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Biomedical subjects

J Adler

Publications and source records attributed to J Adler.

At least 217 records · Page 12Linked to original sources

Removal of glycosaminoglycans from cultures of human skin fibroblasts.

Early-passage human skin fibroblasts were grown as monolayers for 2-3 days in minimum essential medium containing [35S]sulphate, [3H]glucosamine, [3H]fucose, [3H]proline or [3H]leucine to label proteoglycans, glycoproteins or collagen and other proteins. A crude enzyme preparation obtained from a supernatant from sonicated freeze-dried Flavobacter heparinum was added to the cell monolayers. This treatment removed most of the 35S-labelled glycosaminoglycans, with no appreciable removal of the 3H-labelled proteins or 3H-labelled glycoproteins. The cells remained attached and viable as a monolayer. The formation of 35S-labelled glycosaminoglycans was examined after pretreating cultures with crude F. heparinum enzyme, followed by addition of fresh growth medium containing [35S]sulphate. The F. heparinum enzyme did not significantly alter the amount or type of 35S-labelled glycosaminoglycans produced. Thus F. heparinum enzyme can be used to provide cultured-cell monolayers depleted of surface glycosaminoglycans. These cells remain attached, viable and subsequently synthesize normal amounts and type of glycosaminoglycans.

Cell Survival↗

Computed tomographic findings in a case of renal vein thrombosis with nephrotic syndrome.

Renal vein thrombosis is a complication of the nephrotic syndrome presumably related to compression of renal veins by edematous parenchyma and a concomitant hypercoagulable state. The diagnosis has been made by demonstrating marked widening of the left renal vein as it crosses horizontally anterior to the aorta on computed tomography. Inferior venacavography confirmed the presence of thrombosis within the vessels. CT is suggested as a method for noninvasive imaging of the renal veins which might eliminate the need for venography.

Humans↗

Change in intracellular pH of Escherichia coli mediates the chemotactic response to certain attractants and repellents.

Changes in the membrane potential, pH gradient, proton motive force, and intracellular pH of Escherichia coli were followed during the chemotactic responses to a variety of potentially membrane-active compounds. Lipophilic weak acids, decreases in extracellular pH, and nigericin each caused a repellent response. Lipophilic weak bases, increases in extracellular pH, and valinomycin in the presence of K+ each caused an attractant response. Changes in membrane potential, pH gradient, and proton motive force did not correlate with the behavioral responses to these treatments, but changes in intracellular pH did correlate. Furthermore, the strength of the response to a weak acid was correlated with the magnitude of the change of the intracellular pH, and many compounds which could alter the intracellular pH were found to be chemotactically active. Apparently these attractants and repellents are not detected by specific chemoreceptors but rather are detected via the ability of cells to sense and respond to changes in intracellular pH. The pathway of sensory transduction which proceeds through methyl-accepting chemotaxis protein I was found to be involved in the response to a change in intracellular pH.

Acetates↗

Quinine alone versus quinine plus a pyrimethamine-sulfadoxine combination in the treatment of Plasmodium faliciparum cerebral malaria.

Fifty-two patients with severe chloroquine resistant Plasmodium falciparum malaria were treated in a randomized double blind study with either quinine and a single dose of pyrimethamine-sulfadoxine (Fansidar) or quinine alone. Although no statistically significant differences were observed, the 25 patients who received both drugs responded faster and had a more favorable outcome (no deaths) when compared to the 27 who received quinine alone (2 deaths).

Clinical Trials as Topic↗

Morphologic structure of the pedal arch and its relationship to patency of crural vascular reconstruction.

Pedal arch integrity can be determined morphologically and functionally. The former is accessible by contrast studies and intraoperative catheterization, the latter, by flow studies and observation of graft patency. The roengten image of an intact pedal arch corresponds to the anatomic plantar arch. Sixty-four arch studies obtained by adequate intraoperative arteriography were categorized as intact, deficient or inadequate or absent. Patency of crural reconstructions was obtained in 18 of 24 patients with intact arches as compared with 15 of 32, p<0.06, when the arch was deficient. Crural reconstruction in the face of an inadequate or absent arch resulted in predictable graft closure. Qualitative factors, that is, size, calcium and stenotic lesions, are integrally related to over-all graft performance even with intact arches. The deficient arch for tibial and peroneal reconstruction continues as a challenge to the vascular surgeon.

Angiography↗

Involvement of cyclic GMP in intracellular signaling in the chemotactic response of Escherichia coli.

The intracellular signal that produces changes in swimming behavior when bacteria encounter attractants or repellents has not previously been identified. We suggest, based on the following lines of evidence, that cyclic GMP (cGMP) is involved in this signaling process in chemotaxis by Escherichia coli. (i) The addition of attractants to bacteria causes a transient increase in the intracellular level of cGMP, whereas a repellent stimulus decreases the level transiently. These changes do not generally occur in a mutant lacking chemotaxis-specific proteins. (ii) In the absence of chemoeffectors, both addition of cGMP to bacteria and reducing the intracellular cGMP level produce changes in swimming behavior, and a mutant with an abnormal swimming pattern has an altered intracellular cGMP level. (iii) cGMP modulates the demethylation reaction responsible for adaptation to stimuli. (iv) Mutants defective in components of the adaptation system have altered cGMP metabolism.

Bacterial Proteins↗

A novel mechanism of resistance to penicillin-gentamicin synergism in Streptococcus faecalis.

A patient with enterococcal endocarditis, who relapsed after repeated courses of apparently adequate treatment with ampicillin plus gentamicin, was subsequently cured with ampicillin-tobramycin therapy. The organisms isolated from this patient were strains of Streptococcus faecalis that were resistant to penicillin (or ampicillin)-gentamicin synergism but not to penicillin (or ampicillin)-tobramycin synergism. The mechanism of resistance in these strains appears to be related to a specific defect in the intracellular uptake of gentamicin (but not tobramycin) in the presence of penicillin.

Dose-Response Relationship, Drug↗

Genetic and biochemical properties of Escherichia coli mutants with defects in serine chemotaxis.

In Escherichia coli, taxis to certain chemoeffectors is mediated through an intrinsic membrane protein called methyl-accepting chemotaxis protein I (MCP I), which is the product of the tsr gene. Mutants were selected that are defective in taxis toward all MCP I-mediated attractants (alpha-aminoisobutyrate, L-alanine, glycine, and L-serine) but are normal to MCP I-mediated repellents and to chemoeffectors mediated by other MCPs. The mutants could be divided into two classes based on their ability to respond to various concentrations of L-serine. Two MCP I-mediated L-serine systems appear to function in the wild type: one of high and one of lower affinity. The mutations responsible for the serine taxis defects map at about 99 min on the E. coli chromosome and are not complemented by episomes carrying mutations in the tsr gene; this suggests that they are defective in tsr function. Low concentrations of L-[14C]serine specifically bound to wild-type membranes with a Km of 5 microM; in contrast, there was greatly decreased binding to vesicles prepared from the new mutants or from the tsr mutant AW518. Binding of labeled serine to wild-type vesicles was inhibited by MCP I-mediated attractants, but not by MCP II-mediated attractants. The data suggest that MCP I may function as the L-serine chemoreceptor in E. coli.

Bacterial Proteins↗

Methanol formation in vivo from methylated chemotaxis proteins in Escherichia coli.

Chemotactically wild type Escherichia coli were incubated with L-[methyl-3H]methionine to label the methyl groups of their methyl-accepting chemotaxis proteins. Cells were then treated to specifically demethylate these proteins. We have identified the end product of this demethylation as [3H]methanol in the cell-free medium from treated cells.

Bacterial Proteins↗

Effect of cyclic changes in environmental lighting and ambient temperature on the daily rhythm in melatonin excretion by rats.

Melatonin excretion was measured by radioimmunoassay in 6 h or 12 h urine specimens from individual control rats and from animals previously blinded by bilateral orbital enucleation. Among sighted rats, the rate of melatonin excretion was greatest during the daily 12 h of darkness (1.44 +/- 0.06 ng/12 h dark period vs. 0.53 +/- 0.07 ng/12 h light period; P less than 0.001). Moreover, greater quantities of melatonin were excreted in the latter half of the dark period than in the first half (e.g. 0.55 +/- 0.08 ng/first 6 h vs 0.97 +/- 0.05 ng/second 6 h; P less than 0.001). When the onset of the daily light period was shifted forward by 12 h, 5--7 days were needed for the daily rhythm in melatonin excretion to become re-entrained to the new light--dark cycle. Among blinded rats, the rate of melatonin excretion also varied rhythmically; however, the rhythm was neither synchronized with the light-dark cycle nor influenced by alterations in the lighting schedule. Similarly, artificial cycles in environmental temperature were not effective in entraining the daily rhythm in melatonin excretion among blinded rats.

Animals↗

Identification of a methyl-accepting chemotaxis protein for the ribose and galactose chemoreceptors of Escherichia coli.

The ribose and galactose chemoreceptors of Escherichia coli have previously been identified as the ribose- and galactose-binding proteins. We now report the discovery of a methyl-accepting chemotaxis protein that functions in the transfer of receptor signals from these two binding proteins to the flagella. This protein is distinct from previously described methyl-accepting chemotaxis proteins. Its level of methylation is influenced by D-ribose, D-galactose, and certain structural analogues of them. This methyl-accepting protein is required for chemotaxis toward those attractants; mutants in the trg gene, which do not methylate this protein, are devoid of taxis toward D-ribose, D-galactose, and their analogues. In addition, methylation of the methyl-accepting protein in response to each of these attractants requires the appropriate binding protein. The binding protein's chemoreceptor function is required for such methylation, but its transport activity is not. Because the function of this methyl-accepting chemotaxis protein involves two of the best-characterized chemoreceptors, the discovery of this protein represents a promising base for further study of the linkage between chemoreceptors and flagella in bacteria.

Bacterial Proteins↗

Attractants and repellents control demethylation of methylated chemotaxis proteins in Escherichia coli.

A group of methylated proteins, the methyl-accepting chemotaxis proteins (MCP), has been shown to play a central role in bacterial chemotaxis. Both methylation and demethylation of MCP occur continuously in the absence of added stimuli; these two processes are in balance such that a basal level of methylation is maintained. Attractants cause the methylation level to increase to a new value, whereas repellents bring about a decrease in level. Therefore, attractants and repellents must somehow perturb the balance between methylation and demethylation of MCP. In this report the effect of attractants on demethylation of MCP was monitored in two ways: (i) by following the disappearance of [methyl-3H]MCP and (ii) by measuring formation of [3H]methanol, the product of MCP demethylation. Both methods showed that addition of attractants causes a transient inhibition of MCP demethylation. Repellent addition has previously been shown to stimulate MCP demethylation. It is therefore concluded that control of demethylation plays a crucial role in changing the level of methylation of MCP in response to attractants and repellents.

Bacterial Proteins↗

Attractants and repellents influence methylation and demethylation of methyl-accepting chemotaxis proteins in an extract of Escherichia coli.

During bacterial chemotaxis, attractants and repellents alter the methylation levels of the methyl-accepting chemotaxis proteins (MCPs). These methylation levels represent a balance between two enzymatic processes: methylation and demethylation. In vivo experiments previously have shown that chemoeffectors influence the demethylation process; effects on the methylation system have not been reported. Here we show that in a cell-free extract of Escherichia coli both methylation and demethylation of the MCPs are affected by attractants and repellents. Attractants enhance methylation and inhibit demethylation. Repellents inhibit methylation and stimulate demethylation. The cell-free system provides an opportunity for further study of the mechanisms by which attractants and repellents influence the levels of methylation of the MCPs.

Bacterial Proteins↗

Glucagonoma, chronic recurrent peptic ulcer disease, and enhanced amylase-creatinine clearance ratio. Report of a case with review of the literature.

A 53-year-old white woman developed diabetes mellitus, migratory erythema, and anemia, clinical features suggesting the presence of a "glucagonoma." Ten years earlier, after laparotomy and pancreatic biopsy, she had been told that she had an inoperable pancreatic carcinoma. Review of that biopsy together with current hormonal assay now confirms the diagnosis of glucagonoma. The recurrent peptic ulcer in this patient despite high levels of glucagon, a gastric inhibitory agent, is noted but not explained. An enhanced amylase-creatinine clearance ratio supports the notion that glucagon increases the clearances of amylase.

Adenoma, Islet Cell↗

Pleiotropic aspartate taxis and serine taxis mutants of Escherichia coli.

Mutants that at one time were thought to be specifically defective in taxis toward aspartate and related amino acids (tar mutants) or specifically defective in taxis toward serine and related amino acids (tar mutants) are now shown to be pleiotropic in their defects. The tar mutants also lack taxis toward maltose and away from Co2+ and Ni2+. The tsr mutants are altered in their response to a variety of repellents. Double mutants (tar tsr) fail in nearly all chemotactic responses. The tar and tsr mutants provide evidence for two complementary, converging pathways of information flow: certain chemoreceptors feed information into the tar pathway and others into the tsr pathway. The tar and tsr products have been shown to be two different sets of methylated proteins.

Aspartic Acid↗