[Combined action of nickel sulfate and x-irradiation on human lymphoblastoid leukemic cells].

In a first experiment, cells were cultured in media supplemented by nickel sulphate, irradiated in same media and cultured in same media after irradiation. In a second experiment, cells were cultured during 18 hrs. in media supplemented by nickel sulphate, and then cells were washed and cultured in normal media where they were irradiated. The nickel sulphate toxicity appears as a creasing function of the nickel sulphate concentration and the nickel sulphate action endurance. The nickel sulphate toxic effect is amplified by X-Rays. This amplification is a time function that depends on the X-Ray dose, nickel sulphate concentration and period of time from the outset of culture to the irradiation. The nickel sulphate toxic effect appears faster when nickel works after X-Rays.


[Oxygen consumption in human placental lobules in vitro (survival maintained by perfusion)].

The average oxygen utilization coefficient of 26% is calculated from PO2 determinations during the perfusion of the fetal circulation of isolated human term placental lobules. The oxygen consumption approximates 0.4 ml/min/kg placenta when Earle's salt solution is used as a perfusion medium and is equilibrated with a gas mixture containing 5% O2. The oxygen consumption reaches 2 ml/min/kg when the same Earle's solution is equilibrated with a gas mixture containing 95% O2.


[Influence of dietary lactose on the development of lactase activity in the digestive tract of the pig].

Lactase activity has been measured in the pancreas, the small and large intestine of 79 pigs varying in  age from 6-7 months. The endogenous enzyme level fluctuated along the small intestine but the activity did not vary according to the level of lactose fed in the diet either just after weaning or from 25 to 100 kg of live weight. Measurements performed in the content of the intestine showed that lactose could be digested by the enzymes of the microflora mostly active in the ileum, the caecum and the large intestine.


[Identification of 2 phosphorylated amino acids in chicken bone phosphoproteins].

Phosphoproteins of Chicken bone have been extracted by 0.5 M EDTA pH 7.5. Their amino acid composition was similar to that of phosphoproteins of other calcified tissues. The crude EDTA extract contained 80 to 90% proteins, only 70% of the total organic phosphorus was bound to the proteins. We have studied and identified two phosphorylated components. o-phosphoserine and o-phosphothreonine have been identified by amino acid analysis at pH 1.7 from a partial acid hydrolysate, and confirmed by the liberation of the parent amino acids after total hydrolysis. In addition, phosphorus was found equimolecular to both of them. The presence of these phosphorylated groups is important for an understanding of the role of these proteins in the mechanism of mineralization.


[Alpha-hydrazinophloretic acid, competitive inhibitor of fungal tyrosinase].

alpha-Hydrazinophloretic acid, the hydrazino analogue of tyrosine, was shown to behave as a competitive inhibitor of tyrosinase. Some closely related compounds, especially the hydrazino analogue of phenylalanine as well as other hydrazine derivatives, will also inhibit the enzyme, but in these cases, the inhibition observed belonged to the non-competitive type.


[Synthesis of specific proteins by the nucleoid of Escherichia coli].

The induction of beta-galactosidase and alkaline phosphatase by the nucleoid of Escherichia coli was studied. Only the membrane-associated form was active in the presence of S 30. The induction of beta-galactosidase showed an absolute requirement for the inducer and was enhanced by cyclic AMP and cyclic GMP. Further-more, in our hands, the synthetic activity of the membrane-associated nucleoid proved to be far higher than that of the soluble system described by Zubay. Our results suggest that membrane shield the structure which is necessary for the integrity of the initiation step of both transcription and translation.


[Study of marine microvibrios of Roscoff (Microvibrio marinus roscoffensis)].

Marine microvibrios, predators of E. coli, have been detected worldwide, from equatorial waters to the polar regions. The morphology and behavior of two microvibrios have been studied. Their multiplication and aggressiveness in regard to their bacterial prevy are not impeded by dialysis membranes and manifest themselves, away from all direct contact between the predator and its prey.


[Influence of a high-temperature environment on the development of experimental trypanosomiasis of the mouse].

Different evolutions of experimental trypanosomiasis are observed in Mice kept in a permanent 35 degrees C environment. Evolution depends on the individuality or the strain of the host animal. An experimental factor influence on the host mechanism defense rather than on the parasite multiplication rate is shown.


Arteriographic evidence of coronary arterial spasm in acute myocardial infarction.

Coronary arteriography was performed before and after the intracoronary injection of nitroglycerin to determine the presence or absence of spasm in patients within the first 12 hours of acute myocardial infarction. Coronary arterial spasm was demonstrated in six of fifteen (40%) acute myocardial infarctions associated with coronary artery disease. In five of the six instances the interval from the onset of symptoms to arteriography was less than 6 hours. Spasm was superimposed on a high-grade atherosclerotic obstruction and was separated from the catheter tip by a segment of normal vessel in each instance. The coronary artery remained patent (following the initial relief of spasm) in two patients maintained on sublingual nitrates and heparin. Spasm, superimposed on an atherosclerotic obstruction, may be the primary event or a secondary occurrence in the pathophysiology of acute myocardial infarction. Catecholamines could play an important role in the early pathophysiology of acute myocardial infarction by producing spasm and/or platelet aggregation at the site of an atherosclerotic obstruction. A dynamic interaction between spasm, platelet aggregates and the atherosclerotic plaque may precede coronary thrombosis.


Hemodynamic assessment of the glutaraldehyde-preserved porcine heterograft in the aortic and mitral positions.

Although glutaraldehyde-preserved porcine heterograft (PH) valves may have a lowered incidence of thromboembolism compared to mechanical valves, data concerning postoperative function in PH valves are incomplete. Accordingly, 26 patients receiving PH in the aortic (AO) or mitral position (MIT) were studied at cardiac postoperative catheterization (mean 19 weeks). The 12 AO patients had an average peak systolic gradient of 19 mm Hg (range 3-52 mm Hg); mean valve area (VA) 1.33 cm2 (0.75-2.5; two patients had postoperative aortic insufficiency. The 14 MIT patients had a mean gradient of 7.9 mm Hg (0-13.1); VA 1.84 cm2 (0.70-3.2; postoperative mitral regurgitation occurred in two patients. AO stent diameter (SD) related to VA, r = 0.85; and peak gradient, r = -0.75. However, MIT SD did not relate to VA or peak gradient. At the 14-month follow-up examination 9 of 11 AO and 7 of 11 MIT patients improved by at least one functional class. Thus, with the advantage of reduced thromboembolism and generally satisfactory valve hemodynamics, further clinical trial of glutaraldehyde-preserved porcine heterografts is justified.


Heart valve replacement with the Hancock bioprosthesis. Analysis of long-term results.

Between March 1970 and May 1976, 564 patients have undergone single or multiple heart valve replacement with the Hancock "SGP" bioprosthesis in our institution. Of these patients, 335 had single mitral, 102 aortic, one tricuspid, and 126 double or triple valve replacement, for a total of 629 xenografts. The long-term results, in terms of clinical improvement, survival, and complications, have been analyzed. Significant valve insufficiency secondary to primitive tissue alterations occurred in three patients, while reoperations were required in two for endocarditis and in two others for mitral stenosis caused by tissue ingrowth. We found that thromboembolic episodes occurred mainly in the early postoperative period up to the third month in 10 cases (1.76%). Three patients suffered peripheral embolization during the late follow-up period. Anticoagulants were not administered beyond 3 months postoperatively. Hemodynamic re-evaluation has been performed in 42 patients and the prosthesis has been shown to function properly either in the mitral or the aortic position. The data available to date indicate that the glutaraldehyde-preserved porcine valve is durable and we feel that its use is warranted in any valvular position.


Elevated serum concentrations of thyroxine-binding globulin and caeruloplasmin in methadone-maintained patients.

Patients on a methadone-maintenance program had high serum concentrations of thyroxine-binding globulin. This resulted in elevated serum thyroxine and triiodothyronine levels and low triiodothyronine uptake values. Their free thyroxine index was normal, as was serum thyroxine and triiodothyronine when related to thyroxine-binding globulin concentration. Serum caeruloplasmin concentration was also increased in methadone-treated patients.


An improved procedure for isolation of thyroxine-binding globulin from human pregnancy serum.

A convenient method for isolation of TBG from human pregnancy serum is reported. The method is based on batch-wise treatment of serum with hydroxyapatite followed by batch-wise adsorption of TBG to an affinity gel consisting of Sepharose to which thyroxine was bound with a spacer group. After selective desorption the TBG-preparation was practically pure. The small amounts of contaminating proteins were easily removed by affinity chromatography on Concanavalin A-Sepharose. The resulting preparation was shown to be homogeneous by polyacrylamide gel electrophoresis and immunological techniques.


Ribonuclease activity in human serum, cerebrospinal fluid, and urine.

Poly(C)-avid ribonucleases of molecular weight 33 000 are present in the serum, cerebrospinal fluid and urine of humans. Purified human urinary ribonuclease was used to produce a monospecific antibody in rabbits. The antibody was capable of: (i) inhibiting the enzyme activities in the serum, CSF, and urine; (ii) reacting with antigens in the serum and CSF. The antigens in the serum, CSF and urine were found to be immunologically identical. Immunoelectrophoresis data suggested that the urinary and CSF RNAase are chemically identical. Succesful renal transplantation reduced elevated serum RNAase to normal levels. The data suggest that the most likely source of both urinary and CSF ribonuclease activity is the blood stream.


A solid phase fluorescent immunoassay for the quantitation of the C3 component of human complement.

A non-competitive method for the determination of the C3 component of human complement in serum is described. This procedure involves use of a specific antibody covalently attached to derivatized polyacrylamide beads and a fluorescently labeled specific antibody. Reproducible results were achieved for C3 in serum in the range of 20 mg/d1 to 195 mg/d1 within 2 h. C3 levels as low as 125 ng/m1 can also be measured. Fluorescent immunoassay and radial immunodiffusion were used to determine C3 levels in healthy adults. Good agreement was found between the two methods.


Determination of plasma 3-methoxy-4-hydroxyphenyl-glycol by pulsed electron capture gas chromatography.

An improved method is described for determining picogram quantities of 3-methoxy-4-hydroxyphenylglycol (MHPG) in plasma of humans and of other species. The method makes use of gas-liquid chromatography and electron capture detection. Low level nonlinearity of detector response was corrected by operating the detector in the pulsed rather then the customary steady state mode. Detector overloading was prevented by heat coagulation of plasma proteins and subsequent ultrafiltration. Sensitivity was significantly enhanced by utilizing a derivatizing agent carrying a higher number of electrophores. Baseline conditions are described and control values for plasma MHPG of human volunteers, Rhesus monkeys and rats are presented.


Bidimensional electrophoresis in the diagnosis of mucopolysaccharidosis.

Using the modified bidimensional electrophoresis method, characteristic patterns of urinary glycosaminoglycans were obtained for nine different syndromes of mucopolysaccharidoses and normal. Each pattern, portrayed on a 55 mm square cellulose acetate membrane, was visualized by staining the electrophoretically separated GAGs with alcian blue. The method, tested with 38 cases, was precise and sensitive; the first direction of electrophoresis was run for 25 min and the second direction for 60 min. Because the method is qualitative, the usual quantitative measurements and calculations are circumvented. Moreover, any irregular pattern can readily be verified by repeating the bidimensional electrophoresis. Thus, the clarity of the pattern itself offers assurance of its diagnostic reliabilty; consequently, false negative and false positive results should be minimized.


Glucagon and diabetes. I. The failure of hyperglucagonaemia to influence the response of established diabetic ketoacidosis to therapy.

Clinical and biochemical variables were examined during two standardized, low-dose insulin regimens in seven subjects with diabetic ketoacidosis and one with hyperosmolar coma, in order to determine whether glucagon levels can be suppressed in ketoacidosis and whether hyperglucagonaemia influences the clinical and biochemical responses to treatment. Glucagon concentrations were significantly elevated (36.6-697.0 pmol/l) at presentation in all subjects. After institution of insulin treatment (4-8 u/h), glucose and glucagon levels decreased rapidly, and in five of the eight subjects glucagon levels reached undetectable concentrations (less than 3.0 pmol/l) during the initial treatment period. Further, neither plasma glucagon concentrations at presentation, nor the rate of glucagon decline during insulin treatment, appeared to influence the rapidity of the glucose decline or the persistence of the ketoacidosis. Thus, low-dose exogenous insulin suppresses glucagon secretion in diabetic ketoacidosis, and the changes in glucagon concentrations during treatment are unrelated to the clinical response.


Alterations in drug metabolism in workers exposed to polychlorinated biphenyls.

Administration of the polychlorinated biphenyls (PCBs) mixture, Aroclor 1016, to rats elicited a barbiturate type of inducing effect on the hepatic microsomal oxidative enzyme system. Aroclor 1016 caused significant increases in liver cytochrome P-450 content, microsomal protein, and ethylmorphine N-demethylase activity; its effect on benzo(a)pyrene hydroxylase activity was minimal. Unlike the widely studied PCBs mixture, Aroclor 1254, Aroclor 1016 did not induce cytochrome P-448 in liver microsomes. Five workers occupationally exposed to Aroclor 1016 in a capacitor-manufacturing plant showed a significantly lower mean antipyrine half-life (10.8 hr) than the mean half-life of 15.6 hr in non-PCBs-exposed normal subjects. These differences in half-life were accompanied by increased metabolic clearance rates in workers exposed to the PCBs, which strongly suggests that PCBs accelerate the rate of drug metabolism in man. Our studies show that Aroclor 1016 elicits the barbiturate type of inducing effects on drug metabolism in man as well as animals.


Alteration of plasma albumin in relation to decreased drug binding in uremia.

The binding of sulfadiazine in the plasma of normal and uremic subjects was measured by means of an ultrafiltration technique. Patients with uremia had reduced binding of sulfadiazine due to decreased albumin-binding capacity. No conclusive evidence was found to suggest that reduced drug binding in uremia is caused by competing metabolites. Studies of purified normal and uremic albumin revealed differences in amino acid composition and variations in the protein content of the two albumin bands found on isoelectric focusing. It is suggested that decreased drug binding in uremia may be at least partly due to altered albumin composition.


Cromolyn sodium in the treatment of asthma associated with aspirin hypersensitivity and nasal polyps.

The control of asthma by therapy with cromolyn sodium was studied in 28 adults with late-onset asthma associated with hypersensitivity to aspirin and nasal polyps. Four-week periods of treatment with the drug or a placebo were compared in a double-blind crossover study. A subsequent eight-week open trial in 20 patients was compared to their period of receiving placebo. There was slight but significant improvement in the forced expiratory volume in one second (FEV1; P less than 0.05) and the mean forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%; P less than 0.05) after four weeks of therapy with cromolyn sodium and in the FEV1 (P less than 0.05), the forced vital capacity (P less than 0.01), and FEF25-75% (P less than 0.01) after an additional eight weeks of therapy with cromolyn sodium. The improvement in pulmonary function was not associated with changes in the peak expiratory flow rate, the symptoms of asthma, the doses of additional medication, or the index of disability. The dosage of corticosteroids in 22 patients receiving long-term therapy with steroids was no different between the four-week periods of treatment with placebo or drug but was significantly lower (P less than 0.05) during the eight-week open trial. We conclude that administration of cromolyn sodium has a therapeutic effect in this group of asthmatic patients.


[Treatment of postoperative gastrointestinal fistulas by long-term parenteral feeding].

Twenty-nine anastomotic leakages of the gastrointestinal tract were treated by long-term parenteral nutrition; 20 closed spontaneously, the lethality was 18.3%. Especially, well-drained fistulas of the distal small bowel and the colon show a tendency to closure and should be treated by long-term parenteral hyperalimentation (2500-4000 KCal/24 h), if no signs of ileus or diffuse peritonitis are apparent. The technique and chance for success of hyperalimentation are discussed.


Length and interspersion of repetitive and non repetitive DNA sequences in four amphibian species with different genome sizes.

The interspersion period of repetitive and unique sequences was analyzed by two different methods, electron microscopy and agarose gel electrophoresis, for four Amphibian species with different nuclear DNA content, namely the Anura Xenopus laevis (3 pg DNA per haploid genome) and Bufo bufo (7 pg) and the Urodela Triturus cristatus (23 pg) and Necturus maculosus (52 pg). Within each of the two subclasses it has been found that interspecific differences, in DNA content, due to variations in the amount of repetitive sequences, do not involve variations in length of the interspersed repetitive sequences. They remain about 380 base pairs. Furthermore, the unique sequences length has been found to be shorter in Bufo (760 base pairs) than in Xenopus (1600) and in Necturus (880) than in Triturus (1340). A study of the interspersion period has shown that the great difference in DNA content between Anura and Urodela, which had been previously shown not to have involved changes in the relative amounts of the various sequence classes, does not involve changes in the interspersion period.


Direct correlation between a chromosome puff and the synthesis of a larval saliva protein in Drosophila melanogaster.

The structural gene Sgs-4 responsible for larval saliva protein 4 of Drosophila melanogaster was localized, with the help of Notch deficiencies, within the section between bands 3C10 and 3D1 of the X chromosome. In this chromosome section there is, very probably, only one fine band. In the third larval instar chromosome this section is transcriptionally active and forms a puff. When the ecdysone concentration increases, about 5 h before prepupa formation, it becomes inactive.--In section 3C of X chromosomes of third instar larvae of the stock Hikone-R no puff is formed. The saliva of these larvae lacks protein 4. However, female hybrids (H/B and H/O) from Hikone-R crossed with Berlin and Oregon respectively produce a Hikone-specific saliva protein 4h. The synthesis of protein 4h in the hybrids H/B and H/O is ascribed to an activation of the gene Sgs-4 in the Hikone chromosome.--In the saliva of heterozygotes (FM1/H) carrying one inversion chromosome In(1)FM1 and one X chromosome from Hikone, protein 4h could not be detected. In these inversion heterozygotes in 90% of all nuclei the homologues are not paired in 3C, and 3C is puffed only in the FM1 chromosome. This suggests that a precondition for the activation of Hikone gene Sgs-4 in heterozygotes may be intimate homologue pairing.--Intersexes with one of their X chromosomes from Hikone-R and the other from Berlin produce relatively more protein 4h than do diploid H/B females, indicating facilitated transcription as a result of dosage compensation.


[Problematic blood transfusion (author's transl)].

Two patients were admitted with signs of haemolysis due to severe transfusion reactions. Serological investigations showed the presence of the antibodies anti-IKb and anti-Fya. After a short period of haemodialysis the patient with Kidd antibodies died. A further patient with triple antibodies (anti-c, -K, -Lub) was so pre-immunised that with an antigen frequency of over 99.9% no compatible blood could be found in Europe. By means of information from the European Central Index in Amsterdam compatible blood for the operation could be obtained from Australia. In the fourth case the antibody anti-Cob was found which had not previously been described in Germany and with which the phenotype could be determined in 1405 unselected persons in the German population. The frequency of Cob is 7.2%.


[Morphological studies on the effect of lasers on dental pulp and mouth mucosa].

Macroscopic and microscopic findings made in the gingiva, lip, tongue and pulp tissue of monkeys show that from the histological viewpoint there are no objections to the use of Nd:YAG for sealing dental enamel and dentin.


Comparison of preventive effect of T3 and T4 on thyroxine release from thyroid induced by endogeneous TSH after TRH injection.

Comparison of Preventive Effect of T3 and T4 on Thyroxine Release from Thyroid Induced by Endogenous TSH after TRH Injection. Endocrinologia Experimentalis 11, 91-98, 1977. The technique of frequent blood sampling through polyethylene tubings inserted into blood vessels while maintaining isovolemia was used in pentobarbiturate anaesthetized rats weighing 250--300 g. The animals were fed low iodine diet for 4 weeks and injected 125I- (5 microgram Ci per animal daily) for 6 days begining from 8th day before the experiment. The effect of 25 microgram TRH injected through a cannula inserted into carotid artery in cranial direction was evaluated as per cent increase of labelled thyroxine in plasma at 120 min after the injection compared to its level at 30 min. Moreover, the inhibitory effect of various doses of thyroxine (T4; 5, 20 and 80 nmol kg-1) and triiodothyronine (T3; 1.25 and 5 nmol kg-1) injected i.v. at the intervals of 10, 20, 30, 60 and 180 min prior to TRH was investigated. It was found that the effect was time dependent, being negligible after 10 or 20 min, while after 60 and 180 min the increase of labelled T4 after TRH was fully prevented by 20 and 80 nmol T4 kg-1 and by 5 nmol T3 kg-1. The other doses (i. e. 5 nmol T4 kg-1 and 1.25 nmol T3 kg-1) were without effect. Thus, T3 was found to be significantly more active than equimolar doses of T4.


Effects of gamma-aminobutyric acid and histamine on prolactin secretion in the rat.

Histamine releases prolactin (PRL) in estrogen-progesterone primed male rats after both iv and intracisternal (ic) injection, but does not affect in vitro PRL secretion. This stimulatory effect is reversed by the alpha-adrenergic antagonist phenoxybenzamine and the histamine antagonist diphenhydramine, gamma-Amino butyric acid (GABA), which has little in vivo effect of its own, interferes with the activity of histamine and a variety of other stimulators of PRL secretion. These results suggest the involvement of the naturally-occurring substances histamine and GABA in the central regulation of PRL secretion.


Studies on the transfer of steroid hormones across the blood-cerebrospinal fluid barrier in the rhesus monkey. II.

The movement of progesterone (P), cortisol (F) and 17-hydroxyprogesterone (17-OHP) across the blood-cerebrospinal fluid (CSF) barrier was determined using six adult male rhesus monkeys with indwelling canulae in the lateral ventricles of their brains. Tritiated steroids were given iv as a bolus followed by a constant 6 h infusion with continuous collection of CSF and periodic sampling of blood before and during the infusion. The amounts of authentic steroid in the plasma and CSF were determined by recrystallization to constant isotopic ratio and the amount of free plasma steroid was determined by equilibrium dialysis against Ringer's solution. Tritiated progesterone was undetectable in the pooled samples of CSF. The average concentration of tritiated 17-OHP in the CSF was 10.3% of the concurrent plasma level while the concentration of tritiated F was 22.5% of the concurrent plasma level. Plasma free steroid was found to be 2.2% for P, 6.3% for 17-OHP and 22.3% for F, showing a rough correlation between steroid entry into the CSF and free steroid concentration in plasma.


Effects of glucocorticoids on casein gene expression in the rabbit.

Milk protein synthesis is initiated by prolactin and a glucocorticoid. In the rabbit, prolactin alone is sufficient. However, glucocorticoids potentiate the action of prolactin. The stimulatory effect of glucocorticoids was evaluated after injections of hydrocortisone acetate alone or associated with prolactin by measurements of (a) the total RNA and DNA content of mammary glands, (b) the lactose synthetase activity, (c) casein synthesis, and (d) the concentration of casein mRNA in total cellular RNA and in polysomal RNA by hybridization with its cDNA. The glucocorticoid, totally inactive alone, proved to have a stimulatory effect proportional to the dose injected when prolactin was present. This effect was more evident with low doses of prolactin. Glucocorticoids proceeded by amplifying the capacity of prolactin to enhance the concentration of casein mRNA available for translation. A parallel effect of glucocorticoids on translation of casein mRNA was suspected. Glucocorticoids injected with low doses of prolactin were unable to mimic all the effects of high doses of prolactin alone.


Separation of two Salmonella O-antigen polysaccharides by means of a glutaraldehyde-concanavalin-A polymer. Primary studies on the separated fractions.

The Salmonella zuerich (1,9,12,(46),27) cell wall O-polysaccharides have been characterized as a mixture of two immunologically distinct fractions differing in the presence or absence of the antigenic determinant 1 usually carried by side chains of an alpha-D-glucosyl residue. In this paper, we describe the use of concanavalin A in separating the two O-polysaccharides. The procedure involves polymerization of concanavalin A with glutaraldehyde, followed by selective adsorption of the polysaccharide containing O factor 1 and elution with D-glucose. Immunological and chemical analyses showed that the separation was successful and demonstrated chemical differences between these two fractions in relation to their immunological behaviour.


Characterisation of RNA fragments obtained by mild nuclease digestion of 30-S ribosomal subunits from Escherichia coli.

When Escherichia coli 30-S ribosomal subunits are hydrolysed under mild conditions, two ribonucleoprotein fragments of unequal size are produced. Knowledge of the RNA sequences contained in these hydrolysis products was required for the experiments described in the preceding paper, and the RNA sub-fragments have therefore been examined by oligonucleotide analysis. Two well-defined small fragments of free RNA, produced concomitantly with the ribonucleoprotein fragments, were also analysed. The larger ribonucleoprotein fragment, containing predominantly proteins S4, S5, S8, S15, S16 (17) and S20, contains a complex mixture of RNA sub-fragments varying from about 100 to 800 nucleotides in length. All these fragments arose from the 5'-terminal 900 nucleotides of 16-S RNA, corresponding to the well-known 12-S fragment. No long-range interactions could be detected within this RNA region in these experiments. The RNA from the smaller ribonucleoprotein fragment (containing proteins S7, S9 S10, S14 and S19) has been described in detail previously, and consists of about 450 nucleotides near the 3' end of the 16-S RNA, but lacking the 3'-terminal 150 nucleotides. The two small free RNA fragments (above) partly account for these missing 150 nucleotides; both fragments arose from section A of the 16-S RNA, but section J (the 3'-terminal 50 nucleotides) was not found. This result suggests that the 3' region of 16-S RNA is not involved in stable interactions with protein.


Immunochemical evidence for the difference between coenzyme-B12-dependent diol dehydratase and glycerol dehydratase.

Klebsiella pneumoniae ATCC 25955 (formerly named Aerobacter aerogenes PZH 572, Warsaw), which is known to produce coenzyme-B12-dependent glycerol dehydratase when grown anaerobically in a glycerol medium, formed coenzyme-B12-dependent diol dehydratase in a 1,2-propanediol-containing medium. Both the diol dehydratase and the glycerol dehydratase produced by the organism catalyzed the conversion of glycerol, 1,2-propanediol and 1,2-ethanediol to the corresponding aldehydes and underwent concomitant inactivation during the catalysis of glycerol dehydration, as does the diol dehydratase of K. pneumoniae (A. aerogenes) ATCC 8724. However, the two enzymes were distinguishable from each other by the monovalent-cation-selectivity pattern and by substrate specificity; that is, glycerol dehydratase preferred glycerol to 1,2-propanediol as a substrate, whereas diol dehydratase preferred 1,2-propanediol to glycerol, as judged from initial velocity studies. Ouchterlony double-diffusion analysis and immunochemical titration with rabbit antiserum against diol dehydratase of K. pneumoniae ATCC 8724 established clearly that the diol dehydratase of K. pneumoniae ATCC 25955 is immunologically similar to that of K. pneumoniae ATCC 8724, while the glycerol dehydratase of the former is different from the diol dehydratase of both strains. Both the enzymes were found to be distributed in several bacteria of the family Enterobacteriaceae.


The action of lysozyme on peptidoglycan with N-unsubstituted glucosamine residues. Isolation of glycan fragments and their susceptibility to lysozyme.

1. A peptidoglycan preparation N-acetylated at about 30% of glucosamine residues was obtained by the treatment of the lysozyme-resistant cell wall paptidoglycan of Bacillus cereus with acetic anhydride at pH 7. Fractionation of dialyzable material resulting from lysozyme digestion of the glycan component of this peptidoglycan preparation yielded five oligosaccharides designated as S1 to S5 besides the disaccharide GlcNAc-MurAc. 2. Oligosaccharide S3, which accounted for about 30% of the disaccharide units recovered as disaccharides and oligosaccharides, was identified as GlcN-MurAc-GlcNAc-MurAc. Oligosaccharide S1, accounting for about 20% of the disaccharide units recovered, was characterized as GlcN-MurAc-GlcN-MurAc-GlcNAc-MurAc, while oligosaccharide S2, present in a smaller amount, as GlcNAc-MurAc-GlcN-MurAc-glcNAc-MurAc. Oligosaccharides S4, and S5, present in small amounts, were identified as GlcNAc-MurAc-GlcNAc-MurAc and MurAc-GlcNAc-MurAc, respectively. 3. Oligosaccharides S1, S3 and S5 proved to be completely insusceptible to lysozyme, whereas S2 was digsted by lysozyme to produce GlcNAc-MurAc and S3. S1 was found to act as a more potent inhibitor than S3 in lysozyme-catalyzed digestion of polysaccharides. 4. The results obtained show that the lysozyme-catalyzed hydrolysis of peptidoglycan oligosaccharides had an obligatory requirement for the N-acetyl group on the glucosamine residue located in subsite C in the enzyme-substrate complex.


Scanning electron microscopic study of calcium oxalate concretions grown in gel system and calcium oxalate stones.

Calcium oxalate concretions grown in gelatin gel medium, and calcium oxalate renal stones were studied by polarized light and scanning electron microscopy. In both cases, the results obtained confirm that the surface crystals have random axial orientation and that the gross configuration seems to be determined by the fibrous organic matrix. In vitro concretions grown in the gelatin gel medium are more resistant to EDTA demineralization and to ultrasonic irradiation than calcium oxalate stones.


Prostaglandin-induced effects in the primate cerebral circulation.

The effects of intracarotid infusions of prostaglandins E2 and F2alpha on cerebral blood flow (CBF) and oxygen consumption (CMRO2), and on extracranial blood flow, have been studied in anaesthetisex baboons. The 133Xe clearance method was used for measuring CBF, whilst extracranial blood flow was assessed by both the local tissue injection of 133Xe and external carotid artery flowmetry. Both PGF2alpha and PGE2 (10(-7) and 10(-6) g/kg/min) reduced both CBF and CMRO2. Spasm of the internal carotid artery with PGE2 was noted at the higher dose. Following osmotic opening of the blood-brain barrier by the hypertonic urea technique, the effects of small doses of PGE2 and CBF and CMRO2 were greatly potentiated. PGE2 greatly increased extracranial blood flow. Hence, both PGE2 and PGF2alpha reduce CBF and CMRO2, whilst PGE2 greatly increases extracranial blood flow.


Increased prostaglandin synthetase activity in inflamed tissues of the rabbit eye.

Tissues from normal and inflamed rabbit eyes were examined for prostaglandin synthetase activity using homogenates and microsomal preparation. Ocular inflammation was induced with 10 microgram Shigella endotoxin injected into the vitreous body. Homogenates of iris-ciliary processes of normal and inflamed eyes synthesized 2.3 and 5.6 microgram respectively of prostaglandins per g wet weight of tissues from endogenous substrate. Intact tissues from normal and inflamed eyes produced similar amounts of prostaglandins (2.2 and 5.3 microgram/g wet wt. respectively). Microsomes obtained from inflamed tissues produced 565 ng of prostaglandins per mg of protein per 30 min compared with 190 ng synthetized by normal microsomes. The apparent Km for the substrate of prostaglandin synthetase from inflamed tissues compared with that from normal was found to be lower. It is suggested that prostaglandin synthetase activity in the ocular tissues is modified during Shigella endotoxin-induced inflammation.


Slow wave sleep and a state resembling absence epilepsy induced in the rat by gamma-hydroxybutyrate.

The effect of gamma-hydroxybutyrate (GHB) in relatively low doses (12.5--200 mg/kg) on sleep stages, electrocorticogram (ECoG) patterns and behavior was investigated in the rat. 50-100 mg/kg GHB induced slow wave sleep but, in contrast to the cat, not paradoxical sleep. 200 mg/kg induced a hypersynchronous, bilaterally symmetrical ECoG pattern, which was different in amplitude and frequency distribution from normally occurring high amplitude patterns. When the hypersynchrony occurred in bursts, the rats displayed a sudden arrest of motor behavior. Convulsions were not induced. The results, together with the finding of others that GHB is a natural constituent of mammalian brain and our previous observation that the GHB-induced hypersynchrony can be antagonized by anti-absence (anti-petit mal) drugs are discussed in view of the possibility that GHB might play a role in the etiology of absence epilepsy in man.


Susceptibility of spontaneous sympathetic outflow and sympathetic reflexes to depression by clonidine.

The hypotensive activity of clonidine has been attributed to inhibition of sympathetic outflow. The present series of experiments examined the relative influence of clonidine on spontaneous outflow and various sympathetic reflexes in anesthetized cats. Clonidine resulted in dose-related decreases in the former. Increases in efferent sympathetic activity mediated by baroreceptors and supraspinally integrated potentials evoked in the splanchnic nerve by somatic nerve stimulation were inhibited to a lesser extent. Splanchnic potentials evoked by spinal cord stimulation in spinal animals were also diminished. In contrast, baroreceptor induced reflex decreases in sympathetic outflow were only minimally affected. These experiments indicate that clonidine can inhibit central sympathetic mechanisms at various levels including the spinal cord but that considerable differences exist in the susceptibility of sympathetic outflow and various reflexes to depression by the compound.


Mesolimbic involvement in the locomotor stimulant action of thyrotropin-releasing hormone (TRH) in rats.

Thyrotropin-releasing hormone (TRH) injected i.p. in doses of 5 mg/kg and higher had a strong locomotor stimulant action with development of frequent rearing, mild sniffing, grooming, preening and other excitatory behaviours. The locomotor stimulation was also produced by bilateral injection of TRH and dopamine (DA) into the nucleus accumbens but not by bilateral injection of these substances into the caudate nucleus. Unilateral intracaudate injection of TRH provoked no behavioural changes in contrast to a distinct circling response to similarly injected DA. Either i.p. or bilateral intra-accumbens injection of haloperidol or pimozide on low doses effectively blocked the locomotor stimulant action of TRH. These results indicate that the DA system in the nucleus accumbens may be of importance in mediation of the locomotor stimulant action of TRH. Differential affinity of TRH to the two DA systems, the mesolimbic and nigrostriatal DA systems is also suggested.


Diversion of prostaglandin endoperoxide metabolism by selective inhibition of thromboxane A2 biosynthesis in lung, spleen or platelets.

Infusion of arachidonic acid through the guinea pig lung or the cat spleen causes a release of thromboxane A2 and prostaglandins, as measured by bioassay. After incubation of human platelets with arachidonate similar metabolites are formed, as demonstrated chromatographically. Infusion of imidazole (50-75 microgram/ml) through the lung or spleen specifically inhibits thromboxane A2 production and diverts the pathway to the prostaglandins, mainly prostaglandin F2alpha. In human platelets imidazole causes a dose-dependent inhibition of thromboxane A2 formation (ID50 5.5 X 10(-4) M). This inhibition is accompanied by a dose-dependent increase in prostaglandin F2alpha. Since thromboxane A2 induces platelet aggregation and is a potent vasoconstrictor, diversion of pathways to prostaglandins with opposite or less potent action might be of relevance in the treatment of cardiovascular diseases.


Size constancy in rhesus monkeys: effects of pulvinar, prestriate, and inferotemporal lesions.

The present study tested the theory that inferotemporal cortex integrates 1) distance information transmitted via superior colliculus-pulvinar afferents, with 2) form information transmitted via striate-prestriate cortex afferents (Gross, 1973a, 1973b). Monkeys were trained to choose the larger of two objects, independent of distance, to obtain a reward. Based on the integration theory, the following predictions concerning this size constancy discrimination were made: 1) monkeys with pulvinar lesions, unable to code distance, should be impaired and adopt strategies based on retinal image size; and 2) monkeys with prestriate lesions, unable to code retinal image size, should be impaired and adopt strategies based on distance. Contrary to these predictions, pulvinar lesions produced no deficit; and although prestriate lesions did produce an impairment, it was due to a failure to code distance in assessing the true size of the object. Thus, monkeys with prestriate lesions consistently responded to retinal image size instead of object size. Replicating an earlier report (Humphrey and Weiskrantz, 1969), inferotemporal lesions also produced an impairment; however, errors made by monkeys with inferotemporal lesions were random and could not be attributed to any consistent strategy. All monkeys reacquired the discrimmination postoperatively, indicating that there are multiple mechanisms available to the brain-damaged animal for the perception of size constancy.


Bilateral lesions of the medial longitudinal fasciculus in monkeys: effects on the horizontal and vertical components of voluntary and vestibular induced eye movements.

Bilateral transections across the brainstem interrupted the medial longitudinal fasciculus (MLF) in three monkeys trained to make eye movements while subjected to horizontal or vertical angular accelerations. Eye movements measured before and after the lesion revealed deficits in both voluntary and vestibular compensatory eye movements; the deficits differed in the horizontal and vertical directions. Vertical saccades in both directions were normal but eccentric positions of fixation could not be maintained; a drift toward the midline followed by a corrective saccade produced vertical fixation nystagmus. Furthermore, the vertical vestibulo-ocular reflex (VOR) was abolished and vertical smooth pursuit was impaired. Along the horizontal meridian, adduction across the midline could not be achieved during either saccades, smooth pursuit, or the VOR. Temporal saccades were normal whereas nasal saccades were considerably slowed. If the eye was not required to cross the midline, the phase shift during the VOR was within 15 deg of normal in each eye. The gain of the VOR was reduced to about 0.4 immediately after the lesion, but recovered within one month. These findings suggest that the MLF transmits quite different kinds of information to horizontal and vertical oculomotoneurons and that deficits in vertical eye movements may be a sensitive indicator of anterior internuclear ophthalmoplegia.


The morphology and laminar distribution of cortico-pulvinar neurons in the rhesus monkey.

Using autoradiography and the horseradish peroxidase method, the morphology and laminar distribution of cortico-pulvinar neurons and the reciprocity of connections between pulvinar and cortex were examined in five Rhesus monkeys which had received medial, lateral and inferior pulvinar nucleus injections of both tritiated amino acids and horseradish peroxidase. Cortico-pulvinar neurons were identified in one heterotypical cortical area (area 17) and in many homotypical areas in frontal (areas 45, 46, 11, 12), parietal (5, 7), occipital (18, 19) and temporal (20, 21, 22) lobes. The cortico-pulvinar neurons were pyramidal in shape and ranged in size from small to large. In heterotypical cortex they were found in layers V and VI whereas in area 17 they were found only in layer Vb. Reciprocal connections between pulvinar and cortex were a feature of homotypical but not heterotypical cortex.


Discharge properties of neurons in the monkey thalamus tested with angular acceleration, eye movement and visual stimuli.

Monkeys were trained to make visually evoked eye movements while undergoing simultaneous head rotation. Single units were recorded in the pregeniculate nucleus (PGN). PGN neurons discharged during each saccade, but there was no change in activity with horizontal head acceleration or with various combinations of head and smooth pursuit eye movements as previously described in the cat. Therefore, the anatomical homology between LGNv and PGN does not appear to have a neurophysiological basis. Neurons in the oral part of VPL or occasionally in VPI discharged as a function of head velocity but not with saccades, smooth pursuit or fixation eye movements, nor after brief light flashes or during smooth pursuit across structured backgrounds. This suggests that VPLo and VPI are only vestibular relay nuclei and not concerned with vestibular/visual or vestibular/oculomotor interactions.


[Inferotemporal cortex and short term visual memory in monkeys. New data].

The effects of bilateral electrical stimulation of inferotemporal cotex on matching to sample were studied in four monkeys. Each session was defined by four different factors. 1. Number of stimuli: the same pair of stimuli (one-pair condition, OP) or a different pair of stimuli (multi-pair condition, MP) was used, from trail to trial. 2. Location of stimulation: anterior inferotemporal cortex (ITA) or posterior inferotemporal cortex (ITP). 3. No intra-trial delay (simultaneous match to sample, SMS) or 5-secintra-trial delay (delayed match to sample, DMS). 4. Period of stimulation: sample resentation, delay or match period. Stimulation had no effect on SMS in all the combinations of the three other factors. ITP or ITA stimulation had no effect on DMS when applied during the delay, in OP and in MP condition. ITP stimulation during the sample resentation produced a significant deficit in OP and MP condition. ITA stimulation during the match period produced a significant deficit in OP but not in MP condition.


The effect of danazol on anterior pituitary function.

Danazol was given in a daily dose of 600 mg for 15 days to five postmenopausal women and five normal adult men. The basal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and cortisol were determined for 3 days before treatment and during the last 3 days of treatment. A combined intravenous injection of 25 micrograms of gonadotropin-releasing hormone (GnRH) and 200 micrograms of thyrotropin-releasing hormone (TRH) was also given before and on the last day of treatment to each subject. Danazol reduces basal levels of FSH and LH and their cumulative response to GnRH but exercises no significant effect on either basal levels of TSH or PRL or their response to TRH, nor does it modify basal cortisol secretion.


Isolated follicle-stimulating hormone deficiency in man.

Two men with serum levels of follicle-stimulating hormone (FSH) persistently below 3 mIU/ml and normal levels of luteinizing hormone (LH), thyroid-stimulating hormone (TSH), growth hormone, prolactin, cortisol, and testosterone are reported. The intravenous administration of thyrotropin-releasing factor led to a normal increase in TSH and prolactin levels. Gonadotropin-releasing factor stimulation resulted in a net increase of 2 mIU/ml and 25 mIU/ml for FSH and LH, respectively. The administration of clomiphene resulted in a normal FSH increase in both patients, an LH increase in one, and a serum testosterone increase in the other. These results suggest a possible defect for FSH production at a level above the pituitary. Semen analyses revealed abnormalities in motility and morphology. A testicular biopsy from one patient revealed delayed maturation of spermatogenesis. It is recommended that serum FSH determinations be included in studies of male infertility patients.


Ultrasound as a new method of male contraception.

Twenty male cats were treated once or twice with 1 watt/sq cm of ultrasound for 10 minutes. Each of 24 male dogs received one to three treatments with 1 watt/sq cm for 10 minutes. Another six dogs were treated with 2 watts/sq cm for 15 minutes. Four Cebus apella monkeys were treated with the same dosage as that used for the cats and dogs. A dosage of 1 watt/sq cm for 10 minutes was also applied to four human patients without the use of anesthetics, and no pain or side effects were noted. In all treated animals as well as in human patients the results indicate that ultrasound significantly suppresses spermatogenesis according to the dosage and frequency of treatment, without any effect on Leydig cells or blood testosterone levels.


Glycogen metabolism in vesicles of hydatidiform mole in vitro.

Glycogen content, glycogen synthetase, and glycogen phosphorylase were studied in placental tissue of normal pregnancy and in vesicles of hydatidiform mole. The glycogen content of placental tissue of normal pregnancy decreased significantly with increased gestational age: 6 to 10 weeks, 716.6 +/- 55.7 mg/100 gm wet weight (mean +/- standard error of the mean); 15 to 20 weeks, 216.1 +/- 11.2 mg/100 gm; and 37 to 41 weeks, 176.1 +/- 18.1 mg/100 gm. The decrease in placental glycogen content was accompanied by a corresponding decrease in the placental glycogen synthetase enzyme levels, whereas no remarkable change was found in the glycogen phosphorylase enzyme levels. The glycogen content of hydatidiform mole tissue from 10 patients (13 to 20 weeks of gestation) was 507.0 +/- 58.0 mg/100 gm and was significantly (P less than 0.005) higher than that of normal placental tissue with a corresponding period of gestation. A possible cause of this phenomenon may be the marked decrease in the glycogen phosphorylase enzyme level in hydatidiform mole tissue, which was about one-third that of the normal placental tissue.


Luteinizing hormone-releasing hormone, ovariectomy, and silastic vaginal rings in the Rhesus monkey.

The interaction of estradiol and luteinizing hormone-releasing hormone (LRH) may be a critical physiologic mechanism regulating the occurrence of ovulation in many species. These studies were conducted to assess (1) the effects of intramuscular injections of LRH in the intact female rhesus monkey and (2) the effects of estradiol in a Silastic delivery system in ovariectomized female rhesus monkeys. No changes in blood levels of luteinizing hormone (LH) were detected in response to 200 micrograms of LRH. Ovulation did not occur 48 hours after treatment. Ovariectomy decreased estradiol, increased LH, and had no effect on prolactin concentrations in sera. Insertion of a vaginal ring containing 10% estradiol increased blood estradiol levels 100-fold. Serum prolactin levels were unaffected; however, LH concentrations were altered in a multiphasic fashion. After the ring had been in place for 15 days, vaginal blood similar to menstrual flow was observed following removal.


Immunization of mice with heat-solubilized hamster zonae: production of anti-zona antibody and inhibition of fertility.

Immunization of female mice with heat-solubilized hamster zonae pellucidae resulted in the production of antibody specific for the zona pellucida of several species, including that of primates. Complete, although temporary, infertility was produced in the mice. The zonae of ovulated eggs from the immune mice were found to contain antibody and complement. Many also appeared abnormal, but no apparent effect was observed on either vitelli or any of the other tissues that were examined. These results suggest the feasibility of developing a zona vaccine for contraception.


Effect of prostaglandins on steroidogenesis by bovine adrenal cortex mitochondria.

Prostaglandins (PGA1, PGE2, PGF2 alpha) were found to increase cholesterol side-chain clevage activity in isolated bovine adrenal cortex mitochondria, provided calcium was present in the incubation medium. Optimal stimulation was observed at low PG concentrations (10-7 to 10-9 M), with malate or malate-NADPH supported side-chain cleavage. Under the same conditions, two endoperoxide analogs and several fatty acids were ineffective. The PG action was not observed with a mitochondrial acetone powder preparation. These observations suggest that primary PG may act by interfering with calcium distribution at the mitochondrial level, leading to the activation of cholesterol side-chain cleavage. Thus, an intracellular action of endogenous PG may be considered in the regulation of adrenal cortex steroidogenic functions.


Regulation of glycogen synthase interconversion in cultured muscle cells: actions of insulin, calcium, ionophore A 23187 and cytochalasin B.

The glycogen content of cultured chick embryo breast muscle cells changes during their development and can be reduced by starvation. It is demonstrated that the rate of glucose incorporation into glycogen and the degree of interconversion of glycogen synthase are controlled by the actual glycogen content. Stimulation of both corresponding activities by insulin is found in fused and in unfused cells. The insulin response depends on the extracellular calcium concentration and can be mimicked by the ionophore A 23187. These metabolic effects as well as calcium efflux data confirm the hypothesis that insulin acts on its enzyme target via increased cytoplasmic calcium concentration. Cytochalasin B is shown to inhibit the interconversion but does not interfere with the insulin-induced increase of the mitochondrial calcium pool or with the acceleration of the calcium efflux out of 45C-preloaded myotubes.


Hypothalamic regulation of insulin release in rhesus monkeys.

Evidence of a neurohumoral factor capable of stimulating insulin and glucagon secretion was found in perfusates from ventrolateral hypothalamus (VLH) of rhesus monkeys. The perfusates from the VLH were collected via push-pull cannulas and injected into the peripheral circulation. Increase in portal insulin and glucagon was observed following the injection of six different perfusates. The amount of insulin released from isolated rat islets incubated with perfusates was significantly increased at glucose concentrations greater than 5 mM. The perfusates from the VLH appear to have effects on insulin and glucagon secretion that are opposite those of somatostatin.


[The follow-up of high risk pregnancies with the determination of estriol 16-glucuronid excretion. Second: Excretion in preeclampsia, post maturity, intrauterine growth retardation, diabetes, Rh incompatability and intrauterine fetal deaths (author's transl)].

The estriol 16-glucuronid excretion was determined in 186 urine samples in cases with preeclampsia, post maturity, pregnancies past the expected date of confinement, intra-uterine fetal deaths, congenital anomalies, Rhesus incompatability and diabetes mellitus. In groups with mild dystrophy, severe dystrophy, and intra-uterine fetal death, three zones of estriol 16-glucuronid excretion were determined. Zone 1 is suggestive of a possible fetal impairment. Zone 2 shows a high probability of fetal impairment and Zone 3 was considered as lethal zone suggestive of imminent intra-uterine fetal death. The degree of rhesus incompatability, disease of the fetus or of diabetogenic fetopathy was not recognizable by the estriol 16-glucuronid excretion.


Centromeric effect on the degree of nonrandom disjunction in the female Drosophila melanogaster.

From crosses of females possessing a heteromorphic X-chromosome bivalent, FR1/+, the shorter crossover products were recovered on the average more frequently than the longer reciprocals as predicted by Novitski's (1951) hypothesis of nonrandom disjunction (NRD). The present study stemmed from an unexpected result of these crosses. Evidence for a centromeric effect on NRD was obtained, suggested by a negative correlation between the degree of NRD, c, and the distance between the region of exchange and the centromere as inferred from SET's (single exchange tetrads). Studies on sex chromosome systems other than FR1 confirmed these results. An analogous centromeric effect on preferential segregation had been clearly demonstrated in maize (Kikudome 1958, 1959; Rhoades and Dempsey 1966). However, prior to the present investigation, no such effect of the centromere on NRD in Drosophila had been described, although reanalysis of part of the data of Novitski (1951) and Novitski and Sandler (1956) suggests some evidence of a seriation of increasing c values extending from the most distal region of the chromosome toward the centromere. A suggestion that the effect in Drosophila may be related in some way to the time required for chiasma terminalization, i.e., those terminalizing earlier (distally located crossovers) permitting more random disjunction of the chromatids from the asymmetric dyad and those terminalizing later, progressively less random, is considered and rejected since in general the expected pattern of c values for the various double exchange tetrads (DET's) is inconsistent with that prediction and provides evidence suggesting the possibility of reversals, in part, of c values obtained for SET's.


Maternal inheritance of enzymes in the mealybug Pseudococcus obscurus (Homoptera).

In the mealybug Pseudococcus obscurus Essig (Pseudococcidae) two esterases, a tyrosinase and a mannosephosphate isomerase, exhibited an unusual type of maternal inheritance. Electromorphs (alleles) were transmitted by both parent but segregation was delayed by one generation and full sisters always had the same phenotype. Moreover, for esterase-1, in which three alleles were present, some of the females exhibited all three alleles. Several other polymorphic loci exhibited normal transmission and segregation. This mode of inheritance can be readily explained by assuming that most or all of the enzymes coded for by these loci are produced by the mycetocytes. The mycetocytes house intracellular bacteria-like symbionts and are usually formed by the fusion ofthe polar bodies and one or more cleavage nuclei. For a locus with two alleles exhibiting this type of inheritance, the expected frequencies of the three phenotypes are p3, 3pq an equation is presented for estimating the frequency of alleles from the frequencies of the phenotypes and it is shown that for three samples from wild populations there is a good agreement between the expected and observed frequencies of the phenotypes.


The genetic structure of natural populations of Drosophila melanogaster XIII. Further studies on linkage disequilibrium.

The Raleigh, North Carolina, population of Drosophila melanogaster was examined for linkage disequilibrium in 1974, several years after previous analyses in 1968, 1969, and 1970. alphaglycerol-3-phosphate dehydrogenase-1 (alphaGpdh-1), malate dehydrogenase-1 (Mdh-1), alcohol dehydrogenase (Adh), and hexokinase-C (Hex-C, tentative name, F. M. Johnson, unpublished; position determined by the present authors to be 2-74.5) were assayed for 617 second chromosomes, and esterase-C (Est-C) and octanol dehydrogenase (Odh) were assayed for 526 third chromosomes. In addition, two polymorphic inversions in the second chromosomes [In(2L)t and In(2R)NS] were examined, and the following findings were obtained: (1) No linkage disequilibrium between isozyme genes was detected. Significant linkage disequilibria were found only between the polymorphic inversions and isozyme genes [In(2L)t vs. Adh, and In(2R)NS vs. Hex-C]. Significant disequilibrium was not detected between In(2L)t and alphaGpdh-1, which is included in the inversion, but a tendency toward disequilibrium was consistently found from 1968 to 1974. The frequency of two-strand double crossovers within inversion In(2L)t involving a single crossover on each side of alphaGpdh-1 was estimated to be 0.00022. Thus, the consistent but not significant linkage disequilibrium between the two factors can be explained by recombination after the inversion occurred. (2) Previously existing linkage disequilibrium between Adh and In(2R)NS (the distance is about 30 cM, but the effective recombination value is about 1.75%) was found to have disappeared. (3) No higher-order linkage disequilibrium was detected. (4) Linkage disequilibrium between Odh and Est-C (the distance of which was estimated to be 0.0058 +/- 0.002) could not be detected (chi(2) (df=1) = 0.9).-From the above results, it was concluded that linkage disequilibria among isozyme genes are very rare in D. melanogaster, so that the Franklin-Lewontin model (Franklin and Lewontin 1970) is not applicable to these genes. The linkage disequilibria between some isozyme genes and polymorphic inversions may be explained by founder effect.


Isolation of spontaneously derived mutants of Caulobacter crescentus.

Caulobacter crescentus has a penicillinase which precludes the use of penicillin for mutant enrichment. However, two other antibiotics, fosfomycin and D-cycloserine, can be enrich for C. crescentus mutants. In enrichment procedures for C. crescentus auxotrophs, spontaneously derived mutants occur at a frequency of 5-10% among the survivors of an enrichment procedure. Consequently, large numbers of mutants are readily obtained without any need for mutagenesis. These mutants are heterogeneous both with regard to the type of mutation and to the nutritional requirement. A similar procedure has been used to isolate temperature-sensitive mutants.


Analysis of the negative complementation of abruptex alleles in gynandromorphs of Drosophila melanogaster.

Certain Abruptex alleles in the Notch pseudoallelic series of Drosophila melanogaster show strong negative complementation. Heterozygous combinations of some viable alleles are lethal. As a lethal system this is unique. Analysis of this type of allelic interaction in gynandromorphs suggests that the lethal focus has a fate-map site in the anterior part of the fly, probably close to the central part of the thorax. In addition to the lethal effect, negative interaction of the alleles can also be seen in the morphological level, the negative interaction of the alleles can also be seen in the morphogenesis of wings and chaetae of thorax and head. At this morphological level, the negative interaction of the alleles appears to be autonomous.


On the components of segregation distortion in Drosophila melanogaster.

The segregation distorter (SD) complex is a naturally occurring meiotic drive system with the property that males heterozygous for an SD-bearing chromosome 2 and an SD(+)-bearing homolog transmit the SD-bearing chromosome almost exclusively. This distorted segregation is the consequence of an induced dysfunction of those sperm that receive the SD(+) homolog. From previous studies, two loci have been implicated in this phenomenon: the Sd locus which is required to produce distortion, and the Responder (Rsp) locus that is the site at which Sd acts. There are two allelic alternatives of Rsp-sensitive (Rsp(sens)) and insensitive (Rsp(ins)); a chromosome carrying Rsp(ins) is not distorted by SD. In the present study, the function and location of each of these elements was examined by a genetic and cytological characterization of X-ray-induced mutations at each locus. The results indicate the following: (1) the Rsp locus is located in the proximal heterochromatin of 2R; (2) a deletion for the Rsp locus renders a chromosome insensitive to distortion; (3) the Sd locus is located to the left of pr (2-54.5), in the region from 37D2-D7 to 38A6-B2 of the salivary chromosome map; (4) an SD chromosome deleted for Sd loses its ability to distort; (5) there is another important component of the SD system, E(SD), in or near the proximal heterochromatin of 2L, that behaves as a strong enhancer of distortion. The results of these studies allow a reinterpretation of results from earlier analyses of the SD system and serve to limit the possible mechanisms to account for segregation distortion.


Behavior of somatic cells homozygous for zygotic lethals in Drosophila melanogaster.

The behavior in genetic mosaics of 86 EMS-induced sex-linked lethals has been studied. Seventy-five percent of them are autonomous in gynandromorphs. Forty-three lethals nonviable in sex mosaics have been analyzed in X-ray-induced spots in the abdominal tergites and the imaginal wing derivatives. Of the lethals, 90.7% are homozygous viable in mosaic spots, and only 9.3% have been classified as epidermal cell lethal. Thus, the fraction of the Drosophila genome essential for cell viability has been estimated to be about 420 genes. The phenotypes at the cellular level of some cell-viable mutations altering cell parameters (mitotic orientation, differentiation, etc.) are described.


Experimental population genetics of meiotic drive systems. I. Pseudo-Y chromosomal drive as a means of eliminating cage populations of Drosophila melanogaster.

The experimental population genetics of Y-chromosome drive in Drosophila melanogaster is approximated by studying the behavior of T(Y;2),SD lines. These exhibit "pseudo-Y" drive through the effective coupling of the Y chromosome to the second chromosome meiotic drive locus, Segregation distorter (SD). T(Y;2),SD males consequently produce only male offspring. When such lines are allowed to compete against structurally normal SD(+) flies in population cages, T(Y;2),SD males increase in frequency according to the dynamics of a simple haploid selection model until the cage population is eliminated as a result of a deficiency in the number of adult females. Cage population extinction generally occurs within about seven generations.-Several conclusions can be drawn from these competition cage studies:(1) Fitness estimates for the T(Y;2),SD lines (relative to SD(+ )) are generally in the range of 2-4, and these values are corroborated by independent estimates derived from studies of migration-selection equilibrium. (2) Fitness estimates are unaffected by cage replication, sample time, or the starting frequency of T(Y;2),SD males, indicating that data from diverse cages can be legitimately pooled to give an overall fitness estimate. (3) Partitioning of the T(Y;2),SD fitnesses into components of viability, fertility, and frequency of alternate segregation (Y + SD from X + SD(+)) suggests that most of the T(Y;2),SD advantage derives from the latter two components. Improvements in the system might involve increasing both the viability and the alternate segregation to increase the total fitness. While pseudo-Y drive operates quite effectively against laboratory stocks, it is less successful in eliminating wild-type populations which are already segregating for suppressors of SD action. This observation suggests that further studies into the origin and rate of accumulation of suppressors of meiotic drive are needed before an overall assessment can be made of the potential of Y-chromosome drive as a tool for population control.


Linkage disequilibrium in natural populations of Drosophila melanogaster Seasonal variation.

Linkage disequilibrium among ten polymorphic allozyme loci and polymorphic inversions on chromosomes 2 and 3 in a natural population of Drosophila melanogaster was examined early and late in the annual season. Similar to previous studies, little linkage disequilibrium was observed among allozymes. The two significant cases that were observed in the first sample behaved in a contradictory way. One declined much more rapidly than expected due simply to recombination; the other declined slowly as expected. There was littly change in allozyme or inversion frequencies during the season.


The influence of the mating system on the maintenance of genetic variability in polygenic characters.

The traditional models of the effect of assortative mating and inbreeding on the genetic variance of polygenic characters (FISHER 1918; WRIGHT 1921) presume that there is no natural selection or mutation. In a large population, the genetic variance determined by additive genes may then increase by up to a factor of two with local inbreeding, and even more with assortative mating. The classical models are still used to interpret data from natural populations. But contrary to their assumptions, most metrical characters in natural populations are usually thought to be under a type of selection which depletes polygenic variation. Mutation is then necessary to maintain genetic variation. The present models show that with the additional features of mutation and selection, in a large population, the mating system has no influence on the amount of genetic variability maintained by additive genes.


Cyanide-insensitive respiration in Schizophyllum commune.

Two mutants of the hymenomycete Schizophyllum commune, unable to use acetate as the sole carbon source for growth, were isolated. Growth of the mutants on a glucose minimal medium was only slightly inhibited by sodium azide. Genetic analysis revealed mutations in different chromosomal genes in the respective mutants. Both these mutants exhibited a high cyanide-insensitive endogenous respiration. The inhibition of the respiration by 8-hydroxyquinoline showed the mutants to respire predominantly by an alternative respiratory pathway observed in many fungal species, but not in the hymenomycetes so far. An enhanced cyanide-insensitive respiration was also found in a wild-type strain of Schizophyllum commune grown in the presence of sodium azide.


Ontogeny of the ectotympanic-petrosal plate relationship in strepsirhine prosimians.

The two major groups of living strepsirhine prosimians (the lorises and lemurs) display two different forms of the ectotympanic-petrosal plate relationship (EPPR). Ontogenetically, the factors producing this difference primarily relate to (1) the degree of elaboration of the sutural tissues at the ectotympanic-petrosal plate interface and (2) the method of pneumatization of the petrosal bone. These two processes are, in all likelihood, the same ones which determined the EPPRs fossil strepsirhines as well. The important theoretical point which emerges is that the transition from the intrabullar to the extrabullar condition of the ectotympanic (or vice versa) was probably effected partly or wholly in young rather than adults stages of ancestral strepsirhines.


On the sublingual structures of Tarsius (Prosimiae, Tarsiiformes) and some platyrrhine monkeys (Platyrrhina, Simiae, Primates) with casual remarks on the histology of the tongue. In memoriam William Charles Osman Hill.

The sublingual structures of Tarsius, Cebuella and Callithrix are studied microscopically. Tarsius has a well developed but not specialized sublingua. In the platyrrhine monkeys the sublingua is lacking completely, but the frenal lamella (plica sublingualis) is very specialized. From this it is concluded that the sublingual organ of Callicebus is a topographically modified frenal lamella, not a sublingua.


[Long-term treatment with anticonvulsants in childhood. Guidelines for the practice].

Long-term treatment with antiepileptic drugs is based on a differentiated diagnosis. Medication appropriate for a special type of seizures has to be chosen. Treatment must be controlled carefully to avoid side effects. Total blood count, urinalysis and determination of enzymes (alkaline phosphatase etc.) are necessary in regular intervals. Essential in treatment is the psychological guidance of the patient and his parents to handle various problems which arise during development. The treatment is terminated carefully after years when the seizures are controlled and the EEG has been normalized.


[Periarticular ossification following severe brain injury].

A particular ossification should be considered besides primary neurological causes, if there are functional restrictions of the joint movements after severe head trauma. New bone formation has been seen extending from the periarticular tissue. The problems of the new bone formation in both hip-joints are shown in a patient with traumatic apallic syndrome. After exact indication and with careful and atraumatic operative technique functional restitution of the joints can be achieved without danger of recurrence.


Dose-dependent effect of TRH on plasma oleic acid in man.

Administered to normal subjects of either sex, the TRH enhances the plasma oleic acid after 60 minutes without any significantly marked modification in the blood concentration of total FFA. The oleic acid increase is significantly dependent on the amount of administered TRH (200 microgram and greater than or equal to 400 microgram). It is accompanied by 1) a more or less pronounced but acute release of TSH, and 2) a rise in circulating T3 but a submaximal value within the time-course of the experiment (1 h). This elevation is presumably due to a preferential liberation of oleic acid by the adipose tissue, through a direct action of TSH and/or under the permissive influence of the thyroid hormone, among other factors that may intervene in the process.


The red-cell glutamic-pyruvate transaminase, carbonic anhydrase I and II and esterase D polymorphisms in the Ambo populations of South West Africa, with evidence for the existence of an EsDo allele.

This study presents the results of the investigation of the seven closely interrelated Ambo peoples of South West Africa, for variation in four recently described red cell enzyme polymorphisms. Variation was found in only three of these, but was sufficient to provide stron evidence that the Ambo divided into two main ancestral groups prior to their subsequent fissions. There is evidence, not yet absolutely conclusive, that a null allele for esterase D occurs at least among the Kwambi.


Genetic studies of the Macushi and Wapishana Indians. II. Data on 12 genetic polymorphisms of the red cell and serum proteins: gene flor between the tribes.

Blood samples from 509 Macushi (3 villages) and 623 Wapishana (11 villages) of Northern Brasil and Southern Guyana have been analyzed with respect to the phenotype and gene frequencies at the following 12 polymorphic loci: ABO, Kell-Cellano, MNSs, Rh, P, Duffy, Kidd, Diego, Lewis, Group-specific component, and the immunoglobulin allotypes of the Gm and Inv systems. The data suggest that 5-6% of the Wapishana gene pool is derived from non-Indians but only 1-2% of the Macushi. Inter- and intratribal genetic distances between villages are calculated for these data in an effort to understand gene flow between the tribes and to account for the unusual distribution of a newly-discovered genetic polymorphism of erythrocyte esterase A thus far limited to these 2 tribes (Neel et al., 1977). The data are puzzling and consistent with the possibility that both the Carib-speaking Macushi and the Arawak-speaking Wapishana have derived the esterase A allele in question from some third group now extinct or thus far undiscovered. Intertribal genetic distances based on gene frequencies at 6 loci are derived for 20 Amerindian tribes (including these 2); the "central" position of these 2 tribes can in part be explained by the active migration matrix connecting them.


Fish cell culture characteristics of a cell line from the silver perch Bairdiella chrysura.

A cell designated SP-1 was established from tissue of the silver perch, Bairdiella chrysura. Cells were fibroblast-like and grew best at 26 degrees C in Leibovitz medium (L-15) containing 15% fetal bovine serum and 0.150 M sodium chloride. Passage 1 to passage 9 SP-1 cells contained a chromosome number of 48; at passages 27 and 50 the modal numbers were 51 and 54, respectively. Confirmation of the origin of SP-1 cells was made by the cytotoxic antibody dye-exclusion test. This cell line supported the growth of lymphocystis virus from the silver perch but was not found to replicate various other fish and mammalian viruses.


Appearance of a variant of MOPC 104E which does not react with dextran B-1355s.

MOPC 104E is a mouse plasmacytoma which produces an IgM (lambda) myeloma protein. This IgM protein has a binding specificity for dextran B-135s. This report describes a variant of the MOPC 104E tumor which secretes a myeloma protein which does not react with the dextran. The apparent variant of MOPC 104E arose spontaneously during routine passage of the MOPC 104E tumors in Balb/C mice and appears to be stable.


A putatively new antigen (CSAp) associated with gastrointestinal and ovarian neoplasia.

CSAp is an antigen originally identified in the GW-39 human colonic carcinoma xenograft, and also found in gastric and colonic cancers, fetal colon, normal and inflammatory adult colon, and in some ovarian tumors. However, it appears to be increased primarily in inflammatory, benign , malignant, and fetal human intestine, gastric cancer, and ovarian tumors, as determined by an hemagglutination-inhibition assay. Gel immunodiffusion patterns show that CSAp is immunologically distinct from CEA, NCA, AFP, BOFA, and human liver ferritin. CSAp thus appears to be a putatively new fetal substance with a high degree of specificity for gastric, colonic, and ovarian tissues.


Effect of a quinazolinone derivative on the metabolism of Streptococcus faecalis--R (ATCC-8043).

2-methyl-3(3'-methyl-2'-pyridyl)-4 (3H) quinazolinone (SRC-820) and methaqualone inhibited the growth of Streptococcus faecalis-R (ATCC-8043). Phosphoenolpyruvate formation from 3-phosphoglycerate by an enzyme extract of S. faecalis was inhibited by SRC-820. With edetate or fluoride, an additive inhibitory effect by SRC-820 was observed.


Physiological role of dehydroascorbic acid.

Dehydroascorbic acid is present in insignificant amounts in plant and animal tissue but appears in considerable amounts under various physiological and pathological conditions. It is found increased: in blood of patients suffering from infectious diseases; in blood and tissues of thyrotoxic patients; in blood after injection of thyroxin, corticotropin and cortisone. In all the above conditions there is concomitant decrease in L-ascorbic acid and glutathione values of blood and tissues. Dehydroascorbic acid, however, disappears after continued administration of a high dose of ascorbic acid. The accumulation of dehydroascorbic acid seems to be an indication of ascorbic acid deficiency. The extreme sensitivity of the ascorbate system to physiological changes is suggestive of a major biochemical role for this redox system. Accumulated evidences indicate that dehydroascorbic acid possible control cell division.


Loss of antibody activity in human immunoglobulin A exposed extracellular immunoglobulin A proteases of Neisseria gonorrhoeae and Streptococcus sanguis.

Immunoglobulin A (IgA) proteases are extracellular enzymes elaborated by Neisseria gonorrhoeae, N. meningitidis, and Streptococcus sanguis. These enzymes each cleave human IgA1 at a critically situated prolyl-threonyl peptide bond to yield Fab alpha and Fc alpha fragments. To study their effect on the antibody activity of human IgA, we enzymatically digested a group of five human IgA monoclonal immunoglobulins with high-titer rheumatoid factor or cold agglutinin activity and human serum macroamylase, an amylase-IgA complex. In contrast to four control IgM rheumatoid factor monoclonal proteins, whose activity was unaffected by enzyme, gonococcal and streptococcal IgA proteases caused prompt, major reductions of IgA antibody activity to negligible levels and converted macroamylase activity to amylase of normal size, as determined by molecular sieve chromatography. In addition, both enzymes promptly deagglutinated sensitized cells that had been aggregated by IgA rheumatoid factors, indicating that IgA bound to antigen is also susceptible to enzyme cleavage. Fab fragments of Iga protein Chr, a rheumatoid factor, showed essentially no antigen-binding activity despite the high titers observed with the parent protein. These studies emphasize the high degree of specificity of the microbial proteases for IgA and their potential for interfering with antibody activity in the IgA1 subclass.


Effect of indomethacin on intestinal water transport in salmonella-infected rhesus monkeys.

Indomethacin, a nonsteroidal anti-inflammatory agent, will abolish salmonella-induced rabbit ileal secretion when given prior to the establishment of infection. In the present study, we assessed whether indomethacin can inhibit salmonella-induced intestinal secretion when administered after infection and net intestinal secretion are well established. A physiological model of salmonellosis, salmonella-infected rhesus monkeys, was used. This model also permitted an examination of the effects of indomethacin in both the small and large intestines. The effect of indomethacin in control monkeys was also studied. Indomethacin caused a striking enhancement of net intestinal water transport in the jejunum,, ileum, and colon of salmonella-infected monkeys. These effects occurred promptly and were of sufficient magnitude in the ileum and colon to cause a reversal in the direction of net transport from net secretion to net absorption. Indomethacin also enhanced net water transport in the jejunum  ileum, and colon of normal animals. These data show that indomethacin markedly enhances net intestinal water transport in both the small and large intestines of salmonella-infected monkeys, even when administered after salmonella infection and intestinal secretion are well established. Similar enhancement also occurs in the normal intestine. The mechanism(s) by which indomethacin produces these effects is not known.


Immunization with R mutants of Salmonella minnesota. II. Comparison of the protective effect of immunization with lipid A and the Re mutant.

The protective effect of active immunization with Salmonella minnesota Re bacilli or lipid A was assessed in the granulocytopenic rabbit model. Animals were immunized with Re bacilli, lipid A, or Pseudomonas aeruginosa as a nonspecific immunogen. After colonization with one of three enterobacterial strains (two Escherichia coli, one Enterobacter aerogenes), the immunized rabbits as well as controls given saline injections were made leukopenic with nitrogen mustard and monitored for fever, bacteremia, and death. Survival rates were significantly greater in Re-immunized animals than in saline controls or P. aeruginosa-immunized animals. Immunization with lipid A afforded no protection. In addition, rabbits immunized with Re mutant bacilli developed bacteremia less frequently than the others, indicating that antibody to Re may inhibit invasion of the intestinal mucosa as well as protect after bacteremia has developed.


Common (non-type-specific) antigens of group A streptococci.

Two common (non-type-specific) antigens in HCl extracts prepared from group A streptococcal cultures of different types were analyzed by immunodiffusion methods. These antigens are sensitive to trypsin and are apparently related to the cell wall proteins. The common antigens tested belong to a category of nonprotective non-type-specific antigens. The presence of common antigens in the HCl extracts should be taken into consideration when M-proteins are determined. The detection of one of the common antigens may be used as a virulence index, since this antigen is characteristic of the group A streptococcal cultures with enhanced virulence.


Sucrose metabolism by prominent members of the flora isolated from cariogenic and non-cariogenic dental plaques.

Sucrose metabolism by resting-cell suspensions of pure cultures of representative members of the predominant cultivable flora isolated from cariogenic and non-cariogenic dental plaque was investigated by means of radiochemical techniques. Streptocococcus mutans utilized sucrose at a considerably faster rate than S. sanguis, S. mitis, Actinomyces viscosus, A. naeslundii, or Lactobacillus casei, forming lactic acid, intracellular polysaccharide, insoluble extracellular glucan, and lactic acid from intracellular polysaccharide catabolism at faster rates than the other bacteria. The Actinomyces formed more volatile acids than the streptococci, mostly acetic, and S. sanguis formed more soluble extracellular polysaccharide than the other bacteria. The metabolic activity of S. mutans resembled the pattern of sucrose metabolism of cariogenic plaque, whereas the metabolic activity of the Actinomyces species, the predominant members of non-cariogenic plaque flora, resembled the sucrose metabolism of non-cariogenic plaques.


Typhoid: clinical picture and response to chloramphenicol. Prospective study in Bombay (1972).

The clinical picture of 78 cases with proven typhoid and 18 cases with proven paratyphoid A fever is presented. The diagnosis was made by isolating the organisms from the blood. The Widal test could not be used as a diagnostic criterion. By means of chemotherapy with chloramphenicol (initial dose 30-40 mg/kg body weight) defervescence was achieved within an average of 4.5 days. The course of the disease was generally mild; one patient with typhoid fever died. The average hospital stay was 19 days. Four patients of the typhoid fever group were readmitted with a relapse. The laboratory examinations included blood clot culture, phage typing, Widal test, haemoglobin, leucocyte count, transaminases, serum bilirubin, and routine examination and culture of stool and urine. Forty-two patients were infected with intestinal parasites and 25 with Shigella organism. The findings are discussed and compared with findings of similar studies of enteric fever.


Biologic evaluation of filling materials. A comparison of results using cell culture techniques, implantation tests and pulp studies.

The paper presents a comparison of results from cell culture studies, implantation tests and pulp studies using silicate cement, composite material and zinc oxide/eugenol cement. The three techniques allow differentiation between reactions produced by the materials, but a poor correlation exists between the results from the different techniques. This information is considered important for a selection of techniques for biologic testing of dental materials.


Structure and biological functions of human IgD. XIV. The development of a solid-phase radioimmunoassay for the quantitation of IgD in human sera and secretions.

A simple but sensitive radioimmunoassay method for the quantitation of IgD in sera and body fluids has been developed. Specifically purified chicken anti-delta was covalently coupled to cyanogen bromide activated filter paper discs and the discs were incubated together with the samples to be analyzed. The washed discs were next incubated with 125-I-labeled specifically purified chicken or rabbit anti-human delta-antibodies. IgD on the disc was quantified by reference to a standard curve prepared with purified human IgD. The sensitivity of this assay was approximately 10 ng/ml IgD. IgD was demonstrable in cord sera (18 of 18), hypogammaglobulinemic sera (15 of 15), amniotic fluids (6 of 6), salivas (8 of 10), normal cerebrospinal fluids (12 of 13) and cerebrospinal fluids from patients with subacute sclerosing panencephalitis (5 of 5). The finding of IgD in human secretions raises the interesting possibility that IgD may be a secretory antibody.


The molecular components of human transferrin type C.

Immunologically pure human transferrin type C (TfC) was isolated from the plasmas of 11 individual healthy donors. After conversion into the 2Fe-form, the preparations were analysed by polyacrylamide gel electrophoresis and chromatography on DEAE-cellulose. In all samples studied by either method the presence of three components, designated A, B and C, was observed. Calculations from eight chromatograms yielded the following relative proportions for the components: A:6%, B:62% and C:32%. The quantity of iron bound played no role in this chromatographic resolution. The components were immunologically identical but their sialic acid content increased inthe order of A less than B less than C. The presence of galactose as an ultimate residue of the oligosaccharide chains in TfC component A was confirmed by a biological test. This observation together with the results of earlier analyses for hexose, hexosamine and galactose in the subfractions from Behringwerke human transferrin, suggests that sialic acid is probably the only variable among TfC components A, B and C. Loss of sialic acid from component C during the isolation of TfC was excluded as an explanation for the presence of the other two components. The electrophoretic appearance of TfC samples from five patients with liver disease (chronic active hepatitis, cirrhosis or alcoholic liver) did not noticeably differ from that of TfC FROM HEALTHY PERSONS. Baboon transferrin resembles TfC with respect to sialic acid heterogeneity. This species was therefore studied to decide whether sialic acid is gradually lost from transferrin in the circulation or whether transferrin is not fully sialylated before discharge from the hepatocyte. Using DEAE-cellulose chromatography no difference was found between baboon transferrin molecules which were less than 6h old and those which had a mean age of 8.9 days. By inference it is suggested that the reason for the multiplicity of TfC is also likely to be biosynthetic.


Serological study of listeriosis in domestic animals in São Paulo-Brazil.

A serological examination was carried out for L. monocytogenes antibodies on 9,318 domestic animal--7,809 bovine, 838 horses and 671 swine--in São Paulo, Brazil. Serum agglutination in tubes was the method used. Only somatic antigens from serotypes 1, 2, 3, 4a and 4b were employed. It was considered reagent all sera reacting in a titer 1/20 while as positive only sera with 1/320 or above. According this criteria the results showed showed that in cattle 17.8% were reagent but only 8 sera were positive for types 1, 2 and 4b. Only type 1 was found in horses in a rate of 22.7% reagent, and 11 positive samples. For swine the percentage of reagent was 13.3% but none serum was positive, since the highest titer was 1/160.


Cost/benefit analysis of treatment and prevention of myocardial infarction.

The benefits resulting from introduction of coronary care units, mobile coronary care units, and a screening and intervention program to decrease the incidence of myocardial infarction (MI) are reduced to a common basis by modeling the effects of the three strategies as applied to a cohort of 10-years-olds. Published data on MI are used with a semi-Markov model of death from MI and other causes to estimate program effects on long-term survival, and cost/benefit ratios are compared for the three programs with both costs and benefits discounted over the lifetime of the cohort. Some problems of selecting a discount rate for comparing programs that incur costs and accrue benefits at widely separated times are discussed.


Cost-effectiveness analysis and alternative health care programs for the elderly.

A generalized cost-effectiveness technique for comparing alternative health care programs is described, and an example is given of its use in evaluating programs for care of the elderly. The analytical method requires setting criteria and standards for each outcome and cost dimension and assessing the relationship between these standards and patient status. The relative effectiveness and costs of each setting are examined in a simple tabular display that allows comparison of each program's attainments on each criterion so that alternatives may be ranked according to the extent to which they meet standards and incur costs.


Comparative hemodynamic effects of coronary vasodilators and contrast material on the normal and ischemic canine myocardium: determination of the optimal agent for clinical augmentation of coronary blood flow.

The systemic hemodynamic and myocardial effects of potent vasodilators administered directly into the left coronary artery were determined and compared with the actions of contrast material in 10 anesthetized dogs in the normal state and in the presence of segmental myocardial ischemia. Contrast material (Renografin 76) caused systemic hypotension, rise in left ventricular diastolic pressure and decreases in LV dp/dt and dp/dt/LVP in both states. Doses of ATP (7.2 microgram/kg and 20 microgram/kg/min) which are maximally effective in augmenting coronary blood flow caused only mild arterial hypotension and minimal inotropic effects in both states. Nitroglycerin (3 microgram/kg and 10 microgram/kg/min) induced no inotropic effects but slightly greater arterial hypotension than ATP in both states. On the other hand, papaverine HCl (300 microgram/kg and 800 microgram/kg/min) induced profound increases in LV dp/dt and dp/dt/LVP, decreases in LVEDP and arterial hypotension in the non-ischemic state. In the presence of segmental ischemia, papaverine HCl caused significantly less increases in LV dp/dt and dp/dt/LVP, paradoxical increases in LVEDP in 5 dogs and ventricular fibrillation in 3 dogs. Thus, maximally effective vasodilatory doses of ATP causes only small alterations in hemodynamics and myocardial contractile state of the normal and ischemic heart. Similar doses of papaverine induce profound positive inotropic effects which are apparently deleterious to the ischemic heart.


Microangiography in the perfusion-fixed rabbit kidney: a single injection technique for the study of the nephron.

Through the modification of a technique developed by Beeuwkes, microangiography, using barium sulfate, was performed on rabbit kidneys following perfusion fixation with gluteraldehyde. Gluteraldehyde is a rapid fixative which preserves tissues while creating few artifacts on the electron microscopic level. The vessels and tubules are preserved in an open-lumen state with sufficient hardness to resist the artifacts caused by high pressure renal artery injections. By injecting barium sulfate at high pressure through the renal artery it is postulated that microruptures are created in the glomerular tuft. This leads to opacification of the tubules and the demonstration of various anatomic configurations. Low pressure injections were used to selectively demonstrate the vascular anatomy. This method allows the demonstration of the vascular and tubular anatomy without specialized techniques. The mechanism of failure of opacification of the renal vein on conventional microangiography are discussed.


Metrizamide in urography. II. A comparison of 51Cr-EDTA clearance and metrizamide clearance in man.

In nine subjects undergoing urography with metrizamide measurements of total serum clearance of 51Cr-EDTA have been made before, during, and after the urography. During the urography both total serum clearances and renal clearances were determined for 51Cr-EDTA and metrizamide. The present study in man confirms the previous results from investigations in rabbits, that most of the intravenously injected metrizamide is excreted through the kidneys, that tubular reabsorption of metrizamide occurs and suggests that metrizamide might be used with advantage for urography.


Total intravenous feeding of calves.

Total intravenous feeding was accomplished for 5 clinically normal calves and for 1 calf with atresia coli. During the trials, which lasted 8 to 14 days (mean of 12 days), calves were not permitted to ingest any food or water. Body weight and state of hydration remained essentially constant. Plasma protein content decreased, but there were only minor changes in other physiologic measures. Calves were clinically normal at the conclusion of the trials.


Naturally occurring trypanosomiasis (Chagas' disease) in dogs.

Nine fatal cases of canine American trypanosomiasis (Chagas' disease) were encountered from November, 1972, through November, 1975. Of the 9 cases, 7 occurred in dogs from 5 central Texas counties, and all but one case was diagnosed during the months of September, October, or November. The source of infection was discovered in only one case--that being a doghouse heavily infested with Triatoma lectularius occulta. Each of 6 bugs collected had infective forms of the protozoan, Trypanosoma cruzi. Trypanosomiasis usually is not considered in the differential clinical diagnosis of cardiac dysfunction in man or other mammals in the United States. An antemortem diagnosis was made in only 1 of the 9 dogs, with diagnosis in the remaining dogs being made at necropsy. The predominant microscopic lesion in all dogs was necrotizing granulomatous myocarditis associated with the amastigotes of T cruzi.


Ambruticin (W7783), a new antifungal antibiotic.

Ambruticin represents a new class of antibiotics isolated from a strain of Polyangium cellulosum var, fulvum, a bacterium belonging to the class Myxobacteriales. This antibiotic is a cyclopropyl-polyene-pyran acid and is active in vitro against fungi.


Glycinothricin, a new streptothricin-class antibiotic from Streptomyces griseus.

Glycinothricin is a streptothricin-class antibiotic obtained for the first time from the culture broth of a strain of Streptomyces griseus. Glycinothricin, the deformimino derivative of antibiotic LL-AB664, gives N-methylstreptolidine, N-methyl-D-glucosamine and glycine on acid hydrolysis. In comparison with LL-AB664, glycinothricin is less active against gram-positive and gram-negative bacteria and less toxic to mice.


Porphyrin and corrinoid mutants of Bacillus subtilis.

Porphyrin auxotrophs of Bacillus subtilis can be divided into two groups. Strains belonging to the first group (hemA, hemB, or hemC) are not able to synthesize or metabolize porphobilinogen. These strains require cysteine, cystine, and methionine, respectively. Traces of aminolevulinic acid, in a hemin-containing medium, can replace the cysteine requirement in a mutant lacking aminolevulinic acid synthetase. In bacteria belonging to the second group (hemE, hemF, or hemG), porphyrin biosynthesis is blocked at later steps, and the amino acids mentioned above are not required. It is of interest that both the activity of ribonucleotide reductase and the amount of vitamin B12 were significantly lower in the first group. The addition of vitamin B12 to the medium did not promote the growth of strains examined. We assume that porphobilinogen deaminase is essential for the synthesis of corrinoids.


Host cell reactivation of Bacillus subtilis bacteriophages.

Host cell reactivation of ultraviolet-irradiated phage can be used as a probe of the bacterial repair system and to determine phage and cellular contributions to the repair process. Using the Bacillus subtilis phages SPP1, SP01, phie, and phi29, we found that the uvr-1 and polA functions are involved in the host cell reactivation of the four phages. SPP1 was the only phage whose reactivation was also decreased in recA, recD, and recF mutant cells. We studied variations of host cell reactivation for SPP1 during spore outgrowth; at high ultraviolet doses the activity of a spore repair system requiring deoxyribonucleic acid polymerase I became evident. The spore repair system was completely replaced by the vegetative one by 120 min of outgrowth.