Community health screening in Taumarunui. Males and females 30 years and over were invited to participate in a community health screening project. Thirty percent of the target population did so. They were questioned on personal and family medical history, smoking and drinking habits and occupation. Height, weight, blood pressure and ECG were recorded. Haemoglobin, blood sugar, cholesterol and uric acid were analysed. Overweight, hypertension and hypercholesterolaemia were common. About one third of males and females smoked but 23 percent of males had given up smoking at the time of the survey.


A prospective study into thyroid disease in a geriatric unit. A prospective study of thyroid disease in 229 consecutive admissions to a geriatric rehabilitation ward are described. The overall prevalence of thyroid disease in this study was 6.98 percent. It was noted that clinical assessment and thyroid function in the elderly in this study were poorly correlated. The routine use of thyroid function tests in elderly people to detect cases of untreated and undetected thyroid disease is recommended.


The treatment and prevention of chronic otorrhoea in the Northland health district. The operation of a mobile ear clinic within the school medical service in Northland is described. The major justification for the use of a sophisticated unit lies in the opportunity which it affords for the education of children and adults on aural health. The higher costs of treatment may well be more than offset by the long-term benefits resulting from increased awareness and better understanding in our population on the causation of supporative otitis media.


Urinary fibrin degradation products in childhood acute nephritis. Fourteen children with acute post-streptococcal nephritis had daily measurements of urine fibrin degradation products (FDP) excretion during the acute phase of their illness. The amount of FDP excreted daily varied greatly but a general decrease occurred as other parameters showed resolution of the illness. Some children showed no increase in FDP output. We feel, however, this test may help in monitoring the progress of this illness in certain patients. Fibrin degradation products (FDP) are excreted in the urine in many forms of glomerulonephritis (Clarkson and others, 1971). The origin of the FDP is renal and not filtrated from the blood (Ekberg, Pandolfi, 1975). Clarkson further showed that in post-streptococcal glomerulonephritis there is a cessation of FDP excretion at the time of clinical recovery. We have studied a group of children with acute post-streptococcal nephritis in order to further assess the extent and possible value of daily FDP estimations in the management of patients during the acute phase of the disease.


Experiencing grief.

Experiencing grief.


Thyroid carcinoma and radiation therapy.


An experiment in public education.

An experiment in public education.


The New Zealand cancer registry.

The New Zealand cancer registry.


General practitioner training.

General practitioner training.


Report of the Royal Commission on contraception, sterilisation and abortion. The Commission's selection of poor quality data in reaching its conclusion in the chapter "Consequences of Abortion Refused," that being an unwanted child is not necessarily disadvantageous is criticized.  The Commission cited as evidence a newspaper article with questionable statistics and an unpublished study by Lenoski which said 99.1% of child abusers wanted their children, while only 63% of the nonabusers did.  The prime criterion was the month in which the mother began using maternity clothes.  Also, a quote from Helfer in 1968 is used, which the author failed to find and which seems to contradict Helfer's latest study (1976) which says infants born to mothers who were refused abortion are at risk of child abuse.  Strangely, a 21-year and a 10-year follow-up on children born after mothers were refused abortion were not used in the final version of the chapter, though they were discussed at the hearings.


IgE levels on milk and egg-free diets.

IgE levels on milk and egg-free diets.


Sjogren's syndrome in SLE: Part I. The frequency of the clinical and subclinical features of Sjogren's syndrome in patients with SLE. Clinical features of Sjogren's syndrome were found in 31 percent of 32 patients with SLE. Eight patients had features of KCS while four had xerostomia. Subclinical abnormalities were found in six other patients tested with sialography and labial salivary gland biopsy and there were abnormalities in 65 percent of SLE patients in whom labial salivary gland biopsy was performed. The prevalence of Raynaud's phenomenon and renal disease in SLE patients with and without Sjogren's syndrome were similar but four of the five patients with SLE and an erosive arthritis had symptomatic Sjogren's syndrome.


Sjogren's syndrome in SLE: Part 2. An examination of the clinical significance of Sjogren's syndrome by comparison of its frequency in typical and atypical forms of SLE, overlap syndromes and scleroderma. The clinical features of Sjogren's syndrome were found in 24 percent of Glasgow patients with SLE without other atypical features. Sjogren's syndrome was found in one (13 percent) of a group of eight patients with features of both SLE and scleroderma, one of three patients with features of both polymyositis and scleroderma and in three of 12 (25 percent) patients with scleroderma. The highest frequency of Sjogren's syndrome was seen in six patients with features of SLE and an erosive polyarthritis, five of whom (83 percent) had Sjogren's syndrome. In patients satisfying diagnostic criteria for SLE no relationship between the presence of Sjogren's and the presence or absence of renal disease was found.


Vitamin C status of elderly men in a residential home. The vitamin C status of 35 men, over 70 years of age from a residential home has been studied by measuring the plasma and leucocyte vitamin C levels and by assessing the intake of vitamin C. The mean plasma vitamin C level of the group was 16 +/- 15 mumol/l which was significantly lower (P less than 0.005) than that of a similar group of elderly men living alone (26 +/- 20 mumol/l). The mean leucocyte vitamin C levels of the two groups did not differ significantly. Twenty-nine (83 percent) of the institution group had plasma vitamin C levels below 23 mumol/l and 13 men (37 percent) had leucocyte vitamin C levels below 10 microgram/10(8)WBC. The residents who supplemented the institution diet with their own fresh fruit supplies had higher plasma and leucocyte vitamin C levels than the men who did not (P less than 0.01). Some clinical signs possible related to vitamin C deficiency were recorded but these could not later be statistically related to either plasma or leucocyte vitamin C levels. A case is made for vitamin C supplementation of puddings in institutional meals for the elderly.


The clinical significance of low urine oestriol values. Urine oestriol values from 327 pregnancies with antenatal complications were measured between 30 weeks gestation and term. Mean values were much lower than those obtained from pregnancies without complications. When infants were light for dates or developed evidence of neonatal morbidity, oestriol values were more likely to have been below the normal range than in pregnancies resulting in deliveries of normal infants. There was no evidence of severe fetal jeopardy in most pregnancies with oestriol values below normal. Perinatal death was consistently predicted when urine oestriol values lay below a line joining 35 mumol/day at 30 weeks and 65 mumol/day at term.


Intrauterine devices.

Intrauterine devices.


Myocardial infarct in the home.

Myocardial infarct in the home.


Relational ethics in medicine.

Relational ethics in medicine.


Abortion and rape.

Abortion and rape. The letter is an answer to a previous letter which appeared in the same journal and which was discrediting, according to the author of this letter, the Royal Commission on Contraception, Sterilization, and Abortion.  The earlier letter refutes a quote from "Abortion and Social Justice" used by the Commission, regarding the situation in Colorado after rape became an indication for abortion.  The quote reports that although between 1967-1971 the number of abortions for rape totalled 290, no rapist was charged or convicted for the crime.  However, according to the author of this letter, the actual quote reads somewhat differently, and states that, during the same period, "no rapist was ever charged with his crime, much less convicted of it, which casts some real doubts on the reality of the alleged rapes." The meaning of this passage is that none of the alleged rapists had actually caused the 290 pregnancies.  From records and government statistics it is possible to count about 3300 cases of rape known to the police in Colorado for the years 1967-1971.  To suggest that none of these cases were charged or convicted is ridiculous.  The author also states that rape as an indication for abortion will lead to abuse of the law, and that pregnancy for actual rape is rare.


Prevention of postoperative thrombo-embolism.


Prescribing information in drug advertisements. The need for continuing education in clinical pharmacology for practising doctors is seen in the light of a study of the prescribing information contained in recent New Zealand drug advertisements. Less than half of the advertisements contained details of dosage and only a quarter mentioned toxic effects.


Operative cholangiography in two hundred consecutive cholecystectomies. The records of two hundred consecutive patients undergoing cholecystectomy for gallstones in the university department of surgery, Christchurch Hospital, were reviewed to evaluate the benefit and standard of operative cholangiography. The main benefit lay in the avoiding of unnecessary common bile duct exploration. Of the cholangiograms later reviewed by an independent radiologist, only 70 percent were considered satisfactory.


How effective is a reversal procedure following a vasectomy? Twenty patients who have requested a reversal procedure following a bilateral vasectomy for sterilisation have been operated upon using a simple end-to-end anastomotic technique on each vas. In nine couples a successful pregnancy has followed, and in 14 of the 20 patients sperms have reappeared in the semen in normal numbers.


Parathyroid infarcts after tracheostomy.


Hospital consumerism.

Hospital consumerism.


The iron status of children with low leucocyte ascorbic acid levels. A group of young children who had low levels of leucocyte ascorbic acid had iron status assessed. Those children with low ascorbic acid had also concomitant low iron saturation of their blood. The significance of these findings is discussed.


Maori attitudes to sickness, doctors and hospitals.


Management and the medical profession.

Management and the medical profession.


Regular chest x-rays.

Regular chest x-rays.


Phenformin acidosis.

Phenformin acidosis.


ECHO virus 19 outbreak 1975-76.

ECHO virus 19 outbreak 1975-76.


Infection in a neonatal unit.

Infection in a neonatal unit.


Bacterial meningitis in children.

Bacterial meningitis in children. Cases of bacterial, non-tuberculous meningitis among Auckland children aged one month to 13 years were reviewed for the five year period September 1971 to September 1976. The aetiological agent was established in 203 of 227 cases. Haemophilus influenzae was the most frequent cause and together with Streptococcus pneumoniae accounted for all sequelae S. pneumoniae was responsible for most fatal cases. It is an unusually common cause of meningitis in Auckland, particularly in children under a year of age. Polynesians contracted bacterial meningitis almost four times as often as Europeans. For a Polynesian child the risk of death due to bacterial meningitis was 12 times that of European.


Endoscopic retrograde cholangiopancreatography (ERCP): an appraisal. Cannulation of the ampulla of Vater via a fiberoptic duodenoscope to obtain radiographic visualisation of biliary and pancreatic ductal systems is a new technique to many hospitals. The experience of the first fifty examinations by this technique at Auckland Hospital is reported. One serious complication was encountered and this responded to appropriate therapy. It is concluded that some of the difficulties of mastering the technique have been exaggerated and the contribution to management of biliary disease is firmly established. It is possible to diagnose several pancreatic disorders to a high confidence level by pancreatography, but this has not yet been proven to influence the patient's management.


The Lesch-Nyhan syndrome: a family study. Two brothers were found to have athetoid cerebral palsy, mental and growth retardation and evidence of self mutilation. One had passed a renal calculus and both had high serum uric acid levels. The diagnosis of Lesch-Nyhan syndrome was confirmed by the finding of low levels of hypoxanthine-guanine phosphoribosyl transferase in erythrocytes and by autoradiography of fibriblasts. The mother, maternal grandmother, a female sibling and a maternal aunt were identified as carriers of the X-linked mutation which was responsible for the enzyme deficiency in the two male siblings.


Cerebral monitoring by compressed spectral array. Application of a frequency analysis technique, the compressed spectral array (CSA), permits the display of cerebral activity recorded by the electroencephalogram (EEG) over long periods of time in a succinct, graphic manner. This report is a description of a system which is being developed to investigate long-term monitoring of the EEGs of critically ill patients. The computer-based methodology which has been used to implement this system is described, with illustrations of CSA-transformed EEGs.


Barbecue burns.

Barbecue burns. An increasing incidence of methylated spirit burns in barbecue users is documented in a three year retrospective survey. A plea is made for better public education on the correct use of methylated spirit in this context.


Mortality rates with oral contraception.


Involuntary smoking.

Involuntary smoking.


The cost of screening.

The cost of screening.


Tetanus immunisation.

Tetanus immunisation.


Scuba diving and burst lung.

Scuba diving and burst lung.


Health manpower in New Zealand. The swinging pendulum.


An epidemiological approach to the teenage drug addict and his peer group.


Research into breast feeding volumes by serial test weighing.


The contribution of the practice nurse.

The contribution of the practice nurse.


The educational preparation of the practice nurse.


Let's talk about advertising.

Let's talk about advertising.


Incoming president's address.

Incoming president's address.


Sweet indiscretion revisited.

Sweet indiscretion revisited.


A health care assault by auto no fault.

A health care assault by auto no fault.


Code of ethics. Revised December 1977. The Dental Society of the State of New York.


Orthodontic treatment of identical twins.


Symptom severity and silent periods: preliminary results in TMJ dysfunction patients.


Jazz history comes alive for Larchmont orthodontist.


Acute leukemia of childhood and adolescence.


Chronic sclerosing osteomyelitis of the mandible. Scintigraphic and radiographic findings. Fourteen patients with chronic sclerosing osteomyelitis of the mandible were investigated with 99mTc-labeled bone-seeking agents. Scintigraphic findings were compared with radiographic features. High uptake of diphosphonate and polyphosphate was demonstrated in diseased areas. Good agreement was found between radiography and scintigraphy concerning the extent and activity of each process. The use of bone-seeking radiopharmaceuticals in other types of skeletal lesions and differential diagnostic aspects are discussed.


Complex odontoma. Three-year follow-up of tooth movement.


Tooth stain due to electric burn.

Tooth stain due to electric burn.


The effect of partial-pancreatectomy-induced diabetes on would healing subsequent to tooth extraction. Histologic study in rats. A histologic study of the effects of diabetes on wound healing of dental sockets was undertaken in rats. The diabetic sate was achieved by performing partial pancreatectomies. The subjects were perfused with 25 percent glutaraldehyde (fixation) and the healing sockets were studied at 3-day intervals during a period of 22 days. The delayed healing observed in this study, when the diabetic condition was due to partial pancreatectomy, was not influenced by the technique used, but was the result of the metabolic modifications of the induced disease.


Pulmonary nocardiosis associated with primary nocardial infection of the oral cavity. A case of pulmonary nocardiosis associated with primary nocardial infection of the oral cavity in a compromised host is presented. Nocardia asteroides, an aerobic, gram-positive, branching, filamentous fungus, was demonstrated in the sputum and in pathologic specimens from gingival sulci stained by Gram's method and the acid-fast method Kinyoun. The organism was identified in cultures made on Sabouraud's glucose agar. Marked clinical improvement was noted when the patient received high dosage of sulfisoxazole diolamine (8 to 12 Gm. per day) for a prolonged period of time (9 to 12 months). Because of an apparent relative increase in the incidence of nocardiosis and a paucity of information on the subject in the dental literature, this article is timely.


Intraoral isolated herpes zoster.

Intraoral isolated herpes zoster. A case of herpes zoster limited to the right palate and the edentulous alveolar ridge in the absence of concurrent skin lesions or predisposing systemic disease is presented. Because of the relative rarity of isolated mucous membrane lesions of this viral disease, the tendency for intraoral vesicles to break down and ulcerate early, and, in this patient, the additional clinical findings of marked swelling and induration, malignancy rather than herpes zoster was suspected; cytologic smear furthered the suggestion of the former. A biopsy provided the definitive diagnosis.


Ultrastructure of the articular surface of the condyle in temporomandibular arthropathy. The ultrastructure of the surface of normal human mandibular condyles is described and compared with specimens from condyles in cases of degenerative joint disease (arthropathy). Normal surfaces exhibited a nearly structurless layer about 2 microns thick, which seemed to correspond with the lamina splendens of other joints. The underlying structure of dense interlacing bundles of collagen is described. Surfaces of all pathologic condyles showed loss of lamina splendens, alteration of collagen size, and evidence of dissociation of both the collagen and its surrounding ground substance. Deeper levels showed aggregations of bizarre structures, which the authors term "vermiform bodies," and which appear to be collections of abnormal amounts and types of elastic tissue. Its distribution suggests a stress elastosis, which may contribute to the loss of mechanical integrity of articular surfaces in arthropathy. The surface changes may be reflected at the clinical level as impairment of the normal low-friction qualities of joint components associated with limitation of movement and joint sounds.


Myxomas of the paraoral--oral soft tissues. Fifteen cases of soft-tissue myxoma of the paraoral-oral structures have been presented. Eleven cases were garnered from an extensive review of the literature, and four previously unreported cases are described. The myxomas were slow-growing, insidious, infiltrative tumors which occurred in all age groups, with an average patient age of 38 years. Most frequent locations were the cheek, floor of the mouth, and palate. The lesions were present from 2 weeks to 6 years prior to treatment. In this series all the myxomas were treated by surgical excision, with no evidence of recurrences or metastases. The recommended therapy is surgical resection with adequate margins. Other myxomatous lesions which may mimic a myxoma are mentioned.


Oral squamous acanthoma. Two additional cases with comments on etiology. Two new cases of squamous acanthoma are presented, and the their clinical characteristics are compared to the eight cases previously reported. These two additional examples of this lesion are clinically similar to those previously reported. However, one of the two cases exhibits resolution after the removal of sources of trauma, thus lending support to the previously proposed theory of traumatic etiology.


Reparative lesion of the tongue.

Reparative lesion of the tongue. An ulcerative lesion of unknown etiology occurred on the dorsum of the tongue in a 6-month-old infant. Following surgical excision, microscopic examination revealed a benign reparative process with degeneration and regeneration of striated muscle.


Odontogenic epithelial hamartoma.

Odontogenic epithelial hamartoma.


A comparative sealability study of different retrofilling materials. The purpose of the study was to compare the sealing properties of Cavit and zinc polycarboxylate cement with silver amalgam when used as retrofilling materials of root canals. The retrofilling materials were placed at the apices of dogs' teeth and were left there for a 6-month period, after which time the teeth were extracted and the marginal leakage was evaluated by C14-labeled urea. A second part of the study included an in vitro placement of the retrofillings. Previously extracted teeth were used and the same retrofilling materials were placed. They were left to set for 2 days in physiologic saline solution. Then the same evaluation for leakage was used. The purpose of the second part was to compare and evaluate the effect of aging on sealability. Under the conditions of this study, amalgam afforded a better seal in the 6-month group than polycarboxylate cement or Cavit. Both Cavit and polycarboxylate cement showed more leakage in the 6-month group. The deterioration of the seal afforded by Cavit in the 6-month group was statistically significant. The seal of amalgam was the only one which was improved by time.


Antibody formation to dog pulp tissue altered by formocresol uithin the root canal. After pulpal extirpation of twenty teeth in each of five dogs, these animals were primarily immunized intramuscularly by combining formocresol with the dog's own pulp (three dogs), saline solution with pulp (one dog) and injecting sheep erythrocytes (one dog). A sixth dog was used as a control for the Arthus skin test. Secondary immunizations were accomplished via the root canal every 7 days over a 28-day period. Arthus skin-test reactions demonstrated less of a response to the formocresol alone than when the dogs' pulp was conbined with this material. In vitro analysis of hemagglutinating antibody titer showed a tremendous increase when pulp was incubated with formocresol as compared to the saline-treated pulp. Therefore, dogs' pulp tissue became antigenically altered by the formocresol recognized by the host, and a specific humoral response resulted.


"Long-distance" bactericidal effectiveness of formalin on permanent human teeth. The long distance bactericidal effectiveness of 0.005 ml. 25 percent formalin in 80 percent ethanol applied on a cotton pellet to pulp chambers for one week in unreamed, unirrigated permanent human teeth with initial postive cultures was studied. The results showed 59 percent negative cultures on subsequent examination.


Periodic identical intraoral radiographs. A modified Eggen technique. A method for obtaining periodic identical radiographs with a modified long-cone paralleling technique is described. The appliance consists of a modified Eggen film positioner and an aiming device fastened to a long cone. There was no fixed connection between the film positioner and the x-ray machine. Radiographs have been obtained from twenty-five patients participating in a long-term study of apicoectomy with retrograde root filling. The intervals between the radiographs ranged from 0 to 12 months. A long-term error and a short-term error of the method were found. The method proved to be accurate and fast compared to those described previously.


Radiographic manifestations of an unusual combination Types I and Type II dentin dysplasia. Dentin dyslasia is a rare autosomal dominant hereditary variant of dentinogenesis imperfecta. The primary defect is mesodermal and involves the dentin. Two types (Type I and Type II) of dentin dysplasia have been described previously. The current case presents radiographic findings which include characteristics common to both types. It is proposed that either a third type (Type III) be recognized or the variability of the developmental defect precludes definitive subclassification.


Bilateral distomolars impacted high in ramus.


Residual root canal foreign body.

Residual root canal foreign body.


Impacted canines and resorption of permanent central incisors.


Gorlin's syndrome with ameloblastoma.

Gorlin's syndrome with ameloblastoma.


Gemination, fusion, or both?

Gemination, fusion, or both?


Intensive care-5. Acute respiratory failure.


Possibility of nonkinked packing of DNA in chromatin. The idea that DNA in chromatin can be packed smoothly, without breaking of base-stacking interactions, has been explored by both energetical estimations and stereochemical model building. A model of deformed DNA is built that fits reasonably to the known dimensions of a nucleosome. The model has slightly changed torsion angles in the sugarphosphate moieties relative to B DNA, varying gradually along the chains. The angle between planes of adjacent base pairs varies between 1 and 7 degrees. This model of deformed DNA does not have any unusually close nonbonded contacts and is evidently not the only possible model of smooth packing of DNA in chromatin. An energetical estimation of the critical radius of curvature of a smoothly bent DNA molecule is made using approximate potential functions for different van der Waals contracts in the B DNA structure. The critical radius of curvature of the deformed DNA-axis is close to the radius of a nucleosome (similar to 50 A). The smooth packing is a good alternative to models of kinked folding of DNA in nucleosomes.


Phosphorylation of eukaryotic protein synthesis initiation factors. Phosphorylation of eukaryotic initiation factors was examined both in intact cells and in vitro with purified components. Intact rabbit reticulocytes were incubated in a medium containing[32P]phosphate, and eight initiation factors were isolated and partially purified. The purified factors were analyzed on dodecyl sulfate/polyacrylamide gels and compared with highly purified nonradioactive factors. Significant amounts of radioactivity were found associated with initiation factors eIF-2, polypeptide 2 (molecular weight 53,000); eIF-3, polypeptides 2 and 4 (molecular weights 110,000 and 67,000); and eIF-4B. Purfied initiation factors from rabbit reticulocytes were also treated in vitro with [gamma-32P]ATP and a cyclic AMP-independent protein kinase isolated from rabbit erythrocytes. Only the factor polypeptides phosphorylated intracellularly were phosphorylated in vitro. The results suggest that the cyclic AMP-independent protein kinase is responsible for the phosphorylation of specific initiation factors in cells active in protein synthesis and that it may play a role in regulating translation.


Membrane-bound neuraminidase from calf brain: regulation of oligosialoganglioside degradation by membrane fluidity and membrane components. The degradation of lipophilic ganglioside GD1a and hydrophilic sialyllactitol by membrane-bound neuraminidase (EC 3.2.1.18) from calf brain has been studied at substrate concentrations of 0.1 mM. Ganglioside GD1a taken up by cell membranes is hydrolyzed faster membrane-bound neuraminidase than are water-soluble substrates of the enzyme, sialyllactitol and des-GD1a. Availability and enzymic breakdown of the disialoganglioside are enhanced by general anesthetics such as N2O or halothane whereas the degradation of the hydrophilic substrate silayllactitol is not affected or even is decreased by these agents. General anesthetics lower the microviscosity of membranes as indicated by studies of fluorescence depolarization with the indicator 1,6-diphenylhexatriene. Increased fluidity can result in higher lateral diffusion of ganglioside GD1a, thus increasing its chances of presentation to, and interaction with, membrane-bound neuraminidase. Lipophilic derivatives of the disialoganglioside, gangliosides GM1 and GM2 and gangliotriaosylceramide GA2, are strong inhibitors of the ganglioside degradation whereas water-soluble derivatives des-GM1, des-GM2, N-acetylneuraminic acid, and sialyllactose are not. A model is presented that suggests that the activity of membrane-bound neuraminidase on gangliosides of brain membranes is regulated by the viscosity of these membranes and their monosialoganglioside content.


Syncatalytic conformational changes in aspartate aminotransferase determined by hydrogen-deuterium exchange. Catalysis-linked conformational transitions of aspartate aminotransferase (cytosolic isoenzyme from pig heart; L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) have been probed by infrared spectrophotometric measurement of hydrogen-deuterium exchange. In the unliganded pyridoxal form of the enzyme at pH 6.0 and 20 degrees, 43% of the total 411 peptide hydrogens per subunit exchange within the first 10 min. An additional 9% exchange slowly in the following time period to 360 min. A quite similar exchange curve is obtained with the pyridoxamine form of the enzyme, indicating close correspondence in conformation of both unliganded forms of the enzyme. Formation of a nonproductive adsorption complex of the pyridoxal enzyme with 2-oxoglutarate or of the pyridoxamine enzyme with glutamate alters the exchange characteristics only slightly. In contrast, the formation of an equilibrium mixture of the covalent transamination intermediates, which occurs in the silultaneous presence of the amino acid and the keto acid substrate, results in a marked retardation of hydrogen exchange, reflecting a substantial tightening of the structure of the enzyme. The exchange reactions of at least 26 peptide hydrogens per subunit (6% of the total) are retarded by a factor of 6 on the average. The occurrence of such syncatalytic conformational changes reflects energetic coupling of the covalency changes at the active site with conformational changes of the macromolecular protein matrix that may contribute to optimizing the free energy profile of enzymic transamination.


Phospholipid vesicle stimulation of proacrosin activation. Aqueous dispersions of synthetic phospholipids, in the form of anionic, single bilayer vesicles, were observed to stimulate the appearance of acrosin esterase activity from its zymogen precursor, proacrosin. Enzymatic activity measurements, in parallel with polyacrylamide disc gel electrophoresis in the presence of sodium dodecyl sulfate, indicated that the enzymatic activity produced had resulted from the conversion of proacrosin to acrosin (EC 3.4.21.10), and not from the direct stimulation of a possible proacrosin esterase activity. It is suggested that such bilayer lipid vesicles can be used as a model membrane system to study the activation of proacrosin in vitro.


Absence of evidence for an intermediate in the deacetylation of acetylchymotrypsin. A recent paper [Chibber, B. A. K., Tomich, J. M., Mertz, E. T. & Viswanatha, T. (1977) Proc. Natl. Acad. Sci. USA 74, 510-514] presented evidence that was taken to support the existence of an intermediate in the deacetylation of acetylchymotrypsin. It was observed that deacylation, as measured by following the decrease in [(14)C]acetylchymotrypsin (decrease in acid-precipitable radioactivity), occurred at 1/10 the rate of reactivation, as measured by return of activity toward N-acetyl-L-tyrosine ethyl ester. Our experiments have shown that, at pH 6, the deacylation rate constant (measured by the loss of [(14)C]acetylchymotrypsin and by the formation of [(14)C]acetate) is identical (within experimental error) with the rate constant for reactivation (measured by determining the activity of aliquots of reactivating enzyme against N-acetyl-L-tryptophan ethyl ester) and with K(cat) for the turnover of p-nitrophenyl acetate by alpha-chymotrypsin. Part of the 10-fold greater reactivation rate observed by Chibber et al. has been shown to be due to the presence of 10% (vol/vol) isopropanol in their reactivation mixture, and it is argued that the balance of the effect is a manifestation of the "indole effect" produced by the simultaneous presence of 10 mM N-acetyl-L-tyrosine ethyl ester throughout the reactivation experiments. The results presented are entirely consistent with the three-step mechanism of catalysis by alpha-chymotrypsin and negate the existence of the proposed additional acetyl-enzyme intermediate.


Structure of nascent replicative form DNA of coliphage M13. Nascent replicative form type II (RFII) DNA of coliphage M13 synthesized in an Escherichia coli mutant deficient in the 5' leads to 3' exonuclease associated uith DNA polymerase I contains ribonucleotides that are retained in the covalently closed RFI DNA sealed in vitro by the joint action of T5 phage DNA polymerase and T4 phage DNA ligase. These RFI molecules are labile to alkali and RNase H, unlike the RFI produced either in vivo or from RFII with E. coli DNA polymerase I and E. coli DNA ligase. The ribonucleotides are located at one site and predominantly in one strand of the nascent RF DNA. Furthermore, these molecules contain multiple small gaps, randomly located, and one large gap in the intracistronic region.


In vitro inhibition of protein synthesis by purified cores from vaccinia virus. The mechanism of the shutoff of cellular protein synthesis in vaccinia virus-infected cells has been investigated by using in vitro systems. Purified vaccinia cores cause inhibition of endogenous mRNA translation in nonpreincubated reticulocyte lysates and Ehrlich ascites tumor cell-free systems. Translation of viral mRNA from turnip yellow mosaic virus is also impaired in wheat germ cell-free extracts. The block induced by vaccinia cores in protein synthesis is not due to a decrease in the availability of mRNA but rather to an alteration of the cellular translational machinery. No nucleolytic activity able of digesting mRNA could be detected in purified vaccinia cores with three sensitive tests. There is a lack of inhibition in the poly(Phe)-poly(U) system, which bypasses the normal initiation process. An almost complete disaggregation of polyribosomes in the reticulocyte lysate appears when vaccinia cores are present. These results indicate that mRNA translation in a cell-free system is affected predominantly at the level of polypeptide chain initiation.


Insulin-like growth factor: a model for tertiary structure accounting for immunoreactivity and receptor binding. A model for the three-dimensional structure of insulin-like growth factor (IGF) is proposed based on the close sequence homology of IGF with insulin, the tertiary structure of which is known. The IGF molecule is postulated to have an insulin-like main chain conformation for residues equivalent to B6--B27 and A1--A21 and a hydrophobic core nearly identical to that of insulin. A short connecting peptide of twelve residues and an extension at the COOH-terminus are easily accommodated on the molecular surface. The surface involved in dimer formation in insulin is largely conserved, but the zinc-binding histidine and many residues involving hexamerization are very different from those of insulin and it is unlikely that IGF forms zinc hexamers. The model provides a ready explanation for the inability of IGF to bind antibodies to insulin and for its ability to bind insulin receptors with low affinity.


Transient electric dichroism of rod-like DNA molecules. We report transient electric dichroism studies on monodisperse rod-like DNA molecules. By using restriction fragments and DNAs of known length, it is shown that the orientation time is accurately predicted by the theoretically calculated rotational diffusion coefficient. The field dependence of the steady-state dichroism values is not consistent with the induced electric dipole orientation mechanism, and the time dependence is not consistent with the presence of a permanent dipole moment. In order to explain the dependence of the dichroism on the electric field, the ionic strength of the medium, and the length of the macromolecule, we propose a new model in which anisotropic ion flow produces an asymmetric ion atmosphere around the polyelectrolyte, resulting in an orienting torque. From the limiting dichroism at high field, we estimate that the DNA bases are inclined at an angle of 73 degrees or less relative to the helix axis, in good agreement with the revised model of B-form DNA suggested by Levitt, in which the base pairs have a propeller-like twist. Our results establish transient electric dichroism measurements as a technique well suited for study of alterations in the length and base pair inclination of rod-like DNA molecules.


Binding and release of eukaryotic initiation factor eIF-2 and GTP during protein synthesis initiation. The eukaryotic initiation factor eIF-2 forms a ternary complex with Met-tRNAf and GTP. This complex binds to the 40S ribosomal subunit in the absence of mRNA and mRNA binding factors. Highly purified eIF-2 from rabbit reticulocytes was labeled with 125I by using the Bolton-Hunter reagent or with [gamma-32P]ATP by using the heme-regulated translational inhibitor protein kinase. The labeled eIF-2 was bound, together with equimolar amounts of Met-tRNAf and GTP, to the 40S subunit. In the presence of mRNA, mRNA binding factors, and 60S ribosomal subunits (complete initiation assay), eIF-2 was released from the 40S initiation complex in the subunit joining reaction. GTP also was released in this step and probably was hydrolyzed in the reaction that is dependent upon eIF-5 and the 60S subunit. The function of phosphorylated eIF-2 in initiation of protein synthesis is discussed.


Specific binding of messenger RNA and methionyl-tRNAfMet by the same initiation factor for eukaryotic protein synthesis. Affinity chromatography on columns containing globin mRNA, R17 phage mRNA, or double-stranded RNA linked to cellose is used to demonstrate unequivocally that the eukaryotic initiation factor (eIF-2) that forms a ternary complex with Met-tRNAf and GTP also binds  tightly to these RNA species. Affinity chromatography of reticulocyte ribosomal wash yields over 100-fold purification of Met-tRNAf-binding factor. This factor is eluted as one of the most tightly bound proteins, and is active in protein synthesis even after passage over a column of double-stranded RNA-cellulose. eIF-2 binds mRNA and double-stranded RNA in distinctly different modes, protecting essentially all sequences in double stranded RNA, but very few in mRNA, against digestion with ribonuclease. Apparently, eIF-2 recognized the A conformation of double-stranded RNA, but not its sequence. By contrast, globin, Mengo virus, R17 and vesicular stomatitis virus mRNA are shown to possess a high-affinity binding site for eIF-2 that is absent in negative-strand RNA of vesicular stomatitis virus, an RNA that cannot serve as messenger. The results support the concept that eIF-2, the initiation factor that binds Met-tRNAf, recognizes an internal sequence in mRNA essential for protein synthesis.


Binding to saxitoxin to electrically excitable neuroblastoma cells. Saxitoxin inhibits the action potential Na+ ionophore of electrically excitable neuroblastoma cells with a KI of 3.7 nM. Binding experiments detect a single class of saturable binding sites with KD = 3.9 nM and a binding capacity of 156 fmol/mg of cell protein (78 sites per micrometer2 of cell surface). Saturable binding is completely inhibited by tetrodotoxin but is unaffected by scorpion toxin or batrachotoxin. No saturable binding is observed in cultures of clone N103, a variant neuroblastoma clone lacking the action potential Na+ response. Thus, saxitoxin binds specifically to the action potential Na+ ionophore in neuroblastoma cells. Comparison of saxitoxin and scorpion toxin binding reveals that there are three saxitoxin receptor sites for each scorpion toxin receptors site. The implications of this stoichiometry are considered.


On the photosensitivity of liganded hemoproteins and their metal-substituted analogues. We have examined the photosensitivity of low-spin liganded hemoglobin, myoglobin, and peroxidase, and their metal-substituted analogues, using three different metals (Fe, Mn, Co) in several oxidation states and employing a variety of diatomic or pseudo-diatomic ligands (L). We have discovered a number of photosensitive systems, and present an overall stereo-electronic classification scheme for these photodissociation reactions: Linear, formally d6, metal-ligand fragments [e.g., Fe(II) +/- CO; Mn(II) +/- NO] are relatively photoliable, but systems with a bent fragment, and higher electron occupancy [e.g., Fe(II) +/- O2; Co(II) +/- NO] are relatively photoinert. Photostability appears to correlate with the occurrence of long-wavelength features in the optical absorption spectra, and the classification scheme is explained by considerations of electronic structure. The discussions are further applied to d5 systems and to low-spin d6 metalloporphyrins with nitrogenous bases as axial ligands.


Mode of action of the hemin-controlled inhibitor of protein synthesis. Despite the finding that the hemin-controlled translational inhibitor in reticulocyte lysates is a cyclic AMP-independent protein kinase that phosphorylates the small subunit of the initiation factor eIF-2, the mechanism of inhibition of translation remained unexplained. Whereas treatment of hemin-containing lysates with inhibitor in the presence of ATP inhibited translation, the same treatment of highly purified eIF-2 did not affect its ability to form a ternary complex with initiator Met-tRNA and GTP or a 40S initiation complex. We have isolated from ribosomal salt washes a protein (eIF-2 stimulating protein) that enhances the capacity of unphosphorylated eIF-2 to form ternary or 40S initiation complexes but has no effect on the phosphorylated factor. At low concentrations, eIF-2 is virtually inactive without this stimulating protein. Therefore, the translational inhibitor acts by converting eIF-2 to a form that is not stimulated by the stimulating protein.


pppA2'p5'A2'p5'A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. A low molecular weight inhibitor of cell-free protein synthesis effective at subnanomolar concentrations is formed on incubation of cytoplasmic extracts from interferon-treated cells with double-stranded RNA and ATP. It can be conveniently synthesized by incubating a poly(I).poly(C)-Sepharose-bound enzyme fraction from such cells with [3H]- or [alpha- or gamma-32P]ATP. The radioactive inhibitor has been characterized by its behavior on DEAE-Sephadex in the presence of urea and on the basis of the products obtained on enzymic, alkaline, and sequential degradation by periodate oxidation and beta elimination. Its structure appears to be pppA2'p5'A2'p5'A. We have found no evidence for any modification or abnormality other than the 2'-5' linkage. On occasion the inhibitor preparations have included what seems to be the corresponding dimer (pppA2'p5'A), tetramer [ppp(A2'p)3A], pentamer [ppp(A2'p)4A], and higher oligomers in decreasing amounts. The trimer, tetramer, and pentamer are similar in activity, but the dimer is less potent if active at all.


Stochastic theory of ligand migration in biomolecules. When ligand binding to proteins involves the presence of more than one ligand inside a given biomolecule, linear deterministic rate equations become useless. A stochastic approach, however, permits a treatment of the migration and binding of small molecules to proteins even at high ligand concentrations. An appropriate linear master equation and its analytic solution are given. As an example, the binding of carbon monoxide to myoglobin at partial pressures from 1 to 10(3) bars (0.1 to 100 MPa) is treated.


Diphtheria toxin has the properties of a lectin. The inhibition of protein synthesis in Chinese hamster V79 cells by diphtheria toxin is antagonized by the lectins concanavalin A, succinylated concanavalin A, and wheat germ agglutinin but not by Proteus vulgaris phytohemagglutinin or abrus agglutinin. The effects of concanavalin A and wheat germ agglutinin are reversed by methyl alpha-mannoside and N-acetylglucosamine, respectively. The inhibition of diphtheria toxin as a function of concanavalin A concentration fits a model of competitive inhibition with an apparent dissociation constant for concanavalin A of 3 X 10(-8) M. These results suggest that the diphtheria toxin receptor may be an oligosaccharide. To test this hypothesis, we screened several oligosaccharides for the ability to inhibit diphtheria toxin. The cell wall polysaccharide of Salmonella cholera suis and the ovalbumin glycopeptide were effective inhibitors. These studies suggest that diphtheria toxin may have the oligosaccharide binding properties of a lectin with specificity for N-acetylglucosamine and mannose.


Molecular mechanisms for proton transport in membranes. Likely mechanisms for proton transport through biomembranes are explored. The fundamental structural element is assumed to be continuous chains of hydrogen bonds formed from the protein side groups, and a molecular example is presented. From studies in ice, such chains are predicted to have low impedance and can function as proton wires. In addition, conformational changes in the protein may be linked to the proton conduction. If this possibility is allowed, a simple proton pump can be described that can be reversed into a molecular motor driven by an electrochemical potential across the membrane.


Biosynthesis in vitro of fucose-containing glycosphingolipids in human neuroblastoma IMR-32 cells. Two different glycolipid:fucosyltransferase activities involved in the biosynthesis in vitro of blood group-related glycosphingolipids have been detected in a membrane preparation isolated from a human neuroblastoma-derived clonal cell line, IMR-32. The membrane preparation contains an alpha (1,2)-fucosyltransferase (EC 2.4.1.89) that catalyzed the transfer of vucose from GDP--[14C]fucose to neolactotetraosylceramide or neolactopentaosylceramide to form types H-I and B-I glycolipids, respectively. The second fucosyltransferase catalyzes the transfer of fucose to lactotriaosylceramide [GlcNAc(beta1-3)Gal(beta1-4)Glc-Cer] to form a tetraglycosylceramide intermediate of the novel Lea-type glycolipid. UDP-galactose:lactotriaosylceramide beta-galactosyltransferase (EC 2.4.1.86) had 4 times the activity of UDP-galactose:alpha-galactosyltransferase (EC 2.4.1.87) when tested under similar conditions. alpha-Fucosyltransferase activities and the incorporation of [14C]fucose into glycoproteins and glycolipids were also compared in cells differentiated in the presence of 4 micron BrdUrd and 6-mercaptoguanosine.


Bioluminescence of the firefly: key steps in the formation of the electronically excited state for model systems. The chemcial mechanism for formatin of electronically excited-state molecules from the thermal reaction of dimethyldioxetanone was studied. Light production in the presence of certain easily oxidized aromatic hydrocarbons was found not to conform to the classical mechanistic schemes for chemiexcitation. Detailed investigation of the dioxetanone system revealed light formation by the recently discovered, chemically initiated electron-exchange process. This result is extrapolated to bioluminescent systems. In particular, the key high-energy molecule involved in firefly luminescence, which has been identified as a dioxetanone, is postulated to form excited states as a result of intramolecular electron transfer from the phenoxythiazole moiety to the dioxetanone. Subsequent rapid decarboxylation results in direct formation of an excited single state of the emitting amide.


Macromolecular shape and surface maps by solvent exclusion. A quantitative function equivalent to the "molecular" surface proposed by F. M. Richards [(1977) Annu. Rev. Biophys. Bioeng. 6, 151--176] is defined by the closest approach of solvent spheres to a macromolecule. The function can be used to visualize surface topography, polarity, and charge either as a three-dimensional net or by mapping onto a plane; to calculate surface areas; and to demarcate complementary sites in contacts between subunits. Applications to shape-specific recognition in protein structure and aggregation are discussed.


Geometric packing constraints in egg phosphatidylcholine vesicles. This investigation presents a quantitative analysis of the asymmetric transmembrane lipid packing geometry in egg phosphatidylcholine vesicles. The analysis uses hydrodynamic and nuclear magnetic resonance data obtained for homogeneous egg phosphatidylcholine vesicles and demonstrates that the average area per lipid head group and effective length of the lipid are greater on the outer monolayer than on the inner monolayer of the egg phosphatidylcholine vesicle. Results also indicate that the bilayer of the egg phosphatidylcholine vesicles has an asymmetrical interface through its center.


Electronic properties of some protein--methylglyoxal complexes. Steady-state conductivity measurements and dielectric measurements in the frequency range 10(-5) to 100 Hz are reported for samples of bovine serum albumin, casein, and lysozyme complexed with methylglyoxal. Compared with the untreated proteins, the brown complexed proteins exhibit an increased conductivity and free electron spin density, together with a low-frequency dielectric dispersion. These results can be taken as evidence that the interaction with methylglyoxal results in the proteins possessing an increased electronic activity associated with the creation of mobile electron holes within the valence band states of the protein molecules.


Specificity of the effects of cytochalasin B on transport and motile processes. The effects of cytochalasin B (CB) and dihydrocytochalasin B (H2CB) on a variety of transport and motile processes have been compared. CB inhibited transport of D-glucose and L-glucose but not transport of thymidine in human erythrocytes. In contrast, H2CB, which differs from CB by the absence of a single double bond, had little or no effect on any of these processes. Both cytochalasins, however, affected the morphology of cultured fibroblasts and inhibited motile processes such as membrane ruffling, axon growth cone activity, blood clot retraction, cytoplasmic streaming, photodinesis, and cytokinesis. Determination of the partition coefficient of the two cytochalasins in several organic solvent/phosphate-buffered saline systems showed that H2CB has a higher affinity for the hydrophobic phase than CB. These results indicate that the inhibitory effects of CB on sugar transport and on cell motility and morphology are separable and independent events, mediated by the binding of the drug to specific cellular receptors.


Density-dependent regulation of growth of BSC-1 cells in cell culture: control of growth by low molecular weight nutrients. BSC-1 cells, epithelial cells of African green monkey kidney origin, show pronounced density-dependent regulation of growth in cell culture. Growth of the cells is rapid to a density of approximately 1.5 x 10(5) cells/per cm(2) in Dulbecco-modified Eagle's medium supplemented with 10% calf serum. Above this "saturation density," growth is much slower. It has been found that the glucose concentration in the culture medium is important in determining the "saturation density." If the glucose concentration is increased 4-fold, the "saturation density" increases approximately 50%. Reduction of the "saturation density" of BSC-1 cells is also possible by decreasing the concentrations of low molecular weight nutrients in the culture medium. In medium supplemented with 0.1% calf serum, decreasing the concentrations of all of the organic constituents of the medium, from the high levels present in Dulbecco-modified Eagle's medium to concentrations near physiological levels, decreases the "saturation density" by approximately half. The decreased "saturation density" is not the result of lowering the concentration of any single nutrient but rather results from reduction of the concentrations of several nutrients. When the growth of BSC-1 cells is limited by low concentrations of all of the nutrients, some stimulation of growth results from increasing, separately, the concentrations of individual groups of nutrients, but the best growth stimulation is obtained by increasing the concentrations of all of the nutrients. The "wound healing" phenomenon, one manifestation of density-dependent regulation of growth in cell culture, is abolished by lowering the concentration of glutamine in the medium. Density-dependent regulation of growth of BSC-1 cells in cell culture thus appears to be a complex phenomenon that involves an interaction of nutrient concentrations with other regulatory factors.


Animal cells reversibly permeable to small molecules. A cell preparation, useful for studying the regulation of metabolism, was developed by making monolayer baby hamster kidney cells permeable. Hypertonically treated cells were permeable to nucleotides, but retained their gross cellular morphology, intact organelles, 100% of their DNA, and 91% of their total protein. The permeable cell synthesized DNA, RNA, and protein rapidly when supplied with the appropriate substrates and cofactors. They either could remain permeable or were able to "reseal" when replaced in complete medium under appropriate conditions. Optimal conditions for DNA synthesis were established for permeable cells, giving rates equal to those of intact cells. Replication rather than repair was shown by the cell-cycle dependence of DNA synthesis and its discontinuous nature. Ribonucleotide reductase was active in permeable cells, permitting equal rates of DNA synthesis when ribonucleotide diphosphates or deoxyribonucleotide triphosphates were provided. Hydroxyurea did not inhibit DNA synthesis in permeable cells supplied with deoxyribonucleotide di- or triphosphates, but drastically inhibited DNA synthesis when ribonucleotide diphosphates were supplied. Hydroxyurea is therefore primarily an inhibitor of ribonucleotide reductase. Permeability was reversed, exposing permeable cells to [(3)H]thymidine triphosphate, which was incorporated, which labeled nuclei of cells that went on to mitosis. The reversible permeability procedure should prove especially useful in studying the functions of poorly penetrating compounds, such as drugs. Intact cells were unaffected by cytosine arabinoside triphosphate, while cells that had been made permeable and resealed were killed.


Diadenosine 5',5'''-P1,P4-tetraphosphate triggers initiation of in vitro DNA replication in baby hamster kidney cells. Addition of diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) to permeabilized G1-arrested baby hamster kidney cells resulted in the stimulation of DNA synthesis. No stimulation was observed in cells from exponentially growing cultures. The Ap4A-stimulated [3H]dTTP incorporation was inhibited by nalidixic acid, daunomycin, chloroquine diphosphate, EDTA, and N-ethylmaleimide. It was dose-dependent in regard to the amount of permeabilized cells and of Ap4A. Numerous replication eyes were formed in the DNA molecules of stimulated cells. Pulse-chase experiments showed that the synthesis of DNA was discontinuous, resulting in the appearance of approximately 4S Okazaki fragments and their ligation to high molecular weight DNA. These results strongly suggest that Ap4A stimulated the initiation of DNA synthesis in baby hamster kidney cells that had been arrested in G1 by serum deprival.


Cell lineages of the embryo of the nematode Caenorhabditis elegans. Embryogenesis of the free-living soil nematode Caenorhabditis elegans produces a juvenile having about 550 cells at hatching. We have determined the lineages of 182 cells by tracing the divisions of individual cells in living embryos. An invariant pattern of cleavage divisions of the egg generates a set of stem cells. These stem cells are the founders of six stem cell lineages. Each lineage has its own clock--i.e., an autonomous rhythm of synchronous cell divisions. The rhythms are maintained in spite of extensive cellular rearrangement. The rate and the orientation of the cell divisions of the cell lineages are essentially invariant among individuals. Thus, the destiny of cells seems to depend primarily on their lineage history. The anterior position of the site of origin of the stem cells in the egg relates to the rate of the cell cycle clock, suggesting intracellular preprogramming of the uncleaved egg. We used a technique that allows normal embryogenesis, from the fertilized egg to hatching, outside the parent under a cover glass. Embryogenesis was followed microscopically with Nomarski interference optics and high-resolution video recording.


Altruism: its characteristics and evolution. Altruism is a group phenomenon in which some genes or individuals, which must be presumed to be selfish, benefit others at cost to themselves. The presumption of selfishness and the fact of altruism are reconciled by kin-group selection and by reciprocal altruism. Kin-group selection is clearly visible only in special cases; its role even among social insects may be overestimated; it is probably usually inhibited by competition. However, reciprocal altruism is ubiquitous. All altruism is: (i) potentially reciprocal; (ii) potentially profitable to altruists as well as to recipients; (iii) environmentally determined, usually by position of individuals in group or environmental situations; and (iv) a net-gain lottery. These generalizations are illustrated by four idealized cases; the difficulty of applying them to real cases is illustrated by alarm-calling in groups of birds. Although altruism is a group phenomenon, it evolves by individual selection, by processes equivalent to co-evolutions. Its evolution is: (i) opposed by competition; (ii) costly, complex, and slow, and tending to produce an imprecise flexible altruism rather than a precisely detailed one; and (iii) supplemented by group selection (differential extinction of groups). That altruism in human beings conforms to these generalizations is a good working hypothesis. However, analysis does not "take the altruism out of (human) altruism." Humans do not calculate it, but behave altruistically because they have human altruistic emotions.


Silkmoth chorion proteins: sequence analysis of the products of a multigene family. Five polypeptide components have been isolated from the eggshell (chorions) of a silkmoth. Two are homogeneous on sodium dodecyl sulfate and isoelectric focusing gels, and three contain predominantly two proteins each. Amino acid analyses show that all five components are similar to each other. These proteins have been sequenced from the amino terminus. Homogeneous components yielded single sequences; heterogeneous components yielded two residues at some positions, consistent with their containing two major electrophoretic components. Striking similarities are apparent among all these sequences. These similarities can be increased dramatically by separating each of the three protein mixtures into two sequences and introducing a small number of gaps or insertions. This is due in part to bringing into register a portion that contains short repeating subunits found in all sequences. All proteins are also characterized by a region of high cysteine content near the amino terminus followed by a longer low-cysteine region. The data suggest that these proteins share a common evolutionary origin and are encoded by a multigene family.


Determination of capsid size by satellite bacteriophage P4. Satellite bacteriophage P4 requires all morphogenic gene products provided by a helper phage, such as coliphage P2, to assemble its own capsid, which is one-third the volume of the larger helper capsid. We have isolated a satellite phage P4 sid (size determination) mutant that is unable to direct the assembly of the small wild-type-size P4 capsid. Instead, this mutant produces P4 plaque-forming units with large P2-size capsids which contain two or three copies of the P4 sid1 genome. P4 sid1 is evidently mutated in a protein that is specifically responsible for determining the precise size and symmetry of the structure into which the helper P2 gene products will assemble. In addition, we have found that the physical size of the genome does not appear to play an essential role in the proper assembly of the icosahedral capsid, since the majority of the P4 sid1 plaque-forming units do not contain a complete capsidful of DNA.


Temperature-sensitive RNA polymerase II mutations in Chinese hamster ovary cells. Mutant Chinese hamster ovary cell lines temperature-sensitive (TS) for growth and containing TS mutations in RNA polymerase II (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) have been isolated. Wild-type cells were treated with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine and a population of cells possessing mutations in RNA polymerase II was initially selected by isolating alpha-amanitin-resistant clones at 34 degrees . Of 168 such alpha-amanitin-resistant isolates screened for temperature sensitivity, nine were TS for growth at 39.5 degrees . By examining the behavior of the alpha-amanitin resistance of these TS cell lines in somatic cell hybrids, the TS mutation in a number of them was shown to be in RNA polymerase II. Hybrid cells obtained by the fusion of the TS and alpha-amanitin-resistant cells with cells possessing alpha-amanitin-sensitive polymerase II grew at both 34 degrees and 39.5 degrees ; the TS mutations were recessive. At 34 degrees all the hybrids were alpha-amanitin-resistant and possessed a mixture of alpha-amanitin-resistant and sensitive polymerase II. At 39.5 degrees the alpha-amanitin-resistant polymerase II activities in hybrids of four of the TS cell lines were lost; these four lines were alpha-amanitin-sensitive and possessed only alpha-amanitin-sensitive polymerase II. Temperature-insensitive revertants of two of these mutants were isolated. Reversion of the TS phenotype for mutants TsAma(R)-1 and TsAma(R)-8 was accompanied by an alteration in the level of alpha-amanitin resistance of the RNA polymerase II activities in the revertant cells. Together these data provide convincing evidence that TS mutations in RNA polymerase II can be coselected with alpha-amanitin resistance.


Modification of DNA by the benzo[a]pyrene metabolite diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene. The structural modification of double-stranded circular DNA of simian virus 40 and plasmid ColE1 by in vitro binding of r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene was studied. Stepwise hydrolysis with endonuclease S1 and DNase followed by DNA base analysis by thin-layer chromatography provided evidence that binding to adenine caused the local denaturation of DNA, whereas the more than 10-fold greater binding to guanine did not create such local denaturation. Of the  two synthetic double-stranded polymers, poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC), bound to the diol-epoxide, only the former showed a marked hydrolysis after endonuclease S1 treatment, whereas binding occurred 24-fold more on the latter.


A model of kin selection for an altruistic trait considered as a quantitative character. Conditions for natural selection to favor increase of a quantitative character are derived for a model in which individuals associate in groups of size n. It is assumed that the logarithm of the fitness of an individual is the sum of two parts, one proportional to the individual's own phenotype, and the other to the mean phenotype in its group. The resulting conditions for the trait to increase under natural selection are analogous to the results found previously in single-locus kin selection models.


Evidence that tumor antigens enhance tumor growth in vivo by interacting with a radiosensitive (suppressor?) cell population. The growth of a small number of cells from each of two chemically induced BALB/c sarcomas was enhanced when x-irradiated (15,000 rads) cells of the same sarcoma were mixed with the tumor inoculum. This enhancement did not occur if the recipients had been given a total body x-irradiation of 450 rads. Tumor neutralization (Winn) tests showed that tumor cells irradiated in vitro enhanced tumor growth only in the presence of radiosensitive cells present in the spleens of both nonimmune and tumor-bearing mice. On the basis of these findings we postulate that tumor antigen blocks effective tumor immunity by a mechanism that involves a suppressor cell population.


Thyroid and glucocorticoid hormones synergistically control growth hormone mRNA in cultured GH1 cells. We have previously demonstrated that thyroid hormone controls growth hormone synthesis in GH1 cells and that the induction of the growth hormone response by glucocorticoid appears to be highly dependent on thyroid hormone action. Thyroid hormone induces growth hormone synthesis approximately 5- to 20-fold and cortisol increases this response 2- to 6-fold further. Long-term kinetics of the growth hormone response show that, without added thyroid hormone, cortisol can induce a small-growth hormone response after 48 hr of incubation. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of proteins synthesized in intact cells demonstrates that the cortisol enhancement of growth hormone synthesis in cells incubated with thyroid hormone is a relatively selective process. Quantitation of growth hormone mRNA levels by cell-free protein synthesis demonstrates that the regulation of growth hormone synthesis by thyroid and glucocorticoid hormones is explained by a synergistic pretranslational control mechanism, presumably at the level of the growth hormone gene.


Anti-epidermal-cell-surface pemphigus antibody detaches viable epidermal cells from culture plates by activation of proteinase. Immunoglobulin from pemphigus patients binds to the surface of mouse epidermal cells in culture. Cells incubated with the pemphigus antibody are easily detached from culture plates whereas cells incubated with serum from normal patients remain on the plate. Pemphigus antibody-mediated cell detachment is blocked by the addition of the proteinase inhibitors soybean trypsin inhibitor and alpha2-macroglobulin to the culture media. Detachable cells are viable, and activation of the complement cascade is not necessary for cell detachment. The anti-cell-surface antibody of pemphigus appears to disrupt adhesion between viable epidermal cells by activation of proteinase.


Increased turnover of arterial collagen in hypertensive rats. The turnover of total collagen in several tissues of 12-week-old normotensive and hypertensive rats was estimated by using tritium-labeled proline as a precursor. The effect of reutilization of the label was minimized by treatment with large doses of unlabeled proline subsequent to administering the radioactive imino acid. The collagen from skin, tail tendon, aorta, and mesenteric artery in normotensive animals had a half-life of about 60--70 days. In hypertensive animals the half-lives of skin and tail tendon collagen were unchanged but the half-lives of collagen in the aorta and mesenteric artery were reduced to 17 days.


Estrogenic activity in vivo and in vitro of some diethylstilbestrol metabolites and analogs. The diethylstilbestrol (DES) metabolite (beta-dienestrol), which had been identified in mouse, rat, monkey, and human urine, and two proposed metabolic intermediates (diethylstilbestrol alpha,alpha'-epoxide and alpha,alpha'-dihydroxy DES) were synthesized and their estrogenic activities determined. In addition, three DES analogs, alpha-dienestrol, DES-dihydroxy diethyl phenanthrene (DES-phenanthrene), and 1-(alpha-ethyl, 4alpha-hydroxyphenyl)indanyl-5-ol (indanyl-DES), were studied. Estrogenic activities of the compounds in vivo were determined by the immature mouse uterine weight bioassay; in vitro, their estradiol receptor binding activity (competitive equilibrium binding, sucrose gradient analysis, and association rate inhibition assays) was determined. Results of the mouse uterine weight bioassay gave the following order of estrogenicity: DES > alpha-dienestrol >/= DES-epoxide > indanyl-DES > dihydroxy DES > beta-dienestrol > DES-phenanthrene. Results of competitive equilibrium binding analyses of these compounds with estradiol-17beta for the mouse uterine cytosol receptor followed the same order seen for the bioassay, except for indanyl-DES. DES, indanyl-DES, and alpha-dienestrol had the greatest affinities (K(a) values approximately 0.5-19.1 x 10(10) M(-1)), while DES-phenanthrene had the lowest (K(a) = 3.5 x 10(7) M(-1) +/- 1.2). Sucrose gradient analysis of the above competition preparations illustrated the displacement of [(3)H]estradiol from the receptor peak. This displacement was receptor specific and concentration dependent and correlated with the equilibrium binding concentrations. In addition, the most hormonally active substances demonstrated the greatest rate inhibition in the estradiol cytosol receptor association rate reaction (V(0)). The rank order of estrogenicity of the compounds determined in this study should be useful in evaluating alternative metabolic pathways of DES as well as distinguishing biologically active metabolites from relatively inactive ones.


Structure of the orgin of DNA replication of bacteriophage fd. An RNA-polymerase-protected DNA fragment of 125 nucleotides from the origin of single-strand to double-strand replication of bacteriophage fd (ori-DNA) was located on the physical map of the phage genome. A stretch of 187 base pairs of DNA including the ori-DNA was sequenced. This DNA segment contains regions with a highly asymmetric pyrimidine/purine distribution next to regions with 2-fold symmetry that form stable hairpin structures in the viral DNA strand.


Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency. The inherited deficiency of adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) activity in humans is associated with an immunodeficiency. Some of the immunodeficient and enzyme-deficient patients respond immunologically to periodic infusions of irradiated erythrocytes containing adenosine deaminase. It has been previously reported that erythrocytes and lymphocytes from immunodeficient ane enzyme-deficient children contained increased concentrations of ATP, and in the one child studied after erythrocyte infusion therapy, the intracellular level of ATP diminished. Using high-pressure liquid chromatography that resolves ATP and 2'-dATP, we have observed greater than 50-fold elevations of dATP in the erythrocytes of immunodeficient, adenosine deaminase-deficient patients but not in the erythrocytes of an immunocompetent adenosine deaminase-deficient patient. The erythrocyte dATP in two unrelated adenosine deaminase-deficient, immunodeficient patients disappeared after infusion of normal erythrocytes. We propose that deoxyadenosine, a substrate of adenosine deaminase, is the potentially toxic substrate in adenosine deaminase deficiency, and that the mediator of the toxic effect is dATP, a recognized potent inhibitor of ribonucleotide reductase.


Membrane particle aggregates in innervated and noninnervated cultures of Xenopus embryonic muscle cells. Clusters of membrane particle aggregates were found in the cultures of Xenopus embryonic muscle cells. In innervated cultures, the aggregates were usually found in the vicinity of the nerve. In terms of particle density and morphology, they resembled the postsynaptic particle aggregates of adult skeletal muscle fibers, suggesting that they may be related to acetylcholine receptors. Similar particle aggregates were also found in noninnervated cultures. They may correspond to extrajunctional clusters of acetylcholine receptors or "hot spots."


Channel open time and metabolic stability of synaptic and extrasynaptic acetylcholine receptors on cultured chick myotubes. The mean channel open time and metabolic stability of acetylcholine receptors were studied in developing chick muscle fibers in vitro. Analysis of acetylcholine noise recorded from small patches of surface membrane on uninnervated myotubes indicates that the mean ionic channel open time is independent of receptor density. On myotubes innervated in vitro by spinal cord neurons, the mean open time of synaptic receptors was identical to that of extrasynaptic receptors on the same fibers. Receptor stability was estimated by autoradiography of cultures labeled with 125I-labeled alpha-bungarotoxin. Synaptic and extrasynaptic toxin--receptor complexes disappear at the same, relatively rapid rate. Both the mean channel open time and the apparent rate of receptor degradation are comparable to values obtained at extrasynaptic sites on denervated adult muscles in other species.


Distinct protein components from Torpedo marmorata membranes carry the acetylcholine receptor site and the binding site for local anesthetics and histrionicotoxin. Highly purified subsynaptic membrane fragments prepared from Torpedo marmorata electric organ (specific activity, greater than 4 mumol of Naja nigricollis alpha-[3H]toxin per mg of protein) exhibit, on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, two major protein bands of apparent molecular weight 40,000 and 43,000, respectively. Dissolution of these membranes by the nondenaturing detergents Triton X-100 and Berol 043 followed by standard fractionation yielded (i) the 9S acetylcholine-receptor protein which still binds the alpha-[3H]toxin and after further purification yielded, in the presence of sodium dodecyl sulfate, the 40,000-dalton component, covalently labeled by the affinity reagent 4-(N-maleimido)phenyl[3H]trimethylammonium; only serine was found as the NH2-terminal amino acid of this protein; and (ii) a high molecular weight aggregate named 43,000 protein which was resolved in denaturing gels almost exclusively as the 43,000-dalton band, In the absence of detergents, the 43,000 protein binds compounds known to interact with the acetylcholine ionophore: a fluorescent local anesthetic quinacrine and histrionicotoxin (apparent dissociation constant, 7 +/- 1 X 10(-7) M). The regulation of quinacrine fluorescennce by carbamylcholine, observed in the intact membrane, no longer occurs with the isolated 43,000 component.


Demonstration of biological activity of brain gastrin-like peptidic material in the human: its relationship with the COOH-terminal octapeptide of cholecystokinin. The previously described peptide material that reacts with antibodies to gastrin and is found in the central nervous system of various vertebrates is present in only the 100,000 X g pellet of postmortem human cerebral cortical grey matter. This immunoreactive material, extractable in boiling water, is biologically active on rat pancreatic preparations. On the basis of size, charge, immunological specificity, and patterns of biological activity, most of this material is closely related to the COOH-terminal octapeptide of cholecystokinin in its complete, sulfated biologically active form.


Sound transmission in the salamander ear. The mode of stimulation of the ear by sounds is considered in Amphibia, in which it differs among the three Recent orders. Of special interest is the order Caudata, in which this stimulation takes a unique form: sounds applied to the oval window of one ear produce a path of vibratory motion that passes through the brain cavity to the oval window on the opposite side. In this course the vibratory movements traverse both right and left amphibian papillae, and both basilar papillae also in species that contain these endorgans. Thus, in the salamander the hearing is invariably binaural.


Melatonin secretion decreases during the proestrous stage of the rat estrous cycle. Urine was collected from rats during 12 consecutive daily dark periods and assayed for melatonin and norepinephrine; the phase of the vaginal estrous cycle associated with each urine sample was determined from daily vaginal smears. The proestrous phase of the estrous cycle was consistently associated with significant reductions in the excretions of both compounds. The level of melatonin in any urine sample tended to vary as a function of its norepinephrine content; however, the slope of the curve relating these two compounds in metestrous-diestrous samples differed from that for proestrous-estrous specimens. This difference suggests that factors other than the catecholamine (e.g., gonadal hormones) also affect melatonin secretion. Oophorectomy elevated the melatonin concentration of serum but not that of the pineal; this rise was suppressed by the administration of estrogen plus progesterone. The fate of circulating melatonin (as indicated by the proportion of an exogenous dose excreted into the urine) was not affected by the state of the estrous cycle.


Affinity purification of cardiac adenylate cyclase: dependence on prior hydrophobic resolution. The interaction of cardiac adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] with a variety of nucleotide affinity resins was systematically investigated. None of these resins effectively bound the native, detergent-solubilized enzyme. However, after hydrophobic resolution on an uncharged resin consisting of long-chain alkyl groups linked to agarose via ether bonds, 40% of the adenylate cyclase activity biospecifically adsorbed to an ATP affinity resin. Gel filtration without detergent after hydrophobic chromatography demonstrated that the enzyme eluted in the identical position as the native enzyme chromatographed in the presence of detergent. This preparation almost completely biospecifically adsorbed to the same ATP-resin and was not eluted with 5 mM cyclic AMP, pyrophosphate, or GTP. If the GTP-washed immobilized enzyme was subsequently desorbed with ATP, then expected Gpp(NH)p (5'-guanylyliminodiphosphonate) sensitivity persisted. A preliminary purification scheme that resulted in an approximate 5000-fold increase in specific activity is presented. These observations indicate that a membrane-bound enzyme may appear to be intrinsically hydrophobic only by virtue of aggregation with other hydrophobic constituents and that prior separation of hydrophobic chromatography may permit such proteins to be fractionated subsequently by methods conventionally applied to hydrophilic proteins.


Energy conformation study of Met-enkephalin and its D-Ala2 analogue and their resemblance to rigid opiates. Conformational similarities of Met-enkephalin and its D-Ala2 analogue to rigid opiates were studied by both empirical and quantum mechanical methods. By both methods, conformers with maximum resemblance to rigid opiates have the highest energies. Conformers with the lowest energy had no resemblance to rigid opiates. However, several low and intermediate energy conformers were identified in which at least the NH2-terminal tyrosine residue overlaps with the phenethylamine moiety of rigid opiates and which could equally well accommodate either Gly2 or D-Ala2. The conformer among these with greatest additional resemblance to other binding sites of rigid opiates is proposed as the most likely candidate for an induced fit at the receptor site.


Abnormal cellular localization of thyroglobulin mRNA associated with hereditary congenital goiter and thyroglobulin deficiency. The goiters in a breed of hypothyroid goats contain only minute amounts of thyroblobulin-related antigens (0.01% of normal value). We have analyzed these goiters for the presence of mRNA coding for thyroglobulin. Using DNA complementary to beef 33S thyroglobulin mRNA as a probe, we found that the mRNA sequence is present in the goat goiter but at a concentration 1/10-1/40 that of normal goat thyroid. Hybrids of cDNA with either goiter or normal thyroid RNA exhibited identical sharp melting curves which suggests that the same RNA sequence is responsible for hybridization in both tissues. Normal goat thyroid contains a population of large membrane-bound polysomes engaged in throglobulin synthesis. In contrast, such polysomes are absent in the goiter. In regard to subcellular distribution, the relative amount of the thyroglobulin mRNA sequences from the goiter in nuclear RNA was 42% of normal, in cytoplasmic RNA was 7% of normal, and in the membrane fraction was only 1-2% of normal. Our results suggest that the lack of thyroglobulin in these goiters is due to a defect in thyroglobulin mRNA which leads to aberrant processing and/or transport of it from its site of synthesis to the endoplasmic reticulum.


Ovalbumin: a secreted protein without a transient hydrophobic leader sequence. Ovalbumin mRNA was translated in a reticulocyte lysate. The primary translation product starts with methionine derived from Met-tRNAf. When the nascent polypeptide is about 20 residues long, this methionine is removed. The new NH2-terminal glycine is acetylated from acetyl-CoA when the polypeptide is 44 residues long. The sequence of 35 residues at the NH2 terminus of ovalbumin was determined by automated Edman degradation after a method was devised to prevent acetylation during protein synthesis in the reticulocyte lysate. This sequence is the same as that of secreted ovalbumin and does not resemble the transient "signal peptides" associated with most secretory proteins, including three other egg white proteins synthesized in the same cells as ovalbumin.


Aphagia, adipsia, and sensory-motor deficits produced by amygdala lesions: a function of extra-amygdaloid damage. Small bilateral electrolytic lesions confined to the region of the central nuclei of the amygdala failed to affect food and water consumption in male rats. More medially-placed lesions which damaged portions of the internal capsule, entopeduncular nucleus and globus pallidus adjacent to the central nucleus produced transient aphagia and adipsia accompanied by sensory-motor impairments that interfered with the act of feeding, as evidenced by a large postoperative increase in the amount of food spilled. In some cases lesions restricted to the internal capsule and entopeduncular nucleus produced these sensory-motor deficits but no aphagia or adipsia. Small lesions damaging primarily ventral portions of the posteromedial pallidi resulted in aphagia and adipsia but no apparent sensory-motor impairment. The results indicate that at least two, possibly independent, deficits in food intake may be produced by lesions in the immediate area of the dorsomedial amygdala. It is suggested that the effects on ingestive behavior which several investigators have observed in rats with dorsomedial amygdaloid damage may in fact be due to incidental destruction of adjacent tissues.


Insulin-induced hyperphagia in alloxan-diabetic rats fed a high-fat diet. Alloxan-diabetic rats fed a standard, low-fat diet lost body weight and were hyperphagic; those fed a high-fat diet lost comparable amounts of weight, but did not overeat compared to normal animals. When given injections of protamine-zinc insulin, all diabetic rats gained weight; however, while those fed the low-fat reduced food intake from elevated levels, diabetics fed the high-fat diet became hyperphagic. Diabetic rats maintained on a high-fat diet increased food intake during long-term insulin treatment sooner and to a greater extent than normal controls. These findings are interpreted in light of the effects of insulin on storage and supply of metabolic fuels.


Osteosarcoma -- surgery, radiotherapy and chemotherapy.


Action of methoxytryptamine and mao inhibitors on the heart and penis retractor muscle of strophocheilus oblongus (gastropoda, pulmonata).


Clinical and structural features and possible pathogenic mechanisms of dental fluorosis.


Salivary fluoride and calcium concentrations, and their relationship to the secretion of saliva and caries experience. Samples were collected from the stimulated saliva of 113 students enrolled in institutions of higher education. The students were divided into three "carries-diagnostic groups" on the basis of indications given by the Dentocult saliva test, which shows the frequency of lactobacilli and other aciduric microorganisms in saliva. The frequency of such microorganisms in 1 ml saliva in Group A was less than or equal to 103, in Group B greater than 10(3), less than 10(4) and in Group C greater than or equal to 10(4). The rate of secretion of saliva in Group A was significantly higher than in Group C (P less than 0.05). On the average, a rise was noted in the fluoride and calcium concentrations with increasing "caries activity". In the material as a whole, there was a negative and highly significant correlation between the secretion rate of saliva and the concentrations of fluoride and calcium. In the examination by groups, significant correlations were observed between fluoride concentration and rate of saliva secretion in Group A, and with respect to fluoride and calcium only in Group C. The results suggest that the extra salivary fluoride is likely to be derived from the enamel.


Hardness testing of some fissure-sealing materials. The mechanical properties of fissure-sealing materials are of significant importance for their durability, i.e. their wear resistance. One of the methods of evaluating a material's resistance to attrition is to apply a hardness test. In the present investigation, the surface hardness of some fissure-sealing materials was tested. Sealants made from diluted composite materials and with inclusion of inorganic filler particles appeared to have a considerable higher surface hardness than the other sealing materials tested.


Histologic and microradiographic observations on teeth during calcium deprivation in rats. Adult female rats were subjected to severe calcium deprivation by feeding them a calcium-deficient diet containing oxalate (Group a). Furthermore, pregnant and lactating animals were subjected to the same diet (Group b). The mandibular teeth were examined by histologic, microradiographic and fluorescence microscopic techniques. The incisor enamel was found to be nearly unaffected by the experimental regimen; the dentin formed and mineralized during the experimental period was abnormal only in Group b. Characteristic features were reduced thickness, increased width of predentin and numerous globular defects. Both ameloblasts and odontoblasts were seemingly normal. No obvious differences could be observed between the molars from the controls and the test groups (a,b). "Cementolysis" seemed to be present to the same extent in all groups. In some of the animals of Group b some carious or erosional defects were observed in the molars. These may at least partially account for a small reduction in molar ash content observed in this group.


Microstructure of inner surfaces on composite restorations related to filling procedure. The inner surfaces of 40 Concise restorations placed in vivo on permanent molars have been studied by scanning electron microscopy. Only grinding traces could be seen on fillings from cavities which had not been etched, while the morphologic structure of the enamel and dentin was reflected on fillings from acid-etched cavities. Application of low-viscous non-composite resin in the cavities before filling with the composite resin did not influence the enamel pattern on the fillings, while the amount of processes of resin corresponding to the dentinal tubules in etched cavities was significantly increased. In the discussion the difference in surface structure of the fillings is correlated to marginal leakage along similar restorations.


Epithelial-like cells in culture derived from human gingiva: response to nickel. To obtain gingival cell cultures, human gingival tissue was minced and/or subjected to trypsin treatment with or without prior separation into epithelial and connective tissue portions. The tissues were then incubated in Eagle/Earle's MEM with 10% fetal calf serum in a humidified atmosphere of 5% CO2 in air. Fibroblast-like cell cultures were regularly obtained, and one culture showed epithelial-like cell islets that could be transferred and kept in continuous culture. These epithelial-like cells exhibited bone resorption stimulating activity as seen in gingival tissue and retained their growth pattern after prolonged storage. They were able to grow at serum concentrations down to 2.5% and with equal doubling time (about 17h) in rich or minimum essential media. Exposure to nickel gave toxic effects on the growth at concentrations down to 2.5 microgram/ml of nickel. In spite of the affinity of nickel to certain serum components, the serum concentration did not appear to be of specific importance to protect or aggravate the toxicity. It is felt that these cells may be of value for research on cytotoxicity of dental materials.


Agreement between clinical and histologic findings in chronic coronal pulpitis in primary teeth. Pulpotomy, a common endodontic procedure in primary teeth, is usually performed because of carious exposure of the pulp, which means that at least a part of the pulp is chronically inflamed. A favorable outcome of pulpotomy combined with the use of calcium hydroxide presupposes that the root pulp is healthy. No wound dressing is known to induce healing of chronically inflamed pulp tissue. 37 primary teeth with no clinical or radiographic symptoms of total chronic pulpitis were extracted and the pulp was studied histologically by light microscopy. The histologic diagnosis of a healthy root pulp was based on absence of any infiltration of mononuclear lymphocytes. Agreement between the clinical and histologic diagnosis was found in 30 out of 37 teeth.


Long-term prognosis of traumatized permanent anterior teeth showing calcifying processes in the pulp cavity. 122 traumatized teeth with radiographic evidence of abnormal hard tissue formation in the pulp cavity were examined 10-23 years (mean 16 years) after the time of injury. Judged radiographically, partial obliteration (pulp chamber not discernible, root canal markedly narrowed but clearly visible) had occurred in 44 teeth (36%). Normal periradicular conditions were found in all teeth with partial obliteration. Seventy-eight teeth (64%) were recorded as totally obliterated. Pathologic periradicular changes indicating pulp necrosis as a sequel to the total obliteration was observed in 16 teeth (21%). The late development of pulp necrosis was significantly related to teeth classified as severely injured, and to teeth with complete root formation at the time of injury. Furthermore, a comparatively rapid progress of the calcifying process appeared to be correlated with periradicular radiolucency.


Furfurals in chlorhexidine-discolored pellicle. The purpose of the present study was to investigate the possible presence of furfurals in chlorhexidine-discolored pellicle. Pellicle material was scraped off teeth and hydrolyzed in sulfuric acid and the hydrolysate then extracted with ether and examined by thin layer chromatography and gas chromatography-mass spectrometry. The presence of furaldehyde in discolored pellicle was demonstrated by these methods. There were also indications of hydroxymethyl furfuraldehyde in the thin layer chromatograms.


The in vitro phagocytic function of neutrophil leukocytes in patients with severe Candida-induced denture stomatitis.


Variations in structure within the trabecular bone of the mandible. A study of the intramandibular variations in bone mass, coarseness of the bone trabeculae and bone activity between incisor, premolar, and molar regions has been carried out, as well as estimation of possible differences in these variations between groups of mandibles with different dentition. The material consisted of 24 autopsy specimens of half mandibles from normal subjects. Microradiograms of ground sections from incisor, premolar, and molar regions were used. Quantitation of bone mass was done by an electronic point-counting system. The analysis indicates that (1) the variations in bone mass within same region are marked, (2) trabecular bone is denser and more delicately woven in the incisor region than in either premolar or molar regions, where mass of bone is the same, although there is probably more delicately woven trabecular bone in molar region, (3) bone activity lies on the same level all over in trabecular bone within the mandibular body and (4) the variations of these factors seem to be independent of state of dentition in the single mandible.


In vitro corrosion of dental amalgams with different Cu content. Both Cu amalgam and Sn-containing Ag amalgam alloys with Cu contents ranging from 2 to 30% were used in the investigation. The amalgams were placed in artificial saliva and the content of the dissolved Cu was determined after 1 month. The amalgam remained in the saliva for another 5 months. After the amalgams were removed from the solution, metallographic and microprobe examinations were made. The Cu amalgam released about 10 times more Cu to the artificial saliva than any of the other amalgams. The dispersion type amalgams showed a relatively large dissolution of Cu, while a smaller release was found from amalgam made of powder with one composition. The phases that appeared to be corroded first were gamma2 and Cu-Sn phases. In dispersion type amalgams the gamma phase appeared to be attacked. Most of the corrosion products remained inside the amalgam and were identified to be tin oxide chlorides.


Ethical problems in the management of gastroenterological patients.


Erythrophagocytosis by acute lymphoblastic leukaemic cells. Phagocytosis of erthyrocytes and platelets by bone marrow blast cells has been noted in 4 patients in the late relapse of acute lymphoblastic leukaemia (ALL). The underlying mechanism is unclear but prolonged course of the disease seems to be a major factor in the emergence of cells with phagocytic properties.


Exploring child health and its ecology.

Exploring child health and its ecology.


Prophylactic value of synovectomy of the proximal interphalangeal finger joint in rheumatoid arthritis.


Case report: an asthmatic child with a very high consumption of Ventoline respirator solution.


Scanning electron microscopic studies of bronchial mucosa before and during treatment with beclomethasone dipropionate inhalations.


Long-term treatment with corticosteroids in children.


Lung function test for assessment of effects of drugs in asthma.


Volume of trapped gas (VTG) during provoked asthma and after inhalation of salbutamol.


Controlled clinical trials in asthmatics.


Comparison of infused and inhaled terbutaline in patients with asthma.


Laboratory aids. Theophylline levels.

Laboratory aids. Theophylline levels.


Diabetes in pregnancy: a review.

Diabetes in pregnancy: a review.


Colloidal phenomena encountered in the bacterial adhesion to the tooth surface.


The enamel substrate-characteristics of the enamel surface. The outer enamel surface is of considerable interest in dentistry as it is the substrate for the acquired pellicle; the pellicle itself is the plaque carrier. In this paper the interface between outer enamel and pellicle is discussed with special emphasis on the outer enamel from a structural and chemical point of view. The outer enamel layer (less than 1 micron from the anatomical surface) is most likely a non-stoĭchiometric apatite. The chemical composition is obviously strongly different from the composition of bulk enamel. A model for the structure and atomic composition of surface enamel is presented. The available experimental evidence indicates that at an atomic scale, enamel crystallites have mainly phosphate groups (HPO42-groups) on the solid surface; the liquid adhering Stern layer contains most likely large amounts of calcium ions.


Macromolecular components of oral fluids at tooth surfaces.


Adherence of bacteria to tooth surfaces.


Genetic manipulation in higher organisms. I. Goldfish ova as materials of operation, mRNA mediated alteration of the liver specific isozymes. Both crucian and carp egg-mRNAs were found to mediate the transformation of goldfish tail from the double (veil-shaped) to the single (fork-shaped). Livers of these single tailed goldfish were tested for genetic change using lactate dehydrogenase isozymes (LDH) as marker. Electrophoresis of liver extracts on starch gel showed that the liver specific LDH-C4 isozymes of both the egg-mRNA and liver-mRNA injected goldfish resembled the control goldfish except an additional intermediate band. The migration distance of this new band matched the third band of the hybrids (carp X goldfish). These findings lead to the conclusion that carp egg-mRNA contains a fraction partly responsible for liver development. Rat liver was found possessing the cathodally migrating C4 isozymes. Injection of rat liver-mRNA into goldfish eggs resulted in the intensification of the liver specific C4 isozymes. It appears therefore that the input informational molecules (liver-mRNA) and the output molecular products (liver C4 isozymes) are causally related. This causal relationship would pave the way for genetic manipulation in higher organisms.


On the formation of biological films.

On the formation of biological films.


Haloxon as an anthelmintic for dogs and cats.


Correction of facial disability.

Correction of facial disability.


Rapid cytoreduction in acute leukemia. Management of cerebral leukostasis by cell pheresis. A patient with acute myelogenous leukemia and symptoms of cerebral leukostasis failed to respond to initial chemotherapy. Reduction in blast count from 220,000/microliter to 40,000/microliter was accomplished over a five hour period by leukapheresis using an intermittent flow cell separator, and symptomatic improvement was dramatic. The technique is simple and rapidly effective and may prove a useful adjunct in the treatment of patients with acute leukemia and high blast counts.


Use of oral haloperidol following rapid tranquilization of acutely disturbed patients.


The therapy of peptic ulcer disease.

The therapy of peptic ulcer disease.


Hemopoietic dysplasia (preleukemia).

Hemopoietic dysplasia (preleukemia).