Experimental cellular allergic reactions in normal canine and malignant human prostate. This paper describes the histopathology of chronic tuberculin-type hypersensitivity reactions in the normal canine and malignant human prostate. Seven dogs were sensitized by injection of Freund's complete adjuvant and the histological response to the subsequent intra-prostatic injection of 6 mg tuberculin PPD was documented. A chronic mononuclear cell prostatis persisted for 4 weeks and was accompanied by paracortical distension and follicular hyperplasia in regional lymph nodes. Six patients with carcinoma of the prostate were given multiple intraprostatic injections of BCG, which induced a chronic mononuclear cell prostatitis with some evidence of tumour-cell necrosis. The study indicated that the prostate can support chronic cell-mediated allergic reactions to extrinsic antigens and that intra-prostatic injections of BCG can be administered without harmful effects to patients with malignant prostatic disease.


Migration inhibition factor-like activity in inflammatory synovial fluids might be due to proteases. Using an assay of macrophage migration, where the cells emigrate from an agarose droplet, it was found that the neutral proteases trypsin, chymotrypsin, Pronase and elastase have MIF-like activity. Appropriate enzyme inhibitors counteract this effect. To twelve synovial fluids from patients with inflammatory arthritis, which have MIF-like activity (migration index between 0-3 and 0-7) protease indhibitors (Trasylol, ovomucoid and soybean inhibitor) were added. Ten of the fluids lost some of their MIF-like activity with at least one inhibitor. Phenylmethylsulphonylfluoride counteracted totally the MIF-like activity of the two fluids tested. It is concluded that MIF-like activity of inflammatory synovial fluids is due, at least partially, to proteases.


Features of the immune response to DNA in mice II. Participation of B and T cells. The respective roles of thymus-derived and bone marrow-derived lymphocytes in the immune response to DNA was investigated in mice reconstituted with various cell populations using cell transfers. A helper effect of thymus-derived cells in the immune response to DNA was suggested by experiments performed in athymic nude BALB/c mice. Reconstitution experiments performed in low responder DBA/mice indicated that the immune response to DNA can be increased after transfer of bone marrow cells from high responder NZB mice, even in the presence of thymocytes from DBA/2 mice. In NZB X NZW mice, a major role of bone marrow cells, with a possible modulation by thymus-derived cells during aging, was observed in the spontaneous development of anti-DNA antibodies.


Detection of antibody to respiratory syncytial virus by membrane fluorescence. An indirect membrane fluorescent antibody technique was established to study HEp 2 cells infected with respiratory syncytial (RS) virus. It was possible to detect IgG and IgM antibody to RS virus in the sera of patients with respiratory infections using this technique. The technique was further applied to the detection of IgA antibody to the same virus in colostrum.


Enumeration of immunoglobulin-bearing lymphocytes in whole peripheral blood. A new method is described for the detection by immunofluorescence of lymphocyte populations in whole peripheral blood. Lymphocytes are identified by their lack of intracellular peroxidase, and the absolute number of different populations can be accurately enumerated by avoiding procedures for isolating mononuclear cells before fluorescent staining. Among twenty-two normal individuals the mean +/- s.d. percentage and absolute number of lymphocytes with stable surface immunoglobulin were as follows: IgM, 8-1+/-2-3%, 142+/-60/mu1; IgD,8-9+/-2-2%, 212+/-85/mu1;IgA, 2-2+/-1-0%, 41+/-24/mu1; IgG, 2-3+/-1-6%, 60+/-47/mu1. It was confirmed that the detection of true IgG-bearing lymphocytes depends on washing the blood at 37degrees before staining or the use of F(ab)2 anti-IgG antibodies. The proportion of lymphocytes stained by whole IgG polyvalent anti-immunoglobulin antibody, which detects both true immunoglobulin-bearing lymphocytes (B cells) and Fc receptor cells was constant (20-5+/-1-0%) both in and between individuals, but the absolute numbers (380+/-117/mu1) varied with the lymphocyte count.


The prognostic  significance of coronary artery calcification seen on fluoroscopy. Fluoroscopic detection of coronary artery calcification (C.A.C.) has no prognostic significance. Of 440 patients screened 78 were found to have C.A.C. The five year survival of this group was the same as that of a control group. Age, sex, distribution, and extent were also without significance. Improved equipment available today allows recognition of smaller areas of calcification which may have clinical significance.


Effect of topically applied acidulated phosphate fluoride on dental caries. A 4-year clinical trial was conducted to determine the effect on dental caries incidence of the use of acidulated phosphate fluoride (APF 1.23%). 1,653 Egyptian schoolchildren aged 8 years started the trial. Dental caries was assessed annually by clinical examinations. 1,027 children completed the study. After 4 years, the children in the study group showed a mean of 2.58 DMF teeth and 2.68 DMF surfaces. Those in the control group showed 2.58 and 2.67, respectively. No significant reduction in the caries increment was observed at 0.05 level. The findings of this study suggest that topical application of fluoride does not decrease pit and fissure caries.


Bio-emulsifiers.

Bio-emulsifiers. This review discusses the currect state of the art on the subject of emulsifiers, particularly those of biological origins. The basic principles involved in the mode of action of emulsifier molecules are reviewed. Current ideas on the classification, physicochemical properties, stability, and rheological properties of emulsions are discussed. The literature review on bio-emulsifiers emphasizes those of microbial origins and their application in industry. Some of the more common methods for the study of emulsion properties are also outlined.


Products of soil microorganisms in relation to plant growth. A survey has been made of the range and activity of the organic products of soil microorganisms which have a direct influence on plant growth. Microbial metabolites which effect plants indirectly by the modification of the soil environment are also reviewed. The sources of substrates for the production of metabolites in soil and the farming practices which give rise to them are considered. It is stressed that an interdisciplinary approach is needed in the manipulation of microbiological activity in soil.


Double-blind comparison of 3-times daily and single night dosage of amitriptyline, with special reference to side-effects. Forty-one depressed in-patients completed a 4-week trial in which they were given 150 mg amitriptyline either as 3 daytime doses or as a single dose at bedtime (placebo was given at the other times). There was no significant difference in efficacy, as measured by Hamilton and Wakefield scales. Complaints of dry mouth and blurred vision increased in both groups; increased complaints of a "hung-over feeling" after waking occurred in those having the bedtime dose, but fewer of these gained wieght during the trial.


Medical treatment of intermittent claudication: a comparative double-blind study of suloctidil, dihydroergotoxine and placebo. Forty-five patients suffering from intermittent claudication were admitted to a double-blind non-crossover study. Three groups were constituted at random and treated for 2 months with either 100 mg suloctidil t.i.d. or 1.5 mg dihydroergotoxine methylate t.i.d. or placebo. From the results of measurements of pain-free walking distance and venous occlusion plethysmography recordings, suloctidil was shown to be active and significantly superior to dehydroergotoxine and placebo: in the two latter groups a decrease in calf blood perfusion after 2 months was also noted. The physician's overall assessment of response to treatment showed that suloctidil and dihydroergotoxine were significantly superior to placebo, and that suloctidil was significantly better than dihydroergotoxine.


Bumetanide in congestive heart failure.

Bumetanide in congestive heart failure. Bumetanide, a new diuretic exerting its major effect on the ascending limb of the loop of Henle, was evaluated in 20 patients with congestive heart failure. Dosage ranged from 1 mg to 3 mg daily depending on the patient's condition. The results after 3 and 8 days' treatment showed that bumetanide caused a significant diuresis, an increased excretion of sodium, potassium and chloride, and a comparable fall in the serum levels of these electrolytes. Changes in electrolyte levels were directly related to the dose of the drug. The resultant hypochloraemia was accompanied by a slight metabolic alkalosis. A comparative crossover study between placebo, bumetanide and frusemide using equipotent doses was performed in 10 patients. Both drugs had a similar effect upon water excretion and the serum and urinary electrolytes.


A comparative trial of large doses of ketoprofen and indomethacin in the treatment of rheumatoid arthritis. A 4-weeks' double-blind, crossover study in 30 patients with definite or classical rheumatoid arthritis is reported using 300 mg ketoprofen per day and 150 mg indomethacin per day. Both drugs had similar effects upon the patients' subjective improvement of pain. Objectively, the results also suggest that ketoprofen may be more effective in reducing the articular index, i.e. a superior analgesic effect. Further studies are underway to assess the value of ketoprofen administered in high dosage for longer duration.


Double-blind trial of a long-acting bronchodilator preparation ("Nethaprin Dospan") in bronchospastic disease. A double-blind, placebo-controlled, crossover study was carried out in 48 patients with bronchospastic disease to assess the efficacy of a long-acting bronchodilator preparation ("Nethaprin Dospan") containing etafedrine hydrochloride, bufylline, doxylamine succinate and phenylephrine. Patients received 1 tablet nightly, with an extra dose in the morning if necessary, of active drug or placebo for 1 week, and were then crossed over to the alternative medication for a further week. All patients had marked disability, apparent on initial clinical examination and on respiratory function tests. The results showed that FEV1 and VC were significantly improved with the active medication, and patients slept better, had improved appetite and suppression of cough.


Hormones and non-specific humoral factors in the interferences between sodium, glucose and phosphate handling by dog kidney. Some relationships between renal handling of sodium, glucose and phosphate have been investigated comparatively in dog kidneys studied "in situ", transplanted to the neck vessels of a perfusor animal, or perfused by a pump-oxygenator machine. The results can be summarized as follows: a) The values of tm of glucose per ml of glomerular filtration rate are not significantly different in the presence or in the absence of a perfusor animal, thus ruling out an hormonal modulation. b) An identical curvilinear regression relation between tmG and fractional excretion of sodium is found in the three types of experiments; the response to saline loading is identical; therefore an hormonal control of extrarenal origin is excluded. The differences in the decrease of tm glucose at high or low values of sodium excretion seem best explained by a coupling between glucose transport and one component of sodium transport which should be comparatively less influenced when the impairment of proximal reabsorption is high. c) A competition between glucose and phosphate excretion is observed in the isolated kidney; therefore it depends also at least for some part on intrarenal mechanisms. d) Insulin decreases phosphate clearance by direct renal action, probably by enhancing the tubular reabsorption of this ion as well as of sodium.


Aspects of regulation in kidney at the enzymic level: aldolase isozymes, aminopeptidase and alkaline phosphatase. Histochemical and immuno-histochemical studies on kidney sections of adult rats and rats at different stages of development were carried out to estimate enzyme concentrations in nephron segments. Aminopeptidase and alkaline phosphatase were found from 3 days before birth in proximal tubule cells, aldolase-B and aldolase-A in all the nephron and collecting duct. The concentration of the enzymes remained remarkably constant from the 3rd day after birth onwards, except for aldolase-A in the distal tubule cells. The concentration of aldolase-B was higher than of aldolase-A in the distal tubule cells. The concentration of aldolase-B was higher than of aldolase-A, in glomerula and proximal tubules, that of aldolase-A was higher than that of aldolase-B in the ascending thick part of the Henle loop and in the following parts of the nephron. This implies that the concentration of the enzymes is the limiting factor for the regulation of substrate hydrolysis and that the nephron when formed can function as efficiently as the nephron of the adult rat with respect to these enzymes.


Noninvasive measurement of cardiac function during exercise, using resaturation curves. The resaturation curve, a noninvasive indicator-dilution test using an ear oximeter to detect rates of change in arterial oxygen saturation during breathing of various concentrations of oxygen, was used to assess cardiac performance in normal subjects and in 108 patients with cardiac valvular disease. Measurements made during exercise included the time constant of resaturation (tau) and beat-to-beat changes in arterial oxygen saturation (the left heart clearance fraction). At maximum rates of voluntary work, patients had a significantly reduced clearance fraction and longer tau than normal subjects. Clearance fraction and tau improved in patients after aortic valve replacement; deterioration occurred in tau and clearance fraction over time in patients treated medically, as compared to normal subjects who showed little change during a ten-year period. Clearance fraction and tau correlated with hemodynamic data obtained during cardiac catheterization. The resaturation curve provides an objective measure of cardiac impairment that can be readily repeated during follow-up of patients with heart disease.


[Results of nerve repair on the upper limbs]. This paper concerns the clinical results of microsurgical repair to nerve injuries on the upper extremities of 66 patients, who had sustained a total of 126 nerve injuries. The majority of these cases involved lesions of the sensory nerves, occurring in the area of the palmar surface of the hand and flexor surface of the fingers (102 nerves and 24 injuries involving the nerve trunks of the median and ulnar nerves). -- Fifty-five percent of the cases were treated primarily, 25% secondarily, and the remaining 20% required nerve transplants. Forty percent involved crush injuries and 87% had sustained associated injuries. -- Tests for tactile gnosis were performed by means of "blindfold" tests. The analysis of the results was carried out according to accepted methods; the "Sedon" method was adapted in order to be able to judge the sensibility from a more functional aspect. -- The repair to sensory nerves is more successful than that carried out on the motor nerves. The degree of success is dependent upon the age of the patient, the nature of the wounds, and the associated injuries. -- Results of primary nerve suture are considerably better than those resulting from nerve transplants even in cases of unfavorable soft issue conditions. Thus, our opinion is that an experienced hand surgeon trained in the field of microsurgery should not be afraid of undertaking primary repair procedures as long as the technical and administrative requirements are adequate.


Differential rates of sister chromatid exchanges between euchromatin and heterochromatin. In two rodent species, the Chinese hamster and the montane vole (Microtus montanus), the rate of sister chromatid exchange was lower in constitutive heterochromatin than in euchromatin.


The inheritance of radiation induced semi-sterility in Rhodnius prolixus. Eggs from crosses of 40 adult male R. prolixus irradiated with 6K rad gamma-rays with normal females had a mean fertility of 23.9%, only 2 crosses being completely sterile. The 86 F1 progeny of both sexes, when outcrossed with normal mates, had a mean egg fertility of 12.6;, and 43 of these matings were completely sterile. Twenty-eight "F2" bugs reared from F1 X normal crosses were mated with normal partners and had a mean fertility of 44.6%, 6 of them being fully fertile, a reversal towards normal fertility. Cytogenetic examination of F1, "F2" and "F3" males showed that these changes in fertility correlated well with the degree of chromosomal abnormality found. The very high recovery rate of translocations in F1 generation males can be related to the holocentric chromosomes of these bugs which precludes the formation of dicentric chromosomes which are inviable in monocentric species. In F1 and "F2" males the majority of one bug was found with a ring of IV chromosome association and it is suggested that chromosome morphology, combined with a low chiasma frequency, favours chain association. Most chain multivalents showed linear orientation which may lead to duplication deficiencies and zygotic death. However, "parellel", "indifferent" and the more stable "convergent" modes of chain orientation were also all observed indicating that survival of some translocations in this species may be possible. The survival to the "F2" generation of chromosomal fragments confirmed the holocentric nature of triatomine chromosomes. It is suggested that semi-sterile males would prove more effective than releases of completely sterile males for reducing wild populations of R. prolixus, because of the delayed effects of sterilizing radiation consequent upon the holocentric structure of triatomine chromosomes.


Affective psychoses following renal transplant. Six patients who developed affective psychoses following renal transplantation ae reported. Each patient was treated, with careful management, with an appropriate somatic therapy (including phenothiazines, tricyclic antidepressants, electroconvulsive treatments and lithium carbonate). The results of this treatment approach were uniformaly successful. The similarity ofthe affective psychoses that developed in this patient population and those previously described psychoses attributed to steroid therapy is commented upon.


[The method of preparation for VMK-crowns]. In a clinical study, follow-ups were made in 259 tangentially prepared VMK crowns. In 49,4 per cent of the cases, inflammatory changes of the marginal gingiva were found, 34.5 per cent discolorations were observed in the same region. Measurements of the marginal thickness of those 68 VMK crowns prepared in a dental laboratory showed that the average marginal thickness of baked crown margins was 1.13mm. Thus, it falls considerably short of the requirements of a satisfactory thickness of metal and ceramics, but largely exceeds the values given for a micro step. Because of these findings, it must be demanded that tangential preparation of metal ceramic replacement with the crown being placed into the gingival sulcus, be discontinued.


[REM and Hommel tester studies of the dental enamel surfaces after removal of  dental calculus with 2 different scalers]. Removal of gingival calculus was performed with two different scalers on teeth that had been extracted previously. Using scanning electron microscopic prints and the Hommel tester, it was demonstrated that the dental surface had obtained a clearly visible roughness. This is determined by the dental surface, the compressive strength and the characteristics of the various scalers. The use of a Tompkin reamer to smooth the surface produced even deeper criss-cross grooves than the scaler, and not a satisfactory smooth surface.


Estradiol-induced increase of the LH responsive to LH releasing hormone (LHRH) in rat anterior pituitary cells in culture. The effect of 17 beta-estradiol (E2) on LH secretion was studied using rat adenohypophyseal cells in primary culture. Preincubation of cells with 1 X 10(-9) M E2 for 40 h decreased the concentration of LHRH required for half-maximal stimulation (ED50) of LH release from 3.0 +/- 0.3 to 1.6 +/- 0.2 X 10(-10)M (P less than 0.01). Basal LH release was increased from 84 +/- 4 to 182 +/- 8 ng LH-RP-1/ml/4h (P less than 0.01) by E2 pretreatment. Time-course experiments showed that the stimulatory effect of 10(-8)M E2 on the LH response to LHRH can be first measured after 10 h of incubation in the presence of E2 and that this effect is maximal after 24 h of incubation with the steroid. While E2 increases the LH responsiveness to LHRH, androgens decrease the sensitivity of LH-secreting cells to the neurohormone. The LHRH ED50 value of testosterone-treated cells is of 7.2 +/- 0.4 vs. 3.7 +/- 0.3 X 10(-10)M for control cells (P less than 0.01). E2 can only partially reverse this inhibitory effect of androgens on the LH response to LHRH. These data show clearly that E2 can have a direct stimulatory effect on LH-secreting cells to increase the sensitivity of their response to LHRH.


Stimulation of insulin release by elevated pressure gradient. In an attempt to stimulate the contractile events which presumably lead to intracellular translocation and exocytosis of the beta granule, the effect of elevated pressure on the rate of insulin release was studied. In vitro preparations of pancreas were incubated in media of low glucose content (1.65 mM) for several consecutive 15 min periods. The effect of pressure gradients, ranging from 0 to 45 mm Hg above atmospheric pressure, on insulin release was tested during the second period by introducing a mixture of 95% O2-5% CO2 into the incubation flasks. The results have shown that: 1) a rise in the pressure gradient over the gas phase was accompanied by an increase in the concentration of insulin released into the medium; 2) there was a direct relationship between the pressure gradient and the rate of insulin release; 3) the enhanced rate of insulin release caused by elevated pressure was not reversed immediately after release of pressure, but the effect was completely abolished within a period of 15 min; and 4) the stimulating effect of high glucose concentration on the rate of insulin release was completely blocked in the presence of 1 mM DNP, but the pressure-induced stimulation of insulin release was insensitive to this agent. In view of recent evidence implicating the microtubular-microfilamentous system in the secretory process of insulin, it is suggested that the application of pressure to the islet cells provides the necessary motive force to facilitate the intracellular translocation and extrusion of the beta granules normally performed by the beta cell contractile structures.


In vitro release of luteinizing hormone-releasing hormone (LHRH) from rat mediobasal hypothalamus: effects of potassium, calcium and dopamine. A suitable preparation to study the effect of dopamine (DA) on in vitro LHRH secretion is presented. Enzymatic degradation of LHRH in the incubation medium is completely inhibited by bacitracin (2 X 10(-5) M). Ahigh potassium concentration (56mM) induces an increase in LHRH release from entire pieces of mediobasal hypothalamus (MBH), but not from a synaptosomal pellet; this release is inhibited when calcium is omitted. The depolarization-induced LHRH in the MBH. In contrast, DA (10(-6)M) is not effective in vitro on MBH from ovariectomized rats but induces a fast release of LHRH from MBH of normal male and estradiol-pretreated ovariectomized rats. The preparation presented here appears to be of great interest in investigating amine-steroid-LHRH interactions at the cellular level.


Investigations on isolated islets of Langerhans in vitro. XIV. Insulin secretion and insulin stores of cultivated islets from sand rats (Psammomys obesus): investigations of glucose-dose response. Release of immunoreactive insulin activity (IRI) and biological insulin like activity (ILA) from collagenase isolated pancreatic islets of sand rats (Psammomys obesus) maintained on a vegetable diet were examined at 60 min and 24-48 h intervals under culture conditions at 1.0 and 15.6 mM glucose. The glucose-insulin dose response curves for sand rats after 60 min incubation were compared with those after 24 or 48 h of incubation. The pancreatic islets responded to 5mM glucose with a high insulin release especially under culture conditions. A drastic depletion of stored insulin in the islets cultivated for 2 days at 5 or 15 mM glucose is accompanied by a continuous diminution of the glucose-induced insulin release with the prolongation of cultivation up to one week.


Has sodium valproate hypnotic effects?

Has sodium valproate hypnotic effects? Eight fasting normal subjects were given a single dose of sodium valproate, 400 mg, phenobarbital, 60 mg, or the two drugs in combination, in a double-blind placebo-controlled study. The effects were assessed behaviorally and by a standard 30-min EEG, begun 1 hr after the treatments had been given. The recording was rated for the amount of drowsiness and sleep, independent of which drug had been given. The scores obtained indicated that valproate intself has hypnotic action, and there is a tendency for this to be increased by the simultaneous administration of phenobarbital.


A differential diagnosis of the inspirational spells of Muhammad the Prophet of Islam. This paper reviews the spells of Muhammad, the Prophet of Islam. During these spells, Muhammad sensed the approach of a figure whom he thought to be the Angel Gabriel. The inspirational message transmitted to Muhammad during these spells helped form the religion of Islam. This is a review of the historical details of these spells and an attempt to reach a medical diagnosis. Although an unequivocal decision is not possible from existing knowledge, psychomotor or complex partial seizures of temporal lobe epilepsy would be the most tenable diagnosis. An examination of Western civilization's views of Muhammad's spells reveals historical and modern misconceptions about epilepsy.


Bradycardia and cardiac arrest during tracheal suction--mechanisms in tetraplegic patients. The cardiovascular responses to tracheal suction were observed in 4 consecutive recently-injured tetraplegics with physiologically complete cervical spinal cord transections (C3-5) who were in spinal shock and needed artificial ventilation. In all 4 patients tracheal suction induced bradycardia and in 2 patients even cardiac arrest. The bradycardia occurred when the patients were hypoxic, and was prevented by the addition of oxygen to inspired air, or, if this was inadequate, by the administration of atropine. Two of the patients were agains studied several months later, after return of isolated spinal cord activity and spontaneous breathing. In both patients tracheal suction then caused tachycardia and increased respiratory effort. It is concluded that: 1. Tetraplegics with high cervical spinal cord transections who are in spinal shock and unable to breathe spontaneously are prone to bradycardia and cardiac arrest during tracheal suction. This is more likely to occur when they are hypoxic. 2. The bradycardia appears to be due to a vago-vagal reflex for both afferent and efferent limbs of the arc are in the vagus nerve. A number of factors play a part, including (I) absent sympathetic activity; (II) airway receptor stimulation; (III) hypoxia and (IV) the inability to breathe spontaneously (The pulmonary (inflation) vagal reflex which would normally oppose the cardio-inhibition caused by (II) and (III) is absent). 3. The bradycardia in response to tracheal suction can be prevented by adequate oxygenation, or if this cannot be achieved, by repeated atropine.


The organization of intensive care after renal transplantation. The present state of organization of renal transplant intensive care in 14 centers of Austria, Germany and Switzerland is described. Special reference is given to the annual transplantation rate, the number of intensive care beds, the duration of intensive care, the aseptic conditions, the installations and apparatus, and to the medical supervision and the nursing care.


Comparative study of metoprolol and alpha-methyldopa in untreated essential hypertension. The hypotensive actions of metoprolol and alpha-methyldopa have been compared in 37 men with previously untreated essential hypertension; 36 belonged to stage 1 and 1 to stage 2 of the WHO classification. After four weeks of placebo treatment the patients were randomly allocated to treatment with either of the two drugs. Treatment was started with metoprolol 75 mg daily or alpha-methyldopa 375 mg and was doubled after eight weeks. Satisfactory blood pressure control was defined as systolic blood pressure below 160 mm Hg and diastolic below 95 mm Hg. The patients were examined every four weeks and in those with unsatisfactory control the dose was gradually increased up to a maximum daily dose of metoprolol 450 mg or alpha-methyldopa 2250 mg. The trial lasted for 24 weeks after randomization. Five patients dropped out of the study. After six months, satisfactory blood pressure control was recorded in 16 out of 17 patients and 14 out of 15 patients treated with metoprolol and alpha-methyldopa, respectively. The average reduction in blood pressure produced by the two drugs was comparable. One patient in the alpha-methyldopa group developed drug exanthema and two patients a positive Coombs' test. Other side effects were few and did not differ between the two compounds.


Comparison of metoprolol as hydrochlorothiazide and antihypertensive agents. A crossover comparison of metoprolol and hydrochlorothiazide has been performed in 20 patients with mild hypertension. Both drugs caused almost identical statistically significant reduction in blood pressure of about 20 mm Hg systolic and 15 mm Hg diastolic. The side effects during active therapy were few and mild, but 5 patients experienced subjective symptoms during the first few days following abrupt withdrawal of metoprolol, namely general malaise, palpitations, headache, sweating and tremor. The symptoms were more pronounced in the standing position and disappeared at once on resumption of beta-blocker therapy, or gradually over 5 - 7 days when placebo tablets were given. In 11 of the 20 patients hydrochlorothiazide produced subnormal serum potassium levels and potassium supplements were given. The serum uric acid level was also significantly increased during hydrochlorothiazide treatment.


Studies on the relationships between the immunogenicity and catabolism of antigens and their binding to the surface of macrophages. The relationship between immunogenicity of Shigella paradysenteriae, the branched synthetic polypeptide poly-L (Tyr, Glu)-polylpro-polyllys [(T, G)-Pro--L] and human albumin (HSA) interacting with macrophages and kinetics of antigen degradation and degree of binding to the cell surface was studied. Following thioglycollate inoculation into C57BL/6 mice, the peritoneal-stimllated macrophages had higher levels of hydrolases as compared to unstimulated cells. The lysates of the stimulated macrophages catabolized the three labeled antigens faster than did the lysates of unstimulatec cells. However, when degradation of labeled antigens by macrophage cells was assessed, no direct correlation could be demonstrated between the level of cell hydrolases and rate of (T, G)-Pro--L or HSA catabolism. The immunogenicity of antigens following their uptake by unstimulated and stimulated macrophages  was determined by transfer of the antigen-bearing cells into irradiated and nonirradiated syngeneic recipients. No correlation was apparent between the rate of antigen degradation and the capacity to evoke a humoral response. Similarly, no correlation could be demonstrated between the amount of antigen bound to the macrophage cell surface and the immunogenicity of the antigen. It is suggested that neither the rate of antigen catabolism by macrophages nor the amount of antigen bound to the macrophage membrane is the sole factor which determines the immunogenicity of antigens interacting with macrophages.


Malarial immunodepression in vitro: adherent spleen cells are functionally defective as accessory cells in the response to horse erythrocytes. The basis for the depressed response of malarial infected mice to horse red blood cells (HRBC) has been studied in vitro. Results presented show that the adherent spleen cells from infected mice (a) are defective in their ability to allow nonadherent spleen cells of both normal and infected mice to respond to HRBC whereas a response does occur with adherent spleen cells from normal mice (b) do not suppress the response of unfractionated spleen cells from normal mice to HRBC (c) contain phagocytic cells as measured by the uptake of neutral red in numbers which are of the same order of magnitude as in adherent spleen cells from normal mice, but which are unable to take up HRBC. We conclude that a splenic adherent cell, probably the macrophage is functionally defective as an accessory cell in the response to HRBC of mice infected with Plasmodium berghei yoelii.


[Nevus telangiectasis of the facial skin: possibilities and problems of plastic surgery]. If a portwine stain (capillary hemangioma) or a cavernous hemangioma of the facial skin is not camouflaged by cosmetics, surgical excision and full-thickness skin grafting appears to be the method of choice. Exact planning (donor areas) and perfected technique are prerequisites for results in which the grafted skin matches in color, texture, contour and thickness the unaffected facial side.


Increased capillary permeability in guinea pigs and rats by peptidoglycan fraction extracted from Group A streptococcal cell walls. The increased capillary permeability in the skin of guinea pigs and rats was induced by peptidoglycan fraction (PG fraction) extracted from cell walls of group A streptococcus, but not by C-carbohydrate of streptococcal cell walls nor lipopolysaccharide of Escherichia coli and Salmonella abortus. The increased capillary permeability caused by PG fraction was also observed in germ-free rats. It was suggested that the increased capillary permeability for PG fraction might be due to the biological activity of PG fraction. The pattern of the reaction of increased capillary permeability consists of two phases: the leakage of the dye in the first phase appeared immediately after the intracutaneous injection of PG fraction, and the second phase seems to depend upon vasculitis. The increasing activity of capillary permeability to PG fraction may play an important role in inducing initial change of tissue injury by streptococcal cell walls.


Pathology of influenza hepatitis in susceptible and genetically resistant mice. Mice resistant (homozygous or heterozygous for the gene Mx) and mice susceptible to the lethal effect of influenza viruses were inoculated intraperitoneally and intraportally with a hepatotropic variant of influenza A virus. Disease evolution was followed histologically and by immunofluorescence. In susceptible animals, rapidly spreading foci of hepatocyte necrosis with little inflammatory infiltration was observed. Death occurred on the 3rd day, when the entire liver was involved. In resistant animals foci became detectable later, and were fewer and smaller. They were infiltrated by cells morphologically resembling liver macrophages (Kupffer cells), and they regressed from the 4th day after infection. Barriers to virus spread appeared to be present at all stages of the disease.


Identification of gonadotropic cells in the human pituitary by immunoperoxidase technique. Using specific antibodies against the beta-subunits of human LH and FSH, the pituitary cells which produce the two gonadotropins have been localized in the human pituitary by an immunoperoxidase technique. In serial semi-thin sections (2 mum), it was clearly shown that about 90% of gonadotropic cells contained both FSH and LH, whereas the remaining 10% of gonadotrophs were positive only for FSH. At the ultrastructural level, the gonadotrophs containing both LH and FSH were characterized by the presen-e of two types of secretory granules: the smaller ones which whowed a strong immunohistochemical reaction and the larger ones which generally presented a weaker reaction.


Serological classification and typing of Clostridium botulinum. Serological classification of Cl. botulinum, based on the antigenic structure of the toxins produced, is distinguished by the behaviour of the toxin-antitoxin mixtures in in vivo neutralization tests. Observations on the dissimilarity between strains within types, the behaviour of antitoxins in the cross-neutralization tests, the established concepts of the antigenic structure of the toxin types and the lack of a standard methodology for typing, have led to the definition of the terms efficiency, type, subtype, intratypic serological variant (ISV), and degree of serological homology. These definitions are primarily applied to typing and to the establishment of the taxonomic serological categories of type, subtype and ISV. In the case of antitoxin standardization, the accepted standard methods must be followed.


Results of potency tests of a vaccine against Cl. botulinum type C by different methods. The potency of vaccine against Cl. botulinum type C was tested comparatively in mice, guinea pigs and mink, using the test methods employed in the United States, Great Britain and Sweden. Additionally the capacity to withstand challenge to toxin in ferrets was investigated. All species of laboratory animals proved to be protected against high toxin doses. On the other hand the humoral antitoxin titer of the immunized animals was low after one injection. After a second injection or after challenge with toxin the titer increased considerably.


Antitoxin responses to Clostridium botulinum vaccines types C and D in guinea pigs. In guinea pigs, the type C and/or type D antitoxin responses to a single dose of a bivalent or monovalent Cl. botulinum vaccine increase markedly between the fourth and ninth week after injection and still increase markedly by the ninth week. For type C, a similar pattern has been found in cattle. Antigens of types C and D mutually interfere with the antitoxin responses in guinea pigs. Graded doses of vaccine arouse graded antitoxin responses in guinea pigs. Stability trials of vaccines have emphasized the unsatisfactory nature of an absolute-response type of assay, rather than revealing any loss of potency during storage. Attention is drawn to the need for a graded-response type of assay in which vaccines under test are compared with a reference vaccine.


[Method of quantitative determination of vaccine activity against botulism of the mink]. Lyophilized vaccines prepared according to the method of Käber, modified by Achmarine, are utilized in the Soviet Union for the immunization of mink against botulin of the type C-alpha. These vaccines can be conserved more than a year at laboratory temperature without losing their efficacity. A Table allows a rapid and accurate determination of the quantity of vaccine to be injected into the mink to provide the same efficacity as a dose of standard vaccine.


The enteral insulin-stimulation after pancreas transplantation in the pig. The insulin responses to an oral glucose tolerance test (OGTT) and in intravenous glucose infusion (IVGI), designed to copy the changes in serum glucose concentrations found during OGTT, were measured in four pigs before and after heterotopic pancreatico-duodenal allotransplantation and total pancreatectomy. After transplantation and total pancreatectomy a remarkable hyperinsulinaemia occurred during OGTT and IVGI, reflected by an almost two-fold increment in the insulinogenic index after transplantation. This finding might be explained by drainage of the transplanted pancreas into the systemic circulation instead of the portal vein. The magnitude of the enteral stimulus, i. e. the incretin effect on insulin secretion during OGTT was unchanged after transplantation, suggesting that the incretin effect is not mediated by neural influences upon the endocrine pancreas.


Effect of oil-attached BCG cell-wall skeleton on the induction of pleural fibrosarcomas in mice. The effect of oil-attached BCG cell-wall skeleton on the induction of pleural fibrosarcomas by 3-methylcholanthrene in mice was examined. The pleural fibrosarcomas were induced by a substernal injection of 3-methylcholanthrene into the thoracic cavity of ddO mice. One week after the injection of 3-methylcholanthrene, 100 mug of oil-attached BCG cell-wall skeleton was injected subcutaneously every week for 10 weeks. In the observation period of 130 days, the incidence of pleural fibrosarcoma was 67% in the control mice and 39% in the mice treated with BCG cell-wall skeleton. The latent period of tumor induction was prolonged in the mice treated with BCG cell-wall skeleton.


Glucosamine resistance in yeast. I. A preliminary genetic analysis. Mutants of the yeast Saccaromyces cerevisiae which can grow on glycerol medium in the presence of 0.05% D (+) glucosamine have been isolated. Genetic analysis of 13 of these glucosamine resistant (GR) mutants demonstrated two modes of inheritance. One group of mutants (GR 5, 6, 7, 8, 9 and 10) gave results characteristic of non-Mendelian inheritance and it is suggested that these mutants represent one or more new mitochondial loci. Four of the remaining mutants showed clear-cut Mendelian inheritance. These mutants fell into two complementation groups and subsequent mapping experiments demonstrated that two independent loci, gay 1 and gay 2, unlinked to each other or to the centromeres of chromosomes I, II, IV, VIII or IX, were responsible for conferring glucosamine resistance in these mutants.


Testing the heterogeneity of F values: a suggestion and a correction. The use of a pair of populations removes the problems posed by a structured phylogeny (pointed out by A. ROBERTSON) and permits the application of the original test of LEWONTIN and KRAKAUER. In the case of 2n populations studied a suggestion is made to use only n pairs in such a way that no population appears in more than one pair. Data on Dacus analyzed this way show that at least two out of six genes studied are or have been selected.


Deletion and amber mutants of fla loci in Escherichia coli K-12. A rapid screening method for amber fla mutants of E. coli was devised and many mutants were obtained. In addition, strains with deletions of the fla genes in the his-uvrC region were isolated from high-temperature survivors of a lambda cI857 lysogen in which the prophage is located between his and fla. Utilizing these mutants, eleven fla genes (I--XI) and one hag gene were identified in the his-uvrc region, in the following order: his-supD-I-II-(III, IV)-V-(VI, VII)-VIII-IX-hag-(X, XI)-uvrC. The fla genes X and XI and hag are located at about 42.5 min and the other fla genes at about 43.0 min on the E. coli genetic map (Bachmann, Low and Taylor 1976). Mutants of fla gene X showed a slight sensitivity to chi phage, although they lack the flagellar filament.


[Phenotypic manifestation of mutations involving resistance to 2,6-diaminopurine (apt) in the genome of purine auxotrophs of Escherichia coli K-12]. Strains of Escherichia coli K-12 containing various combinations of pur (de novo synthesis of purines), pup (purine nucleoside phosphorylase), add (adenosine deaminase) and apt (adenine phosphoribosyl transferase) mutations have been constructed. The apt mutation blocks the ability of strains of pur add and pur add pup genotype to utilize both adenine and adenosine as sole purine sources. Exogenously supplied histidine (that blocks conversion of AMP to guanine nucleotides) does not reduce the growth rate of the strain of pur apt genotype on adenosine as the sole purine source. Adenine released into the cultural medium of bacteria containing simultaneously apt and pup mutations. This data suggest that cultures of E. coli are unable to phosphorylate adenosine to AMP and that they are capable to degrade adenosine to free adenine without participation of purine nucleoside phosphorylase (gene pup).


[Rate of the spontaneous mutation process in mammalian somatic cells and several related questions]. Various criteria are considered according to which newly arising hereditary changes in somatic mammalian cells can be classified as mutations. The analysis of experimental data reveals that the similarity of spontaneous mutation rates in somatic and germinal cells per generation, implies drastic differences in the probability of their arising per time unit: the mutation rate per time unit is considerably higher in somatic than in germ cells. This phenomenon is discussed from the viewpoint of the spontaneous mutation rate level as an adaptive character of species. The role of spontaneous mutations in ontogenesis is considered.


[Formation of F'-episomes in Flexner shigellae]. Genetic characteristics of Shigella flexneri virulent donor strain 3s, isolated in the laboratory, are studied. The data obtained showed that Sh. flexneri 3s 6832 is of F'protype it did not transmit even closely located chromosome markers, except pro+. The transition of pro+ marker was reproduced in recA- strain. F'pro plasmid was eliminated with a frequency similar to that of F'lac factor in the control strain of Escherichia coli. The study of virulence by means of keratoconjunktival test revealed its retaining in clones which lost F'pro plasmid. Probably, KCP-A gene retained in the chromosome of F'pro strain. Crossing with proA- and procC- C. coli strains revealed a small length of F'pro episome, enly ProA+ hybrids being obtained. A complex mechanism of F'system formation in interspecies genetic recombination between E. coli K-12 and Sh. flexneri 3s is demonstrated.


[Transforming activity of Escherichia coli DNA fragments obtained following endonucleolytic splitting by EcoRI restrictase]. Escherichia coli DNA with molecular weight of 20 - 10(6) daltons was digested by restriction endonuclease EcoR1, and the transforming activity of resctricts was studied. The transforming activity of restricts for two markers (Leu and Arg) was 2-5 fold increased, for two other markers (Thr and His) was not changed, and for one marker (Pro) was completely absent. The molecular weight of E. coli DNA restricts was 7,5-10(6) daltons. An increase and a decrease of the transforming activity for different markers appeared to be the result of two effects: 1) more efficient uptake of low molecular weight DNA into the cell and 2) the inactivation of markers as a result of location close to EcoR1 induced break.


[Post-radiation recovery and the ploidy factor]. Radiobiologicae effects on extensively homozygous Sacharomyces cerevisiae strains of different ploidy from haploid to hexaploid (developed by W. Laskovski) were studied. Radiation (gamma-rays of 60Co) inactivation studies showed a minimum of resistance of haploid strains, a maximum of resistance of diploid or triploid strains and a decrease of resistance with further increasing genome number. The explanation of such dependence of radiosensitivity on ploidy is usually due to the increase of dominant lethal damages and the corresponding decrease of recessive lethal damages with the increase of ploidy. All studied strains (except haploids) were capable of recovery of radiation damages after their storage in non-nutrient media during postradiation period. Since haploids are inactivated almost exclusively by recessive lethal damages, one may suppose that reversible part of radiation damages is due to dominant lethal damages. Then an irreversible part of radiation injury must decrease with the increase of ploidy. Indeed, in studied strains an irreversible component of radiation injury was significantly reduced with the increasing genome number. Any correlation of the probability of recovery from the primary damages with ploidy was not discovered.


[Competency of Escherichia coli cells. IV. Effect of freezing--thawing on the formation of competency in Escherichia coli cells in the presence of Ca++ ions]. The paper is initiated in the aim to use the effect of freezing-thawing in the system of intact Escherichia coli cells treated with Ca++ ions to increase the transfection efficiency. It is demonstrated that freezing-thawing of Ca++ treated cells increases the transfection indices of lambda phage DNA for E. coli Hfr clone with low transfection indices in 20-30 times, and for the strain of E. coli X7026 of high competence-in 5 times. Freezing-thawing efficiently increased the transfection only in cells with a decreasing competence. E. coli Hfr H cells acquired the capacity of more efficient lambda phage DNA perception independently on the growth phase, while in E. coli X7026 cells the maximal transfection increase under the effect of complementary interactions was observed at the beginning of the logariphmic and stationary growth stages, but not during the competence period. Short-term changes emerging in cells during freezing-thawing can probably promote the better penetration of Ca++ ions to active sites on the cell surface, which produces favourable conditions for lambda phage DNA formation.


[Two routes for the development of chromosome aberrations]. Data on cytogenetic investigations using the method of influence of DNA and protein syntheses inhibitors on the chromosome are summarized. The formation of chromosome rearrangements and gaps is considered to be due to the appearance of DNA damage. The formation of these changes is proved to be similar under radiation and chemical mutagenesis. Successive stages of the realization of chromosome aberrations are united by crossing over (contact) hypothesis. The other was of the formation of cytogenetic changes is due to DNA structural degradation. These two ways can combine in radiation and chemical mutagenesis (depending on doses and mutagens).


Mucosal gastrin concentration, molecular forms of gastrin, number and ultrastructure of G-cells in patients with duodenal ulcer. The mean antral immunoreactive gastrin (IRG) concentration of 38 duodenal ulcer (DU) patients was significantly higher (35-9+/-5-2 mug/g) than that of 21 controls (15-9+/-2-6 mug/g). Also the mean IRG concentration in the proximal duodenal mucosa of 15 DU patients (3-2+/-0-8 mug/g) was higher (but not significantly) than that of 10 controls (1-8+/-0-5 mug/g). The number of G-cells in the antral mucosa of 58 DU patients and in the duodenal mucosa of 29 DU patients was not larger than that of controls. The distribution of immunoreactivity in gastrin components has been investigated in the antral and duodenal mucosa of six DU patients and six controls. In the antral mucosa the mean percentage of G-17 was 93-3% in DU patients and 92-0% in controls. G-34 amounted to 4-0% in DU patients and to 5-0% in controls. The G-34 percentage in the duodenal mucosa was higher (however not significantly) in the DU patients than in the controls (50-1% versus 35-8%). Ultrastructurally, the antral G-cells of DU patients had a significantly lower density index of their secretory granules suggesting higher functional activity. It is concluded that the exaggerated serum IRG response of DU patients to different stimuli is not a consequence of an increased G-cell mass.


Identification of the D1-cell as the source of human pancreatic polypeptide (HPP). Immunoperoxidase positive HPP-producing cells have been examined ultrastructurally using the serial semithin-thin section technique. The features of the HPP cells were found to be identical with those of the previously described D1-cell. The D1-cells are scattered throughout the exocrine parenchyma and occur to a minor extent in the islets.


Analysis of the lympho-plasmacytic infiltrate in Crohn's disease with special reference to identification of lymphocyte-subpopulations. Lympho-plasmacytic infiltrates in cryostat sections (resected small intestine or colon specimens and rectal biopsies) from 29 patients with Crohn's disease (CD) were studied with the immunoperoxidase and immunofluorescence technique, by means of specific anti-human lymphocyte globulin (ALG) and specific anti-human T-lymphocyte globulin (ATG). Control specimens were obtained from 16 patients with ulcerative colitis (UC) and 12 subjects without inflammatory bowel disease. Characteristic transmural inflammatory infiltrates in CD consisted mainly of lymphocytes. A wide variation of the relative T-cell proportion was observed. However, in contrast with UC, abundant numbers of T-lymphocytes in CD were often detected, particularly in the deeper layers of the bowel wall. Furthermore, in serial sections immunoglobulin-containing plasma cells were counted, using specific anti-IgA, -IgM, and -IgG antisera. A significant reduction of the IgA/IgM plasma cell-ratio was found in CD in comparison with UC and controls. Our results indicate that in CD a chronic cellular immune reaction is going on within the diseases gut, involving increased numbers of lymphocytes and particularly T-cells. It remains to be established whether a deficient IgA barrier has to be considered of primary pathogenetic importance.


Contrasting features and responses to treatment of severe chronic active liver disease with and without hepatitis BS antigen. To determine the clinical implications of HBSAg in severe chronic active liver disease (CALD), patients with HBSAg positive CALD were compared with those chosen by identical clinical, functional, and morphological criteria in whom this test and anti-HBS were negative. HBSAg positive patients were predominantly males over 40 years of age and more frequently failed to respond to conventional treatment programmes with prednisone. HBSAg negative patients were more often female and younger, had a higher incidence of associated immunopathic disease and immunoserological markers in high titre, and more often responded to treatment with full remission of their disease. HBSAg positive patients failing treatment with conventional doses of prednisone often improved with higher doses, but did not reach full remission of their disease. The benefit-risk ratio of both conventional and high doses of prednisone in HBSAg positive severe CALD needs further clarification.


Immune response to phi X 174 in man. 5. Primary and secondary antibody production in primary biliary cirrhosis. In primary biliary cirrhosis, the primary immune response to the bacteriophage phi X 174 is normal but the secondary response is significantly reduced. The reduction is primarily of IgG antibody, while IgM is proportionately less affected. These changes may be the result of a reduction in helper T lymphocyte function and may contribute to the increase in the ratio of serum concentration of IgM to IgG.


Ionophore a 23187: some effects on platelet aggregation and clot retraction. The ionophore for divalent cations, A 23187, induces plate aggregation and clot retraction. Acetylsalicyclic acid has a potentiating effect on the aggregation induced by A 23187 in platelet-rich plasma, while it inhibits the aggregation of washed platelets. Acetylation of plasma proteins could be the reason of the increased platelet aggregation induced by A 23187 in the presence of acetylsalicyclic acid. Platelet aggregation by A 23187 is probably activated by the passage of Ca2+ through the platelet membrane(s); the aggation, clot retraction by A 23187 requires increased availability in the intracellular space of both Ca2+ and Mg2+.


[Clinical aspects of hypertension under contraceptive steroids]. In Europe, about 1 per cent of women using oral contraceptives develop hypertension. The frequency seems to increase with age and in women who had earlier shown hypertensive disorders of pregnancy. A failure in the feedback mechanisms of the renin-angiotensin-aldosterone system is suggested to be an important factor in the etiology of hypertension induced by oral contraceptives. Usually, blood pressure returns to normal after cessation of treatment with contraceptive steroids; on the other hand, some cases of irreversible hypertension and kidney failure have been described. Besides the measurement of blood pressure before any treatment with hormonal contraceptives is started, blood pressure should be controlled after three months. In the differential diagnosis of hypertension induced by oral contraceptives, primary aldosteronism and renal artery stenosis have to be excluded; these hypertensive disorders show similar biochemical changes, but should be treated by surgical intervention. The choice of other contraceptives by women with this type of hypertensive disease is discussed.


[Clinical significance of sperm pathogens in fertility disorders]. The reasons for systematic microbial examinations of human ejaculates are discussed. The exact establishment of an association between bacteria isolated from human ejaculates and infertility is very difficult. There are several hints for such an association in the case of different micoplasmas though there is no clear-cut evidence. A physical association between these microorganisms and spermatozoa, which was recently observed, possibly could help to facilitate the diagnosis.


Principles, objectives and methods for the control of the gastro-intestinal parasites of pigs in France. Parasitic levels are considered in relation to the size of farms and according to the application of anthelminitic programmes and the age groups of the animals. The most common and important parasites in France against which systematic control measures should be taken are Oesophagostomum, Ascaris and Hyostrongylus in pregnant sows, and  Oesophagostomum and Ascaris in piglets at weaning and fattening pigs. Strongyloides and Trichuris are found occasionally but could be sometimes important (Mestastrongylus is anexceptional finding). As  regards the use of anthelmintics, emphasis is placed on treatment of sows at parturition, or of piglets on transfer to the growing units, with two treatments being given at an interval of 14-21 days. Continuous administration in the food is a complementary solution. Specific treatments for the control of Trichuris and Strongyloides are also examined. In the control of parasites the strict observation of the rules of hygiene is also very effective.


Calcium-antagonists and islet function. V. Effect of R33711. R33711, a new drug with presumed potent calcium-antagonistic property, was found to suppress the insulinotropic action of glucose and gliclazide but not that of theophylline. A 0.2 muM concentration of R33711 was sufficient to abolish glucose-induced insulin release. At this concentration, R33711 inhibited the net uptake of 45Ca2+ by isolated islets, whether in the absence or presence of either glucose or sulfonylurea. In the isolated islets, R33711 failed to affect the glucose-stimulated production of lactate, the rate of 45Ca2+ efflux, the inhibitory action of glucose upon such an efflux and its increase in response to theophylline. These data are compatible with the view that R33711 inhibits entry of Ca2+ into the B-cell and that integrity of such an inward cationic movement usually plays a permissive role in the maintenance of the Ca2+-dependent insulin secretory process.


Pituitary-gonadal function in men with alcoholic cirrhosis of the liver. Fourteen adult males with alcoholic cirrhosis were studied. Gonadotrophin responses to luteinizing hormone-releasing hormone (LRH) and testosterone (T) responses to human chorionic gonadotrophin (HCG) were determined and basal 17 beta oestradiol (E2) levels were measured in each case. The mean basal luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and the mean LH and FSH responses to LRH were not significantly different from a group of age-matched male controls. However, the five men with testicular atrophy all had an elevated basal FSH level and an exaggerated FSH response to LRH. The mean serum T of the cirrhotic men was significantly lower than that of the controls (P less than 0.05), while the mean E2 level was not significantly different. However, the mean E2 level in the eight patients with gynaecomastia was significantly higher than in those without gynaecomastic (P less than 0.05). All patients had a T response to HCG, including those 5 with low basal T levels. A significant negative correlation was found between the maximum rise in T after HCG (delta T) and the maximum LH response to LRH (delta LH), suggesting a mediating effect of T reserve on the LH response to LRH. These findings tend to exclude a suppressive effect of alcohol on the pituitary gland as a cause for the hypogonadism found in men with alcoholic cirrhosis. Furthermore, the evidence of some testicular T reserve despite low basal T levels, and the presence of normal basal LH levels, suggests that the low T production is not primarily due to leydig cell dysfunction.


Effect of a new LH-RH analogue (D-Ser(TBU)6-EA10-LH-RH) on gonadotrophin and gonadal steroid secretion in men. The effect of a new analogue of the gonadotrophin-releasing hormone LH-RH, D-Ser(TBU)6-EA10-LH-RH, on the secretion of LH, FSH, as well as testosterone, oestradiol, HGH, prolactin, TSH, and cortisol was studied in normal men. The same subjects were injected intravenously in 4-day intervals with 1.0, 2.5, 5.0, and 10.0 mug of this substance. A significant LH but no FSH release was seen after doses of 1.0 and 2.5 mug LH-RH analogue, while after 5.0 and 10.0 mug dose-dependent increases of LH and imposed elevations of FSH were observed. Peak levels of LH were reached after 30 min, those of FSH after intravenous injection after 120 min. LH and FSH remained elevated for 8-10 h. LH peak levels after 5 mug of LH-RH analogue were comparable to those seen after injection of 100 mug of the decapeptide LH-RH. Following the release of LH and FSH after doses of 5.0 and 10.0 mug LH-RH analogue, there was a late stimulating effect in testosterone and oestradiol secretion. HGH, TSH, prolactin, and cortisol were not influenced by the LH-RH analogue.


A convenient and rapid bioassay for inhibin. A bioassay for inhibin, based on a dose-dependent suppression of HCG-induced ovarian weight increase in intact, immature female rats, is described. The method is specific and has acceptable sensitivity and precision such that it lends itself to statistically valid quantitative assay of inhibin activity. Being a 24-hour assay, it is conveniently and rapid performed as well as being a multiple bioassay for estimating potencies of various preparations.


Importance of environmental factors in cancer. The present paper reviews the nature of epidemiological studies and their importance as a background for determining the hazard of cancer. An attempt is made to explain how risks in the cancer area may be compared by the use of cumulative data over a lifespan as compared to use of age-specific rates. In addition, the classification of the aetiological factors so far identified is summarized and it is pointed out that to date, the most important environmental risks relate to those of cultural habits. Of the 85% of cancers for which the causes have not yet been established, there is circumstantial evidence that the greater part of these are dependent directly or indirectly on environmental factors.


[Carcinogenic risks associated with radiation pollution]. 1. The cancerogenic pollution by non-ionizing radiations is limited to the case of solar ultraviolet, whose activity at ground level may be increased as a consequence of the stratospheric depletion of ozone, itself produced by certain chemical pollutants: nitrogen oxydes from supersonic aircrafts, freon. 2. As regards ionizing radiations, the discussion is focused on the fundamental problem of the "threshold", aand on the means by which one may obtain some quantitative data related to carcinogenesis by small radiation doses in Man. A new concept, that of a "practical threshold" is proposed. 3. One discusses a theory which links radiocancerogenesis, as well as chemical cancerogenesis, to errors produced in the repair of lesions in the DNA. 4. One presents and discusses the "rads-equivalent" project for chemical mutagens and cancerogens.


Mutagenicity and possible carcinogenicity of hair colourants and constituents. Skin painting experiments showed that two semi-permanent hair colorants applied at low concentrations caused an early appearance of tumours in two strains of mice. Both colorants were mutagenic in S. typhimurium and further investigation revealed that three categories of hair colorant contained mutagenic constitutents.


[Sampling and preliminary treatment of polycyclic aromatic hydrocarbons for analysis]. This review deals with the different methods of sampling of paticulate matter, either suspended or sedimentable, the extraction of the contained carcinogenic hydrocarbons and the pretreatment necessary to allow a good quantitative determination of these potentially hazardous substances. The sampling may be done by filtering a certain volume of air or collecting the sedimentable materials in deposit gauges. In the first case, filters of various nature and porosity are used and the volume of air to be filtered may vary between large limits; but the trend is now to use high volume samplers, two types of which are described. To extract the organic matter from the collected particulates, various solvents may be used, at their boiling point in a Soxlhet apparatus, or at ambiant temperature with the aid of ultra-sonic waves. The solutions, which contain many undesirable products, have to be subjected to a preliminary treatment in order to obtain a purified sample of the compounds to be determined. These treatments include washing with alcaline and acidic aqueous solutions to remove the impurities having phenolic or basic character. Finally, the prepurified solutions may be subjected to various chromatographic procedures, in order to make group separations which simplify the final identification and determination of the individual components present in the initial mixture.


Epidemiological evidence on the carcinogenic risk of air pollution. In summary, higher lung cancer morbidity and mortality in urban than in rural areas and the presence of carcinogens in polluted air suggest that smoking habits and specific occupational exposures cannot account for all the urban air pollution may play a role in this disease. Surveys of lung cancer have shown that differences in excess. Positive correlations between lung cancer death rates and indices of pollution in different places, the experience of migrants and a possibile decline in lung cancer mortality with decline in pollution provide support for the view that air pollution is a factor in this disease. But the effect of pollution cannot be large. It is likely to be a small fraction (possibly a tenth) of the effect of cigarette smoking.


Microbial formation of nitrosopyrrolidine from nitrosoproline. The fate of orally administered NPro was determined in rats. Unchanged NPro could be recovered in the urine, while NPy was detected in the faeces of two of three rats tested. After successive administration of NPro to the same rats, their intestinal contents were inoculated into media containing NPro to test for NPy formation. Decarboxylation of NPro occurred in the faeces cultures from those rats whose faeces had contained NPy. When the faeces from 10 mice were inoculated into the NPro media, all gave negative reactions for NPro decarboxylation. However, when the faeces of eight rats and those of 15 rabbits were tested, two rats and one rabbit exhibited NPy formation. L-Pro and NPro decarboxylase reactions were tested on 24 strains of bacteria and three strains each of E. coli and Proteus mirabilis isolated from rat intestines. It was found that seven bacteria gave a positive reaction with L-pro decarboxylation, while only two species, both belonging to Pseudomonas, could decarboxylate NPro.


Blast injuries to the lungs: clinical presentation, management and course. Five patients with blast injuries to the lungs after bomb explosions are reported. In each patient radiological changes were apparent on the initial chest film taken within 4 hours of the explosions. Arterial hypoxaemia was also present. Four patients were actively treated with continuous positive-pressure ventilation, which was adjudged effective therapy. Two patients died, one owing to bilateral pneumothorax which occurred during anaesthesia, and the other owing to overwhelming infection. Hypoxaemia persisted for 4 months in one of the survivors. Lung function tests which were performed on the same patient 10 monhts after the blast injuries, however, were normal.


Restoration of sensation using a local neurovascular island flap as a primary procedure in extensive pulp loss of the fingertip. A technique using a local composite neurovascular island flap, raised on the volar digital vessels and nerve, is described as a primary procedure for the reconstruction of extensive pulp loss of the fingertip. The results of this technique have been uniformly satisfactory in 8 patients.


A report of a case of non-union following fracture of the neck of the radius. A case of non-union of bilateral fractures of the neck of the radius is reported and their successful treatment by bone grafting.


Mechanisms for the microbicidal activity of cationic proteins of human granulocytes. One oxygen-independent antimicrobial system of human granulocytes consists of granular chymotropsin-like cationic proteins possessing heat-stable microbicidal activity. For elucidation of the mode of action of the cationic protein, effects on bacterial synthesis of macromolecules, ion transport, and oxygen consumption have been studied. Inhibition of incorporation of radioactive precursors into protein, ribonulceic acid, and deoxyribonucleic acid of both Staphylococcus aureus and Escherichia coli was found concomitantly with inhibition of colony formation. Cationic protein inhibited 86Rb+ influx but did not increase the leakage of intracellular 86Rb+, indicating inhibition of energy-dependent membrane transport without a breakdown of the semipermeable character of the membrane. Oxygen consumption was inhibited. Mg2+ and Ca2+ displayed a protective effect against the microbicidal activity, indicating the operation of charge interactions between cationic protein and bacterial surface. The various effects of cationic protein were more pronounced with S. aureus than with E. coli, parallelling the microbicidal activity.


Phage-dependent changes in Shigella flexneri type antigen synthesis. Lysogenic conversion of Shigella flexneri type antigens was studied with the aid of wild-type and thermosensitive mutant phages. With all wild-type phages, the appearance of glycosylated antigen was accompanied by the appearance of polyprenyl phosphate glucose synthetase activity. With some of the mutant phages, the appearance of glycosylated antigen was not followed by the formation of lipid-linked glucose in the enzyme assay. The reverse has also been observed, i.e., the high rate of formation of lipid-linked glucose and the lack of V-type antigen.


Reovirus-like agent (rotavirus) from lambs. Rotavirus particles were demonstrated by electron microscopy in the feces of lambs with diarrhea. Rotavirus antigen was synthesized in cell cultures infected with filtrates of the diarrheic feces, but the virus was not adapted to grow serially in cell cultures. An antigenic relationship between rotaviruses from lambs, pigs, and calves was demonstrated by immunofluorescence. Colostrum-deprived lambs were infected with the lamb rotavirus, and the virus was passaged in lambs. Viral replication occurred in the villous epithelial cells of the small intestine, and the virus was excreted in the feces up to 78 h postinfection. Diarrhea was not observed in the experimentally infected lambs.


Surface properties of extracellular malaria parasites: electrophoretic and lectin-binding characteristics. The surface charge and lectin-binding capacity of isolated malaria parasites and host erythrocytes were analyzed and compared by chromatographic, electrophoretic, and cytochemical methods. Results indicated that at physiological pH values both freshly prepared and glutaraldehyde-fixed parasites and erythrocytes possess a net negative surface charge. Both cell types were strongly bound to cation-exchange resins and underwent cathode-directed electrophoretic migration. The isoelectric points for erythrocyte-free parasites and uninfected erythrocytes were approximately 3.0 and 4.0, respectively. The different effects  of selective enzymatic digestion and solvent extraction on the electrophoretic mobilities of free parasites and erythrocytes suggested that the chemical constituents responsibile for the net negative surface charges on each type of cell are different. The surface charge of the free parasites seemed mainly to be a function of ionized phospholipids rather than of the ionogenic sialic acid moieties, which are the major contributors to the negative charge on erythrocytes. Results of lectin-binding studies indicated that specific glycosidimoieties (i.e., glucose, galactose, mannose, and n-acetyglucosamine), common to the erythrocyte surface, were either absent or in low concentration at the parasite's surface. These observations suggest that the normally intracellular malaria parasites have surface characteristics, differing from those of the host cell, characterized by a scarcity of lectin-binding receptors and sialic acid residues and by the major contribution of lipids to their surface charge.


Hepatic clearance of Candida albicans in rats. The initial clearance of Candida albicans from the blood stream of rats and from perfusion medium by perfused rat livers was characterized. Normal rats cleared over 90% of large doses of intravenously injected yeast cells in 5 min. All were recovered as viable cells among various reticulendothelial organs after 30 min. The perfused rat liver trapped an average of 85% of the yeast cells in a single pass. No significant killing occurred, even in the presence of 10% whole rat blood. Scanning electron microscopy of cryofractured livers revealed that the cells were trapped in liver sinusoids but outside phagocytic cells.


Failure of trehalose-6,6'-dimycolate (P3 or cord factor) to enhance endotoxin lethality in mice. The increased endotoxin lethality in mice pretreated with BCG was not observed in mice pretreated with trehalose-6,6'-dimycolate instead of BCG.


Analysis of T-cell-specific functions in continuous lymphocytic cell lines. II. A T-cell line which forms rosettes with normal thymocytes of the same species. Four T-cell lines of mouse origin (EL-4, S-49, R-1, and L-5178Y) with similar characteristics (Thy-1-positive, and PHA-sensitive) were tested for reactivity with various antigens. EL-4 cells alone were shown to form rosettes at 4 degrees C with thymocytes (positive for either Thy-1.1 or Thy-1.2) and with Thy-1-positive lymph node cells of various mouse strains. Comparable rosette formation did not occur with Thy-1-negative lymphnode cells or red blood cells, nor with rat or rabbit thymocytes. The thymocytes which attached to the tumor cells formed a cluster at one pole of the cell after warming at 37 degrees C for 10 min. After incubation for 40 min at 37 degrees C, most of the rosettes disappeared. This process was blocked by sodium azide and dinitrophenol, suggesting that the movement of thymocytes to one pole of the tumor cell and subsequent release are energy-dependent. These results suggest that the EL-4 cell line, originally derived from a carcinogen-induced lymphoma of C57BL/6, may have been an autoimmune lymphoma reactive against T cells.


Nature of the union between sheep red blood cells and T lymphocytes. Calcium ions acting as salt bridges between the receptor on T lymphocytes and the negatively charged sites on sheep red blood cells (SRBC) are probably involved in rosette formation. Evidence to support this hypothesis includes the results of manipulating the ionic concentration of Ca2+free incubation medium and rosette inhibition in the presence of EDTA. Optimal rosette formation occurred when NaCl was the supporting electrolyte and the ionic strength was 100-150 mM. Neither KCl, CaCl2, MgCl2 nor Na2SO4 were effective as supporting electrolytes.  SRBC pretreated with neuraminidase showed improved rosette formation of lower ionic strength than control cells.


Visualization principles in thin-layer immunoassays (TIA) on plastic surfaces. Macromolecules may adsorb firmly as a monolayer to plastic surfaces and still retain their property to react specifically with antibodies. In the present communication four different principles for visualization of such antigenantibody interactions on plastic surfaces are described. In addition, a diffusion-ingel method for quantitation of antibodies is presented. The described methods offer simple, sensitive and accurate means of assaying antigen-antibody reactions.


[First experiences with BS 100-141, a new antihypertensive substance]. The administration of a new guanidine derivate, BS 100-141, to 20 patients resulted in a statistically highly significant reduction of blood pressure. A comparative clinical trial of BS 100-141 and alpha-methyl-DOPA showed BS 100-141 to be more efficient in lowering the arterial pressure than alpha-methyl-DOPA, especially when the drug was used in the second period of treatment. In the majority of the patients treated with BS 100-141 a slight increase in blood glucose concentration, not exceeding the upper limits of normal values, was found.


Indoprofen in the treatment of osteoarthrosis. A controlled trial in comparison with ibuprofen. A controlled research has been carried out in 39 patients with osteoarthrosis in order to evaluate the efficacy of Indoprofen, a new analgesic-antiinflammatory compound. This product, a phenylpropionic acid derivative, was given by mouth at the dose of 600 mg daily for 7 days. For comparison a treatment with 900 mg daily of Ibuprofen for the same length of time was given to patients according to a double-blind cross-over experimental design. Significant decrease in overall pain intensity was observed together with significant improvement in motility. Indoprofen at the daily dose of 600 mg was comparable in efficacy with 900 mg of Ibuprofen in the relief of pain related to osteoarthrosis. Toleration of the drugs was very good.


Pharmacotherapy with avena sativa - a double blind study. Hundred non-hospitalized smokers with an average consumption of 20 cigarettes per day were treated with an alcoholic extract of Avena sativa for disaccustoming. The study was double blind. By using query-sheets personal contact was excluded. The first result was a placebo-effect of 35% for disaccustoming of smokers and no statistically significant effect of the extract of Avena sativa. The second result was a difference of disaccustoming between light and heavy smokers. It was shown, that the rate of disaccustoming was higher for light smokers than for smokers with a high consumption of cigarettes.


A phase II study of prazosin hydrochloride in hypertensive subjects. The antihypertensive action of Prazosin was studied in 20 hypertensive patients. Sixteen patients completed the 36-week treatment period. The drug produced a gradual and sustained fall in both systolic and diastolic blood pressure. The dosage used was 1 mg TDS. Only 2 patients required 2 mg TDS of Prazosin combined with 1 mg per day of polythiazide, and one of these did not respond. No postural hypotension or weight gain was observed. Side-effects were mild and were not troublesome.


The effects of propranolol, practolol, and placebo on the clinical manifestations of thyrotoxicosis. Thirty patients with thyrotoxicosis were randomly divided into 3 groups of ten which were treated for 8 weeks with either practolol, propranolol or placebo. The pills were administered in a double blind manner and the investigator had the option of doubling the dose at each visit. Propranolol and practolol were equally effective, and better than placebo, at relieving the patients general well-being as well as the tachycardia, subjective and objective tremor, skin warmness and moistness and the intensity of the thyroid bruit.


Photodynamic action of thiopyronine on the respiration and fermentation in yeast. The efficiency of photodynamic treatment with thiopyronine (TP) on the respiration and fermentation of yeast cells, on the metabolic oxygen uptake of isolated mitochondrial preparations from yeast, and on the enzyme activity of alcohol dehydrogenase (ADH) in vivo and in vitro were studied. Respiration was inactivated by treatment with TP and visible light more at the initial stage than was the fermentation. Isolated mitochondria and ADH in vitro were not as sensitive to treatment as were respiration and fermentation in vivo. Inactivation patterns of respiration and fermentation in vivo showed that the inactivation was not due to damage to the DNA. The hindrance of respiration and fermentation might be one of main causes of cell-death resulting from photodynamic treatment.


Cellular mechanisms of tubular protein transport. AT the cellular level different mechanisms have been demonstrated or postulated for the transport and processing of proteins in the epithelium of the proximal tubule. Eight pathways are summarized and numbered in Figure 13: 1. The main transport pathway for proteins consist of endocytosis from the tubule lumen and subsequently lysosomal digestion. 2. Proteins do not pass through the junctional complexes into the intercellular spaces under physiological conditions but may do so in very early embryological stages or if the luminal hydrostatic pressure is experimentally increased. 3. Certain small proteins or polypeptides may be catabolized by membrane digestion at the surface of the brush border membranes. 4. Proteins may normally diffuse retrograde into the intercellular space through the basement membrane and then return unaltered to the peritubular space. 5. Endocytosis from the peritubular cell surface is rare and quantitatively insignificant. 6.-8. There is no convincing evidence for the existence of transcellular transport of intact protein, either directly through the cytoplasm, or by peritubular release of protein-containing lysosomes or endocytic vacuoles.


Clinical comparison of three contrast agents used in cerebral angiography. A total of 139 cerebral angiograms were performed on patients assigned randomly to three groups. The contrast agents used for these groups included meglumine calcium metrizoate, meglumine diatrizoate and meglumine sodium diatrizoate. Pulse rate and blood pressure readings were taken preceding and following injections and pain and heat sensations were graded. There were no significant differences in incidence of nausea or in changes of blood pressure or pulse rate, or in severity of heat sensations. There was a lower incidence of severe injection pain with meglumine calcium metrizoate than with meglumine sodium diatrizoate.


[Results with the second kidney transplantation]. 330 kidneyallotransplantations were performed between 1965-1975 at the Surgical Clinic A of Zurich University Hospital, thereof 31 second set grafts. The one-year-survival rate of the second set recipients was 67% and that of the second set grafts 54%. From our more recent cases we can conclude, that even better results were possible, if retransplantation were planed and attempted an earlier state of graft failure.


Ultrastructural identification of cells storing pancreatic-type glucagon in dog stomach. The oxyntic mucosa of the dog stomach is rich in cells storing pancreatic-type glucagon. The cells were identified by immunocytochemistry and found to be indistinguishable from pancreatic A cells in the electron microscope. Ultrastructural identification of the immunoreactive cells was accomplished by the use of consecutive semithin-ultrathin sections, a technique that permitted the use of optimally fixed material.


Autoradiographic model experiments with 67Ga and 99mTc. In order to evaluate the feasibility to localize correctly 67Ga citrate and 99mTc pertechnetate in tissues, the resolution of these radioactive compounds were measured in a model system using four different autoradiographic techniques, wet as well as dry. Wet autoradiographic techniques gave an almost complete loss of 67Ga. In deparaffinized sections of fixed and paraffin-embedded tissue the remaining 67Ga, which was probably bound to proteins, gave a resolution of 2.6 mu. 99mTc was either completely lost in wet techniques or the procedure could not be performed at all because of the very short half life of 99mTc. The resolution of 67Ga in a dry autoradiographic technique (according to Stumpf) was 6.9 mu and the resolution of 99mTc 22.6 mu. The technique in which frozen sections are thawed on dry film and consequently dryed, gave slightly better resolutions than the dry technique (according to Stumpf) with 67Ga as well as 99mTc. It is concluded that for the histological localization of 67Ga and 99mTc a dry technique is required. However, the use of a wet technique can be considered, provided a loss of the radioisotope is acceptable and the procedure is controlled by a dry technique.


[Reconstruction of the nose following trauma or tumour surgery (author's transl)]. Reliable methods are presented for the reconstruction of various nasal defects following trauma or tumour surgery; they fulfill both functional and esthetic requirements. Pedicle flaps from the immediate surrounding of the defect and particularly from the forehead play a major role. Particularly satisfactory are the fronto-temporal flap for minor defects (mainly for substitution of the ala) and the scalp flap for subtotal or total reconstruction of the nose.


Survey for Salmonellae in porcine bile and cecums and on equipment surfaces in an Ohio abattoir. Porcine bile samples and cecal swabbings and environmental swabbings collected from an abattoir in Columbus, Oh, were examined for salmonellae. Of 40 cecal swabbings, 6 were culture-positive for Salmonella choleraesuis and 2 of 25 swabbings of surfaces that were in contact with edible products were culture-positive for Salmonella typhimurium. All of 500 bile samples were Salmonella-free.


The cellular changes occurring with allografts of marrow-containing cortical bone. The cell population within and around allografts of fresh, marrow-containing cortical bone has been studied. The grafts were implanted into intramuscular sites in rats and removed at intervals over a 4 week period for examination by light and electron microscopy to establish the sequence of changes at both the tissue and cellular levels. The tissue organization and the ultrastructural appearances of the cells found at different times after grafting are described; the possible relationships of the different cell types to each other and their likely roles in both the immunological and histogenic events are postulated and discussed. A comparison of the observations in the allograft and in the previously studied autograft suggests that the cells from the granulationtissue that become osteoblasts in the autograft differentiate into fibrocytes and giant cells in the allograft. Furthermore, the increased period of initial degeneration observed in the allograft (2 weeks) compared with the autograft (less than 1 week) may represent the destruction of early, graft-derived attempts at osteogenesis. This, together with the relative paucity of new bone in the allograft, suggests that some cells of graft origin may contribute to the early osteogenesis observed in the autograft.


Visceral cartilage.

Visceral cartilage. Visceral cartilage is found in the airways and appendages of the respiratory tract. It has a characteristic arrangement at various airway levels. Cartilage maintains the large airways patent and since muscle attachment is in part to cartilage, its arrangement influences the effect of muscle contraction. Bronchi are defined as the airways proximal to the last plate of cartilage. The intra-uterine development of cartilage, its distribution in the adult, change in disease and the bronchial arterial supply of large airways are considered.


On the fixation of catecholamines including adrenaline in tissue sections. Following intravenous or intraperitoneal injections of 3H-l-dopa radioactivity in adrenal medullary chromaffin cells of the mouse has been followed by autoradiographic and radioisotopic assay methods. For autoradiographic purposes tissues were fixed in either phosphate buffered glutaraldehyde or in 1-5% potassium dichromate in glutaraldehyde pH 7-2. A high initial radioactivity is demonstrated by both autoradiography and radioisotopic assay. During the first hour dopamine is the predominant labelled amine. Between 1 and 4 hours after the injection noradrenaline is in highest concentration and from 1 to 24 hours labelled adrenaline appears and becomes the predominant labelled amine (about 70%) after 24 hours. Autoradiographs of tissues fixed in glutaraldehyde alone confirm that adrenaline is lost from sections by this technique. When 1-5% potassium dichromate is added to glutaraldehyde then adrenline is fixed in A cells and these show only a slightly decreased grain count as compared to NA cells at 5 days; this slight decrease is probably due to more rapid turnover of amines by A cells.


A study of psychopathology of parents of psychotic children by structured interview. To improve observer uniformity and objectivity in the psychiatric appraisal of parents of psychotic children, structured psychiatric interviews were administered to 64 parents of psychotic children, including 28 husband--wife pairs and 8 single parents. Judgments were recorded on the Spitzer--Endicott Psychiatric Status Schedule and the past section of their Current and Past Psychopathology Scales. There were no significant differences between fathers and mothers of organic and nonorganic children (children with and without evidence of neurological dysfunction). As a whole, the 56 parents in the 28 participating husband-wife pairs fell between a contrast group of 55 adult subjects attending a psychiatric clinic and another contrast group of 130 subjects living in the community in upper Manhattan in their trends to pathological symptoms as judged by the Psychiatric Status Schedule. Similarly, in the past section of the Current and Past Psychopathology Scales the parents showed a trend to more psychopathology than a community sample of 36 nonpatient adults. Finally, computer diagnoses based on the Psychiatric Status Schedule showed more schizophrenia in the parents of the psychotic children than in a sample of 130 nonpatient adults in the community. The data thus tend to support findings based on the unstructured interview of elevated schizophrenia rates in parents of psychotic children.


Quantitative determination of cholestanol in plasma with mass fragmentography. Biochemical diagnosis of cerebrotendinous xanthomatosis. A simple, sensitive, and accurate method for determination of cholestanol in plasma is described. In this method a fixed amount of cholestane is added to 1 ml of plasma as an internal standard and steroids are saponified and extracted with n-hexane. The amounts of cholestanol and cholesterol are determined by mass fragmentography by monitoring the intensities of m/e 306, m/e 329, and m/e 372 fragment ions. The relative standard deviation of results for cholestanol was about 6.3%. The cholestanol concentrations in the plasma, erythrocyte stroma, and plasma lipoproteins of three patients with cerebrotendinous xanthomatosis were determined by this method.


Propidium diiodide-cesium chloride density gradient centrifugation for buoyant separations of duplex DNA molecules containing single-stranded regions. At increasing dye concentrations in propidium diiodide-CsCl density gradients, the relative buoyant density shift was largest for open-circular duplex phiX174 DNA (RFII), next largest for single-stranded viral DNA, and least for closed-circular duplex DNA (RFI). These differential relative buoyant density shifts permitted discrete separations of these phiX DNA forms. Further, in propidium diiodide-CsCl density gradients, the distinctive density of single-stranded DNA permitted separations of rolling-circle intermediates with a single-stranded tail that occur during single-stranded phiX DNA synthesis. It is suggested that single-strandedness in a duplex DNA structure influences its buoyand density shift due to differential dye binding to the single-stranded region and is an additional physical basis for relative buoyant separations of DNA molecules in propidium diiodide-CsCl density gradients.


Conformational changes and reassociation properties of small subunits of Escherichia coli ribosomes. Studies on the reassociation of ribosomal subunits from Escherichia coli were carried out using an ultracentrifuge equipped with a UV absorption scanner, and the conformational changes of ribosomal subunits were followed by circular dichroism measurements. Reassociation between the fractionated 30S and 50 S subunits was promoted by the addition of uncharged tRNA at 4 degrees. Furthermore, a sharp increase in the amount of reassociated products was observed on treatment of the sample solution at temperatures above 25 degrees. Treatment at higher temperature only affected 30 S ribosomal slbunits. From CD measurements of Mg2+ concentration dependence for both ribosomal subunits, a significant decrease in molar ellipticity [theta] at the 264 nm positive peak and a slight change of [theta] at the 222 nm band were observed for both subunits in dissociation buffer. Samples of 30 S subunits pretreated at 37 degrees for 40 min showed a small CD change at the 222 nm band. The same samples showed a slight increase in S value and enhanced ability to form 70 S particles with 50 S subunits. On the other hand, we detected no significant changes in CD spectra, S value or the ability to form 70 S particles with 50 S ribosomal samples subjected to same heat treatments.


Biosynthesis of norvaline, norleucine, and homoisoleucine in Serratia marcescens. The biosynthetic pathways of norvaline homoisoleucine were examined using regulatory mutants of leucine biosynthesis in Serratia marcescens. alpha-Isopropylmalate synthetase [EC 4.1.3.12], the first enzyme of leucine biosynthesis, catalyzed the condensations of acetyl-CoA with pyruvate, alpha-ketobutyrate, alpha-ketovalerate, or alpha-keto-beta-methylvalerate as well as alpha-ketoisovalerate. These condensations were inhibited by leucine in the alpha-aminobutyrate-resistant mutant, a mutant with derepressed leucine biosynthetic enzymes. However, these condensations were coordinately desensitized in the isoleucine leaky revertant, a leucine accumulator. The formation of norvaline or homoisoleucine was greater in the leucine accumulator, but its leucine auxotroph did not form these unnatural amino acids. Thus, norvaline and homoisoleucine are considered to be formed from alpha-ketobutyrate and alpha-keto-beta-methylvalerate by the leucine biosynthetic enzymes. This view was confirmed by the findings that a norvaline accumulator could be obtained by derivation of the leucine accumulator into an isoleucine-valine auxotroph. Norleucine was also found to be formed from alpha-ketovalerate, an alpha-ketoacid corresponding to norvaline.


Nucleotide sequence and in vitro processing of a precursor molecule to Escherichia coli 4.5 S RNA. A precursor molecule to the stable 4.5 S RNA species of Escherichia coli has been found to accumulate at 42 degrees in a strain thermosensitive for the function of ribonuclease P. The precursor molecule is 130 nucleotides long. Twenty-two extra nucleotides, starting with pppGp, precede the mature sequence at its 5' terminus. At least 1 extra uridine residue can be found at the 3' terminus. The precursor to 4.5 S RNA is cleaved in vitro by RNase P to generate a 5' end identical to that of the mature 4.5 S RNA.


Lipid-protein interactions in Escherichia coli. Membrane-associated f1 bacteriophage coat protein and phospholipid metabolism. The effects of insertion of the major coat protein of f1 bacteriophage into Escherichia coli membranes were investigated. The relative level of phosphatidylethanolamine decreased due to the failure to accumulate phosphatidylethanolamine when the cellular levels of phosphatidylglycerol and cardiolipin were increasing. This decreased accumulation was correlated with a 4-fold reduction in phosphatidylethanolamine synthesis. A 10- to 20-fold increase in cardiolipin content resulted from both a 3-fold increase in cardiolipin synthesis and a decrease in cardiolipin turnover. As long as cell division and protein synthesis continued, the number of cardiolipin molecules per coat protein molecules in the bacterium attained a constant value. The coat protein had little effect of phosphatidylglycerol synthesis. This data suggests that the coat protein froms a specific association with cardiolipin in the host membranes. Additional evidence suggests that cardiolipin also may facilitate the entry of coat protein into membranes.


Biosynthesis of bacterial glycogen. Activator-induced oligomerization of a mutant Escherichia coli ADP-glucose synthase. ADP-glucose synthase (EC 2.7.7.27) was purified to homogeneity from SG5-504, Aa mutant strain of Escherichia coli B. It had a molecular weight of approximately 2 X 10(5) and four identical subunits. In the presence of its allosteric activator, fructose-1-6-P2, the mutant enzyme formed oligomers with several times the tetramer molecular weight, as revealed by sedimentation equilibrium centrifugation, polyacrylamide gel electrophoresis, and gel filtration column chromatography. Enzyme purified from a wild type strain, AC70R1, did not exhibit the activator-induced oligomerization. Catalytically, the mutant enzyme had a 2-fold higher affinity for activator and a 2- to 3-fold lower affinity for the allosteric inhibitors 5'-adenylate and KH2PO4 than the wild type. The two enzymes appeared identical in subunit molecular weight, amino acid composition, COOH-terminal amino acid, and the first 27 residues of the NH2-terminal sequence. Subtle structural differences were revealed by chemical modification of specific residues. Compared to wild type, the mutant enzyme had 1 cysteine/subunit more accessible to modification by Ellman's reagent. SG5-504 enzyme was inactivated more slowly than AC70R1 enzyme by phenylglyoxal and by trinitrobenzenesulfonate. These results reflected an altered conformation of the SG5-504 enzyme molecule. The unique ability of it to oligomerize in the presence of activator may be the result of a single amino acid substitution.