congenital hypoprothrombinemia. A case report.


Sympathoadrenomedullary response of the rat to high oxygen exposures.


Mechanics of respiration during submersion in water.


Digital computer simulation as an aid to the study of arterial wall Na kinetics.


Simultaneous access to renal pedicles of the anesthetized dog.


Release of carbon monoxide from acrylic and polycarbonate plastics.


Heart rate calculator.

Heart rate calculator.


A precision cardiotachometer and arrhythmia detector.


A new theory about the origin of the mitral opening snap.


Construction of a versatile small-animal hyperbaric facility.


Production of isotonic contractions in the intact canine left ventricle.


Bile salt regulation of fatty acid absorption and esterification in rat everted jejunal sacs in vitro and into thoracic duct lymph in vivo. This study was performed to investigate whether the malabsorption of fat in the blind loop syndrome is due to the presence of free bile acids or to a deficiency of conjugated bile salts produced by bacterial degradation of normal bile salts, as well as to learn something of the mechanisms by which bile salts might regulate fat absorption. In the everted gut sac of the rat in vitro, conjugated bile salts were necessary for maximal rates of fatty acid esterification to triglycerides, whereas free bile acids inhibited this process even in the presence of physiologically normal or higher concentrations of conjugated bile salts. In contrast, in the living animal the addition of similar or higher concentrations of free bile acids to infusions of fatty acids in taurocholate micellar solutions produced no reduction in the amount of fatty acid absorbed into lymph or the amount of fatty acid esterified into lymph triglyceride. Both in vitro and in the living animal, reduction in the conjugated bile salt concentration reduced both the rate of fatty acid uptake by the intestine and the esterification into triglycerides. It is concluded that the steatorrhea of the blind loop syndrome or other conditions in which upper intestinal stasis allows bacterial proliferation is not due to presence of increased gut luminal concentrations of free bile acids, but rather is a consequence of lowered concentrations of conjugated bile salts.


Metabolic clearance rate of radioiodinated human growth hormone in man. The nature of the disappearance of radioiodinated human growth hormone (HGH) from plasma has been reexamined. The metabolic clearance rate (MCR) was determined both from single injection and constant infusion studies. After single injection of highly purified radioiodinated HGH, the disappearance curve remained multiexponential during the period of study (4 hr). The shape of the curve was independent of the growth hormone preparation used. Similar disappearance curves were obtained with unlabeled HGH.MCR values calculated from constant infusion studies were 203 +/-7.8 liters/day per m(2) and values derived from single injection studies agreed closely with this. The multiexponential nature of the disappearance curve does not permit meaningful calculation of volume of distribution or half-time of disappearance.


Diaphragm activity in obesity.

Diaphragm activity in obesity. DIAPHRAGM ACTIVITY DURING CARBON DIOXIDE BREATHING AND TOTAL CHEST COMPLIANCE DURING DIAPHRAGM RELAXATION WERE MEASURED IN EIGHT OBESE SUBJECTS: four with normal blood gases and four with hypercapnia and hypoxemia. Whereas there were no significant differences in the values of total chest compliance between the two groups, there were marked differences in diaphragm activity. The increase in integrated electrical activity in the diaphragm, per millimeter increment in carbon dioxide tension in the arterial blood, averaged 66 units (range: 48-90) in the obese-normal subjects and 17 units (range: 12-22) in the obese-hypoventilation subjects. These results suggest that an incapacity to increase the activity in the respiratory muscles, to levels necessary to overcome the load caused by obesity, plays a major role in the genesis of respiratory failure in obese subjects.


Measurement of thrombopoiesis in rabbits using 75selenomethionine. Incorporation of (75)selenomethionine ((75)SeM) has been used to study platelet production in rabbits. Radioactivity of platelets was low after the intravenous administration of (75)SeM and rose to a maximum approximately 3 days after administration. Platelet radioactivity was independent of concurrent plasma levels. The life span of rabbit platelets, as estimated with this technique, was 4-5 days. In vivo reutilization of (75)SeM previously incorporated into plasma proteins was not detected. In vitro incorporation of (75)SeM by platelets in platelet-rich plasma was not demonstrated. Acute hemorrhage 24 hr before administration of (75)SeM increased the incorporation of (75)SeM into platelets. Transfusion-induced thrombocytosis reduced the incorporation of (75)SeM to approximately 30% of that observed in control animals. Suppression of bone marrow function with nitrogen mustard resulted in decreased numbers of platelets in the circulation, and a decrease in incorporation of (75)SeM. Delayed appearance of (75)SeM was observed in circulating platelets during recovery from marrow suppression. Injection of 75-225 ml of plasma from thrombocytopenic donors into normal rabbits increased incorporation of (75)SeM into platelets while normal plasma did not have this effect. The rate of appearance of (75)SeM in circulating platelets appears to provide a sensitive and specific method for the study of production of platelets by megakaryocytes. The data suggest more rapid entry of platelets into the circulation, and a sustained increase in incorporation of (75)SeM into platelet protein after stimulation of platelet production. The results are consistent with the concept of a humoral agent (thrombopoietin) that acts on megakaryocytes to regulate platelet production.


Chromatographic, ultracentrifugal, and related studies of fibrinogen "Baltimore". Chromatographic, ultracentrifugal, and related studies of the fibrinogen of a patient with a congenital disorder of fibrinogen (fibrinogen "Baltimore" have provided evidence of structural differences from normal.Diethylaminoethyl-cellulose (DEAE-cellulose) gradient elution chromatography demonstrated two major peaks in the elution pattern of fibrinogen Baltimore as was the case for normal fibrinogen. However, the first peak of fibrinogen Baltimore was somewhat broader and more symmetrical and was eluted significantly later in the chromatogram than the corresponding peak of normal fibrinogen. Additionally, in some elution patterns, a shoulder on the ascending limb of peak 1 was present, suggesting the presence of chromatographically "normal" fibrinogen. Thrombin time determinations of eluted column fractions from a chromatogram of propositus fibrinogen supported this conclusion by demonstrating that fibrinogen from the ascending portion of peak 1 behaved functionally more like normal than that later in the chromatogram. Chromatograms of mixtures of propositus and normal fibrinogen confirmed the ability of this technique to distinguish normal from Baltimore fibrinogen. Chromatograms of fibrinogen isolated from two affected daughters displayed the characteristic increased anionic binding of peak 1 fibrinogen. Sedimentation velocity experiments indicated that the S(o) (20, [unk]) of fibrinogen Baltimore was slightly greater (8.13S vs. 7.85S) than that of normal fraction I-4. Differences in concentration dependence (- 0.65 c vs. - 1.30 c for normal) of the sedimentation coefficient could be attributable in part to spatial conformational differences. Molecular sieving experiments in acrylamide gels indicated that the molecular weight of propositus fraction I-2 was about the same as that of normal fibrinogen of comparable solubility (i.e. I-4, mol wt 325,000). Studies of the UV spectra, tyrosine/tryptophan ratios, sialic acid and hexose content, and N-terminal amino acids demonstrated no consistent significant differences from normal fraction I-4.


Hemoglobin Philly (beta 35 tyrosine phenylalanine): studies in the molecular pathology of hemoglobin. An abnormal unstable hemoglobin, hemoglobin Philly, was found in three members of a family, each of whom had evidence of a chronic hemolytic state. The presence of the mutant protein was suggested by the rapid appearance of inclusion bodies upon incubation of erythrocytes with brilliant cresyl blue and by the increased heat precipitability of the hemoglobin. However, no abnormal hemoglobin could be demonstrated by electrophoresis or column chromatography. Sulfhydryl titration of the hemolysates with p-mercuribenzoate indicated that there was an average of four reactive sulfhydryl groups per hemoglobin molecule instead of the usual two. The total number of hemoglobin sulfhydryl groups was normal; six groups were measured when denatured globin was reacted with 5,5'-dithiobis[2-nitrobenzoic acid]. This indicated that the increased sulfhydryl reactivity was due to an increased availability to p-mercuribenzoate of the usually unreactive hemoglobin cysteines at beta112 and alpha104. After treatment for (1/2) hr with 4-5 moles of p-mercuribenzoate per mole of hemoglobin, electrophoresis revealed that 30-35% of the hemoglobin had been dissociated into alpha- and beta-chains. Normal hemolysates revealed negligible splitting after 72 hr of similar treatment. The alpha- and beta-chains of hemoglobin Philly were separated from the unsplit hemoglobin A by carboxymethyl cellulose chromatography. Fingerprint and amino acid analyses revealed that tyrosine beta35 was replaced by phenylalanine. In hemoglobin Philly there is loss of the normal hydrogen bond between the tyrosine hydroxyl group and the carboxyl group of aspartic acid alpha126 at the alpha(1)beta(1) contact. This shifts the equilibrium from hemoglobin tetramers toward monomers, exposing the beta112 and alpha104 cysteines. In the cell, precipitation of the unstable monomers may contribute to erythrocyte destruction.


Acute release of thyrotropin in the newborn. Measurements of serum thyrotropin (TSH) concentrations were conducted in maternal and fetal blood during labor and delivery and the early postnatal and neonatal periods. Mean TSH concentration was significantly higher in cord blood (9.5 muU/ml) than maternal blood (3.9 muU/ml), a finding suggesting a fetal-maternal TSH gradient at term. Serum TSH concentration in the newborn increased rapidly to mean levels of 60 muU/ml at 10 min and 86 muU/ml at 30 min of age. Between 30 min and 3-4 hr serum levels decreased rapidly, then fell more gradually to a mean concentration of 13 muU/ml at 48 hr. The half-time of the decrease in serum TSH concentration between 30 and 90 min was 77 min, a value slightly greater than the half-time of disappearance of radioiodinated TSH measured in adults. This indicates that the early high rate of TSH secretion in the newborn ceases by 30 min, and that the rapid rise and fall in serum TSH concentrations may represent release of stored pituitary TSH. A more chronic TSH hypersecretion persisted throughout the first 24-48 hr of extrauterine life. Measurements of serum PBI concentrations were conducted in a separate group of maternal and cord blood samples and in the newborn infants during the first 48 hr of extrauterine life to relate the TSH and serum hormonal iodine concentration changes. Serum protein-bound iodine (PBI) concentrations were similar in maternal and cord blood, increased significantly by 4 hr of age in the newborn, and peaked at about 24 hr, presumably in response to the TSH hypersecretion. The pattern of TSH hypersecretion was similar in infants delivered vaginally and by caesarean section. Maternal serum TSH concentrations were stable throughout the perinatal period. Warming the infants at 99-103 degrees F during the first 3 hr of life did not prevent the early, acute release of thyrotropin. Cooling of warm infants at room temperature (72-78 degrees F) between 3 and 4 hr resulted in a decrease in mean rectal temperature of 3.3 degrees F and produced a significant increment in serum TSH concentration. These data suggest that the mechanism of the early, acute release of thyrotropin in the newborn may involve a potent stimulus other than cooling. However, the increase in serum TSH stimulated by delayed (3-4 hr) cooling indicates that neonatal hyperthyroxinemia is, at least, augmented by extrauterine cooling. Thus, cold exposure is capable of increasing TSH secretion in humans.


Attack rates of acute nephritis after type 49 streptococcal infection of the skin and of the respiratory tract. Prospective studies in a population of American Indian children during an outbreak of acute nephritis associated with the Type 49 Group A streptococcus permitted a comparison of attack rates of renal complications after infection at different sites and at different ages. Acute nephritis or unexplained hematuria developed in 10 of 42 children (23.8%) with Type 49 streptococcal skin infection, in 2 of 44 (4.5%) with Type 49 throat infection, and in 3 of 16 (18.8%) with simultaneous Type 49 infection at both sites. The higher attack rate of nephritis and hematuria in children with pyoderma indicates that skin lesions played a direct and quantitatively greater role than respiratory infection in the pathogenesis of acute nephritis during this outbreak. Skin infections with the Type 49 strain were followed by evidence of renal complications more often in children younger than 6.5 yr (9 of 21 or 43%) than in older children (1 of 21 or 5%). Attack rates of renal complications after Type 49 skin infection were approximately equal in males and females.


Study of calcium absorption in man: a kinetic analysis and physiologic model. A physical model of calcium absorption was developed from analysis of data obtained on 23 subjects, including 13 patients having a variety of abnormalities of calcium metabolism. The model was tested and found consistent in all subjects studied. This technique provides a quantitative description of the rate of entry of oral dose of (47)Ca into the circulation as a function of time by analysis of serum or forearm radioactivity in response to intravenous and oral administration of (47)Ca. The kinetics of the absorption process as proposed by the model are characterized by an initial delay phase of 15-20 min, by a maximal rate of absorption at 40-60 min after ingestion, and by 95% completion of the absorption within 2(1/2) hr. Partial identification of the physiological counterparts of the model was possible by introduction of the isotope at various levels of the gut. Although the region of the duodenum was found to have the greatest rate of absorption per unit length in normal subjects, it was least responsive to stimulation by parathyroid hormone and suppression by calcium loading. Furthermore, the response of the gut to parathyroid hormone was delayed, whereas the suppression of absorption by intravenous or oral calcium loading was rapid and dramatic. The implications of these observations are discussed.


Reversible stimulation of sodium transport in the toad bladder by stretch. Short-circuit current and transepithelial potential difference were measured in toad hemibladders mounted as sacs on glass cannulae. When sac volume was changed by adding or removing fluid, short circuit current responded by increasing or decreasing during the ensuing half-hour. The time course of the response and its magnitude indicated that it was not artefactual. Furthermore, net sodium flux responded similarly. Sac volume, and thus bladder surface area, could be varied from 0.03 to 0.4 cm(2)/mg wet weight. The mean response to either decreases or increases was 10 muA/cm(2). Everted hemibladders, however, responded less. Neither hydrostatic pressure, nor increased chloride conductance, nor increased access of oxygen or glucose to the mucosa was responsible for the response. Tissue conductance did vary markedly with volume, and may have played a role, but sodium conductance did not vary with volume in a consistent manner. The results indicate the existence of an intrinsic mechanism in this tissue which alters sodium transport in response to stretch.


RNase activity in erythroid cell lysates. The characteristics of degradation of reticulocyte ribonucleic acid (RNA) and ribosomes were studied in a whole erythroid cell lysate system. The process followed Michaelis-Menten kinetics, and indicated that RNA degradation in the erythroid cell is mediated by an enzyme previously isolated from reticulocyte hemolysates. Erythroid cell RNase activity had a temperature optimum of 50 degrees C, a pH optimum of 7.0, was not energy dependent, was heat labile at physiologic pH, and was inhibited by Mg(++), Ca(++), and exposure to bentonite and deoxycholate. Free sulfhydryl groups were not essential for RNase activity. Of the substrates occurring naturally within the erythroid cell, isolated ribosomal RNA was most susceptible to the action of the enzyme, intact ribosomes least susceptible, and transfer RNA intermediate between them. Natural substrates were degraded completely to nucleotides in cell lysates. Competitive inhibition studies indicate that one enzyme system is capable of degrading both RNA and ribosomes, although the existence of more than one enzyme has not been excluded. Erythroid cell lysates quickly broke down polyribosomes into single ribosomes. The more rapid degradation of ribosomes, as compared with transfer RNA, which occurs in vivo, as opposed to findings in vitro, suggests that there is a special intracellular mechanism responsible for ribosome degradation in the maturing erythroid cell.


On the influence of extracellular fluid volume expansion on bicarbonate reabsorption in the rat. Bicarbonate reabsorption is classically regarded as a rate-limited process characterized by saturation kinetics. The tubular maximum (Tm), however, varies with glomerular filtration rate. Thus bicarbonate reabsorption, in common with sodium reabsorption, is characterized by glomerulo-tubular balance. The examination of bicarbonate reabsorption is accomplished using the bicarbonate titration technique; however, this method in its traditional form leads to marked expansion of extracellular fluid (ECF) volume. The possibility exists, therefore, that glomerulo-tubular balance for bicarbonate is altered by the volume expansion and thus that the classic pattern of reabsorption may actually reflect inhibited bicarbonate reabsorptive capacity. The present studies were performed in rats to examine this possibility. Bicarbonate titration studies were performed in two groups of animals: (a) those in which ECF volume expansion was minimized; and (b) those in which ECF volume expansion was exaggerated. In the first group, no Tm for bicarbonate was observed either in the majority of individual rats studied or in a group plot for all rats studied despite the fact that plasma bicarbonate concentrations were increased to values in excess of 60 mEq/liter. In the second group, a clear Tm was demonstrated both in individual animals and in group data and there was a lowered threshold for the excretion of bicarbonate. The data thus lend support to the view that the "normal" Tm for bicarbonate may actually represent an inhibited level of bicarbonate reabsorption induced by ECF volume expansion.


Plasminogen activator activity in cultures from human tissues. An immunological and histochemical study. Human tissues and cells from pre- and postnatal life were cultivated and studied for plasminogen activator activity. Cultures were obtained from kidney, renal blood vessels, ureter, bladder, lung, and heart. Local activator activity of cells was demonstrated by histochemical techniques. Activator released by cells into the supernatant culture media was assayed by fibrin plate techniques and was investigated for immunological identity using specific antisera to an activator of human origin, urokinase (UK). Plasminogen activator was produced in primary cultures where cells retain specific functions and generally reflect the enzyme pattern of the tissues of origin. Cells from fetal and adult sources were found to yield activator antigenically identical to UK, as well as activator activity which differed from that of UK in immunoassays and which may represent tissue type activator. Such activity was released after injury or death of cells while UK was produced in cultures containing live, metabolizing cells. Primary cultures of kidney confirmed that this organ is a rich source of UK and demonstrated, in addition, that UK is produced from the early stages of gestation and in increasing amounts thereafter. However, primary cultures also demonstrated that the ability to produce UK is not limited to the kidney but is a function of cells which are distributed widely in body tissues. Thus, activator antigenically identical to UK accumulated progressively after many refeedings in culture supernates of fetal lung and ureter, as well as in supernates of renal blood vessels of adults. These findings indicate continuous formation of UK by the cultured cells and, furthermore, provide evidence of UK production in blood vessels. In cultures from other tissues, particularly those from fetal heart and adult lung and bladder, investigation of activator was hindered by inhibitory activity which accumulated in the supernates. Such activity was derived from cells in culture and was directed selectively against UK, indicating that inhibitor as well as UK are produced by cells of various organs of the body. Plasminogen activator also was produced by serially propagated cells, diploid and heteroploid. However, only diploid cell lines retained activator activity of the original tissues and continued to produce activator antigenically identical to UK. In contrast, heteroploid line appeared to have lost the ability to form UK by yielded activator activity that differed from that of UK in immunoassays. Serially propagated cells thus provide an additional tool for in vitro study of plasminogen activator and may facilitate investigation of the fibrinolytic system in man.


Dopamine (3-hydroxytyramine) replacement and metabolism in sympathetic nerve and adrenal medullary depletions after prolonged thermal injury. After severe thermal injury, the adrenal medulla and the sympathetic nerves can be partially or totally depleted of their adrenaline (epinephrine) and noradrenaline (norepinephrine). The purpose of this paper is to elucidate the rate at which dopamine-2-(14)C, a precursor of noradrenaline, is synthesized into noradrenaline and noradrenaline metabolic products, thereby giving some indication as to dopamine's utilization, turnover, and possible use in treating such noradrenaline-adrenaline depletions. Three burned subjects, 3 wk postburn, were infused with 104.6 muc (872 mug) of dopamine-2-(14)C for 4 hr. Urine was collected at various hourly intervals for the 1st day, and thereafter for 4 days, assayed, and compared with the metabolism of dopamine in normal subjects. Methods for separating, identifying, and counting radioactivity of the various metabolic products of dopamine are described. Normally 87.6 +/-3.1% of the total radioactivity is recovered within 24 hr after an infusion of dopamine-2-(14)C, but in the three severely burned patients, this value was increased to 93.1, 97.3, and 97.5% in 24 hr. There was a marked decrease in the percentage of radioactivity recovered as noradrenaline in all collection periods, and in contrast to normal subjects, no radioactive noradrenaline was recovered after 24 hr. Concomitantly, there was an increase in radioactivity recovered as metabolic products of noradrenaline, reflecting a compensatory shift toward noradrenaline synthesis and utilization at the expense of the dopamine metabolic products. The results indicate that in the burned patients the infused dopamine-2-(14)C was rapidly synthesized into noradrenaline and then rapidly released and metabolized. From these results it seems evident that dopamine would be a useful adjunct in the treatment of sympathico-adrenal medullary depletion in burns.


Absorption of calcium measured by intubation and perfusion of the intact hyman small intestine. Absorption of calcium was measured by direct intubation and perfusion of the small intestine in 10 volunteer normal adult subjects, two adults with celiac-sprue, and one with a parathyroid adenoma. A total of 60 studies were completed using one of two different levels, duodenojejunum or ileum. Solutions containing stable calcium, radiocalcium(47), and a nonabsorbable dilution-concentration marker, polyethylene glycol, were infused at a uniform rate via the proximal lumen of a triple-lumen polyvinyl tube. The mixed intraluminal contents were continuously sampled by siphonage from two distal sites, 10 and 60 cm below the point of infusion. Unidirectional flux rates, lumen to blood and blood to lumen, and net absorption of calcium for the 50 cm segment of small intestine between the two collection sites were calculated from the measured changes in concentration of stable calcium, calcium-47, and polyethylene glycol.Flux of calcium from lumen to blood in the duodenojejunum of normal subjects was appreciable even when the concentration of calcium in the perfusate was below that of extracellular fluid and, as the intraluminal concentration of calcium was increased through a range of 0.5-3.5 mumoles/ml, was positively correlated, ranging from 1.9 to 7.0 mumoles/min per 50 cm. Repeated studies of individual subjects demonstrated a consistent pattern of absorptive efficiency in each, but significant variability from person to person. Flux from lumen to blood in the ileal segment occurred at a much lower rate than that found in the proximal intestine, and there was not a significant dependence upon intraluminal calcium concentration. The opposite flux, from blood to lumen, was low both in the duodenojejunum and ileum (average 0.76 mumoles/min per 50 cm) and was independent of the intraluminal calcium concentration. Unidirectional flux, lumen to blood, from the duodenojejunum was not altered by parathyroid extract administered at the time of the infusion, but was accelerated in the subject with a parathyroid adenoma and markedly reduced in the two subjects with celiac-sprue.


Partial purification and properties of a plasminogen activator from human erythrocytes. The lysis time of euglobulin clots made with whole blood (plasma and red cells) was very much shorter than that of clots made with plasma alone, indicating a fibrinolytic component in red cells. A plasminogen activator was found in the stroma-free hemolysate, and proteolytic activity was found in the stromal fraction. The plasminogen activator, purified by using diethylaminoethyl-cellulose (DEAE-cellulose) in a batch procedure followed by column chromatography, was called erythrokinase (EK). On preliminary characterization, EK appears to activate human and bovine plasminogen in a manner similar to urokinase (UK), as determined by fibrinolytic and caseinolytic assays. The two enzymes can be separated by DEAE chromatography and acrylamide-gel electrophoresis, however, and they hydrolyze acetyl-L-lysine methyl ester and benzoyl arginine methyl ester at different rates.


A study of estrogen metabolic clearance rates and transfer factors. We have attempted to measure the metabolic clearance rates (MCR) and the transfer factors of estradiol (E(2)) and estrone (E(1)) during 2-hr and 12-hr infusions. When estradiol-(3)H was infused for 2 hr, apparent equilibrium was reached at 70 min; the 12-hr infusions showed that plasma estradiol-(3)H levels increased slowly throughout the infusion. When estrone-(3)H was infused, constancy of estrone-(3)H levels was not attained in either the 2-hr infusions or in the two 12-hr infusions. The tritium level in the metabolite of the infused estrogen did not become constant in 50% of the short infusions and increased during all the long infusions. Thus, the conversion ratios C(E1E2) and C(E2E1) continually changed and transfer factors could not be calculated. The apparent "MCR'S" calculated on the basis of the 2-hr studies expressed as liters/24 hr per m(2) +/-SD were: "MCR(E1)" (women) 980 +/-94, (men) 1170 +/-95; "MCR(E2)" (women) 615 +/-17, (men) 830 +/-30. The estradiol "MCR's" differed significantly between men and women. "MCR(E2)" was the same using either estradiol-(14)C or -(3)H and was unchanged by the infusion of 170 mug of estradiol daily. Postmenopausal women had estrogen "MCR's" in the same range as premenopausal women. Excess glucocorticoids increased the "MCR(E2)."


Anemia with spur cells: a red cell defect acquired in serum and modified in the circulation. The sera and red cells of three patients with severe liver disease and "spur cells" were studied. In each case the per cent of serum cholesterol which was free (unesterified) was elevated, and the serum lecithin: cholesterol acyltransferase activity was depressed. Lipoproteins with beta mobility were increased, but exhibited immune reactivity with antisera to both alpha- and beta-lipoproteins. Serum bile salt concentrations were markedly elevated and consisted primarily of chenodeoxycholic acid, with small amounts of lithocholic acid present as well.SPUR CELLS MANIFESTED A STRIKING INCREASE IN CHOLESTEROL CONTENT AND IN THE CHOLESTEROL: phospholipid ratio, but a normal osmotic fragility. When incubated in heated normal serum, spur cells lost their excess cholesterol and became spherocytic and osmotically fragile. Conversely, sera from patients with spur cells readily transferred up to one-third of their free cholesterol to normal red cells, causing normal cells to become resistant to osmotic lysis. In addition, these sera caused normal red cells to acquire thorny membrane projections. Cholesterol transfer to normal cells also occurred from normal serum which had previously been incubated with spur cells. Changes in cell cholesterol were induced by all of the lipoprotein fractions of spur serum. When transfused into a patient with spur cells, normal red cells became more resistant to osmotic lysis over the course of 24 hr. However, over the subsequent 7 days they underwent a progressive increase in osmotic fragility. These normal cells, as well as the patient's own cells, had a shortened survival. Correlating with the moderate decrease in the filterability of red cells spurred in vitro, red cell destruction occurred predominently in the spleen. Red cells in this disorder appear to serve as repositories for free cholesterol loosely bound to serum lipoproteins. Cholesterol acquisition by the red cell membrane increases its surface area and causes the red cell to be resistant to osmotic lysis. The associated alteration in red cell shape leads to further changes in the cell membrane during circulation in vivo resulting in the loss of membrane surface area and culminating in the cell's premature destruction in the spleen.


Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. Renal glucose titration studies were carried out in 10 members of two pedigrees with familial renal glycosuria to test the accepted hypothesis of autosomal dominant inheritance and to investigate the genetic significance of "type A" and "type B" renal glycosuria. In one family, a brother and sister each had a moderately reduced threshold and tubular maximum for glucose (type A), but both of their parents reabsorbed glucose normally. In the second family, two brothers had severe type A renal glycosuria, their mother and one brother had a mild type A defect, and another brother demonstrated a reduced threshold, an exaggerated splay, and a normal tubular maximum, indicative of type B glycosuria.Hexose transport by intestinal mucosa was also investigated in controls and in the three brothers with the most severe renal glycosuria. D-glucose-(14)C and 3-O-methylglucose-(14)C were accumulated by jejunal mucosa from controls by processes which were saturable and concentrative. No differences in hexose transport were observed in the patients with renal glycosuria. We conclude that familial renal glycosuria can be inherited as an autosomal recessive trait; that mild and severe type A renal glycosuria and type B renal glycosuria can occur in the same pedigree; and that defective reabsorption of glucose by the kidney need not be accompanied by abnormalities in intestinal glucose transport. These findings indicate that glucose transport in the gut and kidney are not mediated by identical mechanisms, and that several different mutations are responsible for the phenotypic variability in familial renal glycosuria.


The importance of aerobic metabolism in the renal concentrating process. The extent to which the concentrating function of the kidney depends on oxidative processes was investigated by infusing cyanide into one renal artery of dogs undergoing mild mannitol diuresis while receiving an infusion of vasopressin. This produced an abrupt fall in concentrating capacity (T(c) (H2O)) that was reversed when the cyanide infusion was stopped. The change could not be accounted for by the accompanying solute diuresis, since it was not reproduced by increasing the rate of mannitol infusion. The reduction in T(c) (H2O) induced by cyanide did not result from increased delivery of dilute urine to the collecting ducts, since free water clearance (C(H2O)), studied in other dogs during water diuresis, was unchanged or decreased by cyanide. Cyanide produced renal vasodilatation, as did intraarterial acetylcholine, but in contrast to the striking reduction in concentrating capacity evoked by cyanide, T(c) (H2O) was not significantly changed by acetylcholine. The data indicate that concentrating ability is closely tied to oxidative metabolism in the kidney, and it is suggested that the region where this is critically important is the red medulla and the thick ascending limb of Henle's loop.


Effect of decreased O2 supply to tissue on the lactate: pyruvate ratio in blood. Experiments were performed with trained conscious dogs with permanently implanted intravascular catheters. With the dogs in a basal resting state, the concentrations of lactate (L) and pyruvate (P) in arterial blood fluctuated widely from day to day, whereas their concentration ratio (L/P) remained relatively constant. By contrast, decrease in tissue O(2) supply induced by severe chronic anemia increased the arterial blood L/P, specifically, with only random accompanying changes in the lactate or pyruvate concentrations themselves. When systemic O(2) consumption was increased acutely by muscular exercise, cardiac output increased, and the changes in blood L/P were small and not consistent between different dogs. But when O(2) supply to the tissues was simultaneously limited by anemia, L/P increased during exercise, and the magnitude of the increase was proportional to the severity of the anemia. These results suggest that changes in blood L/P during exercise are related specifically to tissue O(2) supply.


Comparison of the reflex reactivity of skin and muscle veins in the human forearm. To determine the relative participation of skin and muscle capacitance beds of the forearm in venomotor reflexes, epinephrine iontophoresis was combined with forearm plethysmography so that the volume of muscle veins could be estimated simultaneously with the volume of cutaneous veins, at a constant venous pressure. With this technique not only are the cutaneous veins markedly constricted but they also are prevented from filling since skin blood flow is abolished. In 10 normal subjects, the venous volume in the elevated control forearm at a congesting pressure of 30 mm Hg (VV[30]) was 3.16 +/-0.30 SEM cc/100 cc, while in the iontophoresed arm it was 2.54 +/-0.31 cc/100 cc. Thus the forearm cutaneous VV[30] was 1.62 cc/100 cc. With a deep breath, ice to the forehead, and leg exercise, and cutaneous VV[30] decreased 19.8% (P < 0.01), 36.6% (P < 0.01), and 32.6% (P < 0.02), respectively, whereas the muscle VV[30] was not altered significantly. Similar results were observed using the isolated forearm technique and a deep muscle vein. The infusion of epinephrine intra-arterially did not decrease reflex venomotor reactivity until cutaneous blood flow was completely suppressed, indicating that the inability of the veins to react in the iontophoresed arm was not the result of epinephrine diffusion into the muscle bed. Thus, these results indicate that, in the forearm, only cutaneous veins participate in venomotor reflexes. Further, since the forearm is principally composed of skeletal muscle and the hand skin, an explanation is provided for the observation that veins of the forearm, studied as a whole, appear less reactive to stimuli than veins of the hand. An explanation also is provided for fainting which occurs during motionless standing despite intense venoconstriction, thereby emphasizing the importance of the skeletal muscle pump in the legs in preventing postural syncope.


Control of insulin secretion during fasting hyperglycemia in adult diabetics and in nondiabetic subjects during infusion of glucose. In obese adult diabetics, the concentration of insulin in venous plasma was unrelated to the degree of hyperglycemia after an overnight fast. However, in these subjects, insulin rose and fell in proportion to the magnitude of change in plasma glucose induced by small intravenous infusions of glucose. The minimal dose of glucose to cause a significant rise in insulin above the fasting level was similar in normal subjects, obese nondiabetic subjects, and in obese, hyperglycemic adult diabetics. This dose lay between infusion of 60 and 100 mg of glucose per min for 30 min. These results suggested that the secretion of insulin was under regulation by changes in blood glucose but was not stimulated in proportion to the stable raised blood glucose concentration of the hyperglycemic diabetic. Artificial hyperglycemia was induced in fasting normal subjects by constant intravenous infusion of glucose at rates of 100-250 mg of glucose per min for periods up to 8 hr. Plasma glucose rose during the 1st hr of infusion and then remained constantly elevated for up to 8 hr. The concentration of plasma insulin paralleled that of plasma glucose. During the period of constant hyperglycemia and elevated insulin, superimposition of a brief additional glucose load resulted in a prompt rise in glucose and insulin, both returning to the previous elevated levels. Thus in normals as well as obese diabetics, stable hyperglycemia does not produce a pancreatic response sufficient to return the blood glucose to an arbitrary normal fasting concentration, yet the beta cells remain readily responsive to a change in plasma glucose. These data suggest that the beta cells do not operate as a control system with an absolute reference point when presented with systemic hyperglycemia. The behavior of the beta cells during hyperglycemia in the fasting obese adult diabetic suggests that the regulation of the basal insulin secretion may not be determined by factors directly related to the prevailing concentration of glucose. It is postulated that the beta cells adapt to hyperglycemia perhaps through the operation of controls directed toward a normal delivery of free fatty acids or some other cellular metabolic substrate during fasting.


Effect of expansion of extracellular fluid volume on renal phosphate handling. To examine the specific effect of extracellular fluid (ECF) volume expansion on phosphate excretion studies were performed in thyroparathyroidectomized dogs receiving saline solution intravenously. The natriuresis resulting from ECF volume expansion was consistently accompanied by an increase in phosphate excretion. The possible role of increased filtered load of phosphate was eliminated in experiments in which the filtered load of phosphate was reduced by acute reduction in the glomerular filtration rate. Despite considerable reductions in filtered phosphate, ECF volume expansion resulted in a consistent increase in phosphate excretion. Furthermore, the possible contribution of alteration in blood composition was investigated in experiments in which saline was infused during thoracic inferior vena cava constriction. In these experiments saline infusion failed to increase sodium or phosphate excretion. Cessation of saline infusion and release of caval constriction resulted in a prompt natriuresis and increased phosphate excretion. It is concluded from these studies that extracellular fluid volume expansion results in an increased phosphate excretion in the parathyroidectomized dog. This effect is the specific consequence of ECF volume expansion and is not due to increase in the filtered load of phosphate or alterations in blood composition.


Physicochemical basis for formation of renal stones of calcium phosphate origin: calculation of the degree of saturation of urine with respect to brushite. Brushite (CaHPO(4).2H(2)O) was considered to govern the formation of renal calculus of calcium phosphate origin. The degree of saturation of urine with respect to this phase was therefore calculated. This value was obtained from the ratio of the activity product of Ca(++) and HPO(4) (m) (K(sp)) before and after incubation of urine with brushite. The errors in the calculation of K(sp) were largely eliminated by this procedure.The urine of patients with idiopathic hypercalciuria and recurrent calcium-containing renal calculi was supersaturated with respect to brushit largely because of the high urinary concentration of Ca(++). The urine of normocalciuric subjects was undersaturated except at high urinary pH. This technique of estimating the degree of saturation of urine should allow a quantitative assessment of the various therapeutic regimens recommended for patients with nephrolithiasis.


Stimulation of insulin secretion by infusion of free fatty acids. The acute elevation of plasma free fatty acid (FFA) levels by direct infusion of sodium oleate into the plasma of conscious dogs was accompanied by the rapid onset of a 2- to 12-fold increase in plasma immunoreactive insulin, and, subsequently, a marked fall in plasma glucose, even in dogs receiving intravenous glucose throughout the infusion. The magnitude of both the insulin and glucose responses correlated with the mean FFA level during infusion. A large increase in plasma insulin and fall in glucose also occurred when glycerol was infused with oleate in order to simulate endogenous lipolysis more closely. Insulin levels in pancreaticoduodenal vein blood rose markedly during oleate infusion, while plasma ketone levels rose only slightly. In contrast to the effects of oleate infusion, elevation of plasma FFA to correspondingly high levels by triolein ingestion and intravenous heparin produced only small increases in plasma insulin, which did not correlate well with the FFA level reached, and small increases in plasma glucose.The results indicate that under certain conditions elevated FFA levels may be a potent stimulus of insulin secretion. This response is modified under other conditions such as during chylomicron removal under the influence of heparin. This effect may play a role in the regulation of lipolysis and ketone formation, but determination of the exact mechanism of FFA stimulation of the pancreas and its physiological significance will require further investigation.


Infusion of long-chain fatty acid anions by continuous-flow centrifugation. We have developed a method for the rapid infusion into plasma of large amounts of long-chain free fatty acids (FFA). Unanesthetized dogs were connected by a peripheral artery to a closed, continuousflow centrifuge from which cells and plasma emerged in separate lines. Sodium oleate was infused directly into the plasma line before cells and plasma were recombined and returned to the animal through a peripheral vein.The centrifugation procedure itself produced only small changes in circulating levels of glucose, FFA, and electrolytes. Plasma flow rates as high as 100 ml/min could be maintained, and centrifugations of 12 hr were accomplished without complications. During centrifugation, sodium oleate was infused at rates up to 80 muEq/kg per min for 2.5 hr; the maximum molar ratio of FFA to albumin without hemolysis was 10:1. Plasma FFA levels rose rapidly after infusions were started and reached constant elevated levels within 15-20 min. Oleate infusion at 10-50 muEq/kg per min produced a rise in plasma FFA proportional to the infusion rate. The maximum increment in plasma FFA above control values was 1.66 muEq/ml. When infusions ended, plasma FFA declined rapidly to control levels. Oleate infusion at rates below 30 muEq/kg per min did not reduce levels of other plasma FFA. Infusion at high rates was accompanied by a marked fall in blood glucose. This method permits adminsitration of long-chain fatty acids in sufficient quantities to study their individual metabolic effects, and provides a new way to supply lipid calories parenterally.


Heart rate changes in a reaction time experiment with young and aged subjects.


Effect of flavin compounds on glutathione reductase activity: in vivo and in vitro studies. Increases or decreases of red cell glutathione reductase (GR) have been described in connection with many clinical abnormalities. We find that GR activity as measured in hemolysates represents only a portion of the available GR activity. The addition of small amounts of flavin adenine dinucleotide (FAD), but not of flavin mononucleotide or riboflavin, activates the GR of hemolysates. 1 muM FAD results in a maximal activation within 10 min; gradually increasing activation occurs at much lower, for example, 20 mmuM FAD concentrations. Once FAD has activated GR, dilution or dialysis does not reverse activation of the enzyme. Activation of GR by FAD can be inhibited by adenosine triphosphate (ATP), and to a lesser extent by adenosine diphosphate (ADP) and adenosine monophosphate (AMP), if these adenine nucleotides are added before the addition of FAD, but only to a slight extent if FAD is added before the adenine nucleotides. The addition of FAD to GR does not alter its electrophoretic mobility but produces intensification of the bands. The administration of 5 mg of riboflavin daily produces marked stimulation of red cell GR activity within only 2 days. After cessation of riboflavin administration, the GR activity again begins to fall. The degree of stimulation of GR activity by riboflavin is inversely correlated with the level of dietary riboflavin intake. The base line GR activity of normal individuals is directly correlated with the level of dietary riboflavin intake. The previously unexplained variations of glutathione reductase in health and disease must be reevaluated in light of the state of riboflavin nutrition and metabolism of the subject.


Neuro-muscular tests of aging in Hiroshima subjects.


Validity and reliability of a multistage exercise test for older men and women.


Vitamin B12 content of human vascular tissue in individuals of various ages.


Radiographic changes in the rami of edentulous human mandibles.


Aging and location of acid ribonuclease in liver of various animals.