Endometrioid carcinoma of the rectum arising in endometriosis: report of a case. The case of a patient with an endometrioid carcinoma arising in endometriosis of the rectum is presented. This lesion grossly appeared to be a carcinoma arising from the rectal mucosa until microscopic examination of the specimen was completed. The endometrial implant continued to grow and eventually degenerated into a carcinoma in spite of bilateral salpingoophorectomy. This was believed to be due to maintenance of the patient on diethylstilbestrol. This case is believed to be the ninth reported case of carcinoma arising in an endometrial implant in the colon or rectum.


The spectrum of colonic involvement in pancreatitis. Colonic involvement as a result of pancreatitis is an uncommon but interesting complication of the disease. Among the significant manifestations we have seen are: 1) adynamic ileus of the transverse colon, 2) fibrosing, stenosing pericolitis localized to the splenic flexure area, and 3) colonic hemorrhage secondary to necrosis and fistula formation. Ordinarily, conservative treatment will suffice, but in complicated cases, individualized surgical treatment becomes necessary.


The colonoscope in cecal volvulus: report of three cases. Colonoscopy was employed to attempt detorsion of volvulus of the right colon in four patients considered to be high-risk surgical patients. In one patient detorsion was accomplished, so that emergency laparotomy became unneccesary. The site of torsion was reached in every patient. When detorsion does not occur reasonably soon after the colonoscope enters the right colon, persistent efforts are more likely to be harmful than helpful. Abdominal symptoms in a patient who has been ill or injured for some time should suggest the possibility of volvulus of the right colon. Early diagnosis and earlier employment of colonoscopy would almost surely result in an increased rate of success in accomplishing detorsion. When detorsion is accomplished, subsequent resection of the right colon should be seriously considered as, without it, volvulus is said to recur frequently.


Irradiation-induced colonic stricture and colitis cystica profunda: report of a case. A 57-year-old patient was operated upon for a colonic stricture that appeared 18 years after removal of a clear-cell carcinoma of the kidney, followed by irradiation therapy. In addition to typical irradiation-induced changes and fibrotic stricture, colitis cystica profunda was discovered. Review of the literature showed no similar case.


[Vitamin D deficiency and osteomalacia in old people (author's transl)]. The frequency and causes of vitamin D deficiency in old age were investigated in 53 hospital patients, 88 persons from old people's homes, 21 tenants of a hostel, and 29 members of a seniors meeting group, aged between 65 and 93 years. In all persons 25-hydroxyvitamin D, calcium, phosphate, alkaline phosphatase, leucine arylamidase and creatinine were determined. In 27 cases immunoreactive parathormone was measured. In hospital patients there was evidence of vitamin D deficiency significantly more frequently as compared with the other groups. The 25-hydroxyvitamin D concentration was on average lower in the cases from old people's homes and hostels than in the members of the seniors group. The results in the groups investigated showed a relation to the average exposure to the sun. The results in 10 further patients in this age group with florid osteomalacia indicate a multifactorial aetiology of vitamin D deficiency disease due to reduced exposure to sun, inadequate nutrition and reduced absorption of vitamin D.


[Hepatic necroses after infusion cholangiography (author's transl)]. Ten episodes of massive transaminase increase with hepatic necrosis were observed in 7 patients after infusion of megluminioglycamide (Biligram). The patients were 3 men and 4 women aged 49 to 65 years with biliary tract disease (n = 1), recurrent pancreatitis (n = 1), hyperlipidaemia and minimal toxic liver damage (n = 1), pyelonephritis (n = 1), , arteriitis (n = 1), and pseudo-LE (n = 1). In 6 patients there was an increase of the alkaline phosphatase without icterus before the investigation and a slight increase of transaminases in 3 patients. After infusion of 100 ml of Biligram in 5 patients and of 200 ml in 2 patients there was an abrupt increase of GPT (98-2202 U/l) with a lesser increase of GOT. The alkaline phosphatase activity remained unchanged. Three patients showed symptoms such as upper abdominal pain, fever erythema, or conjunctivitis. Histologically all patients showed centrolobular necroses. Transaminases should be checked 2 days after intravenous cholangiograms. In patients with a definite increase reexposure should be avoided.


[Coronary angiographic findings in 308 patients with the clinical diagnosis of intramural myocardial infarction (author's transl)]. 308 patients with the clinical diagnosis of intramural myocardial infarction made elsewhere were re-investigated more than eight weeks after the acute event. ECGs and pulmonary "wedge" pressures were recorded at rest and during exercise and coronary angiography performed (Sones' or Judkin's technique). In the first group (1973/74) of 77 patients, 35 (45.5%) had a normal coronary angiogram, compared with 0.7% in a control group with transmural myocardial infarction. A normal coronary angiogram was found in 85% of the 40 patients who had no angina during exercise. In a second group (1974/77) of 231 patients, there was a steady decrease in the number of patients without angina pectoris during exercise, in parallel with a decrease in the number of those with normal coronary angiograms. This change in pattern was apparently due to improved diagnosis in the referring hospitals. Of the 37 patients (first group) with angina during exercise, all but one were subsequently found to have significant coronary arteriosclerosis. It is suggested that most patients with a normal coronary angiogram had sustained a myocarditis and (or) pericarditis which produced the symptoms and the altered ECGs, leading to the misinterpretation of "intramural myocardial infarction".


[Acute rise in serum calcitonin concentration during haemodialysis (author's transl)]. Calcium and calcitonin concentrations were measured at the beginning, during and at the end of haemodialysis in 31 unselected patients on chronic intermittent haemodialysis. Blood samples were drawn at the end of dialysis under two different conditions: first, at the end of dialysis during which dialysate calcium concentration was always at 1.75 mmol/1 and secondly, at the end of dialysis with dialysate concentration elevated to 3.0 mmol/1 for the last third of the dialysis period. There was a highly significant increase in serum calcium concentration during haemodialysis, due to transmembranous calcium transfer in all instances. Calcitonin was detectable in free dialysis blood samples of 30 among the 31 patients. In 14 patients there was a significant increase in calcitonin concentration due to increasing calcium concentration during haemodialysis, while in 17 patients there was no change in the calcitonin concentration. Where calcitonin secretion could be stimulated there was a highly significant positive linear correlation, on a percentage basis, between calcium and calcitonin concentrations (r = 0.83, P less than 0.001).


[Pneumometer values in healthy children and adolescents (author's transl)]. On the basis of investigations in 764 healthy children aged 3--17 years (398 boys and 366 girls) normal values for the maximal pneumometric expiration were established. There were definite correlations between the pneumometer values and sex, age, height and weight. The correlation coefficients between the pneumometer values and age or height were about + 0,90. The boys have on average higher pneumometer values than the girls, but the differences are not significant.


[Familial liver cirrhosis in pseudohypoparathyroidism in young children (author's transl)]. Two sisters whose mother had pseudo-pseudohypoparathyroidism, simultaneously developed in infancy pseudohypoparathyroidism with severe liver damage leading to cirrhosis and characterised by "ectoplasmic vacuoles", as well as severe anaemia and thrombocytopenia. As any known metabolic or inflammatory liver disease could largely be excluded, a common genetic defect is assumed as the cause of the combined disorder in calcium and hepatic metabolism.


[Effects of oxyfedrine on haemodynamics in patients with acute myocardial infarction (author's transl)]. In 16 patients with acute transmural myocardial infarction the effect of 8 mg of intravenous oxyfedrine followed by an infusion of 0.3 mg/kg body weight per hour on haemodynamics of the pulmonary and systemic circulation and dynamic cardiac indices was investigated. Cardiac rate, systemic arterial blood pressure, minute volume, cardiac output, and tension-time index remained unchanged on the whole. On the other hand oxyfedrine produced a persistant significant decrease of the mean and diastolic pulmonary artery pressure, pulmonary capillary pressure, and of the contraction and pressure-increase time. These effects were also demonstrable in patients previously treated with digitalis. No cardiac arrhythmias were observed. The positive inotropic effect of oxyfedrine is suggested as reason for these changes.


[Evaluation of infarct size using serum concentration of the CK-MB isoenzyme (author's transl)]. The size of infarction was determined in 21 patients with acute myocardial infarction aged 42 to 76 years using serial analyses of the serum concentrations of the total creatine kinase (CK) and of the CK-MB isoenzyme. CK-MB isoenzyme concentrations reached their maximum in serum three hours earlier on average and returned to the initial value 10 to 12 hours before the total CK. CK-MB isoenzyme concentrations reached a maximum of 12.4% of maximum total CK activity. In 17 uncomplicated cases the infarct weight determined from total CK (40 +/- 23 g) and from CK-MB isoenzyme (35 +/- 23 g) was only different by 5 g (r = 0.92). In 4 patients with infarction and defibrillation or reanimation use of total CK led to an overestimation of the infarct size by more than double. The determination of the infarct size from CK-MB isoenzyme values proves that without extracardial CK release, estimation of the infarct size can also be done sufficiently exactly from the total CK concentrations. In complicated cases, however, the specific myocardial CK isoenzyme makes determination of the infarct size possible


[Treatment of acute myocardial infarction with metoprolol (author's transl)]. Metoprolol, a cardioselective beta-receptor blocker, was administered to 12 patients three to ten hours after sustaining a transmural myocardial infarction, and the effect of the drug (10 mg i.v., followed by 50 mg orally every eight hours) was followed for 48 hours. Heart rate decreased by 16% and cardiac output by 27%, while blood pressure and stroke volume decreased little and pulmonary "wedge" pressure was not significantly changed. Even in patients with initially definitely elevated left-ventricular filling pressure (greater than 20 mm Hg) the drug was well tolerated without any further rise in pressure. Since left-ventricular work was significantly decreased (stroke work--15%, cardiac output--31%) and the duration of diastole, decisive for coronary perfusion, was prolonged, it is concluded that early administration of beta-receptor blockers has a favourable effect on myocardial oxygenation and possibly reduce ultimate infarct size.


[Cerebral blood flow and social prognosis after cerebrovascular ischaemia (author's transl)]. Cerebral blood flow (CBF) was measured in 180 patients one to eight weeks after sustaining an acute episode of cerebrovascular ischaemia. The patients were divided into four groups in relation to their performance of daily activities at the time of CBF study: score 0 - full previous activities; 1 - slight; 2 - moderate; and 3 - severe disability. There was a statistically highly significant difference between the flow values of these groups. The patients were regrouped according to their rehabilitation status (score 0 to 3 as above, score 4 - dead) after a mean observation period of 34 months. The differences between flow values were even higher now, significant contingency coefficients being found between flow values and final social scores. When the patients were grouped according to changes in performance scores there again were statistically significant differences in flow values between the groups. The relationship between flow values and social re-integration after cerebrovascular ischaemia indicates the value of CBF measurements for prognosticating a patient's rehabilitation ability after stroke.


[Significance of the radioallergosorbent test (RAST) in the specific diagnosis of atopic bronchial asthma (author's transl)]. The radioallergosorbent test (RAST) is a recently developed radioimmunological in-vitro method for determining IgE-specific serum antibodies in reaginic allergy. There was 63.4% overall correspondence between RAST and bronchial provocation test in 423 tests with a total of eight perennial allergens on adults with asthma. Where there was disagreement, combination of postiive inhalation test and a negative RAST was much more frequent (33.6%) than in the obverse (3%). Agreement between RAST and provocation tests was 79% for the house dust mite Dermatophagoides pteronyssinus, 71.5% for cat and dog epithelium, 70% for the Penicillium mould, 63% for Alternaria, 55% for Hormodendron and Aspergillus and only 53% for house dust. In asthmatics a positive RAST usually indicates clinically relevant sensitization (positive case history or positive provacation test), while negative results (especially in cases of mould or house dust allergy) do not rule out possible significant sensitization. On the other hand, skin tests with moulds and house dust are frequently "false" positive. First test in the specific diagnosis of bronchial asthma remains a thorough case history combined with careful skin testing. When the two disagree, RAST is helpful together with as a "secondary" allergy test.


[Epidemiology of duodenal ulcer (author's transl)]. The epidemiology of peptic ulcer was investigated in 1105 endoscopy patients in a Zurich city hospital and in a random nongastroenterological hospital population. A raised susceptibility for duodenal ulcer was found in young, mainly unskilled, foreign labourers. There was no raised susceptibility in female foreign workers who also suffered less often from gastric ulcer than Swiss women. A tendency to ulceration in certain other diseases previously incriminated and in alcohol and nicotine consumers was not observed. A connection between susceptibility to ulceration and migration is assumed.


[Carcinoembryonic antigens (CEA) in patients with metastatic breast cancer under endocrine and therapeutic treatment (author's transl)]. Carcinoembryonic antigen (CEA) was determined in 72 patients with metastatic breast cancer under various kinds of treatment. In 53 cases, CEA levels were elevated. They correlated with free interval, metastatic spreading, alkaline phosphatase (AP) and gamma-glutamyltranspeptidase (gamma-GT). Serial CEA determinations in 50 of the 72 patients revealed increased CEA levels in connexion with progressive tumour growth and decreased CEA levels in connexion with response to treatment. CEA may therefore be useful in helping to assess the extension of the tumour and the effect of treatment in patients with matastatic breast cancer.


[Asymptomatic chronic-persisting hepatitis B in a young child as source of infection of hepatitis B within a family (author's transl)]. Five members of an eight-member family fell ill with an acute icteric hepatitis B of the same subtype within eleven months. In all probability the source of the infection was a just over one-year-old fostered child with asymptomatic chronic persisting hepatitis B and signs of massive viraemia (usually high HBs antigen concentration, high virus-specific DNA-polymerase activity and positive HBe antigen test). No relation could be demonstrated between HLA constellation and illness in the family members. Since no specific treatment is available, the only possible prophylactic measure is to isolate the child in the present environment, to avoid further cases of the disease.


[Adenoma of the colon or rectum: relationship between histological structure, polyp size and site and age distribution (author's transl)]. Among 1258 polyps from the lower gastro-intestinal tract removed by rectoscopy or coloscopy and examined histologically there were 744 adenomas, 72% tubular, 27% papillary and 1% villous. 96.5% of all adenomas were extracted from patients aged over 40 years. Four fifths of the tumours were found in the rectum and sigmoid colon. Only 6% of the tubular adenomas were more than 15 mm in diameter, compared with 32% of papillary and 57% of villous adenomas. The special significance of the adenomas lies in their potential malignancy (adenoma-to-cancer sequence).


[Influence of furosemide on beta-methyl-digoxin excretion in the urine (author's transl)]. Ten patients were given 0.1 mg, ten other patients 0.2 mg beta-methyl-digoxin in a daily dose for 14 days. Furosemide (80 mg a single daily dose) was given on the 12th, 13th and 14th day of digoxin treatment. Furosemide had no significant effect on blood-serum levels of the digoxin preparations, nor on its urinary excretion. Urinary excretion and serum levels of beta-methyl-digoxin remained unchanged both after simultaneous administration of furosemide with the digoxin and when furosemide was given ten hours after the last digoxin dose.


[Collagenous sprue (author's transl)].

[Collagenous sprue (author's transl)]. Malabsorption is the main functional abnormality in gluten-sensitive enteropathy or endemic sprue. The malabsorption is related to villous flattening, which is the main histological feature. The diagnosis is also based on a good response to gluten-free diet. On the other hand, collagenous sprue is not an independent disease but a variant of gluten-sensitive enteropathy, as documented in three personal cases. Its course is characterised by a malabsorption syndrome unresponsive to gluten withdrawal, with massive subepithelial collagen formation. The pathogenesis remains unknown, prognosis poor, compared to the endemic gluten-sensitive enteropathy.


[Exercise ECG as a screening test in the early diagnosis of coronary heart disease. Result of a trial study (author's transl)]. 1500 men (aged 30-55 years) volunteered in a trial of early recognition of cardiovascular disease. History and clinical as well as biochemical data were obtained and compared with results of exercise ECGs. In the group as a whole abnormal ECGs were obtained in 6.2%, in a subgroup of those without exercise-dependent pain in the thorax, without hypertension and noraml resting ECG it was 3.8%, while in the presence of one or several of these risk factors it was as high as 17.8%. It is concluded that in any screening programme it is not reasonable to perform exercise ECGs in asymptomatic persons without risk factors, because in this group there is likely to be only a small percentage of abnormal findings and the number of false-positive ones is higher than that or correct positive ones. In connection with the known risk factors and risk indicators it would be best to define the risk group and, using selective indications, to go step-by-step from exercise ECG to additional invasive diagnostic measures such as coronary angiography.


[Blood rheology in chronic arterial occlusive disease as influenced by vasodilators (author's transl)]. Increased blood and plasma viscosity was found in patients with chronic arterial occlusion in comparison with healthy probands. The measurements were done at high and low shear rates. Parenteral pentoxifylline (Trental) lowered blood and plasma viscosity of patients significantly, especially when measured at low shear rates. Application of bencyclane (Fludilat) produced variable results. A definite connection between rheological changes and alterations of the protein fractions in plasma could not be established.


[Pharmcokinetics of an echinopsin preparation]. The purpose of the present work is to describe the pharmacokynetic characteristics of the preparation Ehinopsine, which represents N-methyl-gamma-chinoline and is synthetised in NIHFI during 1965. The experiments were carried out on male rats of the strain Wistar with weight of 170 to 190. The authors examine in dynamics plasma and tissues after single intraperitonenal administration of a dose of 30 mg/kg of body weight, plasma after venous administration of 25 mg/kg of body weight and 100 mg/kg of body weight and plasma and tissues-after oral administration of 100 mg/kg of body weight. The excretion of the preparation was examined also in bile, urine and feces after oral administration and there were metabolites in urine. On the basis of the experimental data after oral and venous treatment the respective mathematical models of distribution were determined as well as the basic pharmacokynetic parameters, characterizing the behaviour of Ehinopsine in the organism of rats. The obtained results gave a picture for good resorption of the preparation, quick distribution, weak excretion and wide biotransformation in the organism of the experimental animals.


[Electrophoretic study of pepsinogen in the gastric mucosa of white rats normally and with an experimental gastric stress ulcer]. The authors carried out electrophoretic studies of pepsinogen, obtained from the stomach mucosa of white rats (10 normal animals) and with experimental stress ulcus of the stomach, induced by imobilization and cooling (20 animals). The stomach of the rats was pulled out under light ether narcosis and the stomach mucosa was removed. Pepsinogen was extracted with 0.01 normal solution of hydrochloric acid. The supernatant was examined on agar electrophoresis after centrifugation. Incubation was made with hemoglobin solution of 0.66%. There were 4--5 pepsinogen fractions with well manifested proteolytic enzyme activity and sharply manifested ranges in the control animals. There was a reduction of the number of pepsinogen fraction in the animals with experimental stress ulcus of the stomach, as in 17 animals there was only one fraction with weak electrophoretic mobility, but with well manifested activity and in 3 animals--2 pepsinogen fractions. He discusses some questions about the increased cell-membrane permeability, accompanied by an increased release of pepsinogen and its preliminary activation in the stomach secretion.


[Changes in the electromyographic potentials in cats poisoned with superlethal doses of phosdrin and treated with doline]. The authors carried out studies on 10 cats, anesthetized by urethane, under atropine protection and under the conditions of artificial respiration and examined the influence of therapeutic antidote of phosphorganic pesticides-Doline on the induced eletromyographic activity during total neuro-muscular block, induced by superlethal doses of phosphadrine. It was established that superlethal doses of phosphadrine induced total block of electropotentials in neuro-muscular conduction of the peripheral musculature, which was removed immediately after venous and muscular administration of the antidote Doline.


[Effect of hemodex on the phagocytic activity of peritoneal macrophages in vitro]. The author examined the influence of hemodex (SMT 70 000), high molecular and mean molecular fractions of the same on the phagocytic activity in vitro. The experiments were carried out on macrophages of white mice "Swiss", treated with the preparations for one to ten days. She found that VMF and hemodex after a five-day treatment induced an increase of the phagocytic activity in respect to sheep erythrocytes in comparison with the control group.


[Action of iron, ethanol and tetrachloromethane on lysosomal membrane permeability]. The authors examined the isolated and combined influence of oral administration of iron and ethanol as well as subcutaneous administration of CCl4 on the activity of two lysosomal enzymes in serum as the experiments were carried out on 72 male white rats of the Wistar strain with initial weight of 130 to 190 gm. The two exmained enzymes were: beta-N-acethylglucosaminidase and alpha-manosidase. The increased activity of these enzymes under the action of ethanol, iron plus ethanol, CCl4 was interpreted as a manifestation of increased permeability of lysosomal cellular membrane.


[Stereology of the interstitial cells of the renal medulla in shock]. The authors carried out quantative stereologic studies on the electronograms of intersticial cells of the medulla of the kidney during shock. There was a considerable lowering of the number and volume of lipid granules in comparison with the control nontreated animals. The results were interpreted as a manifestation of the increased release of prostaglandins from the renomedullar intersticial cells as mediators of some local processes in the kidney, enduring shock.


[Immunomorphological studies of chronic hepatitis and liver cirrhosis]. The authors carried out clincial and immunomorphologic studies on 15 patients with chronic hepatitis and liver cirrhosis with unknown etiology. The presence of specific sensibilization of lymphocytes of the patients to liver tissue was examined by blast-transformation test. For this purpose they compared immunomorphologic response to lymphocytes in culture from peripheral blood to liver and renal antigen, using parallel procedure with FHA and cultures, growing spontaneously. Ten clinically healthy and 12 persons with renal polycystosis were examined as controls. The results showed an increased immune response to lymphocytes of the patient with liver cirrhosis to liver antigen as well as to culture, developing spontaneously, which suggested that autoimmune reaction with specific tendency to antigens of liver developed in these persons.


[Antibiotic action on the embryonic development of the fetuses of amphibians]. The effect on the embrionic development of Tr. cristatus of 16 antibiotics (keflin, penicillin, benzazillin, ampicillin, nystatin, kanamycin, streptomycin, novobiocin, brunomycin, erythran, oleandomycin, tetracyclin, chlornytromycin, gentamycin, rimactan, and capreomycin) administered in 3 concentrations was studied. It was established that except kanamycin, keflin and rimactan all the rest damage the embryonic development showing certain phase specifity. Gastrulation turned to be the most sensitive embryonic period.


[Experiment to potentiate the effect of cyclophosphamide combined with tempidon and caffeine in leukemia L1210 and Lewis hepatic carcinoma]. The authors carried out experiments on mice DBA/2 and BDF1 with leucosis L1210 and lung carcinoma of Lewis and found that psycotropic preparations tempidone and caffeine did not manifest antitumorous effect and toxicity after the used doses and scheme of treatment. Tempidone enhanced antitumorous action of small and mean doses of cyclophosphamide in mice with leucosis L1210. In the triple combination (tempidone, caffeine and cycl phosamide) the caffeine enhanced this action of tempidone without raising toxicity in mice with leucosis L1210, but not in mice with lung carcinoma of Lewis.


Virilizing effect of methyltestosterone on female descendants in the rat. Pregnant rats were given daily a subcutaneous injection of methyltestosterone for 4 days from the 17th to the 20th day of gestation, and were allowed to be delivered to their offsprings (F1) which were used for the examination of later reproductive functioning. When observed for 21 weeks after birth, the growth rate of F1 from methyltestosterone-treated groups was higher than that of F1 from the control group. The anogenital distance in 50-microgram-treated F1 females started to become significantly longer on the 14th day and in 5-microgram-treated F1 females on the 28th day after birth than that in F1 from the control. The day on which vaginal opening took place in 50% of females was 34.4 days of age in both the control and the 5 microgram groups, but it delayed until 40.7 days in the 50 microgram group. Furthermore, persistent estrus was observed after about 90 days of age in the 50 microgram group. This persistent estrus disappeared by placing these females with males, resulting no pregnancy. In the 5 microgram group females could be pregnant, but their female fetuses (F2), when examined on the 21st day of gestation, had significantly shortened the length of the urovaginal septum. The observations show that virilization can be induced in the third generation.


Effects of temperature and urea concentration on the chemical modification and ionization behavior of tyrosyl and iodoamino acid residues of porcine thyroglobulin. Acetylation of porcine thyroglobulin with N-acetyl imidazole was performed at various temperatures in the presence of urea. In the medium without urea, the number of O-acetylated iodoamino acid residues formed was constantly 15 above 10 degrees C (originating from all diiodotyrosyl and a few of monoiodotyrosyl residues), while the number of O-acetyl tyrosyl residues increased gradually from 15 at 0 degrees C to a maximum of 70 at 70 degrees C. All (about 25) iodoamino acid residues were acetylated at 20 degrees C in 2 M urea, while the presence of 8 M urea was necessary to acetylate all tyrosyl residues at 20 degrees C. Experiments on the nitration of thyroglobulin with tetranitromethane showed that diiodotyrosyl and thyroxyl residues were easily nitrated even at low temperatures and the low ratio of the reagent to the protein, while tyrosyl residues consisted of three groups: the first group (about 14%) which was very easily nitrated even at 0 degrees C and the low ratio of the reagent to the protein, the second group (about 45%) which was nitrated depending on temperature and the molar ratio of the reagent, the remaining which was definitely unreactive even under extreme conditions. In addition, the ionization of tyrosyl and iodoamino acid residues was studied by spectrophotometric titration at various temperatures in the presence and absence of 8 M urea. It was found that diiodotyrosyl and thyroxyl residues did not change very much with respect to ionization behaviour by the addition of urea, in contrast to clear dependence of tyrosyl residues on urea. Based on these observations, the location of these residues and the structural change of the protein with temperature are discussed.


Effect of cytidine diphosphate choline on growth hormone and prolactin secretion in man. The effect of intravenous infusion of cytidine diphosphate choline (CDP-choline) on the serum levels of growth hormone (GH) and prolactin (PRL) was studied in six normal adult male subjects. Serum GH levels increased and reached a maximum at 60--90 min after the initiation of infusion in all subjects examined. The mean peak value of GH in six subjects was 10.0 +/- 2.1 (mean +/- SE) ng/ml, which was signigicantly higher than the basal level (p less than 0.01). In four subjects, serum PRL levels decreased from 10--24 ng/ml to less than 7.2 ng/ml at 60--120 min, while in the other two no significant change was observed. These results indicate that CDP-choline affects GH and PRL secretion from the anterior pituitary.


Analysis of the positive feedback effect of estrogen on the release of gonadotropin in women. In order to elucidate the positive feedback mechanism of estrogen on gonadotropin release in women, the responses of plasma LH and FSH to the constant infusion of estradiol-17 beta for a prolonged period were studied. The infusion was initiated on various days of the follicular phase and maintained for 36-66 hr at a constant rate of 500 or 1,000 microgram/24 hr. When the stimulus of estradiol was sustained for more than 30 hr in the women of the middle or late follicular phase, a positive feedback effect to elicit gonadotropin surges was observed during the maintenance of the infusion. In contrast, the stimulus of estrogen was ineffective in the early follicular phase, even if sustained for a longer period up to 66 hr. Gonadotropin levels, also, increased after the end of infusion. The magnitude of the responses, however, was much smaller, as compared to spontaneous preovulatory gonadotropin surges. In all cases, the effect of estradiol was greater for LH than for FSH. It is suggested that: 1) Preovulatory gonadotropin surges are triggered by estrogen increments rather than the withdrawal of the negative feedback effect of estrogen. 2) Low levels of estrogen for a certain period of the early follicular phase may play an important role in priming the control system which responds to the positive feedback effect of estrogen.


Somatostatin radioimmunoassay with 125I-Nalpha-tyrosyl-somatostatin. Nalpha-Tyrosyl-somatostatin was synthesized and proved to be homogeneous. Radioiodination of this tyrosine-containing somatostatin analogue by either the lactoperoxidase method or the chloramine T method led to the formation of crude iodinated compound, which was purified by ion exchange chromatography on CM-Sephadex C-25 using a linear ammonium acetate buffer gradient. This purification process was found to be satisfactorily reproducible and suitable for the preparation of 125I-Nalpha-tyrosyl-somatostatin. Using the purified 125I-somatostatin analogue, radioimmunoassay for somatostatin was performed and the assay system was proved to be sensitive and specific for somatostatin. Immunoassays of hot-water extracts of porcine and tupaia brain, pancreas, stomach and various regions of the intestine in the system revealed that those tissues contained immunoreactive somatostatin at various concentrations. Of the results, it was remarkable that somatostatin immunoreactivity was found in the ileum, middle colon and rectum in both animals, although the concentration were lower when compared with those in the stomach, duodenum and jejunum.


The role of estrogens in the regulation of lactate dehydrogenase activity and its submolecular organization in rat anterior pituitary. Estrogens increase LDH activity and decrease H/M subunit ratio in rat anterior pituitary in both the experimental circumstances and the physiological conditions. The cellular messengers mediating estrogenic effect are structure- and stereospecific. The activity increasing and subunit ratio decreasing potency of the three tested estrogens was of following decreasing order: 17 beta-estradiol, estrone, and estriol. 17 alpha-estradiol did not affect activity parameters and submolecular organisation of the enzyme. The estrogen induced activity increase is consequence of the enhanced de novo enzyme protein synthesis which could be inhibited by Actinomycin-D. The lack of adrenocorticoids did not involve the alteration of LDH activity and H/M ratio in female rat anterior pituitary. Accordingly, these steroids do not mediate estrogenic action. 17 beta-estradiol had a substantial increasing effect on LDH activity in the subrenal implanted pituitary homografts and decreased H/M subunit ratio. Pituitary LDH activity in androgenized female rats decreased only after the removal of the polycystic ovaries. The two latter observations suggest that hypothalamic hormones are not involved in the regulation of pituitary LDH activity and its submolecular organization. De novo synthesis of LDH enzyme protein and the regulation its submolecular organization is induced by the direct action on anterior pituitary cells of the estrogens.


Morphometric investigations on endocrine glands. III. The effect of turisynchron and suisynchron on the thyroid gland of the Wistar rats. Karyometric and morphometric investigations on the thyroids of Wistar rats had the following results: complexing of methallibure (Turisynchron) with zinc lowers the inhibiting action of the parent substance on the thyroid in a short time test period.


Effects of epinephrine, glucagon and insulin on glucose metabolism of planaria. Epinephrine and insulin increased glucose uptake in Planaria, but epinephrine did so to a much grater extent. Glucagon proved to be without effect. The experiments support earlier results according to which in unicellular and invertebrate organisms membrane patterns can be found, which are similar to those of higher organisms and behave like receptors.


[In-vitro studies on the effect of D-norgestrel and norethisterone acetate on the formation of sex steroids in the human ovary]. In vitro incubations with slices of four normal human ovaries and 4-(14)C-pregnenolone as precursor were carried out to study the possibility of a direct influence of D-norgestrel and norethisterone acetate on the metabolism of pregnenolone. In agreement with our previous studies the in vitro-synthesis of progesterone, 17 alpha-hydroxyprogesterone, estrone and estradiol represents the characteristic profile of steroids of the ovaries from the corpus luteum phase. The in vitro-synthesis of 17 alpha-hydroxypregnenolone, DHA, androstenediol (basic metabolites) and androstenedione represents the characteristic profile of steroids of the ovaries from the follicle phase. The addition of D-norgestrel and norethisterone acetate to the incubation medium influences these steroid profiles in the same way. The metabolites of these characteristic profiles were inhibited by the progestogens, whereas the basic metabolites increased. In previous studies the same influence was found by addition of chlormadinone acetate. The influence of these progestagens on the two different profiles of steroids indicate that D-norgestrel and norethisterone acetate exert an inhibitory effect on the 3 beta-hydroxysteroiddehydrogenase-delta 5-4-isomerase system and the aromatase system of the human ovary. These results suggest that these progestogens act directly upon ovarian function, an action which may be assumed to be operative in their contraceptive effect.


Endogenous production of ovarian estradiol-17 beta and its plasms levels in young rats. Estradiol-17 beta concentration in the plasma and its production in ovaries of Wistar rats have been assayed from infancy until puberty (i.e. from the 5th till 39th days of postnatal life). The highestest estradiol-17 beta plasma concentration was found between the 15th and 20the postnatal day. 24 hrs before the vagina opened plasma estradiol-17 beta rapidly rose. Estradiol-17 beta reproduction between days 15 and 33 remained at a stable level, but its production was highest at 39 days. The increase in estradiol-17 beta production and its plasma concentration on the 35th postnatal day until the immediate onset of puberty points to a maturation process occurring at a certain period in the development of sex function in which estrogens plays a dominant role.


[A radioimmunoassay for plasma 11-desoxycortisol and its use in the rapid metopirone test]. A radioimmunoassay for the measurement of 11-deoxycortisol in plasma is described. Antiserum against 11-deoxycortisol was produced by immunizing rabbits with the 21-hemisuccinate of 11-deoxycortisol coupled to bovine serum albumin. The method does not require chromatography but instead makes use of a simple extraction procedure which, in combination with the antibody characteristics, is relatively specific for the 11-deoxycortisol determination. The smallest amount measurable is 5 pg. The intra-assay coefficient of variation was 6.3% before metopirone and 7.2% after metopirone. The inter-assay coefficient of variation was 12.5% before metopirone and 10.3% after metopirone. Pituitary-adrenal reserve was evaluated in control and hypopituitary subjects by a simple midnight metopirone test.


Derivation and experimental proof of a new algorithm for the artificial B-cell based on the individual analysis of the physiological insulin-glucose relationship. Normal dogs were submitted to oral glucose loads or to intravenous glucose infusions. Insulin secretion rates (CISR) were calculated considering the resulting peripheral venous concentration differences in short intervals and the experimentally determined half life and apparent distribution space of exogenous insulin. Multiple regression analysis was done between CISR and both the level and the rate of change of plasma glucose. The regression coefficients were used as algorithm parameters for continuous plasma glucose dependent intravenous insulin administration in the same animals after induction of an insulin-dependent diabetes. Normal glycemic regulation over the day could be resotred by this sytem. The insulin responsiveness, however, varies from day to day; tusing this insulin dosage pattern we observed nearly normal plasma glucose curves and slightly elevated insulin reactions after glucose loading. This kind of algorithm could also be used in diabetic humans.


[Glucose-6-phosphate dehydrogenase activity in the liver of rats with experimental hyperthyroxinemia and hypothyroidism]. The activity of glucose-6-phosphate dehydrogenase was investigated in liver of hyperthyroxinemic or hypothyreotic rats. The enzyme activity level in hyperthyroxic rats. The enzyme activity level in hyperthyroxinemic animals was significantly elevated in contrast to the hypothyreotic rats, who showed significantly reduced enzyme activity. The protein concentration in liver extracts of hyperthyroxinemic animals was slightly elevated, while hypothyreotic animals showed significantly reduced protein content of the extract.


Long-lasting ill-effects of neonatal qualitative and/or quantitative dysnutrition in the human. Qualitative dysnutrition (pure bottle-feeding) as well as quantitative dysnutrition (overnutrition as well as undernutrition) during the first trimenon of postnatal life was found to lead to long-lasting mental, psychic and/or physical ill-effects in the human. Females who were completely bottlefed during neonatal life showed significantly decreased school achievements as well as significantly decreased learning capacity and social adaptability at 16 years of age as compared to females who were purely breastfed or breast- plus bottlefed in neonatal life. Males who were artificially overfed during neonatal life also showed significantly decreased school achievements and significantly decreased learning capacity in adolescence as compared to males with normal weight development in neonatal life.


Ten year follow-up of paroxysmal choreoathetosis: a sporadic case becomes familial. A 30-year-old woman is reported who was originally described in 1967 as an isolated instance of paroxysmal choreoathetosis. In the subsequent 10 years, her movement disorder has decreased in severity. However, she now has a 7-year-old daughter with a similar but more persistent and more serious condition. This family emphasizes both variability of manifestations of paroxysmal choreoathetosis and the importance of genetic factors.


Brain amines and convulsions in four strains of parathyroidectomized, pinealectomized rat. The tendency for four strains of parathyroidectomized (PTx) rats to convulse after pinealectomy (Px) was observed in this experiment; telencephalic serotonin, norepinephrine, and dopamine were examined to note any correlation between amines and convulsions. The strains of rats tested were Sprague-Dawley, Wistar, Long-Evans,  and ACI. Duration to onset of convulsions was shortest in the PTx + Px Long-Evans. No convulsions were noted in the PTx +Px ACI strain, but at least 70% of the animals in each of the other PTx + Px groups did convulse. The administration of calcium gluconate (70 mg/kg) intraperitoneally in saline did not alleviate convulsions in the PTx + PTx Sprague-Dawley. Telencephalic serotonin was lowered in the PTx +Px Wistar while norepinephrine was depressed in the PTx + Px Long-Evans rat. Dopamine levels did not change. Previous work in the PTx +Px induced convulsion has led to the implication of norephinephrine alone, but this work indicates serotonin may be involved in some strains. The need for further study of the genesis of convulsions in the PTx + Px rat is clearly indicated.


Anticonvulsant properties of ropizine in epileptic and nonepileptic beagle dogs. Studies were conducted on a colony of purebred beagle dogs. Animals with spontaneous seizures were classed as epileptic beagles (EB). Those without spontaneous seizures were termed nonepileptic beagles (NEB). The median convulsant current for maximal electroshock seizure (MES) threshold was 175(194-158)mA for EB and 390 (417-364) mA for NEB. Similarly the median convulsant dose of pentylenetetrazol (PTZ) was 7.9 (10.1-6.2) mg/kg for EB and 20.2 (24.2-17.6) mg/kg for NEB. Following pretreatment with graded doses of ropizine (SC 13504), the median protective dose against MES was 6.0(9.2-3.9) mg/kg in EB and 3.2(4.8-2.1) mg/kg in NEB. Based on the incidence of ataxia, EB had a median toxic dose (TD50) of 14.0(16.5-11.9) mg/kg, while in NEB it was 18.0(23.6-13.7)mg/kg. The TD50 doses were unable to protect against a convulsive dose of PTZ. It is concluded first that ropizine may have anti-grand mal activity but apparently lacks an anti-petit mal action. Secondly, EB are more sensitive than NEB to the convulsive effects of electric current and PTZ, yet less responsive to the anticonvulsant actions of ropizine.


Paroxysmal discharges triggered by hearing spoken language. We examined the modality of EEG activation by various kinds of acoustic stimulation in a middle-aged Japanese female with epilepsy. Paroxysmal discharges were triggered in the right frontal area (F4) by verval stimulation. For the activation of EEG, concentration of attention on the stimulation was essential; therefore paroxysmal discharges were triggered most easily by verbal stimuli when someone spoke to the patient directly. Stronger responses than usual were triggered by specific words, and apparently reflected the interest and concern of the patient. The latency from stimulation to paroxysmal discharges ranged from 230 to 1,300 msec, suggesting that the responses may have been a function of the perception and recognition of acoustic stimuli. "Heard-word epilepsy" or "Angesprochene Epilepsie" is suggested in this case.


Cerebral cortical cholesterol changes in cobalt-induced epilepsy. The present study was designed to elucidate cerebral cortical cholesterol changes observed earlier in cobalt-induced epilepsy in the rat. This model is produced by insertion of cobalt metal rods into the cerebral cortex. Seven days after implantations of cobalt (or other metals), measurements of cerebral cortical lipid concentrations were made in the direct area of metal implantation (lesion area) and in the nonnecrotic tissue immediately adjacent to the lesion site (adjacent area). The cortical concentration of free cholesterol decreased and the concentrations of cholesterol esters (CE) greatly increased in the adjacent area of rats implanted with epileptogenic metals (cobalt and nickel) but not in those implanted with nonepileptogenic metals (copper and stainless steel). Differences in the fatty acid compositions of CE from plasma and those from cobalt-lesioned cortex indicated that the accumulated CE originated in the brain rather than from the plasma CE pool. A time course study revealed that changes in the cortical concentrations of free and esterified cholesterol precedes the first appearance of epileptiform activity as measured by electrocorticography. The reduction of free cholesterol levels most likely reflects increased cholesterol metabolism in the cobalt-lesioned cortex. A major portion of this free cholesterol appears to be converted to CE, but not to bile acid or neutral sterol (potential products of cholesterol metabolism). The concentration of free fatty acids, the other substrate of CE formation, was decreased in the lesion site. The increased metabolism of cholesterol could not be explained by changes in the activities of CE synthetase and hydrolase(s). Since cholesterol in the brain is found almost exclusively in membranes, it is likely that these sterol changes reflect membrane alterations or disintegration. However, the exact relationship of these changes to the epileptogenic effect of cobalt remains unclear.


Inattentiveness in schoolchildren with epilepsy. Different aspects of "inattentiveness" or related behavior were assessed in 71 children with epilepsy and in 35 nonepileptic children attending ordinary school. Both groups were of similar age and eduational circumstances. Epileptic boys were significantly more inattentive and overactive than nonepileptic boys according to their teachers and parents, and they performed significantly less well on tests of sustained attention and perceptual accuracy. No such differences were seen between epileptic and nonepileptic girls. This contrast between the epileptic groups was not attributable to drug effects or EEG abnormalities. Auditory stimulation reduced the perceptual accuracy of nonepileptic children but appeared to have a beneficial effect on epileptic groups. Teachers' ratings of inattentiveness were not consistently correlated with other measures. These findings conform with other evidence which suggests that epileptic boys are behaviorally more vulnerable than epileptic girls but not simply as a reflection of sex related differences in children in general. The results also suggest that teachers' statements about "inattentiveness" are difficult to interpret and that problem behavior at school needs to be specified precisely.


Creatine kinase and hexose phosphate isomerase activity in skeletal muscles of healthy male adults. Creatine kinase (CPK) and hexose phosphate isomerase (PHI) activities were measured in surgically obtained skeletal muscle samples of healthy adult men (n = 45). Median values of 4,200 for CPK and 275 for PHI (U/g wet weight, 37 degrees C) were found. Duplicate determinations on 7 samples divided and treated separately gave a very good reproducibility. There is a significant relationship between the activity of the two enzymes (r = +0.798, p less than 0.001). The mean activity levels were for both enzymes higher in m. vastus medialis quadricipitis and m. triceps brachii, c. long., than in vastus lateralis quadric. and in deltoideus. PHI frequency distribution was not of the normal type but probably bimodal, suggesting muscle types with lower and higher glycolytic rate in man.


Activity of alcohol dehydrogenase and acetaldehyde dehydrogenases in the liver and placenta during the development of the rat. The ontogenetic development of the enzymes alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenases (ALDH I and II) was followed in rats. ADH could be detected just before birth and increased gradually to reach 82% of adult values at 47 days. ALDH I and II were present from day 15 of gestation, increased rapidly at birth, and reached 80-90% adult values at 47 days. The ratio between ALDH and ADH activities decreased gradually during ontogenesis. The relative subcellular distribution of all enzymes was identical before birth, 7 days after birth and in adults. The placental activities of ADH and ALDH I and II were studied at 15 and 20 days of pregnancy. ADH could not be detected in placentas. Low activities of ALDH I and II were present in placentas studied at 15 days of gestation, and still lower activities were found in placenta at 20 days.


Effect of DL-homocysteine on some hepatic folate enzymes and folate concentration in cobalamin-deficient rats. Male weanling wistar rats were fed either a vitamin B12-deficient diet or a vitamin B12-deficient diet supplemented with DL-homocysteine for 12 weeks. The control group was given a vitamin B12-supplemented diet for 12 weeks. Hepatic folate, hepatic, 5,10-methylene THF reductase (EC 1.1.1.68) and hepatic 5-methyl THF; homocysteine methyl transferase (EC 2.1.1.13) activities were assayed in all the rats after killing. The hepatic folate activity was very low among the homocysteine-supplemented rats. 5,10-methylene THF reductase and 5-methyl THF; homocysteine methyl transferase activities were increased in the homocysteine-fed rats. These results show that dietary DL-homocysteine has some regulatory effect on the two enzymes involved in the production of 'free' THF.


Alkaline phosphatase isoenzymes in liver cirrhosis. The study of a group of 114 hepatic patients allowed us to demonstrate the presence of an isophosphatase band, called ALP4, which can be of value as an index of evolutive cirrhosis. A certain correlation between the presence of this alkaline phosphatase isoenzyme in serum and histological evidence of moderate or extreme inflammatory response in liver biopsies was shown.


Separation and characterization of intestinal brush border enzymes in adult rats and in suckling rats under normal conditions and after hydrocortisone injections. Adult and suckling (13 days old) rat intestinal brush borders have been purified by the procedure of Schmitz et al. (25). Enzymatic proteins have been separated by polyacrylamide gel electrophoresis. In the adult rat, enzyme proteins have been separated by polyacrylamide gel electrophoresis. In the adult rat, enzyme activities in order from the origin were: maltase/glucoamylase/sucrase-isomaltase (protein band 3), lactase (protein band 5), maltase/sucrase-isomaltase (protein band 6) and alkaline phosphatase (protein bands 8 and 9). In the suckling rat, protein band 5 associated with lactase activity was found to be markedly higher compared to the adult rat. Gels were completely devoid of sucrase-isomaltase activity while protein band 3 was strikingly reduced and protein band 6 absent. After hydrocortisone administration to suckling rats, a new band associated with sucrase-isomaltase activity appeared in position 6, whereas protein band 3 markedly increased with the simultaneous appearance of sucrase-isomaltase activity.


[Penetration of external thermal perturbations into homeothermic organisms, part I (author's transl)]. The general importance of the mean surface curvature for heat conduction problems is explained and a special symmetry with constant mean curvature on the isothermal surfaces is defined. The applicability for the body shapes of homeothermic organisms is demonstrated and the partial differential equation of heat conduction for this case is derived. The definition: heat release = real heat production + convective pseudoproduction eliminates the term of convective heat transfer through the blood stream and allows the reduction to a mere heat conduction problem. Formulas for the heat loss to the environment and for steady state temperature profiles are given. In case of sudden change of heat loss the partial differential equation is solved and a formula is derived, using dimensionless coordinates of time and distance. The mean surface curvature has strongest influence to the interior temperature field. The solution shows clearly the importance of thermal inertia of the homeothermic organism, for the external temperature wave penetrates into the body with a long phase displacement in time.


[Penetration of external thermal perturbations into homeothermic organisms, part II (author's transl)]. The penetration of external thermal perturbations into parts of the body with different surface curvatures is discussed. For areas with approximate rotational symmetry a theoretical treatment by means of the variation theory is possible. the mean surface curvature on the rotation axis is constant. Therefore the solution of the partial differential equation given in part I can be applied without change, if the correct value of the mean surface curvature of the body part is used. Also for an exponential form of alteration of the heat loss a solution is deduced. Combining small parts of sudden and exponential changes of heat loss it is possible to approximate almost any reasonable type of external thermal perturbation. Superimposing single solutions with different parameters allows then a complete solution of the problem. The importance of the theoretical results in view of homeothermia is discussed.


[Examination and assessment of time-variant human strain in motor car driving: real situation--simulation (author's transl)]. Time variant processes of activity, activation and strain of man are registrated during several hours of automobil driving (highway-autobahn) for different stress conditions and classified in terms of degrees of fatigue. By comparison with an assessment of strain in a simulated driving task with the same individuum and the same research-methods it is shown that the development of methods for measurement and assessment of time-variant human processes in laboratory experiments can be recommended, field-studies higher degrees of strain were found than under laboratory conditions.


Changes in male exercise performance and anthropometric variables between the ages of 19 and 30. In order to study possible changes in Swedish men between the approximate ages of 19 and 30, 55 men from the Stockholm area were re-examined 11 years after examinations made in connection with compulsory military duty. The most pronounced finding was a 11% increase in body weight accompanied by a 19% increase in waist circumference and a 25-41% increase in skinfold thickness. A 5% increase in work output at heart rate 170 (W170) was observed but the ratio W170/weight decreased by 5%. The observed changes were even more pronounced in a subgroup who had a low exercise level in their spare time at the age of 19 as well as 30. Growth was not quite completed at the age of 19. Of the increase in height amounting to 1.3 cm, 70% was due to growth in tibial length.


Aerobic performance capacity in athletes. Maximal oxygen uptake (max VO2) in leg and arm work, succinate dehydrogenase activity (SDH) and percentage of slow twitch fibers (%ST fibers) in M. vastus lateralis (VL), M. gastrocnemius c.l. (GL) and M. deltoideus (D) were studied in 89 athletes practising 11 different sport events. It was found that maximal oxygen uptake correlated positively with %ST fibers and SDH activity in M. VL. The SDH activity and %ST fibers in M. VL correlated also with one another. The results suggest that oxidative capacity of the muscles is not the limiting factor for maximal oxygen uptake. The role of the oxidative capacity of the muscles might be important during submaximal work of long duration and when a relatively small muscle mass is activated (long-distance running). MaxVO2 might be the most important determinant of performance when large muscle mass is activated during maximal work of a duration from several minutes up to 1 h (cross-country skiing).


[Contribution of the biceps brachii and pronator teres muscles to the efforts of pronation or supination. I. Statistical work (author's transl)]. The electrical activity of the biceps brachii and pronator teres muscles is studied through the prono-supination of the forearm in some isometrical conditions (static work) with different loads and joint positions. If the pronator teres is always being active in pronation, this activity is a function of the load and of the wrist and elbow positions. The same phenomena can be observed for the biceps brachii but when in supination. From the curvilinear relationships between the integrated electrical activity and the load--observed on both muscles--some torque-angle relationships can be established for the biceps brachii which show that a bifunctional muscle seems to be characterized by a very and unique force-length relationship.


[Contribution of the biceps brachii and pronator teres muscles to the efforts of pronation or supination. II. dynamic work (author's transl)]. The electrical activity of the biceps brachii and pronator teres muscles is studied through the prono-supination of the forearm in some anisometrical conditions (dynamic work) when the inertia of the mobile system and the elbow position are being varied. The subjects are required to perform pronation, supination and flexion movements, either isolated or combined. From the findings obtained when the integrated electrical activity (Q) is related to the mechanical work (W), one can conclude that a. the Q-W linear relationship seems to characterize the chief function of a muscle, b. the slope of the Q-W relationship depends on the elbow position, c. the pronator muscles do not inhibit in a selective manner the biceps supinating function. So a bifunctional muscle seems to act as a whole.


Structural studies on the D-arabinose-containing lipid A from Rhodospirillum tenue 2761. Structural studies carried out on the isolated free lipid A of Rhodospirillum tenue 2761 revealed a new type of structure for this lipid. The lipid A backbone of 1',6-linked glucosamine disaccharide (central disaccharide) is substituted by three different sugar residues: the non-reducing end of the disaccharide by 4-amino-4-deoxy-L-arabinose 1-phosphate and its reducing end glycosidically by D-arabinofuranose 1-phosphate; further, the reducing glucosamine of the disaccharide is branched to a third glucosamine residue by a 1'',4-glycosidic linkage. The amino and the hydroxyl groups of the central disaccharide are acylated by 3-hydroxydecanoic acid (amide-linked) and palmitic and myristic acids (ester-linked). Neither amino nor hydroxyl groups of the three external sugar residues are acylated. The results suggest the following chemical structure for the lipid A of R. tenue 2761: (formula: see text).


Small-angle X-ray studies of a human immunoglobulin M. The conformation of a Waldenström immunoglobulin M (IgM) with antibody-like activity for X-ray contrast media, based on 3-amino-2,4,6-triiodobenzoic acid, was studied by small-angle X-ray scattering. The radius of gyration was determined as 12.1 nm, the maximum distance 35 nm, the volume 1900 nm3. A flat star-shaped model was found to be equivalent in scattering. Aggregation of IgM molecules seems to take place as side-by-side combinations of single molecules, manifesting itself as a relatively large increase of the radius of gyration and unchanged thickness of the flat aggregates.


Nucleotide sequence at the 5' extremity of tobacco-mosaic-virus RNA. 1. The noncoding region (nucleotides 1-68). The sequence of the 5' noncoding region of tobacco mosaic virus RNA has been determined. The noncoding region is 68 nucleotides long and is unusual in that it contains no internal guanosine residues. The long T1 oligonucleotide containing the guanosine-free tract was isolated from a T1 ribonuclease digest of tobacco mosaic virus RNA and sequenced by labelling techniques in vitro using polynucleotide kinase. The guanosine-free tract is terminated by the first potential initiation codon in the RNA molecule and several lines of evidence suggest that this AUG triplet is operational in initiating viral protein synthesis (see following paper). The 5'-noncoding region cannot base-pair extensively with the 3'-terminal sequence of 18-S ribosomal RNA from rabbit reticulocytes.


Nucleotide sequence at the 5' extremity of tobacco-mosaic-virus RNA. 2. The coding region (nucleotides 69-236). In the preceding paper it was shown that the first A-U-G codon in tobacco mosaic virus RNA is separated from the 5' terminus by a sequence of 68 nucleotides devoid of internal guanosine residues. In this paper we present the sequence of 165 residues immediately following the first potential initiation codon. The characterized sequence contains four nonsense codons but none are in phase with the prospective initiation codon. Several lines of evidence, including direct characterization of the portion of the RNA molecule which binds to and is protected by the ribosome in the course of initiation, all support the idea that the A-U-G at position 69-71 is a functional initiation signal for viral protein synthesis.


Synthesis of cellulose precursors. The involvement of lipid-linked sugars. Particulate preparations from the Chlorophyta Prototheca zopfi catalyze the incorporation of [14C]glucose from UDP-[14C]glucoe into lipids. These lipids have been characterized as lipid-P-glucose, lipid-PP-glucose, and lipid-PP-oligosaccharides. The lipid-linked oligosaccharides were a mixture ranging from a disaccharide to approximately a decasaccharide. Cellulase digestion and periodate oxidation showed that the oligosaccharides seem to be built of beta-1,4-linked glucoses. The lipid moiety had the properties of dolichol. The glucolipids described appeared as precursors of a water-soluble polymer. Treatments of this polymer with hydrolytic enzymes and periodate oxidation that it could be a glycoprotein containing beta-1,4-linked glucoses. When GDP-glucose was added to the incubation mixture, the 14C-labelled soluble polymer became insoluble in hot alkali. This insoluble polymer had the properties expected for cellulose. A scheme is proposed with the reactions involved in the initiation of cellulose biosynthesis.


Characterization of proteins from nucleolar preribosomes of mouse leukemia cells by two-dimensional polyacrylamide gel electrophoresis. Proteins of isolated 80-S and 60-S nucleolar preribosomal particles were characterized by means of two-dimensional polyacrylamide gel electrophoresis, in the lymphocytic mouse leukemia cells L5178Y. Their identification and metabolic relationships with ribosomal subunit proteins were investigated using co-electrophoresis of unlabeled polysomal proteins with labeled proteins of either nucleolar preribosomes or ribosomal subunits. The large and small ribosomal subunits contain 40 and 31 proteins, respectively. The nucleolar 80-S preribosomes were analysed after 2 and 5 h of incubation with tritiated valine and leucine and were shown to contain about 55 proteins. Most of them were identical to cytoplasmic ribosomal subunit proteins. The nucleolar 60-S preribosomes contain all the proteins which are common to 80-S preribosomes and large ribosomal subunits, and one additional protein (L10). The ribosomal proteins which were absent from nucleolar particles were found to be labeled in the cytoplasmic ribosomes after the same incubation period. Thus, in addition to the association of the bulk of ribosomal proteins with 45-S RNA within the 80-S preribosomes, results indicate that a group of ribosomal proteins and particularly from the small subunits, become associated at later stages of the maturation process of mammalian ribosomes. It was further shown that a set of 10 proteins, different from ribosomal polypeptides, were present in nucleolar preribosomal particles. Several of them were associated with polyribosomes in the cytoplasm, whereas the others were unique to the nucleolus.


Glycosylation in vitro of Semliki-Forest-virus and influenza-virus glycoproteins and its suppression by nucleotide-2-deoxy-hexose. Cell-free enzyme preparations from cultured fibroblasts infected with Semliki forest virus or fowl plague virus (an influenza A virus) incorporate [14C]-mannose into dolichol-phosphate-mannose, lipid-linked oligosaccharides and into endogenous virus-specific glycoproteins. When GDP-2-deoxy-D-[14C]glucose serves as substrate 2-deoxy-D-[14C]glucose is transferred to dolichol phosphate yielding dolichol-monophosphate-2-deoxy-D-[14C]glucose. UDP-2-deoxy-D-[14C]glucose gives rise also to a lipid which, however, is not a polyprenol derivative. The transfer of [14C]mannose to lipid-extractable fractions and glycoproteins in vitro is blocked by GDP-2-deoxy-D-glucose. It can be restored by exogenous dolichol monophosphate only with regard to the formation of dolichol-monophosphate-[14C]mannose-labelled oligosaccharides into glycoproteins. UDP-2-deoxy-D-glucose has no inhibitory effect on transfer reactions of [14C]mannose from GDP-[14C]mannose into various lipid fractions or into glycoprotein. It is concluded therefore, that the inhibition of glycosylation brought about by 2-deoxyglucose in vivo is caused by an interference of its GDP derivative with the formation of a correct lipid-oligosaccharide.


Effect of choline deficiency on the enzymes that synthesize phosphatidylcholine and phosphatidylethanolamine in rat liver. Activities have been determined in subcellular fractions of livers from choline-deficient and normals rats for the enzymes that convert choline and ethanolamine to phosphatidylcholine and phosphatidylethanolamine respectively, that methylate phosphatidylethanolamine to yield phosphatidylcholine, and that oxidize choline to betaine. The activities of ethanolamine kinase, phosphoethanolamine cytidylyltransferase, and CDP-ethanolamine: 1,2-diacylglycerol phosphoethanolaminetransferase are not changed in the livers from choline-deficient rats for at least 18 days. Similarly, the activities of choline kinase and CDP-choline: 1,2-diacylglycerol phosphocholine transferase were unaffected by choline depletion. A decrease of 30-41% was observed, however, in the mitochondrial oxidation of choline to betaine. Also, the activity of the phosphocholine cytidylyltransferase was reduced in the choline-deficient livers to 60% olf the control values. The only observed increase in enzyme activity was a 62% elevation of the phosphatidylethanolamine-S-adenosylmethionine methyltransferase activity after 2 days of choline deficiency. This increased activity was maintained for at least 18 days of choline deprivation. The results suggest a lack of adaptive change in the levels of these phospholipid biosynthetic enzymes as a result of choline deficiency.


Immunological studies on CTP:phosphocholine cytidylyltransferase from the livers of normal and choline-deficient rats. Chickens were immunized with the purified low-molecular-weight form of CTP:phosphocholine cytidylyltransferase from rat liver cytosol. The antiserum was obtained and fractionated to yield immunoglobulin. The antibodies specifically inhibited the enzymatic activity of the partially purified low-molecular-weight form of the enzyme from pH 6.0 to 8.5. Antibodies against the low-molecular-weight form of the enzyme cross-reacted with the high-molecular-weight form of the enzyme from cytosol as well as with the cytidylyltransferase associated with the microsomal fraction. The antibodies were used for the immunochemical determination of the amount of cytosolic phosphocholine cytidylyltransferase in the livers of normal and choline-deficient rats. The amount of enzyme in rat liver cytosol was not changed for at least 18 days of choline deficiency. The decrease in specific activity of the enzyme in choline-deficiency may be caused by factors other than adaptive changes in the level of enzyme.


Interaction between membrane functions and protein synthesis in reticulocytes: specific cleavage of 28-S ribosomal RNA by a membrane constituent. A factor isolated from rabbit reticulocyte white ghosts by Triton X-100 treatment blocks protein synthesis at the elongation-termination stage. Factor-treated ribosomes were found to have an identical buoyant density to that of control ribosomes. When incubated with either reticulocyte ribosomes or ribosomal RNA, the factor products specific cuts in the 28-S ribosomal RNA compenent without damaging the 18-S RNA. Incubations of pancreatic or T1 RNase, with ribosomal RNA, at similar protein-synthesis inhibitory concentrations effected a complete breakdown to oligo and mononucleotides. When challenged with isolated 28-S or 18-S reticulocyte ribosomal RNA, the highly purified factor only attacked the 28-S RNA species. There was no accumulation of nucleotides or oligonucleotides and we concluded that the membrane factor causes inhibition of protein synthesis by having a specific endonucleolytic cleavage activity.


ABH-blood-group antigens and glycolipids of human saliva. The nature of ABH-blood-group antigens in saliva was investigated. Human saliva was examined serologically for ABH-blood-group activity in its native form and after various treatments. The activity of the native form persisted in the delipidated samples, but was entirely lost after alkaline degradation. The lipid portion of saliva was completely inactive in the ABH hemagglutination inhibition system. The same results were obtained when purified glycolipid fraction of saliva was used instead of whole lipid extract. Neither alkaline treatment nor excessive amounts of salivary lipids effected antigenic activity of A-active glycosphingolipids of hog gastric mucosa admixed to saliva samples before alkaline degradation and/or in presence of large amounts of salivary lipids. The isolated glycolipid fractions contained at least eight glycolipids, each of which was composed of glucose, glyceryl ethers and fatty acids and differed from others with respect to number of glucose residues. Sphingosine and sugar residues involved in formation of ABH antigenic determinants were not detected. These findings together with data on stomach secretion [1,2] led us to the conclusion that ABH-blood-group antigens of saliva are exclusively of glycoprotein nature.


Freeze-fracture appearance and disposition of band 3 protein from the human erythrocyte membrane in lipid vesicles. Single bilayer lipid vesicles were formed by removal of Triton X-100 with Bio Beads SM-2 from a mixture of egg lecithin and a Triton X-100 extract of human erythrocyte ghosts. Upon freeze-fracturing, these vesicles showed intramembrane particles, similar to those seen in the erythrocyte membrane. Similar particles were also observed when a partially purified band 3 preparation was used instead of the crude Triton X-100 extract. In the reconstituted vesicles an equal distribution of the intramembrane particles between the two fracture faces was observed. This is in contrast to the unequal distribution of the particles in the erythrocyte membrane, which did not seem to be altered by removal of the extrinsic proteins. From digestion studies with trypsin and chymotrypsin of vesicles, reconstituted from the crude X-100 extract, it is concluded that band 3 protein in the vesicle bilayer has a similar orientation as in the native membrane.


Isolation of soluble proteins capable of stimulating aerobic plasmalogen biosynthesis. The terminal step during aerobic plasmalogen biosynthesis is catalyzed by a microsomal desaturase system which converts 1-O-alkyl-2-acyl-sn-glycerophosphoethanolamine to 1-O-alk-1'-enyl-2-acyl-sn-glycerophosphoethanolamine (ethanolamine plasmalogen). The reaction depends on oxygen and NAD(P)H and is stimulated 3-10-fold by soluble activating factors contained in the 100 000 X g supernatant. Two stimulating proteins have been isolated from pig kidney; the partially purified proteins have identical molecular weights (27 000) but differ in their respective isoelectric points (protein I, 5.1 and protein II, 4.9). Both proteins behave identically in the biochemical studies conducted. Exogenous substrate binds to the stimulating proteins; the transfer of ethanolamine, but not of choline phospholipids, from liposomes to microsomes is enhanced by the stimulating proteins. They stimulate plasmalogen synthesis from either exogenous or endogenous substrate (synthesized from alkylglycerophosphoethanolamine by microsomal transacylases). The stimulating proteins have no enzymatic activity themselves; it is suggested that they affect events within the membrane and function as specific mediators between the membrane-bound enzyme system and the lipophilic substrate.


Interaction of the acetylcholine (nicotinic) receptor protein from Torpedo marmorata electric organ with monolayers of pure lipids. Membrane fragments rich in cholinergic (nicotinic) receptor protein were purified from the electric organ of Torpedo marmorata. Their lipid composition is essentially characterized by the prominence of cholesterol, phosphatidylethanolamine and phosphatidylcholine, long-chain fatty acyl constituents, and the absence of sphingomyelin. Solubilised receptor was purified from these fragments and the concentration of sodium cholate lowered by dialysis to 0.01% (w/v). When this preparation was injected under a lipid monolayer, an increase of surface pressure developed, which was not observed with the detergent alone nor in the absence of lipid film. When covalently radiolabelled receptor preparations were injected at a constant surface pressure the radioactivity recovered with the film was proportional to the increase in area. It is concluded that the pressure or area increases are due to the penetration of the cholinergic receptor protein into the lipid film. Incorporation experiments into films formed from various pure lipids showed that the protein interacts more readily with cholesterol than with ergosterol, phosphatidylcholine, or other phospholipids. Its affinity is also higher for long-chain phosphatidylcholines than for short-chain ones. The degree of unsaturation and fluidity of the 3-sn-phosphatidylcholine (lecithin) films are of secondary importance. Parallel experiments with covalently and non-covalently labelled receptor preparations showed that part of the protein recovered with the film lost its alpha-toxin binding ability during the penetration. Similar data were obtained with the receptor purified from Electrophorus electricus electric organ.


Membranes rich in acetylcholine receptor: characterization and reconstitution to excitable membranes from exogenous lipids. Characterization of acetylcholine-receptor-enriched membranes from Torpedo californica electric tissue by negative-staining electron-microscopy and by lipid analysis is described. The protein/lipid ratio is 70%/30%. The lipids consist of 70% phospholipids (46% phosphatidylcholine, 31% phosphatidylethanolamine, 14% phosphatidylserine, 7% sphingomyelin, 2% phosphatidylinositol of the phospholipids determined) and 20% cholesterol. The acetylcholinesterase-enriched membranes show a similar composition. The only differences are a lower protein/lipid ratio (45%/55%) and a lower phosphatidylcholine/sphingomyelin ratio of 39%/14% as compared to 46%/7% for the receptor-enriched membranes. A method of preparing single-walled phosphatidylcholine vesicles by gel filtration on Sephadex G50 according to Brunner et al. (Biochem. Biophys. Acta, 455, 322--331, 1976) is used to recombine the lipid-depleted receptor complex with artificial lipid vesicles. Starting from a lipid mixture of 46% phosphatidylcholine, 31% phosphatidylethanolamine, 14% phosphatidylserine, 7% sphingomyelin, 2% phosphatidylinositol and 15% cholesterol we obtained vesicles associated with the acetylcholine receptor complex. These receptor vesicles are chemically excitable by 10 micrometer carbamoylcholine as measured by efflux of 22Na+ from the vesicles. The excitability is blocked by preincubation with 0.5 mM alpha-toxin from Naja naja siamensis venom and by reduction with 5 mM dithioerythritol.


Membrane lipid metabolism in Acholeplasma laidlawii A EF 22. Influence of cholesterol and temperature shift-down on incorporation of fatty acids and synthesis of membrane lipid species. 1. Membrane lipid metabolism in Acholeplasma laidlowii A EF 22 has been studied under different conditions by applying three different techniques for changing membrane viscosity: fatty acid and cholesterol supplementation and temperature changes. 2. The molar relationship between the two dominating membrane lipids, monoglucosyldiglyceride and diglucosyldiglyceride, is to a large extent determined by membrane viscosity properties. This is shown by the varying metabolic responses occurring during incorporation of different fatty acids with and without cholesterol and by temperature shift-down experiments. Higher viscosity in membranes stimulates synthesis of monoglucosyldiglyceride at the expense of diglucosyldiglyceride. Synthesis of phospho and phosphoglucolipids is affected as well. 3. Temperature shift-down from 37 degrees C to 17 degrees C results in an immediate synthesis of monoglucosyldiglyceride accompanied by an increased incorporation of unsaturated fatty acids into this lipid. Synthesis of the other membrane lipid species (containing more unsaturated fatty acids) lags behind temporarily. 4. Incorporation from an equimolar mixture of palmitic and oleic acids together with cholesterol yields greater amounts of oleic acid in membrane lipids than incorporation in the absence of cholesterol, indicating that incorporation is viscosity dependent. 5. Studies of precursor relationships reveal that all main lipids have an active turnover which differs depending on membrane composition and conditions. Furthermore, this turnover proceeds with different intra-lipid pools. 6. Isolated membranes contain no detectable lipolytic enzymes capable of hydrolyzing membrane phospho or glycolipids. It is suggested that lipid turnover is partly mediated by enzymatic interlipid conversions, thus not allowing intermediates to accumulate.


Phosphoglycerate kinase B from ram testis. Purification, characterisation and comparison with the muscle isoenzyme. 1. The testis-specific isoenzyme of phosphoglycerate kinase (phosphoglycerate kinase B) has been isolated from ram testes using a procedure which separates it from 'normal' phosphoglycerate kinase which is also present in testis tissue. The purification procedure is described. 2. The best preparations had no detectable impurity on electrophoresis, and had specific activities comparable with the same enzyme from other sources. 3. Kinetic studies indicated that the two isoenzymes have identical properties, within experimental error, for substrate affinity (for MgATP, 3-phosphoglycerate and MgADP), energy of activation and thermal denaturation. 4. The molecular weights of both isoenzymes were not distinguishably different from those previously reported, as measured by polyacrylamide/dodecylsulphate electrophoresis. The amino acid compositions showed only slight differences, and tryptic peptide maps showed that there was close homology of sequence. Starch gel electrophoresis at pH 6.5 indicates that the B isoenzyme has 1--2 more positive charges than the A. 5. Phosphoglycerate kinase A isolated from sheep muscle was shown, within experimental error, to be identical to the phosphoglycerate kinase A isolated from testis. 6. The results further substantiate the suggestion that the B isoenzyme is coded by a gene which was duplicated from the phosphoglycerate kinase A gene.


Single and multiple dose pharmacokinetics of pindolol. The pharmacokinetics of pindolol were studied in six healthy individuals following a single 10 mg dose (SD) and multiple (5 mg tid over 6 days) dose (MD). The plasma elimination half-life was identical after SD (4.7 +/- 0,8h) and MD (4.1 +/- 1.1h). Steady state plasma concentrations were reached after 36 h and remained stable thereafter. The variation in steady state concentrations was small in each individual and also between individuals. The steady state concentration of pindolol can be predicted from the pharmacokinetic data obtained after a single dose. The results of the present study suggest that the disposition of pindolol is linear over the concentration range studied.


Correlation between serum concentration and pharmacological effect on atrioventricular conduction time of the antiarrhythmic drug propafenone. Seven patients with cardiac dysrhythmias received a single, oral, therapeutically effective dose of the antiarrhythmic drug propafenone. The serum levels correlated well with changes in atrioventricular conduction times during the postabsorptive elimination phase (r = 0.8610, p less than 0.001). The mean half-lives of the serum level and the electrocardiographic effect (PQ-time) were 3.6 +/- .2 h and 3.8 +/- 0.6 h, respectively.


Bioavailability of norethindrone in human subjects. A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.


Pharmacokinetics of furosemide in anephric patients and in normal subjects. The pharmacokinetics of furosemide 40 mg i.v. were compared in 7 anephric patients and in 7 normal subjects. The average serum clearance was 66 ml/min in the patients and 219 ml/min in the normal subjects, and the corresponding weight corrected clearances were 1.33 ml/min . kg and 2.96 ml/min . kg. Binding to serum proteins was significantly decreased in the anephric subjects, in whom a significant negative correlation was found between the percentage binding and the volume of distribution VDSS. In the patients, but not in the normal subjects, there was a significant positive correlation between VDSS and serum clearance. Both in normal and anephric individuals 4-chlor-5-sulphamoyl-anthranilic-acid (CSA) was found, but there was no evidence of special accumulation either of CSA or anthranilic acid in the anephric patients. In the patients the initial increase in serum concentration of sodium and protein followed by a more conspicuous decrease were more pronounced, but none of the changes were statistically significant.


Effect of metoprolol on blood glycerol, free fatty acids, triglycerides and glucose in relation to plasma catecholamines in hypertensive patients at rest and following submaximal work. Studies were performed in nine male patients with moderate hypertension. Treatment with metoprolol, 50--150 mg three times daily for 4--17 weeks, had no effect on the plasma level of glycerol, free fatty acids, triglycerides or glucose under basal conditions, neither in the supine nor in the upright position. Submaximal work, performed postprandially, increased plasma glycerol before medication but not during metoprolol, in spite of a marked increase in plasma noradrenaline. The work load employed caused no change in free fatty acids, triglycerides or glucose, neither before medication nor during metoprolol.


Liver size and indices of drug metabolism in alcoholics. The role of liver size in drug metabolism was investigated in 34 chronic alcoholics and 28 controls by comparing antipyrine half-life with biopsy content and total amount of hepatic cytochrome P-450 (P-450) and liver weight. Liver size was significantly greater in alcoholics than in controls. Total P-450 was increased and antipyrine metabolism was enhanced in alcoholics with normal histology of the liver. In subjects with alcoholic hepatitis or cirrhosis, the antipyrine half-life was prolonged and P-450 was decreased. Alcoholics with fatty liver had a reduced P-450 content, but the total amount of P-450 and the antipyrine half-life were normal. The results demonstrate in alcoholics that an enlarged liver of normal histological appearance is associated with enhanced drug metabolism. In subjects with fatty liver the drug metabolizing capacity per unit weight of liver is often impaired, but the increase in liver size leads to undisturbed total oxidizing capacity and normal in vivo metabolism. In alcoholic hepatitis drug metabolism is impaired in spite of hepatomegaly. In cirrhosis the enlargement of the liver appears to compensate for the decreased P-450 content resulting in only slightly decreased total P-450, and the severly impaired in vivo drug metabolism may be due to derangement of blood flow.


Metabolism of phenazone in man after hydrocortisone administration. The influence of a high plasma concentration of hydrocortisone on the metabolism of phenazone in humans has been studied. Two series of experiments were carried out, Group A to demonstrate any enzyme-inducing effect of hydrocortisone, and Group B to study the immediate effect of hydrocortisone on the metabolism of phenazone. 9 subjects (Group A) received a total 250--400 mg hydrocortisone i.m. twice daily for three days and the 24-hour elimination of phenazone was studied before and afterwards. In a further 5 subjects (Group B) the elimination of phenazone was examined during administration of hydrocortisone of placebo. The elimination rate and the apparent volume of distribution of phenazone remained unchanged under both experimental conditions.


Distinct chemokinetic and chemotactic responses in neutrophil granulocytes. Evidence has been presented to show that chemokinesis and chemotaxis of human neutrophil granulocytes can be controlled by distinct cellular mechanisms and by different chemicals. Materials such as human serum albumin or fibrinogen had chemokinetic but no chemotactic properties. Highly purified preparations of serum-derived peptides containing classical anaphylatoxin had detectable chemotactic activity only. Chemokinetic as well as chemotactic substances were required for the expression of chemotaxis in the form of efficient directional locomotion. The roles of chemokinesis and chemotaxis in the regulation of directional locomotion have been analyzed. Further experiments showed that the chemotactic response conforms to the law of Weber-Fechner. The number of cells which had accumulated in response to a chemotactic simulus was proportional to the logarithm of the concentration of the chemical substance. Readaptation from high to low chemotactic stimulus occurred only to a limited extent.


Immune responses to weakly immunogenic virally induced tumors. I. Overcoming low responsiveness by priming mice with a syngeneic in vitro tumor line or allogeneic cross-reactive tumor. This report describes model systems which show low primary in vitro syngeneic cytotoxic responses to a Moloney-induced YAC tumor (syngeneic in A mice) and a Rauscher-induced RBL5 tumor (syngeneic in C57BL/6 mice) and examines different approaches to overcome these defects. Two major findings were obtained: (a) spleen cells from A mice, injected with tumor cells from an in vitro tumor line YAC-1, derived from YACL, could generate a significant syngeneic cytotoxic response. In contrast, spleen cells from A mice injected with tumor cells from the in vivo tumor line failed to generate a syngeneic cytotoxic response. Thus, tumor cells from the in vitro line were more immunogeneic that those from the in vivo line. (b) Spleen cells from A mice which were injected with the cross-reactive allogeneic tumor RBL5, could generate significant cytotoxic responses to the syngeneic tumors YAC and YAC-1. Similarly, spleen cells from C57BL/6 mice injected with the cross-reactive allogeneic tumor YAC-1, could generate a significant cytotoxic response to the syngeneic tumor RBL5. Thus, cross-reactive allogeneic tumors could stimulate syngeneic cytotoxicity. The theoretical and the practical implications of these studies are discussed.


Mazindol effects on schedule-controlled responding of the pigeon. The effects of mazindol, a non-phenethylamine anorexic, were determined in pigeons key pecking under a multiple fixed-ratio 30 response, fixed-interval 5 min schedule of food presentation. The low average rates of responding under the fixed-interval schedule were greatly increased (from 0.7 response/sec to 2 responses/sec) at doses from 0.1 to 10 mg/kg. The higher rates of responding under the fixed-ratio schedule were only decreased by increasing doses of mazindol. Throughout the fixed interval, mazindol tended to produce a constant rate of responding completely disrupting the normal, positively accelerated pattern of responding. These rate-increasing effects of mazindol were much greater than those of phenethylamines tested under similar conditions. The large increases in rates of responding under the fixed-interval component were discussed in terms of the known biochemical effects of mazindol.


A possible mechanism of choleretic action of 3-(2,4,5-triethoxybenzoyl)-propionic acid (AA-149) in dogs. The choleretic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) was studied in anesthetized dogs. AA-149 produced a dose-dependent increase of the bile flow with both i.v. and intrajejunal administration of doses 1 mg/kg and higher. Biliary clearance of 14C-erythritol showed that AA-149 stimulated canalicular bile formation without enhancement of water secretion and/or inhibition of bile reabsorption in the biliary ductules and ducts. AA-149 did not increase the excretion of bile acids into the bile, but enhanced the excretion of the biliary electrolytes, in particular sodium ion, in proportion to an increase of the bile flow. About 3--4% of AA-149 administered i.v. was excreted into the bile during the first 1 h period, so that biliary AA-149 was insufficient to increase the bile flow via its osmotic effect. These results strongly suggest that the choleretic action of AA-149 is attributable to stimulation of a bile acid-independent bile formation in the canaliculi coupled with an active sodium transport system.


Triamcinolone-induced mammary activation in virgin mice. Intact ICR mice receiving Triamcinolone showed extensive proliferation within the mammary gland. Galactophores and ducts were enlarged. In contrast with the non-treated animals, those treated with Triamcinolone had an evident lobuloalveolar system. Triamcinolone failed to activate the glands of oophorectomized animals. It is thus evident that systemic administration of Triamcinolone to young virgin mice causes mammary stimulation and that this effect only occurs in the presence of the ovary.


Tryptophan and 5-hydroxyindoles in different CNS regions following acute morphine. Morphine induces naloxone-reversible increases of tryptophan and 5-hydroxyindoles in rat cerebral hemispheres, thalamus and cerebellum, but does not do so in striatum, hypothalamus, hippocampus and brain stem. Morphine also induces a rise in spinal cord 5-HIAA which is antagonized by naloxone, but there is no parallel change in tryptophan. Increases in brain 5-hydroxyindoles may be related to greater availability of tryptophan, but the elevation in spinal cord 5-HIAA appears to be unrelated to precursor availability.


The influence of cocaine and desipramine on the cardiac responses to exogenous and endogenous norepinephrine. In open-chest, anesthetized dogs, cocaine and desipramine potentiated the pressor, chronotropic, inotropic and coronary sinus blood flow responses to norepinephrine (NE) infusions. The chronotropic and inotropic responses were also prolonged, the former more markedly than the later and the extraction of exogenous NE from the coronary blood stream was diminished. Cocaine and desipramine also potentiated the pressor and coronary sinus blood flow responses, but not the chronotropic or inotropic responses, to stimulation of the left ansa subclavia. The inotropic response was slightly prolonged, however, and the chronotropic response was markedly prolonged. The overflow of NE into the coronary sinus blood was not increased by either neuronal uptake blocking agent. It is proposed that cocaine and desipramine, at the doses employed, diminish the release of NE from the cardiac nerve endings at the same time that they inhibit reuptake of the neurotransmitter. Their mechanisms of action and their side effects on the circulatory system do not appear to differ significantly.


Some observations on the gastric effects of phentolamine in rats. The effects of graded doses of phentolamine on gastric secretion, gastric emptying rate, gastric mucosal mucus content and gastric mucosal lesion incidence were studied in conscious rats 2 h after intramuscular administration. In pylorus-occluded rats, phentolamine (5, 10 or 20 mg/kg) produced dose-dependent decreases in the gastric secretory volume and total acid output. Similar doses of the drug also produced dose-dependent decreases in the gastric emptying rate in animals without pylorus occlusion (intact rats), but did not affect the gastric mucosal mucus content. The incidence of gastric mucosal lesions in pylorus-occluded or intact animals rose with increasing doses. The findings are discussed in the light of the possibility that phentolamine, in the dose range examined, possesses a sympathomimetic action which would underlie the gastric lesions observed.


A correlative study of the antiulcer effects of zinc sulphate in stressed rats. The effects on zinc sulphate pretreatment of rats on stress-induced gastric ulcers and on changes in mast cell counts were studied and correlated with changes in gastric mucosal microcirculation. The effects on zinc sulphate on blood pressure responses and on growth were also examined. Stress (2 h restraint at 4 degrees C) produced marked glandular mucosal ulceration, lowered the stomach wall mast cell counts and increased the microcirculatory blood volume in the superficial glandular mucosa. Zinc sulphate (22, 44 or 88 mg/kg; injected i.p. 48 h before stress) reversed all these changes in a dose-related manner. Blood pressure responses to i.v. acetylcholine, adrenaline or histamine were unaffected and growth of the rats as observed for 7 days after injection was not impaired. On the basis of these findings the mechanism of the antiulcer action of zinc sulphate is the following: inhibition of the stress-induced release of vasoactive agents from gastric mast cells and thus prevention of the subsequent microciculatory changes known to produce mucosal ulceration. Interference with vascular responses through direct blockade or toxicity is unlikely.


Electrical stimulation of the nigrostriatal pathway after HA-966 block of triatal dopamine release. Striatal dopamine (DA) of rats increased twofold 1 h after blockade of DA release by either an electrolytic lesion of the substantia nigra (SN) or systemic administration of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966). If the treatments were combined, no further increase was observed. The decrease in DA induced by alpha-methyl-p-tyrosine (alphaMT) in otherwise untreated animals was not enhanced by a 20 min electrical stimulation of nigrostriatal fibres. If, however, in addition to synthesis blockade by alphaMT, DA release was interrupted by a lesion of the SN and/or by HA-966, electrical stimulation caused a significant decrease in striatal DA. It is assumed that HA-966 exerts its action in the dopaminergic nigrostriatal system by way of blockade of the nerve impulse flow at the level of the SN.