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Biomedical subjects

J F Martin

Publications and source records attributed to J F Martin.

At least 289 records · Page 16Linked to original sources
PubMed1977

Effect of exogenous nucleotides on the candicidin fermentation.

Addition of cyclic-AMP (c-AMP) to Streptomyces griseus fermentations inhibited candicidin formation. In a phosphate-free resting cell system, c-AMP inhibited net candicidin formation and incorporation of labeled propionate and p-aminobenzoic acid into the antibiotic but did not inhibit protein synthesis. All nucleotides tested, regardless of the position of the phosphate ester, were effective inhibitors; nucleosides and free bases were not. Inhibition occurred whether the nucleotide was added early or late. The results indicate that inhibition of antibiotic formation by exogenous nucleotides, including cyclic nucleotides, is similar to the effect produced by inorganic phosphate.

Adenine↗
PubMed1977

Hemoperfusion through albumin-conjugated agarose gel for the treatment of neonatal jaundice in premature rhesus monkeys.

Hemoperfusion through albumin-conjugated agarose gel (AAG) effectively removes bilirubin (BR) and other albumin-bound materials from whole blood or plasma. We have used this technique to treat neonatal jaundice in premature rhesus monkeys with a specially designated apparatus which permits continuous perfusion through one of four columns arranged in parallel while the others are sequentially washed with saline and regenerated with ethanol. Less than 15 per cent of the animal's blood volume is required in the extracorporeal circuit at any time. Results indicate that (1) compared with five control monkeys which had a peak BR concentration ([BR]) averaging approximately 4 mg./100 ml., six experimental monkeys showed a significant (p less than 0.01) reduction, averaging 60 per cent, in [BR] after each of two perfusions at approximately 20 and 26 hours of age; (2) AAG hemoperfusion was even more effective in lowering [BR] in monkeys with higher preperfusion concentrations produced by BR infusion (average reduction = 68 and 87 per cent at preperfusion concentrations of 11.9 and 24.2 mg./100 ml., respectively); and (3) overall, BR eluted from the column averaged 93 per cent of the estimated preperfusion plasma BR pool. Unlike previous studies in rats, perfused monkeys showed significant platelet losses, although it was possible to prevent these losses by the use of "regional citrate" during perfusion. These studies suggest that AAG hemoperfusion is effective in the treatment of neonatal jaundice, although potential problems such as sterility and platelet loss need further evaluation before it can be considered for human use.

Albumins↗
PubMed1977

The use of calcium chelating agents and prostaglandin E to eliminate platelet and white blood cell losses resulting from hemoperfusion through uncoated charcoal, albumin-agarose gel, and neutral and cation exchange resins.

Hemoperfusion through adsorbents such as charcoal, cation exchange (e.g., AG 50W-X8) and uncharged (e.g., XAD-2) resins, and albumin-agarose gel (AAG) has been proposed for use in patients with hepatic failure. However, the loss of white blood cells and, particularly, platelets caused by each of these adsorbents remains a major deterrent to their clinical use. In vitro studies demonstrate that addition of citrate, ethylenediamine tetraacetate (EDTA), or oxalate to heparinized human blood eliminated this loss of formed blood elements during hemoperfusion. The improvement in postperfusion platelet counts (per cent of preperfusion values) produced by citrate were XAD-2, 13 leads to 95 per cent; AG 50W-X8, 10 leads to 94 per cent; AAG, 17 leads to 94 per cent; and charcoal, 44 leads to 96 per cent. Prostaglandin E1 in high doses (5 mug/ml.) markedly reduced platelet losses. Lower doses were less uniformly effective. Three young rhesus monkeys were hemoperfused for 160 minutes with columns containing AAG, XAD-2, and charcoal. During the first 80 minutes, citrate and calcium were infused into the column inflow and outflow lines respectively. For all three adsorbents, average platelet counts in the monkeys (115 per cent) and column effluent (95 per cent) were unchanged from preperfusion control values during the first 80 minutes but fell promptly to 13 and 7 per cent, respectively, after the citrate infusion was stopped. Each of the monkeys tolerated the procedure without ill effects. Use of a system analogous to that described here may facilitate clinical application of the technique of hemoperfusion through a variety of adsorbents.

Albumins↗
PubMed1977

"Pseudostone" of the gallbladder. Ultrasound findings and case report.

The ultrasonic criteria for the diagnosis of gallbladder calculi are: (1) echo-dense structures which disturb the smooth contour of the posterior border of the gallbladder; (2) sonic shadowing, and (3) echoes from within the gallbladder. Diagnostic confidence increases greatly in cases in which internal echoes, contour irregularities, and sonic shadows have occurred simultaneously. A case is presented in which all three criteria are fulfilled, but which represents an artifact, i.e., "pseudostone." This was confirmed by varying the patient's respiration and showing that the "pseudostone" represented echoes from a loop of bowel which produced a significant impression on the posterior wall of the gallbladder during deep inspiration. The absence of cholelithiasis was confirmed by oral cholecystography.

Cholecystography↗
PubMed1976

Rapid incorporation of precursors into candicidin by resting cells of Streptomyces griseus.

Labeled acetate, propionate and p-aminobenzoic acid were efficiently incorporated into candicidin by phosphate-limited resting cells of Streptomyces griseus. The efficiency of incorporation in short-term experiments using phosphate-limited resting cells was similar to that achieved previously in long-term experiments using growing cells. (2-14C)Propionate was more efficiently incorpoated than (1-14C)propionate, (U-14C)propionate, or (U-14C)-acetate. p-Aminobenzoic acid incorporation is linear over a 10-hour period while those of acetate or propionate reach a constant level after approximately 4 hours of incubation. Double-labeled candicidin of high specific activity was prepared by supplementing the resting cell system with (3H)acetate and (14C)p-aminobenzoic acid.

4-Aminobenzoic Acid↗
PubMed1976

Vinyl chloride-associated liver disease.

Although polyvinyl chloride has been produced from vinyl chlride monomer for more than 40 years, recognition of toxicity among vinyl chloride polymerization workers is more recent. In the mid 1960s, workers involved in cleaning polymerization tanks were found to have acro-osteolysis. In 1974, the same population of workers was found to be at risk for an unusual type of hepatic fibrosis and angiosarcoma of the liver. We describe two cases of vinyl chloride-associated liver injury, one of hepatic fibrosis and one of angiosarcoma. Histologic features of these lesions are similar to the hepatic fibrosis and angiosarcomas resulting from chronic exposure to inorganic arsenicals. Preliminary studies suggest that the toxicity of vinyl chloride may result from formation, during high-dose exposure, of active metabolites by mixed function oxidases of the liver. Epidemiologic studies indicate an increased incidence not only of liver disease, but also of cancers of the brain, lung, and possibly other organs.

Adult↗
PubMed1976

Abnormal hepatic transport of indocyanine green in Gilbert's syndrome.

The plasma fractional disappearance rate of indocyanine green (kICG, min-1) and the absolute hepatic ICG removal rate (VICG, mg per kg per min) were determined in 26 patients with Gilbert's syndrome (GS) and 19 normal control volunteers following intravenous administration of doses of 0.5, 2.0, 3.5, and 5.0 mg per kg of dye. The diagnosis of GS was based on studies of radiobilirubin kinetics in all cases and liver biopsy in 22 cases. The patients were further classified into 3 subgroups, based on patterns of sulfobromophthalein (BSP) kinetics, as follows: GS I (15 patients) had normal BSP metabolism; GS II (5 patients) had a defect in BSP metabolism beyond the stage of initial hepatic uptake; and GS III (6 patients) had a defect in the initial hepatic uptake of BSP (Gastroenterology 63:472-481, 1972). Both kICG and VICG were significantly reduced, compared to normal controls, in the GS III group with defective BSP uptake, but did not differ significantly from normal in the GS I and GS II groups. Michaelis-Menten analysis of the data indicated that VMAX for ICG uptake in the GS III group (1.2 +/- 0.6 mg per min per kg) was significantly reduced compared to the previously established normal value of 3.6 +/- 0.6 mg per min per kg; (P less than 0.01). For the total population of 26 patients with Gilbets' syndrome, there was a highly significant correlation (r= 0.77, P less than 0.01) between kICG and lambda21BSP, the fractional hepatic uptake rate for BSP. These studies confirm previous work indicating that patients with Gilbert's syndrome constitute a heterogeneous population with regard to defects in hepatic organic anion transport, some of the defects not being attributable to glucuronyl transferese deficiency. Future studies of Gilbert's syndrome must take into account the existence of these subgroups, since they may have different underlying pathogenetic mechanisms.

Adolescent↗
PubMed1975

Specific inhibition of candicidin biosynthesis by the lipogenic inhibitor cerulenin.

Cerulenin, an inhibitor of fatty acid synthesis, inhibits specifically the biosynthesis of the polyene macrolide candicidin by resting cells of Streptomyces. 50% inhibition was achieved with a cerulenin concentration of 1.5 mug/ml. Cells in which candicidin synthesis was inhibited for 10 h remained capable of candicidin synthesis after removal of the inhibitor. Cerulenin inhibits specifically the incorporation of [14C] propionate into candicidin but does not affect total protein or RNA synthesis. The uptake of [14C] propionate was not inhibited under conditions which totally prevented the incorporation of propionate into candicidin. Incorporation of p-amino[14C] benzoic acid NH2 [14C] BzO- into the aromatic moiety of candicidin was also inhibited by cerulenin. The inhibitory action of cerulenin was not reversed by exogenous fatty acids. Since cerulenin is known to block the condensation of malonyl-CoA subunits in the formation of fatty acids, it is concluded that the polyene macrolide candicidin is synthesized via the polyketide pathway by condensation steps similar to those occurring in fatty acid biosynthesis.

Aminobenzoates↗
PubMed1975

Quantitative thin-layer spectrodensitometric determination of the components of polyene macrolide antibiotice complexes.

A direct spectrodensitometric method for quantitating the components of polyene macrolide complexes after separation by thin-layer chromatography is described. Resolution of the components of the candidin and candihexin complexes was good up to 2.5 and 10 mu-g/spot, respectively. The peak areas were linear with the amount spotted up to the same levels. Maximum peak areas for the components of the candidin and candihexin complexes were obtained using light wavelengths of 360 and 340 nm, respectively. Spotting errors rather than instrumental parameters were responsible for the variance of repeated determinations. Minimal relative standard deviation values were found at intermediate concentration levels in the linear range.

Anti-Bacterial Agents↗