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Biomedical subjects

B Chin

Publications and source records attributed to B Chin.

At least 19 recordsLinked to original sources

Solvent replacement for green processing.

The implementation of the Montreal Protocol, the Clean Air Act, and the Pollution Prevention Act of 1990 has resulted in increased awareness of organic solvent use in chemical processing. The advances made in the search to find "green" replacements for traditional solvents are reviewed, with reference to solvent alternatives for cleaning, coatings, and chemical reaction and separation processes. The development of solvent databases and computational methods that aid in the selection and/or design of feasible or optimal environmentally benign solvent alternatives for specific applications is also discussed.

Air Pollution↗

Global cardiac function using fast breath-hold MRI: validation of new acquisition and analysis techniques.

Calculation of global cardiac function parameters has been validated using fast, segmented k-space, breath-hold, gradient-echo, magnetic resonance images. Images of phantoms, experimental animals, normal volunteers, and patients were acquired with a 1.5 T clinical scanner. Humans were imaged using two phased-array surface coils in multicoil mode. Myocardial contours were extracted using a new interactive, semi-automated method based on the active contour model method. Images were acquired in the short-axis orientation, and, using a new imaging and analysis strategy, in rotating plane long-axis orientations, to provide better definition of the valve planes and the apex, and also to reduce the number of slices (compared with the short-axis method) required to sample the whole heart. Validation was accomplished through calculation of the volumes of phantoms and left and right ventricular masses of animal hearts. Functional parameters from MRI were compared with those from echocardiograms and radionuclide angiograms in normal volunteers and patients, respectively.

Adult↗

Proteinases of rat mast cells. Peritoneal but not intestinal mucosal mast cells express mast cell proteinase 5 and carboxypeptidase A.

Six basic proteins of 26 to 38 kDa with isoelectric points (pI) > or = 8.5 were abundant in proteins separated by two-dimensional SDS-PAGE from adult rat peritoneal mast cells (MC). One was identified previously as rat mast cell proteinase (RMCP) 1, a chymase of 26 to 28 kDa, pI > 9.0. Microsequence analyses showed that two polypeptides of about 29 and 30 kDa had NH2 terminal amino acid sequences homologous to mouse MC proteinase 5 (MCP-5), whereas the amino terminals of the 33, 35, and 36 kDa proteins were homologous to MC carboxypeptidase A (MC-CPA). Rabbit Abs produced against synthetic peptides of the identified NH2 terminal sequences were used in immunoblot studies. At least three proteins reacted with Abs to MC-CPA, whereas Abs to MCP-5 detected three adjacent polypeptides, rather than just the two identified by using microsequence analysis. Removal of oligosaccharide side chains using peptide:N-glycosidase F reduced the heterogeneity of each set of three polypeptides (MCP-5 and MC-CPA) to a band of each protein of a lower M(r). The serine proteinase inhibitor [3H]diisopropylfluorophosphate ([3H]DFP) bound to a proteinase of 30 to 35 kDa, which is probably MC tryptase (pI < or = 6.0). Immunoblot analysis of proteins from intestinal mucosal mast cells showed RMCP-2, but not RMCP-1, MCP-5, or MC-CPA. This is the first report of MCP-5 in the rat and of clearly distinguishable glycosylated forms of MC CPA. These proteinases appear to be restricted in their distribution to selected MC populations, but little is known about their functions.

Amidohydrolases↗

MOMs (multiples of the median) and DADs (discriminant aneuploidy detection): improved specificity and cost-effectiveness of biochemical screening for aneuploidy with DADs.

OBJECTIVE: Our purpose was to assess the efficacy of double- and triple-screening paradigms for Down syndrome and to develop a more logical, statistical approach to risk prediction that will decrease the cost of screening and allow the incorporation of new parameters appropriately weighted for their contribution. STUDY DESIGN: Data from 24,504 patients who had biochemical screening for Down syndrome by single (alpha-fetoprotein), double (alpha-fetoprotein, beta-human chorionic gonadotropin), or triple screening (alpha-fetoprotein, beta-human chorionic gonadotropin, unconjugated estriol) who had complete outcome information were analyzed by (1) existing gaussian-based methods, (2) the Glasgow ratio method, and (3) a new statistical approach (i.e., directly adjusted data sets for discriminant aneuploidy detection [DADs]) RESULTS: By use of individual risk-based thresholds for "at risk" status, both double and triple screening performed far better than single screening, but the percentages of patients at risk varied widely. When the percentages at risk were held constant, the sensitivity of double and triple screenings was similar, suggesting that there are no benefits of using estriol as a third marker. For 25,000 patients the use of only alpha-fetoprotein and beta-human chorionic gonadotropin would save about $500,000, with no decrease in sensitivity. With the DADs approach a statistically sound model giving more stable estimates was developed that permits each factor to be analyzed for its own explained proportion of variance and allows each parameter to have different weighting. For this data set the same sensitivity was seen with, conservatively, a 1% reduction in the percentage of patients at risk, which would reduce by 250 the number of amniocenteses, at a further savings of about $400,000. CONCLUSIONS: By use of existing methods, double screening is equally as effective as triple screening, so that the expense of estriol is unnecessary. The DADs approach, by allowing for variable weighting of parameters, lowers the at risk percentage and will permit a much more flexible approach as new parameters become available. Changing to DADs and eliminating estriol should achieve higher specificity for the same sensitivity and save, conservatively, about $900,000 in this series. Extrapolated nationally, if confirmed, the annual savings could approach $72,000,000.

Adolescent↗

Interferons differentially regulate histamine and TNF-alpha in rat intestinal mucosal mast cells.

Mast cell (MC) heterogeneity has been well characterized in the rat where it has been shown that connective tissue MC, often represented by peritoneal MC (PMC), and the intestinal mucosal MC (IMMC) exhibit many differences in mediator content and responsiveness to secretagogues and anti-allergic drugs. Pretreatment (20 hr) of PMC with interferon (IFN)-alpha/beta or IFN-gamma, significantly reduced antigen-stimulated histamine release. By contrast, for IMMC, the same IFN treatment did not modify antigen-stimulated histamine secretion. Although IFN treatment differentially modulates histamine secretion from PMC and IMMC, pretreatment of both MC types with IFN-alpha/beta or IFN-gamma inhibited their tumour-necrosis factor-alpha (TNF-alpha)-dependent cytotoxicity. In 20 hr of culture, IMMC spontaneously released 98 pg/10(6) MC of TNF-alpha, whereas PMC released about threefold more TNF-alpha, 282 pg/10(6) MC. In addition, direct assessment of stored TNF-alpha established that IMMC store less TNF-alpha (68 pg/10(6) MC) than PMC (404 pg/10(6) MC). In summary, TNF-alpha content of PMC and IMMC was different, but IFN inhibited TNF-alpha-dependent cytotoxicity by both MC types. By contrast, treatment with IFN-alpha/beta or IFN-gamma inhibits antigen-induced histamine secretion by PMC, but does not modify antigen-induced histamine secretion by IMMC. Thus, IFN differentially regulate the secretion of histamine and TNF-alpha in PMC and IMMC.

Animals↗

Nutritional status of Kadazan children in a rural district in Sabah, Malaysia.

The nutritional status of 896 Kadazan children below 6 years of age from 23 villages of Tambunan District were studied. When stunting and wasting were defined as those who were below two standard deviations of height-for-age and weight-for-height (Waterlow et al, 1977) and based on the National Center for Health Statistics reference population, 67.6% of boys and 66.8% of girls were stunted while 12.3% of boys and 8.3% of girls were wasted. Weaning foods and toddler feeding practices were unsatisfactory. The role of health education on child care and feeding practices is emphasized.

Anthropometry↗

Effects of isradipine, a new calcium antagonist, versus hydrochlorothiazide on serum lipids and apolipoproteins in patients with systemic hypertension.

The effect of isradipine versus hydrochlorothiazide on the lipid profile of 44 hypertensive patients was investigated in a double-blind, randomized, 2-center trial. Lipid profiles included total cholesterol, serum triglycerides, high density lipoprotein (HDL) cholesterol, HDL subclasses, (HDL2 and HDL3), low density lipoprotein cholesterol, very low density lipoprotein cholesterol, apolipoprotein A-1 and apolipoprotein B. Isradipine had no effect on the lipid profile in short- (4 and 10 week) or long-term (52 week) studies. Hydrochlorothiazide increased serum triglycerides in 11 of 13 patients by a mean of 8% for the group (p less than 0.05) in long-term (52 week) studies, and total cholesterol by a mean of 9 and 16%, respectively (p less than 0.01) in 2 of 13 patients, with no difference in other lipid or lipoprotein parameters in short- or long-term studies.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗