Inhibition of prolactin  secretion and synthesis by dopamine, noradrenaline and pilocarpine in cultured rat pituitary tumour cells. Clonal strains of rat pituitary tumour cells (GH3-cells) synthesize and secrete prolactin into a chemically defined culture medium. Short time treatment (0.5-2 hrs) of cell cultures with noradrenaline (10(-3) M) and dopamine (10(-3 M) reduced the spontaneous secretion of prolactin by 50% and 30%, respectively, while pilocarpine (10(-3) M) had no effect. Long-term treatment (20 hrs) with noradrenaline (10(-3)M) or with pilocarpine (10(-3) M) inhibited prolactin synthesis by 45% and 65% of control cultures, respectively. Neither compounds affected  cell growth. The inhibitory effect of noradrenaline, but not that of pilocarpine, was completely reversed 4 hrs after cessation of treatment. Adrenaline, dopamine and acetylcholine in concentrations up to 10(-3) M did not change prolactin synthesis. In contrast thyroliberin treatment (2 X 10(-8)M) caused a 45% increase in prolactin secretion, and resulted in a 40% increase in hormone synthesis after treatment for 20 hrs. It is concluded that both noradrenaline and dopamine are able to inhibit prolactin section. Prolactin synthesis could be inhibited by noradrenaline and pilocarpine. How, only the effect of noradrenaline is easily reversible on cessation of treatment.


Absence of restricted diffusion in cutaneous capillaries. Capillary permeability in cutaneous tissue for 57Co-cyanocobalamin (57 Co-B12) was determined by the single injection, external registration method. The capillary diffusion capacity, CDC (the permeability--surface area product, PS) was 2.3 ml/100 g-min. Capillary extraction was 0.48 at a plasma flow of 4.1 ml/100 g-min. Results were compared to 51Cr-EDTA data from a previous study with identical method and preparation. As CDC(51Cr-EDTA)/CDC(57Co-B12) was 1.61 and as D(51Cr-EDTA)/D(57Co-B12), the ratio between the free diffusion coefficients in water at 37 degrees C, was 1.79 it is concluded that restricted diffusion does not occur in cutaneous tissue for 57Co-B12 as compared to 51Cr-EDTA, i.e. 51Cr-EDTA and 57Co-B12 diffuse across the capillary membrane of cutaneous tissues at rates proportional to their respective free diffusion coefficients in water. The Pappenheimer equivalent pore radius estimate of 30 A and the Karnovsky interendothelial 40 A slit width are both defective in explaining the experimental data. The transendothelial patent  channel system of fused vesicles (Simionescu, Simionescu and Palade 1975) is a possible structural equivalent for the present findings. The results support the hypothesis that capillaries of continuous type exhibit similar permeation characteristics regardless of the tissue in which they are located.


Low-dose insulin treatment of diabetic ketoacidosis. Twenty-four consecutively admitted episodes of acute diabetic dysregulation in 22 patients were treated with a low-dose insulin regimen, given as hourly i.m. injections of 5 IU insulin. The fall in blood glucose was almost linear during the first 8 hours of treatment, on an average 10 percent per hour of the initial value. The hyperglycemia and acidosis were corrected by 2-12 hours of treatment. The deficiency of water and electrolytes, especially potassium, was treated with infusion from the beginnning, and the fluid balance was corrected within 12-16 hours. A severe fall in plasma potassium was never seen, but hypokalemia (less than 3.6mEg/I) was still present in some cases after 24 hours of treatment. One patient died on account of a large myocardial infarction, but otherwise the patients were restored to habitual condition in 1-4 days. The regimen was found to be simple, safe and effective in all cases, without risk of late hypoglycemia or severe hypokalemia. The study indicates, however, that the parenteral supply of potassium advocated previously, 12.5 mEq/hour, is not sufficient when the plasma potassium on admission is below 5.0mEq/I. In such cases it is recommended that the rate of potassium infusion is increased.


The dynamic shear modulus of bone in dependence on the form. Torsional testing of fresh cortical bovine bone showed highly divergent shear moduli at various sites in the middle part of the diaphysis of the right metacarpus. Two hundred samples taken from twenty-five bones were investigated with a free oscillating torsional pendulum to determine the dynamic shear modulus. The results clearly demonstrate the mutual dependence between the shape of the metacarpus and the modulus of the material. On the basis of the analysis of forty-eight samples, a positive correlation was found between the amount of Ca2+ and PO4(3)-ions in the bone and the shear modulus. The hypothesis is put forward that in bone, normal adaptation to increasing stress is obtained by a change in the modulus values, Wolff's law only being operative for extreme cases.


Chromosomal damage by alcohol in vitro and in vivo. Alcohol has no damaging effects on human chromosomes in vitro. The chromosomes of alcoholics, however, show a significant elevation of aberrations. Alcohol inhibits cellular and cell free RNA synthesis. One possible reason for the mutagenic activity of alcohol in vivo may be an inhibition of cellular repair.


Possible genetic predisposition for alcohol addiction. In a group of male addictive alcoholics, some palmar and fingerprint characteristics were determined, as well as the ABO, MN, Ss, Kell, Duffy, Lewis, and P blood groups, Rh and Hp phenotypes, HLA and Au antigens, immunoglobulins, blood sugar, cholesterol, SGOT, SGPT, and karyotypes. In comparison with the normal population the alcoholics show increased occurrence of whorls and arches on the fingers, decrease in the total ridge count, sharpening of the atd angle, and separation of the lower from the upper transverse line. Genetic markers in the blood of alcoholics show different frequencies of A, Lewis a-b+, Lewis a-b-, Duffy a-, Duffy a+, SS, and M blood groups, CcD-ee, Hpl-1, Hp2-1 phenotypes, and HLA-5, HLA-7, w10, w16, and w5 antigens. These findings may be expected to lead soon to detection of the predisposition to the development of alcohol addiction caused by some genetic malformations.


Introduction of new crosslinks into proteins. Analysis of the crosslinks epsilon-(gamma-glutamyl) lysine and epsilon- (beta-aspartyl) lysine present in treated wool has been improved by modifying the enzymic digestion. Treatment of wool with either monocarboxylic acid chlorides in dimethylsulfoxide or with 1-fluoro-2,4-dinitrobenzene in the presence of acetate considerably decreased epsilon-amino groups and solubility. Since no information of interchain amide crosslinks was observed, the hypothesis of so-called self-crosslinking postulated by ZAHN has to be withdrawn. The effects of both treatments are explained in the light of new results. The reaction of wool with glutaraldehyde leads to a stabilization of the fiber. Experiments with glutaraldehyde and  primary alkyl amines as model componds revealed that the cyclic form of the aldehyde gave the unstable N-alkyl-2,6-dihydroxypiperidine, which either looses water to give N-alkyldihydropyridine or condenses with 2,6-dihydroxytetrahydropyran to yield a copolyether which was isolated. According to recent publications, crosslinking of proteins by glutaraldehyde is due to the formation of quaternary pyridinium compounds.


Chemical modificiation of collagen and the effects on enzyme-binding: mechanistic considerations. The effect of structural modification on the enzyme-binding capacity of collagen has been studied using beta-galactosidase (E. coli K12) immobilized to collagen membrane by the impregnation procedure. The apparent steady-state activities of the resultant collagen-enzyme complexes were determined as a means of evaluating the enzyme-binding capacity of the modified collagen. In addition, the amount of enzymic protein bound to the collagen support was determined by the tryptophan content of the complex. The tertiary structure of the collage matrix was modified by cross-linking with the difunctional reagent, glutaraldehyde, and by aging in the dry state. Such structural modifications were found to markedly reduce the enzyme (beta-galactosidase) binding capacity of collagen films. The enzyme-binding capacity of the crosslinked collagen membrane was completely restored by proteolytic enzyme treatment of the aged film but only partly so for the glutaraldehyde treated films. Proteolytic enzymes used to treat a dispersion of collagen microfibrils prior to casting into a membrane also resulted in an increase in enzyme-binding. The effect of structural modification of collagen on enzyme-binding and the locus of enzyme attachment are discussed.


Further characterization of the sensitizing bursa cells and of the target for suppression in the transfer of agammaglobulinemia. Presensitization of BX donors with B cells appears obligatory in order for their T cells to acquire suppressor capacity against the adoptive humoral antibody response of bursa cells to B. abortus. Although anti-Ig + C treatment of bursa cells removes their capacity to "immunize" BX chickens for suppressor activity, BX chickens cannot be sensitized for this effect by the injection of chicken IgM + IgG. Both embryonic and allogeneic bursa cells can "immunize" the T cells of BX chickens. The observation that spleen cells from BX chickens can cause absence of plasma cells and germinal centers in the spleen and mucosal lining of cecal tonsils of histocompatible recipients within 1-2 weeks after transfer suggests that the suppressor cells mediate their effect by acting directly on B cells at one or more stages during their development.


Prophylactic chelation therapy in occupational lead poisoning: a review. Chelating agents are useful in the therapy of acute overexposure to lead. However, prophylactic use of chelating agents, particularly under conditions of continued exposure to lead can be harmful to health. Potential adverse effects include kidney damage, symptomatic lead poisoning, increased absorption of lead from the gastrointestinal tract and disruption in the metabolism of trace metals other than lead. Prophylactic chelation is an unacceptable medical practice which cannot be condoned.


Hemodynamic advantage of combined administration of hydralazine orally and nitrates nonparenterally in the vasodilator therapy of chronic heart failure. Patients with severe left ventricular failure generally have both reduced cardiac output and increased pulmonary and systemic venous pressures. A study was therefore made of the use of combined vasodilator therapy with nonparenterally administered nitrates, which act primarily on venous capacitance vessels and thus reduce preload, and orally administered hydralazine, which acts on arteriolar resistance vessels and thus reduces afterload. Twelve patients with chronic refractory heart failure were given these drugs individually and in combination during continuous hemodynamic monitoring. Heart rate and arterial pressure did not change significantly. Nitrates significantly reduced filling pressures of both ventricles without affecting cardiac index. Hydralazine did not alter filling pressures but dramatically increased cardiac index. The hemodynamic effects of each drug were additive during combined therapy, resulting in a 36 percent (28 to 18 mm Hg) mean decrease in left ventricular filling pressure and a 58 percent (2.1 to 3.3 liters/min per m(2)) mean increase in cardiac index. The seven patients who have continued to receive combined therapy for 3 to 10 months have shown sustained clinical improvement.


Immunologic quantitation of serum immunoglobulins. The methods available in the clinical laboratory for measuring serum immunoglobulins (G, A, M, and D) include radial immunodiffusion, electroimmunodiffusion and nephelometry. All these immunochemical technics require specific antisera and stable standards for reproducible and accurate results. Discrepancies between the quantity of protein measured by any of these technics and the actual chemically or physically measured quantity arise when the unknown and standard differ in molecular size, electrophoretic mobility, or antigenic valence. These differences may lead to over- or under-estimation of the quantity of immunoglobulin. Quantitation of immunoglobulins, especially in context with protein electrophoresis, does provide useful information for diagnosis and treatment of selective disorders.


Serologic studies of the diagnosis and nosology of human leukemia. Nonhuman primate antisera to human leukemia-associated antigens and to normal T- and B-lymphocyte antigens are useful reagents for detecting and classifying leukemic cells in a microcytotoxicity assay. These antisera are able to distinguish lymphocytic from myeloid leukemia cells, and can also identify acute myelomonocytic leukemia and chronic myelocytic leukemia blastic crisis cells from cells of other types of leukemia. The advantages and disadvantages of the reagents in the nosology and clinical management of leukemia patients are discussed in depth. However, despite certain shortcomings in the microcytotoxicity assays, the reagents and method do provide the necessary tools for antigenic isolation and identification. Purified antigen may then serve to open new horizons in the detection, diagnosis, classification and perhaps therapy of human leukemia.


Cost effectiveness of renal disease screening. Diseases of the kidney and their complications represent a major cause of disability and death. Search for evidence that the prognosis for a substantial portion of patients with chronic renal disease might be effectively influenced by early screening has been largely unrewarding. There is limited evidence that the progressive course of many chronic renal diseases can be arrested by presently available therapeutic methods. Thus, except for detection of bacteriuria in pregnant women, it would seem unreasonable to seek early identification. In addition, screening of asymptomatic individuals may create unnecessary, serious, economic and psychosocial problems for the many patients with benign or transient urinary abnormalities.


Alpha heavy-chain disease in southern Iran. A prospective study of 32 patients with primary upper small intestinal lymphoma in our region revealed 10 cases of alpha heavy-chain disease. Patients were mostly in the second and third decades of life and males predominated. Weight loss, diarrhea, and abdominal pain were the most common complaints and clubbing the most frequent physical findings. Laboratory tests revealed a malabsorption pattern on intestinal x-rays, and malabsorption of xylose, fat, and vitamin B12 was frequently noted. Dense plasmacytic infiltrate of the lamina propria of small bowel was the most frequent pathologic finding while true neoplasm of the lymphoid system (ie, immunoblastic sarcoma) was encountered in 20% of the cases.


Clinical use of 10% soybean oil emulsion. The pharmaceutical and therapeutic aspects of the use of 10% soybean oil emulsion in total parenteral nutrition (TPN) are reviewed. The composition of the commercial preparation (intralipid), comparison with cottonseed oil emulsion, advantages and disadvantages of use, metabolism, toxicity, therapeutic monitoring, clinical uses, and evaluative studies are discussed. Soybean oil emulsion is a useful source of calories and essential fatty acids in TPN. The product is more expensive than other solutions used in TPN. Woybean oil emulsion should be considered for use in small hospitals and in home therapy because of the advantage of peripheral administration.


Clinical response of patients with gonococcal endocervicitis and endometritis-salpingitis-peritonitis to doxycycline. The clinical response to single-drug therapy with doxycycline was evaluated in 25 patients with gonococcal endoceruicitis and was correlated with the bacterial isolates present within the cul-de-sac. The 10 patients with gonococcal salpingitis salpingitis and the three patients with gonococcal peritonitis exhibited excellent clinical responses. When polymicrobial infection coexisted with gonococcal peritonitis or functioned without the concomitant presence of Neisseria gonorrhoeae, a significantly altered therapeutic response was observed in four of the 12 patients. Four patients in this grouping exhibited either secondary temperature elevations or lack of a significant alteration of the white blood cell count, two features which were not characteristic of the patients with either gonococcal salpingitis or peritonitis. In the cases of polymicrobial peritonitis, there was a poor correlation between ensuing clinical response and in vitro resistance of one or more cul-de-sac isolated to doxycycline. The presence of a resistant organism did not preclude a good or satisfactory clinical response. The absence of a resistant organism correlated well with a good clinical response.


Regulation of tension in skinned muscle fibers: effect of high concentrations of Mg-ATP. The control of tension in skinned fibers by Mg-ATP and Ca described in previous publications has been studied at high substrate concentrations over a wide range of temperature and salt concentration. Curves of tension versus pCa shift systemically to the right as [Mg-ATP] increases. The maximum Ca-activated tension of a skinned fiber declines at sufficiently high substrate concentrations. This behavior is described by a generalization of the scheme given in the earlier reports.


Inhibition of dopamine-induced release of growth hormone by thyrotropin-releasing hormone. The effects of thyrotropin-releasing hormone (TRH) and dopamine (DA) on serum growth hormone (GH) levels were examined in the adolescent male baboon. Intravenously administered DA (40 microgram/kg-min-1 for 20 min) raised serum GH and glucose and lowered serum insulin concentrations but caused no increase in blood pressure. Concomitant intravenous infusion of TRH at 2 doses (96 ng/kg-min-1 and 40 microgram/kg-min-1 for 20 min) blocked the DA-induced increase in serum GH. The relatively low effective doses of TRH used to suppress the DA-induced GH increase suggest an interaction with catecholamines at the hypothalamic and/or pituitary to influence GH release.


Endocrine activation and altered muscle metabolism after hemorrhagic shock. Studies were conducted to examine glucose and amino acid metabolism by skeletal muscle isolated from rhesus monkeys before and sequentially after an episode of resuscitated hemorrhagic shock. After shock and reinfusion, the tissue exhibited decreased effect of insulin on glucose utilization increased leucine oxidation, and a reduced rate of leucine incorporation into protein. These changes were observed 15 min after reinfusion and persisted in part for at least 3 days. All of the observed abnormalities were more pronounced 24 h after shock and reinfusion than 15 min after and returned to normal by 2-4 wk. The shock-induced metabolic abnormalities in skeletal muscle occurred in spite of prevention of shock-induced adrenal steroid and catecholamine secretion and of changes in blood insulin concentration using adrenalectomized-streptozotocin diabetic monkeys receiving replacement cortisol and insulin infusions. This study thus demonstrated that hemorrhagic shock in rhesus monkeys was followed by insulin resistance plus abnormalities of glucose and amino acid metabolism by skeletal muscle that were not dependent on the concurrent changes in plasma levels of adrenal steroids or catecholamines or on altered circulating insulin levels associated with shock.


Cortisol-mediated synchrinization of circadian rhythm in urinary potassium excretion. Conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 h daily (LD 12:12) display a prominent circadian rhythm in renal potassium excretion. The characteristics of this rhythm were reproduced in adrenalectomized monkeys by infusing 5 mg cortisol and 0.001 mg aldosterone, or 5 mg cortisol alone, between 0800 and 0900 h daily. When the timing of cortisol adminisration (with or without aldosterone) was phase-delayed by 8 h, the urinary potassium rhythm resynchronized by 80% of the cortisol phase shift, but only after a transient response lasting 3-4 days. With the same daily dose of adrenal steroids given as a continuous infusion throughout each 24 h, urinary potassium excretion showed free-running oscillations no longer synchronized to the light-dark cycle. These results indicate that the cirdacian rhythm of plasma cortisol concentration acts as an internal mediator in the circadian timing system, synchronizing a potentially autonomous oscillation in renal potassium excretion to environmental time cues and to other circadian rhythms within the animal.


Mechanical work in terrestrial locomotion: two basic mechanisms for minimizing energy expenditure. The work done during each step to lift and to reaccelerate (in the forward direction) and center of mass has been measured during locomotion in bipeds (rhea and turkey), quadrupeds (dogs, stump-tailed macaques, and ram), and hoppers (kangaroo and springhare). Walking, in all animals (as in man), involves an alternate transfer between gravitational-potential energy and kinetic energy within each stride (as takes place in a pendulum). This transfer is greatest at intermediate walking speeds and can account for up to 70% of the total energy changes taking place within a stride, leaving only 30% to be supplied by muscles. No kinetic-gravitational energy transfer takes place during running, hopping, and trotting, but energy is conserved by another mechanism: an elastic "bounce" of the body. Galloping animals utilize a combination of these two energy-conserving mechanisms. During running, trotting, hopping, and galloping, 1) the power per unit weight required to maintain the forward speed of the center of mass is almost the same in all the species studied; 2) the power per unit weight required to lift the center of mass is almost independent of speed; and 3) the sum of these two powers is almost a linear function of speed.


Effects of colchicine on phagosome-lysosome interaction in retinal pigment epithelium. II. In vitro observations on histio-organotypical retinal pigment epithelial cells of the pig (a preliminary report). Phagocytic activity of histiotypical and organotypical retinal pigment epithelial cells was studied by SEM and EM. After a latent period polystyrene microspheres of different diameter were captured by newly formed microvilli. No mechanism of discrimination according to the size of microspheres was observed. After engulfment, microvilli of histiotypical cells decreased in length and finally disappeared. Lysosomes increased in number when compared to unstimulated cells and fused with many latex-containing phagosomes. Colchicine, when added at 5 X 10(-5) M to the medium, inhibits phagosome-lysome interaction, thus confirming in vivo observations.


Glycogen and development of outer segment in monkey fetuses. Glycogen particles in developing photoreceptors were investigated in monkey fetuses of various ages under the electron microscope. Glycogen particles were first observed at 100 gestational days in primitive outer segment sacs and inner segments, prior to the appearance of tubulous disc membranes in the peripheral region of outer segment sacs. The particles gradually increased in number as the outer segments differentiated, decreased in number by 143 gestational days, and finally disappeared in the photoreceptors by 160 gestational days, when the photoreceptors were almost formed as in adult monkeys. It is therefore postulated that glycogen particles seen in the photoreceptors are closely concerned with the rapid differentiation of outer segments for a short duration in the developing stages.


[Sarcosporidias of cloven-hoofed wild animals. Sarcosporidias in wild deer]. 500 adult roes and 100 fawns were examined microscopically for the presence of Sarcocystis gracilis von Ratz, 1901. 95.80 per cent of the roes examined had Sarcosporidias. The parasites were noticed macroscopically in less than a third of them. The abdominal muscles were affected most frequently and most strongly. The leg muscles were affected least of all. Roe bucks were affected to a lesser extent than does. From the third month of life the fawns showed an incidence of parasites which increased with advancing age. During the period of research from May till November hardly any significant difference of parasitical attack occurred in adult roes.


[Radial complement fixation test and convex lens method for the determination of antibodies in tissues]. The radial complement fixation test has to be made in forms in 1.4% layer of agar in physiological saline in a Petri dish. These forms have to be of the same thickness as the reaction itself, usually about 1 mm. In the first layer, it is recommended to mix antigen with complement and sheep erythrocytes in agarose and this mixture is to be poured over the tissue fragments examined. Following the primary incubation (at room temperature overnight), another mixture of haemolysin in agarose is poured over the first layer in form of optical convex lenses. The haemolytic phase is performed at room temperature, too. The complement is titrated together with the optimal amount of antigen and a drop of positive serum is placed in the well just in the centre of the first layer. In this way an optimal dilution of complement is detected, which is capable of producing a full hemolysis outside the zone of the positive serum diffused during the first, primary incubation period, whereas the zone itself remains untouched with the haemolytic activity of complement.


Behavioural and hormonal responses of male rhesus monkeys introduced to females in the breeding and non-breeding seasons. Six adult male rhesus monkeys were introduced individually to an all-female group for 10 days during the mating season. The initial aggressive responses of the females were rapidly replaced by positive social behaviour, and each male achieved alpha status and had access to social and sexual partners. A repetition of this paradigm in the non-breeding season produced significantly more female aggression, and no male attained high rank or engaged in sexual or other social behaviour. Male testosterone levels rose following introduction to the females in both seasons, but were significantly higher during the breeding season. Hormonal levels following removal from the females suggest a complex interplay between social, sexual and seasonal variables and recent social experiences. The differences in female social behaviour with newly introduced males, as a function of season, suggest an explanation for the seasonal limitation of male troop transfers.


Cromolyn sodium prophylaxis in asthmatic children under five. A technique for the administration of cromolyn sodium in 58 severely afflicted asthmatic children is described. This technique offers no difficulty in the youngsters and had no observable side effects.


Comparison of aerosolized atropine, isoproterenol, atropine plus isoproterenol, disodium cromoglycate and placebo in the prevention of exercise-induced asthma. In 15 asthmatic children post-exercise bronchospasm was partially inhibited by placebo and by aerosolized atropine sulphate (1 mg) compared with no treatment, not significantly inhibited by atropine alone compared with placebo, partially blocked by disodium cromoglycate (20 mg) and by isoproterenol (0.625 mg) and completely blocked by the combination of isoproterenol and atropine. Pre-treatment with isoproterenol or atropine resulted in post-exercise values for specific conductance which were significantly greater than those following disodium cromoglycate by virtue of the bronchodilator effect of these drugs independent of or in addition to any specific inhibition of exercise-induced asthma. These results suggest that the bronchoconstrictor response to exercise is partially influenced by suggestion but is influenced to a significantly greater degree by mediator release and beta-adrenergic mechanisms and that bronchodilator drugs have therapeutic advantages over an inhibitor of mediator release in the prevention of exercise-induced asthma.


Dual asthmatic responses to prosopis juliflora. Case histories of two asthmatic patients who are allergic to the pollen allergen of Prosopis juliflora, a perennial tree abundantly seen in Delhi and northern India, are presented. Both developed immediate (Type I) as well as late (Type III) responses to intradermal, as well as inhalation, provocation tests. Prior inhalation of disodium cromoglycate inhibited the dual asthma response to inhalation tests but did not inhibit the response to intradermal tests.


Refractometry as a measure of the immunoglobulin status of the newborn dairy calf: comparison with the zinc sulfate turbidity test and single radial immunodiffusion. Immunoglobulins were quantitated by single radial immunodiffusion in 34 female Holstein-Friesian calves which had been kept with their dams for the first 24 hours of life. The mean immunoglobulin G1 (IgG1) concentration was 1.063 g/dl; IgG2, 0.093 g/dl; IgM, 0.171 g/dl; and IgA, 0.125 g/dl. Both serum total protein as measured by refractometer and zinc sulfate turbidity measured at 498 nm gave good correlations with total protein, which were significant, P less than 0.001. Plasma total protein had a slightly poorer correlation with total immunoglobulins, presumably due to variable fibrinogen content. Plasma total protein gave a better correlation with total immunoglobulins than did any of the immunoglobulin classes individually. Total protein by refractometer underestimated naturally occurring or added immunoglobulins by one-third.


Comparison of cardiorenal functions between women and female rhesus macaques. Selected cardiorenal functions for conscious and chaired rhesus macaques were compared directly and indirectly with corrections for body weights and surface areas to well-established base-line values for human subjects. Certain functional differences between species and conditions of measurement do not allow all experimental results from the rhesus macaque to be extrapolated to man. However, this comparative study provides evidence that can be useful in attempting to evaluate cardiorenal data from macaques in relationship to human studies.


Bactericidal activity of streptomycin, isoniazid, rifampin, ethambutol, and pyrazinamide alone and in combination against Mycobacterium Tuberculosis. Log-phase cultures of Mycobacterium tuberculosis in Tween-albumin medium were exposed to streptomycin, isoniazid, rifampin, ethambutol, and pyrazinamide in concentrations in the range likely to be present in serum during treatment of patients. The bactericidal activity of the drugs was measured as the decrease in viable counts at 4 and 7 days. The activity of single drugs was highest for streptomycin and next highest for rifampin and isoniazid, but ethambutol only started to kill after 4 days. When exposed to 2 drugs, bactericidal synergism was found with streptomycin/isoniazid and isoniazid/ethambutol; additivity, with streptomycin/rifampin; indifference, with isoniazid rifampin and streptomycin/ethambutol; and antagonism, with rifampin/ethambutol and isoniazid/pyrazinamide. When cultures were exposed to the 3 drugs, isoniazid, rifampin, and ethambutol, marked antagonism was found between isoniazid and rifampin, whereas the addition of isoniazid or an increase in its concentration increased the bactericidal activity.


Drug resistant tuberculosis in a large southern California hospital. Rates of in vitro resistance to antituberculous drugs were examined for all patients hospitalized with active tuberculosis between January 1969 and December 1972, and between March 1975 and September 1976. During the former period, in 31.5 per cent of patients, tuberculosis was resistant to one or more drugs, and in 12.3 per cent of patients was resistant to 2 or more drugs. During the latter period, 35.5 per cent of patients had tuberculosis that was resistant to one or more drugs, and 19.6 per cent had tuberculosis resistant to 2 or more drugs. Resistance to isoniazid and ethambutol increased significantly, whereas resistance to para-aminosalicytic acid decreased. Age, national origin, and length of residence in the United States were not good predictors for the presence of in vitro resistance.


[Resistance to streptogramin antibiotics in "Staphylococcus aureus" (author's transl)]. Pristinamycin and virginiamycin, two antibiotics belonging to the streptogramin group, are widely used in France against staphylococcal infections. They are mixtures of two different active compounds, pristinamycin I and II, virginiamycine S and M. The present study describes five clinical isolates of Staphylococcus aureus with unusual resistance to these antibiotics. This resistance, whose level is variable according to the strains, concerns both compounds of these antibiotics. It is lost at high frequency spontaneoulsy or after treatment by curing agents, suggesting that the resistance is plasmid mediated. The drug inactivation by the resistant strains supports the hypothesis of an enzymatic mechanism of resistance. Furthermore, this new resistance seems to be linked, in some strains, to either of the two aminoglycoside resistance patterns recently described in S. aureus.


[Validity of quantitative protein A determination of "Staphylococcus aureus" by radial immunodiffusion]. The validity of quantitative determination of protein A by radial immunodiffusion has been tested using human serum, human IgG and porcine serum. The best results are obtained with porcine serum. Maximal sensitivity is obtained after 48 h of incubation with 15 microliters of porcine serum per 13 ml of gel. For these particular conditions the range of linearity varies between 20 and 300 microgram/ml.


The frequency in Japanese of genetic variants of 22 proteins II. Carbonic anhydrase I and II, lactate dehydrogenase, malate dehydrogenase, nucleoside phosphorylase, triose phosphate isomerase, haemoglobin A and haemoglobin A2. This paper presents the results of a survey of Japanese for electrophoretic variants of CA I, CA II, LDH, MDH, TPI, NP, HB A and A2, the number of determinations per system ranging from 738 to 4029. Four similar variants of CA I (designed CA IHIR1), one of LDH (designated LDHNGS1), one of MDH (designated MDHS 7HIR1), two of HB A (one a reascertainment of HB Hijiyama, the other not characterized), and one characterized by the absence of HB A2 (delta-thalassaemia) were observed and are described. The CA IHIR1, LDHNAG1 and MDHS 2HIR1 variants have not been previously observed in Japan. No electrophoretic variants were found in the TPI and NP systems.


Systematic variation in early hominid corpus dimensions. Regression analysis is used to show that the same breadth/height relation characterizes all of the early Plio-Pleistocene hominids, regardless of the number of taxa represented.


[Carminomycin in drug combination in breast cancer and soft tissue sarcomas]. Thirteen patients with neglected mammary cancer were treated with karminomycin in combination with hexamethylmelamine. Twelve out of the 13 patients were previously subjected many times to cytostatic and hormonal therapy. A significant therapeutic effect was registered in 5 out the 13 patients (38 per cent), the total rate of the objective effect being 54 per cent. The remission period with a significant effect was 6 to 9 months. Fifteen patients with sarcoma metastases in the soft tissue were treated with karminomycin in combnation with methotrexate and cyclophosphane. A significant therapeutic effect was observed in 45 per cent of the cases with synovial sarcoma, hemangyopericitoma and leuomyosarcoma, the remission period being 4 to 12 months. The side effects of the above combinations were determined.


Disodium phosphonoacetate in cream base as a possible topical treatment for skin lesions of herpes simplex virus in cebus monkeys. Disodium phosphonoacetate (PAA) in a cream-ointment base was applied to herpesvirus skin lesions on the genitalia of cebus monkeys. The lesions had been produced by the intradermal injection of herpes simplex virus type 2. Concentrations of 0.2, 2, and 5% PAA were used. Liberal application of PAA at concentrations of 2 and 5% proved extremely irritating and produced extensive, severe lesions over the treated area. The 2% PAA, when applied carefully to the lesion area, proved less irritating, but did not reduce healing time when compared with the placebo-treated animals. The 0.2% PAA caused slight reduction in lesion size and duration, but these differences were not statistically significant when compared with placebo-treated animals.


Factors involved in beta-lactam antibiotic resistance in Pseudomonas aeruginosa. A temperature-sensitive mutant, strain SS, which is assumed to be devoid of beta-lactamase activity and deficient in a permeability barrier to antibiotics, was isolated from a beta-lactamase-less mutant, strain L-2, derived from Pseudomonas aeruginosa IFO 3080. By comparing the beta-lactam antibiotic susceptibility between strains IFO 3080, L-2, and SS, the involvement of both beta-lactamase and a permeability barrier in determining the beta-lactam antibiotic resistance was estimated.


Comparative pharmacology of amphotericin B and amphotericin B methyl ester in the non-human primate, Macacca mulatta. The pharmacokinetics of amphotericin B methyl ester hydrochloride (AME) and commercial deoxycholate-stabilized amphotericin B (AMB) were compared after single doses of 5 mg and 1 mg/kg of body weight, respectively, given intravenously in a period of 3 h to adult female rhesus monkeys (Macaca mulatta). By bioassay, the concentrations of AME were 12.2 to 7.2 times higher in the serum and 7.8 to 2.5 times higher in the urine during the 8 h after infusion. The decline in concentrations of the drugs in sera was consistent with a three-compartment, open pharmacokinetic model; rate constants of transfer of the drugs between the compartments and volumes of distribution were calculated. The overall rate of elimination from the central compartment (the bloodvascular space) was about four times greater for AME than for AMB. Serum urea nitrogen and creatinine concentrations were mildly and transiently increased after infusion of AME, whereas the more severe azotemia that followed infusion of AMB persisted for 5 days. AME was less toxic and achieved a greater urinary outfall than AMB. As the antifungal activity of AME is comparable to that of AMB by testing in vitro, further study is warranted.


Nutritional and biochemical characterization of Methanospirillum hungatii. To ascertain its physiological similarity to other methanogenic bacteria, Methanospirillum hungatii, the type species of the genus, was characterized nutritionally and biochemically. Good growth occurred in a medium consisting of mineral salts, cysteine sulfide reducing buffer, and an H2-CO2 (80:20) atmosphere. Addition of amino acids and B vitamins stimulated growth. Cell-free extracts contained methylcobalamin-coenzyme M methyltransferase, methylreductase, and formate hydrogenlyase. Cells contained coenzyme M and coenzyme F420. Coenzyme F420 was required for formate hydrogenlyase activity. Coenzyme F420 purified from M. hungatii had identical properties to that purified from species of Methanobacterium. The physiological basis of the family Methanobacteriaceae is strengthened by these findings.


Long-term control of central nervous system leukaemia. Seventy-four children with acute lymphoblastic leukaemia had one or more episodes of central nervous system (CNS) leukaemia. 5 children had CNS involvement at diagnosis; 4 survived for less than one year. In 35 children who had not had a previous bone marrow relapse on treatment and who received combination chemotherapy, the median duration of haematological remission from the time of first CNS relapse was almost 3 years. 5 children received full dose (2400 rads) craniospinal irradiation after their first CNS relapse; 4 have remained in CNS and haematological remission for 2 1/2 years or more. 18 children who had a CNS relapse after irradiation received 4-weekly intrathecal methotrexate; in 8 children this was given via an intraventricular reservoir. The median duration of CNS remission in children receiving intrathecal methotrexate was 2 years. Systemic and intrathecal treatment was stopped in 7 children after 2 1/2 years in continuous remission and in 2 children after 2 years. 4 of these 9 children remain in remission at intervals from 41 to 69 weeks off treatment but one is severely retarded. These results show that CNS disease is compatible with prolonged survival, but illustrate the difficulties of eradicating established CNS leukaemia.


Determination of glomerular function in advanced renal failure. In 15 children with advanced chronic renal failure, glomerular filtration rate was determined by different methods. Inulin clearance correlated well with the mean of creatinine and urea clearance, and also with 51-chromium edetic acid (EDTA) clearance measured over 24 hours. The absolute values of creatinine clearance and of 51Cr-EDTA clearance measured up to 8 hours were higher than inulin clearance. In advanced renal failure both the 51Cr-EDTA clearance measured over 24 hours, and the mean of creatinine and urea clearance, provide acceptable estimates of true glomerular filtration rate.


Comparison of effects of aspirin and indomethacin on human platelet prostaglandin synthetase. Human platelets were incubated in vitro with either aspirin or indomethacin and the prostaglandin synthetase activity of the resultant microsomal fraction from each incubation measured using a radiometric technique. Whereas aspirin produced a dose-related inhibition of the enzyme, indomethacin produced little or no inhibition over the same concentration range (10(-6) mol/l--10(-3) mol/l). Furthermore, administration of aspirin (600 mg) to volunteers produced a highly significant, prolonged inhibition of platelet microsomal prostaglandin synthetase whereas no inhibition was found with indomethacin (50 mg). As indomethacin is considerably more potent than aspirin as an inhibitor of human platelet prostaglandin synthetase in vitro, the results suggest a fundamental difference in the nature of the inhibition produced by each drug, aspirin being an essentially irreversible inhibitor whereas the inhibition produced by indomethacin is reversible. Studies with [3H-acetyl] aspirin have confirmed previous findings (Roth and Majerus, 1975) that aspirin produces an irreversible acetylation of a particulate fraction protein from human platelets.


Platelet consumption by arterial prostheses: the effects of endothelialization and pharmacologic inhibition of platelet function. The thrombogenic mechanism of arterial grafts has been studied by determining the relative utilization of platelets, fibrinogen and plasminogen by human arterial prostheses, and by direct examination of arterial grafts in a baboon model. Forty-one survival and turnover measurements of (51)Crplatelets, (131)I-fibrinogen and (125)I-plasminogen in ten patients with aortofemoral knitted Dacron prostheses demonstrated platelet consumption after graft placement (platelet survival 4.2 days +/- 0.5 and turnover 68,000 plat/ul/day +/-10,000 compared with 8.2 days +/- 0.3 and 35,000 plat/ul/day +/- 5,000 respectively for control subjects with stable vascular disease, p < 0.01). In vitro platelet function test results were normal. Platelet consumption was interrupted by dipyridamole or a combination of dipyridamole and acetylsalicylic acid, and platelet survival normalized spontaneously during nine months postoperatively. No significantly increased consumption of fibrinogen or plasminogen was found in these patients with arterial grafts. Placement of impervious knitted Dacron velour aortic grafts in baboons reproduced platelet consumption that progressively normalized over six weeks postoperatively. Platelet survival measurements correlated directly with endothelial cell coverage of the graft luminal surface in these animals implying that endothelialization of the graft surface was also occurring postoperatively in patients.


Parenteral nutrition in the treatment of acute pancreatitis: effect on complications and mortality. Clinical characteristics of 46 cases of acute pancreatitis treated with total parenteral nutrition were examined. Hyperalimentation may be used in these severely ill patients with minimal technical or metabolic morbidity. This method of nutritional support can maintain patients with nonfunctional gastrointestinal tracts for several months. Catheter-related sepsis was more common than expected early in the course of acute pancreatitis but caused minimal morbidity. The incidence of catheter-related sepsis late in disease was minor. Hyperalimentation had little if any effect on the pathophysiology of acute pancreatitis as judged by the overall mortality and the incidence and severity of the complications of acute respiratory failure and acute renal failure. It is not clear that parenteral hyperalimentation alters the course of acute pancreatitis but it is a useful adjunct for nutritional support in this illness.


The variation in hospital charges: a problem in determining cost/benefit for cardiac surgery. Based on 417 itemized bills from 45 American hospitals that responded to a randomized, geographically stratified survey covering January to June, 1976, the middle 50% of hospital charges for cardiac operations ranged between $5,914 and $10,315. Nonitemizing hospitals submitted lower, but less accurate, estimates. As 60% of the itemized bill consisted of high charge/cost items such as laboratory and pharmacy fees, total charges were not lowered merely by increasing case load or decreasing operating room times. Careful individualization of services in 1 hospital, however, reduced charges up to 16%. Charge per day was a poor index of efficiency because patients staying longer had lower average daily charges. The variation in hospital charges and lack of accounting uniformity preclude meaningful quantitation of either the "typical" charge or the numerator of the cost/benefit ratio for cardiac operations.


Low-dose insulin in the treatment of diabetic ketoacidosis. Severe diabetic ketoacidosis remains a lethal condition. Many deaths occur during therapy and are avoidable. Treatment includes rehydration, administration of insulin and potassium, and clinical care. For many years very large doses of insulin were used. Recently, it has been suggested that such large doses are unnecessary and lead to undue hypokalemia, hypoglycemia, and osmotic disequilibria. Many studies are now available that show that low doses of insulin given as continuous intravenous infusions (4 to 10 units/hr) or as hourly intramuscular injections (20 units initially, then 5 units/hr) are as effective as large doses in treating severe ketoacidosis. The new regimens are simple to use, predictable, and safe. Potassium shifts are less than with large insulin doses and insulin resistance has been shown to be a relatively minor problem. The new regimens are particularly suitable for use in nonspecialist centers.


Low-dose continuous insulin therapy for diabetic ketoacidosis. Prospective comparison with "conventional" insulin therapy. Low-dose insulin infusion has recently been used to treat ketoacidosis. We have prospectively compared patients with ketoacidosis either treated with insulin infusion at the rate of 6 units per hour or with high-dose, intermittent subcutaneously administered insulin, with emphasis placed on the hormonal responses. Basal glucagon, cortisol, and growth hormone levels were elevated in both groups. Cortisol and growth hormone levels did not fall with therapy in either group but glucagon levels fell in parallel with glucose levels in both groups. There was no difference in the time taken for glucose levels to fall below 250 mg/100 ml between groups. Whereas both methods of therapy appeared to be equally effective, low-dose infusion had the advantages of ease of administration, a predictable, relatively linear rate of fall of glucose levels, and ability to be stopped abruptly in the event of hypoglycemia.


Listeria monocytogenes infection after renal transplantation. Listeria monocytogenes infection has been observed in 13 patients, of a group of more than 700 renal transplants, treated during the past 13 1/2 years. The infection usually was manifested as bacteremia or meningitis. Twelve of the 13 patients survived the infection; one died of brain-stem herniation due to increased intracranial pressure. The recommended treatment is intravenously given ampicillin sodium.


Cellular immunity in adult marasmus.

Cellular immunity in adult marasmus. Twelve patients with recent weight loss to less than 85% of standard weight-height ratio and a serum albumin level of at least 3 gm/100 ml were considered to have the adult equivalent to marasmus. Cellular immune function was assessed by delayed hypersensitivity skin testing to Monilia and streptokinase-streptodornase, peripheral lymphocyte count, proportion of T and B cells, whole blood and isolated lymphocyte transformation to phytohemagglutinin, pokeweed mitogen, concanavalin A, Monilia, and streptokinase-streptodornase. Significant impairment of skin test reactivity while in vitro responsiveness remained intact was noted in the marasmic patients. No impairment was found in 12 individuals with recent weight loss who remained at a weight greater than the 85% weight-height ratio. In four marasmic individuals in whom weight loss was arrested by nutritional repletion, skin reactivity returned without substantial change in weight. In this type of marasmus, both depleted nutritional status and weight loss must be present for impairement of skin test responsiveness. These findings confirm relative sparing of more vital functions dependent on protein metabolism in adult marasmus compared to the kwashiorkor-like syndromes of hypoalbuminemic malnutrition seen in adults.


Teichoic acid antibody test: its use in patients with coagulase-positive staphylococcal bacteremia. We have studied the occurrence and specificity of teichoic acid antibodies (TAAs), measured by double diffusion in agar, in 114 patients with bacteremia of whom 47 had coagulase-positive staphylococcal bacteremia. A total of 30% of the 47 patients with coagulase-positive staphylococcal bacteremia had a TAA titer of 1:8 or more, and an additional 30% had a titer of 1:2 or 1:4. High TAA titers were most often connected with coagulase-positive staphylococcal endocarditis, osteomyelitis, and deep wound infections. None of the six coagulase-negative patients with staphylococcal bacteremia nor any of the 92 controls had titers exceeding 1:1. A total of 10% of the other patients with bacteremia showed positive results on the TAA test at low titer levels. Compared to the antistaphylolysin value, the TAA test was about equally specific but more sensitive.


Giant kidneys in Waldenström's macroglobulinemia. A patient with Waldenström's macroglubulinemia had the unique feature of having one kidney infiltrated with malignant cells to such an extent as to produce a large palpable abdominal mass. Other unusual aspects of this case include the destruction of renal tubules by the invading cells that resulted in interstitial fibrosis and was probably responsible for the appearance of whole IgM in the urine.


[Chemotaxis and phagocytosis of polymorphonuclear leukocytes in malnourished children]. Chemotactic activity of neutrophil polimorphonuclear cells, liberation of chemotactic factors by plasma proteins and phagocytic function of PMN cells by nitroblue tetrazolium reaction were evaluated in 20 malnourished children (from grade 1 through grade III) and in 20 normal children with similar age and sex, without any apparent infection. Also quantitative determination of immunoglobulins A, G and M and C3 complement fraction concentration in serum was made. Chemotactic and phagocytic activity were normal. Serum levels of Igs and C3 complement were within the lower limits of the normal range.


[Comparative study of different methods of evaluation of left ventricular volume by monoplane angiocardiography]. The authors compare 5 methods of evaluating left ventricular volume and the ejection fraction by monoplanar angiocardiography in the 30 degrees right oblique incidence: the method of Green (1 and 2), Snow and Dodge, and by trapezoidal integration which was used as a reference. The have calculated the regression ordinates and the correlation coefficients for various systolic and diastolic volumes as well as for various ejection fractions. For these latter, Dodge's quadratic equation can also be used. Provided there is no gross distorsion of ventricular contolr, there is fairly good correlation, but there is a marked discrepancy for large volumes or small ejection fractions (less than 0.40). When more elaborate methods are not available, it seems reasonable to use a single method to calculate these parameters, but it is essential to have recourse to other techniques when there are gross changes in the left ventricle.


[French evaluation of cardiac stimulation]. A national enquiry into the problems related to definitive cardiac pacemakers, carried out in 1975, has yielded certain essential findings: the number of first-time implantations of pacemakers has been increasing by about 20% per annum; 92% of electrodes are currently implanted by an endocavitary technique, thoracotomy having now practically been abandoned; 90% of pacemakers implanted in 1975 were threshold models, inhibited by a QRS complex; the indications have become progressively wider, and are essentially related with the various forms of bradycardia, most frequently those due to atrio--ventricular block. In 1976, we have now reached a figure of about 200 new implantations of pacemakers per million inhabitants; those using lithium are increasingly superceding the mercury and isotope models.


[Coronary arteriography in the threatened infarction syndrome]. Although greater than in patients with stabilised coronary insufficiency, the risks of carrying out coronary arteriography during the period of a threatened infarction are still modest in the hands of an experienced team. In a series of 66 such investigations under these conditions over an 18 month period, there were no deaths as immediate sequelae. Three myocardial infarctions occurred, one of which was probably encouraged by ceasing the propranolol prior to arteriography. Analysis of the results confirms the frequency of lesions affecting all three trunks (47% of cases), the anterior descending branch being the most commonly affected. A collateral circulation was established in 23% of cases. Ventriculography was normal in one third of cases. The mean value for the ventricular ejection fraction was 0.57 over the entire series. In 58% of cases, all the arteriographic and ventriculographic criteria of operability were satisfied. It therefore appears that coronary arteriography is justifiable during the period of threatened infarction; it may be undertaken at an early stage if the angina does not respond to medical treatment. It is always best to carry it out several days after cessation of the pain where possible. The investigation may lead to urgent surgical intervention.


[Changes in left ventricular function with effort in the coronary patient. l]. The altered haemodynamics of the coronary patient have been investigated in 30 patients both at rest and under conditions of maximal effort as carried out on the bicycle ergometer under the usual conditions for an exercise electrocardiogram. Patients with angina of effort but no previous infarction have normal left ventricular function at rest; under the ischaemia induced by exercise there is acute dysfunction of the left ventricle as witnessed by a reduction in maximal cardiac output, a raised end-diastolic pressure, and changes in compliance which are more marked than those in contractility. Patients with a healed infarct but without sequelae have a rigid left ventricle, but it is not failing; they show normal changes in dP/dt max and in the indices of left ventricular work, but a pathological form of negative peak of dP/dt, of end-diastolic pressure, and of deltaP/deltaV (which reflects myocardial compliance). Patients who have had an infarction with sequelae such as angina or attacks of left ventricular failure have filling pressures which are already elevated at rest, and cardiac failure, which becomes evident on exercise.


[Left ventricular function with effort in the coronary patient. Study of the correlations with the data on echocardiography, effort ECG, and the teleheart. 2]. Correlations were established, for 30 coronary patients, between the haemodynamic findings and those adduced from non-invasive techniques - electrocardiography, both at rest and on exercise, telethorax, and echocardiography. Left ventricular function in the coronary patient can be assessed, even before catheterisation, by means of: 1. The clinical findings: angina of effort, an uncomplicated infarct, and an infarct with sequelae each has its own peculiar haemodynamic pattern at rest and on exercise; 2. The ECG finding of an extensive anterior infarct implies a haemodynamic picture vastly different from that with a limited posterior infarction; 3. The appearance of an ischaemic shift in the ST segment on exercise implies an acute malfunctioning of the left ventricle; 4. On the echocardiogram, an end-diastolic volume greater than 150 ml/m2, an ejection fraction less than 0.50 and VCF greater than 0.8 c/s are always accompanied by disturbances in the haemodynamics. By contrast, the cardio-thoracic ratio, except in post-infarct cases complicated by left ventricular failure, gives no predictive indication of cardiac function. These various examinations should therefore be applied to the coronary patient as an index of cardiac function.


[Echocardiographic study of the left ventricle in aortic insufficiency. Comparison with the data of clinical development and hemodynamic results]. A series of 20 patients with pure and severe major aortic incompetence was studied, and three different groups were distinguished: group I, with no previous defect in function; group II, with cardiac failure as a result of aortic incompetence of more than 5 years' standing; group III, with cardiac failure secondary to acute aortic incompetence. The internal diameter of the left ventricle and the mode of closure of the mitral valve were studied by echocardiography, and compared with the clinical and haemodynamic findings. Left ventricular dilatation appeared early, and occurred to the same degree in the three groups. The diastolic diameter of the left ventricle showed a fairly close correlation (r equals 0.61) with the degree of regurgitation as measured from clour dilution curves; by contrast, the length of time the aortic incompetence had been present had little influence on the degree of dilatation of the left ventricle. Premature closure of the mitral valve was significantly associated with a raised LVEDP and a low systolic index; it represents a defect in the compliance of the left ventricle, and is a poor prognostic factor because of the clinical progression into very rapid and severe heart failure. Moreover, there is a distinct aetiological factor (Infective endocaditis) in the most marked forms of premature closure. The other ecocardiographic findings (appearances of the aorta, mitral echo, slope EF of the mitral valve) give no information on the degree of tolerance to the cardiac defect.


[The heart and lithium. Apropos of a case of lithium poisoning with intracavitary electrocardiographic exploration]. Among the secondary effects of the salts of Li+, which are widely used in psychiatric treatment, cardiac toxicity appears to be rare. The authors report the case history of a female of 24 years of age, with no previous cardiac history, who presented with Li+ intoxication and a supra-His atrio-ventricular block, followed by episodes of sinus arrest (or of sino-atrial block), accompanied by either a junctional rhythm or by periods of prolonged asystole. The results of the endocavitary electrocardiographic investigation are described. These cardiac effects are compared with the general findings reported in the literature; ECG modifications of the T wave are more common, but Li+ may cause other changes: sinus, atrial or ventricular arrhythmiás, disorders of AV conduction, and cardiomyopathies. The main modes of action which have been suggested are of interference with the other cations (K+, Na+, Ca++) in exchanges across membranes, and an effect on membrane adenyl-cyclase stimulated by catechol-amines.


[Dromotropic effects of drug combinations. Initial results bearing on a combination of deslanoside and ajmaline]. The electrophysiological effects of the cardiotropic drugs have been studied in man by the agency of endocavitary electrocardiography. The effects of drug combinations, which are often prescribed therapeutically, have been studied less often. The authors report the results of a preliminary study of the combination of deslanoside with ajmaline in 26 patients; its effects were compared with those using each drug separately. This combination seems to have true dromotropic effects; although deslanoside alone, in the doses used, does not modify conduction below the bundle of His, it can still act synergistically with ajmaline at this level. A detailed study of the pharmacological effects as a function of the original status of conduction shows that at the level above the bundle His, the dromotropic action is quantitively less on healthy conducting tissue than on abnormal tissue. The effects of ajmaline on the conduction times below the bundle seem to be similar whether or not there is any conduction defect under basal conditions. The difficulties in obtaining and interpreting such measurements in man are discussed in the hope of arriving at a general protocol for studying drug combinations.


[Value of the exercise test after aortocoronary bypass]. The 100 patients who underwent an exercise test and a follow-up coronary arteriogram at a mean interval of 10.1 months after an aorto-coronary bypass had suffered preoperatively from incapacitating angina 50%), a threatened infarction syndrome (35%), or Prinzmetal's angina (15%). The majority had a single bypass graft (72%), but 28% had two or three grafts. The exercise test was positive 39 times, negative 51 times, and indeterminate in 10. Correlation with the clinical picture shows that 27% of the patients in functional category I had a positive exercise test. Correlation with coronary arteriography shows that a positive test is reliable evidence for a defect or occlusion of the graft. On the other hand, a negative exercise test is a less reliable indicator of a good result. No instances of positive exercise tests were found when there was complete alleviation of the coronary condition.


[Oral contraceptives and myocardial infarct]. In the light of four proven cases of myocardial infarction in patients under treatment with hormonal contraceptives, the authors point out: the sudden 'inaugural' appearance of the infarction during a therapeutic course; the appearances of the lesions on coronary arteriography; on 2 occasions a lacunar form on the proximal segment of a main coronary trunk, in one case lesions more redolent of atheroma, and in one case a completely normal vascular tree. These appearances had not changed at follow-up arteriography; the existance in 3 cases of multiple associated risk factors, especially of a mixed type of hyperlipoproteinaemia associated with tobacco consumption. The current relative frequency of coronary episodes in patients with multiple risk factors would seem to point towards caution in prescribing hormonal contraceptive treatment, especially for females of over 35 years of age.


Gender and environment as determinants of behavior in infant common baboons (Papio cynocephalus). Two groups of infant baboons were observed. The breast-fed group was housed in a gang cage with nursing mothers (n = 13) and the other motherless group was in a wire-cage nursery habitat (n = 20). Differences in behavior due to gender and environment were tested by analysis of variance. The results do not support the hypothesis that innate sex differences exist in baboons aged 0-3 months. Nursery-reared subjects had significantly higher scores for rough-and-tumble play, stereotypy, threat, avoid, explore, high tension, and nonaggressive social behaviors, but these behaviors are not significantly different between sexes in either groups.


[Intestinal uptake and transfer of zinc after supplement of 2,4-dinitrophenol and ouabain]. The effect of the inhibitors 2,4-dinitrophenol (DNP) and g-strophantin (ouabain) on the intestinal uptake and cellular transfer of zinc (Zn) and the effect of the organic ligands histidine and EDTA were studied in vitro with everted intestinal sacs of normally maintained rats. Zn was added to the incubation solution as ZnCl2 or as ZnCl2 mixed with histidine in a molar ratio of 200 : 1 and mixed with EDTA in a molar ratio of 1 : 1 or 10 : 1. The DNP in a concentrationof 0.05 mM proved sufficient to greatly inhibit the uptake and transfer of Zn from the solution containing ZnCl2 mixed with an excess of histidine. DNP also reduced Zn absorption when ZnCl2 alone as added. On the other hand, the presence of DNP in the solution containing ZnCl2 with EDTA was found to increase the transfer of Zn and its ligand. In the presence of EDTA, Zn absorption may, therefore, be controlled by the uptake and transfer of the ligand. Ouabain at the contration of 5 mM and 10 mM greatly reduced Zn uptake by the intestinal wall and the celluar Zn transfer from the solution containing ZnCl2 and histidine. There was only a small effect of ouabain on Zn absorption whether ZnCl2 is added alone or with EDTA. The addition of an excess of histidine as ligand to ZnCl2 in the control groups markedly improved Zn absorption. In contrast to this, the addition of EDTA to ZnCl2 reduces the intestinal Zn uptake and increases the transfer of Zn compared to ZnCl2 alone.


Vascular clearance of venezuelan equine encephalomyelitis viruses as a correlate to virulence for rhesus monkeys. The epizootic Trinidad donkey strain of Venezuelan equime encephalomyelitis virus (VEE) was cleared slowly from the circulation of rhesus monkeys following intravenous inoculation, while the live, attenuated vaccine strain, TC-83, was cleared rapidly. The efficent clearance of TC-83 vaccine may be a factor in the lower viremia and benign course of TC-83 virus infection in rhesus monkeys.


Café-au-lait spots of the fundus in neurofibromatosis. Mild pigmentary changes found in the fundi of two patients with neurofibromatosis, resembled café-au-lait spots homologous with skin manifestations of the disease. In one, associated retinal hamartomas were present. The café-au-lait lesions were clinically distinct from previously reported uveal melanomas and may represent a hitherto unrecognized sign of ocular neurofibromatosis.


Ocular pathology of the congenital varicella syndrome. Congenital anomalies are rare in infancy following maternal varicella during pregnancy. Abnormalities do occur, however, and form a specific pattern including cicatrical skin lesions, atrophic limb, low birth weight, and chorioretinal scarring. We saw an infant who had immunologic evidence of varicella-zoster virus contact in utero, microphthalmos of one eye, and chorioretinal scarring of the fellow eye. Ophthalmologists confronted with such ocular anomalies in children should inquire about the possibility of maternal varicella during pregnancy. Conversely, infants born of mothers known to have had varicella during pregnancy should be examined for fundus abnormalities.


Corneal wound healing and antiviral medication. Masked, controlled rabbit studies were done to determine the toxic effects on corneal wound healing of 0.1 percent idoxuridine drops, 3 percent adenine arabinoside monophosphate drops, and 1 percent trifluorothymidine drops, the clinically used concentrations. Neither idoxuridine nor trifluorothymidine significantly retarded closure of epithelial wounds. All three drugs caused toxic changes in the regenerating epithelium clinically and by histopathologic examination. Treatment with arabinoside monophosphate, the monophosphate ester of vidarabine, significantly retarded closure of epithelial wounds and caused impressive toxic changes in the regenerating epithelium. Vascularization of the corneal stroma was present in all eyes treated with this drug. The trifluorothymidine and idoxuridine had much milder toxic effects on regenerating epithelium and appeared equal in regard to production of such effects. The strength of stromal wounds was somewhat reduced by idoxuridine and trifluorothymidine and significantly increased by arabinoside monophosphate when compared to controls, These findings were confirmed by hydroxyproline assay of the stromal scars.


[Fibrous dysplasia, "inverse" intravascular form of ossification (author's transl)]. Histologic analysis of 22 cases of fibrous dysplasia was performed. 1. In each case separately 100 immature bony trabeculae were counted, giving a total of 2200 counts. It was concluded, that on a given section, 75,7 per cent of the trabeculae were in contact with vascular cavities. The remaining 24,3 per cent seemingly "metaplastic" bony trabeculae were examined further by serial section. In different layers of the block material the obvious connection with vascular spaces could be shows. 2. The vascular (not metaplastic) origin of immature bony trabeculae was demonstrated too. The development of this pattern of bone starts and continues in contrast to normal ossification within the capillaries and sinusoids in an "inverted" manner. Later the trabeculae "grow out" from the vascular cavities but keep their contact with them.


Fastigial evoked eye movement and brain stem neuronal behavior in the alert monkey. Single units in the brain stem were recorded in the awake monkey during concomitant adequate vestibular stimulation, eye movement, and electrical stimulation of the fastigial nucleus in areas that produce short-latency horizontal saccades. Forty-eight percent of the recorded brain stem cells were associated with eye movements; 40% respond only to head rotation; and the remainder are unrelated to either. The activity of the majority of the eye movement-related cells was similar for spontaneously and fastigially evoked saccades. The activity of the head rotation and unrelated cells show no consistent relationship to fastigial stimulation.


Gelatin film. A useful adjunct in rhinoplastic surgery. Gelfilm is a nonporous, rigid, cellophane-like absorbable gelatin. Its use in preventing adhesions in neurosurgery and ophthalmic, otologic, and chest surgery has been well described. It has not been previously reported for nasal surgery. It incorporates many characteristics of an ideal absorbable implant. The material has been used clinically as a dorsal nasal implant either alone or as a vehicle for autogenous cartilage grafts. Its main function is to diminish adhesions between the nasal bones and dorsal skin after surgery on the nasal pyramid. Its benefits seem most applicable in traumatic or revisionary rhinoplasty. Its use has been well documented in 40 cases with a one-year follow-up. The only disadvantage is a slight prolonged dorsal edema until the implant resorbs. The results have been impressive in both early and late postoperative follow-up because the nasal dorsum appears smoother and the skin nonadherent.


Variation in the direction of selection applied by pentenol to the alcohol dehydrogenase locus in Drosophila melanogaster. This paper describes selective effects of pentenol-impregnated media on six genotypes at the alcohol dehydrogenase (Adh) locus in D. melanogaster. In the laboratory population studied, developmental times of pre-adults homozygous for an alcohol dehydrogenase "null" allele increased with increasing pentenol concentrations. The developmental times of the other five genotypes, which produced active alcohol dehydrogenases, increased slightly at pentenol concentrations up to 0-0033%, but above this concentration they decreased markedly. In fact on 0-067% pentenol, the highest concentration tested, developmental times of these five genotypes were between 9 and 24 h less than their developmental times on media lacking pentenol. The magnitude of the reduction in developmental time differed significantly between genotypes and was positively correlated with alcohol dehydrogenase activity. Pentenol had toxic effects on adults and significant differences were found between survival percentages of adults of different genotypes on pentenol-impregnated media. These survival percentages were negatively correlated with alcohol dehydrogenase activities. Therefore selective differences between genotypes in adult survival were negatively correlated with those in developmental times. The variations in the direction of selection are discussed in terms of their possible biochemical basis and their effects on the maintenance of Adh polymorphisms.


The psychotherapy of character disorder. Patients suffering from character disorder are often rejected as unsuitable for psychotherapy. Those with anxiety and depression often seek help, and should be assessed for their potential to be helped by a carefully structured long term psychotherapeutic relationship controlled by the therapist to reduce acting out behaviour. The therapist acts throughout as a model for the patient. As the patient develops basic trust in the therapist, identification develops and a major sustained improvement can occur. The therapy described is current-behaviour orientated and the importance of clear, unambiguous communication, particularly verbal communications, is stressed. The principles of therapy are applicable to all contacts with character-disordered patients. Briefly described is the long term therapy of two patients with hysterical personality disorders and acting-out behaviour, as examples of one type of the wide variety of character disorders that can be treated, and where the nine year follow up was adequate to ensure that improvement was sustained.


Behavioral role of the sexcombs in Drosophila melanogaster and Drosophila simulans. The sexcombs were amputated from males of three strains of Drosophila melanogaster and one strain of D. simulans in order to assess the importance of these structures in the sexual behavior of these species. In D. melanogaster the sexcombs are important in attempts to copulate with the female. Their removal delays copulation but does not suppress it entirely. Other aspects of courtship are not influenced by removal of the sexcombs. Strain differences in quanitative aspects of courtship were found, and also in the insemination rates of females by males without sexcombs. The present evidence suggests that the sexcombs are primarily structures adapted to grasping the female securely during the act of intromission.


Courtship latency in male Drosophila melanogaster. Male Drosophila melanogaster differ in the age at which they reach sexual maturity following eclosion from the pupa. Courtship latency, which is the time taken by a male to initiate courtship of a conspecific female, is related to age. Young males take significantly longer than older males to begin courtship. The probability that a male will initiate courship is influenced by the physiological state of the female. Males of different genotypes readily court mature (3-day-old) virgin females, but they differ significantly in their reaction to immature (12-hr-old) and fertilized females. Genes located on the third chromosome largely control male courtship latency, but responses to immature and fertilized females have different genetic bases, suggesting that the relevant stimulus inputs governing these responses also differ. The adaptive significance of courtship directed toward immature or fertilized females, which rarely mate, probably depends on the average level of sexual responsiveness of potentially receptive mature virgin females in a given population.


The design of mazes to study Drosophila behavior. Although mazes have been widely used in studying phototaxis, geotaxis, and, more recently, learning in Drosophila, there is no uniformity in maze design, and little is known about the effects such apparatus differences may have on behavior. The new maze design described here is based on T-junctions, molded individually in acrylic, and provides an inexpensive and standardized means of building mazes to any desired specification. The need for uniformity in maze design is demonstrated with an experiment on three variables at the start of a maze that affect the subsequent response of four strains of D. melanogaster in different ways. Some implications for future Drosophila research using mazes are considered.


[Analysis the incidence of HL-A-system antigen incidence in children treated for acute lymphoblastic leukemia]. Correlation between some histocompatible antigens and leukemia has been described both in men and in experimental animals. In 1970 Walford found an exceptionally high association between the illness and antigens of the HLA system in children with acute leukemia who had long life duration. It is therefore supposed that these antigens should not be associated with predispositional factors of the illness, instead, they are more likely to have influence over the course of the illness itself. Consequently, the authors have examined 15 children of various age who had acute leukemia. All children were examined for all antigens of the first and second HLA system, as well as for ABO and Rh genotype. The patients' blood was also checked for existence of cytotoxic antigens. Frequency of certain antigens and haplotypes was found in both children and their parents so that a comparison with antigen and haplotype frequency was also made.


[Hemolytic disease of the newborn due to anti-S-antibodies]. In the serum of S-negative secundi para woman a specific anti-S agglutinin of the IgG type was identified. The same agglutinin was identified in the serum and on the eritrocytes of the newborn with sympthomes of a light Hemolytic disease. Exchange transfusion was not necessary. The anti-S described is an immune warm agglutinin showing the efect of dose and is discovered only by the Coombs technique.


Effects of proteolytic digestion by chymotrypsin on the structure and catalytic properties of reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase from bovine heart mitochondria. 1. Incubation of NADH-ubiquinone oxidoreductase (Complex I) with chymotrypsin caused loss of rotenone-sensitive ubiquinone-1 reduction and an increase in rotenone-insensitive ubiquinone reduction. 2. Within the same time-course, NADH-K(3)Fe(CN)(6) oxidoreductase activity was unaffected. 3. Mixing of chymotrypsin-treated Complex I with Complex III did not give rise to NADH-cytochrome c oxidoreductase activity. 4. Gel electrophoresis in the presence of sodium dodecyl sulphate revealed selective degradation of several constituent polypeptides by chymotrypsin. 5. With higher chymotrypsin concentrations and longer incubation times, a decrease in NADH-K(3)Fe(CN)(6) oxidoreductase was observed. The kinetics of this decrease correlated with solubilization of the low-molecular-weight type-II NADH dehydrogenase (subunit mol.wts. 53000 and 27000) and with degradation of a polypeptide of mol.wt. 30000. 6. Phospholipid-depleted Complex I was more rapidly degraded by chymotrypsin. Specifically, a subunit of mol.wt. 75000, resistant to chymotrypsin in untreated Complex I, was degraded in phospholipid-depleted Complex I. In addition, the 30000-mol.wt. polypeptide was also more rapidly digested, correlating with an increased rate of transformation to type II NADH dehydrogenase.


Fragments produced by digestion of human immunoglobulin G subclasses with pepsin in urea. It was previously shown that digestion of human IgG1/kappa myeloma proteins with pepsin in the presence of 8 M-urea produces fragments which differ from other proteolytic fragments of IgG, including those produced by peptic digestion in aqueous buffers. The two large urea/pepsin fragments each consist of three peptides, and together account for all of the constant region of the light chains and most of the constant region of the heavy chains. Myeloma proteins of subclasses IgG2, IgG3 and IgG4 with kappa light chains were digested with pepsin in 8 M-urea, and the resulting fragments compared with those produced from IgG1/kappa proteins. Gel filtration, starch- and polyacrylamide-gel electrophoresis and sequence analysis have shown that the peptides from each subclass are analogous with those from IgG1. A brief investigation of the products of urea/pepsin digestion of myeloma proteins with lambda light chains has shown that in these proteins light-chain cleavage occurs at residue leucine-182, instead of or as well as at residue 117, where cleavage takes place in kappa chains. Comparison of sequences around sites of urea/pepsin cleavage has shown that pepsin has quite restricted specificity under these conditions.


Glutamine as a precursor to N-terminal pyrrolid-2-one-5-carboxylic acid in mouse immunoglobulin lambda-type light chains. Amino acid-sequence variability at the N-terminal extra piece of lambda-type light-chain precursors. The mRNA molecules coding for three mouse immunoglobulin lambda-type light (L) chains (MOPC-104E lambda(1), RPC-20 lambda(1), MOPC-315 lambda(2)) programme the cell-free synthesis of precursors larger than the mature proteins. Radioactive amino acid-sequence analyses of each of the three precursors labelled with [(3)H]alanine, [(3)H]serine, [(3)H]glutamine, [(3)H]glutamic acid and [(3)H]threonine showed that an extra piece, at least 18 residues long, is linked to the N-terminus of the mature L-chains. The N-terminal extra-peptide segment may be 19 residues long, since analyses of precursors labelled with [(35)S]methionine indicated an additional N-terminal methionine residue which was recovered in low yields. Presumably this is the initiator methionine, which is known to be short lived in eukaryotes. The mature forms of MOPC-104E, RPC-20 and MOPC-315 lambda L-chains are blocked at the N-termini by pyrrolid-2-one-5-carboxylic acid (pyroglutamic acid). Sequence analyses of precursors labelled with [(3)H]glutamine and [(3)H]glutamic acid showed incorporation only of glutamine in a position that matches with the position of pyrrolid-2-one-5-carboxylic acid in the mature forms of all three precursors, and incorporation of glutamic acid in other positions. The data showed the absence of glutamine-glutamic acid interconversion, since the radioactive peaks obtained from either (3)H-labelled amino acid were discrete, and free from cross-contamination. These results prove that glutamine is the precursor amino acid of pyrrolid-2-one-5-carboxylic acid at the N-termini of the mature MOPC-104E lambda(1), RPC-20 lambda(1) and MOPC-315 lambda(2) L-chains. Thus the formation of pyrrolid-2-one-5-carboxylic acid by cyclization of glutamine is a post-translational event which occurs after, or concomitant with, cleavage of the extra piece from the precursor to yield the mature L-chain. The variable (V) regions (110 amino acid residues) of mouse lambda L-chains are quite similar: when compared with that of MOPC-104E lambda(1) chain, the V-region of RPC-20 lambda(1) chain differs in one residue, and the V-region of MOPC-315 lambda(2) chain differs in 11 residues. The partial sequence data show that the N-terminal extra pieces of the two lambda(1) L-chain precursors have, so far, identical partial sequences; the extra piece of the lambda(2) L-chain precursor differs from these in at least three out of 19 positions.


The soluble methane mono-oxygenase of Methylococcus capsulatus (Bath). Its ability to oxygenate n-alkanes, n-alkenes, ethers, and alicyclic, aromatic and heterocyclic compounds. 1. Methane mono-oxygenase of Methylococcus capsulatus (Bath) catalyses the oxidation of various substituted methane derivatives including methanol. 2. It is a very non-specific oxygenase and, in some of its catalytic properties, apparently resembles the analogous enzyme from Methylomonas methanica but differs from those found in Methylosinus trichosporium and Methylomonas albus. 3. CO is oxidized to CO2. 4. C1-C8 n-alkanes are hydroxylated, yielding mixtures of the corresponding 1- and 2-alcohols; no 3- or 4-alcohols are formed. 5. Terminal alkenes yield the corresponding 1,2-epoxides. cis- or trans-but-2-ene are each oxidized to a mixture of 2,3-epoxybutane and but-2-en-1-ol with retention of the cis or trans configuration in both products; 2-butanone is also formed from cis-but-2-ene only. 6. Dimethyl ether is oxidized. Diethyl ether undergoes sub-terminal oxidation, yielding ethanol and ethanal in equimolar amounts. 7. Methane mono-oxygenase also hydroxylates cyclic alkanes and aromatic compounds. However, styrene yields only styrene epoxide and pyridine yields only pyridine N-oxide. 8. Of those compounds tested, only NADPH can replace NADH as electron donor.


Restoration of beta-galactosidase to Escherichia coli M15. Complementation studies. Carboxymethylated beta-galactosidase from Escherichia coli was dissociated at 100 degrees C to form carboxymethylated fragments A and B. The mol.wts. of carboxymethylated fragments A and B were determined by gel filtration to be 64300 and 22400 respectively. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of carboxymethylated fragments A and B that had been pretreated with 2-mercaptoethanol and sodium dodecyl sulphate yielded mol.wts. of 64000 and 22100 respectively. Carboxymethylated fragments A and B had arginine as their C-terminal amino acid. When a crude extract of E. coli M15 was filtered through a column of Sepharose 6B, it was found that carboxymethylated fragment B could restore beta-galactosidase activity when added to fractions having mol.wts. estimated to be 123000, 262000 and 506000. These fractions are referred to as ;complementable fractions'. Similarly, it was found that carboxymethylated fragment A could restore enzyme activity to tractions having mol.wts. estimated to be 63000, 253000 and 506000. Estimates of the molecular weights of the beta-galactosidase activity obtained by restoration with carboxymethylated fragments A and B were made by filtering the active enzyme through another column of Sepharose 6B. The enzyme obtained by complementation with carboxymethylated fragment B, i.e. the complemented enzyme, had mol.wt. 525000, and that obtained with carboxymethylated fragment A had mol.wts. of 525000, 646000 and 2000000. The latter finding suggests that multiple forms of complemented beta-galactosidase can exist.


A fluorimetric study of the role of calcium ions in the stability of thermolysin. 1. Fluorimetric techniques were used to characterize the environment of tryptophan residues in thermolysin and apo-thermolysin. The apo-thermolysin was obtained by dissolving the enzyme in the presence of 10mm-EDTA, which removed the functional Zn(2+) ion and the four Ca(2+) ions/molecule from the enzyme. 2. At 25 degrees C in aqueous solution the fluorescence-emission spectrum of the native holoenzyme, on excitation at 290nm, was essentially characteristic of tryptophan, with an emission maximum at 333nm. The emission maximum of the apoenzyme is red-shifted to 338nm and the relative intensity of fluorescence is decreased by 10%, both effects indicating some unfolding of the protein molecule, with the indole groups being transferred to a more hydrophilic environment. 3. Fluorescence quenching studies using KI, N'-methylnicotinamide hydrochloride and acrylamide indicated a more open structure in the apoenzyme, with the tryptophan residues located in a negatively charged environment. 4. The thermal properties of the apoenzyme, as monitored by fluorescence-emission measurements, are dramatically changed with respect to the native holoenzyme. In fact, whereas the native enzyme is heat-stable up to about 80 degrees C, for the apoenzyme a thermal transition is observed near 48 degrees C. The apoenzyme is also unstable to the action of unfolding agents such as urea and guanidinium chloride, much as for other globular proteins from mesophilic organisms. 5. The functional Zn(2+) ion does not contribute noticeably to the stability of thermolysin. 6. It is concluded that a major role in the structural stability of thermolysin is played by the Ca(2+) ions, which have a bridging function within this disulphide-free protein molecule.


Phenol sulphotransferase and uridine diphosphate glucuronyltransferase from rat liver in vivo and vitro. 2,6-Dichloro-4-nitrophenol as selective inhibitor of sulphation. Microsomal UDP-glucuronyltransferase and cytosolic sulphotransferase share many substrates, such as phenols and hydroxamic acids. In a search for a selective inhibitor of sulphation, several phenolic compounds were tested. 2,6-Dichloro-4-nitrophenol is introduced as a selective inhibitor of sulphation in vivo, having no effect on UDP-glucuronyltransferase activity. As substrate for both conjugating enzymes the phenolic drug harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole) was used. In the rat in vivo 2,6-dichloro-4-nitrophenol caused almost complete inhibition of harmol sulphation after a single intraperitoneal injection (26mumol/kg) for 48h; the percentage of harmol sulphated decreased from 75% in controls to 5% in the treated rats. The percentage of harmol glucuronidated increased from 25 to 95%. Pentachlorophenol was equally effective but also highly toxic. Salicylamide had only a very-short-lasting inhibitory effect on sulphation. In vitro, 2,6-dichloro-4-nitrophenol inhibited sulphation of harmol by a rat liver postmitochondrial supernatant completely at 1mum, whereas even at 100mum it had no effect on glucuronidation of harmol. It is concluded that 2,6-dichloro-4-nitrophenol is a selective inhibitor of sulphation and, further, that its long duration of action makes it suitable for studies on the regulatory role of sulphation in some biological processes.


Purified human liver acid beta-D-galactosidases possessing activity towards G(M1)-ganglioside and lactosylceramide. Our studies with purified human liver acid beta-D-galactosidases (EC 3.2.1.23) indicate that 4-methylumbelliferyl beta-D-galactosidase and G(M1)-ganglioside beta-D-galactosidase activities are identical with lactosylceramidase II activity. Evidence for this includes co-purification of all enzyme activities by affinity chromatography to yield a single band on polyacrylamide-gel electrophoresis and coincident elution from Sepharose 6B of all three enzyme activities.


Effects of suloctidil on lipid metabolism in experimental animals. A novel potent vasoactive agent, 1-(4-isopropyl-thiophenyl)-2-n-octylaminopropanol (suloctidil, Sulocton), lowers excess of plasma cholesterol and tends to normalize the plasma hyperbetalipoproteinemia of Rhesus monkeys fed a high-cholesterol, high-fat diet. The drug shows an inhibitory effect on the cholesterol biosynthesis in rat liver homogenates.


The radioimmunological determination of glibenclamide and its metabolites in serum. This report describes a sensitive and specific radio-immunological method for determining serum levels of the oral anti-diabetic agent 1-(p-[2-(5-chloro-2-methoxy-benzamido)-ethyl]-benzensulfonyl)-3-cyclohexylurea (glibenclamide) and its metabolites. The antigen was prepared by coupling a metabolite to bovine serum albumin. Antibodies could be demonstrated in serum after immunisation of rabbits. The separation of free and antibody-bound glibenclamide was achieved by a dextran-charcoal suspension. Presence of serum did not influence the binding characteristics. The limit of detection was 20 ng/ml. The affinity of the metabolites differed only slightly from that of glibenclamide. The presence of related drugs from the sulfonylurea series such as tolbutamide, glibornuride and the sulfonamide sulfamethoxazol did not affect the determination. Only closely related substances showed a variable degree of affinity towards antibodies. As an example of the possible application of this method, the serum concentration of glibenclamide was determined over a period of 8 h after a single i.v. injection to a volunteer. The data are in close accordance with the results of authors using radioactive glibenclamide.


Rubella vaccination and anti-D immunoglobulin administration in the puerperium. The serum conversion rates and post-vaccination rubella haemagglutination inhibiting antibody titres of a group of women given both anti-D immunoglobulin and rubella vaccine in the puerperium have been compared with those of a similar group of patients who were given vaccine but no immunoglobulin. The serological response to rubella vaccination in susceptible women was satisfactory even when anti-D immunoglobulin was given shortly before vaccination.


Proton relaxation study of the hog kidney diamine oxidase active center. Proton relaxation studies of the interactions with hog kidney diamine oxidase of water, substrate-analogue inhibitors, and product analogues indicate that the active site Cu(II) is not located near the oxidizing site of the enzyme, rather near the nonoxidized end of the binding substrate. The studies with histamine derivatives provide evidence for a concentration-dependent occupation of two sites. The site which is populated at high concentrations provides proximity of the imadazole ring nitrogen N1 to the Cu(II). Water binds at the Cu(II) of the native enzyme. However, this water is probably not involved in the hydrolysis of the enzyme-substrate imine bond to eliminate the first reaction product. O2 does not compete with H2O for a site on the Cu(II) ion. In the case of one of the probes, namely the ammonia (product) analogue dimethylamine, the validity of the protein relaxation results was verified by also observing the nitrogen (15N) relaxation rates of ammonia itself. The conclusion that the ammonium ions is not directly bonded to the active site Cu(II) is reached from both the proton and nitrogen relaxation experiments.


The effect of ATP on calcium efflux in dialyzed barnacle muscle fibres. Calcium efflux has been studied in barnacle muscle fibres under internal dialysis conditions. Prolonged dialysis of these fibres, with a medium free of ATP and containing 2 mM cyanide and 1 mM iodoacetate, causes the ATP in the perfusion effluent to fall to less than 20 micrometer. The mean calcium efflux from fibres dialyzed with EGTA buffered solution containing 0.3 micrometer ionized Ca and and no ATP is 0.6 pmol-cm-2-s-1. A two-fold stimulation of the calcium efflux is observed when ATP is added to fibres previously dialyzed with an ATP-free medium. Withdrawal of Na+ and Ca2+ from the external medium causes a  marked drop in the Ca2+ efflux in the presence of internal ATP.


Development of intestinal brush border membrane proteins in the rat. 1. The proteins of the intestinal microvillus membrane have been studied during post-natal development in the rat (days 12--37). 2. In suckling animals (up to age 20 days), the majority of alkaline phosphatase, glucoamylase and lactase activities in the distal half of the intestine were located in the supernatant fraction (100000 X g, 60 min). These enzymes were attached to the membrane from the proximal intestine at all ages. 3. Alkaline phosphatase, maltase and lactase activities in the supernatant fractions chromatographed in Sephadex G-200 in positions similar to the corresponding membrane enzyme. Corresponding activities for lysosomal counter-parts of maltase and lactase present in the supernatant fraction chromatographed differently. Moreover, pH optimum of the soluble enzymes was 9.2 for phosphatase and 5.5--6.0 for glycoamylase and lactase. The soluble lactase and alkaline phosphatase were inhibited minimally by p-chloromercuribenzoate, and sodium fluoride respectively. L-Phenylalanine (20 mM) did inhibit the soluble phosphatase by 90%. Thus, the soluble enzymes are not mainly of the lysosomal origin, but have characteristics of membrane-bound enzymes. 4. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate revealed 18 protein bands which were present in adult membranes. Two other proteins were unique for membranes of distal intestine in suckling rats. The proteins corresponding to known enzyme activity changed as expected with age (e.g. sucrase, maltase increased, lactase decreased). Most of the other proteins were also altered in amount during development. Thus, the changes in the microvillus membrane during development in the rat are not limited to specific enzymes.


Dynamic light scattering study of calcium-induced fusion in phospholipid vesicles. Acidic sonicated phospholipid vesicles can undergo dramatic morphological changes due to fusion in the presence of divalent metal ions. For example, small spherical phosphatidylserine vesicles can form scroll-like cylinders which precipitate in the presence of Ca2+ above a threshold concentration. Subsequent addition of EDTA will yield large, unilamellar vesicles. These events have previously been established through the combined use of differential scanning calorimetry and freeze-fracture electron microscopy. We have applied the technique of dynamic light scattering to follow these fusion events rapidly, accurately, and non-perturbatively as they occur in solution at calcium concentrations slightly below threshold for precipitation.


Purification of cohesive-end-producing restriction endonuclease from Bacillus subtilis G. A new restriction endonuclease was partially purified from Bacillus subtilis G (IAM1247). This restriction endonuclease (endonuclease RBsuG) seems to produce cohesive ends at its cleavage site.