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Biomedical subjects

J L Ryan

Publications and source records attributed to J L Ryan.

At least 73 records · Page 4Linked to original sources

Stimulation of rat mesangial cell proliferation by macrophage interleukin 1.

Conditioned media from LPS-activated rat peritoneal macrophages enhanced the proliferation rates of cultured rat glomerular mesangial cells. This macrophage-derived activity extensively co-purified with interleukin 1 (IL 1) activity through sequential ammonium sulfate precipitation, S-200 gel chromatography, DEAE-cellulose anion exchange chromatography, and phenyl-Sepharose chromatography. In addition, the macrophage-derived factor was heat-labile (80 degrees C) and inactivated by phenylglyoxal, thus allowing tentative identification as IL 1. Macrophage supernatants and purified IL 1 enhanced the proliferative rates of mesangial cells only in the presence of serum; the use of platelet-poor plasma or serum depleted of platelet-derived growth factor was without effect. IL 1 acted to increase the percentage of cycling cells, without a change in the length of the individual cell cycle times. These findings provide a potential mechanism whereby activated macrophages, in combination with platelet factors, enhance mesangial cell proliferation. Such processes may contribute to the mesangial hypercellularity frequently found in immune-mediated glomerulonephritis.

Animals↗

The effect of mass on the gastrointestinal absorption of plutonium and neptunium.

Absorption and retention of plutonium were determined in mice after intragastric administration of either 6 X 10(-4) or 1.5 mg/kg in bicarbonate, citrate, or nitrate media. At the higher concentration, absorption of the citrate was greater than that of the nitrate; at the lower concentration, chemical form was not an important factor in absorption. Concentration and chemical form had much less influence on absorption by the neonatal (versus the adult) rat. The transfer factor (f1) for neonates was between one and two orders of magnitude higher than for adults. Absorption and retention of neptunium were determined in rats and/or mice after intragastric administration at doses ranging from 2.2 X 10(-7) to 43 mg/kg in nitrate solutions of pH 1.5. At the higher concentrations, absorption was 1.5 to 2.7%. For lower concentrations, absorption was 25 to 65 times less. In contrast to results obtained in adult animals, absorption of neptunium by neonates decreased with increasing dose. The data obtained in adult animals suggest that the f1 factor recommended by the ICRP for plutonium should be increased by a factor of 10, but the neptunium f1 factor, in contrast, should be decreased by a factor of 10.

Animals↗

On the disulfiram-like activity of moxalactam.

A three-way crossover study was undertaken in 10 healthy subjects to characterize the reported disulfiram-like activity of moxalactam and to assess its influence on ethanol and acetaldehyde metabolism. On different occasions separated by at least 2 wk subjects were given in random order: 0.5 gm/kg ethanol orally, 0.5 gm/kg ethanol followed in 1 hr by 1.0 gm IV moxalactam, and 1.0 gm IV moxalactam every 8 hr for four doses followed by 0.5 gm/kg ethanol. Mean ethanol elimination rates of 13.1 +/- 0.76, 10.1 +/- 1.11, and 10.9 +/- 1.06 mg/dl/hr (mean +/- SEM) were observed in the three protocols, respectively. Corresponding mean estimated acetaldehyde clearance rates were 103.7 +/- 15.55, 92.8 +/- 13.79, and 97.3 +/- 10.41 l/min (mean +/- SEM). While no consistent moxalactam effect on ethanol or acetaldehyde elimination was observed, two subjects experienced mild disulfiram-like reactions to ethanol after moxalactam pretreatment. In one subject this reaction was associated with markedly elevated blood acetaldehyde concentrations. We conclude that moxalactam pretreatment may induce a disulfiram-like reaction after ethanol ingestion in some, probably due to inhibition of aldehyde dehydrogenase, and that alcoholic beverages are contraindicated in patients receiving moxalactam. We suggest, however, that such reactions will not occur when moxalactam is given after ethanol ingestion.

Acetaldehyde↗

In vitro activity of MK-0366 against clinical urinary pathogens including gentamicin-resistant Pseudomonas aeruginosa.

MK-0366, a new derivative of nalidixic acid, was tested against 250 urinary pathogens including Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa. This new agent was more active than any of the other antibiotics tested, which included carbenicillin, ampicillin, cephalexin, tetracycline, trimethoprim, trimethoprim-sulfamethoxazole, and nalidixic acid. Gentamicin-resistant P. aeruginosa were highly sensitive to MK-0366, with a 90% minimal inhibitory concentration of 0.8 microgram/ml. Serratia strains were the most resistant organisms, with a 90% minimal inhibitory concentration of 3.1 micrograms/ml. These results suggest that clinical trials should be designed to investigate the clinical usefulness of this new drug in urinary infections.

Anti-Bacterial Agents↗

Lysosomal enzymes in glomerular cells of the rat.

Whole isolated rat glomeruli (WG) were incubated with bacterial collagenase to separate epithelial cells (EC) from the cores of glomerular tufts (GC), which consisted of mesangial and endothelial cells, as demonstrated by electron microscopy. Lysates of WG, EC, and GC and of renal tubules were prepared by hypo-osmotic shock and freeze-thawing. Activities of the following acidic lysosomal hydrolases were measured: acid phosphatase, beta-glucuronidase, cathepsin-D, non-specific esterase, and aryl sulfatases A and B. The glomerular cell preparations showed activities of all studied enzymes. GC had higher activities than EC, save for nonspecific esterase. Studies of the recovery of acid phosphatase and beta-glucuronidase revealed that approximately 2/3 of the hydrolase activities present in WG was still measureable after collagenase treatment and that the bulk of this was found in the GC lysates. These findings demonstrate that the rat glomerulus and its cell components have considerable biochemical activities of acidic hydrolytic enzymes. These appear to be most prominent in the combined mesangial and endothelial cells of the GC components.

Acid Phosphatase↗

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Hospital Bed Capacity, 100 to 299↗

The oxidative metabolism of thioglycollate-elicited mouse peritoneal macrophages: the relationship between oxygen, superoxide and hydrogen peroxide and the effect of monolayer formation.

The oxygen and glucose metabolism of peritoneal macrophages harvested from untreated mice (resident cells) and mice given an i.p. injection of thioglycollate broth (thioglycollate cells) were examined. Thioglycollate cells consumed approximately 3 times as much O2 at rest and during phagocytosis as resident cells, but oxygen reduction products (superoxide and hydrogen peroxide) could be recovered in only minimal amounts despite triggering by phagocytosis or exposure to PMA. Indirect evidence for the formation of oxygen reduction products such as O2- by thioglycollate cells was obtained by observation of the major pathways for glucose oxidation and NBT dye reduction. When thioglycollate cells were allowed to adhere to a glass surface O2- and H2O2 were easily recovered in the extracellular medium with a 20-fold increase above cells in suspension exposed to PMA. This study suggests that thioglycollate-elicited macrophages have a vigorous oxidative metabolism but that recovery, and perhaps utilization, of O2 reduction products formed will depend on the conditions of incubation. These events may be significant both for the study of parameters of macrophage "activation" in vitro as well as the function of these cells in vivo.

Animals↗

Lymphocyte mediation of lipopolysaccharide-stimulated macrophage metabolism.

LPS activation of murine macrophage metabolism and arginase production may be mediated by products of B lymphocytes. Splenic nonadherent cells, containing both B and T lymphocytes, splenic T cells, and thymocytes all stimulated macrophage glucose metabolism in co-culture. Supernatants derived from preculturing each of these cells in the absence of serum or other exogenous stimulant were also active in enhancing macrophage glucose utilization. When lipopolysaccharides were used to stimulate the lymphocyte populations, only the B lymphocyte containing NASC and purified B cells exhibited increased stimulatory activity. Thus, it appears that LPS does not directly activate T cells to produce macrophage-activating factors. The converse does not appear to be true, however, because LPS-stimulated macrophages enabled thymocytes to exhibit an enhanced ability to stimulate further macrophage glucose utilization. The active supernatant from NASC was heat resistant and remains to be chemically defined. These experiments clearly demonstrate that LPS-induced macrophage activation may be mediated by the products of lymphocytes, and that products derived from nonactivated lymphocytes are capable of stimulating macrophage metabolism and arginase production.

Animals↗

Enterococcal meningitis: combined vancomycin and rifampin therapy.

Intrathecal vancomycin and oral rifampin have been used together to successfully treat a patient with enterococcal meningitis who was allergic to penicillin and who had failed a course of treatment with chloramphenicol. This therapy was tolerated very well and represents an alternate mode of therapy which should be considered in penicillin allergic patients with enterococcal meningitis.

Administration, Oral↗

Stimulation of peritoneal cell arginase by bacterial lipopolysaccharides.

The conditions under which bacterial endotoxins stimulate arginase production in mouse peritoneal macrophages have been defined. Both lipid-A and lipid-A-associated protein are potent activators. Fetal calf serum and normal mouse serum enhance macrophage arginase levels in the presence and absence of lipopolysaccharide (LPS). LPS in the amount of 10(-1) microgram/ml represents a maximal stimulus for macrophage arginase production and release. Thioglycollate-elicited peritoneal cells have increased arginase activity, compared with resident cells. This activity can be stimulated further by the addition of LPS. Arginase levels may alter the outcome of in vitro immunologic processes by depleting arginine and may also serve as a useful indicator of the state of activation of macrophages.

Animals↗