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Biomedical subjects

M Wolfson

Publications and source records attributed to M Wolfson.

At least 91 records · Page 5Linked to original sources
PubMed1990

Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects.

Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure. We therefore performed a four center, double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis. Thirty-eight patients received up to six months of L-carnitine infusions (20 mg/kg) post-dialysis and 44 patients received placebo infusions. In both groups of patients, baseline pre-dialysis plasma and red blood cell total carnitine levels were normal, but pre-dialysis plasma-free carnitine concentrations and free/total ratios were subnormal, and plasma acyl levels were elevated. Post-dialysis plasma free and total carnitine concentrations were also subnormal. Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients, but were unchanged from baseline in those receiving placebo. There were no significant changes observed in plasma triglycerides, HDL-cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups. We conclude that carnitine metabolism is altered in uremia. Furthermore, in a randomly-selected hemodialysis population, L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood (and perhaps tissue) carnitine levels, but this is not associated with any major effects on lipid profiles.

Carnitine↗
PubMed1990

Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects.

Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis, we studied the effects of intravenous infusion of L-carnitine or placebo at the end of each dialysis treatment. The trial, which lasted seven months (one month baseline, 6 months treatment) was multicenter, double blind, placebo controlled, and randomized. Eighty-two long-term hemodialysis patients, who were given either carnitine (N = 38) or placebo (N = 44), completed this study. In each group, clinical and biochemical parameters during treatment were compared with baseline values. Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group, while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups. Maximal oxygen consumption, measured during a progressive work exercise test, improved significantly in the carnitine group (111 +/- 50 ml/min. P less than 0.03) and was unchanged in the placebo group. L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen, creatinine and phosphorus (means +/- SEM, 101 +/- 4.5 to 84 +/- 3.9, 16.7 +/- 0.67 to 14.7 +/- 0.64, and 6.4 +/- 0.3 to 5.5 +/- 0.4 mg/dl, respectively, P less than 0.004). No significant changes in any of these variables were noticed in the placebo group. Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients. Calculated mid-arm muscle area increased in the carnitine patients (41.37 +/- 2.68 to 45.6 +/- 2.82 cm2, P = 0.05) and remained unchanged in the placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Carnitine↗
PubMed1989

Effect of persistent measles virus infection on protein kinase C activity and c-fos protooncogene expression in neuroblastoma cells.

The effect of persistent measles virus infection on c-fos protooncogene and protein kinase C (PKC-I) gene expression in a murine neuroblastoma cell line was studied. Overexpression of c-fos protooncogene by infected NS20Y/MS cells was detected when compared with uninfected NS20Y cells. The level of PKC-I-specific mRNA was increased in infected NS20Y/MS cells. In addition, the level of total PKC activity in these cells was also enhanced. We conclude that persistent measles virus infection can alter both protooncogene expression and signal transduction in cells of neuronal origin.

Animals↗
PubMed1988

Partial down-regulation of protein kinase C in C3H 10T 1/2 mouse fibroblasts transfected with the human Ha-ras oncogene.

Biochemical and immunological comparison of mouse C3H 10T 1/2 fibroblasts and C3H 10T 1/2 fibroblasts transfected with human activated Ha-ras oncogene indicated significantly lower levels of protein kinase C (PKC) activity and protein in the ras-transfected cells. This effect was observed in three clonal cell lines transfected with an activated ras oncogene. Cytosolic extracts of the ras-transfected cells contained calcium-activated, phospholipid-dependent protein kinase (PKC) activity at 61% of the level of activity present in C3H 10T 1/2 cells. A similarly decreased level of phorbol ester-binding activity was observed in these cells. Analysis of the subcellular distribution of PKC activity in cells failed to indicate significant differences between these cell lines. Immunoblots showed a lower abundance of the Mr 80,000 PKC in ras-transfected cell homogenates and extracts compared to C3H 10T 1/2 cells. Both C3H 10T 1/2 cells and cells transfected with ras expressed only one of the PKC isozymes as resolved by hydroxylapatite chromatography demonstrating that ras transfection of cells did not induce expression of alternative PKC isozymes. These observations indicate that PKC was partially down-regulated in ras-transfected cells, perhaps resulting from constitutively elevated levels of products of phosphatidylinositol-4,5-bisphosphate hydrolysis. Although C3H 10T 1/2 cells were previously shown to be distinct from NIH 3T3 cells in their sensitivity to transformation by the T24-ras oncogene, ras transformation appears to partially down-regulate PKC in C3H 10T 1/2 cells in a manner identical to that for ras-transformed NIH 3T3 cells. This indicates that down-regulation of PKC directly results from the expression of an activated ras oncogene independently of cellular sensitivity to transformation by expression of ras. The common action of ras transformation and phorbol esters to down-regulate PKC provides a possible mechanism for synergism during multistage carcinogenesis.

Animals↗
PubMed1988

Postrelational database implementation for newborn screening and tracking.

Development of microcomputer based systems for the management of data in newborn screening programs has posed special difficulties. This paper describes the specific requirements for implementing an effective newborn screening database system using a unique postrelational database system. This system has been developed by Neometrics Inc. for use by laboratories engaged in running high volume newborn screening programs, and is currently operational in a number of state health laboratories.

Database Management Systems↗
PubMed1988

Inhibitory effect of retinoic acid on the respiratory burst of adult and cord blood neutrophils and macrophages: potential implication to bronchopulmonary dysplasia.

Infants suffering from bronchopulmonary dysplasia (BPD) are known to have low levels of vitamin A, a factor which may be implicated in the pathogenesis of the condition. The ability of retinoic acid (RA) (one of the active forms of vitamin A) to influence the production of superoxide anion (02-) and hydrogen peroxide (H2O2) by stimulated human adult or cord blood neutrophils and macrophages has been studied. RA was found to inhibit the O2- and H2O2 production in a dose-dependent manner. The time required for maximal inhibition was 30 min for neutrophils and 24 h for macrophages. Although cord blood neutrophils produced larger quantities of O2- and H2O2 both with and without RA, the degree of inhibition was similar in both adult and neonatal cells (40-60%). The results suggest that retinoic acid may prevent neutrophil and macrophage mediated lung damage by inhibiting the production of toxic oxygen compounds, especially in BPD conditions.

Adult↗
PubMed1986

Modulation of protein kinase C and Ca2+ lipid-independent protein kinase in lymphoma induced by Moloney murine leukemia virus in BALB/c mice.

We investigated the possible role of protein kinase C (PKC) in the progression of Moloney murine leukemia virus (Mo-MuLV)-induced lymphoma in BALB/c mice. Mice injected with Mo-MuLV on the first day after birth developed lymphoma within 1 1/2-3 months. The development of lymphoma was characterized by a gradual increase in the number of spleen cells. However, no analogous changes could be detected in the thymuses of these mice, although cells of both organs were found to be virus producers as early as 3-4 weeks after inoculation. PKC activity, which was assayed in extracts of spleen and thymus cells, declined gradually during the development of lymphoma. Concomitantly with this decline, a progressive appearance of Ca2+/lipid-independent protein kinase activity was observed. TPA treatment of intact cells from normal mice reduced the level of soluble PKC activity, while inducing Ca2+/lipid-independent phosphorylation. By contrast, TPA had no effect on these enzymatic activities in cells derived from leukemic mice. Spleen enlargement caused by injection of a non-leukemogenic inflammatory agent such as mineral oil was ineffective in this respect, suggesting that the PKC-Ca2+/lipid-independent protein kinase modulation is associated with the virally induced leukemogenesis.

Animals↗
PubMed1986

Phenotypic heterogeneity in 3-methylcholanthrene-induced transformation of normal rat kidney cells infected with Moloney murine leukemia virus.

Normal rat kidney cells, infected with Moloney murine leukemia virus, were treated with 3-methylcholanthrene at passage 5 postinfection. Foci of transformed cells appeared after 9-11 passages following this treatment. Characterization of four different randomly isolated foci revealed a striking diversity with respect to various tested phenotypic parameters. Remarkable differences were observed among these transformed clones regarding their cell morphology, growth rate, saturation density, serum requirements, virus release and its response to rat and mouse fibroblast interferons. This study demonstrates that cell transformation by chemical-retroviral co-carcinogenesis may lead to the formation of phenotypically heterogeneous tumor cells.

Animals↗
PubMed1986

Clinical characteristics and diagnostic considerations in acquired renal cystic disease.

Acquired multiple bilateral cystic transformation of kidneys has been increasingly noted in patients with long-standing renal failure treated by chronic dialysis. To study the clinical characteristics of this newly described disease and assess the utility of available diagnostic methods, 130 patients with chronic renal failure (100 on dialysis, 30 nondialyzed) were studied with ultrasonography and/or computerized tomography (CT). Among patients on dialysis, 22% had acquired renal cystic disease (ARCD), an additional 30% had one to three solitary cysts, and 48% had no cysts. In nondialyzed patients, 7% had ARCD, 53% had one to three solitary cysts, and 40% had no cysts. Among these 130 chronic renal failure patients (nondialyzed and dialyzed), 21 of 86 males compared to 1 of 44 females had ARCD (P less than 0.001). Duration of dialysis therapy and age were greater in patients with ARCD (49.8 +/- 8 months, 55 +/- 4 years, respectively) compared to those with solitary cysts (28 +/- 6 months, 45 +/- 2 years) or no cysts (15 +/- 3 months, 42 +/- 2 years). The diagnostic accuracy of ultrasound (US) was compared to CT. CT is purportedly 100% accurate in the characterization of renal cysts. We are disappointed at the low level of diagnostic accuracy for both CT and US in the detection of renal cysts in chronic uremia. It appears both a negative CT and ultrasound are necessary to absolutely exclude either ARCD or solitary cyst.

Adult↗
PubMed1986

Effect of vitamin B-6 deficiency on plasma amino acid levels in chronically azotemic rats.

Chronic renal failure is associated with many abnormalities in plasma amino acids. Since patients with renal failure are frequently deficient in vitamin B-6, this study examined whether vitamin B-6 deficiency may be a cause of any of the abnormal plasma amino acid concentrations observed in chronic renal failure. Sham-operated and chronically azotemic rats were pair-fed diets deficient in or replete with vitamin B-6 for 21 d. By the end of 21 d, the EGOT index rose significantly in the B-6-deficient rats but not in the B-6-replete animals. There were several differences in plasma amino acid concentrations between azotemic and control rats. Azotemia and B-6 deficiency each lowered the plasma serine concentration and raised the glycine-to-serine ratio. Plasma glycine was affected by a two-way interaction between azotemia and vitamin B-6 deficiency whereby the highest values were found in the sham-operated vitamin B-6-deficient animals. Plasma alanine and asparagine were reduced by B-6 deficiency and unchanged by azotemia. These results suggest that vitamin B-6 deficiency may contribute to several of the abnormalities in the plasma aminograms observed in chronic renal failure.

Amino Acids↗
PubMed1985

Effect of mouse interferon on chemical carcinogenesis in normal rat kidney cells infected with Moloney murine leukemia virus.

The present study was carried out with a normal rat kidney cell clone that was initiated from a single cell infected by only one infectious particle of the non-transforming retrovirus, Moloney murine leukemia virus. Although the parental cells were highly resistant to chemical carcinogenesis, this infected clone was rendered susceptible to transformation by chemical carcinogens. However, when it was exposed to the tested carcinogen at a low subculture passage post-infection, cell transformation was detectable only after many subsequent passages. On the other hand, if it was exposed to the carcinogen at a high passage post-infection, cell transformation was detectable sometimes even without further passage, or in other cases after the first subsequent passage. Mouse interferon could inhibit the transformation by carcinogen employed at the low but not at the high passage post-infection. This inhibitory effect was reversible; if interferon was removed, even after the cells had been passaged many times in its presence, cell transformation became visible at passage 11 after interferon removal, although no treatment with the carcinogen was repeated. Interferon had no effect on the replication or the focus-forming capacity of cells transformed by such chemical-retroviral co-carcinogenesis. The possibility that this carcinogenic process depends on amplification of the integrated provirus DNA, and that this amplification can be inhibited by interferon is discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Phorbol myristate acetate mediates redistribution of protein kinase C in human neutrophils: potential role in the activation of the respiratory burst enzyme.

Protein kinase C may be important in leukocyte function, because it is activated by phorbol myristate acetate (PMA), a potent stimulus of the respiratory burst in neutrophils. The localization of protein kinase C was compared in unstimulated and PMA-stimulated human neutrophils. Protein kinase C was primarily cytosolic in unstimulated cells but became associated with the particulate fraction after treatment of cells with PMA. The particulate-associated kinase activity did not require added calcium and lipids, but when extracted by Triton X-100 (greater than or equal to 0.2%), calcium and phospholipid dependence could be demonstrated. The EC50 of PMA for stimulating kinase redistribution and activation of NADPH oxidase, the respiratory burst enzyme, were similar (30 to 40 nM). Redistribution of protein kinase C occurred rapidly (no lag) and preceded NADPH oxidase activation (30 sec lag). These results suggest that redistribution of protein kinase C is linked to activation of the respiratory burst in human neutrophils.

Alkaline Phosphatase↗
PubMed1984

Nutritional status and lymphocyte function in maintenance hemodialysis patients.

Nutritional status and lymphocyte transformation were examined in 30 clinically stable men who underwent maintenance hemodialysis for 1 to 141 months. The men displayed decreased relative body weight, triceps and subscapular skinfold thickness, midarm circumference, midarm muscle circumference, serum total protein, albumin, transferrin, IgG, IgA, IgM, and C3 concentrations. There were many abnormalities in the plasma amino acid pattern. Lymphocyte transformation stimulated by phytohemagglutin or pokeweed mitogen was reduced. Many nutritional parameters correlated with each other and with the rate of lymphocyte transformation. There was a tendency (p = 0.06) for higher mortality in the malnourished patients during a mean follow-up period of 43.3 months. These findings suggest that clinically stable men undergoing maintenance hemodialysis are typically malnourished. Poor nutritional status may be a cause of impaired lymphocyte function. Malnutrition or wasting may indicate that the patient is at risk for a higher mortality rate.

Adult↗
PubMed1984

Ventricular function in thyrotoxicosis complicated by atrial fibrillation.

The radionuclide gated ventriculogram was used to study the association between thyrotoxic atrial fibrillation and underlying ischaemic heart disease. Comparison between ten patients with atrial fibrillation induced by thyrotoxicosis which reverted to sinus rhythm after return to a euthyroid state, and ten age-matched controls with treated hyperthyroidism who never developed atrial fibrillation, showed no significant difference in the incidence of underlying ischaemic heart disease. This study suggests that further investigation for underlying coronary arterial disease is not indicated in simple, reversible, thyrotoxic atrial fibrillation.

Atrial Fibrillation↗
PubMed1984

Incomplete activation of intraperitoneal clindamycin phosphate during peritoneal dialysis.

Clindamycin phosphate (C-PO4) must be hydrolyzed to the active antibiotic, but whether this occurs within the peritoneal cavity during peritoneal dialysis is unknown. Therapeutic peritoneal levels are difficult to achieve after intravenous administration, so direct intraperitoneal instillation is preferred in treating dialysis-associated peritonitis. Therefore, the activation of C-PO4 in peritoneal dialysate was investigated. Fresh and 'uremic' peritoneal dialysates of 1.5 and 4.25% dextrose concentrations at pHs of 5.1 and 7.4 did not activate C-PO4. Clindamycin hydrochloride in this same fluid was active, ruling out uremic deactivators. A patient with peritonitis was treated with intraperitoneal C-PO4, and therapeutic (greater than 5 micrograms/ml) serum and peritoneal levels were achieved. Infected (exudative) peritoneal dialysate drained from another patient with peritonitis activated C-PO4 in vitro. Commercial alkaline phosphatase added to uremic dialysate also activated C-PO4 in vitro. C-PO4 was instilled into the peritoneal cavities of 10 noninfected patients. Exposure to the peritoneal membrane at two concentrations resulted in a 3% activation of C-PO4. From these observations it is clear that C-PO4 is only partially activated intraperitoneally. Uremia or uremic products in the dialysate do not deactivate the antibiotic. Exudative material (bacteria, white blood cells and proteins) in infected dialysate contribute to activation of C-PO4. The peritoneal membrane further assists in activation. We recommend that C-PO4 be administered at a concentration of 167 mg/l of dialysate to ensure therapeutic peritoneal levels of the active antibiotic, especially after the exudative phase clears.

Alkaline Phosphatase↗