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Biomedical subjects

N Brautbar

Publications and source records attributed to N Brautbar.

At least 19 recordsLinked to original sources
PubMed1997

Methyl tertiary-butyl ether antibodies among gasoline service station attendants.

Occupational exposure to petroleum products (gasoline) and elevated blood levels of MTBE have been demonstrated among gasoline station attendants. While MTBE and its metabolites have been considered environmentally inert, immunologically these materials could be reactive. This study was conducted to assess the immunological reactivity of humans to MTBE. Blood samples from 24 gasoline station attendants and 12 healthy controls were examined for levels of IgG, IgM, IgA, and IgE against MTBE by ELISA. In the gasoline-exposed group 7 out of 24 exhibited optical densities or antibody levels of 3-15-fold (OD 0.6-2.68) of the levels detected in controls (OD < 0.2). The detected antibodies both against MTBE-BSA or MTBE-HSA were of IgG and IgM but not IgA or IgE isotypes. These antibodies at much lower levels (OD of 0.45) were detected in only 1 of the 12 healthy control groups. The specificity of these antibodies was evidenced by absorption of MTBE antibodies in different sera using the same haptenic group bound to a different carrier. These results indicate that immune reactions to MTBE do occur through hapten carrier reactions which, in some individuals, end with specific IgG and IgM production.

Antibodies↗
PubMed1997

Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water.

1. In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce programmed cell death. 2. Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene-contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene. 3. Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry. 4. When apoptotic lymphocytes from exposed individuals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 +/- 1.8 and 12.1 +/- 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals (P < 0.0001, Mann-Whitney U-Test). MTBE and benzene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumulated at the S-G2/M boundaries. 5. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kappa B). NF-kappa B was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kappa B activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kappa B activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death.

Adolescent↗
PubMed1996

Magnesium depletion impairs myocardial carbohydrate and lipid metabolism and cardiac bioenergetics and raises myocardial calcium content in-vivo: relationship to etiology of cardiac diseases.

This study examines the effects of Mg depletion on myocardial bioenergetic, carbohydrate, lipid and phospholipid metabolism. Rats were studied after long-term (12 week) selective dietary restriction of Mg (20% normal dietary intake). Myocardial biopsy samples were examined for glucose 6-phosphate and glycogen to evaluate carbohydrate pathways and for glycerol phosphate and mitochondrial fatty acid oxidation and phospholipid contents to evaluate lipid and phospholipid turnover. Dietary Mg deficiency resulted in falls in myocardial glycogen, glucose-6-phosphate, glycerol phosphate, as well as the contents of phosphatidylcholine (PC), phosphatidylethanolamine (PE), diphosphatidyl glycerol (DPG), phosphatidyl inositol (PI) and total phospholipid phosphorus. These observations demonstrate impaired phospholipid metabolism, probably at the biosynthetic level. The mitochondrial oxidation of long-chain fatty acids was also impaired after Mg depletion. Mg depletion (serum Mg fell 60%) also resulted in significant falls in myocardial [ATP], phosphocreatine (PCr), and Mg with a concomitant rise in myocardial Ca content. These observations are consistent with the tenet that prolonged low [Mg2+]zero can result in marked reduction in oxygen and substrate delivery to the cardiac myocytes, with concomitant changes in membrane phospholipids (potentially resulting in a pro-oxidant state) probably as a result of coronary vasoconstriction.

Adenosine Triphosphate↗
PubMed1995

Silicone breast implants and autoimmunity: causation, association, or myth?

In vivo and in vitro studies, case reports and population studies show that: (1) silicone is immunogenic; (2) silicone is biodegradable and transported via the reticuloendothelial system to distant locations; (3) silicone breast implants "leak" and in turn silicone migrates outside the breast tissue; (4) case reports and population studies document an autoimmune reaction and immunological dysfunction in patients with silicone breast implants; (5) these immunological abnormalities and symptoms are reversible upon removal of the breast implants (in 50-70% of cases). The criteria to establish medical causation are defined, and based on those criteria it is concluded that silicone breast implants cause immunological disease.

Animals↗
PubMed1994

Antibody to silicone and native macromolecules in women with silicone breast implants.

Silicone implants have been associated with the development of multiple organ system abnormalities, including rheumatic disorders, nervous system, pulmonary dysfunction associated with autoantibodies and abnormalities of cellular immunity. In this regards a number of case reports and series of articles have been described. We hypothesized that an immune reaction to silicone breast implants would include the host reactivity against silicone and the macromolecules within the microenvironment of the implant, and these autoantibodies may react with other tissue antigens far from the site of the implant. To test this hypothesis 520 Symptomatic women with Silicone Implants which have developed Silicone related Immunological disorders and have typically complained of breast pain, Myalgia-Arthralgia, fatigue, or generalized pain, were examined by their physician. Blood samples were obtained and examined for the presence of Silicone antibodies, Myelin Basic Protein and human serum albumin antibodies. These samples were then compared to 520 matched controls without implants. At least at the level of two standard deviation silicone specific antibodies, IgG, IgA IgM, IgE and IgG+IgA+IgM antibodies were detected above the mean of normal controls. When these antibodies were classified based on the specialty of the examining physician, the % of patients with Silicone Antibodies were varied; general practice 51.6, Rheumatology 58.7, and Plastic Surgery 83.3, which may relate to the severeness of the disease. Being that a large % of patients demonstrated very high levels of Myelin Basic Protein Antibodies, possible cross reactive antibodies were sought. However, absorption of highly positive sera for Silicone Antibodies with MBP did not change the levels of Silicone Antibodies. On the other hand, Silicone-HSA was able to reduce the antibody values significantly. This reduction in antibody levels by Silicone is the best indication for the specificity of these antibodies. Moreover when data for silicone antibodies and MBP antibodies was analyzed in patients some with high and others with medium or low levels of silicone antibodies, MBP antibodies did not correspond to the silicone antibody levels. Similarly human serum albumin antibodies which was significantly higher in patients with silicone implants did not correlate with levels of silicone antibodies. These results indicate that immune reaction to silicone and different tissue antigens do occur and they are initiated through different mechanisms. And since predominant antibody class against silicone, MBP and HSA was IgM, clonal activation of IgM is possible which certainly warrants further investigation.

Adult↗
PubMed1994

Effect of relatively long-term hypomagnesemia on the chondro-osseous features of the rat vertebrae.

Cartilage and bone in the lumbar vertebrae of magnesium-deficient (LoMg) rats were studied after 4 and 8 weeks of Mg restriction. LoMg animals receiving 0.03% Mg intake had significantly reduced serum Mg levels compared to controls (receiving 0.2% Mg) at both 4 weeks [0.66 +/- 0.06 mg% mean +/- SE (n = 10)] and 8 weeks [0.74 +/- 0.02 mg% (n = 3)] of study. Mean width of the vertebral growth plate was significantly decreased in LoMg animals at 4 weeks [54.7 +/- 3.5 microns (n = 9) vs. control 68.0 +/- 3.0 microns (n = 6)] and 8 weeks [39.5 +/- 2.8 microns (n = 3) vs. control 57.5 +/- 3.6 microns (n = 3)]. The mean number of cells/cartilage column in the growth plate was also less at 4 weeks [5.8 +/- 0.18 (n = 5) vs. control 7.2 +/- 0.19 (n = 5)] and 8 weeks [4.9 +/- 0.19 (n = 3) vs. control 6.2 +/- 0.08 (n = 3)]. A significant proportion of LoMg animals possessed decreased pericolumnar diastase-PAS reactivity at 4 and 8 weeks of study; this indicates a decrease in cartilage glycoprotein content during Mg deficiency. Quantitative histomorphometric analysis determined that vertebral trabecular bone possessed significantly decreased percentage of osteoid surface (2.49 +/- 0.54 vs. control 6.98 +/- 2.8) and significantly decreased percentage of osteoid area (0.18 +/- 0.05 vs. control 0.82 +/- 0.38) after 4 weeks of Mg deficiency. These findings document significant alterations in both bone and cartilage histologic features following relatively long-term Mg deficiency.

Animals↗
PubMed1991

Magnesium absorption: mechanisms and the influence of vitamin D, calcium and phosphate.

Magnesium absorption has been studied in both humans and animals under diverse experimental conditions. As a result, the data often appear confusing and conflicting. In this review we attempt to summarize information concerning Mg absorption and, where possible, to reconcile apparently conflicting observations. Most studies suggest that Mg is absorbed predominantly in the distal intestine. At usual Mg intakes, Mg absorption occurs primarily by intercellular diffusional and solvent drag mechanisms. There is evidence for a saturable component of Mg absorption in the small intestine and the descending colon that is important at low dietary Mg intakes. Pharmacological doses of vitamin D increase Mg absorption in both vitamin D-deficient and vitamin D-replete animals. A substantial amount of Mg absorption, however, occurs independent of vitamin D. In addition, vitamin D may reduce Mg retention through increases in urinary Mg excretion. Intestinal interactions between Mg and calcium or phosphate have been demonstrated in both humans and animals. The nature of these interactions cannot be readily explained by data currently available.

Animals↗
PubMed1990

Site and mechanism of intestinal magnesium absorption.

Despite considerable research on magnesium (Mg) absorption there is still uncertainty regarding the site and mechanism of intestinal Mg transport. A careful review of the literature indicates that while Mg is absorbed throughout the intestine, the predominate site is the distal small intestine. There are three mechanisms by which Mg has been shown to cross the intestine:passive diffusion, solvent drag, and active transport. The importance of each of these mechanisms to total Mg absorption is discussed. Studies in both humans and experimental animals indicate that passive diffusion through the paracellular pathway accounts for the majority of Mg absorbed. Investigators have also consistently demonstrated the existence of a saturable component. Studies in everted gut sacs, however, have failed to demonstrate that Mg is actively transported against a concentration gradient in young or adolescent rats. Recent studies using the Ussing chamber have documented that Mg is actively transported in the descending colon.

Animals↗
PubMed1988

Effects of magnesium depletion on myocardial high-energy phosphates and contractility.

The effect of prolonged magnesium depletion on contractility, phosphorylating activity, and organic phosphates of spontaneously beating isolated rat atria was studied. Rats were fed a Mg-deficient diet for 8 weeks, during which serum Mg fell from 1.85 +/- 0.02 to 0.52 +/- 0.10 mg/dl. Atrial contractile activity was measured for 1 hr and at the end of this period tissue samples were taken for the determination of the phosphorylated intermediates. Mg depletion was associated with (a) reduced intracellular inorganic phosphorus and adenine nucleotides; (b) elevated creatine phosphate; (c) reduction in contractile force (CF) with no change in atrial beat rate (BR). There were no significant differences in the activities of creatine phosphokinase and adenylate kinase in control and Mg-depleted rat atrial homogenates determined in the presence of 5 mM MgCl2. Addition of various concentrations of MgCl2 to the medium resulted in an immediate reduction in both CF and BR of normal and Mg-depleted rat atria. Intraperitoneal administration of MgCl2 to Mg-depleted rats resulted in complete recovery of CF of isolated atria. This improvement in CF occurred without changes in the levels of inorganic phosphate and adenine nucleotides. The reduced intracellular level of high-energy phosphate or inorganic phosphate cannot therefore be responsible for the impaired contractility seen in Mg-depleted heart muscle. On the other hand, the fact that the creatine phosphate levels were higher in magnesium depletion suggests that myofibrillar utilization of creatine phosphate is more impaired than production, analogous to phenomena seen in postanoxic recovery.

Adenine Nucleotides↗
PubMed1988

Effect of parathyroid hormone on random migration of human polymorphonuclear leukocytes.

Derangements in leukocyte function occur in patients with primary hyperparathyroidism and in those with uremia, which is a state of secondary hyperparathyroidism, suggesting that parathyroid hormone (PTH) may affect leukocyte function. We examined the interaction between PTH and random migration of human polymorphonuclear leukocytes (PMNL) utilizing a modified Boyden chamber. Intact 1-84 PTH but not its amino-terminal (1-34 PTH) or its carboxy-terminal (53-84 PTH) fragments produced marked and significant (p less than 0.01) stimulation of random migration in a dose-dependent manner. Inactivation of 1-84 PTH abolished its effect and other peptide hormones (calcitonin, glucagon, insulin and vasopressin) did not stimulate migration of PMNL. The effect of PTH on migration was not due to action of the hormone on chemotaxis. PTH did not enhance cAMP or cGMP production by PMNL. The stimulation of PMNL motility by PTH was independent of calcium concentration in media, was not mimicked by calcium ionophore and was not blocked by verapamil. Quinidine also produced significant (p less than 0.01) increase in random migration of PMNL and this effect was not additive to that of PTH. Prolonged exposure to PTH (16-20 h) was associated with significant inhibition of random migration of PMNL. The migration of PMNL from patients with advanced renal failure was significantly (p less than 0.01) reduced and there was a significant (p less than 0.01) inverse relationship between random migration of PMNL and serum levels of PTH. Also PTH produced only modest stimulation of random migration of PMNL in most patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Migration Inhibition↗
PubMed1987

Hypophosphatemia and hypomagnesemia result in cardiovascular dysfunction: theoretical basis for alcohol-induced cellular injury.

Although it has been known for many years that prolonged ingestion of ethanol may be associated with numerous side effects, among them cardiovascular alterations, e.g., hypertension, cardiac arrhythmias, strokes, and cardiomyopathy, a direct cause and effect between alcohol and injury to the cardiovascular system has only been accepted recently. However, what mechanism is responsible for these cardiovascular alterations remains to be determined. Since it is well known that chronic alcohol consumption leads to hypophosphatemia and hypomagnesemia, we designed experiments to determine if controlled depletion of either phosphorous or magnesium (Mg2+) lead, in themselves, to cardiovascular disturbances and what effects these mineral depletions exert on myocardial cellular bioenergetics. Biochemical studies were carried out on left ventricular muscle, including mitochondrial and myofibrillar preparations. With respect to phosphate depletion, myocardial creatine phosphate, ATP, and ADP levels were reduced. Phosphate depletion also reduced mitochondrial and myofibrillar creatine phosphokinase activities; significant alterations in mitochondrial oxygen consumption, acid-extractable phospholipid precursors, and mitochondrial oxidation of long chain fatty acids were noted. With respect to magnesium depletion, significant reductions in inorganic oxygen consumption was also reduced. Utilizing these data, we have proposed several schemes for possible alcoholic-induced myocardial and vascular injury.

Adenosine Diphosphate↗
PubMed1986

Intestinal phosphate absorption: influence of vitamin D and non-vitamin D factors.

The transport of inorganic phosphate (P) was measured in the absence of electrochemical gradients across rat jejunum in vitro. Active P absorption was demonstrated in young, vitamin D-deficient (-D) rats, whereas active P secretion was found in normal, non-vitamin D-deficient adult rats, suggesting regulation of intestinal P transport by age-dependent but vitamin D-independent mechanisms. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulated mucosal-to-serosal P flux (Jm----s) without affecting serosal-to-mucosal P flux (Js----m), causing further increases in net P absorption (Jnet) in -D rats and reduction in net P secretion in normal adult rats, confirming a previously described role of this hormone on P absorption. We then examined the effect of increasing extracellular (buffer) P concentration [P] on this 1,25(OH)2D3-stimulated active P absorption in jejunum from -D rats. At [P] of 0.024, 0.24, and 2.4 mM, 1,25(OH)2D3 consistently stimulated Jm----s without affecting Js----m, causing an increment in Jnet. At 7.5 mM [P], however, this Jm----s stimulatory effect of 1,25(OH)2D3 was no longer observed. Moreover, at this [P] the Js----m exceeded Jm----s in both -D and 1,25(OH)2D3-repleted rats, converting the active P absorption into active P secretion in both treatment groups. These observations suggest the participation of local mechanisms, such as the ambient [P] of the transporting enterocytes, in the regulation of intestinal P absorption. Finally, the influence of dietary P deprivation on P absorption was studied in -D rats, with or without either vitamin D3 or 1,25(OH)2D3 repletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗