Age-related chemical changes in human elastins from non-atherosclerotic areas of thoracic aorta. Elastins from normal appearing areas of human thoracic aortae with varying degrees of mineralization were taken from subjects of different ages and purified by autoclaving their amino acid compositon, Ca and P contents and N terminal profiles were determined before and after EDTA decalcification. (1) Decrease in desmosine concentration with increasing age was accounted for by dilution of the elastin by autoclave-resistant polar glycoproteins. (2) The appearance and growth of a mineral phase with a Ca/P molar ratio typical of apatites was accompanied by an increased association of polar contaminants with elastin. (3) After 24 h EDTA treatment, small and constant amounts of Ca were still apparent although P was absent, in elastins from all age groups. (4) The undialyzable fraction of the material solubilised by EDTA consisted mainly of elastin fragments, glycoproteins and Ca. (5) All the elastin samples showed the same type of N-terminal amino acids. In low and medium mineralized samples the concentration of amino end-groups was slightly increased, while in highly mineralized elastin the content of N-terminal residues was three times greater than in normal young elastin. Extraction with EDTA reduced the amount of end-groups to a normal level. It is suggested that in the initial stages of elastin fibre mineralization, an increased amount of autoclave-resistant glycoproteins becomes associated with elastin; and that with ageing, degradative changes involving peptide-bond cleavage may occur. However, evidence of degradation is found only in old and highly mineralized elastin samples.


Enzymes of DNA synthesis in isolated nuclei of swin aorta. Enzymes of DNA synthesis, thymidine kinase (ATP-thymidine-5'-phospho-transferase, EC 2.7.1.21), DNA polymerase (EC 2.7.7.7) and nuclease activities were investigated in isolated purified nuclei of swine aorta. Thymidine kinase which is detectable in these nuclei can be stimulated by the addition of phospholipase C. DNA polymerase activity of isolated nuclei is strongly dependent on addition of an exogenous template; the preferred template is activated DNA. The activity in the absence of an added template is very low except when labelled dCTP is used as the precursor. This incorporation of labelled dCTP does not require the addition of the other three triphosphates, and under these conditions, dCTP seems to be incorporated into what may be a homopolymer. As with other tissues, solubilized preparations of aortic nuclei have two DNA polymerase activities which also prefer activated DNA template. There is no detectable endonuclease in aortic nuclei.


Vitamin A and lysosomal stability in rats fed an atherogenic diet. The relation between vitamin A status and lysosomal stability was studied in rats fed a high fat-cholesterol diet. Increase in the total activity of lysosomal enzymes as well as that in the nuclear fraction, intact lysosomal fraction and free activity (activity present in the 15,000 X g supernatant) in the liver was observed in rats fed an atherogenic diet with adequate vit. A. Vitamin A deficiency and hypervitaminosis (10,000 IU) augmented this increase in the total enzyme activity as well as the activity in the subcellular fractions except in the case of intact lysosomes where the activity was not significantly altered. At 2,000 IU, there was no significant alteration in either the total activity or the activity of the subcellular fractions. An analysis of the ratio of soluble activity (released from the lysosomes) to the activity present in the intact lysosomes, showed that hepatic lysosomal stability was decreased in the rats fed an atherogenic diet with normal dose of vit. A. Vitamin A deficiency as well as hypervitaminosis decreased the lysosomal stability still further. At a dose of 2,000 IU, lysosomal stability increased as compared to the rats fed an adequate dose of vit. A, while total lysosomal activity remained not significantly altered. Studies on the rate of release of enzymes from the lysosomes revealed that there was significantly more release of the enzyme between 30 and 45 min in the liver and aorta in the rats fed a high fat-cholesterol diet with adequate vit. A This release was still more in the rats fed a low dose of vit. A. At 2,000 IU, there was no significant difference in the enzyme release. But the pattern of change in the liver and aorta in the hypervitaminotic group was different. In the case of hepatic lysosomes, there was an increase in the enzymes released while in the aorta there was significant decrease. This has been attributed to the fact that lytic concentration of the vitamin A is not attained in the aorta.


Lipid-lowering activity of phytostanols in rats. In the present study, the hypocholesterolemic activity of phytosterols and phytostanols was compared. Phytostanols were prepared by hydrogenating a phytosterol mixture from corn oil and were fed at different levels (0.1-1.0%) to male rats for 10 to 14 days with or without cholesterol (1.0%). In an appropriate combination with cholesterol, phytostanols showed significantly greater activity in lowering the plasma and possibly liver cholesterol levels in comparison with the corresponding phytosterols. The stanols further stimulated the fecal recovery of cholesterol. The rate of intestinal absorption of phytostanols appeared obviously lower than that of phytosterols and thus the deposition into plasma and liver lipids was almost negligible.


Preprandial drinking and plasma lipids in man. A group of normolipemic subjects who consumed alcoholic drinks before their evening meals for a period of 7 consecutive days demonstrated a significant increase in their fasting plasma triglyceride levels. On cessation of alcohol consumption, the fasting triglyceride levels reverted to their pre-experimental levels. The plasma cholesterol levels did not show any consistent changes.


Effect of unilateral nephrectomy of the localization of aortic sudanophilic lesions in cholesterol-fed rabbits. The method of polar coordinate mapping of lesions on the aortic wall around orifices was used to study the effect of unilateral nephrectomy on sudanophilic lesions in rabbits. Four groups of six rabbits each were studied. Group I had a right nephrectomy with a short renal artery stump. Group II had a sham right nephrectomy. Group III had a left nephrectomy with a short renal artery stump and Group IV a sham left nephrectomy. All groups were allowed to recover for one week and were then fed rabbit chow enriched with 2% cholesterol and 6% corn oil for a four-week period. Groups I and III showed a marked alteration in lesions around the stump with both proximal and distal peaks. Group I also showed the development of skewing of the left renal lesion to the left, presumably because of a change in aortic flow due to removal of the proximal right renal flow. The right renal artery had a lesion skewed to the right; this was not altered by left nephrectomy and was probably due to coeliac flow. The data provides strong evidence that sudanophilic lesions in rabbit aortas are altered by local flow disturbances.


Factors stimulating collagen synthesis from the livers of hypercholesterolemic rats. Hypercholesterolemia was induced in rats by feeding them a high cholesterol olive oil diet. The livers were homogenized in modified Krebs-Ringer medium and centrifuged at 35,000 x g. The supernatants from livers of both hypercholesterolemic and normal rats were found to stimulate collagen synthesis in freshly isolated embryonic chick-tendon fibroblasts. However, this was significantly greater in the supernatants from fatty livers. The stimulating principle proceed to be dialyzable, non-lipid and heat-stable. There were at least two factors involved, the more effective of which was trypsin-sensitive, with a molecular weight below 2,000. The results suggest that a mediator is formed in the livers of hypercholesterolemic rats which might be responsible for the enhanced collagen synthesis of fibrotic processes vivo, e.g., in atherosclerosis and liver cirrhosis.


Mechanical and histological study of aortic valve tissue from a patient with Marfan's disease. A comparison between a normal and a Marfan's disease aortic valve has been attempted in terms of their tissue stress-strain characteristics and their histology. The diseased valve tissue was found to be more compliant by an order of magnitude than the normal valve, which is related to the disorientation of its collagen fibers, and the proliferation of mucopolysaccharides.


[Postmenopausal bleeding (author's transl)]. In the study reported here, 554 cases of postmenopausal bleeding were analyzed, i.e. 4.1% of the gynecological cases admitted during the 11 years from 1961 to 1971. In over one-third of these cases (35.3%) bleeding was caused by genital carcinoma. Among nonmalignant causes, endometrial atrophy was the most common (28.5%) followed by uterine polyposis (21.2%). As expected, corpus carcinoma (51%) was the most commonly found malignant genital disease, followed by cervical cancer (38%) which, surprisingly, is almost as common. The time-lapse between onset of bleeding and hospitalization with diagnosis is alarmingly long. In our patients it averages 19.2 weeks, is 36.3 weeks in corpus carcinoma cases and 16.3 weeks in women with cervical cancer.


The effect of ileal bypass on sterol balance and plasma cholesterol in the White Carneau pigeon. The effect of ileal bypass on steady-state sterol balance and plasma cholesterol was studied in sham operated (SO) and ileal bypass (IB) White Carneau pigeons 6 months (Group I) and 18 months (Group II) after surgery while fed their usual cholesterol-free diet. Unlike what has been noted in other animals, the bile acid (BA) and neutral sterol (NS) excretion (mg/kg per day) in IB was not statistically different from that in SO. Group I: BA, 40.2 (SO) vs 39.0 (IB); NS, 13.3 (SO) vs 17.3 (IB). Group II: BA, 55.7 (SO) vs 54.1 (IB); NS, 9.57 (SO) vs 8.84 (IB). IB pigeons had only slightly lower plasma cholesterol levels (postoperative) than SO pigeons. Group I, 329 (SO) vs 271 (IB) mg/dl (P less than 0.05); Group II, 374 (SO) vs 312 (IB) mg/dl. This study indicates that the response to ileal bypass by White Carneau pigeons in terms of cholesterol excretion and plasma cholesterol changes is different than what has been observed in other species.


[Surgical treatment of occlusive diseases of visceral branches of the abdominal aorta]. Sixty two patients having chronic circulatory disorders in visceral branches of the abdominal aorta were operated upon by the authors. An adequate circulation was restored as a result of reconstructive (44), conventionally reconstructive (14) and palliative (4) operations. A number of technics considerably facilitating these complicated reconstructive procedures are described: transaortic endarterectomy from the abdominal aorta, visceral branches and renal arteries: resection of the thoracoabdominal aorta followed by a plastic reconstruction of the celiac trunk ostium and others. In 47 patients (90.3%) a clinical effect was gained: the signs of ischemia of the digestive organs have disappeared.


[Umbilical cord hernias].

[Umbilical cord hernias]. The authors observed 38 children with umbilical cord hernias. In 27 of them some other defects were noted. Among 25 children there were 14 deaths (56.2%). Conservative therapy was conducted in 13 patients with umbilical cord hernia, 10 children died (76.9%).


[Isolation and properties of the acid carboxypeptidase of Aspergillus oryzae]. Caboxypeptidase with pH optimum 4--5 for peptide substrates is isolated from "oryzine", the enzyme mixture produced by Aspergillus oryzae, by means of successive salt fractionation, Sephadex G-75 gel filtration, chromatography on amberlite IRC-50, hydroxylapatite, DEAE-cellulose and polyacrylamide gel electrophoresis. Its molecular weight, as determined by means of polyacrylamide gel electrophoresis in the presence of sodium dolecylsulphate, was found to be 37 000. The enzyme has a broad substrate specificity and does not possess dipeptidase and esterase activities. Acid carboxypeptidase from Asp. oryzae is not a metalloenzyme, it is inactivated by specific inhibitors of serine proteases and by compounds blocking SH-groups. The enzyme is suggested to contain functionally important serine and cysteine residues and to be acid carboxipeptidase.


[Carcinoma after gastric operations (author's transl)]. The incidence of carcinoma after gastric operations for benign lesions was analysed in the patient material of five gastroenterologists in private practice in Switzerland. Of 534 such patients 346 had had a gastric resection with gastrojejunostomy (Billroth II), 58 with gastroduodenostomy (Billroth I), and 130 other kinds of gastric operations. Among 326 patients who had a Billroth II procedure there were 21 with proven carcinoma in the residual stomach, but none after Billroth I and other operations. The incidence after Billroth II was 15.1% at or after ten years. Of 69 patients 10-19 years after gastric resection, six had developed carcinoma, compared with 15 of 70 who were 20 years or more after the resection. The incidence is unexpectedly high. On the other hand, among 29361 non-operated patients there were 279 with carcinoma of the stomach. The average interval between operation and the diagnosis of carcinoma in the residual stomach was 23.8 years. It is recommended that gastric resection should if possible be avoided for benign disease. All patients who have had a gastric resection should be endoscopically controlled annually from ten years after the resection onwards.


[Transaminases and acid phosphatase in the ejaculate and their relation to fertility]. The values of the transaminases (GOT, GPT) and the acid phosphatase in the ejaculate do not differ between men of known fertility and infertile men.


[Immunological response of mice to diphtheria toxoid]. Following the determination of immunological response in mice, by titration, 1.5 Lf diphtheria toxoid was found as an optimal plasma cell activator. Groups of mice were subcutaneously injected with 1.5 Lf diphteria toxoid and on 2, 3, 4, 6, 10, 15 and 25th days of injection mice were killed and their blood, spleen, thymus, lymph nodes and lungs preserved. Section from these specimens were stained by methyl-green, pyronine and toluidine. Lymphocytes, plasma cells, and mast cells were counted in 10-20 fields in each preparation. Mature plasma cell ratio was calculated against lymphocyte counts. Mature plasma cell and mast cell counts and ratios of test mice were found increased when compared with that of normal control mice. The difference in thymus, spleen and lungs was found to be insignificant, however it was significant, p less than 0.05 in lymph. nodes. Maximum cell counts were seen at ten days. The sera of the test mice were also examined for humoral antibodies with precipitation and Römer's skin test. on 2, 3, 4, 6 and 10th days no antitoxin could be demonstrated in the sera of the test mice in controls either. In the sera taken on 15 and 25th days antitoxin was detected.


[Animal experiments on ozone therapy of non-irradiated and irradiated tumors. II. Ehrlich ascites carcinoma in vivo]. Mice, carriers of the Ehrlich ascites carcinoma, were exposed to a fractionated whole-body irradiation with four times 750 R. Before resp. after each exposure, an ozone-oxygen mixture was intraperitoneally injected. In other cases, the ozone-oxygen mixture was given without irradiation. Ozone had no essential effect upon the transplantation capacity neither in irradiated ascites cells nor in cells not exposed to radiation. Ehrlich ascites tumor cells, transplanted into a subcutaneous air-pocket under the abdominal skin of the mouse, developed a solid tumor and a fluid accumulation without cells. A diminution of the fluid was brought about by means of a fractionated local irradiation with five times 200R, by a secondary treatment with ozone and also by ozone alone. Evidence of damage to the tumor cells, however, is only to be produced by investigations into the metabolism and reproductive capacity of these cells.


[Venous wall graft in Peyronie's disease (author's transl)]. One patient with Peyronie's disease (induratio penis plastica) was treated utilizing plastic surgery to correct the penile curvature. The plaques which invaded the corpora were transversely incised and a section of the greater saphenous vein was sewn into the gap. Postoperatively, the penis is quite straight and the patient has resumed normal sexual intercourse.


[Pathogenetic mechanisms and classification of manic-depressive psychosis]. A study of the heredity and exogenic factors in 340 patients with manic-depressive psychosis makes it possible to draw a conclusion that the disorder is polyetiological. In a bipolar development there is mainly a hereditary loading and organic noxious factors, in a monopolar depression--exhaustive factors. The assumption of an existence of 2 independent psychoses (bipolar and monopolar) which was made by several foreign authors was not confirmed.


[Cytophotometric analysis of proteins in human embryo hypophyseal cells in normal and pathologic pregnancies]. As it is known, formation of the adenohypophysis in the human fetus takes place at early stages of ontogenesis. The objective of the present work was to find out whether the adenohypophysis, already at these early stages of development, was capable to response to changes in the environment, in this case to those in the mother's organism. Two groups of the human adenohypophyses obtained as a result of artificial abortion were studied: 1) from fetuses which developed under normal pregnancy; 2) from fetuses which developed under pathological pregnancy (toxemia in the first half of pregnancy). The method of quantitative cytospectrophotometric analysis of simple and conjugated proteins of a various nature were used. The data obtained indicated to early appearance of simple and conjugated proteins in the cells of the anterior lobe of the hypophysis of the human fetus and to their definite dynamics depending upon the course of pregnancy. It was established that at early stages of ontogenesis the adenohypophysis of the human fetus produces a certain reaction to changes in the environment, in particular, to changes occurring in the mother's organism.


Evaluation of an emergency department observation ward. To evaluate the usefulness of an observation or holding area in the operation of an emergency department, the 166 cases held in the observation area of the Harbor General Hospital Emergency Department during September, 1974, were reviewed. Among the 166 patients, who made up 2% of the 10,452 patients seen in the ED that month, drug overdose and alcohol withdrawal were the primary disorders admitted, 42 and 34 respectively. Neurological disorders were next with 29 cases. Fluids administered intravenously, analgesics and sedatives were the most common therapeutic modalities used. Psychiatric was the type of consultation required most often. Seventy-seven of the 166 patients went home; 61 were admitted to the hospital and none died. Fifteen were transferred to nursing homes, 8 to to detoxification centers and 5 to a mental hospital. The advantages and disadvantages of an observation ward are listed and discussed.


Acute coronary syndromes following abrupt cessation of oral propranolol therapy. Abrupt cessation of oral propranolol therapy was followed by 15 acute coronary events in 14 patients with severe angina who had been receiving propranolol in daily doses of 80 to 400 mg for periods of 7 days to 6 years. Propranolol had been stopped 1 to 14 days before each acute event because of angiographic study (seven patients), increasing symptoms (three), acute coronary insufficiency (one), asymptomatic bradycardia (one), elective surgery (one) and unknown reasons (two). Before abrupt cessation of propranolol treatment anginal symptoms had been stable in six instances but had increased in the other nine. Cessation was followed by rapid progression of symptoms prior to 11 of the 15 acute events. There were six acute transmural myocardial infarctions with three deaths, three intramural myocardial infarctions, one with ventricular fibrillation, and six episodes of acute coronary insufficiency, Unstable angina followed nine of the events and responded to propranolol therapy (160 to 320 mg/d) in eight instances. Three other patients underwent aortocoronary bypass surgery; perioperative acute myocardial infarction occurred in two. These data suggest that in a minority of patients abrupt cessation of propranolol may be hazardous, particularly in severe or unstable disease. Cessation or propranolol therapy in such patients should be gradual and closely observed. Recurrent symptoms respond to reinstitution of propranolol therapy.


Factor-analytic structure of patient internal states. The present analysis represents a relatively simple technique that can be used to study patient internal states. Thus, when patients were asked to indicate the extent to which they experienced each of 33 feelings, consistent with previous literature, they viewed their feelings in generally positive or negative terms. Inconsistent with previous results, when show that therapists produce a highly differentiated factor structure when asked to describe their patient's feelings, the present study also found that therapists saw their patients in generally positive or negative terms. This result was attributed to the experience level of the therapists, as the present study utilized only inexperienced therapists, whereas experienced therapists were used in previous analyses.


The Leeds scales for the self-assessment of anxiety and depression. Self-rating scales are finding an increasing use in psychiatric work. Not only are they widely used in research, but they provide the clinician with a score indicating the patient's psychiatric state at any one time, and these scores if repeated throughout the duration of treatment may be considered to provide a continuing measure of the severity of the illness, as does a temperature chart in a febrile illness. Most scales could be improved by item analysis, and in this study the Wakefield Self-Assessment of Depression Inventory, with added items, was subjected to statistical analysis. It was found that valid scales could be constructed for the measurement of anxiety and of depression in general psychiatric disorders, as well as scales for the measurement of the severity of endogenous (primary) depression and of anxiety states. In addition, the derivation of a 'diagnostic' score was confirmed in a cross-validation study and may be found of use both in research and in clinical practice.


The relationship between different evaluations of drinking behaviour. Prisoners' attitudes to their drinking behaviour, although largely accurate, minimize problems in terms of other assessments made at interview. Semantic differences are apparent in the use of the terms 'heavy' and 'problem' as descriptions of drinking behaviour; thus men who admit heavy but deny problem drinking are often reported to be problem drinkers by their family and myself. There is close agreement between the family's reported attitude to a man's drinking and the assessment made in a structured psychiatric interview.


Effect of stimulation of carotid chemoreceptors on total and regional cerebral blood flow. This study was performed to determine whether stimulation of the carotid chemoreceptors increases total or regional cerebral blood flow and whether activation of arterial chemoreceptors contributes to cerebral vasodilation during systemic hypoxemia. In anesthetized and ventilated dogs, carotid chemoreceptors were stimulated with nicotine or hypoxic and hypercapnic blood. To measure total and regional cerebral blood flow, we used labeled 15-mu microspheres. Stimulation of chemoreceptors did not increase cerebral blood flow or produce significant redistribution of cerebral blood flow, even though the chemoreflex was intact in these animals (as manifested by vasoconstriction in muscle, kidney, and small bowel) and the cerebral vessels dilated in response to systemic hypercapnia. In other studies in anesthetized, ventilated dogs and rhesus monkeys, cerebral vasodilator responses to systemic hypoxemia were observed before and after denervation of carotid and aortic chemoreceptors. Systemic hypoxemia produced large and equivalent increases in cerebral blood flow before and after chemodenervation. We conclude that stimulation of carotid chemoreceptors does not produce cerebral vasodilation and that chemoreceptors do not contribute significantly to cerebral vasodilation during systemic hypoxemia.


Gallbladder visualization in adrenal scanning: case report. A patient suspected of having adrenal hyperfunction was scanned with 131I-iodocholesterol. Intense gallbladder activity persisted for several days and was eliminated by a fatty meal. The possibility of confusion with unilateral adrenal localization is discussed.


The relation of severe malnutrition in infancy to the intelligence of school children with differing life histories. The IQ's of Jamaican boys aged 6-10 were associated significantly with the presence or absence of severe malnutrition in infancy, with height at time of IQ testing, and with a measure of the boys' social background. A multiple correlation coefficient of 0.674 was obtained between IQ and the three factors. Social background contributed 0.294 of the variance, height 0.112, and severe malnutrition 0.049. The two extreme groups of boys, i.e., those malnourished, small at follow-up, and with unfavorable social backgrounds and those not malnourished, tall at follow-up, and with favorable social backgrounds had average IQ's of 49.4 and 74.9, respectively (from Table 5). Only two of the boys in the most advantaged group had IQ scores that overlapped with the most disadvantaged group. Boys with severe malnutrition in infancy, but who are tall at follow-up and have a favorable social background have an average IQ 11 points higher than boys who did not experience severe malnutrition, but who are short at follow-up and have a unfavorable social background. The difference in IQ between boys who did and did not experience severe malnutrition in infancy varies under different conditions of height and social background when those are held constant for both groups. Under the most favorable conditions of being tall and having an advantageous social history the average IQ of the malnourtished boys in only 2 points lower than those not malnourished. Unde the most unfavorable conditions of short stature and a disadvantageous social background the IQ of the malnourished boys is 9 points lower than those not malnourished (Table 6 and Fig. 1).


Growth and nitrogen retention of children consuming all of the day's protein intake in one meal. To ascertain that linear growth and weight gain continue while consuming a diet in which all the day's protein is given in one meal, six children (ages: 8.5 to 25 months, weight: 6 to 8 kg) who were convalescing from malnutrition were placed on such a diet for 60 to 67 days. All diets provided 125 to 150 kcal and 2.0 to 2.5 g protein/kg/day, recalculated weekly. Energy was evenly divided among five feedings but the entire day's protein was given at the third meal. Increases in height age relative to increases in chronological age were appropriate for the stage of recovery. Height quotient (height age/chronological age times 100) increased during the study in four children and remained constant in two. Increases in weight age were greater than corresponding increases in chronological age. Nine-day control periods prior to and after the growth study allowed comparative N balances, which confirmed previous findings that apparent N retention from the unevenly distributed protein (32 +/- 10% of intake) was less, although not significantly so, than that from the control diet (34 +/- 15% of intake). Fecal facts were elevated during the study period (18 +/- 7.5% of intake) relative to the control period values (9 +/- 3.9% of intake) in all but one child.


Clinical effects and pharmacokinetics of different dosage schedules of adriamycin. Adriamycin was administered to 60 adults and 21 children by 3 different dosage schedules: 22.5 mg/sq m (0.6 mg/kg) daily for 4 days, 15 mg/sq m (0.4 mg/kg) every 8 hr for a total of 6 doses, and 50 to 120 mg/sq m as a single dose every 3 to 4 weeks. Objective responses lasting more than 1 month occurred in 5 subjects with acute leukemias or lymphoma, 3 with transitional cell carcinomas, 2 with sarcomas, 2 with Ewing's sarcoma and 1 each with bronchogenic carcinoma, orchidoblastoma, and thymoma. Toxic reactions included nausea, vomiting, stomatitis, alopecia, and hematopoietic depression, but significant cardiac toxicity occurred in only 1 patient. Pharmacokinetic data, collected in 25 patients by fluorometric and chromatographic assay, suggested a biphasic plasma clearance of drug with initial and secondary half-lives of about 1.5 and 14 to 21 hr, respectively. When drug was given every 8 hr there was evidence of loss of an initial very rapid phase of distribution of adriamycin and its metabolites. Urinary excretion accounted for 3.4 to 38.1% of administered fluorescence over a 72-hr period; in the first 24 hr, between 48.2 and 100% of this urinary material was in the form of adriamycin; leter, this fraction declined. No adriamycin or its fluorescent metabolites could be extracted from the stools.


Estrogenic effects of an antiestrogen, MER-25, on eating and body weight in rats. Ethamoxytriphetol, MER-25, which acts as an estrogen antagonist on other estrogen-sensitive behaviors and in peripheral tissues, was found to be fully estrogenic with respect to eating behavior and body weight regulation. The MER-25 causes decreases in eating and weight gain that are not due to toxicity, as indicated by its failure to induce a learned aversion to saccharin and by its failure to alter spontaneous activity. Estradiol benzoate (EB) and MER-25 similarly affect eating and body weight in gonadectomized rats: Both cause a transient decrease in food intake and a permanent decrease in body weight relative to controls; the eating and body weight effects of both MER-25 and EB are attenuated by progesterone; and both MER-25 and EB affect females more than males. Because of its full estrogenicity, MER-25 fails to antagonize the effects of EB on eating and body weight while simultaneously antagonizing effects of EB on sexual behavior, the uterus, and the vagina. The results indicate that the systems mediating the effects of estrogens on eating and body weight differ biochemically from other behavioral and somatic estrogen-sensitive systems.


Practical considerations in the development of a human cancer vaccine. Factors involved in the development of a human oncornavirus vaccine are discussed. The isolation and purification of subviral gp69/71 antigenic components enhance the feasibility of developing safe vaccine. The recent isolation of a C-type virus (the HL-23) from a human leukemic patient and its similarity to the simian sarcoma virus presents us with a unique opportunity to test the safety and potency of a vaccine in nonhuman primates.


Mitral valve prolapse in children: a problem defined by real-time cross-sectional echocardiography. The cross-sectional echocardiographic features of mitral valve prolapse were defined in 26 children (ages 2-18 years) using a real-time, multiple-crystal ultrasound scanner. In each patient the physical findings of the mitral valve click-murmur syndrome were present and mitral valve prolapse had been diagnosed previously by conventional single crystal echocardiography. Mitral prolapse occurred in a familial setting in eight patients and was associated with the Marfan syndrome in five. Real-time two-dimensional echocardiography uniformly disclosed maximum mitral arching and the superior-posterior prolapse. These visual observations were confirmed by M-mode recordings derived from single elements within the array of 20 crystals. The method allowed a complete M-mode description of the phasic motion of the entire mitral apparatus and observations of the spectrum of prolapse from discrete late systolic prolapse to "hammock-like" holosystolic prolapse. Further, the recording of multiple systolic M-mode lines occurred when the ultrasound beam intersected the arched leaflets more than once. Pseudosystolic anterior motion was observed often and resulted clearly from a superimposition of echoes from the mitral annulus and from the posterior-superiorly arched prolapsed leaflets. A major finding in 22 patients was the association with prolapse of biconvex enlargement of the aortic sinuses of Valsalva and a significant increase in the diameter of the aortic root. Aortic root dilatation was most marked in, but not confined to, patients with the Marfan syndrome and was a prominent finding in six patients with minor musculoskeletal abnormalities. The presence of aortic root dilatation in children with normal body habitus raises important questions concerning the generalized nature of an abnormality of cardiac connective tissue in patients with mitral prolapse. The cross-sectional approach significantly enhances the noninvasive evaluation of mitral valve prolapse and provides an explanation for many of the single crystal observations reported previously.


Metabolism of resorcinylic compounds by bacteria: alternative pathways for resorcinol catabolism in Pseudomonas putida. Two strains of Pseudomonas putida isolated by enrichment cultures with orcinol as the sole source of carbon were both found to grow with resorcinol. Data are presented which show that one strain (ORC) catabolizes resorcinol by a metabolic pathway, genetically and mechanistically distinct from the orcinol pathway, via hydroxyquinol and ortho oxygenative cleavage to give maleylacetate, but that the other strain (O1) yields mutants that utilize resorcinol. One mutant strain, designated O1OC, was shown to be constitutive for the enzymes of the orcinol pathway. After growth of this strain on resorcinol, two enzymes of the resorcinol pathway are also induced, namely hydroxyquinol 1,2-oxygenase and maleylacetate reductase. Thus hydroxyquniol, formed from resorcinol, undergoes both ortho and meta diol cleavage reactions with the subsequent formation of both pyruvate and maleylacetate. Evidence was not obtained for the expression of resorcinol hydroxylase in strain  O1OC; the activity of orcinol hydroxylase appears to be recruited for this hydroxylation reaction. P. putida ORC, on the other hand, possesses individual hydroxylases for orcinol and resorcinol, which are specifically induced by growth on their respective substrates. The spectral changes associated with the enzymic and nonenzymic oxidation of hydroxyquinol are described. Maleylacetate was identified as the product of hydroxyquinol oxidation by partially purified extracts obtained from P. putida ORC grown with resorcinol. Its further metabolism was reduced nicotinamide adenine dinucleotide dependent.


Formation of cyanamides from secondary amines in human saliva. 1-Morpholinocarbonitrile (1-cyanomorpholine) was formed from morpholine when this amine was incubated in whole human saliva. Several other secondary amines appeared to form analogous products, and this transformation may therefore represent a general metabolic pathway for amines in saliva.


Distribution of hexosamines in bovine cornea. Excised bovine cornea were sectioned from epithelium to endothelium into 6 to 8 fractions. The glucosamine/galactosamine ratio steadily increases from epithelium to endothelium in all bovine corneas investigated. The glucosamine/galactosamine ratio reflects the keratan sulfate/chondroitin-4-sulfate ratio in the cornea. The significance of this topographic distribution is discussed in terms of the different hydration properties of proteoglycans containing predominantly keartan sulfate or chondroitin-4-sulfate chains.


Effects of wheat germ agglutinin on fertilization of mouse ova in vivo and in vitro. Mouse ova with or without follicular cells (denuded) were treated with wheat germ agglutinin (WGA) in concentrations ranging from 5-500 mug/ml and fertilized in vitro. Ova subjected to concentrations greater than 10 mug/ml WGA were incapable of fertilization in vitro, although sperm were observed adhering to the zona pellucida after treatment in concentrations as high as 500 mug/ml WGA. At concentrations of 50 mug/ml or higher, WGA adversely affected the shape of the vitellus. Of various saccharides employed to block the effects of WGA D-glucose was the most effective. Injections of 0.03 ml of 100 mug/ml WGA into the ovarian bursa two to three hours before the expected time of ovulation had little or no effect on fertilization in vivo.


Fluorophotometry and the rate of aqueous flow in man. I. Instrumentation and normal values. A new objective fluorophotometer, based on a previous model but with changes in electronic circuitry, was designed and built. The fluorometric method was applied to 38 normal eyes to obtain the aqueous outflow rate and fluorescein decay constant. Aqueous outflow rate has a direct correlation with the anterior chamber depth and an inverse correlation with age. The aqueous flow rate is higher in whites than in blacks, but in our sample, mean pressure was lower in whites. Acetazolamide decreases the aqueous flow rate and the fluorescein constant; the mean decrease in 10 eyes of 5 patients was approximately 38% and 22%, respectively. Fluorophotometry gives a higher value for the aqueous outflow rate than that calculated by tonography.


Structure-activity relationships in nitrosamine carcinogenesis. Statistically significant correlations have been demonstrated between carcinogenic activity, toxicity and number of carbons per molecule for an extensive set of nitrosamines. Such correlations, involving only bulk molecular properties indicate that the chemical nature of the alkyl substituents need not be the sole determinants of carcinogenic activity. These structure-activity relationships can be used to estimate carcinogenic activity with some degree of confidence.


Biliary excretion of digoxin in man.

Biliary excretion of digoxin in man. We have measured the biliary excretion of 3H-digoxin in normal subjects by intestinal perfusion methods which impose minimal interruption of the enterohepatic circulation. In contrast to data obtained in patients with liver disease and postoperative patients with biliary fistulas, our data show that about 30% of an intravenous dose of 3H-digoxin reaches the digestive tract in 24 hr. Most of the excreted radioactivity is chloroform-soluble and presumably reabsorbably and most of this fraction is probably biologically active drug. The results suggest that (1) consideration of hepatobiliary function may be relevant in observations regarding digoxin pharmacokinetics and that this route may be exploited in trials of therapy designed to shorten the duration of digoxin intoxication.


Adipocyte beta-adrenergic receptors. Identification and subcellular localization by (-)-[3H]dihydroalprenolol binding. (--)-[3H]Dihydroalprenolol, a potent beta-adrenergic antagonist, was used to identify binding sites which have the characteristics of beta-adrenergic receptors in membranes from rat adipocytes. The subcellular distribution of the (--)-[3H]Dihydroalprenolol binding sites was examined. The binding sites were predominantly in the plasma membrane fraction, consistent with the proposal that the physiologically significant beta-adrenergic receptors are localized in the adipocyte plasma membrane. Binding of (--)-[3H]dihydroalprenolol to unfractionated adipose membranes was saturable with 0.24 pmol bound/mg of protein at saturation. Half-maximal saturation occurred at 15 nM providing an estimate of the equilibrium dissociation constant, KD, for the interaction of (--)-[3H]dihydroalprenolol with its adipocyte receptor. Kinetic analysis of (--)-[3H]dihydroalprenolol binding provided a value of 2.4 X 10(7) M-1 min-1 for the forward bimolecular rate constant, k1. Dissociation of (--)-[3H]dihydroalprenolol was a first order reaction with a rate constant, k2, of 2.94 X 10(-1) min-1. The ratio k2/k1 = 12 nM provides an independent measurement of the KD for the interaction of (--)-[3H]dihydroalprenolol with its receptor which is in good agreement with the values obtained by steady state analysis (12 to 15 nM). Beta-Adrenergic agonists and antagonists competed for the binding sites in unfractionated adipocyte membranes with a typical beta1-adrenergic specificity. The order of potency of agonists was (--)-isoproterenol greater than (--)-norepinephrine congruent to (--)-epinephrine. The beta-adrenergic antagonist, (--)-propranolol, potently competed for the binding sites with a KD of 17 nM. Compounds such as dihydroxyphenylaline, dihydroxymandelic acid, normetanephrine, pyrocatechol, and phentolamine which are structurally related to beta-adrenergic agents, but are devoid of beta-adrenergic physiologicl effects in adipocytes, did not compete for the binding sites. Binding was highly stereospecific, the (+) isomers of adrenergic agonists and antagonists requiring 23- to 330-fold higher concentrations to half-maximally inhibit binding than the corresponding (--) stereoisomers. (--)-[3H]Dihydroalprenolol binding was examined highly enriched plasma membrane, mitochondrial, and microsomal (endoplasmic reticulum) fractions of adipocytes. In the presence of 12 nM (--)-[3H]dihydroalprenolol, the specific activity of binding in the plasma membrane fraction was 5-fold higher than that of the mitochondrial fraction and 8-fold higher than that of the microsomal (endoplasmic reticulum) fraction. The specificity and affinity characteristics of the plasma membrane binding sites were found to be virtually identical with those of the unfractionated adipocyte membranes. The observation that (--)-[3H]dihydroalprenolol binding sites are predominantly localized in the plasma membrane fraction suggests the potential usefulness of this ligand as a marker for adipocyte plasma membranes.


Side-dependent effects of internal versus external Na and K on ouabain binding to reconstituted human red blood cell ghosts. The side-dependent effects of internal and external Na and K on the ouabain binding rate, as promoted by inside MgATP, has been evaluated utilizing reconstituted human red blood cell ghosts. Such ghost systems provide the situation where [Na]i, [K]i, [Na]o, and [K]o can each be varied under conditions in which the others are either absent or fixed at constant concentrations. It was found that, in the presence of Ko, increasing either [Na]i or [K]i resulted in decreasing the rate at which ouabain was bound. Changes in [Na]i or [K]i in the absence of Ko were without effect on the ouabain binding rate. Thus, the ouabain binding rate was found to vary inversely with the rate of Na:K and K:K exchange but was independent of the rate of Na:Na exchange. The effect of Ko in antagonizing ouabain binding, as well as the influence of Nao on this interaction, were found to require the presence of either Nai or Ki. The results are interpreted in terms of a model relating the availability of the ouabain binding site to different conformational states of the pump complex. Differences were observed in the ouabain binding properties of red cell ghosts compared to microsomal preparations but it is not known whether the basis for the differences resides in the different preparations studied or in the lack of control of sidedness in the microsomal systems.


Audiologic evaluation of deaf children.

Audiologic evaluation of deaf children. This paper describes an audiologic test battery for hearing-impaired children which includes otoscopic examination, tympanometry, pure-tone audiometry, speech perception testing, and hearing aid evaluation. Several of the procedures and modifications to apparatus have been developed specifically for use with deaf children. Clinical data are presented from 160 hearing-impaired children (age range three-16 years). Eighteen percent of their ears were found to contain excessive cerumen and to require ear canal irrigation. The incidence of abnormal tympanograms was high for young children but decreased with increasing age. A simple auditory speech perception test designed for use with both severely and profoundly deaf children is described, which provides for evaluation of a child's ability to recognize words, categorize them into stress patterns, or both. The children's word recognition and word categorization scores were found to relate to their audiometric averages. The overall test battery is easy to administer and also is efficient, in that considerable audiologic information can be obtained quickly.


Enzyme replacement therapy--an experiment of nature in a chimeric mannosidosis calf. Enzyme replacement therapy was studied in a chimeric mannosidosis calf which had received a natural transplacental transplant of normal lymphocytes from its co-twin. There was considerable reduction in the pathology of certain organs and in the amount of storage oligosaccharides, but the clinical course of this neurologic disease was not significantly altered. It was postulated that if this disease had been purely visceral the transplant would have been relatively effective.


Total and regional cerebral blood flow during stimulation of carotid baroreceptors. The concept that reflex control of cerebral vessels is unimportant has been challenged by recent studies which suggest that carotid baroreceptors have an important role in regulation of cerebral blood flow (CBF). In this study we have tested the hypothesis that arterial baroreceptors contribute to regulation of total or regional CBF. CBF was measured in anesthetized dogs with 15 mu microspheres. Stimulation of carotid baroreceptors, by raising carotid sinus pressure, did not alter or redistribute cerebral flow. Responses to baroreceptor stimulation were intact, as manifested by vasodilation in skeletal muscle. CBF decreased during systemic hypocapnia and increased during hypercapnia, which indicates that failure of cerebral flow to change during baroreceptor stimulation was not due to unresponsiveness of cerebral vessels. During hypercapnia, baroreceptor stimulation also failed to alter CBF. In other studies CBF was measured during increases in systemic arterial pressure, before and after denervation of arterial baroreceptors. Increases in arterial pressure did not increase CBF either before or after denervation of baroreceptors. We conclude that baroreceptor stimulation does not alter total or regional CBF and that baroreceptors do not regulate cerebral flow during systemic hypertension.


Rabbit muscle pyruvate kinase. Amino- and carboxyl-terminal studies. Amino-terminal analysis of rabbit muscle pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) failed to detect the presence of any free amino-terminal residues. Acetyl group analysis demonstrated the presence of between 3.7 and 4.0 mol of acetyl groups per mol of enzyme. The acetylated amino-terminal residue was isolated from pronase digests of the enzyme and identified as N-acetylserine. Quantitative recovery experiments indicated that all acetyl residues are found at the amino termini. Carboxyl-terminal analyses using the tritium exchange method suggested the presence of a blocked carboxyl-terminal residue, supporting previous hydrazinolysis and carboxypeptidase studies.


Cancer mortality correlation studies. II. Regional associations of mortalities with the consumptions of foods and other commodities. The age-corrected mortalities from cancer at 17 sites were correlated with the consumptions of 12 major food items and the apparent consumptions of alcoholic beverages, cigarettes, beer, coffee, tea and solid fuel, in different countries. Significant direct and inverse correlations with food consumption variables were observed: the results are in essential accord with those of other workers employing different methods of statistical analysis. A modification of the diet in western industrialized nations is proposed as a means of lowering the human cancer risk. For cancers of the mouth and neck, and for liver in males, significant associations with the wine alcohol consumption were observed. Statistical evidence for liver cirrhosis as liver-cancer, and for stomach ulcer as stomach-cancer-predisposing conditions was obtained.


Distribution of aflatoxins in some samples of peanuts. Naturally occurring G aflatoxins were found at approximately 20 times the level of B aflatoxins in one lot of roasted, blanched peanuts. Official methods, as well as high-pressure liquid chromatography, were used to confirm this finding. Additional routine sample analysis data of raw and roasted peanuts revealed that this finding is not so unusual formerly thought. It was found that 9.8% of the raw peanut samples contained higher levels of G than B aflatoxin; 4.9% containing 2-8 times more G than B aflatoxins. In a smaller sampling of roasted peanuts, 28% of the contaminated peanuts contained more G than B aflatoxins.


An analysis of the subjective marijuana experience. Two hundred and thirty-six marijuana users who volunteered for a study in which they would use the drug were administered a Drug History and a Marihuana Effects Questionnaires. In addition to obtaining descriptive information of drug experiment volunteers and a factor analysis of the marijuana experience, the relationship between experience and effect variables were studied. The results of the above analysis suggest that the "typical"  subject in marijuana experiments is not a "typical" user, that the marijuana experience is verbally definable, and that prior expectancies and histories of effect alter the experience.


A case of blood-illness-injury phobia treated behaviorally. A patient with a 24-year history of blood-illness-injury phobia associated with bradycardia and syncope was treated behaviorally. He was taught to prevent bradycardia and resulting syncope occurring in the presence of phobic stimuli by provoking anger in himself using appropriate imagery. Within a few weeks, the patient was able to use the procedure successfully to prevent syncope in everyday situations. At 6 months follow-up he remained comfortable in the presence of previously phobic stimuli and he no longer needed to use self-induced anger to prevent syncopal episodes.


[Reflexotherapy (acupuncture) in painful facial syndromes. Preliminary note]. The early clinical results of using acupuncture in painful face syndromes are reported. A nosological classification is given and techniques used and therapeutic indications presented in brief.


Preparation and testing of vaccines prepared from the envelopes of Venezuelan, eastern, and western equine encephalomyelitis viruses. Envelope components were separated from Venezuelan, Eastern, and Western equine encephalomyelitis viruses after treatment of the virions with detergent. Vaccines prepared from the envelope component were capable of stimulating mice to produce humoral antibodies. Protective efficacy studies were performed using mono-, di-, and trivalent vaccine combinations. These elicited varying degrees of homologous protection, and Eastern and Venezuelan equine encephalomyelitis envelope products appeared to confer protection to mice challenged with Western equine encephalomyelitis virus.


A method of teaching counselling.

A method of teaching counselling. The major part of one section of a teaching-methods course for general practitioner teachers (Harris et al., 1976) was concerned with teaching counselling skills. This paper describes the methods used to do so, in the setting of a residential course lasting for only a few days. The functions and objectives of counselling are defined, and the counselling process is divided into six stages which are reflected in the organization of the teaching. Five specific skills required are isolated, to clarify the teaching and to permit assessment of the members' learning. Three roles in a counselling interview are described, and members work in trios where they experience each of these roles. The problems at which the members work have to be real and unresolved problems in their own lives. Some conclusions are offered, drawn from the writers' experience and from the evaluation and assessment techniques employed.


[Age-specific learning ability in Japanese quails (Coturnix coturnix japonica)]. The main question of our investigation is: Do there exist age-specific learning abilities in animals? 120 QUAILS (Coturnix coturnix japonica) of 12 different age groups (between one day and 20 weeks) were tested in a combination apparatus 0y using two training methods. 60 quails were trained with decreasing (1), 60 other quails with increasing learning assistance (2). In each case the learning period lasted 5 days after which the animals were tested in a two-way choice apparatus and in a simple maze. Retention was tested 3 weeks later. - The 2 methods led to different results. In general the younger animals learnt better than the other ones when trained by method 1. No differences in learning performance between the 12 age groups were obtained by method 2.


Byssinosis and other respiratory ailments: a survey of 6,631 cotton textile employees. A Pulmonary Function Survey involving a questionnaire and pulmonary function testing was carried out in 14 plants of a large cotton textile manufacturing corporation. The edited records of 6,631 employees were analyzed to help identify the prevalence and location of byssinosis and other respiratory ailments and to explore the environmental conditions associated with them. A majority of the complaints of byssinosis were found among the relatively small subset of employees located in the high dust work areas of opening, picking, and carding. Byssinosis was significantly associated with bronchitis. Smoking was significantly associated with byssinosis for employees in opening, picking, and carding. While 3% of the population had subjective symptoms (history) of byssinosis, 0.8% indicated both symptoms and objective sign by a 10% or greater drop during the working day of the one-second forced expiratory volume (FEV1). The techniques commonly used to predict FEV1 should employ race as a predictive factor.


Epidermoid cyst of the spleen: case report. The classification, incidence, and clinical, radiologic, and scintigraphic findings of benign nonparasitic splenic cysts are presented with a case report of epidermoid cyst of the spleen.


[Etiology and therapy in anorexia nervosa (author's transl)]. ASPERGER (1963) mentioned as a very important etiological aspect of anorexia nervosa a desintegration of intellectual and thymical functions causing the fact, that these patients are not able to accept the role of an adult, especially that one of a woman. We discuss that statment in connexion with ERIKSON'S (1974) concept about "ego-identity" ("Ich-Identitat") and "negative-identity" ("negative Identitat"). The pathological family-structure seems to reinforce the situation and the existence of inadequate behavior of patients with anorexia nervosa, who are often introverted and predestinated for conditioning. The therapy of these patients should focuse on the development of ego-identity, including the treatment of the family members, the modification of the inadapted behavior and a special endocrinological therapy.


Transjugular obliteration of the gastric coronary vein. The feasibility of transjugular entry into the portal vein for catheterization and obliteration of the left gastric vein is demonstrated in a human. This technique may play a significant role in the nonsurgical management of bleeding esophageal varices.


The asymmetrically hypertrophied septum. Further differentiation of its causes. Fifty-eight subjects with echocardiographic criteria for an abnormal septal to left ventricular posterior wall ratio were studied. Echocardiographic findings were related to clinical cardiac status. Abnormal ratios were found in normal children and in children with a variety of cardiac lesions, only one of which was obstructive or non-obstructive cardiomyopathy. In those without cardiomyopathy, the abnormal ratio usually resolved by one or two years of age. Persistence of abnormal ratio usually occurred in patients with increased right ventricular anterior wall thickness or idiopathic hypertrophic subaortic stenosis. The cause of abnormal ratio is multifactorial.


Asymetric septal hypertrophy in childhood. Although considerable information is available concerning the clinical features and natural history of asymmetric septal hypertrophy (ASH) in adults, little is known of this disease in children. The clinical characteristics and course of 46 children with ASH, who were evaluated at the National Heart and Lung Institute, have been analyzed. Twenty-four children had obstruction to ventricular outflow; 22 children had no obstruction to ventricular outflow, including 11 patients without overt manifestations of cardiac disease other than echocardiographic evidence of ASH. Thirty-five of the 46 children have been followed for one to 16 years (average 7.4 years). These latter children represent that subgroup of patients with ASH referred to the National Heart and Lung Institute and diagnosed prior to the general availability of echocardiography. The clinical course of these patients was variable. Fourteen (40%) of the 35 patients improved or remained stable, including four patients who received propranolol. Ten (29%) of the 35 patients deteriorated clinically and 11 (31%) of the 35 patients died suddenly (4% mortality per year). Two of the patients who died suddenly had previously undergone operation (six and 13 years previously) with resultant abolition of the outflow gradient; four others were taking propranolol. Neither symptomatology, electrocardiographic abnormalities, heart size, left ventricular ejection or upstroke time, magnitude of outflow gradient, or left ventricular end-diastolic pressure proved predictive of sudden death. Excluding patients who had previous operation, eight (40%) of 20 patients with obstruction who were followed long term and one (9%) of 11 patients without outflow obstruction died suddenly. Thus, the clinical and hemodynamic spectrum of ASH in childhood is broad. However, deterioration in clinical condition or sudden death has been relatively common in children with overt signs of cardiac disease.


Subaortic stenosis caused by two discrete membranes. A case of subaortic stenosis caused by two discrete membranes is presented. Following demonstration of the two distinct sites of obstruction by intraventricular pressure gradients and angiocardiogram, the two membranes were excised through a transaortic approach. The importance of being aware of the occurrence of this rare anomaly is stressed, and its surgical implications are discussed.


Effects of heparin on lipolytic enzyme activities in vivo and in vitro. The in vivo and in vitro effects of heparin on the lipolytic enzyme activities of normal rabbit serum and tissues were investigated. An acute intravenous injection of heparin produced the following changes in enzyme activities: in serum, phospholipase and lipase were increased, cholesterol esterase unchanged; in tissues phospholipase was increased, lipase was increased in heart and liver but decreased in aorta, cholesterol esterase was increased in heart but decreased in liver and aorta. In vitro phospholipase and lipase were increased by low concentrations of heparin, but decreased by high concentrations. Cholesterol esterase was decreased irrespective of heparin concentration. It is suggested that heparin may affect lipolytic enzyme activities by influencing the ionic state of the enzyme and substrate.


Affinities of Teilhardina (Primates, Omomyidae) with description of a new species from North America. Teilhardina is a fifth primate found in Early Tertiary rocks of both Europe and North America. Both T. belgica and the new North American species are anaptomorphines; however, neither species is ideally suited for the ancestry of the New World Omomyidae. Pelycodus and the Adapidae are not closely related to Teilhardina and Torrejonian Palenochtha is probably not in the ancestry of omomyids. A combination of dental characters in earliest Anemorhysis suggest this primate is the most generalised known omomyid.


Angiosarcoma of the skin. A clinicopathologic and fine structural study. A study of ten cutaneous angiosarcomas is presented. These tumors characteristically involve the scalp or face of elderly individuals, where they present as bluish or violaceous plaques and nodules. They have a marked tendency for local spread in surface and depth, and a third of them eventually give rise to distant metastases, particularly to cervical lymph nodes and lung. Microscopically, angiomatous areas of freely anastomosing channels lined by atypical endothelial cells are seen alternating with Kaposi-like spindle cell areas and undifferentiated foci. By electron microscopy, the tumor cells are seen to have all the features of endothelial cells, including pinocytotic vesicles, tubulated bodies, and in one case closed fenestrations. They also exhibit a cytoplasmic specialization here interpreted as the intracellular formation of a vascular lumen. Pericytes and cells resembling smooth muscle cells are also present. In the differential diagnosis this entity has to be distinguished from other clinical types of angiosarcoma of the skin and from a number of benign and malignant conditions. It is suggested that surgery be used for solitary, well circumscribed tumors and radiation therapy for tumors that either are multicentric or have ill defined margins.


Regulation by calcium of the proliferation of heart cells from young adult rats. Cells of primary and secondary cultures of rat heart ventricle were grown in a medium supplemented with homologous plasma to avoid the non-specific proliferogenic effects of foreign sera. Specific chelation of calcium from the medium arrested the cells' progression through their cycle at the G1 phase. A permanent or brief restoration of the extracellular calcium level (48 hr later) was followed, after a 5 to 6 hr delay, by a burst of DNA synthesis, and the resumption of mitotic activity.


The synthesis of cartilage collagen by rabbit and human chondrocytes in primary cell culture. This report describes a method for preparing primary cell cultures of differentiated rabbit sternal and human vertebral cartilage cells. These cell cultures were shown to synthesize primarily alpha1 chains, which is taken to mean that at least 82% of the collagen produced is cartilage specific collagen (type II).


Disulfide bond-modified trypsinogen. Role of disulfide 179-203 on the specificity characteristics of bovine trypsin toward synthetic substrates. Disulfide 179-203 of trypsinogen was cleaved and the free sulfhydryls were modified by S-carboxymethylation, S-carboxyamidomethylation, or by S-aminoethylation. The enzymatic properties of the activated, modified zymogens toward specific and nonspecific trypsin substrates were studies. The three S-alkylated trypsins hydrolyzed N-benzoylarginine ethyl ester and N-tosyl-lysine methyl ester with Kcat values similar to those of trypsin but with Km values that were increased by 2 to 3 orders of magnitude. The binding constant of the competitive inhibitor benzamidine to the S-alkylated trypsins was increased by 2 orders of magnitude by the modifications. The association constant of soybean trypsin inhibitor with S-carboxyamidomethyl trypsin was several orders of magnitude less than normal. Hydrolysis of benzoyl arginine amide with S-carboxymethyl trypsin was not detected, but this was ascribed to poor binding since a KI of 0.3 M was estimated from competitive inhibition studies. The altered kinetics did not depend on the type of chemical group used for the S-alkylated derivative, nor were the kinetics of any derivative significantly influenced by changes of pH or ionic strength. Nonspecific substrates, such as acetylglycine p-nitrophenyl ester and p-nitrophenylacetate, were hydrolyzed at equal rates by both trypsin and disulfide-modified trypsins, and both substrates had identical kcat/Km ratios with unmodified trypsins. For S-alkylated trypsins, kcat/km with lysine and arginine substrates were lower than normal and were the same order of magnitude as the values found for nonspecific substrates, suggesting normal catalytic behavior but a loss of specificity in binding substrates. The kinetic evidence suggested that the role of disulfide 179-203 in the mechanism of action of trypsin is to maintain the geometry of the specificity pocket by keeping appropriate residues of the pocket in a rigid framework.


The structure of the pelvis in the immature human kidney. Examination of the renal pelvis of late fetal and neonatal kidneys shows that in about one quarter of the calyces examined the arrangement is similat to that in the rat, the outer medulla being separated from the calyceal cavity by a very thin epithelium. It is suggested that this presents a vulnerable area through which intrarenal damage can occur as a result of vesico-ureteric reflux in the immature kidney.


Cardiac conduction abnormalities produced by chronic alcoholism. While conduction disturbances and arrhythmias are seen frequently in alcoholic cardiomyopathy, the specific relationship of these changes to ethyl alcohol has been unclear. To investigate the long-term effects of ethanol upon cardiac conduction, alcoholism was induced in 11 male mongrel dogs for 7 to 33 (mean 14.4) months by feeding up to 36 per cent of total daily calories as ethanol while adequate nutrition was maintained. His and left bundle branch electrograms in the intact anesthetized animals were recorded along with high-speed, high-frequency ECG's. While resting left ventricular pressures, volumes, and stroke outputs were normal, H-Q time was prolonged in the alcoholic animals drinking for longer than one year (35 +/- 3 msec., normals 26 +/- 1 msec.-P less than 0.001). QRS widening (to 80 +/- 4 msec.) was also evident after one year as compared with normals (62 +/- 2 msec.-P less than 0.001), and both H-Q and QRS alterations correlated with duration of intake. These changes were less after shorter ingestion periods, could not be reproduced in normals by acute ethanol infusion, and were not associated with ventricular hypertrophy, inflammation, or necrosis. No abnormalities of atrial conduction were noted. Morphologic correlates of the conduction abnormalities included accumulation of Alcian Blue-positive interstitial material as well as dilatation and localized swelling of the nonspecialized region of the intercalated discs in ventricular muscle and Purkinje fibers. Thus, prolonged ethanol intake in the absence of evident malnutrition resulted in demonstrable intraventricular conduction abnormalities and morphologic alterations which were related to duration of ingestion, consistent with a cumulative toxic effect of ethanol.


Comparison of active participants and dropouts in CAPRI cardiopulmonary rehabilitation programs. Of 547 men and 56 women enrolled up to April 1974 in Cardiopulmonary Research Institute (CAPRI) community programs for cardiopulmonary rehabilitatation, 84.5 percent had clinical manifestations of coronary heart disease. These medically supervised programs of physical training involved 30 to 60 minutes of graded levels of working, calisthenics and, if indicated, jogging for 3 mornings/week. Altogether 352 (58.4 percent) dropped out after an average of 8.6 months for men and 5.7 months for women. The remaining 230 men and 21 women remained active for 22 and 20 months, respectively. In retrospect, there were few minor differences between active participants and dropouts in physical characteristics, clinical diagnoses and responses to exercise testing on enrollment. Elapsed time to morbidity tended to be longer in active persons than in dropouts. Over one half of active men and about one third of dropouts were working. Of six early deaths, one occurred before training was instituted, and five within the first 2 weeks of training. Among men, the respective total mortality rates were 2.7 and 4.7/100 person-years for active participants and dropouts; among women, the rates were 0 and 3.8 respectively. Whereas 24 episodes of cardiac arrest occurred in 13 men, with three fatalities outside the training program, in 11 instances of exertional arrest during class training all defibrillations were successful. Without this benefit of medical supervision there would have been little difference in mortality experience.


Community surveillance for coronary heart disease: the Framingham Cardiovascular Disease survey. Comparisons with the Framingham Heart Study and previous short-term studies. It appears likely that intervention trials on a community scale against one or more coronary heart disease risk factors will begin in the near future. Prerequisite to the evaluation of the effectiveness of these trials is the accurate determination of coronary heart disease incidence rates. The Framingham Cardiovascular Disease Survey was undertaken to test the hypothesis that a short-term surveillance study of a defined population can generate accurate incidence rates for at least some categories of cardiovascular disease and that these rates are comparable with those obtained by longitudinal survey of the same population. In conjunction with the 1970 U.S. census, a 1 year survey was made of all new coronary heart disease events occurring in the town of Framingham, Mass. Surveillance was performed by several methods that were intentionally overlapping. During the study period, 244 coronary heart disease events occurred. Despite the relatively small size of the population, many of the well established epidemiologic characteristics of this disease were evident. The rates obtained by the cardiovascular disease survey were comparable with those obtained by the Framingham Heart Study, for the harder end points of myocardial infarction and death from coronary heart disease, but much smaller for the softer end point of angina pectoris, especially in women. These data and those from similar studies indicate that periodic short-term surveillance studies of target populations of major intervention programs can provide an economic method of generating incidence data for the evaluation of the impact of such programs on myocardial infarction and death from coronary heart disease.


Anterolateral muscle bundle of the left ventricle, bulboventricular flange and subaortic stenosis. A hitherto unrecognized muscle bundle in the left ventricular outflow tract is described. Found between the left coronary aortic semilunar cusp and the anterior leaflet of the mitral valve, this anterolateral muscle bundle of the left ventricle is present in approximately 40 percent of normal hearts. On embryologic grounds it is suggested that this bundle is a muscular remnant of the left extremity of the bulboatrioventircular flange. It can be very prominent, causing obstruction of both the left ventricular inflow and outflow tracts.


Paradoxic response of the murmur of idiopathic hypertrophic subaortic stenosis to the Valsalva maneuver. A case of documented severe idiopathic hypertrophic subaortic stenosis in which the Valsalva maneuver resulted in paradoxic attenuation of the systolic ejection murmur is presented. Such a response should not be considered incompatible with the diagnosis of this disease.


Management of isoimmune neonatal thrombocytopenia. Two infants, who presented at birth with isoimmune thrombocytopenic purpura, are the basis for this report. The problems confronting the physician in treating an affected infant, as well as in the management of subsequent pregnancies after an infant with isoimmunization has been delivered, are discussed. In view of the small but serious risk of intracranial hemorrhage during the birth process in these infants, delivery by cesarean section is advocated for all pregnancies known to be at risk i.e., after a previous infant has been shown to be affected.


Ethchlorvynol (Placidyl)-induced pulmonary edema. Two patients experienced severe nonhemodynamic pulmonary edema following the intravenous injection of 25 and 40 mg/kg of body weight of ethchlorvynol (Placidyl). The pulmonary edema cleared rapidly. Injection of Placidyl (12 to 80 mg/kg of body weight) intravenously into dogs caused acute, severe, nonhemodynamic pulmonary edema (as evidenced by markedly elevated lung weights and microscopic evidence of intra-alveolar edema), hypotension with a relative bradycardia, and a decreased cardiac output. Injection of polyethylene glycol, the vehicle in which ethchlorvynol is diluted, did not reproduce the syndrome.


Delayed correction of anorectal incontinence due to anal sphincteral injury. True anorectal incontinence, often the result of obstetrical or surgical injury to the anal sphincteral muscles, can be identified precisely. Although a variety of surgical procedures are available for correction of this defect, this report describes the repair method of overlapping the severed ends of the anal sphincteral muscles. Five patients had injuries associated with the birth of children; one patient had had a previous surgical injury; and one patient had anal tuberculosis. Only the last patient did not have an excellent result, and he experienced considerable improvement.


Mechanism of action of acetyl kidamycin. I. Interaction with DNA. Acetyl kidamycin, an antitumor antibiotic, was strongly bound to DNA in vitro, consequently, the melting temperature of DNA was significantly increased, and its buoyant density was decreased. From these results, it was suggested that acetyl kidamycin stabilized residual links between complementary strands by binding to DNA. An additional action was observed in that acetyl kidamycin caused single-strand scission of DNA in an alkaline sucrose density gradient solution.


Comparison of early embryonic and differentiating cell surfaces. Interaction of lectins with plasma membrane components. 1. Cells of the unincubated as well as those of primitive streak chick blastoderm, which are preparing for or are involved in morphogenetic movements, are agglutinated by wheat germ agglutinin, Ricinus communis agglutinin and concanavalin A, but not by fucose-binding protein. 2. Agglutination of these cells with soybean agglutinin occurs only after neuraminidase treatment, while that induced by concanavalin A, wheat germ and Ricinus communis agglutinins is not affected. 3. Trypsin treatment of blastoderm cells had no effect on lectin-mediated agglutination. 4. In contrast, cells derived from 10-and 12-day differentiating chick liver were agglutinated by wheat germ agglutinin only after trypsinization. 5. Mechanically dissociated embryonic liver cells, which are not agglutinated, bind more 3H-labelled wheat germ agglutinin per cell than trypsinized cells, suggesting that during differentiation there may be a spatial reorganization of wheat germ agglutinin receptors within the plasma membrane. 6. Membranes isolated from the above cell types were examined by analytical polyacrylamide gel isoelectric focusing and, in combination with affinity chromatography using wheat germ agglutinin conjugated to agarose, membrane material in the differentiating liver membrane, which binds to this lectin, was identified.


Interpretation of osmotic pressure in solutions of one and two nondiffusible components. Osmotic pressure data from aqueous solutions of nondiffusible serum albumin (BSA), chondroitin sulfate (CHS), and dextran T110 (D110), taken singly and in binary combinations, were interpreted in terms of excluded volume. The principal solvent was phosphate-buffered saline, pH 7.2, at 23 degrees C. Osmotic pressures were measured with a membrane osmometer fitted with Amicon PM-10 membranes. Data from each solution were fit by stepwise regression with a three- or four-term polynomial in integral powers of total nondiffusible solute concentration in accordance with the general solution theory of McMillan and Mayer (1945, J. Chem. Phys. 13:276) as extended by Yamakawa (1971, Modern Theory of Polymer Solutions, Harper & Row, New York). The date display a high internal consistency, and the results correlate well with published molecular weights and exclusion data where available. Number average molecular weights calculated from the "first virial coefficients" are: BSA, 67,000 +/- 11%; D110, 76,000 +/- 11%, CHS, 39,000 +/- 6%. Excluded volumes (in cubic centimeters per molecule) calculated from the "second virial coefficients" are: BSA, 0.97 X 10(-18); D110, 3.04 X 10(-18); CHS, 14.3 X 10(-18); BSA-D110, 6.8 X 10(-18); BSA-CHS, 7.8 X 10(-18). Uncertainty is about 30%. An empirical model for interpretation of calculated excluded volumes is proposed. It appears that CHS has the "largest" exclusion effect of the three molecules.


Early malnutrition and postnatal changes in brain and behavior in the mouse. The effects of early undernutrition were studied by rearing mice in small, intermediate or large litters (respectively 4, 8 or 16 pups). Measures of reflexes and electrocorticographic activity applied from birth to weaning indicated that malnutrition resulted in a clear ontogenetic retardation which was followed by permanent body and brain stunting. The mice from the large litters were characterized by increased exploratory activity and by lower avoidance learning ability as measured 45 days after nutritional rehabilitation.


Comparison of regional serotonin levels and turnover in the brain of naturally high and low aggressive rats. Rats, matched by weight and goal approach, were tested for aggressiveness using a food-competition paradigm. Those winning and those losing all of their matches were designated as high and low aggressive, respectively. A third group of randomly selected rats never fought and were used as a control for the fighting experience. Half of the rats were used to determine serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in discrete brain regions. The other half were used to estimate 5-HT turnover in the same brain regions. High and low aggressive rats did not differ with regard to 5-HT or 5-HIAA levels, but high aggressive rats showed faster 5-HT turnover than low aggressive rats. The turnover differences reached statistical significance in only two of the 3 brain regions examined: (a) all structures (minus olfactory bulbs) rostral to the level of the anterior commissure, and (b) the brain stem (hypothalamus-midbrain-medulla). The observed differences cannot be attributed to differing behavioral experiences since the high and low aggressive groups pooled did not differ from the no-fighting control. These findings are discussed with respect to the involvement of serotonin in rat intraspecies aggression.


Intraoperative recording of the His bundle electrogram in man. An assessment of its precision. To estimate the effect of distance between the electrode and the signal source on the amplitude of the His bundle electrogram (HBE) recorded during open heart surgery, a specially designed probe, containing six pairs of closely spaced (1 mm) electrodes was placed on the endocardial surface of the right atrium such that each electrode pair was parallel to the course of the His bundle. The amplitude of the HBE recorded through electrodes closest to the His bundle ranged from 0.76 to 2.44 mV, at 1mm from 0.38 to 1.13 mV, at 2mm from 0.27 to 0.86 mV, and at 3 mm from 0.2 to 0.44 mV. Maximal amplitude of HBE decreased by 57% at 1mm, 73% at 2 mm, and 82% at 3mm. The percent decrease was initially rapid, then declined more slowly at distances greater than 1 mm, resembling in form data obtained previously in animal studies by different techniques. Since the maximum HBE was greater than 1.0 mV in nine of 11 patients, and equal to or greater than 1.0 mV in only two of 11 patients at 1 mm, and less than 1.0 mV in all patients 2.0 mm from the maximal HBE, the anatomic location of the His bundle can be estimated from HBE amplitude. Intracardiac electrograms, recorded through closely spaced bipolar electrodes during open heart surgery, afford clinically useful precision in locating the specialized conduction tissue of the heart.


[Determination of serum transcortin levels by electroimmunodiffusion (author's transl)]. The isolation of transcortin in a pure form made possible the preparation of a monospecific anti-human transcortin rabbit serum. Serum transcortin levels were measured by electroimmunodiffusion. Experimental results expressed as errors by the calculating of interserial reproducibility were 4.74 per 100. The mean value was significantly different for men (36 subjects: 39.7 +/- 3.6 mg/l) from women (36 subjects: 42.1 +/- 3.9 mg/l). The transcortin determination was performed in pregnancy serum and in serum of women during oestroprogestative treatment. Some studies were performed in pathological cases (hyper- and hyperthyroidism, hyper- and hypocorticism, Kahler disease, ascitic cirrhosis).


Collagen glucosyltransferase. Partial purification and characterization of the enzyme from whole chick embryos and chick-embryo cartilage. A purification of over 2000-fold is reported for collagen glucosyltransferase from Triton X-100 extract of whole chick embryos and one of about 160-fold from similar extract of chick embryo cartilage. The addition of the detergent more than doubled the enzyme activity in the homogenates. The purified enzyme preparations from whole chick embryos showed one major band and two or three minor bands in polyacrylamide gel electrophoresis and were entirely free of collagen galactosyltransferase activity. The molecular weight of collagen glucosyltransferase from both sources was about 52000 -- 54000, as determined by gel filtration. In some enzyme preparations an additional form was observed, with an elution position corresponding to a molecular weight of about 130000. Manganese was the most effective metal co-factor for the purified enzyme, but partial replacement could be obtained with Co2+, Mg2+ and Ca2+, whereas no replacement was found with other metals. The activity of the purified enzyme was stimulated by the addition of dithiothreitol to the incubation system and inhibited by preincubation with p-mercuribenzoate. UDP-glucose or the collagen substrate partially protected the enzyme against p-mercuribenzoate inactivation in the presence of Mn2+ but not in its absence. Some protection was also noted with Mn2+ alone.


Structural organization and processing of the genetic transcript in the cellular slime mold Dictyostelium discoideum. The organization of the genome and the synthesis and processing of heterogeneous nuclear RNA (HNRNA) in the cellular slime mold Dictysotelium discoideum have been analyzed. Approximately 60-70% of the genome of Dictyostelium consists of interspersed reiterated and single-copy sequences. The interspersed reiterated sequences have an average length of 250-400 nucleotides. Approximately 50% of the reiterated DNA sequences consist of long noninterspersed sequences. The results of analyses of ynRNA synthesis and processing have been incorporated into a model. According to the model the primary genetic transcript of Dictyostelium is synthesized as a molecule that is 25% larger than mRNA. The bulk of the hnRNA is synthesized from a unit consisting of a short reiterated DNA sequence transcript at the 5' end of the molecule and a single-copy sequence of approximately 1,200 nucleotides in length. In the processing of the mRNA precursor, there appears to be a loss of the majority of the repetitive sequence at the 5' end. The genome contains interspersed sequences of poly (dT)25. These sequences, which appear to be at the 3' terminus of the transcription unit, are transcribed directly into the heterogenous nuclear RNA and are contained within the messenger RNA. During the processing of the heterogeneous nuclear RNA, a poly (A) sequence of approximately 125 nucleotides in length is added posttranscriptionally to the 3' end of the molecule.


Interaction of nicotine and other amines with the endocytic and exocytic functions of macrophages. Nicotine inhibits endocytosis and stimulates exocytosis in macrophages. At the same concentrations (5-15 mM) that the alkaloid exerts these effects, it is also vacuologenic. Consideration was given to one hypothesis that the membrane internalization was a result of surfactant activity. Nicotine was found to have surfactant properties. Studies involving measurements of the contact angles of a sessile drop of saline on cell monolayers suggested that nicotine increased the hydrophilicity of the membrane. The possibility has been considered that this may be indicative of membrane expansion and that this expansion leads to collapse and vesicle formation. This would be analogous to the effects of surface-active amines (e.g., local anesthetics, tranquilizers, antihistamines) on lipid monolayers and erythrocytic membranes. It is suggested that if such a mechanism does occur, then the possibility exists for a variety of amines to nonspecifically alter membrane and receptor availability of the macrophage.


Calcium-induced spikes in cultured pigment epithelium of chick retina. Resting membrane potentials, electrical resistance, and coupling of chick retinal pigment epithelium cells in tissue culture have been measured with micropipette electrodes. Topical application of NaCl, KCl, MgCl2, and CaCl2 produce rapid, reversible changes in the membrane potentials of these cells. CaCl2 uniquely induces a slow hyperpolarizing wave that can lead to barrages of depolarizing action potentials or spikes and a slow, reversible vacuolization of the cells.


Keloidal blastomycosis (Lobo's disease) with lymphatic involvement: a case report. Keloidal blastomycosis (Lobo's disease) is reported in a 34-year-old man from the Brazilian Amazon area. His left ear and posterior auricular region were involved. He is the eighth of 99 patients known to have lymph node involvement.


Studies on vesicourethral reflexes. II. Urethral sphincteric responses to spinal cord stimulation. A bipartite bladder model was developed with and without complete muscular separation in order to isolate and analyze separately sphincteric  and detrusor responses. Spinal cord stimulation of the sacral micturition center evoked responses in the detrusor compartment as well as in the urethral sphincteric compartment. The micturition center was easily definable in the spinal cord at a variable point lying in the segment L51/2 to L6 vertebral levels. It was not possible to isolate a separate detrusor center from a sphincteric center. They did overlap-with the sphincteric center extending both above and below the detrusor center. Parameters of stimulation were tested and it was noted that 1 to 3 v, frequency of 10 to 15 cps, and duration of 1 msec gave the optimal responses. Complte muscular separation did not alter sphincteric response to spinal cord stimulation. Nerve-mediated impulses resulted in rise in detrusor pressure and a simultaneous rise in urethral pressure that interfered with proper voiding and hindered bladder emptying. This problem remains to be solved before central spinal cord stimulation for the  purpose of controlled bladder evacuation becomes fully effective.


Transmission of equine infectious anemia virus by Tabanus fuscicostatus. The mechanical transmission of equine infectious anemia (EIA) virus by Tabanus fuscicostatus was investigated. In 1 of 7 transmission trials, a single horsefly transmitted EIA virus from an acutely infected pony to a susceptible pony. Groups of horseflies isolated for 3, 10, or 30 minutes before refeeding transmitted EIA virus, whereas those isolated for 4 or 24 hours did not. Data from field studies indicate that the home range or flight distance of horseflies may exceed 4 miles. That information together with our observations suggest that segregation of infected horses (usually defined as at least 200 yards from susceptible horses) as a control measure for EIA may not be an adequate safeguard against transmission in areas where horseflies are numerous.


Extracellular and protease-released pullulanases. The extracellular form of pullulanase (EC 3.2.1.41) from Klebsiella aerogenes has been purified to homogeneity by successive chromatography through diethylaminoethyl-cellulose, Sephadex G-200, and 1,6-diaminohexane-Sepharose. In addition, the cell-bound form of pullulanase has been released by the action of a serine endopeptidase obtained from Pronase and purified to apparent homogeneity. Protease-released pullulanase has a slightly larger molecular weight and a specific activity over twice that of the extracellular protein. The properties of each of these forms of pullulanase have been compared with those reported for the detergent-released form. Each form has different features as examined by amino acid composition, specific activity, molecular weight, or inhibition pattern, which distinguish it from the other pullulanases. It is hypothesized that a single gene product consisting of a single polypeptide chain generates these different enzyme forms after selective cleavages by endogenous or applied proteases.


Utilization of exogenous thymidine by Chlamydia psittaci growing in the thymidine kinase-containing and thymidine kinase-deficient L cells. The incorporation of [3H]thymidine into the deoxyribonucleic acid (DNA) of Chlamydia psittaci (strain 6BC) growing in thymidine kinase (adenosine 5'-triphosphate-thymidine 5'-phosphotransferase, EC 1.7.1.21)-containing L cells, L(TK+), and thymidine kinase-deficient L cells, LM(TK-), was examined by autoradiography. Label was detected over C. psittaci inclusions in L(TK+) but not LM(TK-) cells. No evidence for a chlamydia-specific thymidine kinase activity in either L(TK+) or LM(TK-) cells was obtained. Entry of [3H]thymidine into the DNA of C. psittaci growing in L(TK+) cells was quantitated by measuring label in purified C. psittaci. It was 265 times less efficient than entry into infected host cell DNA. It is concluded that low levels of exogenous thymidine are incorporated into the DNA of C. psittaci and that this incorporation is dependent on a fully competent host thymidine kinase activity. Evidence also is presented that L cells possess at least two thymidine kinase activities, both of which are capable of supplying thymidylate precursors for nuclear DNA synthesis.


Biosynthesis of chondroitin sulfate. Role of phospholipids in the activity of UDP-D-galactose: D-xylose galactosyltransferase. The role of phospholipids in the activity of UDP-D-galactose: D-xylose galactosyltransferase (galactosyltransferase I) from embryonic chick cartilage was investigated. Phospholipase C treatment of particulate galactosyltransferase I caused inactivation of this enzyme to the extent of 60 to 70% as well as hydrolysis of 75 to 80% of the membrane phospholipids. Addition of phospholipid restored activity to nearly control levels. The order of effectiveness of various phopholipids in reactivating phospholipase C-treated galactosyltransferase I was as follows: lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylethanolamine, phosphatidylcholine. The effect of phospholipase A on galactosyltransferase I activity was also examined and was found to be concentration-dependent. At concentrations less than 10 mug/mg of pellet protein, phospholipase A slightly activated galactosyltransferase I. whereas at higher concentrations it inhibited the activity in a manner similar to phospholipase C. Galactosyltransferase I was activated moderately and also solubilized by treatment with Nonidet P-40 in the presence of 0.5 M KCl. Following solubilization and purification by gel filtration and affinity chromatography, galactosyltransferase I could be inactivated by detergent removal by dialysis and subsequently reactivated by addition of detergent. Neither phospholipase C treatment nor exogenous phospholipid had any significant effect on three of the other chondroitin sulfate glycosyltransferases (UDP-D-xylose: core protein xylosyltransferase, UDP-D-glucuronic acid:3-O-beta-D-galactosyl-D-galactose glucuronosyltransferase, and UDP-N-acetyl-D-galactosamine:(BlcUA-GalNAc-4-sulfate)j N-acetylgalactosaminyltransferase). On lipid analysis by thin layer chromatography, phosphatidylcholine and phosphatidylethanolamine were found to be the major phospholipids of particulate and solubilized glycosyltransferase preparations from embryonic chick cartilage, while lysopholipids of particulate and solubilized glycosyltransferase preparations from embryonic chick cartilage, while lysophosphatidylcholine and lysophosphatidylethanolamine were barely detectable components. The concentration of these specific phospholipids was diminished greatly following phospholipase C treatment.


Site of cleavage of superhelical phiX174 replicative form DNA by the single strand-specific Neurospora crassa endonuclease. Experiments with the Neurospora crassa single strand-specific endonuclease have provided evidence for the existence of regions of partially single-stranded character in covalently closed superhelical replicative form DNA of phiX174. The nuclease converts the superhelical molecules to either singly hit relaxed circular or doubly hit linear molecules. We show that the initial cleavage of phiX174 superhelical DNA is a "nick" bounded by a 5'-phosphate and a 3'-hydroxyl; no nucleotides are excised as evidenced by the ability of T4-polynucleotide ligase to reform the phosphodiester bond. The nick can be found in either strand of the double-stranded DNA and is either randomly distributed or at least can be found at any one of many possible locations in the genome. Thus, the regions in phiX174 superhelical molecules that are sensitive to the N. crassa nuclease do not occur at highly specific sites in the genome.


Non-histone chromosomal proteins from HeLa cells. A survey by high resolution, two-dimensional electrophoresis. Analysis of HeLa non-histone chromosomal protein by two-dimensional polyacrylamide gel electrophoresis has revealed more than 450 components, most of which are rare (less than 10,000 copies/cell) and are not detectable in cytoplasm. Chromatin prepared from nuclei isolated by a nonaqueous technique contains essentially all of the proteins found in chromatin from aqueous nuclei, implying that cytoplasmic contamination is not significant. The complexity of chromatin is comparable to that of cytoplasm (500 proteins detected) and greater than that of nucleoplasm (300 proteins detected). Approximately 60 proteins occur in chromatin, nucleoplasm, and cytoplasm; one of these appears to be actin.


Structural proteins of ribonucleic acid tumor viruses. Purification of envelope, core, and internal components. Murine type C virus structural proteins, the envelope glycopeptides, 30,000 dalton major core protein, and 15,000 dalton internal protein have each been purified to near homogeneity and in high yield from the smae batch of virus by use of phosphocellulose column chromatography and gel filtration procedures. Evidence that these proteins are specified by the viral genome was obtained by competition radioimmunoassay analysis, comparing these polypeptides from Rauscher virus cultivated in a variety of mammalian cell lines; all of the reactive antigenic determinants of these proteins appeared to be virus-specific.


Spindle and kinetochore morphology of Dictyostelium discoideum. The metaphase spindle of haploid Dictyostelium discoideum (n = 7) is 2 mum long. It consists of some 20 microtubules which seem continuous between the spindle pole bodies and there are about 20 chromosomal microtubules at each end of the spindle. During anaphase the central spindle elongates and the chromosomal microtubules shorten. The spindle length and structure at this stage suggests that lengthening is caused by elongation as well as parallel sliding of the nonchromosomal microtubules. The nuclear envelope remains mostly intact during mitosis, and nuclear separation through medial  constriction takes place when the spindle is 6 mum long. Cytokinesis occurs when the spindle is 10 mum long. At that time the kinetochores double in size. During interphase, the spindle pole body separates from the nucleus to a distance of 0.7 mum, and it returns at the onset of the next prophase when it becomes functionally double, thereby starting the formation of a central spindle. When comparing mitosis in the cellular slime molds Polysphondylium violaceum and D. discoideum, several similarities and some differences are apparent.


Femoro-popliteal by-pass with bovine heterografts. Modified bovine heterografts were used in 28 patients, primarily extremity salvage problems, found to have unavailable or unusable saphenous veins. The accumulated 3 year patency rate was 35%. Of the 18 graft  failures, 11 required major amputation. A high failure rate of 39% in the first six-month interval was observed. Electromagnetic flowmeter recording were of limited value in predicting patency. Continued evaluation of bovine grafts for femoro-popliteal reconstruction in the absence of saphenous vein is recommended.


Intercellular adhesive selectivity. I. An improved assay for the measurement of embryonic chick intercellular adhesion (liver and other tissues). An improved assay for measuring intercellular adhesive selectivity of embryonic chick liver cells is described. Three major improvements over earlier procedures are noted: (a) enhanced reproducibility of liver cell-liver cell aggregate adhesion (homotypic adhesion) was achieved; (b) 25-70% of the input cells adhered to the collecting aggregates during the course of routine experiments as compared to the 0.25% in earlier assays. This increase in cellular adhesion suggests that the observed cell pick-up is a characteristic of the majority of the dissociated liver cell population; (c) the rate of intercellular adhesion was increased 1,000-fold. The main feature of the assay is that it measures the tissue adhesive selectivities of the dissociated cell population. Studies were undertaken on three embryonic chick tissues (liver, neural retina, and mesencephalon) to determine the tissue selectivity of intercellular adhesion of these dissociated cell types. Some general properties of liver cell homotypic adhesion have been studied and are reported.