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Biomedical subjects

J M Lopez

Publications and source records attributed to J M Lopez.

At least 55 records · Page 3Linked to original sources

Effects of type I interferon-inducing agents on hepatic metallothionein.

Two inbred strains of mice were used in this study, the C57BL/6J which is reported to be a high interferon producer and the C3H/HeJ which is reported to be a low interferon producer. Each mouse received a single i.p. injection of either Newcastle disease virus (NDV) or the double-stranded nucleotide, polyinosinic acid-polycytidilic acid (poly (rI.rC], both type I interferon inducers, or cadmium chloride, a known inducer of metallothionein (MT), and were killed 24-hr later. Treatment of the C57BL and C3H mice with 1 mg Cd/kg caused a 14- and 16-fold increase in hepatic MT concentrations, respectively. In both strains, this induction was accompanied by an increase in the hepatic concentration of zinc but not copper. There were no observed changes in the circulating levels of interferon. In the C57BL mice, both the administration of poly (rI.rC), at a dose of 10 mg/kg, and NDV, at a dose of 512 hemagglutinating units/mouse, produced a 4-fold increase in the hepatic concentration of MT. Although both treatments caused an increase in levels of interferon, the increase seen with NDV was greater than that seen with poly (rI.rC). In the C3H mice, the results were quite different. Although both treatments induced hepatic MT concentrations 4- to 5-fold, the increase in interferon levels observed following the administration of poly (rI.rC) was higher than that seen with NDV and some 50-fold higher than the increase produced by the polynucleotide in the C57BL mice. The results of this study indicate that two interferon-inducing agents, poly (rI.rC) and NDV, are also capable of inducing hepatic metallothionein.

Animals↗

Linkage analysis with RFLPs in families with androgen resistance syndromes: evidence for close linkage between the androgen receptor locus and the DXS1 segment.

Three families with androgen resistance syndromes--two with testicular feminization and one with Reifenstein syndrome--have been studied for linkage analysis. Using three cloned DNA sequences from the centromere region and the proximal long arm of the X chromosome (p8, pDP34, and S9, which define respectively the chromosomal segments DXS1, DXYS1, and DXS17), we found no recombination between the DXS1 locus and the mutant genes in the three families. Assuming that these disorders are the result of allelic mutations at the same locus for the androgen receptor, we can conclude that there is a close linkage between DXS1 and the androgen receptor locus, with a maximum lod score zeta = 3.5 at a recombination fraction theta = 0.0 using the LIPED program (Ott 1974).

Androgen-Insensitivity Syndrome↗

The postnatal development of serum zinc, copper and ceruloplasmin in the horse.

1. Serum samples were collected from ten foals at predetermined times during the first 12 months following birth and zinc and copper concentrations and ceruloplasmin activity were evaluated. 2. Serum zinc concentrations were found to be quite variable with respect to age (range = 67-95 micrograms/dl). 3. Serum copper concentrations increased in a linear fashion from day 0 to day 28 before levelling off at 190-247 micrograms/dl. 4. Ceruloplasmin activity was found to correlate with the concentration of serum copper (r = 0.92) and reached a plateau at an activity of 30-38 IU by day 28.

Aging↗

Isolation and partial characterization of a cadmium-binding protein from the liver of alligators exposed to cadmium.

Seven American alligators, Alligator mississippiensis, were each administered a single, intracardiac injection of cadmium chloride, at a dose of 1.0 mg Cd/kg body wt. At sacrifice, the highest concentration of Cd was found in the liver, bound to a cytosolic protein with characteristics similar to mammalian metallothionein (MT). Gel filtration (Sephadex G-75) of the cytosol revealed a peak containing Cd and to a lesser extent, zinc (Zn), having the same relative elution volume (Ve/Vo) as rat hepatic Cd, Zn-MT. Anion-exchange chromatography (DEAE-Sephacel) of material having a Ve/Vo of 1.7-1.9 revealed a major Cd-peak corresponding to rat Cd, Zn-MT(I) and a minor peak corresponding to Cd, Zn-MT(II). Neither peak contained significant amounts of Zn. Heat treatment of alligator hepatic cytosol, followed by selective acetone precipitation, yielded material having a molar Cd:Zn ratio of 9.15:1 compared to 0.67:1 in material purified from Cd-pretreated rat liver. Spectral analysis of the material purified from both sources showed an absorbance peak between 250 and 260 nm and no absorbance peak at 280 nm, characteristic of mammalian MT.

Alligators and Crocodiles↗

Congenital 11 beta-hydroxysteroid dehydrogenase deficiency associated with juvenile hypertension: corticosteroid metabolite profiles of four patients and their families.

Four children with 11 beta-hydroxysteroid dehydrogenase deficiency are described. All patients had severe hypertension, hypokalaemia, and low plasma aldosterone and renin activities. Two of the patients were siblings and two were unrelated. The most noticeable biochemical feature of these individuals was the extremely low excretion of cortisol metabolites containing an 11-carbonyl group compared to the excretion of the 11 beta-hydroxyl containing metabolites. Although this condition is readily diagnosed in affected individuals by urinary steroid analysis, carriers of the defect do not differ from normal in their urinary steroids. Both parents of the affected siblings had normal 11-oxo-steroid/11 beta-hydroxysteroid ratios under baseline conditions and the lesions could not be revealed by ACTH administration.

11-beta-Hydroxysteroid Dehydrogenases↗

[Myrhaug's operation. Apropos of 8 cases].

Myrhaug's operation was performed in 5 patients with recurrent dislocations, including two after failure of buttress operations, and 3 cases of temporomandibular joint pain and dysfunction syndrome. The particular conditions for choice of patient for this operation are emphasized, these excluding all cases followed up after occlusal reconstruction and requiring rapid and effective solutions apparently supplied by this surgical procedure.

Adolescent↗

Penetration of different human pathogenic viruses into sand columns percolated with distilled water, groundwater, or wastewater.

The adsorption of several enteroviruses and rotavirus SA11 to sand from an aquifer in the Federal Republic of Germany was estimated in sand-filled columns loaded with ca. 10(7) PFU and run at a velocity of 2.5 m/day for 12 h. After either distilled water, groundwater, secondary effluent, or tertiary effluent was percolated, the sand core was slowly extruded out of the column and cut in 1-cm slices. The slices were eluted with nutrient broth, and the amount of viruses in the broth was estimated. The best adsorption was promoted by groundwater and tertiary effluent, followed by distilled water and secondary effluent. Similar experiments, carried out at different percolation rates, indicated that a 50-day underground stay of recharged water probably suffices to eliminate viruses in the groundwater-recharged tertiary effluent. However, when viruses and sand were incubated in the presence of the surfactants sodium dodecyl sulfate, nonyl phenol, dodigen 226, or alkylbenzylsulfonate, the adsorption of the viruses was substantially diminished. Experiments in the presence of nonyl phenol seem to indicate that hydrophobic interactions are involved in the adsorption of viruses to sand.

Adsorption↗

Aldosterone-producing adrenocortical carcinoma. Preoperative recognition and course in three cases.

Three patients with primary aldosteronism due to adrenocortical carcinoma were studied, two with hyperaldosteronism alone and one also with hypercortisolism; in the later stages all three had hypersecretion of glucocorticoid and androgenic hormones. Although clinical presentations were similar to those of patients with benign adenoma, all had significantly higher concentrations of deoxycorticosterone and aldosterone and more profound hypokalemia. Stimulation with adrenocorticotropin in two patients showed a good cortisol response but no aldosterone response. The circadian rhythm for cortisol was normal but absent for aldosterone and deoxycorticosterone. Sequential 24-hour circadian studies in one patient showed that as the disease progressed, corticosterone and finally cortisol lost their circadian rhythms. Treatment with spironolactone, mitotane, or aminoglutethimide had transient clinical effects. The patients died 2 to 13 years later.

Adrenal Cortex Neoplasms↗

Effect of decoyinine on peptidoglycan synthesis and turnover in Bacillus subtilis.

The sporulation of Bacillus subtilis can be induced in the presence of amino acids and glucose by partially depriving the cells of guanine nucleotides. This can be achieved, e.g., by the addition of decoyinine, a specific inhibitor of GMP synthetase. To determine the effect of this and other inhibitors on cell wall synthesis, we measured in their presence the incorporation of acetylglucosamine into acid-precipitable material. The rate of wall synthesis decreased by 50% within 5 min after decoyinine addition; this decrease was prevented by the presence of guanosine. A comparison with the effects of other inhibitors of cell wall synthesis indicated that decoyinine inhibited the final portion of the cell wall biosynthetic pathway, i.e., after the steps inhibited by bacitracin or vancomycin. Decoyinine addition also prevented cellular autolysis and cell wall turnover. It is not known whether these two effects of decoyinine on cell wall synthesis are causally related.

Adenosine↗

[Efficiency of current technics for the isolation of viruses in water].

In an attempt to evaluate the efficiency of the current methodology for the concentration of viruses from water and wastewater, we have determined the viral concentration in raw sewage using three procedures: a) inoculation of cell cultures directly with the filtered sewage, b) concentration of the viruses from the sewage using nitrocellulose filters at a pH of 3.5 in the presence of AlCl3, followed by elution with Nutrient Broth and inoculation of the cell cultures with the eluant and c) flocculation of the Nutrient Broth after the elution as in b, dissolution of the precipitate in cell medium and inoculation of the cell cultures with this solution. The results show that this concentration procedure with nitrocellulose filters as recommended in the "Standard Methods for the Examination of Water and Wastewater" has an efficiency of 33% if compared with the direct inoculation. In a separate study, we have looked at the properties of electropositive Filters to bind polioviruses Typ I, Strain Lsc 2ab at neutral pH in the absence of salt. These filters, which could be used several times, were able to retain more then 99.5% of the viruses. However, they bound the viruses stronger that nitrocellulose filters and the elution with Nutrient Broth was never complete. After the problems with the elution are solved, these filters promise to simplify substantially the procedure for concentrating viruses from water.

Collodion↗

GTP pool expansion is necessary for the growth rate increase occurring in Bacillus subtilis after amino acids shift-up.

After addition of amino acids to a Bacillus subtilis glucose culture the intracellular guanosine triphosphate (GTP) concentration increased. The growth rate and the rate of RNA accumulation increased too. With mycophenolic acid, an inhibitor of inosinate dehydrogenase, it was possible to adjust the intracellular GTP concentration to values ranging between that of the glucose culture and that of the culture which had received amino acids. This led to intermediate growth rate values. Guanosine abolished the mycophenolic acid inhibition of GTP synthesis. It also counteracted the drug effects on growth rate and RNA accumulation. In cultures growing on Nutrient Sporulation Medium, in which the growth rate decreases as cell density increases, the GTP concentration did correlate with the growth rate.

Adenosine Triphosphate↗

[Virus removal from municipal wastewater by biological sewage treatment].

During a period of ten months, we have determined once a week the amount of viruses in the untreated sewage and in the effluent of two communal sewage treatment plants. Besides, we have compared the virus content of chlorinated and unchlorinated effluent and have determined the amount of viruses in the river in which the effluent is discharged, and in groundwater. In order to concentrate the viruses, the AlCl3-treated samples were filtered through cellulose nitrate filters and the adsorbed viruses eluted with cell culture medium containing 10% fetal calf serum. This medium was used for inoculating cell cultures which were monitored several times weekly for CPE. After the treatment in the plants, the number of viruses was reduced 99.15 and 97.9% respectively. Chlorination of the effluent further reduced the number of viruses by a factor of 5. None of the groundwater samples was viruspositive.

Chlorine↗

Nitrofurantoin prompts the stringent response in Bacillus subtilis.

Nitrofurantoin causes the stringent response in Bacillus subtilis. After exposure of a stringent strain to this drug, the intracellular concentrations of guanosine 3'-diphosphate 5'-diphosphate (ppGpp), guanosine 3'-diphosphate 5'-triphosphate (pppGpp) and ATP increased, while that of GTP decreased. In a relaxed strain no accumulation of ppGpp or pppGpp was observed, but both GTP and ATP declined after the addition of nitrofurantoin. Protein synthesis was equally sensitive to nitrofurantoin in both the stringent and relaxed strains, but the drug inhibited RNA accumulation only in the stringent strain, not in the relaxed strain. Nitrofurantoin also caused the accumulation of ppGpp in Escherichia coli and Serratia marcescens.

Bacillus subtilis↗

Induction of citric acid cycle enzymes during initiation of sporulation by guanine nucleotide deprivation.

In Bacillus subtilis, conditions causing partial deprivation of guanine nucleotides initiated sporulation and caused the synthesis of citrate synthase, aconitase, and alpha-ketoglutarate dehydrogenase. Alpha-ketoglutarate dehydrogenase could also be induced by acetate, and the specific activity of this enzyme was elevated in mutants that had high intracellular acetyl coenzyme A concentrations because they lacked citrate synthase activity. After deprivation of guanine nucleotides, the intracellular concentration of acetyl coenzyme A also increased, which explained the induction of alpha-ketoglutarate dehydrogenase. Furthermore, the decreases in alpha-ketoglutarate and L-malate concentrations observed during this deprivation accounted for the observed increases in citrate synthase activity (which was repressed by alpha-ketoglutarate and malate) and aconitase activity (which was repressed by alpha-ketoglutarate).

Acetates↗

Response of guanosine 5'-triphosphate concentration to nutritional changes and its significance for Bacillus subtilis sporulation.

We have investigated the changes in the guanosine 5'-triphosphate (GTP) and P-ribosyl-PP pools in stringent and relaxed strains of Bacillus subtilis under conditions frequently used to initiate sporulation. After a shift-down from a Casamino Acids-glutamate to a glutamate medium (Sterlini-Mandelstam shift-down), the pools of adenosine 5'-triphosphate and P-ribosyl-PP increased in both strains; in the stringent strain, ppGpp and pppGpp increased and GTP decreased rapidly, whereas in the relaxed strain, ppGpp and pppGpp increased only slightly and GTP decreased only slowly and less extensively. The stringent strain sporulated well, whereas the relaxed strain sporulated late and poorly. Addition of decoyinine, an inhibitor of guanosine 5'-monophosphate synthetase, caused a further decrease of GTP and initiated good sporulation of the relaxed strain. After a shift-down from a glucose-lactate to a lactate medium (Ramaley-Burden shift-down) the pool of P-ribosyl-PP (and GTP) decreased in both strains, indicating a shortage of purine precursors. This shift-down also caused a stringent response which prevented the consumption of nucleotides, as shown by the maintenance of adenosine 5'-triphosphate at a high concentration in the stringent strain but not in the relaxed strain. After a delay, the relaxed strain, in which GTP decreased as fast as in the stringent strain, sporulated also as efficiently. In nutrient sporulation medium the stringent strain and, less effectively, the relaxed strain accumulated ppGpp and pppGpp transiently towards the end of exponential growth. Eventually, the P-ribosyl-PP pool decreased drastically in both strains. In all cases the initiation of sporulation was correlated with a significant decrease of GTP. Granaticin, an antibiotic which prevents the charging of leucyl-transfer ribonucleic acid, was used to show that the stringent response inhibited the formation of xanthosine monophosphate from inosine monophosphate. It prevented the accumulation of xanthosine monophosphate in decoyinine-treated cultures of the stringent strain but not in those of the relaxed strain.

Adenosine Triphosphate↗

Catabolite repression of enzyme synthesis does not prevent sporulation.

In the presence of excess glucose, a decrease of guanine nucleotides in Bacillus subtilis initiated sporulation but did not prevent catabolite repression of three enzymes. Therefore, the ultimate mechanism(s) repressing enzyme synthesis differs from that suppressing sporulation.

Acetoin Dehydrogenase↗

The decrease of guanine nucleotides initiates sporulation of Bacillus subtilis.

Massive sporulation of Bacillus subtilis normally begins when carbon, nitrogen or phosphorus sources able to support rapid growth are no longer available. Sporulation can also be induced in exponentially growing cultures, in the presence of rapidly utilizable ammonia, glucose and phosphate if growth is partially but not completely inhibited either by inhibitors of nucleotide synthesis (hadacidin, decoyinine or 6-azauracil) or by purine deprivation in purine and especially in guanine auxotrophs. All these conditions allowing sporulation result in a decrease in the intracellular concentration of guanosine di- and tri-phosphates and usually uridine di- and triphosphates while other nucleotides decrease in some but increase in other cases. A decrease of uracil nucleotides alone, in a uracil auxotroph, does not produce massive sporulation. Our results demonstrate that the partial reduction of a guanine nucleotide, probably relative to some other compound, suffices to initiate sporulation. This reduction may always play a decisive role in the initiation of sporulation, as we have observed it under all conditions so far known to produce massive sporulation.

Bacillus subtilis↗