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Biomedical subjects

M Merchant

Publications and source records attributed to M Merchant.

31 records · Page 2Linked to original sources
PubMed1993

Calcium and magnesium mass transfer in peritoneal dialysis patients using 1.25 mmol/L calcium, 0.25 mmol/L magnesium dialysis fluid.

OBJECTIVE: To examine the effect of a reduced calcium/magnesium dialysis fluid (1.25/0.25 mmol/L, respectively) on calcium and magnesium mass transfer in both 1.36% and 3.86% glucose solutions. DESIGN: Each patient underwent four test exchanges, two with a standard dialysis fluid containing 1.36% and 3.86% glucose, and two with a reduced calcium/magnesium fluid containing 1.36% and 3.86% glucose. Calcium and magnesium were measured in dialysate and serum at 0 and 240 minutes. SETTING: Single renal unit of a university teaching hospital. PATIENTS: Sixteen patients established on CAPD, and peritonitis-free, for at least 3 months. RESULTS: A lower dialysate calcium results in negative mass transfer when serum-ionized calcium exceeds dialysate calcium (mean -0.21 +/- 0.15 mmol/exchange), and positive mass transfer when serum-ionized calcium is less than dialysate calcium in 1.36% glucose solutions (mean 0.57 +/- 0.18 mmol/exchange). A negative correlation was found between serum-ionized calcium level and calcium mass transfer. With a 3.86% reduced calcium/magnesium solution, calcium mass transfer is always negative (-0.88 +/- 0.18 mmol/exchange) due to ultrafiltration and solute drag. Fifteen patients were found to be hypermagnesemic at the time of the study. Magnesium mass transfer was neutral with the standard 1.36% glucose fluid (mean -0.01 mmol/exchange), but negative with the reduced calcium/magnesium 1.36% glucose fluid (mean -0.58 +/- 0.13 mmol/exchange). With the 3.86% glucose solution, both fluids produced negative magnesium mass transfer (mean -0.32 +/- 0.11 and -1.07 +/- 0.11 mmol/exchange for standard and reduced calcium/magnesium fluids, respectively). CONCLUSIONS: We conclude that this fluid formulation should reduce hypercalcemia and hypermagnesemia in CAPD patients.

Adult↗
PubMed1993

alpha-Naphthoflavone-induced CYP1A1 gene expression and cytosolic aryl hydrocarbon receptor transformation.

alpha-Naphthoflavone (alpha NF) is a weak aryl hydrocarbon (Ah) receptor agonist and inhibits the induction of CYP1A1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin. It has been suggested that the Ah receptor antagonist activity is due to the formation of alpha NF-cytosolic Ah receptor complexes that fail to undergo transformation. This hypothesis is consistent with data obtained in this and other studies using alpha NF concentrations from 10 to 1000 nM. However, 10 microM alpha NF exhibited Ah receptor agonist activity in several assays. Incubation of rat hepatic cytosol with 10 microM alpha NF caused transformation of the Ah receptor, as determined in a gel retardation assay using a 32P-labeled oligonucleotide containing a single dioxin-responsive element (DRE). Incubation of rat hepatoma (H-4-II E) cells with 10 microM alpha NF not only resulted in the induction of CYP1A1 mRNA levels but also increased chloramphenicol acetyltransferase activity from a DRE-containing chloramphenicol acetyltransferase reporter plasmid. Moreover, the DRE-transformed cytosolic Ah receptor complex liganded with either alpha NF or 2,3,7,8-tetrachlorodibenzo-p-dioxin did not undergo significant dissociation at 4 degrees. These data confirm that alpha NF is an Ah receptor agonist and, based on the results of previous studies, exhibits partial antagonist activity via competition for receptor binding sites.

Animals↗
PubMed1992

Mechanism of action of aryl hydrocarbon receptor antagonists: inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYP1A1 gene expression.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 gene expression as determined by increased CYP1A1 mRNA levels and ethoxyresorufin O-deethylase (EROD) activity in mouse Hepa 1c1c7, rat hepatoma H-4II E and human Hep G2 cancer cell lines. In contrast, treatment of these cell lines with either alpha-naphthoflavone (alpha NF) or 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) at concentrations as high as 10(-6) M resulted in only minimal induction of CYP1A1 mRNA levels or EROD activity. Cotreatment of the cells with 10(-9) M TCDD plus different concentrations (10(-8)-10(-6) M) of MCDF or alpha NF resulted in a concentration-dependent decrease in TCDD-induced CYP1A1 mRNA levels and EROD activity in the three cell lines. Moreover, using 10(-9) M [3H]TCDD, it was shown that the alpha NF- and MCDF-mediated antagonism of TCDD-induced CYP1A1 gene expression was paralleled by a decrease in levels of the nuclear [3H]TCDD-Ah receptor complex as determined by velocity sedimentation analysis of the nuclear extracts. The binding of nuclear extracts from the treated cells to a synthetic consensus dioxin responsive element (DRE) (a 26-mer) was determined by gel retardation studies using 32P-DRE. In cells treated with 10(-9) M TCDD or TCDD plus 10(-8)-10(-6) M alpha NF, the concentration-dependent decrease in TCDD-induced CYP1A1 gene expression by alpha NF was also paralleled by decreased levels of a retarded band associated with the nuclear Ah receptor-DRE complex. In contrast, the results of the gel shift assay of nuclear extracts treated with 10(-9) M TCDD or TCDD plus 10(-8)-10(-6) M MCDF indicated that there were relatively high levels of nuclear MCDF-Ah receptor complex in the cells co-treated with TCDD plus the antagonist but this was not accompanied by induced CYP1A1 gene expression. The results suggest that alpha NF and possibly MCDF compete with TCDD for cytosolic Ah receptor binding sites; however, MCDF may also inhibit the induction response by competing for and/or partially inactivating genomic binding sites.

Animals↗
PubMed1992

Mechanism of benzo[a]pyrene-induced Cyp1a-1 gene expression in mouse Hepa 1c1c7 cells: role of the nuclear 6 s and 4 s proteins.

Treatment of wild-type (wt) aryl hydrocarbon (Ah)-responsive mouse Hepa 1c1c7 cells with benzo[a]pyrene (B[a]P) caused a concentration-dependent induction of ethoxyresorufin O-deethylase (EROD) activity. In contrast, B[a]P was inactive as an inducer in Ah nonresponsive class 1 and class 2 mutant cell lines. In parallel experiments, the nuclear fractions from wt cells treated with 10(-7) M [3H]B[a]P contained both the 4 s carcinogen binding protein and the 6 s (Ah receptor) complexes, whereas only the 4 s complex was present in the nuclear fraction of the class 2 mutant cells. The results obtained from cotreatment of wt Hepa 1c1c7 cells with 10(-6) or 10(-7) M B[a]P and 5 x 10(-7) or 10(-7) M 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) showed that MCDF inhibited the induction of EROD activity and Cyp1a-1 mRNA levels by B[a]P. Moreover, using 10(-7) M [3H]B[a]P and unlabeled MCDF, it was shown that MCDF not only inhibited the induction response but also caused a concentration-dependent decrease in levels of the nuclear 6 s complex but not the 4 s complex. In contrast, in situ competition studies with unlabeled 10(-6) M benzo[ghi]-perylene (B[ghi]P) resulted in the elimination of the nuclear [3H]B[a]P 4 s complex (but not the 6 s complex); however, the EROD activity and Cyp1a-1 mRNA levels in cells treated with 10(-7) M B[a]P in the presence or absence of 10(-6) M B[ghi]P were not significantly different. These results indicate that the 4 s binding protein is not required for the induction of Cyp1a-1 gene expression in Hepa 1c1c7 cells and suggest that B[a]P and 2,3,7,8-tetrachlorodibenzo-p-dioxin induce Cyp1a-1 gene expression via a common mechanism which involves binding to the Ah receptor.

Animals↗
PubMed1992

6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) as an antiestrogen in human and rodent cancer cell lines: evidence for the role of the Ah receptor.

6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) is a relatively nontoxic analog of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Treatment of aryl hydrocarbon (Ah)-responsive MCF-7 human breast cancer cells with 100 nM MCDF resulted in the inhibition of 17 beta-estradiol-induced proliferation and the secretion of the 34-, 52-, and 160-kDa proteins. After treatment of the cells with 17 beta-[3H]estradiol, 100 nM of MCDF caused a decrease in the accumulation of the radiolabeled nuclear estrogen receptor (ER) complex in these cells. In parallel experiments, the antiestrogenic effects of MCDF were also determined in Ah-responsive wild-type Hepa 1c1c7 cells and Ah-nonresponsive class 1 and class 2 mutant cells. Treatment of the wild-type cells with 17 beta-[3H]estradiol and 100 nM MCDF caused a decrease in the accumulation of radiolabeled nuclear ER complex in these cells whereas no significant effects were observed in the mutant cells as determined by velocity sedimentation analysis. Comparable results were obtained using ER antibodies to measure the decrease in immunoreactive nuclear ER. In addition, both actinomycin D and cycloheximide inhibited the MCDF-mediated decrease of nuclear ER levels in the Hepa 1c1c7 wild-type cells. Although 100 nM MCDF did not induce cytochrome P-450-dependent monooxygenases in the MCF-7 or Hepa 1c1c7 cell lines, incubation of nuclear extracts from the MCF-7 cells treated with 100 nM MCDF with a synthetic consensus dioxin responsive element (an oligonucleotide duplex of 26 bases) gave a retarded band in a gel-retardation assay. The data suggest that the antiestrogenic effects of MCDF does not require the induction of the CYP1A1 gene expression but may involve the induction of other genes.

Animals↗
PubMed1990

The mechanism of action of alpha-naphthoflavone as an inhibitor of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYP1A1 gene expression.

Treatment of rat hepatoma H-4-II E cells with alpha-naphthoflavone (alpha NF) (10(-8), 10(-7), 10(-6)M) resulted in only minimum induction of ethoxyresorufin O-deethylase (EROD) activity and cytochrome P4501A1 mRNA levels only at 10(-6)M. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused maximum or near maximum induction responses at 10(-8) and 10(-9)M. In a time-course study with TCDD (10(-9)M), and TCDD plus alpha NF (cotreated), alpha NF significantly inhibited the induction of EROD activity and cytochrome P4501A1 mRNA levels by TCDD for 6-24 h after initial exposure of the cells to the chemicals. In addition, treatment of the cells with 10(-9)M TCDD in the presence or absence of 10(-8), 10(-7), and 10(-9)M alpha NF showed that the latter compound inhibited the induction effects by TCDD in a concentration-dependent manner and these inhibitory effects could be overcome, in part, by a higher concentration of TCDD (10(-8)M). Treatment of the rat hepatoma H-4-II E cells with [3H]TCDD showed that within 60 min, there was an initial rapid increase in nuclear [3H]TCDD receptor complex levels (38 fmol/mg protein) which decreased to less than 10 fmol/mg protein within 4 h and remained relatively constant for up to 24 h. However, in cells treated with [3H]TCDD (10(-9)M) plus alpha NF (10(-6)M) the levels of the nuclear [3H]TCDD receptor complex were less than 5 fmol/mg protein throughout the 24-h time course. These data, coupled with the results which indicate that the alpha NF competitively inhibits the binding of [3H]-TCDD to the cytosolic aryl hydrocarbon (Ah) receptor, suggest that alpha NF inhibits the TCDD-mediated induction of CYP1A1 gene transcription and translation by direct competition for cytosolic Ah receptor binding sites.

Animals↗
PubMed1990

Respiratory changes associated with the in vitro evagination of Taenia solium cysticerci.

The metabolic adaptability of Taenia solium cysticerci was studied in vitro, by measuring their respiratory rate before, during, and after trypsin-induced evagination. Under aerobic conditions, the oxygen consumption increased about 40% during evagination of the cysticeri and returned to basal rates after the process was completed. The percentage of evagination induced by trypsin was not affected under anaerobic conditions or in the presence of respiratory poisons such as cyanide and carbon monoxide. These data indicate that cysticerci use either aerobic or anaerobic pathways according to oxygen availability in the environment. Results from experiments of irreversible respiratory poisoning using cyanide suggest the presence of an alternative respiratory chain. Proteolytic action of trypsin on a fibrous layer surrounding the invaginated larvae is suggested by histological evidence.

Aerobiosis↗
PubMed1982

Application of body surface mapping to exercise testing: S-T80 isoarea maps in patients with coronary artery disease.

Body surface electrocardiographic maps were recorded before and after exercise in 25 men with angiographically documented coronary disease. Torso potential distributions at 192 locations were derived from a 32 lead electrode array using methods previously described in our laboratory. The S-T segment was characterized by the spatial distribution of the integral of S-T segment voltage over 80 ms (S-T80). Body surface regions where the S-T80 areas were =8 mV . ms or greater were identified in 18 of 25 patients. The most negative S-T80 site on the map was called the "S-T80 minimum." The S-T80 minima were located 1 or 2 electrode rows away from the standard V4--V6 electrode positions in 6 of 18 patients who developed S-T80 areas of -8 mV . ms or greater. Our data suggest that standard electrocardiographic leads may not be optimal for identifying S-T segment depression in all patients with coronary disease. Furthermore, body surface mapping during exercise provides a more quantitative and qualitative method for characterizing the ischemic response to exercise.

Adult↗
PubMedDate not supplied

A rapid protein profiling system that speeds study of cancer and other diseases.

To realize its potential to transform research and medicine, genomics must be complemented by protein expression data. Analysis by SELDI-TOF-MS technology, implemented in the ProteinChip System, overcomes the limitations of traditional protein analysis methods by enabling rapid analysis of small amounts of crude protein extracts and providing size and functional characterization on total cellular or tissue populations of proteins. The system has already been put to constructive use in many laboratories and has enabled researchers to determine unique protein profile signatures characteristic of progression from healthy to diseased states and back. In addition to its research applications, recent experimental successes suggest that the technology may soon find use in the important work of early diagnosis and treatment of infectious diseases, cancer, and other medical conditions.

Antibodies↗