Affinity of bronchial secretion glycoproteins and cells of human bronchial mucosa for Ricinus communis lectins.

The coupling of Ricinus communis lectins to Sephadex G 25 was used in order to study mucins and other glycoproteins from human bronchial secretion. The major part of human bronchial mucins and other glycoproteins such as immunoglobulins A, bronchotransferrin and alpha1-antichymotrypsin were isolated by this procedure. A parallel study of human bronchial mucosa was achieved with peroxidase labeled Ricinus communis lectins; this study characterized goblet cells and mucous cells which contain mucins, and serous cells which are involved in the synthesis or the secretion of the other glycoproteins.


[Isolation and some properties of phospholipase D from Bacillus subtilis G-22].

A method of isolating highly purified phospholipase D from Bac. subtilis G-22 is described. It includes ammonium sulphate fractionation, thermal denaturation, chromatography on lipoprotein bound with sepharose 6B and AH-sepharose 4B. The enzyme is 130-fold purified, its yield exceeds 90.0%, its specific activity is 164 units per mg of protein. The homogeneity of the enzyme is demonstrated by polyacrylamide gel electrophoresis, ultracentrifugation, isoelectric focusing and N-terminal amino acid determination by means of dinitrophenylation and dancylation. Proline is found to be N-terminal amino acid. The molecular weight of the enzyme, as determined from gel filtration through Sephadex G-100, is 21500 +/- 300, its sedimentation constant is 1.4S, isoelectric point is at pH 4.2. The molecular weight calculated from amino acid composition, is 21000--22000. Polypeptide chain contains of 196--205 amino acid residues. Phospholipase D develops its maximal activity at pH 8.5 and does not contain free SH-groups. Benzylsulphofluoride does not inhibit the enzyme activity. Phospholipase D is activated by Cd2+, Co2+, Zn2+, Ca2+ and is inhibited by EDTA, pIi50 being about 2.6.


Blood group D antigen content of nucleated red cell precursors.

The D antigen content of nucleated red cell precursors in human bone marrow was estimated using autoradiography and 125I-anti-D. D antigen first appeared in the pronormoblast, and the quantity of antigen progressively increased during red cell maturation. Maximal anti-D binding occurred on mature red blood cells. Pronormoblasts, basophilic normoblasts, polychromatophilic normoblasts, and orthochromatic normoblasts, respectively, had approximately 1/4, 1/2, 2/3, and 3/4 the quantity of antigen found on mature red cells. None of the other cell types were found in bone marrow labeled with anti-D.


The effect of banol and paraoxon on the NADPH-cytochrome c reductase activity and cytochrome P-450 content in rats.

We investigated the effect of banol and paraoxon on the activity of NADPH-cytochrome c reductase and cytochrome P-450 concentration in microsomes of rats treated in vivo with these compounds alone, or in the presence of phenobarbitone. The results showed that banol reduced the NADPH-cytochrome c reductase activity and the concentration of cytochrome P-450, while paraoxon reduced the activity of NADPH-cytochrome c reductase, but increased the cytochrome P-450 concentration. Phenobarbitone stimulated an increased NADPH-cytochrome c reductase activity and cytochrome P-450 concentration. When applied with banol and paraoxon, phenobarbitone lowered their inhibitory effect.


Longitudinal studies on the effects of malnutrition, nutritional supplementation, and behavioral stimulation.

Six major Western Hemisphere longitudinal studies of malnutrition and development are in their final stages. These studies are taking place in Columbia, Guatemala, Mexico, and the United States. As a step toward synthesis of the results, a conference was held at Cali, Colombia, with the aim of clarifying differences and similarities. The following features of each study were considered: The starting and completion dates; the research design (including scheduled periods of observation and the presence or absence of nutritional supplements and/or stimulation); the populations involved, their home diets, and the specific supplements and stimulation received; procedures and measurements used in the study; and any general conclusions reached. The conference also identified opportunities and needs for exchange of information between projects and for a collaborative approach to such specific problems and topics as birth-weight, physical growth, and behavioral development.


The effects of sodium cromoglycate on histamine aerosol-induced reflex bronchoconstriction in the anaesthetized dog.

1 The effects have been studied of sodium cromoglycate (SCG), given by aerosol or intravenously, on reflex bronchoconstriction induced by histamine aerosol in the anaesthetized dog. 2 Four breaths of an aerosol generated from a 2% solution of SCG significantly inhibited the vagally mediated increase in total lung resistance (RL) produced by histamine. 3 SCG given intravenously as bolus injections (5-500 microgram/kg) produced a dose-dependent reversal of a sustained reflex bronchoconstriction induced by histamine aerosol. Propranolol (500 microgram/kg) did not prevent this reversal. 4 SCG did not inhibit the increase in RL produced by supramaximal electrical stimulation of a vagus nerve. 5 The possibility is discussed that SCG may reduce the activity of lung irritant receptors in the anaesthetized dog.


Unusual bone images in hyperparathyroidism.

Whole-body scans with 99Tcm-Sn polyphosphate were performed on four patients suffering from hyperparathyroidism. Two of the patients were investigated twice, at intervals of five and eight months. A variety of unusual but symmetrical images were obtained, not always confined to the skeleton. It is suggested that in conditions of renal failure the radiopharmaceutical may be avidly accumulated on first passage by calcifying areas in the soft tissues. Deteriorating blood supply to the bones reduces uptake of 99Tcm in the the skeleton.


Treatment of intestinal fistulas.

There have been three major advances in the treatment of small bowel fistulas since 1960: irrigation with lactic acid; total or parenteral nutrition; and continuous low flow enteric nutrition. The causation and clinical features of these fistulas are reviewed. The different unfavourable prognostic features are evaluated with reference to a series of 384 cases published by Edelmann et al. (1975). The different methods of treatment, both medical and surgical, are analysed. In spite of the great progress in medical management, surgery retains an important place. The guidelines for this medicosurgical policy are laid down. The mortality of intestinal fistulas was around 60 per cent before 1960 and has now diminished by half. It should be possible to lower it still further to around 10 per cent in future years, by careful application of the methods described.


Local and surgical management of enterocutaneous fistulas.

Intensive nutritional treatment is now recognized as the single most important factor in achieving closure of enterocutaneous fistulas, replacing attempts at early surgical closure. Operation in the early stages of management should be confined to the drainage of abscesses, the defunctioning of diseases or disrupted bowel and the formation of feeding enterostomies. In those few cases where spontaneous closure of the fistula does not occur, definitive surgical operation can be carried out when malnutrition has been corrected. The combination of nutritional treatment, skin protection and judicious surgery can reduce the mortality to below 10 per cent.


Limbic and sensory connections of the inferior parietal lobule (area PG) in the rhesus monkey: a study with a new method for horseradish peroxidase histochemistry.

The caudal part of the inferior parietal lobule (area PG) was injected with horseradish peroxidase (HRP) in 6 hemispheres of 5 rhesus monkeys. The retrograde transport of HRP resulted in the labeling of neurons in diverse cortical and subcortical areas. In cortex, labeled neurons were noted in prefrontal cortex (areas 8, 45, 46), in the banks of the intraparietal and superior temporal sulci, in medial parietal cortex, in cingulate cortex, in the retrosplenial area, in area TF and the caudal portions of the parahippocampal region. Subcortical sites with labeled neurons included the necleus basalis of the substantia innominata, the claustrum, the pulvinar and intralaminar thalamic nuclei, the pretectal area, the nucleus locus coeruleus and the raphe nuclei. Although many of the labeled neurons were seen in layers IIIc and V, each cortical area had an individual laminar pattern of labeled neurons. In these experiments, a benzidine dihydrochloride (BDHC) method was used which yields a blue reaction-product at sites containing HRP. BDHC affords superior visibility of labeled neurons, and a significant improvement in sensitivity when compared to a diaminobenzidine procedure in matching series of sections. Additional sections were also stained with a method which allows the simultaneous demonstration of HRP (blue) and acetylcholinesterase (reddish-brown). These revealed that virtually all substantia innominata (nucleus basalis) neurons which project to area PG are also rich in the enzyme acetycholinesterase. These afferents of PG may be classified into 'sensory association', 'limbic' and 'reticular' categories. It is argued that this arrangement of afferent imput may afford a convergence of limbic and sensory information in area PG and that this may subserve a significant function in the process of sensory attention.


Uptake studies of taurine in vivo and its effects on the course of experimental focal epilepsy in rats.

The passage of orally administered taurine across the intestinal wall to the blood plasma and target sites of neuromuscular excitability has been studied. This has been correlated with the effect of repeated oral dosing on the manifestations of cobalt-induced epilepsy in the rat. The blood-brain barrier and the organ distribution of taurine uptake have important implications in testing its effect on hyperexcitability phenomena.


Projections from the paraventricular nucleus to the zona externa of the median eminence of the rhesus monkey: an immunohistochemical study.

Immunoperoxidase techniques and light microscopy were used to investigate the origin of the fibers containing vasopressin, oxytocin and related neurophysins (neurohypophyseal peptides), in the zona externa of the median emience of the rhesus monkey. Unilateral lesions were produced in the paraventricular nucleus using a modified Halasz-type knife. Complete destruction of the paraventricular nucleus resulted in a total depletion of all four neurohypophyseal peptides in the ipsilateral zona externa of the median emience. Partial lesions of different segments of the paraventricular nucleus resulted in depletion in different parts of the zona externa. These observations indicate that the paraventricular nucleus is the source of vasopressin, oxytocin and neurophysin in axons which end in the zona externa of the median eminence. These projections are strictly ipsilateral and arranged topographically, so that the more caudal paraventricular neurons project to the dorsal part of th zona externa and the rostral ones to the ventral segment. The supraoptic nucleus does not appear to project to the zona externa, and sends the great majority of its fibers to the neurohypophysis.


The effects of calcium deficiency on the electrical activity of Nitella flexilis.

Calcium chelators such as ethylenediaminetetraacetic acid and sodium citrate produce repetitive activity and prolong the spike of internodal cells of Nitella flexilis. Removal of Ca2+, Mg2+, Na+, and K+ from the outside of the cell by washing the preparation with Tris propionate or Tris chloride hyperpolarizes the cells but does not initiate repetitive activity or increase the duration of the spike appreciably. It was concluded that cell-bound Ca2+ controls the threshold for stimulation and the duration of the spike, and that the removal of Ca2+ from the cell membrane, either by chelation or displacement, changes the normal behaviour of the cell by altering its permeability to some other ion or ions.


Isometric tension and instantaneous stiffness in amphibian skeletal muscle exposed to solutions of increased tonicity.

The instantaneous elasticity and maximum isometric tetanic tension of isolated frog and toad sartorii have been measured in hypertonic Ringer solution. Although the mechanical response of contraction muscle continued to decrease as the tonicity of the bathing solution was increased to 1.26 X R, 1.52 X R, and 2.04 X R, a similar change in the instantaneous stiffness could not be shown. This finding was not expected on the basis of our current model of the cross-bridge mechanism which predicts that the instantaneous stiffness is a measure of the total number of tension-generating cross-bridges formed in a stimulated muscle. The compatability of our findings with an electrostatic theory of the cross-bridge mechanism proposed by Iwazumi (1970) is discussed.


Inhibition of diptheroid esterase by Micrococcus luteus.

Micrococcus luteus produced a diffusible, esterase inhibitory factor (EIF) which inhibited the activity of cutaneous diphtheroid esterases on Tween 80-CaCl2 agar media. Esterases of Staphylococcus, Micrococcus, Bacillus, and Serratia were not susceptible. EIF did not appear to combine with the substrate or to prevent enzyme synthesis; it was unable to reverse the precipitation of calcium oleate. The composition of the medium, especially peptones, influenced the production of EIF. EIF was synthesized in the absence of diphtheroids, but production required the presence of Tween. The interaction was observed on agar medium of pH 5.5-8.5, at 25-43 degrees C, under an atmosphere of 10-20% CO2, in the presence of urea, but not after the addition of NaCl or dextrose. Supernatants of broth cultures had to be concentrated to detect EIF. Crude dialyzed and concentrated preparations of EIF withstood 60 degrees C for 60 min but were inactivated after 100 degrees C for 10 min. EIF may possibly be associated with a lipoid substance, since it did not precipitate in ethanol.


Numerical taxonomy of heavy metal-tolerant bacteria isolated from an estuary.

A total of 230 strains of metal-tolerant bacteria from water and sediment samples collected in Chesapeake Bay were isolated on a medium containing cobalt, lead, mercury, or molybdenum. In addition, a set of 71 cultures were simultaneously isolated on glucose tryptone yeast extract agar medium without metals. Twenty-three reference strains were also included in the numerical taxonomy study of these bacteria, bringing the grand total of strains examined to 324. All strains were examined for 112 biochemical, cultural, morphological, and physiological characters. The taxonomic data obtained were analyzed by computer and the simple matching (SSM) and Jaccard (SJ) coefficients were calculated. Clustering achieved by unweighted average linkage is presented and, from sorted similarity matrices and dendrograms, 294 strains, i.e., 97% of the total, were recovered in 12 phenetic groups defined at the 75 to 80% similarity level. Among the strains there were nine phena presumptively identified as Bacillus, Erwinia, Mycobacterium, Pseudomonas, and coryneforms. From the results of the taxonomic study, it is concluded that metal tolerance in estuarine water and sediment bacteria occurs among a restricted range of taxa distributed throughout the estuarine environment.


Physiological control of alkylsulfatase synthesis in Pseudomonas aeruginosa: effects of glucose, glucose analogs, and sulfur.

Pseudomonas aeruginosa (isolated from soil) synthesizes an alkylsufatase allowing this bacterium to utilize sodium hexan-1-yl sulfate as a source of carbon and sulfur for growth. The formation of the enzyme was induced by this and by other (C4-C16) primary alkylsulfate esters as well as by some (C-8 and C-9) primary alkylsulfonates. Secondary (2-yl) alkylsulfate esters did not act as inducers. The induction of alkylsulfatase was markedly inhibited by L-cysteine, L-methionine, sodium sulfide, and by high (greater than 2mM) concentrations of D-glucose and other related monosaccharides. Similar inhibitory effects by four glucose analogs which will not support growth suggest that prior metabolism was not a requirement for glucose-mediated inhibition. The inhibition by D-glucose of the same inducible system in P. aeruginosa (PAO-57) supported this conclusion since this glucose transport-positive mutant is deficient in the further metabolism of the monosaccharide. At low (0.1-1.0 mM) concentrations, D-glucose or D-glucose 6-O-phosphate (20 mM) caused a marked enhancement of alkylsulfatase induction in the isolate. This novel enhancement was reproduced using P. aeruginosa strain PAO. However, both monosaccharides acted as potent inhibitors of alkylsulfatase formation occurring in mutant PAO-57 which, unlike the parent strain PAO, exhibits low glucose-6-phosphate dehydrogenase activity. These results suggest that D-glucose (0.1-1.0 mM) must be metabolized to enhance the synthesis of the enzyme.


Partial characterization of the mode of action of benzoic acid on aflatoxin biosynthesis.

Aflatoxin production by a toxigenic strain of Aspergillus flavus was greatly reduced by benzoic acid and sodium benzoate in synthetic media. The reduction was accompanied by the appearance of a yellow pigment. Spectral analyses partially characterized this pigment as closely related to an acetyl derivative of a versiconal-type compound. A cell-free extract prepared from A. flavus grown in synthetic media was active in converting this yellow compound into aflatoxin B1 in the presence of reduced nicotinamide adenine dinucleotide phosphate at 25 degrees C (pH 7.4). In the presence of benzoic acid and its salt or autoclaved cell-free extract, conversion of yellow compound to aflatoxin B1 was prevented. These results suggest that the yellow compound is an intermediate in the secondary metabolic cycle involved in aflatoxin B1 production. Benzoic acid, sodium benzoate, or autoclaving the cell-free extract appear to have respectively blocked or denatured an enzymatic step late in the biosynthetic pathway of aflatoxin B1.


The effect of Waring Blendor treatment on transformation in Bacillus subtilis.

Treatment of competent Bacillus subtilis in a Waring Blendor for 10 s increases transformability of the culture about twofold while reducing the attachment of DNA to competent cells by 80%. The effectiveness of attached DNA in producing transformants is increased 10-fold by this treatment. The uptake of transforming DNA into a DNase-resistant state is progressively reduced by 70% during a 120-s blending treatment. Blending for 30-45 s diminishes transformability to about 10% of the original nonblended value without affecting the viable cell titer. No effect is produced by 30 s of blending on transformability if the irreversible uptake of DNA has been completed. Thus, the inhibition occurs at an early step in the transformation sequence. Treatment of the competent culture for 60 s or longer in the Waring Blendor reduces both the number of transformants obtained and the total number of viable cells.


Accessory pigment fluorescence for quantitation of photosynthetic microbial populations.

The in vivo fluorescence of the primary accessory pigments in purple bacteria (carotenoids), green bacteria (bacteriochlorophyll), green algae (chlorophyll), and cyanobacteria (phycocyanin) was found to be a linear function of cell concentration over three of four orders of magnitude. The lowest cell concentrations detectable were 10(4) cells/ml for procaryotes and 10(3) cells/ml for eucaryotes.


Square pegs in round holes: a study of residents in long-term institutions in London, Ont.

A large random sample of people in the long-term institutions (homes for the aged, nursing homes and continuing care hospitals) of London, Ont. was studied to assess the suitability of these people, according to physical and mental status, for the institution in which each resided. The results indicated a relative need for beds in homes for the aged and nursing homes. A high proportion (29% to 54%) of people in the three types of institutions were unsuitably placed. Greater flexibility is needed in institutional arrangements, and institutions should be examined for their potential to provide support in maintaining the elderly at home. The findings of this study add some weight to the arguments of those calling for more and better home care programs for the disabled.


Alterations in fecal microflora enzymes related to diet, age, lactobacillus supplements, and dimethylhydrazine.

The bacterial enzymes, beta-glucuronidase, azoreductase, and nitroreductase, have been measured in the fecal microflora of rats. The effects of diet, advanced age, Lactobacillus acidophilus supplements, and dimethylhydrazine on these microbial enzymes activities have been determined. The shift from a grain to a meat diet resulted in 1.5--2.5-fold increase in the activity of all three enzymes. Animals over 20 months of age, consuming a meat diet, showed further increases in fecal beta-glucuronidase activity, while the levels of all three microbial enzymes increased in old rats fed a grain diet. Feeding supplement of L. acidophilus significantly lowered the activity of fecal nitroreductase and azoreductase in meat-eating animals, but had no effect on nitroreductase activity in grain-fed animals. Dimethylhydrazine increased the fecal beta-glucuronidase activity in both grain- and meat-fed animals, but the carcinogen had no effect on nitroreductase or azoreductase activity. These findings have relevance to known features of the epidemiology and etiology of large bowel cancer, and suggest certain approaches to prevention.


Damage and repair of DNA in cultured mammalian cells with N-diazoacetylglycine amide.

N-Diazoacetylglycine amide, a diazochetoalkane, has been studied in vitro for DNA damage and repair in cells of a cloned subline from a BALB/c mouse. To our present knowledge, none of these compounds have been investigated for such activities. At nontoxic levels, a prolonged dose-dependent unscheduled DNA synthesis was observed by autoradiography. DNA damage was studied by sedimentation through alkaline sucrose gradients after the cells were lysed on the gradients. Treatment of the cells for 1 hr with nontoxic doses of N-diazoacetylglycine amide resulted in slower sedimentation of DNA. The number of single-strand breaks appeared rather linearly dose dependent for a large range of concentrations. Breaks were at their maximum after 1 hr of treatment, and no further increase in the number of breaks was seen. Some repair of the breaks probably occurs, but repair was sluggish even 68 hr after treatment. A significant part of the breaks was observed after incubation at 4 degrees in an ethylenediaminetetraacetate hypotonic solution. This seems to indicate that the compound does not require metabolic activation. Nontoxic doses of N-diazoacetylglycine amide and other similar derivatives exert mutagenic and carcinogenic activities. The presence of DNA damage and the difficulty in its repair at such doses could be related to both of these biological properties.


Modifications of 3'-methyl-4-dimethylaminoazobenzene carcinogenesis of rat liver and carcinogen metabolism by portacaval anastomosis.

The effect of portacaval shunt on hepatocarcinogenesis was studied in rats fed 3'-methyl-4-dimethylaminoazobenzene. Portacaval anastomosis resulted in a decrease of hepatocarcinogenesis as reflected by a delay in the early peak of alpha-fetoproteins, an absence of late appearance of alpha-fetoproteins, and a significantly lower incidence of tumors than in nonshunted rats. Reduction of hepatocarcinogenesis in shunted rats was associated with a decrease of the binding of 3'-methy-4-dimethylamioazobenzene metabolites to liver proteins. This effect seemed to be related to modifications of carcinogen-metabolic pathways. While the detoxifying azoreductase activity was not affected by portal diversion, the activating pathway leading to the binding of 4-dimethylaminoazobenzene metabolites to DNA, a major step for cell carcinogenesis that is mediated by microsomal enzymes, was decreased in shunted rats to about 50 percent of control values. The decrease of liver weight that occurred in shunted rats without loss of body weight produced a very significant reduction of the total capacity of liver to activate 4-dimethylaminoazobenzene while the total capacity of detoxification remained unchanged. This could be a direct consequence of portacaval anastomosis, as has been shown for other microsomal enzymes.


Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys.

The pharmacologic disposition of DL-alanosine was studied in mice, rats, dogs, and monkeys. The major portion of the parenterally administered drug was excreted in the urine by all of the species studied; however, in rodents an important fraction of the dose was expired as CO2. Organs in which DL-alanosine accumulates include the kidneys, lungs, liver, and small intestine. Considerable drug-derived radioactivity persists for periods up to 14 days in the hepatic and renal parenchyma. Studies on the clearance of DL-alanosine in mice using a specific enzymatic assay procedure indicated that the plasma half-life of the parent drug was shorter than the half-life of total radioactivity. In both cases, however, the kinetics were complex and not readily resolvable into discrete phases. In murine lymphoblasts (L5178Y/AR) the transport of DL-alanosine was found to be a sodium-stimulated, saturable, and thermosensitive process which was inhibited by L-threonine, L-asparagine, L-glutamine, L-serine, L-leucine, L-isoleucine, L-valine, L-cysteine, and L-homoserine. Kinetic studies on the influence of L-asparagine and L-glutamine on this transport revealed that the inhibition was competitive in nature.


An extended transition probability model of the variability of cell generation times.

The transition probability model of variability of cell generation times is extended so that the rate constant for the transition from the A-state to the B-phase of the cell cycle depends on on time which a particular all has already spent in the A-state. A specific time dependence of this rate constant is introduced. It is determined by the value of one constant which is then an additional parameter of the model. The corresponding cell population kinetics are calculated and compared to existing experimental evidence. The model accounts satisfactorily for the generation time distribution function and for the shortening of the G1 phase of binucleate cells. The time dependence of the transition probability is related to the cell kinetics of an hypothetical cell constituent. A possible relationship is proposed between the chemical parameters with the cell and the parameters of the cell population kinetics.


Trysinase positive oculocutaneous albinism in the goldfish, Carassius auratus l., and ultrastructural and biochemical study of the eye.

Ultrastructural studies, and cytochemical and biochemical determinations of tyrosinase activity were conducted on the pigment epithelium of albino and xanthic goldfish eyes. In eyes of xanthic goldfish, two types of melanosomes are present, spherical and elongated. Melanized melanosomes are absent in the eyes of the albino goldfish, but elongated lamellar premelanosomes are observed. Internal vesicles are present in both melanosome types in the pigment epithelium of the xanthic goldfish but are absent in premelanosomes of the albino. There are also differences in the distribution of lipid droplets, smooth endoplasmic reticulum and Golgi complexes with the latter two being more abundant in the albino. Tyrosinase was not identified cytochemically; however, the enzyme was demonstrated biochemically in the pigment epithelia of both albino and xanthic goldfish. The enzyme is associated with the particulate and soluble fractions fo both types of eyes. Particulate albino tyrosinase may be solubilized by triton X-100 treatment. Tyrosinase inhibitors are present in the particulate fractions of both albino and xanthic goldfish eyes. Thus, in the goldfish, ocular albinism appears to be a multiple defect at the molecular and ultrastructural levels.


Effect of cyproterone acetate on prolactin secretion in the female Rhesus monkey.

Adult female rhesus monkeys were given cyproterone acetate orally in doses of 0.04, 0.4, 4 and 40 mg per kg per day for 12 weeks. Its effects were assessed on serum prolactin (PRL) concentration, the morphology of the PRL cells, and the development of the mammary glands. Serum PRL was relatively unchanged in the control animals from the fourth through the twelfth weeks of the study. In contrast, PRL was significantly elevated in each group of drug-treated animals during the same time periods. There was no development of the mammary glands nor was there any evidence of milk secretion in the control animals; however, in the monkeys given cyproterone acetate the mammary glands had extensive lobuloalveolar growth and milk-like secretion that could be expressed as early as the fourth or fifth week of the study. By immunocytochemistry and differential light microscopic staining techniques, the PRL cells in the pituitary glands of the experimental animals were found to be more numerous and much larger than those present in the controls. They displayed a well developed Golgi complex and had an abundance of cytoplasmic RNA. These data suggest that PRL secretion is markedly enhanced by cyproterone acetate.


Stereological and biochemical analysis of prolactin and growth hormone secreting rat pituitary cells in culture. Stereology combined with non-parametrical statistics.

The secretion of prolactin is increased by treatment of prolactin producing rat pituitary cells with the hypothalamic tripeptide thyroliberin. To investigate the underlying mechanisms we used three closely related rat pituitary tumor cell strains (GH1 2C1, GH3 and GH4C1), which synthesize and spontaneously secrete prolactin and/or growth hormone. Growth hormone and prolactin released into the culture medium over a period of 24 h were measured by radioimmunoassay. Initial rates of synthesis were measured by immunoprecipitation of intracellular growth hormone and prolactin after incubation of cell cultures with 3H-leucine. The observed increase in prolactin synthesis and release was correlated with morphological effects of thyroliberin treatment. The volume density of Golgi complexes and the volume and surface densities of rough endoplasmic reticulum were compared in untreated cells and thyroliberin treated cells. As normal distribution could not be assumed the non-parametric rank test of Wilcoxon was used whereby the densities calculated for each cell section were ranked. All three morphological parameters increased after thyroliberin treatment in cells secreting prolactin only (GH4C1), implying that the increase of prolactin secretion, at least in part, is due to increased prolactin synthesis.


Deletions of two heat-activated loci in Drosophila melanogaster and their effects on heat-induced protein synthesis.

Deficiencies that delete two heat-induced puffs in Drosophila melanogaster have been isolated. Two deficiencies delete the puff arising from 87C1, and one deletes the two puffs at 87A and 87C1. Homozygotes for these deletions can be recognized by their abnormal, transparent malpighian tubules. The influence on heat-induced protein synthesis of deleting one or both of these puffs has been examined. Unexpectedly, deleting only the 87C1 puff has no apparent effect. Deleting both the 87A and 87C1 puffs eliminates synthesis of a 71,000 dalton protein. We map a coding locus for the 71,000 dalton heat-induced protein to 87A7-B3, a seven band region which also contains a heat-induced puff. The roles of the 87A and 87C1 puffs in coding for heat-induced proteins are discussed in the light of these results.


In vivo repair of rat liver DNA damaged by dimethylnitrosamine or diethylnitrosamine.

Effects of hepatocarcinogens dimethylnitrosamine (DMN) and diethylnitrosamine (DEN) on the sedimentation pattern of rat liver DNA in alkaline sucrose gradients were studied with regard to time and dose dependency. Both DMN (10 mg/kg body weight) and den (13.4 or 134 mg/kg) induced appreciably decreased DNA sedimentation rates at 24 h after injection. DMN at 10 mg/kg was as effective in decreasing the DNA sedimentation rate at 24 h after injection as was the higher dose of DEN (134 mg/kg). Sedimentation patterns at 1, 6 and 14 days after injection indicated that damage induced by DEN (134 mg/kg) was repaired at a substantially lower rate than DMN (10 mg/kg) induced damage. When effects of equimolar doses of DMN (10 mg/kg) and DEN (13.4 mg/kg) were compared at 1, 6 and 14 days after injection, it was observed that the more pronounced damage of rat liver DNA induced by DMN was repaired at a faster rate than was the DEN-induced damage. At the molecular level this difference in repair between damage induced by the two nitrosamines is probably related to different DNA alkylation patterns. The relatively persistent nitrosamine-induced DNA lesions (observed especially after DEN administration) are thought to represent phosphotriesters which give rise to single strand DNA breaks at strongly alkaline conditions of lysis on top of the gradient. The results are discussed in relation to the possible significance of alkylation and repair of DNA in the formation of (pre)cancerous lesions in rat liver.


[Anatomical identification of the vestibulo-olivary and cerebello-olivary projections in the cat].

Injections of horseradish peroxidase were made into different parts of the inferior olive in the Cat. It is shown that the vestibular nucleus Z and, to a lesser extent, the nucleus f send off fibres to the ipsilateral medial accessory olive. The ventral part of the nuclei inter-positus and dentatus send off fibres to the ventrolateral outgrowth of the opposite side.


The first multi-flagellate spermatozoa in the animal kingdom, discovered in Mastotermes darwiniensis.

In this paper the spermatozoa of Mastotermes darwiniensis is described. It is the first example of multiflagellate animal sperm cell, consisting of a conical head and about hundred flagella. Other remarkable features are the absence of acrosome, the centrioles made up by doublets instead of triplets and the axonemes devoid of central tubules and with doublets bearing only one arm. The flagella are feebly motile.


[Adenyl cyclase activity of the cell membrane throughout the cell cycle: ultrastructural study of the cell line BHK 21/C 13].

Adenylate cyclase activity in the surface membrane of baby Hamster kidney (BHK 21/C13) cells is ultrastructurally studied as a function of the cell cycle. Cells are synchronized by a physical method suited to structural and functional investigations. The activity is highest through G1, decreases in S, markedly drops as cells traverse G2 and is very low or often seems not present at all in M.


[Comparison in genetically obese and normal rats of the uptake and incorporation of labelled lauric acid, oleic acid, and glycerol by the isolated perfused liver].

Lauric acid, labelled oleic acid and glycerol are perfused in isolated liver of fafa Rats and Wistar Rats previously subjected to fasting. They synthesize TG and PL de novo, though in long time experiments with the normal Rat, the most important method of synthesis is an exchange of AG of the endogenous glycerolipids. However PL are not synthesized with lauric acid. In the livers of fafa Rats the synthesis of TG with oleic acid and glycerol is higher than in livers of Wistar Rats: 16:0 18 : 1 18: 1, 16:0 18: 1 18: 2, 18 : 1 18 :1 18:1, 16 : 0 16 :0 18 : 1 (this TG is not present in liver of Wistar Rat). The hepatic synthesis of PL by the fafa Rat, is less important after 15 min while it is important with Wistar Rats. The synthesized TG with lauric acid (only the TG 12 : 0 12 : 0 12 : 0 with the fafa Rat) are more rapidly oxidized by liver of obese Rat than by liver of normal Rat.


[Identification using glass microelectrodes of the activities recorded in the neighborhood of axons and cell bodies of the trigeminal sensory complex].

Using glass micropipettes unitary activities were recorded at the level of the trigeminal sensory complex. Iontophoresis of pontamine blue allowed us to localise the recording loci. Two types of spikes were observed, they were distinguished on the basis of their shape: one corresponds to an axon spike, the other to a cell body spike.


[Immunohistochemical localization of carbonic anhydrase C in the rat central nervous system].

With obtention of specific antibodies against isoenzyme C of Rat carbonic anhydrase it was possible to realize an immunohistochemical localisation in central nervous system of Rat. Results showed that this enzyme was mainly localized in cytoplasm of oligodendroglial cells and in low concentration in myelin sheath.


[Concentration and method of cadmium fixation by a marine Vibrio].

In many organisms, intracellular fixation of cadmium involves specific proteins, the metallothioneins. A similar phenomenon was demonstrated in a marine bacterium belonging to the genus Vibrio. The accumulation of the metal is a function of its concentration in the medium. The uptake is also increased by cysteine, which decreases the toxicity of the metal.


[Inhibition of biological methylations by t,t-farnesylacetone, a constituant of the androgenic gland of the male crab, Carcinus maenas].

t, t-farnesylacetone 1 and hexahydrofarnesylacetone 2 have been previously identified in extracts from the androgenic gland of the male Crab Carcinus maenas. These compounds inhibit in vitro the methylation of E. coli B tRNA and of Calf thymus histones with S-adenosylmethionine methyl-14C as methyl donor and methylases from Crab testis. Rat liver or a 1-adenine methylase from a Mouse plasmocytoma (1 is approximately 200 times more active than 2).


[Mutants of Bacillus thuringiensis with altered sporulation: morphologic responses to several treatments applied in the exponential phase].

During log-phase of growth, wild strain and and oxytetracycline-resistant mutants with altered sporulation exhibit distinct responses to some treatments, autolysis, osmotic pressure, ultraviolet irradiation and bacteriophage infection.


[Stimulation of hematopoietic stem cells by antilymphocyte serum].

The physiopathogeny of aplastic anemia is still unknown, it can be related to a stem cell defect or a microenvironment disease. An autoimmune origin is suspected but not as yet proved. To demonstrate the autoimmune origin of some cases of aplastic anemia, we have studied the effect of antilymphocyte globulin (ALG) on the hematopoiesis of aplastic patients by serial hematological and bone marrow investigation including blood counts, bone marrow cellularity, scanning with indium and technetium and granulocytic colonies in agar, 8 out of 17 patients had a response to ALG as shown by a rise of granulocytes and reticulocytes counts, increase of bone marrow cellularity and number of granulocytic colonies. This study tends to show that ALG has a stimulating effect on hematopoiesis in some cases of severe aplastic anemia.


[Preferential affinity of acetylcholine receptor protein for certain lipids studied using monolayer cultures].

The interaction of the cholinergic (nicotinic) receptor protein purified from Torpedo marmorata electric organ with lipidic monomolecular films is studied at constant film area or constant superficial pressure. In both experimental situations, it is incorporated more efficiently into cholesterol than into egg lecithin films without showing any selectivity for a particular phospholipid class.


[Influence of nitrogen components of wine on the growth of lactic acid bacteria].

Three different fractions of nitrogen compounds have been extracted from wine: proteins, peptides, amino acids. They have been tested to support the growth of malolactic bacteria in acid medium: only the peptidic fraction supports this growth.


[Tubular and glomerular nephropathy induced in rabbits by injection of a heterologous antitubular basement membrane serum].

A nephropathy affecting both tubules and glomeruli has been induced in Rabbits by the injection of an heterologous immune serum directed against Rabbit tubular basement membrane. It differs from experimental antiglomerular basement membrane nephropathy by the fixation of antibodies and C3 on tubular basement membrane and by the occurrence of glucosuria.


[Antitumor effects of keto-nucleosides. Study of the antitumor activity of y(3'-O-acetyl-4', 6'-dideoxy-beta-L-glycero-hex-3'-eno-pyranosyl) theophylline and 1(4'-keto-2'-3'-O-isopropylidene-alpha-L-''rhamnosyl''O thymine against L 1210 leukemia in mice].

The effects of two keto-nucleosides on survival time of Mice with i.p. L 1210 leukemia were studied. The purine unsaturated keto-nucleoside was shown to be much more active than the pyrimidine keto-nucleoside.


[Membrane lipids and electron transfer. Effects of four detergents on NADH-ferricyanide reductase and NADH-cytochrome c reductase activities of potato tuber microsomes].

The NADH-ferricyanure reductase activity of Potato microsomes is stimulated by non ionic detergents (Triton X100 and Tween80) and is partially inhibited by ionic detergents (sodium-cholate and deoxycholate). All these four detergents progressively decreased the NADH-cytochrome c reductase in the following order: sodium deoxycholate greater than Triton X100 greater than sodium cholate greater than Tween80.


[Shape acoustical recognition and characteristics of sonar signals by the dolphin T. truncatus].

During the shape acoustical recognition process, the signal processing reveals two phases in the T. truncatus sonar emission. In the course of the first phase, the wide-band signals are invariant, during the second phase, near the end of the approach, their temporal and spectral characteristics change along with the shape of the objects to identify.


[Aversive effects of halothane anesthesia in the rat, using extinction of tasks by positive reinforcement].

Immediate posttrial halothane anaesthesia accelerates the extinction of two previously acquired operant tasks--barpress learning or modified K-maze learning. This acceleration is not due to any motor impairment. These results are not consistent with the hypothesis of amnestic effects of halothane anaesthesia; they are interpreted in terms of aversive effects.


[Evolution of testosterone and dihydrotestosterone in plasma, testicle and ovary of the guinea pig throughout fetal life].

High testosterone concentrations were found in the plasma of male fetus at the stage of sexual differentiation. Then the fetal testis is the principal source of circulating testosterone; its action on the Wolffian duct would occur by the systemic pathway. In female fetus, androgens were synthesized by the gonad and the relatively high levels found in the plasma have probably another source.


[Preliminary findings concerning the in vitro effect of estradiol on differentiation of mammary glands in rabbit embryos].

The mammary buds of rabbit embryos between 18 and 24 days of age were ultrastructurally studied after being cultivated in synthetic liquid medium. The response to estradiol involves an increase in lipid synthesis and the occasional appearance of malformations.


Effect of dopamine infusion on the hemodynamics of normal and sympathectomized rhesus monkeys in endotoxin shock.

Infusion of endotoxin in chemically sympathectomized monkeys caused a fall in the mean aortic pressure, but the cardiac output, stroke volume, and central venous pressure were well maintained. Endotoxin-induced tachycardia in monkeys with functional sympathetics was not seen in the sympathectomized animals. Infusion of dopamine improved the hemodynamic and cardiovascular status, probably by causing vasoconstriction of the splenic and hepatic artery where the pooling of blood is believed to occur in endotoxin shock. However, these beneficial effects were not apparent when dopamine was administered in the chemically sympathectomized animal infused with endotoxin. Since chemical sympathectomy did not affect the endotoxin-induced decline in the systolic and mean aortic pressure or the severity of the endotoxin shock, it is suggested that catecholamines may not be the primary initiator or trigger substances in endotoxin shock.


The effect of hemorrhagic shock and resuscitation on regional blood flow in cynomulgus monkeys.

The effect of hemorrhagic hypotension and resuscitation on regional blood flow was studied in the Macaca fascicularis monkey. The majority of the splanchnic vasculature demonstrated a profound decrease in flow. Following fluid expansion and correction of acidosis, flow increased in these circulations but did not reach control values. Exceptions were the small bowel flow which fell only moderately and hepatic arterial flow which did not significantly change. Both coronary and adrenal circulations maintained flow during the shock and resuscitation periods, whereas brain and kidney blood flows fell significantly without recovery. There was a significant rise in serum glucose, lactate, and pyruvate during shock, with an increase in the lactate/pyruvate ratio. Following resuscitation, the ratio decreased, implying a return toward aerobic metabolism.


Studies on the mechanism of pulmonary vascular responses to miliary pulmonary embolism.

The nature and mechanisms of pulmonary vascular responses which follow miliary pulmonary embolism were examined in intact dogs in which the isolated left lower lobe was perfused at constant blood flow. Embolization of the lung with plastic microspheres increased total pulmonary vascular resistance, whereas, in contrast, vascular resistance of the isolated perfused left lower lobe which was protected from embolization was decreased. This vasodilation was prevented by chronic denervation of the lobe and by ganglionic blockade. Cervical vagotomy also blocked the response but atropine failed to alter the vasodilation. The response, which appeared to be reflex in origin and involve efferent sympathetic pathways, was prevented by beta-adrenergic receptor blockade produced by propranolol. Since the lobar vascular response to norepinephrine was significantly enhanced by propranolol, it was concluded that embolization of the lung evokes pulmonary vascular reflex vasodilation which is mediated over the sympathetic nervous system via a beta-adrenergic receptor mechanism.


Influence of reduction of preload and afterload by nitroglycerin on left ventricular diastolic pressure-volume relations and relaxation in man.

To clarify the mechanisms of afterload reduction on left ventricular diastolic function, the influence of nitroglycerin upon ventricular diastolic pressure-volume relations was studied in 22 patients during catheterization. After nitroglycerin, average ventricular systolic pressure declined by 25 mm Hg (18%) and end-diastolic pressure by 7 mm Hg (28%) (P less than 0.005). End-systolic and diastolic ventricular volumes decreased by 37% and 23% respectively (P less than 0.005). Although peak negative dP/dt fell by 22% (P less than 0.0005), "T", an index of the time course of isovolumic diastolic ventricular relaxation, was insignificantly changed. Diastolic pressure-volume curves were significantly displaced downward and leftward without significant change in slope, suggesting that a family of pressure-volume curves for each ventricle with similar slope but positions depend upon immediate loading conditions. Absence of change in slope or of "T" suggests that this displacement may be mediated indirectly, perhaps by relaxation of extracardiac constraints to ventricular distensibility. Accordingly, improvement in ventricular function by vasodilators may be partly due to downward displacement of the pressure-volume relation, with associated reduction of wall tension and myocardial oxygen consumption.


Effects of sublingual nitroglycerin on resting pulmonary gas exchange and hemodynamics in man.

Simultaneous hemodynamic, ventilation and blood gas measurements were performed in 19 males during cardiac catheterization for evaluation of chest pain syndrome before and 3 to 5 min after 0.4 mg sublingual nitroglycerin. Pulmonary arterial pressures and total pulmonary vascular resistance fell (P less than 0.001 for both), and mean systemic arterial pressure decreased (P less than 0.05). However, peripheral vascular resistance, cardiac output, and mixed venous PO2 did not change. Total and tidal ventilation, PCO2, pH, and base excess remained unchanged. However, the arterial PO2 decreased from a mean of 80 +/- 3 (SEM) to 72 +/- 2 mm Hg (P less than 0.001) and mean venous admixture increased from 8.8 +/- 1% to 12.6 +/- 1.5% (P less than 0.001). The alveolar arterial PO2 difference increased (P less than 0.001) and the dead space tidal volume ratio rose (P less than 0.05). We conclude that the decrease in arterial PO2 following sublingual nitroglycerin is caused by redistribution of pulmonary blood flow with imbalance in ventilation-perfusion relationships or shunting.


Nifedipine therapy for Prinzmetal's angina.

A case is described in which nifedipine, a new coronary vasodilator, was effective in relieving attacks of Prinzmetal's angina unresponsive to conventional therapy. The extreme frequency of the anginal attacks provided evidence that lower doses of nifedipine lost their effectiveness approximately 4 hours after administration. A month after initiation of nifedipine, nitrates were withdrawn since they had been ineffective in controlling the attacks. A myocardial infarction occurred immediately, presumably due to coronary spasm.


Serum gentamicin assay by high-performance liquid chromatography.

We describe a high-performance liquid chromatographic method for the quantitative determination of gentamicin in serum. The antibiotic was separated from serum by passage through a silicic acid column, derivatized with o-phthalaldehyde, and eluted with ethanol. The derivatized gentamicin was then separated into all three of its major components by reversed-phase chromatography and quantified by fluorometry. Concentrations in serum as low as 0.5 mg of gentamicin per liter could be accurately determined. A standard curve showed a linear response for serum containing gentamicin at concentrations ranging from 0 to 20 mg/liter. Tobramycin, amikacin, ampicillin, penicillin G, methicillin, carbenicillin, chloramphenicol, clindamycin, and cephalothin did not interfere with the gentamicin assay. Comparison with an accepted microbiological assay yielded a correlation coefficient of 0.99. This chemical assay is rapid (less than 30 min), sensitive, accurate, specific, and appears to be applicable to other aminoglycosides.


GM1-ganglioside beta-galactosidase in leukocytes and cultured fibroblasts.

GM1-ganglioside hydrolysis by leukocytes and fibroblasts, tissues easily obtainable from patients, was investigated using 3H-labeled GM1 and was found to be at least as active as that reported for any other tissue. Sodium taurocholate was required for the reaction, the crude bile salt at an optimum concentration of 0.4% producing twice as much activity as pure taurocholate at its optimum concentration of 0.8%. Leukocyte GM1-ganglioside beta-galactosidase and 4-MU-beta-gal cleaving activities were similar, 134.5 +/- 23.3 and 179.8 +/- 25.4 nmol/h/mg protein, respectively. In cultured skin fibroblasts and amniotic fluid cells these enzyme activities were 4 to 5 times higher. Homozygotes for GM1-gangliosidosis showed negligible activity while in heterozygotes the leukocyte GM1-cleaving activity was reduced to one-third of control values. In leukocytes from patients with four other sphingolipid storage diseases the activity was either normal (Krabbe's, Tay-Sachs, Metachromatic leukodystrophy) or increased (adult Gaucher's).


A radioimmunoassay for thyroxine on Sephadex columns. Investigations on the influence of some buffers on the binding of thyroxine to serum proteins.

A thyroxine radioimmunoassay procedure (T4RIA) based on incubation and separation on Sephadex columns is presented. The assay is rapid and easily to perform; if necessary columns may be regenerated. The raising of antibodies against thyroxine in goats is described in detail. The specificity of the antiserum towards the coupling of several compounds related to thyroxine has been tested. Influence of some buffers on the binding of thyroxine to serum proteins has been investigated. The results of T4RIA in patient sera were in agreement with those obtained by a competitive binding method. The within-day variation was approximately 4% (coefficient of variation, C.V.); day-to-day variation was 7% C.V.


Determination of gold in plasma and plasma fractions by atomic absorption spectrometry and by neutron activation analysis.

Three techniques of gold analysis, flame and electrothermal atomic absorption spectrometry and neutron activation analysis, have been compared, using plasma and plasma fractions (derived by gel chromatography) from rheumatoid patients receiving aurothiomalate therapy and from plasma samples incubated with aurothiomalate in vitro. The three methods correlated well in the analysis of gold in whole plasma, but only neutron activation analysis was suitable for the assay of all the plasma fractions. The susceptibility of the two atomic absorption methods to interference by sodium chloride was investigated.


A new theoretical description of the binding of thyroid hormones by serum proteins.

A theoretical model is proposed which describes the binding of thyroid hormones to serum proteins in terms of easily determined parameters, Not only free hormone concentration but also the distribution of hormone among various binding sites may be computed. The mathematical approach is capable of dealing with models of differing complexity of binding from simple 'one binding site per protein molecule' systems to those involving 'negative co-operativity'. The approach gives predictions of thyroid function parameters which are in good agreement with those observed in practice.


Bronchial findings in pulmonary tuberculosis.

A total of 297 bronchoscopies were performed on 238 patients with pulmonary tuberculosis at the Paivarinne Chest Hospital during the period 1967--1973. The tuberculous process was deemed active in 172 patients and inactive in 66. Active endobronchial tuberculosis was diagnosed in 20 patients, 11.6% of the active cases, whereas inactive sequelae of endobronchial tuberculosis appeared in 7% of the total material. Bronchography was performed on 163 patients; a normal bronchogram was obtained in 54% of the cases with minimal changes, 35% of the moderately advanced cases, 13% of the far advanced and 23% of the inactive cases. Sputum samples were more often positive for tubercle bacilli than the bronchial aspirates, and bacterial cultures from sputum samples were less reliable indicators of infection than were cultures from bronchial aspirates. Cytological smears revealed no difference between these two sampling methods.


The neurological examination in dementia.

The thesis of this chapter is that the neurological phenomena discussed and numerous others omitted or not yet recognized relate primarily to a release of primitive activity when diffuse brain damage erodes cerebral inhibition mechanisms. Anatomical correlations are always difficult when there are multiple lesions, and those that have been made have not completely explained these phenomena. A phylogenetic explanation is not completely adequate either but certainly does not bar further investigations. Indeed such a concept points out the necessity to continue to search for other fetal or developmental responses in dementia, to assess the interrelationships between these reflexes, and to quantify the stimulus as well as the response. The prognostic value of these reflexes is not emphasized, because it is not known. In the evaluation of dementia, one of the last obvious frontiers of neurological science, both specific observations and general principles await discovery.


Biochemistry of lipoxygenase in relation to food quality.

A renewed interest in lipoxygenase has led to detailed studies of its isoenzymes, substrate specificity, and the nature of its reaction products. Lipoxygenase is highly specific for cis,cis-1,4-pentadiene systems such as linoleic, linolenic, and arachidonic acid (or ester) and catalyzes the formation of the corresponding hydroperoxides with a cis,-trans-conjugated diene system. The hydroperoxides can then undergo enzymic or spontaneous degradation, producing a range of carbonyl compounds. This review will discuss the biochemical properties of this enzyme and its contribution to the quality of raw and processed food products. An attempt has been made to discuss both the desirable and undesirable effects associated with the action of lipoxygenase, citing specific food examples where appropriate.


Impact of external influences on food packaging.

Since the food supply is dependent upon an effective packaging system, threats to packaging represent implied threats to food processing and distribution. Enacted and potential legislation and regulation are retarding technological and commercial progress in food packaging and have already restricted some food packaging/processins systems. The results of these external influences is not simply the sum of the individual acts, but is a cascading self-imposed arresting of food packaging/processing advancement. The technological bases for the enacted and proposed legislation and regulation are presented in the enumeration of the external influences on food packaging. Economic and sociological arguments and facts surrounding the issues are also presented. Among the external influences on food packaging detailed are indirect additives, nutritional labeling, benefit:risk, solid waste and litter, environmental pollution, universal product code, and food industry productivity. The magnitude of the total impact of these external influences upon the food supply is so large that assertive action must be taken to channel these influences into more productive awareness. An objective and comprehensive public communications program supported by the technological community appears mandatory.


Localization of sequences coding for histone messenger RNA in the chromosomes of Drosophila melanogaster.

In situ hybridization of sea urchin (Psammechinus miliaris, Lytechinus pictus and Strongylocentrotus purpuratus) histone messenger RNA has been used to map complementary sequences on polytene chromosomes from Drosophila melanogaster. The sea urchin RNA hybridizes to the polytene regions from 39D3 through 39E1-2, including both of these bands (39D2 may also be included). This region is identical to the one which hybridizes most heavily with non-polyadenylated cytoplasmic RNA from D. melanogaster tissues. Sea urchin mRNAs coding for several individual histones each hybridize across the entire region from 39D3 (or D2) through 39E1-2, as would be expected if the individual mRNA sequences are interspersed. In view of the apparently even distribution of sequences complementary to histone mRNA within the 39D3-39E1-2 region, the significance of the several polytene bands in this region remains an open question. Biochemical characterization of the hybrids between sea urchin histone mRNA and D. melanogaster DNA suggest that sea urchin mRNAs for several of the histone classes have some portions which retain enough sequence homology with the D. melanogaster sequences to form hybrids, although the hybrids have base pair mismatches. In situ hybridization of chromosomes in which region 39-E is ectopically paired show no evidence of seqence homology in the chromosome region with which 39D-E is associated.


Treatment of herpetic keratitis.

Idoxuridine which was first used in 1960 (Kaufman et al., 1962), has been for many years the only antiviral agent available in the treatment of herpetic keratitis. It is however no more successful than is mechanical removal of diseased epithelium (Patterson & Jones, 1967), and furthermore it may give rise to serious toxic side effects. The search for an alternative medication is therefore a pressing one. Trifluorothymidine (F3T) has, in recent years, been shown to be more effective than IDU and to be free from significant toxicity. Both of these drugs are pyrimidine nucleosides. Adenine Arabinoside or Arabinoside-A (Ara-A) is, by contrast, a purine nucleoside. It is thought to exert its antiviral effect by blocking DNA polymerase and ribonucleotide reductase.


[Haemodialysis in diabetics with terminal renal failure].

Long-term dialysis treatment of diabetics with terminal renal failure is beset with severe complications. In 19 unselected diabetics in terminal renal failure (13 juvenile diabetics and 6 maturity-onset diabetics) the clinical course during long-term dialysis was observed. A total of 1377 dialyses during 167 months of treatment were performed. Diabetic angiopathy, hypertension, and hyperhydration were the most prominent complications. The interval between the onset of diabetes and the beginning of dialysis treatment was 21,5 years in the juvenile diabetics and 5,2 years in maturity-onset diabetes. The survival time during dialysis was on average 13,2 months for the juvenile diabetics and 0,6 months for maturity-onset diabetics. The patients died chiefly from cardiovascular complications.


Use of total parenteral nutrition as a "medical colostomy" in management of severe lacerations of the sphincter: report of a case.

A case of anal-sphincter injury with total fecal incontinence is presented. The use of total parenteral nutrition (TPN) as a "medical colostomy" is stressed. After four weeks of support by TPN, the perineal wound had healed and successful sphincteroplasty was performed. TPN was used in the postoperative period to delay bowel movements for one week. The general concept of the use of TPN in sphincter injury is presented giving the surgeon an option in management of these injuries without resorting to a preliminary colostomy.


[Hormone replacement in patients with carcinoma of the thyroid (author's transl)].

82 patients with well-differentiated thyroid carcinoma had been treated by total thyroidectomy and radioiodine destruction of any residual thyroid tissue. They were then given high doses of L-thyroxine (T4), enough to suppress endogenous stimulation by TSH, the recommended dose being at least 300 microgram daily. Six weeks after starting 150 microgram T4 daily there was no significant response to 400 microgram TRH i.v. in 56% of the 82 patients. The T4 dose was then increased until all TRH tests had become negative. There was a significant correlation between the number of negative tests and body surface: at a dose of 40-60 microgram/m2 none of the tests was negative, while at a dose of 80-100 microgram/m2 the test was negative in 83%, the frequency of negative tests increasing up to 94% at higher doses. Mild hyperthyroidism occurred in 17%. It is concluded that after adequate surgical and radioiodine treatment 80-100 microgram/m2 T4 should be given to patients with well-differentiated thyroid carcinoma. The effectiveness of suppressing TSH levels should be checked with the TRH test after six weeks.


[Steroid metabolism in primates. XIX. Urinary excretion of C21-steroids in Cercopithecus aethiops and Erythrocebus patas].

In male Cercopithecus aethiops (green monkey; grivet) and Erythrocebus patas (dancing red monkey; patas monkey), the pattern of urinary C21 steroids was estimated and compared with those of man, baboon and rhesus monkey. The results indicate diminished 11 beta- and 17 alpha-hydroxylation in steroid biosynthesis as well as diminished delta 4-3-keto reduction and increased 20 beta-reduction in metabolism in these two species.


Construction, isolation and implications of repressor-galactosidase - beta-galactosidase hybrid molecules.

Escherichia coli heterogenotes, which produce hybrid molecules between the chimaeric protein repressor-galactosidase and the enzyme beta-galactosidase, were constructed. Repressor-galactosidase in which fully active lac repressor is covalently linked to active beta-galactosidase, is an aggregate with a core structure of four beta-galactosidase parts and two peripheral lac repressor dimers. The lac repressor dimers, which are separated by tetrameric beta-galactosidase, retain all the biological activities of tetrameric lac repressor. Substitution of repressor-galactosidase subunits with beta-galactosidase subunits leads to hybrid molecules with y beta-galactosidase subunits aggregated with (4-y) repressor-galactosidase subunits (where y = 1, 2 or 3). A 2:2 hybrid, i.e. a tetrameric beta-galactosidase core with one lac repressor dimer grafted to it, binds at least 100 times less strongly to 32P-labelled  lambdaplac DNA than pure lac repressor or repressor-galactosidase. The data suggest a model in which lac repressor binds with two subunits to lac operator and with the other two subunits elsewhere on the DNA, possibly on sequences like the lac operator.


Putrescine-sensitive (artifactual) and insensitive (biosynthetic) S-adenosyl-L-methionine decarboxylase activities of Lathyrus sativus seedlings.

The crude extracts of 3-day-old etiolated seedlings of Lathyrus sativus contained two S-adenosyl-L-methionine decarboxylase activities. The artifactual putrescine-dependent activity was due to the H2O2 generated by diamine oxidase (EC 1.4.3.6) of this plant system and was inhibited by catalase. This observation was confirmed by using an electrophoretically and immunologically homogeneous preparation of L. sativus diamine oxidase. In the presence of putrescine, diamine oxidase, in addition to S-adenosylmethionine, decarboxylated L-lysine, L-arginine, L-ornithine, L-methionine and L-glutamic acid to varying degrees. The decarboxylation was not metal-ion dependent. The biosynthetic S-adenosylmethionine decarboxylase (EC 4.1.1.21) was detected after removing diamine oxidase specifically from the crude extracts by employing an immunoaffinity column. This Mg2+-dependent decarboxylase was not stimulated by putrescine or inhibited by catalase. The enzyme activity was inhibited by semicarbazide, 4-bromo-3-hydroxybenzoylamine dihydrogen phosphate and methylglyoxal-bis (guanylhydrazone). It was largely localized in the shoots of the etiolated seedlings and was purified 40-fold by employing a p-hydroxymercuribenzoate/AH-Sepharose affinity column, which also separated the decarboxylase activity from spermidine synthase.


The effect of electron donors and acceptors on light-induced absorbance changes and photophosphorylation in Rhodospirillum rubrum chromatophores.

Light-induced difference spectra between 400 and 640 nm of Rhodospirillum rubrum chromatophores were performed in the presence and absence of exogenous electron donor/acceptor systems and compared with the chemical oxidation spectrum. The results indicate that the component previously defined as P430 is not a unique entity but rather represents different species, or a mixture of species, under various conditions. Under all conditions in which the reaction center bacteriochlorophyll is reversibly photooxidized, as indicated by the bleaching around 600 nm, it is also contributing to the absorbance increase around 430 nm. In one case, in presence of reduced dichloroindophenol and in the absence of oxygen, the photooxidation of reaction center bacteriochlorophyll is fully supressed. Under these conditions an irreversible change around 430 nm is still observed and seems to be due to the Soret band of b-type cytochrome. In the presence of reduced dichloroindophenol and absence of oxygen there is a marked inhibition of photophosphorylation. This inhibition is apparently due to the complete reduction of the cyclic electron carriers. Addition of the low potential dye benzyl viologen facilitates an almost complete recovery of the reversible photooxidation of reaction center bacteriochlorophyll as well as of photophosphorylation. These results indicate that the apparent mid-point potential of the primary electron acceptor in Rhodospirillum rubrum chromatophores is probably in the range of that of benzyl viologen (E'o = - 340 mV).


Immunological studies on beef-heart ubiquinol--cytochrome c reductase (complex III)

Antibodies against isolated beef-heart ubiquinol--cytochrome c reductase (complex III) have been characterized. Antibodies to complex III react strongly with isolated beef heart complex III and intact beef heart mitochondria, as shown by immunodiffusion and rocket electrophoresis experiments. The complex III content of intact mitochondria can be quantitated with rocket electrophoresis using isolated complex III as a standard. Antibodies to complex III also react with beef liver mitochondria and with both heart and liver mitochondria from rats. The latter are very weak antigens compared to beef heart material. Antibodies to complex III do not react with respiratory chain complexes I and IV, or F1-ATPase from beef heart mitochondria, but gives a slight, but variable, reaction with complex II and the membrane fraction isolated from complex V (oligomycin-sensitive ATPase). Antigenic sites are located on at least five of the seven peptides of complex III. These peptides are presumably lacking in respiratory chain complexes which do not react with antibodies to complex III, and are assumed to be uniquely located in complex III. Antiserum against complex III inhibitis duroquinol--cytochrome c reductase activity in isolated complex III and in complex III incorporated into phospholipid vesicles. Oxidation of NADH and succinate is not affected in submitochondrial particles treated with 6-times more antibody than required for complete inhibition of enzyme activity in free complex III or in complex III-phospholipid vesicles.


Comparative studies of lactate dehydrogenases in lactic acid bacteria. Amino-acid composition of an active-site region and chemical properties of the L-lactate dehydrogenase of Lactobacillus casei, Lactobacillus curvatus, Lactobacillus plantarum, and Lactobacillus acidophilus.

The molecular weight, the amino acid composition and the N-terminal and C-terminal amino acids of two allosteric (Lactobacillus casei, L. curvatus) and two non-allosteric (L. plantarum, L. acidophilus) L-lactate dehydrogenases, purified to homogeneity by affinity chromatography, were determined. The amino acid composition of the only tryptic peptide unequivocally common to the fingerprints of the 4 enzymes is virtually identical with that of the arginine peptide, called Arg6 of the the substratebinding site of the L-lactate dehydrogenase dehydrogenase of several animals. However, the 'essential' cysteine residue 165 is replaced by threonine, as it is in the L-lactate dehydrogenase of lobster. In addition, the 4 bacterial peptides differ by one or two changes in single amino acid residues from each other as well as from those of animals. The data indicate that not only the animal L-lactate dehydrogenases, but also the allosteric and lactate dehydrogenases from bacterial sources may have evolved from a common gene.


Human alpha-N-acetylglucosaminidase. 1. Purification and properties.

alpha-N-Acetylglucosaminidase was purified from human urine to a state of apparent homogeneity. alpha-N-Acetylglucosaminidase is a glycoprrotein with an extensive charge heterogeneity. The molecular weight determined by gel filtration is 307000. Polycarylamide gel electrophoresis in the absence and presence of sodium dodecyl sulfate indicates molecular weight heterogeneity of isocharged forms of the purified enzyme. The enzyme has a pH optimum of 4.5 +/- 0.3 and KM and V values of 0.14-0.74 mM, and 1.04-3.68 mumol mg-1 min-1 for three aryl 2-acetamido-2-deoxy-alpha-D-glucosides and UDP-N-acetylglucosamine. Heparan sulfate, heparin and dermatan sulfate are competitive inhibitors. The enzyme is inhibited by Hg2+ and Cu2+. --SH-protective reagents and thiol reagents have no effect on the enzyme activity. Heating at 65 degrees C and pH values below 5 inactivate the enzyme rapidly.


The preparation of ligandin with glutathione-S-transferase activity from porcine liver cytosol affinity chromatography on bromosulphophthalein-Sepharose.

A simple and rapid method for the purification of porcine ligandin with glutathione-S-transferase activity is presented. After ion-exchange chromatography on DEAE-Sephadex, ligandin is isolated from porcine liver cytosol by affinity chromatography on bromosulphophthalein-Sepharose and gel filtration of Sephadex G-100. Evidence is presented that the purified ligandin is homogeneous with respect to polyacrylamide-gel electrophoresis (7.5%) and sodium dodecylsulphate-gel electrophoresis. Physico-chemical investigations show that the purified ligandin has properties similar to those of ligandin isolated from other species with respect to molecular weight, amino-acid composition, secondary structure and catalytic activity. As is the case for human and rat ligandin, porcine ligandin binds bilirubin. Evidence is also presented that porcine liver cytosol contains several bromosulphophthalein-binding proteins with basic isoelectric points lacking catalytic activity.


The effect of pindolol on plasma renin activity in patients with essential hypertension.

Twenty-two patients with essential hypertension were treated for 3 months with pindolol, and blood pressure and plasma renin activity were measured at rest and after stimulation (upright posture stimulation and insulin induced hypoglycaemia stimulation). Beta-receptor blockade produced a significant decrease in systolic and diastolic blood pressure. After treatment with pindolol the plasma renin activity was significantly lower. Under conditions of renin stimulation such as orthostasis and insulin produced hypoglycaemia, plasma renin activity was significantly lower in treated patients. There was no correlation between the fall of plasma renin activity and the decrease of blood pressure. Renin suppression is probably only one of the factors involved in the reduction in the blood pressure in these patients.


The effect of beta-adrenergic blockade on patterns of urinary sodium excretion, blood pressure and plasma renin activity in patients with essential and renovascular hypertension.

The effects of beta-adrenergic blockade, using oxprenolol, were studied in plasma renin activity, urinary sodium excretion and blood pressure in ten normal subjects and in 120 patients with essential and renovascular hypertension. Blood pressure was reduced by oxprenolol administration. The hypotensive action of the drug was independent of either the basal plasma renin activity or of the plasma renin activity response. Oxprenolol decreased plasma renin activity in normal subjects and in patients with essential hypertension with normal or high basal plasma renin activity. Patients with low plasma renin activity may show a lack of response to the beta-blockade. In patients with renovascular disease the response of plasma renin activity to oxprenolol was not a discriminant factor between patients cured or not cured by surgery. Some renovascular patients were unresponsive to beta-blockade with oxprenolol.


Determination of splenic blood flow by inhalation of radioactive rare gases.

We have evaluated the 133Xenon inhalation method for the determination of splenic blood flow. In twenty-two healthy persons the blood flow was on average 109 +/- 4 mg/100 g X min, which is equivalent to a total blood flow of about 170 ml/min. In patients with chronic fatty liver hepatitis specific blood flow was reduced (81 +/- 10 ml/100 g X min) as it was in patients with cirrhotic liver without splenomegaly (75 +/- 2 ml/100 g X min). With increasing weight of the spleen, the total blood flow rises, although specific blood flow is low. Our results obtained by the 133Xenon inhalation method are similar to results obtained by others using intraarterial injection of tracer gas. The advantages of the inhalation method as a non-traumatic method are: (1) the stress for the patient is very small; (2) blood flow measurements can be repeated within short periods of time. We consider for the present the 133Xenon inhalation method to be the method of choice for the determination of the splenic blood flow.


Serum octopamine, coma, and charcoal haemoperfusion in fulminant hepatic failure.

Serum octopamine levels were significantly higher in twenty patients with fulminant hepatic failure (FHF) during the first 48 h of grade IV coma than in health control subjects (3.38 +/- 0.20 ng/ml and 1.75 +/- 0.19 ng/ml respectively, P less than 0.001). Serial measurements in five patients who died without regaining consciousness showed serum octopamine to remain raised, and concentrations in the cerebrospinal fluid at death reflected serum levels. In five patients who regained consciousness, improvement in encephalopathy was associated with a significant reduction in serum octopamine. Renal failure in patients with FHF was found to contribute to raised serum octopamine but could not alone account for the observed levels. Patients given neomycin therapy did not have significantly lower serum octopamine levels than an untreated group. There was, however, a significant correlation between elevated serum octopamine and the occurrence of gestrointestinal bleeding during the previous 24 h. Charcoal haemoperfusion did not appreciably reduce serum octopamine levels.


Influence of cholic and chenodeoxycholic acid on biliary cholesterol secretion in man.

The interrelationships between biliary bile acid, lecithin and cholesterol secretion rates were studied druing depletion of the bile acid pool and during duodenal administration of cholic or chenodeoxycholic acid in thirteen patients 7-12 days after operation for uncomplicated gallstone disease. The mean lecithin secretion rate was signigicantly higher during cholic acid than during chenodeoxycholic acid infusion. The relationship between bile acid and cholesterol secretion rates was curvilinear, y = x/(a + bx) during bile acid pool depletion and during duodenal cholic acid infusion. At low bile acid secretion rates, during bile acid pool depletion and during cholic acid infusion, the lecithin secretion rate was significantly correlated to the cholesterol secreation rate. The bile acid and cholesterol secretion rates were not significantly correlated during chenodeoxycholic acid infusion. However, under this experimental condition a significant curvilinear relationship between lecithin and cholesterol secretion rates was found. The hepatic bile became unsaturated in cholesterol at significantly lower bile acid secretion rate during chenodeoxycholic acid infusion (10.7 +/- 0.3 mumol min-1) than during cholic acid infusion (15.6 +/- 0.5 mumol min-1).


Renin levels and spironolactone treatment in general practice: similar blood pressure lowering effect of spironolactone in low and normal renin patients.

We examined the predictive value of plasma renin activity (PRA) in ambulatory patients in the selection of hypertensive patients for treatment with spironolactone. The patients were classified as frusemide responders or non-responders according to their PRA response to 80 mg frusemide orally. After an initial 4 weeks placebo period forty-five patients with the clinical diagnosis of benign hypertension (WHO stage I-II) entered a 4 X 4 week double blind treatment period during which they received spironolactone (Aldactone) 400, 300, 200 and 100 mg/day, respectively. Five out of the forty-five patients who started the trial were withdrawn on account of side-effects and five patients for other reasons. Of the thirty-five patients who completed the study eighteen belonged to the group of non-responders to frusemide, seventeen to the responders. A gradual and significant decrease in mean blood pressure occurred during the period with the high doses of spironolactone, without any significant difference between the groups. The blood pressure lowering effect obtained with the initial high doses was maintained during the consecutive periods when the doses was reduced to a half or even a fourth, in both groups. We conclude that PRA measurement in ambulatory patients is of little, if any, value for the selection of hypertensives for spironolactone treatment; this in contrast to similar selections performed on hospitalized patients.


The influence of hydrazine, phenelzine and nialamide on gluconeogenesis and cell respiration in the perfused guinea-pig liver.

Hydrazine (2 mmol/l) and phenelzine (0.5 mmol/l), which are known to produce hypoglycaemia, inhibit glucose formation from lactate in the perfused guinea-pig liver. The hydrazone formed from pyruvate and phenelzine exerted the same effect at concentrations of only 0.05 mmol/l. It is suggested that the hydrazones are the substances which are effective. All these compounds inhibited pyruvate consumption and decreased CO2 production by the perfused liver which, togeteher with the pattern of hepatic metabolite concentrations, indicate that they diminish pyruvate metabolism. None of them influenced the activities in vitro of pyruvate carboxylase, phosphoenolpyruvate carboxykinase and pyruvate dehydrogenase. The hydrazone compound caused an increase of the ATP/ADP ration at lower concentrations and an opposite effect above 0.5 mmol/l. Nialamide, another hydrazine derivative, also reduced hepatic glucoeogenesis but led to a marked decrease in the hepatic ATP/ADP ratio and liver cell respiration accompanied by a rise in the 3-hydroxybutyrate/acetoacetate ratio.


Biocompatibility of coated and uncoated charcoal during haemoperfusion in healthy dogs.

The biocompatibility of two commercially available charcoal columns, one containing coated and the other uncoated but immobilized charcoal, was compared during four haemoperfusions with each in eight healthy greyhounds. Reductions in arterial levels of platelets (49% and 42% respectively) and leucocytes (both 21%) were similar. Microaggregates, detected by the Swank screen filtration pressure technique, were found in blood leaving the columns during three of the four perfusions with each column. Another twelve perfusions with the uncoated column were carried out with the addition of one or other of the following three agents which inhibit platelet aggregation: sulfinpyrazone, dipyridamole, or citrate-phosphate-dextrose. With none of these were platelet losses less as compared with the four perfusions in which heparin only was used. However, rises in screen filtration pressure were less pronounced. In other perfusions, where its dosage was varied, heparin was shown to reverse, and in large doses delay, the appearance of micro-aggregates. Thrombus in the column itself may be a source of microaggregates, but platelet aggregation in the absence of thrombus deposition may be responsible. The relation of these findings to micro-aggregate formation, which has constituted a clinical problem during charcoal haemoperfusion in humans with fulminant hepatic failure, is considered.


Body composition and adipose tissue cellularity before and after jejuno-ileostomy in severely obese subjects.

In severe obesity with adipose tissue hyperplasia it is difficult to achieve and sustain weight decrease by conventional therapy. Fifteen severely obese patients (mean body weight 135 kg) with hyperplastic obesity had a jejuno-ileostomy according to Payne to induce weight reduction by controlled malabsorption. Body composition, adipose tissue cellularity, and glucose tolerance were studied before and after the operation when the patients had reached a new stable weight (WS) a mean 21 months after surgery. Preoperative fat cell number was unchanged at follow-up in contrast to all other variables of body composition. Reductions in fat cell size were evenly distributed in different major subcutaneous regions. Body potassium was determined immediately after operation and at 6 months intervals until WS. The postoperative decrease stopped at 6 months, thus differing from the decrease in body weight. Significant positive correlations between the postoperative decrease in body weight or body fat, and preoperative body weight, body fat and body cell mass were analysed by multiple stepwise regression. Preoperative body weight and body fat were shown to predict postoperative weight loss at a leve of P less than 0.005. A positive correlation between body fat decrease and fat cell number could be explained hypothetically by an increased caloric demand in hyperplastic obesity.


Hereditary deficiency of phosphoglycerate kinase: a new variant in erythrocytes and leucocytes, not associated with haemolytic anaemia.

An X-chromosome linked phosphoglycerate kinase deficiency in erythrocytes and leucocytes was discovered in a large German kindred. Seven males of two generations were found to have only 21% of the normal enzyme activity in their erythrocytes, and twelve females of three generations showed various degrees of this defect. The differences in the expression of the deficiency in heterozygote females are explained by the Lyon hypothesis. The deficiency is caused by a variant enzyme, named phosphoglycerate kinase München. Although it differs from the normal enzyme electrophoretically, the two enzymes resemble one another closely in many respects. They have essentially the same Km for the substrates of the backward reaction, identical pH optima and similar rates of thermal inactivation. In contrast to the nine previously described phosphoglycerate kinase deficiencies, all of which are associated with haemolytic anaemia, the carriers of phosphoglycerate kinase München show no overt clinical symptoms. The erythrocyte concentrations of adenine nucleotides and 2,3-diphosphoglycerate are normal.


Consequences of myocardial reperfusion following temporary coronary occlusion in pigs; effects on morphologic, biochemical and haemodynamic findings.

The effects of myocardial reperfusion have been examined following a 1 h coronary occlusion and compared to a permanent coronary ligation in pigs. Haemodynamic investigations were carried out throughout the surgical intervention and repeated after 7 days. Cellular injury was estimated by serial serum enzyme determinations (creatin phosphokinase, alpha-hydroxybutyric dehydrogenase, aspartate aminotransferase, lactic dehydrogenase) during the first 5 postoperative days; infarct size was assessed morphometrically by a histochemical staining procedure 1 week after the temporary or permanent coronary occlusion. A linear correlation was found between the logarithmically plotted peak serum activity of AST, HBDH, CPK and the morphometrically determined infarct size. Based upon enzyme and morphometrical studies no significant difference could be detected between the two experimental groups. In the animals subjected to transient coronary occlusion, however, the development of a ventricular aneurysm had been prevented to early and sustained reperfusion. Early re-establishment of coronary circulation appears to accelerate the proliferation of a more resistant granulation tissue into the infarcted area. Cardiac performance was not improved by myocardial reperfusion.


Acid-base induced alterations in glutamine metabolism and ureogenesis in perfused muscle and liver of the rat.

The effects of altered acid-base balance on the production of urea and the metabolism of glutamine were investigated in the isolated perfused liver and hindquarter of the rat. In the isolated perfused rat liver, lowering of perfusate pH without altering bicarbonate concentration significantly reduced urea production and increased net glutamine synthesis, although the converse did not obtain. In the isolated perfused rat hindquarter when perfusate pH and bicarbonate were simultaneously reduced glutamine synthesis was significantly increased. The combined hepatic and muscle increase in glutamine synthesis accounted for 89% of the decrease in hepatic urea synthesis under these experimental conditions. These changes in nitrogen metabolism are interpreted in terms of adaptations which offset the initial alterations in hydrogen ion homeostasis.


Isoenzyme pattern of alkaline phosphatase in the serum of children with leukaemia after long-term chemotherapy.

Chemotherapy was discontinued in thirteen children with acute lymphoblastic leukaemia after 2-3 years without relapse. In the following months, a continuous increase was observed in the serum alkaline phosphatase. A maximum was reached at different times but all patients had normal values again after 19 months. The rise in the total activity is due to an isolated increase of the bone isoenzyme. Increased enzyme activity in this post-therapy phase of the disease does not signify liver damage from the preceding chemotherapy, but rather is due to an increased osteoblast activity associated with a temporary increase in growth rate.


The brush border membrane in hereditary sucrase-isomaltase deficiency: abnormal protein pattern and presence of immunoreactive enzyme.

In a child with hereditary sucrase-isomaltase deficiency immunoreactive enzyme was present in the intact duodenal mucosa. Polyacrylamide gel electrophoresis carried out with membrane fragments of an intestinal biopsy showed an abnormal protein band without enzyme activity. The mucosa had a relatively high residual isomaltase activity which was recovered from the gel in a position suggesting higher than normal molecular weight. The results indicated that in this patient the primary structural defect was in the sucrase moiety which was enzymatically inactive. The isomaltase subunits may have aggregated into a large molecular weight complex because of unavailability of their partners. The observation also provided evidence for separate biosynthesis of the two moieties of the sucrase-isomaltase complex.


Idiotype suppression by maternal influence.

In BALB/c mice, antibodies to the alpha-(1-3) glucosidic linkage of some dextrans (Dex) carry the idiotype of the BALB/c myeloma protein J558. Both specific antibody and idiotype are inherited in a dominant fashion, linked to the immunoglobulin (Ig) (heavy chain) allotype Igla of BALB/c mice (Eur. J. Immunol. 1975. 5: 775). In F1 hybrid mice from the parent strains SJL and BALB/c, we were able to suppress the expression of anti-Dex antibodies by immunizing prospective SJL mothers to the J558 idiotype. The state of suppression in the progeny was ascertained by immunization with Dex, and tests for the following were carried out: (a) antibodies specific for Dex; (b) inhibition of such antibodies (if present) by antiidiotypic serum to protein J558; (c) presence of the J558 idiotype; and (d) concentration of lambda1 chains (which are associated with the 558 idiotype) in the serum. SJL mothers, once immunized, conferred suppression upon several successive litters, spanning a period of 4-5 months. Suppression in F1 progeny animals lasted for 16 weeks or more. Spleen cells from suppressed F1 mice which had neither been treated with Dex nor with J558 protein, were able to confer suppression to further F1 newborn mice.


Electrophoretic variation in esterases in 3 wild-type and respective mutant strains of Aspergillus flavus.

Wild-type strains and auxotrophic mutants of Aspergillus flavus, differing regarding aflatoxin production, were tested for esterases isozymes. Esterases variation was found in all strains used, and a possible correlation between the pattern of esterase bands and aflatoxin production is suggested.


Purification and immobilization of human carbonic anhydrase B by using polyacrylamide gel.

Human erythrocyte carbonic anhydrase B was purified and immobilized in polyacrylamide gel. As compared to the soluble enzyme, the immobilized enzyme was considerably more resistant to heat and sulphanilamide action.


[Types of receptive fields of neurons in different laminae of the rabbit visual cortex].

Neurons of the primary rabbit visual cortex were classified into 7 large groups according to features of their receptive fields. The neurons with receptive fields were mostly revealed in the layers IV and VI, those with uniform directional receptive fields--in layer V, those with simple I-in layer VI, those with simple II--in layer II + III, and those with hypercomplex--in layer IV. The neurons with concentric receptive fields and those without responses to visual stimuli were equally distributed over the layers. The data obtained in rabbits, cats, and monkeys suggest that the tendency towards function stratification of primary visual cortex is successive in an evolutionary order of mammals.


[Therapeutic experience with 5-chloro-8-hydroxyquinoline].

This paper reports on the clinical trials of an antimycoticum using 5-chlorine-8-hydroxychinolin as an antimycotic agent. 142 patients with surface dermatomycoses were treated locally with the preparation for 5 to 6 weeks. Clinical and mycological healing was achieved in 68% of the cases. The results of the treatment, the epicutaneous tests and the additional UV exposition are discussed. The best results of treatment were obtained in the case of superficial dermatomycoses, in particular Trichophytia inguinalis.


Studies on the control and dynamics of thyrotropin secretion from isolated adenohypophyseal cells.

Thyrotropin (TSH) secretion from isolated anterior pituitary cells has been studied using the technique of cell column perifusion. The consistency in secretory rate and temporal profiles of TSH output in response to stimulation illustrated that the system is suitable for studying the kinetics of stimulation and inhibition of secretion. During perfusion TSH release was stimulated in response to a variety of secretogogues, namely TRH, raised potassium concentrations and phosphodiesterase inhibitors. The onset and termination of the secretory responses were rapid and displayed a temporally biphasic pattern of secretion. Dose-related increases in TSH output in response to TRH and consistent responses to repetitive pulses of TRH (5.5 X 10-10 M) during a 4 h period were demonstrated. Studies on the dynamics of thyroid hormone feedback on TRH-stimulated TSH secretion indicated that inhibition was manifest within 1 h and reached a maximum after 2 1/2 h during continual exposure to thyroid hormones. Isobutylmethylxanthine (IBMX) potentiated the effect of raised K+ as well as that of TRH on TSH secretion, suggesting an as yet unidentified relationship between Ca2+ and cyclic AMP.


On the interpretation of mutagenically induced mosaicism in Drosophila.

This paper draws attention to the formal parallelism that exists between chromosomal-loss mosaicism and mutagenically induced mosaicism in Drosophila and suggests that, although the underlying processes by which these two types of genetic mosaics are generated are very different, the more refined methodology employed in developmental analyses of genetically induced chromosomal-loss mosaics may be profitably extrapolated to mutagenesis studies. Results obtained from various studies of genetically induced mosaics and from a previous EMS mutation induction experiment at the yellow locus are utilized to illustrate this methodology and to estimate the total mutagenicity rates of EMS.-The following are some of the tentative conclusions that have been drawn in this report regarding an EMS concentration that produced 31% F(2) lethals in the standard X-linked recessive lethal test: (1) The frequency of cuticular mosaics is at least 5 times that of F(3) lethals. (2) At least 60% of all cuticular mosaics go undetected in the standard X -linked recessive lethal test since their mutant tissue does not extend into the germ line. (3) The frequency of EMS-induced cryptic mosaics is probably less than 10% the frequency of cuticular mosaics. (4) Some EMS-induced mutations are probably bona fide completes; if confirmed, this inference must be taken into consideration in estimating the total mutagenicity rates of this agent and in molecular interpretations of its mechanism of action. (5) The fact that the proportion of mutant tissue in EMS-induced mosaics is greater than 25% is consistent with the suggestion that the action of EMS is occasionally delayed until after the first cleavage division of the embryo. (6) Such an EMS concentration causes on the average more than 5 independent genetic alterations in the entire haploid genome of an X-bearing sperm.-This report clarifies the experimental evidence that must be generated, and the methodology that can be used to analyze this evidence, if it is of interest to render these and related conclusions regarding the effect of EMS on D. melanogaster more accurate, or if it is of interest to conduct a similar analysis for other mutagens that cause a significant degree of mosaicism.


Genetic modulation of RNA metabolism in Drosophilia. I. Increased rate of ribosomal RNA synthesis.

It has been suggested that a particular Y chromosome which is rDNA-deficient (YbbSuVar-5) may be associated with an increased utilization of rDNA template in adult testes (Shermoen and Kiefer 1975). To extend the observations on this chromosome, experiments were designed to determine if the chromosome has an effect on rRNA synthesis in bobbed adults and on classic bobbed phenotypes (shortened and thinner scutellar bristles and delayed development). Specific activity measurements were made on rRNA extracted from adult males of the genotypes car bb/YbbSuVar-5, which are rDNA-deficient to the same extent, and from Samarkand+ isogenic (Sam+ iso), which is a wild-type stock. The resulting data demonstrated that the presence of the YbbSuVar-5 chromosome increases the rate of ribosomal RNA synthesis in adult flies. In addition, it was found that the presence of this particular Y chromosome restores wild-type bristle phenotype and development time. Appropriate genetic crosses indicate that the observed effects (increased rRNA synthesis, restoration of wild-type phenotype) are a function of this particular Y chromosome, and are not due to autosomal factors. The results of these experiments suggest that the rate of rRNA accumulation is under genetic control.