Biomedical subjects

J L Rabinowitz

Publications and source records attributed to J L Rabinowitz.

At least 19 recordsLinked to original sources

PubMed1992

Liver lipid profiles of adults taking therapeutic doses of aspirin.

The distributions of lipids of hepatic specimens obtained at autopsy from 7 adult patients who had been taking large amounts of aspirin for arthritis were compared to 7 control samples obtained from livers of autopsied adults without prior liver disease. The total neutral lipid levels of control livers were approximately one-third lower than those observed for livers of patients on aspirin. In addition, the phospholipid content of control specimens was significantly greater than that of livers from adult patients that had been on a high dose of aspirin for a long time. Examination of individual lipid classes showed that the concentrations of free fatty acids, triacylglycerols, and mono- and diacylglycerols were highest in livers of patients with aspirin exposure, and that all phospholipids were diminished. Phosphatidylcholines and phosphatidylethanolamines showed the greatest decrease. These results suggest that the livers of patients taking large amounts of aspirin may accumulate fatty acids and neutral lipids due to an impairment in the oxidation of fatty acids by hepatocytes. The data obtained also suggest that needle biopsy of the liver with measurement of distribution of hepatic lipids, perhaps together with histopathologic examination, may provide useful diagnostic information.

Aspirin↗

PubMed1992

Metabolism of inositol-1,4,5-trisphosphate in the taste organ of the channel catfish, Ictalurus punctatus.

1. The metabolism of inositol-1,4,5-trisphosphate was studied in the taste organ (barbel) of the channel catfish, Ictalurus punctatus. 2. Homogenates of epithelial barbel scrapings were incubated with [3H]-1,4,5-IP3, whose dephosphorylation or phosphorylation was assayed under first-order conditions by measuring the production of either [3H]-1,4-IP2 (representing the activity of IP3-5-phosphatase) or [3H]-1,3,4,5-IP4 (representing the activity of IP3-3-kinase). 3. Both enzymes were predominantly cytosolic, magnesium-dependent and maximally active at pH 6.4. For IP3-phosphatase, Km = 6 microM and Vmax = 10.5 nmol/min/mg. For IP3-kinase, Km = 0.23 microM and Vmax = 0.05 nmol/min/mg. 4. Neither enzyme was significantly affected by the presence of taste stimuli (amino acids), GTP gamma S, cAMP or phorbol esters. 5. In the presence of physiological levels of free calcium (0.05-12 microM) IP3-phosphatase was moderately activated whereas IP3-kinase was moderately inhibited. 6. IP3-phosphatase was moderately activated by Mn2+, unaffected by LiCl, and strongly inhibited by 2,3-diphosphoglycerate, Na-pyrophosphate, CdCl2, HgCl2, CuCl2, FeCl3 and ZnSO4 7. IP3-kinase was strongly activated by 2,3-diphosphoglycerate, Na-pyrophosphate, CdCl2, HgCl2, FeCl3 and LiCl and inhibited by ZnSO4 and Mn2+. 8. IP3-kinase was significantly activated in a calcium-dependent manner by exogenously-added phosphatidylcholine and sphingomyelin, and to a lesser extent by diacylglycerol. IP3-phosphatase was unaffected by exogenously-added lipids. 9. IP3-phosphatase may participate in taste transduction since calculations based on the first-order rate constant (6.9 sec-1) indicate that it is capable of dephosphorylating basal levels of IP3 with a half-life of 0.1 sec.

Animals↗

PubMed1991

I-E expression does not by itself influence growth of or T cell unresponsiveness to SJL lymphomas.

The nature of the antigen on SJL lymphoma (reticulum cell sarcomas, RCS) cells that is strongly stimulatory to syngeneic CD4+ T cells is still elusive. Previously, we showed that the response to RCS of T cells from F1 hybrids of SJL by strains expressing I-Ak,d and/or I-Ek,d was much lower than that of T cells from SJL mice or from F1 hybrids of SJL by H2b- or H2s-bearing strains. We now show that removal of CD8+T cells from the responding cell population of (SJL x BALB/c)F1 or (SJL x A.TL)F1 mice does not enhance their responses, suggesting that the negative effect of H2k,d is not due to suppressor cells. Moreover, repeated injections of RCS cells into such F1 mice also fail to enhance the response, suggesting that these mice lack responder cells. T cells from I-E alpha transgenic (C57BL x SJL)F1 mice backcrossed to SJL respond to RCS as do T cells from I-E alpha- littermates or SJL mice. Similarly, I-E alpha+ SJL mice support RCS growth in vivo to the same (LN + spleen)/body weight ratio as do I-E- littermates. Thus, while I-E appears to have a negative influence on T cell responsiveness and RCS growth in F1 mice, it does not have such an effect when present, by itself, on a SJL background. The role of V beta 17 a+ T cells in the response of SJL T cells to RCS was also examined, because such cells are known to be responsive to I-E. The responses of V beta 17a(+)-depleted (0.3% V beta 17 a+) and V beta 17 a(+)-enriched (25.3% V beta 17a+) SJL T cell populations to RCS were examined by limiting dilution. We found the incidence of responding cells to be slightly higher in the depleted (0.016%) than in the (0.006%) enriched population. Furthermore, lymph node blast cell populations responding to RCS do not exhibit a higher percentage of cells staining for V beta 17a than do blast cells responding to Con A or unstimulated lymph node cells.

Animals↗

PubMed1991

Lipid composition and biosynthesis in the gingiva of the domestic cat.

Periodontal disease in the domestic cat may assume debilitating and serious consequences; however, little is known of the biochemical composition or metabolism of feline gingiva in health or disease. In this report the chemical composition and metabolism of gingival lipids from inflamed an non-inflamed sites is presented and compared to other species with naturally occurring periodontitis. The neutral and phospholipid composition of feline gingiva was found to be distinct from that of porcine and human. As a measure of de novo lipid synthesis, the total incorporation of 14C-acetate into fractionated lipid components was determined and revealed an approximate 2 to 3 fold decrease in inflamed versus non-inflamed gingiva. The decrease in 14C-acetate incorporation appeared to result from a 2-fold increase in free acetate pools in inflamed compared to non-inflamed gingival samples, since total lipase and phospholipase activity were comparable in inflamed and non-inflamed gingiva and total lipid composition was not changed between inflamed and non-inflamed sites. These data are similar to those reported for periodontally involved human gingival tissue and suggest a common effect of periodontal inflammation on lipid metabolism in both species.

Acetates↗

PubMed1990

Germinal center cells are a major IL-5-responsive B cell population in peripheral lymph nodes engaged in the immune response.

Germinal center formation and the development of B cell memory in lymphoid tissue is a T cell-dependent process. The specific B cell-T cell interactions, and/or cytokines, resulting in germinal center cell growth have not yet been identified. Germinal center B cells were separated from other lymph node (LN) B cells by panning on peanut agglutinin (PNA)-coated dishes. Resulting fractions enriched for PNA+ (germinal center) B cells, and the PNA- (other) LN B cells from immune SJL mice were assayed for proliferation in the presence of cytokines. PNA+ and PNA- B cells responded equally to IL-4 in the anti-mu co-stimulator assay. In contrast, PNA+ B cells responded to murine (r)IL-5 or human B cell growth factor in the dextran sulfate (DxS) co-stimulator assay, to a much greater degree than did PNA- B cells. The same results were obtained with PNA+ and PNA- cells from LAF1 mice. Unfractionated LN B cells from nonimmunized SJL or BALB/c mice did not respond to IL-5 with or without DxS. B cell populations from BALB/c mice such as from spleen and peritoneal cavity, which are known to be high in Ly-1+B cells, responded to IL-5 alone, and more dramatically, to IL-5 as a co-stimulator with DxS. Such populations of cells from SJL mice, which are known to contain low numbers of Ly-1+B cells, responded markedly less. These results are consistent with those of others which show that in nonimmunized mice, Ly-1+B cells are a major IL-5 responsive subpopulation. IL-1 enhanced the proliferation of PNA+ cells in response to rIL-5 and had no effect on PNA- cells. IL-4 and IL-5 did not enhance each other's effects as co-stimulators of proliferation. In contrast to PNA+ B cells from immune LN, B cells activated by Escherichia coli endotoxin exhibited no responses to rIL-5. The present results indicate that in immune LN, PNA+, germinal center B cells constitute a prominent IL-5-responsive population.

Animals↗

PubMed1990

Lipid metabolic interrelationships and phospholipase activity in gustatory epithelium of Ictalurus punctatus in vitro.

The catfish, Ictalurus punctatus, is an important model for studying the biochemical mechanisms of taste at the peripheral level. The type, amount and metabolic activity of the lipids within this tissue play important roles in taste transduction by forming the matrix in which the receptors for taste stimuli are imbedded and by acting as precursors to second messengers. The metabolic interconversions that occur among the lipids on the taste organ (barbels) of this animal are reported here. When sodium [32P]phosphate was incubated with minced pieces of epithelium from the taste organ of I. punctatus, phospholipids became labeled. Maximal incorporation occurred near 20 min for lysophosphatidylcholines (LPC), phosphatidylcholines (PC) and phosphatidylinositols (PI). The phosphatidylethanolamines (PE) and phosphatidylserines (PS) became labeled more slowly. The label in LPC and PC declined from 20 min to 120 min, while that of the other fractions increased or was stable over the 20-120 min time period. Upon addition of 1,2-di-[1'-14C]palmitoyl-sn-glycero-3-phosphocholine to the medium, 14C was found within minutes in all of the phospholipids assayed. The amount of label incorporated increased with time, with maximum labeling for all phospholipids occurring at 15 min. However, 14C appeared predominantly first (by 5 min) in a neutral lipid fraction (fraction AG, consisting of free fatty acids, mono- and diglycerides, triglycerides and methyl esters), then declined rapidly as the phospholipids gradually incorporated more label. Within minutes of addition of 1-[1'-14C]palmitoyl-sn-glycero-3-phosphocholine (lysophosphatidylcholine) the 14C-label was detected in the neutral lipid fraction AG, then in the PC fraction, and later in the other phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Lipid characterization and 14C-acetate metabolism in catfish taste epithelium.

The catfish, Ictalurus punctatus is an important model system for the study of the biochemical mechanisms of taste reception. A detailed lipid analysis of epithelial tissue from the taste organ (barbel) of the catfish has been performed. Polar lipids account for 62 +/- 1% of the total, neutrals for 38 +/- 1%. Phosphatidyl-cholines, serines and ethanolamines are the major constituents of the polar fraction. Plasmalogen concentration is high relative to that of non-neural tissues. [14C]-Acetate is incorporated into cell lipid fractions after incubation of barbel tissue at 37 degrees C for 60 min. Percentage amounts of most lipids change with time during this in vitro incubation. The phospholipids are the most metabolically active fractions. This work yields information for continuing reconstitution experiments and indicates that the taste epithelium of this important model system is a metabolically active tissue capable of supporting lipid turnover/synthesis.

Acetates↗

PubMed1989

Changes in whole body lipid composition in a murine model of insulin-dependent diabetes mellitus.

To assess the effect of experimentally induced insulin-dependent diabetes mellitus (IDDM) on total body lipid composition, homogenates of neonatal (0-day) and 6-day Sprague-Dawley rat pups treated on day 0 with 65 mg/kg body weight of streptozotocin (STZ) or citrate buffer alone were compared using thin-layer and gas-liquid chromatographic techniques. STZ-treated littermates in a parallel study were markedly hyperglycemic, hypoinsulinemic and attained only 50% of the gain in weight of citrate-treated controls. Although both groups were similar in protein to body weight ratios, STZ-treated pups exhibited 60% of the total lipid content of citrate-treated littermates when compared by weight. The decrease in total lipid content in the STZ-treated group resulted specifically from decreased neutral and not phospholipid content, although a small increase in phosphatidic acid and sphigomyelin was observed in this group. The changes in relative whole body lipids with short-term, high-dose STZ parallel those reported in human IDDM.

Animals↗

PubMed1988

Altered Na+-K+-ATPase, cell Na+ and lipid profiles in canine arterial wall with chronic cigarette smoking.

1. We evaluated the influence of cigarette smoking on arterial wall membranes, using Na+-K+-ATPase activity, free cholesterol (FC) and phospholipid (PL) contents as indices of membrane structural and functional integrity. 2. Segments of aorta, carotid and femoral arteries were obtained from normal dogs (controls) and dogs subjected to chronic cigarette smoking for 2 yr (12 cigarettes a day). 3. Na+-K+-ATPase activity was assessed in segments of carotid and femoral arteries using a ouabain-sensitive 86Rb uptake procedure for intact tissues. 4. Free cholesterol and phospholipids were separated, identified, and quantitated from extracts of aortic samples by means of two dimensional thin-layer chromatography. 5. Na+-K+-ATPase activity was reduced in the smoker group in both carotid and femoral arteries. This reduced enzyme activity was accompanied by a rise in cell Na+ levels at both arterial sites. 6. Aortic FC was elevated and the PL profile was altered in the smoker group; as a result, phosphatidylcholine was reduced, whereas lysophosphatidylcholine, phosphatidic acid, and cardiolipin were elevated. 7. Phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and sphingolipid levels were unchanged. In addition, the FC/PL ratio was increased in the smokers. 8. Taken together, the changes in Na+-K+-ATPase activity, FC/PL ratio and phospholipid profiles observed are consistent with the hypothesis that chronic cigarette smoking causes a reorganization of the phospholipid bilayer in the smooth-muscle cell membrane of the arterial wall.

Animals↗

PubMed1988

Tissue uptake and intracellular distribution of 140-lanthanum after oral intake by the rat.

The ability of lanthanum to stabilize hydroxyapatite against acid dissolution is well known. It is possible to use lanthanum to experimentally alter hard tissues in vivo and in vitro. It was, therefore, of interest to determine the tissue distribution of lanthanum following oral ingestion of a LaCl3 solution. Oral intake of 140-lanthanum (as LaCl3 in drinking water) in adult rats over a 3-d period was voluntary and amounted to 0.27 mmol LaCl3 per animal per day. The teeth sowed increases in 140-lanthanum uptake with time. Distribution of 140-lanthanum within the incisors of animals drinking the LaCl3 solution showed that the highest specific activity of 140-lanthanum was associated with the outer layer of the tooth (that portion exposed to the oral environment). The soft tissues, such as lung, kidney, and liver, maintained a constant 140-lanthanum concentration after the first day of intake. The intracellular distribution of 140-lanthanum was measured in liver, with the soluble fraction showing the highest content. No histological changes were observed in the rat tissues after 3 d of oral intake (0.27 mmol/d) of lanthanum.

Administration, Oral↗

PubMed1988

Effect of 2 ppm ozone exposure on rat lung lipid fatty acids.

Based on in vitro studies, the initial damage to lung cells by ozone exposure is believed to result in part from the breakdown of lipid polyunsaturated fatty acids to aldehydes, ozonides, and peroxides. The present study measured lipid breakdown products in lungs isolated from rats pretreated with [1-14C]acetate 12 h before exposure for 4 h to either air or 2 ppm ozone. Lipid fatty acid breakdown was indicated by a 112% increase in thiobarbituric acid-reactive substances on ozone exposure and by changes in chemical and radioactive measurements of mono- and dicarboxylic acids formed by treatment of lipid fractions with hydrogen peroxide. Ozone exposure resulted in a 63% increase in recovery of short-chain fatty acids accounted for by increased recoveries of malonic acid by 37%, hexanoic acid by 47%, nonanoic acid by 118%, and azelaic acid by 107%. Recovery of glutaric acid was enhanced 15-fold by ozone exposure. Although decreases in tissue arachidonic acid could not be detected, oleic acid was significantly decreased by 36%. Recovery of radiolabel as short-chain fatty acids was increased by 65% on ozone exposure and was mainly accounted for by enhanced labeling of nonanoic and glutaric acid fractions. The failure to observe significant increases in 14C recovery in the other fractions suggested ozone-induced breakdown of unlabeled fatty acids. These results demonstrate the cleavage of unsaturated fatty acid double bonds following in vivo exposure of lungs to ozone. Breakdown of arachidonic and oleic acids was specifically identified by increased recoveries of glutaric and nonanoic acids, respectively.

Animals↗

PubMed1988

Incorporation of 140-lanthanum into bones, teeth and hydroxyapatite.

The incorporation of lanthanum in the form of 140-lanthanum onto the surface of teeth, bone and synthetic hydroxyapatite was investigated. A small amount of lanthanum was taken up by the surface of all of the materials studied regardless of their origin. The depth of penetration into bone and teeth was dependent upon lanthanum concentration and time of incubation and, in these experiments, ranged from an estimated 5 to 15 microns. An exchange of lanthanum for calcium in the apatite matrix may be responsible for increased resistance of the hard tissues to acid dissolution. The effects of pH, temperature, time and concentration of the lanthanum solutions on this incorporation were investigated. Possible clinical uses of this effect are discussed.

Animals↗

PubMed1987

A simple spectrophotometric assay for micromolar amounts of lanthanum in the presence of calcium and phosphate.

A sensitive spectrophotometric assay for micromolar amounts of lanthanum in the presence of calcium and phosphate (as hydroxyapatite) was developed utilizing the change in absorption (at 652 nm) when the dye arsenazo III was complexed with lanthanum. Arsenazo III was used at a level of 25 microM and the solution pH was maintained at 3.1 with 0.2 M sodium acetate. Lanthanum concentrations down to 0.5 microM could be reliably assayed. Calcium ion did not complex well with arsenazo III at pH 3.1. With calcium present at 100 microM and lanthanum at 10 microM, the assay was 115 times more sensitive for lanthanum. The assay is simple, rapid, reproducible and, unlike the assay using radioactive lanthanum, can be performed at any time.

Arsenazo III↗

PubMed1987

In vivo and in vitro studies of hypocholesterolemic effects of diosgenin in rats.

There is evidence that diosgenin when given orally or parenterally decreases cholesterol plasma levels in rat, chicken and rabbits that have had a diet-induced hypercholesterolemia. 2. The per-oral administration of [3H]diosgenin yielded 12% of the given dose distributed throughout: liver, spleen, epididymal fat, brain and carcass of the rat. 3. In everted gut sacs, [3H]diosgenin was better absorbed than cholesterol. 4. In these tests diosgenin was recovered esterified from the tissues and the recovered cholesterol showed less esterification in the presence of diosgenin than in its absence.

Administration, Oral↗

PubMed1987

A comparative study of three methods for the estimation of total plasmalogens in lingual taste epithelium and other tissues.

The total plasmalogen content of lingual and other tissues was analyzed using the iodine-addition (Method 1), the p-nitrophenylhydrazone (Method 2), and the two-dimensional thin layer chromatography procedure (Method 3). Methods 1 and 2 were simple, rapid and reproducible, yielding values usually in close agreement with each other, and values higher than those of Method 3. Method 3 exhibited poor reproducibility. All three methods were of comparable sensitivity (less than 20 nmol of total plasmalogen per sample). According to Methods 1 and 2, there was more total plasmalogen in lingual epithelium containing taste buds compared with lingual epithelium devoid of taste buds. Plasmalogen content of bovine and rat brain, heart and liver agreed with literature values.

Animals↗

PubMed1986

Alterations of lipid composition in a dystrophic muscle cell line.

The composition of neutral lipids and phospholipids was determined in normal (Cb7) and dystrophic (DyA4) cell lines, derived from cloned satellite cells from control and dystrophic C57BL/6J/dydy mice. The results obtained showed that dystrophic cells contain a higher relative distribution of phospholipids than their normal counterparts. Moreover, the distribution of individual phospholipids differs between normal and dystrophic cells, with increased percentage of acidic phospholipids and reduced proportion of phosphatidylcholine in dystrophic cells. Cholesterol was increased but free fatty acids decreased in dystrophic cells. The possible pathogenetic significance and functional consequences of these abnormalities are discussed.

Animals↗

PubMed1986

Current concepts in the treatment of rheumatoid arthritis.

The treatment of RA is complex and often frustrating. The pathologic process of RA is composed of acute inflammation, chronic immunologic phenomenon, and chronic connective tissue degradation. It is important to understand not only the pathophysiology of RA but also the mechanism of action of our therapeutic drugs so that treatment can be tailored to affect the important aspects of the process leading to end-organ damage. Despite the many drugs available, therapy is still unsatisfactory. Many drugs work in only certain patients. This could be secondary to variability in the disease state or to difference in drug metabolism. A better understanding of both disease and therapeutic agents may lead to better use of our present agents and development of new, more effective treatment modalities.

Adrenal Cortex Hormones↗

PubMed1986

Comparison of fatty acid patterns of polar and neutral lipid classes and cyclo-oxygenase activity in taste and non-taste epithelium of steer tongues.

Epithelial tissues and papilla from several regions of the steer tongue were isolated and the fatty acids from each lipid class in the polar and neutral fractions were assayed. The observed profiles indicated regional differences. Arachidonic acid and other fatty acids containing long carbon chains (greater than 22) were found in all tissues sampled, particularly in the phosphatidyls of the inositols, ethanolamines, cholines, and in the cholesterylesters. Production of prostaglandin E2 was measured through cyclo-oxygenase activity and the presence of plasmalogens was observed in the phosphatidylethanolamine and choline fractions. Higher rates of PGE2 synthesis and greater amounts of plasmologens were found in taste-related epithelial samples compared to lingual epithelial control samples not containing taste buds. The heterogeneity of patterns of lipids and fatty acids found in the epithelium of the tongue suggests possible zonal specialization to satisfy regional physiological needs.

Animals↗