Measurement and prediction of the disappearance rates from soil of 6-chloropicolinic acid. 6-Chloropicolinic acid is the sole detectable metabolite, other than carbon dioxide, arising from decomposition of 2-chloro-6-(trichloromethyl) pyridine in soil. The pyridine compound is a potent inhibitor of nitrification now in use with ammonium fertilizers. The purpose of this study was to evaluate the relative influence of various soil and climatic factors on rates of degradation of 6-chloropicolinic acid in soil. Experiments with a wide range of soil types (23 soils) demonstrate that the most important factor influencing the decomposition rate of 6-chloropicolinic acid is soil temperature. When temperature is not a variable, the quantity of organic matter (0.9 to 6.9% by weight) and pH (4.8 to 8.1) significantly affect the rate of decomposition, but sand, silt, and clay percentages do not. Moisture content was without apparent effect because the range of values investigated was too narrow. A fractional-order rate law (0.7) describes the disappearance rate best. Application of the Arrhenius equation to the data for the decomposition of 6-chloropicolinic acid in soil indicates an activation energy of 6.57 kcal per mole, suggesting that the chemical is biologically rather than chemically degraded. It was not possible to develop a suitably precise equation for prediction of loss rate as affected by the above soil and climatic factors because undefined biological factors in the soils override the effect of measurable properties of soil and climate.


Does conjugated bilirubin displace unconjugated bilirubin from albumin.


Insecticide and nutrient transport in water, related to agricultural land use of a stream basin in Ontario, Canada. Transport by stream water of insecticides and nutrients in Big Creek, Norfolk County, Ontario, Canada, was examined by combining concentrations of substrates with flow data. Big Creek has its headwaters in dairy cattle country, its central basin area is mainly devoted to tobacco growing, and its lower reaches contain mixed farming, corn and vegetables, etc., before it flows into Lake Erie. Three sampling sites were chosen to represent these 3 different land uses. Generally concentrations of substrates in the water were quite uniform at the 3 sites resulting in transport of quantities in proportion to stream flow. Certain anomalies occurred and are discussed. The 2 chief insecticides found were DDT and dieldrin. Analyses for potassium, calcium and magnesium indicated that these nutrient losses into the stream were area-rather than usage-dependent. Midseason variations in loss of nitrogen and phosphorus may be the result of agricultural practices in the three areas represented in this study. The largest quantities of all nutrients lost occurred early in the season before crops were established.


Disappearance of dislodgable residues of five organophosphate pesticides on citrus leaves and fruit during dry and wet weather in Florida. Citrus leaf discs and fruit taken from trees sprayed at recommended levels and twice recommended levels with ethion, parathion, azinphosmethyl, carbophenothion, and dioxathion were shaken with water and wetting agent for removal of dislodgable residues at 0, 1, 3, 5, 7, 14 and 21 days following treatment. The first portion of the field experiment was performed during a period of no rainfall (April) and the second when there was rainfall (July) in 1973. Four replicates of 50 leaf discs and 4 fruit, respectively, were averaged from each sampling to give data reported. A gas chromatograph equipped with a flame photometric detector was used for analysis. Dislodgable residues found decreased with increasing time following application and samples from the wet period were lower than those from the dry period. Moisture and temperature could account for the differences in the two sampling period.


Toxic, neurochemical and behavioral effects of dieldrin exposure in mallard ducks. Toxic, neurochemical and behavioral alterations were evaluated in ducks fed various dietary levels of dieldrin. Increasing amounts of dieldrin in the diet caused an appreciable decrease in the levels of three biogenic amines in whole brain, i.e. serotonin, norepinephrine and dopamine. No effect was noted in whole brain gamma aminobutyric acid contents. Hepatic microsomal enzymes were assayed in these birds using p-nitroanisol and O-ethyl-O-p-nitrophenyl benzenethionophosphate as substrates. Sublethal amounts of dieldrin caused an increase in hepatic drug metabolizing enzymes. Similar alterations were noted in liver protein, deoxyribonucleic acid and ribonucleic acid contents. Studies involving encounters between mallard drakes indicated a decline in the tendency for dieldrin exposed drakes to take the initiative and establish rights of access in approach confrontations. Although many of these changes are compatible with life processes, their significance is not well understood, especially in terms of lifelong exposure to persistent pesticides. The possible relationship between neurochemical alterations and the mechanisms of insecticide neurotoxicity is discussed.


Alteration of O,O-dimethyl S-[alpha-(carboethoxy)benzyl] phosphorodithioate (phenthoate) in citrus, water, and upon exposure to air and sunlight. The fate of 32P- and 14C-labeled O,O-dimethyl S-[alpha-(carboethoxy)benzyl] phosphorodithioate (phenthoate) was determined in citrus, water, and upon exposure to air and sunlight. The products recovered from citrus and glass plates exposed to sunlight were unchanged phenthoate, phenthoate oxon, demethyl phenthoate, mandelic acid, bis-[alpha-(carboethoxy)benzyl] disulfide, O,O-dimethyl phosphorothioic and phosphorodithioic acid. Similar products generally were found in citrus leaf and fruit extracts. Phenthoate was fairly stable in phosphate buffered water with a half-life of approximately 12 days at pH 8.0. The major hydrolysis products were phenthoate acid, demethyl phenthoate and demethyl phenthoate oxon.


The effect of normal human serum on trypanosomes of distinct antigenic type (ETat 1 to 12) isolated from a strain of Trypanosoma brucei rhodesiense.


Cysticercosis of pigs in the Republic of Zaire and its relation to human taeniasis.


Frequencies of the polymorphic types of red cell acid phosphatase in Zairians and in Belgians. Relation between phenotypes and enzymatic activities.


Abnormalities in gallbladder morphology and function in patients with cholelithiasis. Thirty-seven symptomatic cholelithiasis patients who had cholecystectomy were studied to determine the relationships between clinical manifestations, histologic findings and gallbladder absorptive capability. A clinical score was calculated from clinical data which we thought might be predictive of abnormal gallbladder histology. Histologic parameters indicative of gallbladder disease were used to calculate a histologic score. Shortcircuit current measurements, which reflect gallbladder sodium absorption,were used to assess absorptive function. Patients with very high clinical scores, indicative of pronounced clinical score was not predictive of histologic findings or absorptive function of the gallbladder is directly related to the degree of histologic abnormality, and that absorptive capability is not an all-or-none phenomenon. The data also show that visualization on oral cholecystography is an unreliable measure of gallbladder absorptive capability.


Recurrent hyperparathyroidism.

Recurrent hyperparathyroidism. Recurrent hyperparathyroidism occurred in 11 of 295 patients from 10 months to 34 years after an initially successful operation. Seven patients with recurrent hyperparathyroidism had either multiple endocrine adenomatosis type I (MEA) or familial hyperparathyroidism (FHP), one patient had parathyroid cancer, and two patients had renal failure at the time of recurrence. Four of these patients ahd their initial operations elsewhere. Recurrence developed in 33% of patients with MEA or FHP but in only 0.4% of 242 patients without MEA or FHP. The presence of MEA or FHP was known before parathyroid exploration in 18 (86%) of the 21 patients. In patients with MEA or FHP, subtotal parathyroidectomy should be performed if there is more than one gland involved. Other patients should be treated by selective removal of an adenoma because recurrence is rare. Subtotal parathyroidectomy should be reserved for patients with diffuse hyperplasia.


Pancreatectomy for chronic pancreatitis. Of one hundred and forty-nine patients (101 male and 48 female) 4-67 years of age, 117 were alcoholics and underwent pancreatectomy because of episodic or continuous abdominal pain or complications or chronic pancreatitis. Nineteen patients underwent pancreaticoduodenectomy, seventy-seven 80-95% distal resection, anf fifty-three 40-80% distal pancreatic resection. There were 3 operative death and 30 late deaths 6 months to 11 years post pancreatectomy. Twenty-one patients were lost to followup, 1 to 11 years post pancreatectomy. Ninety-five patients are known to be alive, 4 of whom are institutionalized. Indications for pancreatectomy in addition to abdominal pain include recurrent or multiple pseudocysts, failure to relieve pain after decompression of a pseudocyst, pseudoaneurysm of the visceral arteries associated with a pseudocyst, recurrent attacks of pancreatitis unrelived by non-resective operations, duodenal stenosis and left side portal hypertension. The choice between pancreaticoduodenectomy or distal resection of 40-80% or 80-95% of the pancreas should be based on the principle site of inflammation whether proximal or distal in the gland, the size of the common bile duct, the ability to rule out carcinoma, and the anticipated deficits in exocrine and endocrine function. The risk of diabetes is very significant after 80-95% distal resection and of steatorrhea after pancreaticoduodenectomy. When the disease process can be encompassed by 40-80% distal pancreatectomy this is the procedure of choice.


Proximal gastric vagotomy: effects of two operative techniques on clinical and gastric secretory results. PGV performed in 39 patients by separating the lesser omentum from the stomach beginning 6 or 7 cm proximal to the pylorus and skeletonizing the distal 1 to 2 cm of esophagus was followed by 15.4% of proven and 10.2 of suspected recurrent ulcers. Insulin tests were done during the first 3 months postoperatively on 31 of the patients, including the 6 with proven and the 4 with suspected recurrent ulcers. The peak acid output to insulin minus tha basal acid output (PAOI-BAO) was less than 5 mEq/hr in 16 cases (52%) and from 5 to 25 mEq/hr in the remaining 15 cases. In 6 patients with proven recurrent ulcer, PAOI-BAO averaged 21.9 mEq/hr (range, 11.3 to 41.8); in the 4 patients with suspected recurrence, 9.5 (range, 4.4 to 11.8). The operative technique was changed in one respect; the distal 5 to 7.5 cm of the esophagus was skeletonized. In 14 patients, the mean PAOI-BAO +/- S.E. within 3 months of PGV was 1985 +/- 0.7 mEq/hr, and 13 of 14 values were less than 5 mEq/hr. One patient developed recurrent ulcer and required re-operation; this patient's value for PAO-BAO was 1.8 mEq/hr. The results show quantitatively that great differences in the completeness of PGV result from differences in the periesophageal dissection and emphasize its importance if optimal results are to be obtained and, especially, if the efficacy of the operation is to be judged.


The value of thymectomy in myasthenia gravis: a computer-assisted matched study. In the absence of a prospective randomized study of patients treated conservatively or with thymectomy, a computer-assisted retrospective matches study was devised. Of 563 patients treated for myasthenia gravis without thymoma up to 1965, 104 had thymectomy. With computer assistance, each surgical patient was matched with a medical patient on the basis of age, sex, and severity and duration of disease. On this basis 80 of the 104 surgical patients could be matched satisfactorily. There were 16 males and 64 females in each of the matched surgically treated and medical control groups. A complete remission was experienced by 27 of the 78 patients in the surgical group as compared to 6 of the medical group. Improvement was noted by 26 of 78 surgically treated patients and 13 of 78 receiving medical treatment. Survival for patients having thymectomy. Thirty-four patients in the medical group had died as compared to 11 in the surgical group. Comparison of survival in relation to sex, duration of symptoms, or age (less than 30 or less than 30 years) did not show a significant difference. Until more effective treatment is available for myasthenia gravis, thymectomy deserves consideration for both sexes, and with increased age or long duration of symptoms.


Ultrasonography as an aid in the diagnosis and management of surgical diseases of the pelvis: special emphasis on the genitourinary system. Technological advances, particularly the advent of the gray scale technique, has greatly extended the application and usefulness of this modality to clinical diagnoses and surgery. The ultrasonic beam uniquely provides anatomical profiles in the transverse (cross-sectional) and sagittal (longitudinal) planes of the body. Intra-rectal and intra-vaginal ultrasonic probes have provided unique definition of both the normal and pathologic anatomy of the pelvic organs. The present report is drawn from a continuing experience with ultrasonography of the genitourinary system with an update of current technological advances. Ultrasonography has proven especially valuable in the following clinical applications: 1) Early diagnosis of cancer (especially of the prostate); 2) Accurate staging of cancer of the bladder and prostate; 3) Monitoring of the response of the pathologic process to therapy.


Prognosis of gastric ulcer: twenty-five year followup. Four hundred twenty-two patients with gastric ulcer treated during 1950-1960 were followed up to 25 years with a mean followup of 9 years. Nonoperative treatment was used in 59% with a hospital mortality of 35%, one-third of these deaths being directly due to gastric ulcer perforation or hemorrhage. Operative treatment was used in 41% of patients. The most common operation (86%) was gastric resection without vagotomy. Overall operative mortality was 16%; 34% for emergency procedures and 6% for elective procedures. Cachexia seemed to be the most important factor related to operative mortality. Nonoperative treatment resulted in more than twice the hospital mortality compared to operative treatment. Approximately one-half of all patients treated non-operatively had a recurrent gastric ulcer at some time during this study. The recurrence rate following definitive gastric resection was 1.3% compared with 16% during nonoperative therapy. Three-fourths of recurrences occurred later than two years and nearly half of recurrences after more than 5 years of followup. Patients with a prior history of overt bleeding from gastric ulcer disease particularly were at risk for further bleeding. There were coincidental duodenal ulcers in 10% of our patients and a 0.8% incidence of gastric cancer during followup. Long term followup demonstrates the superiority of operative treatment of gastric ulcer and also reveals the continuous propensity of such ulcers to recurrence following nonoperative treatment. Earlier elective operation in patients with overt bleeding, recurrence or persisting symptoms should decrease overall mortality and result in a lower overall long-term risk of ulcer complications.


Parotid neoplasms: a report of 250 cases and review of the literature. A 25-year experience with parotid tumors was reviewed. From a total of 250 neoplasms, 173 were histologically benign and 77 were malignant. Benign mixed tumors accounted for 59% of all lesions. Clinical parameters used to diagnose parotid neoplasms were found to be unreliable in determining whether a given tumor was benign or malignant. The mean age for malignant lesions was 10 years greater than for benign lesions. The phenomenon of malignant transformation of a benign tumor was considered in four patients. Complete surgical excision is the safest and preferred method for diagnosis. Preoperative needle or incisional biopsy are associated with a high degree of local recurrence. The appropriate management of any parotid tumor is predicated on special histological type. Local excision or enucleation no longer have a place in the surgical management of benign parotid tumors. Postoperative tumor recurrence and morbidity are directly related to awareness of surgical anatomy and pursuit of correct surgical techniques for adequate resection. The five-year recurrence rate for 102 benign mixed tumors was 6%. Recurrence in malignant tumors varied with specific histological types but was generally high. Five-year survival for all malignant parotid tumors was 48%.


Comparison of Payne and Scott operations for morbid obesity. One hundred five patients were operated upon for morbid obesity using accepted criteria for operation. Forty-five patients with the Payne operation (35 cm of jejunum anastomosed end-to-side to 10 cm of ileum) were compared with 45 patients having the Scott operation (30 cm of jejunum anatomosed end-to-end to 15 cm of ileum with the proximal cut end of ileum vented into the transverse colon). The weight loss in the first two years was similar, although the Scott procedure patients lost slightly more weight. Comparison of the two groups by a new grading system also showed little difference in the two procedures. The Scott procedure takes longer and subjects the patient to an additional anastomosis. Study of a smaller group of patients having the Scott operation with varying lengths of jejunum and ileum indicates that there should not be less than 30 cm of jejunum nor more than 15 cm of ileum left in continuity. The length of jejunum is particularly important in the production of weight loss, and accurate intraoperative measurement of intestinal length is crucial. In the postoperative period the length of functional jejunum and ileum can be determined by upper gastrointestinal barium roentgenograms.


Antihypertensive activity of a propranolol analog (ORF 12,592) in rodents. Studies were carried out to determine the antihypertensive effects of the 5-hydroxy derivative (ORF 12,592) of propranolol. Acute administration of ORF 12,592 produced a reduction in mean systolic blood pressure in desoxycorticosterone acetate (DOCA) rats and in spontaneously hypertensive rats (SHR). Propranolol was not effective in DOCA rats and produced a significant blood pressure reduction in SHR 48 hr after acute administration. These results demonstrated antihypertensive activity of an analog of propranolol and support the concept that the antihypertensive effects of propranolol may be mediated through a metabolite.


A comparison of skeletal, cardiac, and smooth muscle actions of dantrolene sodium--a skeletal muscle relaxant. Dantroline sodium, a skeletal muscle relaxant, has been proposed to inhibit the relase of Ca++ from the sarcoplasmic reticulum. Such a mechanism suggests that other muscle contractile systems operating with the same Ca++ denominator should also be affected by the drug. In the present studies dantrolene sodium effects on smooth, cardiac and skeletal muscle have been evaluated with in situ and in vitro techniques. In anesthetized dogs in situ skeletal muscle contractions were inhibitied in a dose-dependent manner, but cardiac muscle contractions were not. Effects on intestinal smooth muscle responses were highly variable and of short duration. In vitro, ED50 values were developed with dantrolene sodium (0.15-120 mg/l) in DMSO for each tissue. Skeletal muscle was the most sensitive (ED50 = 4.1 mg/l), cardiac muscle contractions were not inhibited by the drug and intestinal smooth muscle (ED50 = 59.0 mg/l) was approximately 1/14 as sensitive as skeletal muscle. It is concluded that skeletal muscle is uniquely sensitive to dantrolene sodium. A hypothesis for this specific action is offered.


The effect of acetylcholine on biliary excretion of ouabain in the physostigmine pretreated isolated perfused rat liver. The effect of acetylcholine (ACh) on bile flow and biliary excretion of 3H-ouabain was studied in the physostigmine pretreated isolated perfused rat liver. ACh added into the perfusion medium to give a concentration of 1 X 10(-4)M after the addition of physostigmine (2 X 1 X 10(-5)M) transiently decreased bile flow and biliary concentration of tritium, originated from 3H-ouabain. A deficit of 34 mul of bile during the decreased bile flow could be calculated, compared to the control group. This deficit in bile flow possibly reflects an inhibitory secretory effect of ACh on canalicular bile secretion, or enhanced reabsorption of water in the biliary tree. The decline in the concentration of 3H-oubain in the bile after the addition of ACh indicates that ACh inhibits biliary transport of ouabain by an unknown mechanism, in addition to its effect on bile flow. Physostigmine alone possibly was without an effect on biliary elimination of ouabain. The results show that ACh retards the biliary elimination of ouabain through its influence on bile flow and biliary concentraton of ouabain.


Neurotoxicity of digitoxin in adult and newborn rats: drug distribution. Electrocardiographic monitoring of adult and 1 week old (newborn) rats during severe acute digitoxin toxicity demonstrated a lack of acrdiotoxicity despite marked neurotoxicity in both age groups. To examine the possibility that drug disposition is a factor in the unusual digitoxin sensitivity of newborn rats, 3H-digitoxin distribution in liver, heart, brain, kidney, adrenal, blood and fat was compared in 1 and 3 week old (weanling) rats at 2, 12 and 24 hr. H3-label was rapidly sequestered by the liver in weanlings but not in newborn rats. Newborns had significantly higher concentrations of 3H-substance in all other organs, particularly in brain (greater than 25% of the administered dose at 24 hr), indicating a cerebrotoxic basis for the newborn's sensitivity to digitoxin. Only trace amounts of 3H-substance were recovered from adult rat brain during severe neurotoxicity (72 hr) suggesting that digitoxin metabolites may be potent cerebrotoxins. Extremely high adrenal concentrations were noted in all animals.


An increase of liver uptake of thyroxine, an initial step of an increased fecal loss of thyroxine in response to propylthiouracil in rats. Propylthiouracil augmented fecal loss of thyroxine (T4), but methimazole was without effect in this respect in rats. In vitro uptake of labeled T4 by the liver was significantly enhanced by a small amount of propylthiouracil in the presence of dilute rat plasma. Methimazole was without effect under comparable conditions. In contrast, propylthiouracil and methimazole failed to affect in vitro uptake of labeled T4 by the kidney and diaphragm in the presence of dilute rat plasma. Since deiodination of T4 does not occur in the presence of dilute rat plasma, it is suggested that propylthiouracil specifically stimulates liver uptake of T4 as an initial step of an increase of biliary-fecal excretion of T4 in rats.


The effects of digitoxin and its metabolites on the transmembrane potential and contractile characteristics of guinea-pig ventricle strips. The effects of 10(-7) and 10(-6) M digitoxin, and some of its metabolites, digitoxigenin-bis-digitoxoside, digitoxigenin-mono-digitoxoside and digitoxigenin on the transmembrane potential and contractile characteristics of guinea-pig right ventricle strips were studied to define the role of the sugar side-chain in these cleavage products of digitoxin. Digitoxin and digitoxigenin produced their maximum inotropic responses, without induction of arrhythmias, at about 30 min. However, the bis and mono compounds produced arrhythmias within 12 min, so the inotropy recorded may not be the maximum response. Digitoxin with 3 sugar residues and the bis compound with 2 sugar residues produced a prolongation in the action potenital duration. In contrast, the mono compound with one sugar residue and the digitoxigenin with no sugar residue produced a shortening of the action potential duration. There may be a relationship between the number of sugar moieties and the action potential duration; digitoxin and its bis derivative increased the action potential duration and mono- and digitoxigenin decreased the action potential duration. There also appeared to be an unusual relationship between the number of sugar moieties and induction of arrhythmias; arrhythmogenicity occurred at the doses employed with only the bis- and mono-digitoxoside. Finally, there appeared to be no simple relationship between chemical structure and inotropic potency.


Relationships between chronotropic effect, 1-3H-noradrenaline uptake and tissue concentrations of desipramine, protripyline and doxepin in rat isolated atria. The pharmacological effects of three tricyclic antidepressant agents (desipramine, protriptyline and doxepin) are evaluated in rat isolated atria in relation to their accumulation and efflux kinetics. The pharmacological effects studed are: inhibition of 1-3H-noradrenaline uptake, potentiation of 1-noradrenaline chronotropic response, and changes in spontaneous atrial rate. All drugs inhibit noradrenaline uptake and potentiate noradrenaline chronotropic response (desipramine congruent to protriptyline greater than doxepin). Desipramine and protriptyline, at concentrations of 10(-7) -- 10(-6)M stimulate the spontaneous rate; higher concentrations (greater than 10(-6)M) depress it. Doxepin has only a negative chronotropic effect. When the drugs are removed from the incubation medium, the depressing effect starts to disappear immediately for doxepin and desipramine and after 20 min for protriptyline. On the contrary the stimulating effect persists after repeatedly washing the preparations. Desipramine, protriptyline and doxepin extensively accumulate in the myocardial tissue (desipramine larger than or equal to protriptyline greater than doxepin). In the efflux studies doxepin is washed out more rapidly than desipramine and protriptyline. Although the kinetics of uptake and efflux of the three compounds are not sufficient to interpret their different pharmacological activities in isolated atria, they give useful information on the persistance of the sympathomimetic effect and the rapid disappearing of the negative chronotropic effect after washing.


Effects of droperidol on cardiovascular adrenoceptors. The influence of droperidol on the pressor effect of noradrenaline was investigated in pithed rats injected with propranolol. Droperidol induced a dose-dependent shift of the noradrenaline dose-response curve to the right, but proved to be 20 times less potent than phentolamine. Droperidol produced a considerably more pronounced inhibition of the effect of tyramine than of that of noradrenaline.--The influence of droperidol on the increase in tension induced by noradrenaline was determined in isolated aortic strips of rats. The drug caused a marked parallel shift of the noradrenaline concentration-response curve to the right (pA2:7.99). In this preparation droperidol and phentolamine were equieffective.--Droperidol did not produce a significant shift of the noradrenaline concentration-response curves obtained for the positive chronotropic and inotropic effects in spontaneously beating right guinea-pig atria and in electrically driven left atria, respectively.--It is concluded that droperidol is a competitive inhibitor of the vascular alpha-adrenoceptors, leaving the beta-adrenoceptors of the heart unaffected, and that it inhibits the neuronal uptake mechanism of noradrenaline.


Calcium-dependent, iproveratril-resistant contractions of aortic strips induced by a convulsant barbiturate. At 3 X 10(-5) M concentratons, 5-(2-cyclohexylideneëthyl)-5-ethyl barbituric acid (CHEB) causes a contraction of rabbit aortic strips that is equivalent to about half of the maximal response to norepinephrine. If a calcium-free medium is substituted for normal bathing solution and drug is added immediately thereafter, there is no response to the convulsant barbiturate but a nearly normal response to norepinephrine. When calcium is replaced in stepwise increments, the contractor response to CHEB appears in corresponding increments. The prompt influence of changes in external calcium-concentration suggests that CHEB-induced contraction occurs as a result of calcium influx into cells rather than a release of free calcium from previously accumulated intracellular stores. CHEB effect, like that of potassium, is prevented by pretreatment with lanthanum (5 X 10(-3)M). CHEB differs from potassium in that its effects are even more sensitive to changes in extracellular calcium concentration. Nevertheless, CHEB can contract aortic strips in the presence of iproveratril at a concentration (10(-4)M) that blocks all response to potassium (100 mM).


Effect of some antihypertensive drugs and catecholamine depletors on the plasma renin activity in the rat. The effect of some antihypertensive drugs and catecholamine depletors on the plasma renin activity (PRA) has been investigated in the rat. Diazoxide and CIBA 4416-Go. increased and clonidine decreased the PRA significantly. The increase in PRA following diazoxide was partially blocked by oxprenolol, adrenalectomy and demedullation. Adrenal cortex does not seem to contribute to this increase in PRA following diazoxide. Pretreatment of rats with reserpine, guanethidine or 6-hydroxydopamine alsine, guanethidine and 6-hydroxydopamine when given acutely or repeatedly (for 3 days) did not produce any significant change in PRA. It is concluded that vasodilators like diazoxide and CIBA 4416-Go. increase PRA resulting from sympathetic activation which follows hypotension; this increase is blocked by catecholamine depletors like reserpine, guantethidine and 6-hydroxydopamine.


Role of neuronal and extraneuronal factors in temperature mediated responsiveness of adrenoceptors. Changes in bath temperature caused changes in the adrenergic responsiveness of rabbit iris dilator muscle as indicated by shifts in dose-response curves along the log axis and changes in maximum responses. Responses of control tissues to an alpha agonist (norepinephrine) were increased at lower temperatures and responses to a beta agonist (isoprenaline) were increased at higher temperatures. Responses of control tissues were compared with responses of tissues pretreated with cocaine or with responses of adrenergically denervated tissues (chemical and surgical). Changes in ED50 values with temperature change are similar in control, cocaine pretreated or denervated muscles. In contrast, changes in maximum response with temperature change are reversed by cocaine pretreatment or denervation. Pretreatment of tissues with an inhibitor of catechol-o-methyl transferase (tropolone) or an inhibitor of monoamine oxidase (iproniazid) did not affect the temperature sensitivity of adrenoceptors. Also, responses to terbutaline, a beta agonist not susceptible to catechol-o-methyl transferase, changed with temperature. These data indicate that for rabbit iris dilator muscle both a neuronal and an extraneuronal component are involved in adrenoceptor response changes induced by temperature change and that changes in rates of activity of metabolizing enzymes are not involved.


Differential species sensitivity to the inhibitory effect of cardiac glycosides on 3H-1-noradrenaline accumulation by tissue slices. Effects of three cardiac glycosides on the accumulation of 3H-1-noradrenaline (3H-1-NA) by slices of heart and spleen were studied. Ouabain, digitoxin and digoxin, all produced a concentration dependent inhibition of 3H-1-NA uptake in both types of tissue slices. The maximum amount of 3H-1-NA accumulated as well as the rate of uptake was decreased. Digitoxin and ouabain were equipotent; however, digoxin was significantly less potent. Tissues from different mamalian specis did not exhibit the same degree of sensitivity to the inhibitory effect of cardiac glycosides on 3H-1-NA accumulation. Dogs were most sensitive and guinea-pigs an order of magnitude less sensitive. Rats were least sensitive by roughly two orders of magnitude when compared with guinea-pigs. The relationship of the effect of digitalis on 3H-1-NA accumulation to digitalis-induced cardiac arrhythmias is discussed. Finally, the pattern of species sensitivity found here is compared with that observed in relation to inhibition of Na+-K+-ATPase by cardiac glycosides.


Ouabain cardiotoxicity, a reassessment of methodology. The capacity of ouabain (1 mug/kg/min and 2 mug/kg/min) to induce cardiotoxicity was explored in control cats and cats after spinal cord transection. In cats receiving 1 mug/kg/min, a higher dose of ouabain was needed to produce lethal arrhythmias in spinal cats compared to intact cats. However, in cats receiving 2 mug/kg/min, there was no difference in dose to death between intact and spinal cats. At death, the serum level and ventricular contents of ouabain was higher in animals with spinal cord transection regardless of the rate of ouabain infusion. Thus it appears that determination of the myocardial tissue digitalis concentration more accurately reflects the state of digitalis sensitivity than the administered dose. Additionally, seemingly paradoxical findings with regard to dose are explicable when serum and tissue concentration are simultaneously evaluated.


Haemodynamic effects of prazosin.

Haemodynamic effects of prazosin. Parzosin, 0.001 to 10 mg/kg, was administered intravenously to anesthetized normal rats. In the dose range 0.001 to 0.01 mg/kg, the drug induced highly significant, dose-related falls in blood pressure, pulse pressure and heart rate. With doses above 0.01 mg/kg, there was a plateau in hypotensive efficacy and a diminution in negative chronotropic activity. Both actions of prazosin (0.01 mg/kg) were unaffected by vagal blockade with atropine, while hypotensive potency was unimpaired after beta-adrenoreceptor blockade. The vasodilator, diazoxide, lowered blood pressure, widened pulse pressure and caused tachycardia in rats pre-treated with pentolinium. In contrast, all effects of prazosin were abolished by ganglion blockade. These findings, together with the absence of compensatory tachycardia or gross renin hypersecretion during prazosin-induced hypotension, are compatible with an antisympathotonic mode of action for the drug. However, consistent with its effects on cyclic nucleotide distribution, prazosin appears to enhance isoprenaline-induced beta-receptor stimulation.


On the mechanism of action of bombesin on gastric and pancreatic secretion of the chicken. The present experiments have been carried out in order to establish whether the stimulatory effect of bombesin on the chicken gastric acid secretion is a direct effect or is mediated by the release of hormones, such as the Avian Pancreatic Petide and/or Gastrin. removal of the pancreas, which is known to be the site of starage of the Avian Pancreatic Polypeptide, does not produce any decrease of the stimulant effect of bombesin on gastric secretion. Removal of the zone between the gizzard and duodenum, which shows histological features similar to those of the mammalian antrum and in which gastrin cells have been described, sharply decreases the basal values of gastric secretion as well as the stimulant effect of bombesin, while the effectiveness of caerulein, a gastrin-like peptide directly acting on oxintopeptic cells, is maintained. In chickens deprived of the duodenum-gizzard zone, bombesin shows a stimulant effect on pancreatic secretion indistinguishable from that observed in intact animals. It is concluded that the gastric but not pancreatic, action of bomtesin is mediated through the release of a factor(gastrin) from the gizzard-duodenum junction. Release of Avian Pancreatic Polypeptide from the pancreas is not involved in the mechanism of the action of bombesin on gastric secretion of the chicken.


The effect of apomorphine and haloperidol on the RNA content of brain structures of the rat. At a dose of 0.5 mg/kg, apomorphine caused an increase of the RNA content of the septal nucleus of rats (n. medialis + n. lateralis + n. accumbens); after 2.5 mg/kg this effect became more marked and, in addition, there was an increase of RNA in the caudate nucleus. All effects were antagonized by 0.5 mg/kg of haloperidol. These data suggest that apomorphine acts, at different dose levels, on different sites of the brain. This might be related to the also different behavioral effects of apomorphine at those two dose levels. Haloperidol on its own caused a fall of RNA in the amygdaloid nucleus which was not counteracted by any of the two doses of apomorphine. Neither drug had any influence on hypothalamic RNA concentration.


The local anesthetic activity of saxitoxin alone and with vasoconstrictor and local anesthetic agents. STX (saxitoxin), alone and with various vasoconstrictor and local anesthetic agents, was evaluated for its ability to produce topical anesthesia on the rabbit cornea, peripheral nerve block in the rat, and epidural anesthesia in the dog. High frequency and long duration of block can be attained if sufficiently high concentrations of STX are used, although latency is long and the doses used may produce systemic toxicity. Frequency of satisfactory blocks and mean duration of block can be increased and systemic toxicity reduced if STX is administered with a vasoconstrictor agent. Conventional local anesthetic agents also enhance the nerve blocking activity of STX. When appropriate concentrations of STX, vasoconstrictor and local anesthetic agents are used, systemic toxic effects are not manifested and the blocks produced exhibit the rapid onset and high frequency of block characteristic of the local anesthetic agent and the remarkably long duration of STX.


Anti-ulcer activity of colloidal bismuth subcitrate in Shay-rats. The anti-ulcer action of colloidal bismuth subcitrate (CBS) was tested in rats with a ligated pylorus (the Shay preparation). The liquid form used in the clinic displayed a dose-related inhibition of gastric ulceration. the recently developed solid form appeared to be just as effective. On the other hand, non-processed, non-colloidal bismuth salts and the CBS vehicle blank were completely inactive. The anti-ulcer activity of CBS was found to be unrelated to its buffering capacity.


Effect of furosemide on renal hilar lymph flow. Furosemide is known to increase total renal blood flow. The purpose of this study was to determine the relationship between this hemodynamic change and renal hilar lymph flow. Renal blood flow was measured with an electromagnetic flowmeter placed on the left renal artery of anesthetized dogs. Lymph was collected from a cannulated hilar vessel. Urine volume loss was not replaced. In the first 10 min after furosemide (1 mg/kg i.v.), lymph flow was significantly increased and then declined toward control within 30 to 40 min. The decline in lymph flow lagged behind the decline in blood flow by about 10 min. In 11 experiments in which there was a significant increase in renal blood flow, renal hilar lymph flow also increased. In 5 experiments in which renal blood flow did not increase after furosemide, lymph flow also did not increase. In both groups, urine volume was significantly increased but the diuresis was less in the group in which renal blood flow and lymph did not increase. When hydrochlorothiazide (5 mg/kg, i.v.) was administered, neither renal blood flow nor hilar lymph flow was altered. The effect of equi-diuretic doses of furosemide and hydrochlorothiazide on renal tissue water content were compared. The amount of water present after furosemide was significantly greater than the amount present after hydrochlorothiazide. These data support the concept that changes in renal hilar lymph flow are more a consequence of changes in renal blood flow than in urine volume.


Olfactory nerve reconstitution in the homing pigeon after resection: ultrastructural and electrophysiological data. Homing pigeons were subjected to uni- or bilateral resection of the olfactory nerves. A control of the operated region carried out five months later, showed that the olfactory nerves were continuous from the olfactory mucosa to the bulb. Cross sections of the regenerated nerve, observed under the electron microscope, showed morphological alterations with respect to the normal. Total measurement of the cross surface of both olfactory nerves showed that the regenerated nerve is always smaller than the intact nerve; this is also apparent in the total number of the fibres counted. Electrophysiological tests, performed on the regenerated nerve showed that the conduction along the resected nerve is restored.


Effects of scopolamine and methscopolamine on acquisition and retention of rat one-way shuttle box behavior and total brain acetylcholine. The effects of scopolamine HBr (0.032 to 10.0 mg/kg), methscopolamine Br (1.0 and 10.0 mg/kg) and 0.36 mg/kg NaBr on acquisition and retention of one-way avoidance behavior and total brain acetylcholine (ACh) were studied in male albino rats. Compared to equimolar NaBr, scopolamine caused a dose-related impairment in acquisition of avoidance responding while methscopolamine did not. Retention of avoidance behavior in trained rats was also disrupted, but the detrimental effect was smaller and occurred only following large doses of scopolamine. The per cent escape behavior was not decreased by any of the treatments. It increased as avoidance was decreased. Scopolamine caused a dose-related increase in latency and avoidance and escape responding compared to equimolar NaBr. However, scopolamine increased the latency of avoidance at lower doses and to a greater degree than it increased the latency of escape. Escape latencies were significantly increased only at the largest dose (10 mg/kg). These dose-related effects of scopolamine were greater during acquisition than during retention. Small doses (0.032 mg/kg) shortened latency of avoidance during retention. Methscopolamine increased avoidance and escape latencies only at the largest dose (10 mg/kg). Scopolamine produced a dose-related decrease in brain ACh which correlated well with the per cent avoidance in acquisition (r = 0.95) and retention (r = 0.88) trials. It is concluded that a muscarinic cholinergic antagonist with central actions like scopolamine affects selective aspects of avoidance behavior in low doses, and that these changes are highly correlated with brain ACh levels.


Temporal distribution of rapid eye movements and related monophasic potentials in the brain stem following injection of an anticholinesterase. The temporal distribution of the horizontal rapid eye movements and the related monophasic potentials recorded from the ascending MLF following intravenous injection of o.i mg/kg of anticholinesterase has been investigated in precollicular decerebrate animals. In particular the intervals between individual MLF potentials occurring during successive REM episodes have been evaluated over a total period of 2000 sec on each experiment. 2. There was a bimodal distribution of intervals due to the fact that all the rapid eye movements and the related MLF potentials were grouped in bursts which occurred at quite regular intervals. 3. During the cholinergically induced episodes of REM, there were usually bursts of REM in one direction followed by bursts of REM in the opposite direction. The mean number of individual eye movements within each burst was 4.67 +/- 0.84, S.D., while the average interval between the individual eye movements corresponded to 167 +/- 36 msec, S.D. 4. There was a great regularity in the periodic occurrence of the bursts of REM. In particular the mean interval between the beginning of a burst of REM in one direction (i.e., towards the left side) and that of the next train oriented in the opposite direction (i.e., towards the right side) was 1.97 +/- 0.47 sec, S.D., while the mean interval between the beginning of this last train and that of the successive train oriented in the former direction corresponded to 2.97 +/- 0.48 sec, S.D. Moreover, the duration of the whole period corresponding to the interval between two successive bursts of REM oriented in the same direction (i.e., towards left or towards right) corresponded on average to 4.94 +/- 0.55 sec S.D. and 4.99 +/- 0.52 sec, S.D. respectively. 5. In addition to these "simple bursts" of rapid eye movements oriented in one direction, there were "complex bursts" in which an alternation of the individual eye movements within each burst was observed. In these instances the mean number of spikes was greater (5.35 +/- 1.20, S.D.) and the mean interval shorter 119 +/- 44 msec, S.D.) than those observed in the "simple bursts", About 10-15% of the bursts occurring during the cholinergically induced REM episodes were of the complex type. 6. These findings obtained from an individual experiment were confirmed in all the decerebrate animals treated with the same dose of anticholinesterase; only slight quantitative differences were detected from case to case. 7. Since the bursts of REM induced by the anticholinesterase depend upon the activity of the vestibular nuclei, it is postulated that cholinergic reticular neurons activate structures which show waxing and waning in their activity before acting on the vestibulo-oculomotor system. This system probably contains the inhibitory interneurons which transform the regularly modulated input into  a rhythmic vestibular output...


Study of genetic relationships among marine species of the genera Beneckea and Photobacterium by means of in vitro DNA/DNA hybridization. Strains representative of species of the marine genera Beneckea and Photobacterium were used as reference standards in in vitro DNA/DNA competition experiments. Within a given species, strains were found to be related by over 80% competition. (Competition was defined as the amount of radioactive DNA displaced by heterologous DNA relative to the amount displaced by homologous DNA.) On the basis of interspecies competition values (expressed as averages), the following groupings could be made: 1. "Photobacterium" fischeri was related to strain ATCC 15382 by a competition of 38% and was distinct from all the other strains tested (competition less than or equal to 11%). 2. The genus Photobacterium consisted of 3 species, P.phosphoreum, P.leiognathi, and a newly designated species, P.angustum (composed of non-luminous strains). The latter species was found to be related to P.leiognathi and P.phosphoreum by 56 and 28% competition, respectively, while P.phosphoreum was related to P.leiognathi by 29%. 3. In the genus Beneckea, 65% competition was detected between B.harveyi and B.campbellii as well as between B.parahaemolytica and B.alginolytica. These pairs of species were related to each other by 51-58% and to B.natriegens by 34-56% competition. A newly designated pathogenic species, B.vulnifica, appeared to have a low but significant relationship to all the above mentioned species of Beneckea. 4. Two biotypes, related by 68% competition, were recognized in the species B.splendida. Similarly, B.pelagia was found to consist of 2 biotypes related by a competition of 67%. The competition values between these species were 38-40%. 5. B.nereida, B.nigrapulchrituda, and "Vibrio" anguillarum had competition values less than or equal to 30% to each other as well as to other species of Beneckea. 6. With Vibrio cholerae as the reference standard, V.albensis was found to be related by a competition of 82%, while V.proteus and V.metschnikovii had competition values of 22 and 12%, respectively. These results suggested that V.albensis should be synonymized with V.cholerae, while the latter two organisms should remain distinct from this species. V.cholerae as well as the other terrestrial organisms tested did not appear to be significantly related to any of the marine strains (competition values less than or equal to 27%). The speciation derived from the results of the DNA/DNA competition experiments was compared to previous speciation based on phenotypic similarities.


Chemotaxis in Actinoplanes.

Chemotaxis in Actinoplanes. The chemotactic properties of spores of Actinoplanes brasiliensis were examined. The spores are attracted to chloride and bromide solutions but not to a number of organic compounds that are capable of supporting growth in chemically defined media. Chloride attraction has been tested in several other species of the genus and in a number of Actinoplanes strains isolated from soils. Some are attracted to chloride, but most strains are indifferent to the halide. In dense suspensions, the spores of A. brasiliensis show an apparent microaerophilic behavior. The ecolotical implications of the chemotactic properties of the A. brasiliensis spores are discussed.


Desulfuromonas acetoxidans gen. nov. and sp. nov., a new anaerobic, sulfur-reducing, acetate-oxidizing bacterium. Anaerobic sea or fresh water media with acetate and elemental sulfur yielded enrichments of a new type of strictly anaerobic, rod-shaped, laterally flagellated, Gram-negative bacterium. Three pure culture-strains from different sulfide-containing sea water sources were characterized in detail and are described as a new genus and species Desulfuromonas acetoxidans. The new bacterium is unable to ferment organic substances; it obtains energy for growth by anaerobic sulfur respiration. Acetate, ethanol or propanol can serve as carbon and energy source for growth; their oxidation to CO2 is stoichiometrically linked to the reduction of elemental sulfur to sulfide. Organic disulfide compounds, malate or fumarate are the only other electron acceptors used. Butanol and pyruvate are used in the presence of malate only; no other organic compounds are utilized. Biotin is required as a growth factor. The following dry weight yields per mole of substrate are obtained: in the presence of sulfur: 4.21 g on acetate, 9.77 g on ethanol; in the presence of malate: 16.5 g on acetate, 34.2 g on ethanol and 46.2 g on pyruvate. Accumulations of cells are pink; cell suspensions exhibit absorption spectra resembling those of c-type cytochromes (abs. max. at 419, 523 and 553 nm). Malate-ethanol grown cells contain a b-type cytochrome in addition. In the presence of acetate, ethanol or propanol, Desulfuromonas strains form robust growing syntrophic mixed cultures with phototrophic green sulfur bacteria.


The effect of a non-metabolizable analog on mandelate catabolism in Pseudomonas putida. DL-2,3,4,5,6-pentafluoromandelic acid (PFM) specifically inhibits the growth of Pseudomonas putida (ATCC 12633) on medium containing mandelate as sole carbon and energy source by competitive inhibition of mandelate dehydrogenase. PFM is not metabolized and is neither an inducer of the mandelate catabolic enzymes nor an antagonist of induction. Mutants resistant to the inhibitory effects of PFM (PFMr) were isolated; most prove to be superinducible, i.e. synthesize corrdinately the mandelate-specific catabolic enzymes at elevated levels following induction. In at least one case the PFMr mutation maps very near the structural genes that encode the enzymes functional in the first two steps of mandelate catabolism. It is reasoned that the PFMr mutation is of the promotor type. Resistance to substrate analogs such as PFM offers a general method for isolation of regulatory mutants in catabolic metabolism.


Characterization of a benzoate permease mutant of Pseudomonas putida. A spontaneous mutant of Pseudomonas putida (PRS 2017) has been isolated which is incapable of growth on benzoate, does not induce the enzymes of the catechol branch of the beta-ketoadipate pathway when grown in the presence of benzoate, cannot accumulate radioactively labeled benzoate, yet grows well with mandelate as sole source of carbon and energy. This strain apparently lacks a benzoate permease, which in the wild type shows a Km of about 0.1 mM for benzoate, is inducible, and is not under the control of the regulatory system which governs the induction of the enzymes of the catechol branch of the beta-ketoadapate pathway. The lesion in PRS2017 is apparently single site and maps near other genes governing benzoate dissimilation.


The uptake of 2-ketogluconate by Pseudomonas putida. The uptake of 2-ketogluconate is inducible in Pseudomonas putida: 2-ketogluconate, glucose, gluconate, glycerol and glycerate were each good nutritional inducers of this ability. 2-Ketogluconate uptake obeyed saturation kinetics (apparent Km in 2-ketogluconate-grown cells was 0.4 mM). 2-Ketogluconate was transported against a concentration gradient, apparently in an unchanged state, and the process required metabolic energy, all of which indicate an active transport system. A number of independently isolated mutants with deranged activity of a common glucose-gluconate uptake system were found to be also defective in 2-ketogluconate transport. Strains unable to transport 2-ketogluconate which grew readily on glucose and gluconate were also isolated. These results suggest that 2-ketogluconate transport is governed by at least two genetic elements: one which is also required to take up glucose and gluconate and another which appears to be specific for 2-ketogluconate transport. Similarly, glucose and gluconate transport appears to require at least one factor which is not necessary for 2-ketogluconate transport, as suggested by the lack of induction of the common glucose-gluconate uptake system by glycerol and glycerate, substrates which are good inducers of 2-ketogluconate uptake.


The bacterial oxidation of nicotinic acid. N-formylmaleamic and N-formylfumaramic acids. N-Formylmaleamic acid, a probable intermediate in the bacterial metabolism of nicotinic acid, has been synthesized by photoisomerization of its trans isomer, N-formylfumaramic acid. The compound previously reported to be N-formylmaleamic acid has been shown to be N-formylfumaramic acid.


Fatty acid composition of selected prosthecate bacteria. The cellular fatty acid composition of 14 strains of Caulobacter speices and types, two species of Prosthecomicrobium, and two species of Asticcacaulis was determined by gas-liquid chromatography. In most of these bacteria, the major fatty acids were octadecenoic acid (C18:1), hexadecenoic acid (C16:1) and hexadecanoic acid (C16:0). Some cyclopropane and branched chain fatty acids were detected in addition to the straight chained acids. Hydroxytetradecanoic acid was an important component of P.enhydrum but significant amounts of hydroxy acids were not detected in other prosthecate bacteria examined.


Bacterial carotenoids. L. Absolute configuration of zeaxanthin dirhamnoside. Zeaxanthin dirhamnoside is the major carotenoid of Corynebacterium autotrophicum. The absolute configuration 3R,3'R followed from CD-properties of its hexaacetate, alpha-L-assignment and 1C4 conformation were concluded from 1H NMR data by comparison with model compounds.


Enzymatic synthesis of poly-beta-hydroxybutyrate in Zoogloea ramigera. The enzyme activity synthesizing poly-beta-hydroxybutyrate (PHB) was mainly localized in the PHB-containing particulate fraction of Zoogloea ramigera I-16-M, when it grew flocculatedly in a medium supplemented with glucose. On the other hand, the enzyme activity remained in the soluble fraction when the bacterium grew dispersedly in a glucose-starved medium. The soluble PHB synthase activity became associated with the particulate fraction as PHB synthesis was initiated on the addition of glucose to the dispersed culture. Conversely, the enzyme activity was released from the PHB-containing granules to the soluble fraction when the flocculated culture was kept incubated without supplementing the medium with glucose. PHB synthase was also incorporated into the newly formed PHB fraction when partially purified soluble PHB synthase was incubated with D(-)-beta-hydroxybutyryl CoA in vitro. Although attempts to solubilize the particulate enzyme were unsuccessful, and the soluble enzyme became extremely unstable in advanced stages of purification, both PHB synthases had the same strict substrate specificity for D(-)-beta-hydroxybutyryl CoA, and showed the same pH optimum at 7.0.


On the mechanism of salt tolerance. Production of glycerol and heat during growth of Debaryomyces hansenii. As glycerol was suggested as an osmotic agent in the salt tolerant Debaryomyces hansenii the concentrations of total, intracellular, and extracellular glycerol produced by this yeast was followed during growth in 4 mM, 0.68 M, and 2.7 M NaCl media. The total amount of glycerol was not directly proportional to biomass production but to the cultural salinity with maximum concentrations just prior to or at the beginning of the stationary phase. In all cultures the cells lost some glycerol to the media, at 2.7 M NaCl the extracellular glycerol even amounted maximally to 80% of the total. A distinct maximum of intracellular glycerol, related to dry weight or cell number, appeared during the log phase at all NaCl concentrations. As the intracellular calculated glycerol concentrations amounted to 0.2 M, 0.8 M, and 2.6 M in late log phase cells at 4mM, 0.68 M, and 2.7 M NaCl, respectively, whereas the corresponding analysed values for the glycerol concentrations of the media were 0.7 mM, 2.5 mM, and 3.0 mM, glycerol contributes to the osmotic balance of the cells. During the course of growth all cultures showed a decreasing heat production related to cell substance produced, most pronounced at 2.7 M NaCl. At 2.7 M NaCl the total heat production amounted to--1690 kJ per mole glucose consumed in contrast to--1200 and--1130 kJ at 4 mM and 0.68 M NaCl, respectively. The Ym-values were of an inverse order, being 129, 120, and 93 at 4 mM, 0.68 M, and 2.7 M NaCl respectively.


Purification, some properties and quaternary structure of the D-ribulose 1,5-diphosphate carboxylase of Alcaligenes eutrophus. D-Ribulose 1,5-diphosphate carboxylase has been purified from autotrophically grown cells of the facultative chemolithotrophic hydrogen bacterium Alcaligenes eutrophus. The enzyme was homogeneous by the criteria of polyacrylamide gel electrophoresis. The molecular weight of the enzyme was 505000 determined by gel filtration and sucrose density gradient centrifugation, and a sedimentation coefficient of 18.2 S was obtained. It was demonstrated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis that the enzyme consists of two types of subunits of molecular weight 52000 and 13000. Electron microscopy on the intact and the partially dissociated enzyme lead to the construction of a model for the quaternary structure of the enzyme which is composed of 8 large and 8 small subunits. The most probable symmetry of the enzyme molecule is 4:2:2. Michaelis constant (Km) values for ribulose 1,5-diphosphate, Mg2+, and CO2 were 0.59 mM, 0.33 mM, and 0.066 mM measured under air. Oxygen was a competitive inhibitor with respect to CO2 suggesting that the enzyme also exhibits an oxygenase activity. The oxygenolytic cleavage of ribulose 1,5-diphosphate was shown and a 1:1 stoichiometry between oxygen consumption and 3-phosphoglycerate formation observed.


Spirochaeta halophila sp. n., a facultative anaerobe from a high-salinity pond. A facultatively anaerobic spirochete isolated from a high-salinity pond grew optimally when 0.75 M NaCl, 0.2 M MgSO4, and 0.01 M CaCl2 were present in media containing yeast extract, peptone, and a carbohydrate. The organism failed to grow when any one of these three salts was omitted from the medium. Aerobically-grown colonies of the spirochete were red, whereas anaerobically-grown colonies showed no pigmentation. Non-pigmented mutants of the spirochete were isolated. The spirochete used carbohydrates, but not amino acids, as energy sources. Glucose was fermented to CO2, H2, ethanol, acetate, and a small amount of lactate. Determinations of radioactivity in products formed from glucose-1-14C and enzymatic assays indicated that glucose was dissimilated to pyruvate mainly via the Embden-Meyerhof pathway. Pyruvate was metabolized through a clostridial-type clastic reaction. Cells growing aerobically performed an incomplete oxidation of glucose mainly to CO2 and acetate. Comparison of aerobic and anaerobic growth yields indicated that oxidative phosphorylation occurred in cells growing aerobically. The guanine + cytosine content of the DNA of the spirochete was 62 moles %. It is proposed that the spirochete described herein be considered a new species and that it be named Spirochaeta halophila.


Growth and pigment production by Arthrobacter pyridinolis n. sp. A new bacterium capable of growing on 2-hydroxypyridine as sole source of carbon and nitrogen was isolated from soil. During its growth on solid medium, approximately 50% of this substrate was converted to a brilliant blue crystalline pigment which was deposited extracellularly in the colony mass. The pigment was identical to that produced by Arthrobacter crystallopoietes during its growth on 2-hydroxypyridine. The new isolate exhibited the typical cycle of morphogenesis characteristic of the genus Arthrobacter. The organism is different from all other reported species of Arthrobacter. It is proposed that the organism be named Arthorbacter pyridinolis n. sp.


Hyphal tip growth in Phytophthora. Gradient distribution and ultrahistochemistry of enzymes. Germinating cysts and isolated walls from germinating cysts incorporated 14C-UDPG into wall material of which 22.5 and 15% respectively were insoluble in boiling 1 N HCl, indicating that part of the synthetase activity is located in the wall itself. A combination of Urografin and Ficoll density gradients was used to separate various intracellular fractions. A consistent separation of beta-glucanase and UDPG-transferase enriched fractions was achieved. The beta-glucanase fraction contained dictyosome vesicles and fragments along with some plasma membranes. The UDPG-transferase fraction was relatively rich in membranes resembling rough and smooth ER. The results suggest the two enzymes are transported to the wall by different intracellular routes, and two types of vesicle may be involved. Alkaline phosphatase, beta-glucosidase and acid phosphatase were found extracellularly and their distribution in density gradients determined. The results of histochemical staining for acid phosphatase, alkaline phosphatase and polysaccharide are described and compared with the biochemical data. beta-1,3-glucanase, found intra- and extracellularly, induced distorted growth of germ tubes and also removed most of the apical wall when added to the incubation medium. None of these responses were observed with cellulase. Determinations of the osmotic pressure of germinating cysts and incubation medium revealed that the turgor of germinating cysts amounts to about 1.8 at under the conditions used.


Photorespiration in diatoms. IV. Two pathways of glycolate metabolism in synchronized cultures of Cylindrotheca fusiformis. Cylindrotheca fusiformis is shown to be able to convert glycolate to glycerate via tartronic semialdehyde as well as by the better known route involving transamination to glycine. Enzymes related to photorespiration were compared in light-dark synchronized cultures of C. fusiformis kept in continuous light in a complete synthetic seawater medium or starved for nitrogen or silicon. Glycolate oxidation remained constant throughout the cell cycle and was unaffected by starvation. Transamination of glyoxylate was stimulated by light, inhibited during nitrogen starvation, and dramatically stimulated by reintroduction of nitrate to the medium. Glyoxylate carboligase was also stimulated by light and inhibited during nitrogen-starvation but only partially recovered activity after reintroduction of nitrate.


Chemical and biochemical studies for the differentiation of coagulase-positive staphylococci. The cell wall composition, the configuration of lactic acid produced from glucose under anaerobic conditions, the occurrence of fructose-1,6-diphosphate (FDP) activated L-lactate dehydrogenase (L-LDH), and the esterase pattern were determined from more than 80 strains of coagulase-positive staphylococci isolated from man and animal. Strains isolated from man, swine, bovines and hares form a rather homogeneous group. They exhibit a similar cell wall composition, produce predominantly D,L-lactate and have a characteristic and simple esterase pattern. Coagulase-positive staphylococci isolated from dogs, horses, minks and pigeons are quite distinct from typical Staphylococcus aureus strains. They exhibit a different cell wall composition, produce only L-lactate, possess an L-LDH which is specifically activated by FDP, and have a quite complex esterase pattern.


Regulation of amino acid transport in growing cells of Streptomyces hydrogenans. II. Correlation between transport capacity and growth rate in chemostat cultures. The uptake of various amino acids into Streptomyces hydrogenans grown in chemostatically and turbidostatically controlled steady state cultures has been investigated. A close correlation between transport capacity and the growth rates of the cells was found. As shown by kinetic analysis, the increased transport is due to elevated maximum uptake rates, the apparent Michaelis constants remaining unchanged. Analysis of the unidirectional fluxes of cycloleucine revealed that not only the influx is raised as the growth rate is increased but also the efflux. Hence, the conclusion is drawn that the growth-rate dependent modulation of transport capacity is, at least, partially due to the variation of the concentration of active transport components. Since the cells were grown in the absence of external amino acids the results suggest that amino acid transport into S. hydrogenans is under control of endogenous effectors.


The role of energy-spilling reactions in the growth of Klebsiella aerogenes NCTC 418 in aerobic chemostat culture. When cell-saturating amounts of glucose and phosphate were added to steady state cultures of Klebsiella aerogenes that were, respectively, glucose- and phosphate-limited, the organisms responded immediately with an increased oxygen consumption rate. This suggested that in neither case was glucose transport the rate-limiting process, and also that organisms must possess effective mechanisms for spilling the excess energy initially generated when a growth-limitation is temporarily relieved. Steady state cultures of mannitol- or glucose-limited organisms also seemingly generated energy at a greater rate than was required for cell synthesis since gluconate-limited cultures consumed oxygen at a lower rate, at each corresponding growth rate, than did mannitol- or glucose-limited cultures, and therefore expressed a higher YO value. Thus, mannitol- and glucose-limitations must be essentially carbon (and not energy) limitations. The excess energy generated by glucose metabolism is one component of "maintenance" and could be used at lower growth rates to maintain an increased solute gradient across the cell membrane, imposed by the addition of 2%, w/v, NaCl to the growth environment. The maintenance rates of oxygen consumption of K. aerogenes also could be caused to increase by adding glucose discontinuously (drop-wise) to a glucose-limited chemostat culture, or by exchanging nitrate for ammonia as the sole utilizable nitrogen source. The significance of these findings to an assessment of the physiological factors circumscribing energy-spilling reactions in aerobic cultures of K. aerogenes is discussed.


Induction of D-6-hydroxynicotine oxidase in resting cells of Arthrobacter oxidans. Resting cell suspensions of Arthrobacter oxidans were shown to synthesize the inducible enantiozyme, D-6-hydroxynicotine oxidase, in the presence of D-nicotine or D-6-hydroxynicotine. The corresponding L-enantiomers, as well as gamma-methylaminopropyl-(6-OH-pyridyl-3)-ketone, which is the product of the reaction catalyzed by the enzyme, were ineffective as inducers. L-6-Hydroxynicotine inhibited induction by D-nicotine and D-6-hydroxynicotine while L-nicotine inhibited induction by D-6-hydroxynicotine and had no effect on induction by D-nicotine. Enzyme induction was also found to be inhibited by glucose, 2-deoxy-D-glucose and by several intermediates of the tricarboxylic acid cycle. An absolute requirement for protein synthesis and for oxygen was also demonstrated to be necessary for the reactions involved in the covalent attachment of flavin adenine dinucleotide to pre-existing precursor protein to yield the catalytically active D-6-hydroxynicotine oxidase.


Growth of Hansenula polymorpha in a methanol-limited chemostat. Physiological responses due to the involvement of methanol oxidase as a key enzyme in methanol metabolism. Hansenula polymorpha has been grown in a methanol-limited continuous culture at a variety of dilution rates. Cell suspensions of the yeast grown at a dilution rate of 0.16 h-1 showed a maximal capacity to oxidize excess methanol (QmaxO2) which was 1.6 times higher than the rate required to sustain the growth rate (QO2). When the dilution rate was decreased to 0.03 h-1, QmaxO2 of cells increased to a value of more than 20 times that of QO2. The enzymatic basis for this tremendous overcapacity for the oxidation of excess methanol at low growth rates was found to be the methanol oxidase content of the cells. The level of this enzyme increased from 7% to approximately 20% of the soluble protein when the growth rate was decreased from 0.16 to 0.03 h-1. These results were explained on the basis of the poor affinity of methanol oxidase for its substrates. Methanol oxidase purified from Hansenula polymorpha showed an apparent Km for methanol of 1.3 mM in air saturated reaction mixtures and the apparent Km of the enzyme for oxygen was 0.4 mM at a methanol concentration of 100 mM. The involvement of an oxygen dependent methanol oxidase in the dissimilation of methanol in Hansenula polymprpha was also reflected in the growth yield of the organism. The maximal yield of the yeast was found to be low (0.38 g cells/g methanol). This was not due to a very high maintenance energy requirement which was estimated to be 17 mg methanol/g cells X h.


The characterization of the rumen bacterium Eadie's oval, Magnoovum gen. nov. eadii sp. nov. The rumen bacterium Eadie's Oval was examined by means of cell wall analysis and biochemical tests with a view to determine its taxonomic position. The purified cell walls contained components consistent with the organism being a Gram-negative bacterium, and despite its large size no abnormal cell wall constituents were found. The biochemical tests indicate that Eadie's Oval is not a member of a previously described family. The name Magnoovum gen. nov. eadii sp. nov. is proposed.


Acetate metabolism in Rhodopseudomonas gelatinosa and several other Rhodospirillaceae. When Rhodopseudomonas gelatinosa was grown on acetate aerobically in the dark both enzymes of the glyoxylate bypass, isocitrate lyase and malate synthase, could be detected. However, under anaerobic conditions in the light only isocitrate lyase, but not malate synthase, could be found. The reactions, which bypass the malate synthase reaction are those catalyzed by alanine glyoxylate aminotransferase and the enzymes of the serine pathway. Other Rhodospirillaceae were tested for isocitrate lyase and malate synthase activity after growth with acetate; they could be divided into three groups: 1. organisms possessing both enzymes; 2. organisms containing malate synthase only; 3. R. gelatinosa containing only isocitrate lyase when grown anaerobically in the light.


Macromolecular synthesis and cell division during morphogenesis of Arthrobacter crystallopoietes. The sphere-rod-sphere morphology cycle of Arthrobacter crystallopoietes was accompanied by changes in the rate of growth and the rates of DNA, RNA and protein synthesis. The patterns of macromolecule synthesis resembled those found in other bacteria during a step-up followed by a step-down in growth rate. During the step-up in growth spherical cells grew into rods and macromolecules were synthesized in the absence of cell division. During step-down, successive rounds of septation produced progressively smaller cells which did not separate and remained in chains. The morphology of the cells was dependent on the growth rate and could be altered by changing the dilution rate in the malate-limited chemostat. Gradual transitions in morphology and gradual increases in macromolecule content of the cells occurred as the growth rate was increased in the chemostat. Sphere to rod morphogenesis occurred when DNA synthesis was inhibited by treatment with mitomycin C or by thymine starvation. The DNA-deficient rods did not divide and eventually lysed. DNA, RNA and protein synthesis were continuously required for the reductive division of rods to spheres.


Surface coat transformation and capsule formation by Leuconostoc mesenteroides NCDO 523 in the presence of sucrose. When Leuconostoc mesenteroides NCDO 523 was grown in MRS browth, electron microscopy of cells fixed in the presence of ruthenium red showed that the cell wall was covered with a thin layer of filamentous material. When MRS-grown cells were resuspended in the same medium supplemented with 3.6% sucrose, this surface coat doubled in thickness and a number of radial thickenings appeared within it. After 3 h, the filamentous component of the surface coat had disappeared leaving only the radial projections. The progressive accumulation of polymer to produce a capsule visible by light microscopy was observed in only about 20% of the population. In this minority of cells, a dense globular dextran composed of fibrillar and particulate elements was always produced in the initial stages of synthesis. After 18 h, the dextran capsule was generally composed of an inner globular and outer fibrillar layer. It appeared that the outer layer was derived from the globular dextran of the capsule by a process of dispersion.


S-formylgluthathione: the substrate for formate dehydrogenase in methanol-utilizing yeasts. Formaldehyde dehydrogenase and formate dehydrogenase were purified 45- and 16-fold, respectively, from Hansenula polymorpha grown on methanol. Formaldehyde dehydrogenase was strictly dependent on NAD and glutathione for activity. The Km values of the enzyme were found to be 0.18 mM for glutathione, 0.21 mM for formaldehyde and 0.15 mM for NAD. The enzyme catalyzed the glutathione-dependent oxidation of formaldehyde to S-formylglutathione. The reaction was shown to be reversible: at pH 8.0 a Km of 1 mM for S-formylglutathione was estimated for the reduction of the thiol ester with NADH. The enzyme did not catalyze the reduction of formate with NADH. The NAD-dependent formate dehydrogenase of H. polymorpha showed a low affinity for formate (Km of 40 mM) but a relatively high affinity for S-formylglutathione (Km of 1.1 mM). The Km values of formate dehydrogenase in cell-free extracts of methanol-grown Candida biodinii and Pichia pinus for S-formylglutathione were also an order of magnitude lower than those for formate. It is concluded that S-formylglutathione rather than free formate is an intermediate in the oxidation of methanol by yeasts.


Transmission and scanning electron microscopy of the human ceruminous apocrine gland. I. Secretory glandular cells. The secretory portion of the apocrine sweat gland of the human external auditory meatus which is also called the ceruminous gland was observed by transmission and scanning electron microscopy. The secretory glandular cells contain a well developed smooth endoplasmic reticulum and Golgi apparatus. Cisternae of rough endoplasmic reticulum are often closely applied to large round mitochondria. These large mitochondria have no relationship to the secretory granules. Near the concave surface of the Golgi lamellae several tubules can be found. In these golgi-associated tubules a dark substance may accumulate to form specific large dense granules. Many less dense droplets or vacuoles may appear in these dark prosecretory granules and become liberated from their surface. Vacuoles formed in this manner then migrate to the apical cell surface and often discharge their contents into the gland lumen by the mechanism of exocytosis. Also, some of these vacuoles may be released into the lumen by the pinching off of small protrusions of cytoplasm, that is, they are released by the so-called apocrine secretory mechanism. Acid phosphatase activity was demonstrated not only in the dark prosecretory granules but also in clear vacuoles situated at the apical end of the cell and in the gland lumen. Such a histochemical finding may indicate that the secretory substance of the apocrine sweat gland may contain hydrolytic enzymes derived from lysosomes, which are the prosecretory granules of this gland, and these enzymes may play a role in dissolution and break down of the material extruded into the lumen by apocrine secretion. Apocrine secretory process of various sizes were observed on the luminal surface with the scanning electron microscope.


Transmission and scanning electron microscopy of the human ceruminous apocrine gland. II. Myoepithelial cells. The myoepithelial cells of the human ceruminous apocrine gland were observed with transmission and scanning electron microscopes. The myoepithelial cells are long fibrous cells about 100-150 mum in length and 3-5 mum in width. They are arranged in parallel with each other, and their long axes are parallel to that of the secretory tubule itself. The tips of cells are often sharply pointed and their lateral tapering surface may be contiguous with adjacent cells forming a side-by-side contact, while other cells may have a blunt tip which is conjuncted with a similar tip of the next cell forming an end-to-end junction. The myoepithelial cells are joined to each other by desmosomes and there are also desmosomes at their junction with secretory cells. The outer surface of the cell abutting on the basal lamina has some exaggerated densities which are undoubtedly identical to the hemidesmosomes of epidermal cells. There are well developed foldings in the plasma membrane of the secretory cells, but the surface of the myoepithelial cells has very few foldings and projections. The relative shortage of intercellular attachment devices between the secretory and myeopithelial cells makes it easy to peel off the secretory cells to disclose the myoepithelium, a useful feature of scanning electron microscopy. The nucleus-containing part of the cell protrudes slightly upward and invades the secretory epithelium. The cytoplasmic rim surrounding the nucleus contains a small Golgi apparatus and some other organelles. The cytoplasm of the basal half of the cell contains closely packed myofilaments running parallel to the long axis of the cell. There is no definite arrangement of thin and thick myofilaments. Microtubules which often occur in pairs are arranged parallel to the myofilaments.


An electron microscopic study on the innervation in the taste buds of the mouse circumvallate papillae. Taste buds of the mouse circumvallate papillae were studied by electron microscopy to elucidate the innervation involving the adrenergic nerve supply. Typical afferent synaptic contacts, with increased density of the membranes and aggregations of synaptic vesicles in the cytoplasm adjacent to the nerve endings, were demonstrated between the type III cells and the nerve endings. Along the regions of contact between the type II cells and the nerve endings, cisternae of endoplasmic reticulum were often seen beneath the cell membrane, and the nerve endings contained relatively many synaptic-sized vesicles. Such an innervation seems to be efferent in nature. For the detection of the adrenergic nerve supply, 5-hydroxydopamine (5-OH-DA) was injected after pretreatment with L-DOPA and nialamide. The mice showed numerous adrenergic nerve fibers in the connective tissue underlying the taste buds. On very few occasions, the adrenergic nerves penetrated the basal lamina of the taste buds and came into contact with the bud cells. Some adrenergic nerves were distributed among the epithelial cells around the taste buds. The reaction product from acetylcholine esterase activity was found around the adrenergic nerve fibers labeled with 5-OH-DA.


Microcirculation of the rat small intestine as studied by the injection replica scanning electron microscope method. Mucosal blood supply in the rat small intestine was studied by the injection replica scanning electron microscope method. The blood vascular plexus in the villus is originated at the tip of the villus and confluenced near the base of the villus. This supports the classical "fountain pattern" of MALL in the villous microcirculation. The capillary plexus in the crypt is derived at the base of the crypt and converged near the base of the crypt. The capillary plexuses in the villus and the crypt communicate with each other. It is considered that the basal segment of the villus, where the arterial termination is lacking, is supplied by the cryptal capillaries via this communication.


Scanning electron microscopic study on the saccus vasculosus of the rainbow trout. Both free and cracked surfaces of the saccus vasculosus in adult rainbow trout (Salmo gairdneri) have been investigated by scanning electron microscopy (SEM). The saccus vasculosus is the rich-folded epithelium composed of highly specialized coronet cells, supporting cells, and presumable liquor-contact neurons. The coronet cells are characterized by both numerous specialized cilia, so-called "globules" projecting into the saccus lumen and abundant smooth endoplasmic reticulum in the cytoplasm. By the appearance of these globules, coronet cells are roughly divided into two types: botryoidal coronet cells and flower-like. The former is supplied with grape-shaped globules, whose density is 60-80 pieces a cell. The latter contains club- or petal-shaped globules, which number 50-60 pieces a cell. The functional significance of these globules is additionally discussed. The free surface of the supporting cells is relatively smooth, and short microvilli lie scattered on the surface. The cells called liquor-contact neurons (the third type) possess a head-like protrusion where long solitary cilia can be recognized.


Changes in glucoamylase activity under the influence of drugs affecting the adrenergic receptors in myocardium and skeletal muscle. The activity of neutral glucoamylase and alpha-amylase were determined in the myocardium and skeletal muscle after in vivo pharmacologic stimulation of adrenergic receptors. The activity changes of these enzymes were found to not always occur parallelly. The activity of both these enzymes is decreased under beta-agonistic influence of isoprenaline, adrenaline, as well as under the influence of acetylcholine. On the other hand, alpha-agonistic function of phenylephrine mainly results in the increase of neutral glucoamylase activity. Similar effects are obtained by suprarenal ligation. The above pharmacological effects did not appear when the said pharmacologic drugs were added to incubated muscle extracts.


Synthesis and pharmacologic properties of pyridoyl derivatives of 3-methylaminoindole 2-methyltryptamine and isotryptamine. Six new pyridoyl derivatives of 3-methylaminoindole, 2-methyltryptamine and isotryptamine were synthesized by condensation with chlorides of nicotinic and isonicotinic acids. The central action of these compounds seems to depress the central nervous system, as they reduce spontaneous motility (I, II, IV, V, VI) and amphetamine hypermotility (II, IV, V), prolong hexobarbital sleeping time (II, IV, V, VI), display analgesic action in the "writhing test" (all compounds) and in the "hot plate test" (IV, V). The compounds do not change body temperature and display no anticonvulsant action.


Search for new aminoguanidine derivatives with immunosuppressive and cytostatic properties. II. Synthesis of cyclic derivatives of amino-, nitroamino-, and diaminoguanidine.


Potential acetylcholinesterase reactivators: oxime and amidoxime derivatives. Out of 12 oximes and amidoximes (3 of which were new to the literature) the following showed a distinct antilethal effect in DFP poisoning: RA14 (1-methylbenzimidazole-2-aldoxime methiodide), RA14 (pyridine-4-aldoxime dodecyl bromide), and RA24 (pyridine-2-aldoxime dodecyl bromide). These compounds also reactivated acetylcholinesterase (AChE) in vitro, but had no effect on this enzyme in vivo. Moreover, addition of the dodecyl chain to pyridinealdoxtimes, or in a less degree replacement of the pyridine ring with benzimidazole in aldoximes, distinctly increased acute toxicity and lipophilicity when compared with the parent pyridine compounds, along with protective action in DFP poisoning.


Evaluation of the influence of epoxide resins and their hardeners on the female body. II. Biochemical studies. In women employed in an industrial plant in direct contact with epoxide resins and their hardeners, the following biochemical parameters were determined in blood: total protein, seromucoid, haptoglobin, hemoglobin variants, methemoglobin, alpha1-inhibitor of trypsin, lactate dehydrogenase, aspartate and alanine aminotransferases, alkaline and acid phosphatase, gamma-glutamyl transpeptidase, leucylaminopeptidase, and alanine aminopeptidase. Depending on duration of work, Hb A2 fraction and lactate dehydrogenase increased significantly, and aspartate aminotransferase, acid and alkaline phosphatase activities decreased. In pregnant women, leucylaminopeptidase activity and isozyme of placental alkaline phosphatase were decreased.


Hydroproteolytic activity of the pancreas after single or fractionated x-ray irradiation of rats. The enzymic activity of lipase, lysosomal markers (beta-glucuronidase and acid phosphatase) and cathepsin was checked in the pancreatic subcellular fraction of control and whole-body X-irradiated rats. Incubation of granules (zymogen and mitochondrial fraction) under hypoosmotic conditions resulted in greater activity of lipase and cathepsin in the irradiated than in the control group. However, formation of different pattern of enzymatic activity was found (both in the sediments and in the supernatant) in single and fractionated irradiated pancreas.


Flashbacks: a personal follow-up.

Flashbacks: a personal follow-up. During the period 1971-1973, it was found that 53 out of 91 young drug abusers in a psychiatric hospital had experienced flashbacks. This applied to as many as 50 out of the 65 patients who had used LSD, but also to abusers of organic solvents and cannabis. As many as 38% of the patients were found to be severely incapacitated by their flashbacks. On a personal follow-up 1 1/2-4 years after the first therapeutic contact, 35 patients were still troubled by flashbacks. On the whole reactions were less intense than at the time of the first contact. No relation between the flashbacks and protracted psychotic development could be established. The overall clinical and social course was worse for patients with flashbacks than for the rest of the population. Patients still bothered by flashbacks used drugs and alcohol as sedatives to a greater extent than the rest.


Restricted associations of aphasics and schizophrenics. Matched groups (N = 25) of fluent and nonfluent aphasics, brain-damaged and normal controls as well as schizophrenics were requested to name (1) as many animals and (2) as many things that are typically yellow as possible within 5 min. The main results of Gloning & Müller (1972) as to smaller numbers of correct responses, higher percentages of repetitions, shorter association clusters, and higher popularity in aphasics could be replicated for animal task. Comparing the data from both tasks for fluent and nonfluent aphasics with the various control groups led to considerable doubts as to what extent these results follow directly from quantitative differences in verbal output or have to be interpreted as qualitative differences in memory storage, retrieval, and self-editing processes.


Effects of selective sleep deprivation on sleep-linked prolactin and growth hormone secretion. 1. The secretion of prolactin and growth-hormone (hGH) was investigated during sleep in 10 healthy volunteers (8 males and 2 females): The comparison of one baseline night, one night after daytime physical exercise, and one night with selective deprivation of sleep stages 3 and 4 and paradoxical sleep showed clear differences of prolactin and hGH secretion during sleep. 2. Prolactin secretion is entrained into the sleep cycle of Non-REM and REM periods. A maximum of plasma hormone elevations occurs during the first quarter of sleep cycles, i.e., during Non-REM periods and less frequent rises at the end of the cycles, mainly during REM periods. 3. In contrast to growth hormone, concentrations of prolactin remain high also during later cycles occurring toward morning. This shows that high prolactin, but not high concentrations of hGH, regularly occur during sleep cycles with small amounts of slow-wave sleep. 4. Maximal prolactin concentrations during sleep are affected neither by preceding daytime physical exercise nor by selective deprivation of slow sleep stages 3 and 4. This is further evidence that slow-wave sleep stages are not necessary for the development of high plasma prolactin concentrations. However, peak values of growth hormone in the first and second cycle are significantly diminished after selective deprivation of sleep stages 3 and 4. 5. In abnormally long sleep cycles with artificial delay of the first REM period, the cyclical rhythmicity of prolactin release seems disturbed. This is further evidence for the sleep-dependent rhythmicity in the secretion of this hormone.


Season of birth and Schneider-oriented diagnosis of schizophrenia, "neurosis" and psychopathy. Most earlier studies and all studies on national samples in Scandinavia and in England and Wales have shown that schizophrenics have a significant excess of births in the early months of the year when compared with the expected distribution of the normal population. The present German study, carried out on schizophrenic patients diagnosed in a strongly Kurt Schneider--oriented clinic, in contrast to almost all other authors, demonstrated no such significant overrepresentation of births in the winter months. Thus, the findings of Danneel's (1973) German report, also utilizing Schneider-diagnosed schizophrenics, seem, at least for the present, to be confirmed.


The fate of pesticides in aquatic environment. II. Hydrolysis of dichlorvos in a model system and in river water.


Study of the lymphocyte in vitro response to rubella antigen and phytohemagglutinin by a whole blood method. A whole blood culture method was used to study lymphocyte in vitro responses to rubella antigen and to phytohemagglutinin (PHA) in rubella infection. The acute phase of infection in four cases was characterized by high spontaneous incorporation of 14C-thymidine in the cultures, unresponsiveness of lymphocytes to rubella antigen, and absence of response, or relatively low response, to PHA. Cells showing vigorous in vitro response to rubella antigen appeared at about two weeks after the onset of rash. Lymphocyte PHA response returned to normal by day 31. Three rubella vaccinees exhibited a similar response. The use of whole blood lymphocyte cultures stimulated with multiple doses of mitogen and with antigen appears to be a promising technique for studies of "general" and "specific" cell-mediated immunity in viral infections.


Pneumatosis cystoides intestinalis associated with jejunoileo bypass. A case report.


Nuclear medicine.

Nuclear medicine.


Radiology case of the month. Case no. 17.


The Arizona Maternal Mortality Committee.


Hairy women or hirsute patient?

Hairy women or hirsute patient?


Pemphigus -- a review.

Pemphigus -- a review.


Fourteen year cardiological follow-up of patients with high and low levels of low density lipoproteins. I. The value of low density lipoprotein determination in serum as a reliable prognostic index of future myocardial infarction.


Double-outled right ventricle concept and classification.


Presentation and detection of chronic renal disease in children and adults. Chronic renal failure develops slowly and insidiously in most patients. Prevention depends on the early detection and full assessment of the patient at risk. Indications for investigation in children and adults with glomerulonephritis and urinary infection are outlined.


Osteoporosis--some thoughts by a non-physician.


Investigation of urinary infection in childhood. The first proven urinary infection in both girls and boys should be investigated with an IVP and micturating cystourethrogram. If both investigations are normal, recurrent infections will not produce renal scars. Renal scars will develop in 10 per cent of children with reflux, unless renal infections are prevented by appropriate drug or surgical treatment.


SI units in clinical pathology.

SI units in clinical pathology. By now, most doctors in Australia will have had some experience with the new SI units which are being used for pathology test results, especially chemical pathology. While the usage of SI units has spread rapidly through public hospitals in Australia, spread in the non-hospital sector has been slower. However, the change will occur, and so the following is presented to assist general practitioners to understand the reasons for the change, and to interpret results expressed in the new system.


Geriatric nursing care--a philosophy.

Geriatric nursing care--a philosophy.


Problems in practice--head injury.

Problems in practice--head injury.


Survey of general practice--1971.

Survey of general practice--1971. In this survey an attempt has been made to document a profile of certain aspects of the work carried out by a general practitioner in Australia. This includes the type of practice, and especially the range and frequency of the procedures he carries out. It is realised that, as this survey was conducted in 1971, some of the facts may have become dated. However, a proportion of the information given is unobtainable elsewhere, and it is believed that through publishing the survey, interested readers may be prompted to seek additional information from the author.


Extending the role of the nurse into family practice.


Country doctors in Western Australia.

Country doctors in Western Australia.


Effects of the sympathetic nervous system and the adrenal medullary hormones on dog hind limb blood flow after haemorrhage. The contributions of the sympathetic nervous system and the adrenal medullary catecholamines to the response of dog hind limb resistance vessels to haemorrhage were examined. Anaesthetized dogs were bled either 30% or 45% of blood volume. There was little difference between the vascular conductance response in untreated hind limbs and sympathectomized limbs. Conductance in limbs that had been both sympathectomized and alpha-adrenergically blocked with phenoxybenzamine was markedly above that of untreated limbs. Blood flow in both the untreated limbs and the sympathectomized limbs was closely similar to that predicted from the pressure-flow curve for the hind limbs obtained in non-bled dogs. Flow was higher than predicted in the limbs with combined sympathectomy and alpha-adrenergic blockade. It is concluded that the sympathetic nervous system exerted little vasoconstrictive influence after haemorrhage, but that circulatory catecholamines exerted a strong vasoconstrictive influence that was opposed in the normal limbs by an almost equally powerful vasodilatory force of undetermined origin.


Release of gastrin by vagal stimulation in the acid secretory response to food. Gastric pouches were constructed in 8 dogs; in 4 they were of denervated type and in 4 the innervation was intact. An oesophageal fistula was then prepared in each dog. The acid secretory response to oral, tube and sham feeding was determined before and after denervation of the pyloric antrum. The results support the view that vagal release of gastrin makes a relatively small contribution to the total acid secretory response to food.


The origin of immunoglobulins in salivary secretion of sheep. A comparative study was made on the secretion of IgG1 and IgA into parotid and submaxillary saliva of sheep. The purpose of the study was to examine the suggestion that in the external secretory organs of ruminants there is an inverse relationship between the capacity to selectively transfer IgG1 and the development of the IgA secretory system. Despite a marked difference in the secretion of IgA between the parotid and submaxillary salivary glands, the magnitude of selective transfer of IgG1 was similar. Thus, there appears to be no relationship between the selective transfer of IgG1 and the secretion of IgA into the saliva of sheep.


An evaluation of selective broths based on the bi-selenite ion and on hypertonic strontium chloride in Salmonellae detection in egg products. Of the 104 isolations of Salmonella sp. from egg pulp, 97 were obtained from strontium chloride M broth, 42 from strontium selenite broth and 57 from strontium selenite A broth. The results suggest that the first medium may be used more successfully than bi-selenite based media for enrichment and subsequent detection of salmonellae in egg products; however, the growth of S. pullorum was not satisfactory in strontium chloride M broth.


Relationship between vasoconstriction and histamine induced vasodilation. Histamine produced significantly greater vasodilation in rabbit ear arteries constricted by noradrenaline than when the same arteries were constricted by either caffeine or barium. Histamine dilation in the presence of caffeine was also significantly greater than that in the presence of barium. These results suggest that histamine may produce vasodilation through at least two different modifications of intracellular calcium mobilisation.


Passive transfer of immunity to infection with Nematospiroides dubius from immunised mice to their offspring. The results given below show that, whilst it is not possible to transfer immunity to infections with Nematospiroides dubius passively with serum from immune mice to normal adult mice, young born to immune females are resistant to this infection. The immunity is dependent on an intake of immunoglobulin via the milk for a period longer than 24 h. The passive transfer of immunity from immune mothers to neonatal mice does not appear to be dependent on a specific class of immunoglobulins.