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Biomedical subjects

B Chin

Publications and source records attributed to B Chin.

At least 37 records · Page 2Linked to original sources
PubMed1988

Synergism of mutant frequencies in the mouse lymphoma cell mutagenicity assay by binary mixtures of methyl methanesulfonate and ethyl methanesulfonate.

The effect of mixed mutagen exposures on the rate and type of induced mutants was studied in the L5178Y/TK+/-----TK-/- mouse lymphoma cell mutagenicity assay. In this assay, exposure to ethyl methanesulfonate (EMS) results in more mutants that form large colonies than small colonies. Exposure to methyl methanesulfonate (MMS) results in more mutants that form small colonies than large colonies. Other reports in the literature suggest that large colony TK-/- mutants appear to result from small-scale, perhaps single-gene mutations, and that small-colony TK-/- mutants appear to be associated with chromosomal mutations. Treating cells for 4 h with simple, 2-component mixtures containing 6.45 micrograms/ml MMS and either 261, 392, 560 or 712 micrograms/ml EMS resulted in synergism of mutants at each mixture level. The frequencies of total mutants were synergized 12, 20, 35 and 72%, respectively, in mixed exposures with graded doses of EMS, above the sums of the mixture components. Small colony mutants were synergized to a greater extent than large colony mutants. The frequencies of small colony mutants in mixed exposures were increased 31, 54, 73 and 123%, respectively, while the frequencies of large colony mutants were increased -7, -6, 11 and 39%. Statistical analyses provide strong evidence of synergism (within the limits of the assay) for total and small-colony mutants at all doses of EMS tested, and for large-colony mutants above 400 micrograms/ml EMS. Similar magnitudes of synergism resulted when other constant levels of MMS (4.30 or 8.60 micrograms/ml) were mixed with the same graded doses of EMS. The degree of synergism was dependent on EMS concentration but not on MMS concentration.

Animals↗
PubMed1986

Improvement of the lipid profile during long-term administration of pindolol and hydrochlorothiazide in patients with hypertension.

The effect of the combined administration of pindolol (10 or 20 mg daily) and hydrochlorothiazide (50 mg daily) on the serum lipid and lipoprotein levels of 34 hypertensive patients was investigated for 6 to 18.5 months (mean 13.3). Placebo control data were compared with the results obtained during treatment periods in each patient by paired t tests. Mean levels of high-density lipoprotein cholesterol increased by 17% (p less than 0.01), low-density lipoprotein cholesterol decreased by 4% (p less than 0.01) and the high-density lipoprotein: low-density lipoprotein cholesterol ratio increased by 28% (p less than 0.01). Total serum cholesterol, serum triglycerides and very low-density lipoprotein cholesterol showed no statistically significant changes from control values. These findings suggest that the long-term administration of this beta blocker combined with a diuretic results in serum lipid changes considered beneficial in the evaluation of risk factors for coronary artery disease.

Adult↗
PubMed1985

Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line.

We report the isolation and characterization of 19 classes of nonrearranging T cell-specific cDNA clones and two cDNA clones encoding the alpha and beta chains of the T-cell antigen receptor from a human T-cell line, Jurkat. Results indicate that the human alpha-chain gene, like its beta-chain counterpart, undergoes somatic rearrangement in T cells. In addition, it shows sequence homology to its beta-chain counterpart and immunoglobulin, indicating that the human alpha chain is also a member of the immunoglobulin supergene family. Sequence comparison suggests that the alpha chain also may be composed of variable (V), diversity (D), joining (J), and constant (C) region gene segments. The protein deduced from the cDNA sequence has a molecular weight of 29,995 and possesses six potential N-glycosylation sites. The availability of alpha- and beta-chain genes of the T-cell receptor from the same T-cell line provides tools to study their possible roles in recognition of antigens and major histocompatibility complex products by the human T-cell receptor.

Amino Acid Sequence↗
PubMed1985

Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain.

The organization and sequences of the human beta-chain T-cell receptor diversity, joining, and constant region segments are described. The beta chain of the human T-cell receptor, analogous to the mouse counterpart, consists of two distinct constant region genes approximately equal to 10 kilobases apart. The two constant region genes, C beta 1 and C beta 2, are very similar not only in sequence but also in genomic organization. The coding sequences of each of these C beta constant region genes are divided into four exons. The first two exons encode most of the extracellular constant domain. The third exon encodes a major part of the presumed transmembrane portion, and the last exon contains the cytoplasmic coding sequence as well as 3' untranslated sequences. Except for a stretch of approximately equal to 95 highly conserved nucleotides extending 3' of the first exon of the C region genes, little homology can be found between the intron sequences of C beta 1 and C beta 2. A small cluster of joining region (J beta) gene segments is located approximately equal to 5 kilobases upstream of each of these two constant regions. The first cluster, J beta 1, contains six functional J gene segments while the second, J beta 2, contains seven functional J gene segments. In addition, diversity region (D beta) gene segments are located approximately equal to 600 base pairs upstream of each J beta. Recombinational signals containing highly conserved heptamer and nonamer sequences separated by 12 or 23 bases are found adjacent to all of these D beta and J beta gene segments. These signal sequences are thought to be involved in the somatic recombination processes. These results indicate that what appears to be a gene duplication event giving rise to these two distinct regions must have arisen a long time ago in the evolution of this gene locus.

Base Sequence↗
PubMed1985

Somatic rearrangement of T-cell antigen receptor gene in human T-cell malignancies.

A cDNA clone representing the gene encoding the beta chain of the human T-cell antigen receptor has been isolated recently. By using fragments of this cDNA as hybridization probes in Southern blot analysis of restriction endonuclease-digested genomic DNA, we have now examined the structure of the gene in DNA from 26 patients with acute leukemia and from 23 normal individuals. We have found that the T-cell antigen receptor gene has undergone somatic rearrangement in 14 of 14 patients with the phenotypic diagnosis of T-cell acute lymphoblastic leukemia. In this group of patients, similar patterns of rearrangement appear to occur in different patients. This finding suggests that there is either a limited repertoire of possible rearrangements or an association between the development of leukemia and specific patterns of rearrangement. DNA from 6 patients with acute myeloblastic leukemia, 6 patients with non-B, non-T acute lymphoblastic leukemia, and 23 nonleukemic individuals showed no rearrangement or polymorphism. One case of T-cell acute lymphoblastic leukemia, however, showed rearrangement of both the T-cell receptor beta chain and the constant region of the immunoglobulin gene. Studies with mixtures of DNAs from leukemic bone marrow cells and cultured skin fibroblasts, as well as with remission and relapse marrow DNAs from the same patients, indicate that this technique can detect 1% leukemic cells in a mixed population. In addition, DNA from the marrow of a patient in relapse contains a similar rearrangement to that found in the marrow sample taken at the time of diagnosis, which suggests that the original clone of leukemic cells was responsible for relapse. Our results indicate that assessment of rearrangement of the T-cell antigen receptor gene will be valuable in the diagnosis and management of leukemia and can be used to evaluate clonality in T-cell neoplasia.

Chromosome Mapping↗
PubMed1985

Evaluation of the S-Plus IV.

An evaluation of a Coulter Counter Model S-Plus IV hematology analyzer was undertaken at Memorial Sloan-Kettering Cancer Center to assess performance characteristics and to determine accuracy in analyzing both normal and clinical specimens. Special emphasis was placed on the platelet parameter. Precision, linearity, and carryover were found to be well within the manufacturer's specifications. A total of 222 patient samples were analyzed in the routine laboratory and on the Model S-Plus IV. Coefficients of correlation of 0.99 or higher were obtained for white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hgb), platelets (Plt), except mean cell volume (MCV) (r = 0.93). Results from 99 selected normal samples were compared with those from manual reference methods. Coefficients of correlation of 0.98 or higher were obtained for WBC, RBC, and Hgb. For MCV, the correlation coefficient was 0.85 and for Plt, 0.89 was obtained. The lower coefficient of correlation for these two parameters may be a function of the imprecision of the manual reference methods. In a previous study with an original Model S-Plus, the Plt parameter occasionally exhibited spuriously high counts. With the advent of third-generation S-Plus instruments, represented by the Model S-Plus IV, the possibility of reporting aberrant Plt values virtually has been eliminated. Data from the current study verify this. However, 93% of the flagged Plt results proved to be accurate, checking slides on these introduced inefficiencies in the laboratory.

Evaluation Studies as Topic↗
PubMed1984

Some observations on the zinc metabolism of the rabbit lens.

Rabbits' lenses contain about 100 mumol kg-1 wet wt (145 mumol kg-1 water) of zinc. This metal appears to be quite uniformly distributed throughout the organ and more than 90% is firmly incorporated into the tissue so as not to be readily exchangeable. The concentration of Zn in the aqueous and vitreous humors is about 10(-5) M (one-fourth the concentration in the blood serum). Lenses incubated in vitro can accumulate Zn from solutions containing this concentration of the metal. This process is concentration-dependent and is increased following damage produced by metabolic inhibitors. The process probably involves diffusion and is increased in the presence of a low external calcium concentration and the Ca ionophore A 23187. Amino acids which are known to bind zinc did not influence its accumulation by the lens, with the exception of cystine which increased it. Accumulated Zn (using 65Zn as a tracer) was able to leave the lens, but this process was quite slow and was reduced by the presence of lanthanum and low Ca concentrations. It is suggested that Ca and Zn may share common binding sites in the tissue, and they could be utilizing the same channels to cross the cell membrane.

Age Factors↗
PubMed1983

Absorption of 4,4'-methylenebis [2-chloroaniline] by human skin.

A system was developed to measure percutaneous absorption of water-insoluble environmental agents into human skin. Percutaneous absorption of 4,4'-[14C]methylenebis [2-chloroaniline] (MBOCA) was measured during dry contact exposure of MBOCA with organ cultures of neonatal foreskin. Time-dependent exposures, autoradiographs, and thin-layer chromatography indicated that MBOCA was rapidly and progressively absorbed and passed through the skin without being metabolized. The transepithelial penetration of MBOCA was temperature dependent. Under certain conditions, the stratum corneum contained more MBOCA than other layers in the skin, which suggested that the stratum corneum may not be the main barrier for percutaneous absorption of MBOCA. An assessment of risk confirmed that skin exposure is a cause for concern.

Autoradiography↗
PubMed1983

Calcium metabolism of the rabbit lens.

The Ca concentration in the rabbit lens is less than that in its bathing aqueous and vitreous humors. This Ca is not distributed evenly in the tissue; it has a higher concentration in the outer peripheral than the inner parts of the organ. About 60% of the total lenticular Ca is present in a layer extending about 0.5 mm down from the outer surface (25% of the total tissue in the lens). When incubated in a solution containing 45Ca about 40% of the lenticular Ca readily exchanges with the isotope in 3 hr; no further change occurred over the next 21 hr. This exchange appeared to occur across either the anterior or posterior side of the lens. The accumulated 45Ca was found to be present in a surface layer about 1 mm deep. The remaining 60% of the lenticular Ca was difficult to displace. Incubation for 5 hr in a Ca-free solution containing EDTA or following freezing and thawing resulted in a loss of only an additional 20% of tissue Ca. The remaining 'immobilizable' Ca (40%) was present in both the nuclear and peripheral zones of the lens. When the Ca concentration of the external medium is raised, lens Ca rises also, and when the external concentration is reduced the tissue level declines. In the presence of metabolic inhibitors (iodoacetate plus cyanide) lenticular Ca rises. This effect is slow; little change was seen in 5 hr. Ca accumulation in the lens was enhanced by the Ca ionophore A23187 but an effect was not detectable in 5 hr. Incubation in Na-free media or ouabain did not influence Ca accumulation suggesting that a Ca-Na exchange is not involved in regulation. Quercetin and orthovanadate, which can inhibit Ca-activated ATPase in some tissues were without effect on lens calcium. The phenothiazine trifluoperazine (TFP), however, enhanced accumulation of Ca. Efflux of accumulated 45Ca from the lens was rapid; 60% in 10 min and 90% in 3 hr. Lanthanum reduced the latter to 60% loss. Efflux of Ca from the lens was unchanged, under experimental conditions, by metabolic inhibitors, by EGTA, verapamil, TFP and vanadate.

Animals↗
PubMed1983

Some observations on the magnesium metabolism of the rabbit lens.

The (Mg) concentration in the rabbit lens is about 3.25 mmol/kg wet wt or 4.7 mM. This level is much greater than that in the bathing aqueous and vitreous humors. The Mg concentration in the peripheral part of this tissue is about four times greater than that in the inner 'nuclear' regions. Exchanges of Mg between the lens and its bathing fluids are very slow; under control conditions the lens appears to be virtually impermeable to Mg. Exposure to metabolic inhibitors, depolarizing concentrations of potassium, ouabain or replacement of Na with Li had little effect on the Mg content of the lens. Incubation of lenses in solutions containing EDTA or following freezing and thawing suggested that much of the Mg is present in a bound form. The ionophore A-23187 increased the permeability of the lens to Mg. Adjustment of the external Mg level in the presence of A-23187 indicated that the internal 'free' Mg concentration was about 3 mM. This result suggests that about 35% of the lenticular magnesium is bound.

Animals↗
PubMed1983

Kinetics of tissue distribution and elimination of 4,4'-methylene bis(2-chloroaniline) in rats.

The tissue distribution kinetics and elimination of 4,4'-methylene bis(2-chloroaniline) (MBOCA) in rats was studied after a single dose of [14C]MBOCA (0.49 mg/kg body weight, i.v.). The highest concentrations of radioactivity were in the small intestine, liver, adipose, lung, kidney, skin, and adrenals. For most tissues, a rapid decrease in radioactivity was followed by a slower decrease except for the small intestine, adipose and skin which demonstrated transient increases. Subcellular distribution in liver at 1 h showed radioactivity in all cell fractions. Although very lipophilic, [14C]MBOCA was completely eliminated within 48 h with the major route via the feces (73.4%).

Adipose Tissue↗
PubMed1982

Effect of gemfibrozil on serum lipids in man.

The effect of gemfibrozil, a new lipid-lowering agent, was studied in 22 patients. Each patient served as his own control in a double blind study. The administration of gemfibrozil, for a period of 24 months, 1200 mg daily, reduced mean serum triglyceride levels by 45.6% (p less than 0.001) and mean serum cholesterol levels by 8.3% (p less than 0.001). Mean serum HDL cholesterol was increased by 32.3% (p less than .0001) and mean serum LDL cholesterol levels were decreased by 11.4% (p less than 0.01). Mean serum VLDL cholesterol was decreased by 45.9% (p less than 0.001). A 3-hour glucose-tolerance test was done in each patient during a placebo-control period and during the administration of gemfibrozil. Mean plasma glucose was moderately increased during the administration of gemfibrozil at all points on the glucose tolerance curve, and to levels of significance at one (p less than 0.05) and two hours (p less than 0.02). There was no effect of the drug on serum immunoreactive insulin. No subjective side effects were apparent.

Adult↗
PubMed1980

Automated platelet counters: a comparative evaluation of latest instrumentation.

An extensive evaluation of performance characteristics and accuracy of clinical results for two automated multiparameter whole-blood cell counters (the Coulter Counter Model S-Plus and the Ortho ELT-8) and two single-parameter semiautomated platelet counters (the J. T. Baker MK-4/HC and the Clay-Adams Ultra-Flo 100) is described. Results of comparative assays performed on more than 1,200 clinical specimens are analyzed. These results are compared with manual determinations where appropriate. Particular attention is accorded to the accuracy of platelet counts, especially at abnormal levels below 70 X 10(3)/cu mm, where falsely elevated platelet counts may lead to serious clinical consequences. Both multiparameter instruments yielded accurate results, with the exception of low values reported by the ELT-8 for mean corpuscular volumes above 100 cu micrometer. Results for platelet counts were accurate for most specimens on all four instruments; the ELT-8 was the most reliable (P < 0.01), especially for the critically low counts. Although no instrument is infallible in determining platelet counts at all levels, the authors conclude that addition of platelet-counting capability represents a significant advancement over existing instrumentation.

Evaluation Studies as Topic↗
PubMed1980

Effect of phenolic antioxidants on the mutagenicity of aflatoxin B1.

The Ames assay employing Salmonella typhimurium TA100 and TA98 was used to investigate potential interactions between aflatoxin B1 (AFB1) and the phenolic antioxidants butylated hydroxytoluene, butylated hydroxyanisole, and propyl gallate. AFB1 doses were within the linear response range, and the antioxidants were used at levels of 0 to 50 micrograms per plate. All three antioxidants were nonmutagenic in either bacterial tester strain, with or without the hepatic S-9 enzyme preparation; toxic effects were observed at doses higher than 20 micrograms per plate. Butylated hydroxytoluene and butylated hydroxyanisole substantially increased AFB1-induced mutagenesis in the two tester strains with microsomal activation. The addition of 5 to 20 micrograms of butylated hydroxytoluene or hydroxyanisole to 5 to 20 ng of AFB1 per plate caused more than a twofold increase in the number of His+ revertants. Addition of propyl gallate resulted in only a moderate increase in the number of revertants. Whereas several anticarcinogenic and antimutagenic effects by phenolic antioxidants have been reported, particularly in studies with polycyclic aromatic hydrocarbons, the enhancement of mutagenic potency of AFB1 by these compounds suggests a specificity with respect to the chemical nature of AFB1.

Aflatoxins↗