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T Fischbach

Publications and source records attributed to T Fischbach.

17 recordsLinked to original sources
PubMed1996

Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine.

Skeletal muscle catabolism, low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection. In addition, a high glycolytic activity is commonly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigated (a) whether an "an-aerobic physical exercise" program causes similar changes in plasma amino acid levels, and (b) whether low plasma glutamine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects over longer periods suggest that the age-related loss of BCM occur mainly during episodes with high venous glutamate levels, indicative of decreased muscular transport activity for glutamate. A significant increase in venous glutamate levels from 25 to about 40 microM was seen after a program of "anaerobic physical exercise." This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only with the amino acid levels at baseline examination, but also with an increase in plasma glutamine, arginine, and cystine levels during the observation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a group of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, suggesting that body protein had been converted into other forms of chemical energy. The decrease in mean BCM/body fat ratios was prevented by N-acetyl-cysteine, indicating that cysteine indeed plays a regulatory role in the physiological control of BCM.

Acetylcysteine↗
PubMed1996

Some statistical procedures for analytical method accuracy tests and estimation.

In 1974 the National Institute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration joined to complete exposure standards promulgated by federal regulations. In that effort NIOSH scientists developed an accuracy criterion (AC) and a statistical protocol for evaluating fulfillment of that AC by an analytical method. This article extends that foundation and proposes a new approach to accuracy analyses. It concentrates on the case of known bias, but attempts to bridge the procedures from that case to one in which the bias is estimated. The article emphasizes a general and flexible approach to the design and analysis of more informative and effective method accuracy studies. These empower the user/investigator to design and analyze studies to be most useful and informative for specific requirements.

Bias↗
PubMed1996

Corrections to the target and critical values for the National Institute for Occupational Safety and Health validation tests.

In 1974 the National Institute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration joined to complete exposure standards promulgated by federal regulations. In that effort NIOSH scientists developed an accuracy criterion (AC) and a statistical protocol for evaluating its fulfillment. That AC and those procedures have been widely used ever since. This article presents corrections to the target and critical coefficients of variation published as part of the statistical protocol.

Bias↗
PubMed1996

S-adenosylhomocysteine as a physiological modulator of Apo-1-mediated apoptosis.

APO-1/Fas (CD95) is a member of the tumor necrosis factor/nerve growth factor receptor superfamily and mediates apoptosis in various cell types. Here we show that L929 cells, expressing human APO-1 treated with agonistic antibodies (anti-APO-1), elicit an early and transient increase of S-adenosylhomocysteine (AdoHcy), a potent inhibitor of S-adenosylmethionine (AdoMet)-dependent methylation reactions. In contrast, anti-APO-1 did not induce an AdoHcy increase in L929-APO-1 Delta4 cells expressing a C-terminally truncated APO-1 lacking part of the 'death domain' known to be required for the transduction of apoptotic signals. Addition of adenosine and D, L-homocysteine also led to an increase of cellular AdoHcy thus enhancing anti-APO-1-induced killing of L929-APO-1 cells. Treatment with anti-APO-1 also induced release of arachidonic acid from phospholipids: this effect was augmented by elevated levels of AdoHcy. In contrast, AdoHcy had only a minor effect on anti-APO-1-mediated DNA fragmentation. These findings suggest that AdoHcy functions as a physiological modulator of APO-1-mediated cell death in L929 cells and enhances anti-APO-1-induced cell killing at least partially by acting via the phospholipase A2 pathway.

Adenosine↗
PubMed1995

Lymphocyte subpopulations and concentrations of soluble CD8 and CD4 antigen after anaerobic training.

In 13 middle-aged, moderately trained men (40-60 yr) we investigated the influence of anaerobic training on immunological parameters measured at rest. The 4 week anaerobic training program (two 30-min sessions weight lifting and one interval training per week; lactate levels 4-6 mM and 8-10 mM, respectively), caused a significant increase of the mean arm muscle force by 7% (handgrip test, p < 0.05). Evaluation of lymphocyte subsets was performed by means of three-colour immunofluorescence analysis (FACS). After 4 weeks of training we found a significant reduction of the CD4+ T-cell counts by 15% (p < 0.05) paralleled by a fall of naive cells (CD3+/CD4+/CD45RA+) by 16%, which, however, was statistically not significant. While percentages of CD3+ lymphocytes decreased significantly by 6% (p < 0.001), absolute numbers of CD3+ T-lymphocytes were not detectably affected and also the relative ratio of CD8+ T-cell subsets, i.e. the ratio of suppressor vs cytotoxic T-cells (CD3+/CD8+/CD11b+, CD3+/CD8+/CD11b- respectively) remained unchanged. Likewise the serum concentrations of the soluble CD8 and CD4 antigen (sCD8/sCD4) as determined by sandwich enzyme immunoassays were found to be unaffected. We conclude that 40-60 years old healthy human subjects performing anaerobic training experience on average a significant decrease of circulating CD4+ T-lymphocytes, while other parameters including the activation parameters sCD8 and sCD4 remained unchanged.

Adult↗
PubMed1994

Effect of glutathione depletion and oral N-acetyl-cysteine treatment on CD4+ and CD8+ cells.

HIV-infected individuals and SIV-infected rhesus macaques have, on the average, decreased plasma cysteine and cystine concentrations and decreased intracellular glutathione levels. We show that the cysteine supply and the intracellular glutathione levels have a strong influence on the T cell system. A study of healthy human subjects revealed that persons with intracellular glutathione levels of 20-30 nmol/mg protein had significantly higher numbers of CD4+ T cells than persons with either lower or higher glutathione levels. Persons who moved during a 4-week observation period from the optimal to the suboptimal range (10-20 nmol/mg) experienced, on the average, a 30% decrease in CD4+ T cell numbers. This decrease was prevented by treatment with N-acetyl-cysteine (NAC). NAC caused this relative increase of CD4+ T cell numbers in spite of decreasing glutathione levels and not by increasing the glutathione level. Our studies suggest that the immune system may be exquisitely sensitive not only against a cysteine and glutathione deficiency but also against an excess of cysteine.

Acetylcysteine↗
PubMed1993

Plasma amino acid dysregulation after lentiviral infection.

The absence of AIDS-like symptoms in HIV-infected chimpanzees and SIV-infected African Green monkeys (AGMs) may provide important clues about the pathogenic mechanism of AIDS and about mechanisms of resistance. HIV-infected persons and SIV-infected rhesus macaques have, on the average, markedly decreased cysteine, cystine, and glutathione levels and elevated plasma glutamate concentrations. Glutamate inhibits the membrane transport of cystine and a combination of low plasma glutamate and high cystine levels was found to be correlated with high CD4+ T cell numbers even in HIV-negative healthy human individuals. We have now found that glutamate and cystine levels are also correlated with CD4+ T cell numbers in chimpanzees. But infection of chimpanzees, AGMs, and goats with HIV-1, SIV, and caprine arthritis encephalitis virus (CAEV), respectively, does not induce significant changes in plasma cystine or glutamate levels, although infected AGMs and goats have, on the average, significantly elevated plasma levels of the biochemically related amino acid proline.

Amino Acids↗
PubMed1992

Silica exposure in hand grinding steel castings.

Exposure to silica dust was studied in the grinding of castings in a steel foundry that used conventional personal sampling methods and new real-time sampling techniques developed for the identification of high-exposure tasks and tools. Approximately one-third of the personal samples exceeded the National Institute for Occupational Safety and Health recommended exposure limit for crystalline silica, a fraction similar to that identified in other studies of casting cleaning. Of five tools used to clean the castings, the tools with the largest wheels, a 6-in. grinder and a 4-in. cutoff wheel, were shown to be the major sources of dust exposure. Existing dust control consisted of the use of downdraft grinding benches. The size of the casting precluded working at a distance close enough to the grates of the downdraft benches for efficient capture of the grinding dust. In addition, measurements of air recirculated from the downdraft benches indicated that less than one-half of the respirable particles were removed from the contaminated airstream. Previous studies have shown that silica exposures in the cleaning of castings can be reduced or eliminated through the use of mold coatings, which minimize sand burn-in on the casting surface; by application of high-velocity, low-volume exhaust hoods; and by the use of a nonsilica molding aggregate such as olivine. This study concluded that all these methods would be appropriate control options.

Air Pollutants, Occupational↗
PubMed1990

Risk of neuropsychiatric disability among painters in the United States.

Scandinavian studies have suggested that working with solvents is associated with chronic neuropsychiatric disease. In the United States the Social Security Administration's records of white male recipients of disability compensation were used in a case-referent study on this topic. The cases were defined as men with any one of several neuropsychiatric diseases, and the referents as men with other disabling conditions. The men were considered exposed if they had worked as a painter prior to disability and unexposed if they had worked as a bricklayer. A job-exposure matrix verified the painters' potential exposure to solvents and the bricklayers' lack of potential exposure. The painters had a significant excess of neuropsychiatric disability [adjusted odds ratio (OR) 1.42, 95% confidence interval (95% CI) 1.04-1.94]. Construction painters had an excess of neuropsychiatric disability [OR 1.47 (95% CI 1.07-2.02)] in contrast to spray painters [OR 0.77 (95% CI 0.38-1.54)]. The limitations of the data are discussed, including potential diagnosis bias and exposure misclassification.

Adult↗
PubMed1985

The metabolism of N-hydroxyphenacetin in vitro and in vivo.

N-Hydroxyphenacetin (100 mg/kg) injected i.p. into rats rapidly appeared in the blood and disappeared with a t1/2 of 14 min; phenacetin and 4-acetamidophenol were major metabolites in blood. Ferrihaemoglobin was formed, but 4-nitrosophenetole was not detected in blood. N-Hydroxyphenacetin injected i.p. into rats was excreted in the urine unchanged (partly conjugated 2.1% of the dose, 2% was excreted as phenacetin, 19% as 4-acetamidophenol) and 1.8% as 2-hydroxyphenacetin. In addition, small amounts of 3-hydroxyphenacetin (0.4%) and traces of N-[4-(2-hydroxyethoxy)phenyl]acetamide (beta-HAP) (0.05%) were found. Time-course kinetics have shown that N-hydroxyphenacetin is metabolized in vitro to phenacetin, 2- and 3-hydroxyphenacetin, and 4-acetamidophenol by microsomal and cytosolic preparations of rat and rabbit liver. However, after the initial reaction, the formation of phenacetin and 2- and 3-hydroxyphenacetin did not continue with time, indicating that these products were not formed enzymically. N-Hydroxyphenacetin incubated with rat erythrocytes formed ferrihaemoglobin; the relationship between ferrihaemoglobin, phenacetin and 4-nitrosophenetole concn indicated that N-hydroxyphenacetin was oxidized by oxyhaemoglobin to acetyl 4-ethoxyphenyl nitroxide, which yielded phenacetin and 4-nitrosophenetole spontaneously.

Acetaminophen↗
PubMed1985

Additional routes in the metabolism of phenacetin.

omega-Hydroxylation of the ethyl moiety of phenacetin by rabbit-liver microsomal preparations was slow, but was increased 10-fold by pretreatment of the animals with phenobarbitone (PB), and was decreased 2.8-fold by treatment with 3-methylcholanthrene (3-MC) or beta-naphthoflavone (beta-NF). N-[4-(2-hydroxyethoxy)phenyl]acetamide (beta-HAP), the omega-hydroxylation product, which was detected in trace amounts only in the urine of rabbits injected with phenacetin, was converted into [4-(acetylamino)phenoxy]acetic acid (4-APA) by the microsomal and cytosolic fraction of liver homogenate and NADP+ or NAD+. Rabbits excreted 56% of a dose of beta-HAP as 4-APA in the 48 h urine. Phenacetin, injected i.p. into rabbits previously treated with PB, was excreted in the urine as 4-APA (12.2% of dose). beta-HAP formed endogenously or added as substrate in vitro was recovered as the O-acetyl derivative, when ethyl acetate was used for extraction of metabolites from microsomal incubation mixtures. (omega-1)-Hydroxylation of the ethyl moiety of phenacetin, which gave 4-acetamido-phenol, occurred rapidly with rabbit-liver microsomal preparations, and was not increased significantly after pretreatment of animals with either PB or 3-MC. omega-Hydroxylation of the acetic moiety of phenacetin by rabbit-liver preparations to give N-(4-ethoxyphenyl)glycolamide (4-GAP) was slow, but was increased three-fold after pretreatment of animals with 3-MC or beta-NF, whereas PB had no effect. 4-GAP was detected in trace amounts only in the urine of rabbits injected i.p. with phenacetin. N-Hydroxylation of phenacetin by rabbit-liver microsomal preparations was slow, but increased three-fold after treatment of animals with 3-MC, and was unchanged by PB. N-Hydroxylation of phenacetin by hepatic microsomes from 3-MC-treated rabbits was 26 times slower than that of 2-acetylaminofluorene; no N-hydroxy derivatives of N-(4-chlorophenyl)acetamide and propanil were detected in vitro.

Acetylation↗
PubMed1984

N-Hydroxy-N-arylacetamides. I. Toxicity of certain polycyclic and monocyclic N-hydroxy-N-arylacetamides in rats.

Of the two carcinogenic N-hydroxy-N-arylacetamides tested, N-hydroxy-4-acetylaminobiphenyl was as active as the monocyclic analogs in the oxidation of hemoglobin, whereas N-hydroxy-2-acetylaminofluorene produced less ferrihemoglobin after IP injection into female and male rats. Monocyclic N-hydroxy-N-arylacetamides, such as N-hydroxy-4-chloroacetanilide or N-hydroxyphenacetin, were more toxic than the parent N-arylacetamides, LD50 in mice being 190 mg/kg for N-hydroxy-4-chloroacetanilide vs 755 mg/kg for 4-chloroacetanilide, and 702 mg/kg for N-hydroxyphenacetin versus 1,220 mg/kg for phenacetin. The higher acute toxicities are probably due, at least in part, to the production of more ferrihemoglobin by the N-hydroxy-N-arylacetamides. Chronic toxicity of N-hydroxy-4-chloroacetanilide was tested on 10 male and 10 female Sprague Dawley rats after IP or SC injection of 20 mg (0.11 mmol)/kg twice weekly for 16 weeks into two groups of 10 animals each (five males, five females, total dose: 3.5 mmol/kg). The experiment, which was terminated after 2 years, did not yield any hint that N-hydroxy-4-chloroacetanilide was carcinogenic in the rat. Subchronic toxicity of N-hydroxyphenacetin was tested in two experiments on male and female Sprague Dawley rats after IP or SC injection of 50 or 100 mg (0.26 or 0.51 mmol)/kg. In the first experiment, two groups of 15 rats each (seven males, eight females) were injected either IP or SC with 50 and 100 mg/kg twice weekly for 29 weeks, and in the second experiment groups of 10 males and 10 females were injected SC with 100 mg/kg twice daily on 5 days a week for 12 weeks. The experiments, which were terminated after 29 weeks and 12 weeks treatment, respectively, did not provide evidence for chronic interstitial nephritis or tumor growth in the kidney. N-Hydroxy-N-arylacetamides were found to be inferior to the corresponding arylhydroxylamines in their ferrihemoglobin-forming capabilities in female rats. Large differences in activity of the arylhydroxylamines and no close relation to the number of rings was observed, N-hydroxy-2-acetylaminofluorene being the least active and N-hydroxy-4-acetylaminobiphenyl being as active as the monocyclic compounds, and exceeding all in the duration of its activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetamides↗
PubMed1983

[Digital subtraction angiocardiography: accuracy of left ventricular volume determination using intravenous injection of contrast medium].

The usefulness and accuracy of intravenous digital subtraction angiography of the left ventricle was proved by comparison with conventional left ventricular angiocardiography. During heart catheterization two cineangiograms were performed in 20 patients at rest: one with direct injection of contrast medium into the left ventricle and the other with intravenous injection. The intravenous angiocardiograms were processed by a hardwired digital image-processing system designed by our own group. Image enhancement was obtained by subtracting a mask image from the contrasted image of the left ventricle. The utility of four different mask modes was examined by correlating end-diastolic and end-systolic volumes determined from conventional and intravenous digital subtraction angiocardiograms of the left ventricle respectively. Reliable quantitative results could only be achieved by obtaining mask and contrasted images from the same phase of the cardiac cycle. Using these special mask modes, the standard deviations of the residuals amounted to +/- 33 and +/- 36 ml respectively. The results show that intravenous digital subtraction angiocardiography allows a quantitative determination of left ventricular volumes at rest.

Angiocardiography↗
PubMed1983

[Reliability of digital subtraction angiocardiography for the evaluation of left ventricular function and physical stress].

The reliability of determinations of left ventricular dimensions from digital subtraction angiocardiographies during exercise using intravenous injection of contrast material was proved in 20 patients. All angiocardiograms could be analyzed qualitatively and quantitatively only by means of the time-interval-difference (TID-) mode. Compared with other mask modes the superiority of the TID-mode results from the close temporal relationship between mask and contrasted frame. Thus, changes in position and brightness of the background structures are small, and left ventricular contours can be determined accurately despite intense respiratory movements. The intra-observer variability of determinations of end-diastolic and end-systolic volumes was +/- 12 ml (i.e. 7.5% of the mean value), corresponding inter-observer variability was +/- 24 ml (i.e. 17% of the mean value), respectively. Intra-observer deviation in determining ejection fraction was 2.8% (i.e. 4.5% of the mean value). The intra-observer variability in determining left ventricular axes was basal +/- 0.40 cm (i.e. 7% of the mean value), equatorial +/- 0.73 cm (i.e. 13% of the mean value) and apical +/- 0.34 cm (i.e. 8% of the mean value). Deviations of corresponding circumferential fiber shortening rates were basal +/- 0.22 s-1 (i.e. 14% of the mean value), equatorial +/- 0.32 s-1 (i.e. 22% of the mean value), and apical +/- 0.18 s-1 (i.e. 13% of the mean value). The results show that left ventricular dimensions can be determined accurately from intravenous angiocardiograms during exercise using digital subtraction angiocardiography.

Adult↗