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Biomedical subjects

T Cheng

Publications and source records attributed to T Cheng.

At least 73 records · Page 4Linked to original sources

Delayed effects of early nutrition with cholesterol plus saturated or polyunsaturated fatty acids on intestinal morphology and transport function in the rat.

This study was undertaken to test the hypotheses that: (1) the fatty acid and/or cholesterol composition of a nutritionally adequate isocaloric semisynthetic diet given in early life has lasting consequences for intestinal nutrient uptake and morphology; and (2) early life feeding experiences with diets of varying fatty acid or cholesterol composition influence the ability of the intestine to adapt to an altered nutrient uptake in later life. Weanling female Sprague-Dawley rats were fed nutritionally adequate isocaloric semisynthetic diets enriched with beef tallow, beef tallow plus 1% cholesterol, fish oil or fish oil plus 1% cholesterol. Animals fed fish oil or fish oil plus cholesterol for 11 weeks had a lower food intake but greater weight gain than animals fed beef tallow or beef tallow plus cholesterol. The age of the animals influenced lipid and hexose uptake. The uptake of these nutrients could also be changed by the addition of cholesterol to the diet. This cholesterol-related effect depended on the type of fat in the diet (saturated vs. polyunsaturated). These changes in nutrient uptake were associated with but not necessarily explained by alterations in food intake, body weight gain, intestinal mucosal weight or surface area. Finally, these changes in nutrient uptake and morphology may or may not be reversible. We speculate that dietary lipids may affect the ability of the intestine to adapt to an altered nutrient intake in later life.

Adaptation, Physiological↗

Binding of lipoprotein lipase to heparin. Identification of five critical residues in two distinct segments of the amino-terminal domain.

Binding to heparan sulfate governs many aspects of the physiological action and regulation of the lipolytic enzyme, lipoprotein lipase (LPL). In an attempt to identify the structural determinants which mediate this interaction, basic residues in three segments of the primary sequence of human LPL (residues 147-151, 279-282, and 292-304) were replaced with alanine, either singly or in various combinations, and variant proteins were subjected to affinity chromatography on heparin-Superose. Five basic residues in two distinct segments of the primary sequence were critical determinants of the high affinity for heparin manifested by the active enzyme (R279, K280, R282, K296, R297). By contrast, no such evidence could be detected for basic residues in the first cluster (K147, K148) or for other basic residues in the third cluster (K292, R294, K304), while the evidence for K300 was unresolved. The conformation of this heparin-binding domain can be inferred by reference to the three-dimensional structure of the homologous enzyme, pancreatic lipase (Winkler, F. K., D'Arcy, A., and Hunziker, W. (1990) Nature 343, 771-774). Affinity of the active enzyme for heparin could not be reduced below a threshold, suggesting that other heparin-binding determinants exist elsewhere in the molecule, as supported by recently published evidence (Davis, R. C., Wong, H., Nikazy, J., Wang, K., Han, Q., and Schotz, M. C. (1992) J. Biol. Chem. 267, 21499-21504).

Amino Acid Sequence↗

Glucocorticoid-induced growth inhibition and differentiation of a human megakaryoblastic leukemia cell line: involvement of glucocorticoid receptor.

A human megakaryoblastic leukemia cell line, HIMeg, was established recently. Previous studies have shown that retinoic acid (RA) and 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] have potent effects on the proliferation and differentiation of HIMeg cells. Recently, the effect of dexamethasone (Dex), a synthetic glucocorticoid, on HIMeg cell growth and differentiation was examined in comparison with RA and sex steroid hormones. It was observed that in a methylcellulose culture system, Dex suppressed the clonal proliferation of HIMeg cells in a dose-dependent manner. The inhibitory effects of Dex could be reversed by RU486, a potent glucocorticoid antagonist. In contrast, sex steroid hormones had little effect on the clonal proliferation of HIMeg cells. In a liquid culture system, only 2% of HIMeg cells expressed glycoprotein IIb/IIIa (GPIIb/IIIa) antigen without hormone treatment, whereas 45% and 30% of the cells expressed GPIIb/IIIa following the addition of RA and Dex, respectively. To examine the molecular basis of the hormone-induced cell differentiation, glucocorticoid receptor (GR) expression was studied by Scatchard analysis. It was shown that there existed a saturable, high-affinity GR in HIMeg cells and the GR number was altered after Dex or RA treatment of the cells, suggesting that the cellular effects of glucocorticoids on HIMeg cells were mediated by GR.

Cell Differentiation↗

Sensitive enzyme-linked immunosorbent assay for detection of Clostridium botulinum neurotoxins A, B, and E using signal amplification via enzyme-linked coagulation assay.

A new immunoassay amplification method has been applied to the measurement of toxins A, B, and E from Clostridium botulinum. The technique is a modified enzyme-linked immunosorbent assay (ELISA) which relies on the detection of sandwich complexes on microtiter plates by a solid-phase coagulation assay known as ELCA, or enzyme-linked coagulation assay. In the method, a coagulation activating enzyme (RVV-XA) isolated from the venom of Russell's viper is conjugated to affinity-purified horse antibodies specific for toxin type A, B, or E. Plates are coated with affinity-purified antibodies, and standard captag (capture-tag) protocols using labeled antibody are employed to bind the toxin from solution. Complexes are detected by adding a modified plasma substrate which contains all the coagulation factors mixed with alkaline phosphatase-labeled fibrinogen and solid-phase fibrinogen; deposition of solid-phase, enzyme-labeled fibrin on the solid phase is then a reflection of formation of toxin-RVV-XA-antibody complexes on the solid phase. Because of the ability to detect RVV-XA by this coagulation assay at concentrations < 0.1 pg/ml, it was possible to measure C. botulinum toxins A, B, and E at mouse bioassay levels (< 10 pg/ml, or < 0.07 pM) for both purified neurotoxin and crude culture filtrates obtained from strains known to produce appropriate single toxins. ELISA-ELCA should be applicable to measurement of toxins in most of the materials (contaminated food, blood, and excreta) for which the comparably sensitive mouse bioassay is currently employed. This method has the potential of broad application to the measurement of low concentrations of any antigen for which appropriate immunochemical reagents are available, in a color test format.

Animals↗

Effect of endothelin, angiotensin II and ANP on proliferation of vascular smooth muscle cells and cardiomyocytes.

By means of cell culture, 3H-thymidine (3H-TdR) incorporation and c-fos oncogene dot plotting technique, it was found that endothelin (ET) and angiotensin (ANG II) could promote proliferation and DNA synthesis of cultured vascular smooth muscle cells (VSMCs) and myocardial cells, and stimulate expression of c-fos oncogene of VSMCs. However, atrial natriuretic peptide (ANP) antagonizes the above effects of ET and ANG II.

Angiotensin II↗

[Changes of Leu-enkephalin in striatum and hypothalamus of rats during hyperbaric oxygen exposure].

The purpose of this study is to investigate the changes of Leu-Enkephalin (L-Enk) content in striatum and hypothalamus of rats during hyperbaric (HBO) oxygen exposure. Thirty-two male rats in the experiment were randomly divided into four groups: normobaric air group, normoxic hyperbaric nitrox group, nonconvulsion HBO group and convulsion HBO group. L-Enk content in striatum and hypothalamus was determined by radioimmunoassay. The results show that L-Enk content in the striatum and hypothalamus of rats exposed to hyperbaric oxygen environment were markedly higher than that of rats exposed to normobaric air and normoxic hyperbaric nitrox. The experimental results suggest that the elevation of L-Enk content in striatum and hypothalamus shows a positive relationship with the HBO exposure duration of animals and that there was no marked relationship with normoxic hyperbaric nitrox environment and compression-decompression method.

Animals↗

Effects of 1,25-dihydroxyvitamin D3 analogue 1,24(OH)2-22-ene-24-cyclopropyl D3 on proliferation and differentiation of a human megakaryoblastic leukemia cell line.

The novel analogue of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3), 1,24(OH)2-22-ene-24-cyclopropyl D3 (calcipotriol, MC903), exhibits similar effects on cell proliferation and cell differentiation in a newly established human megakaryoblastic leukemia cell line (HIMeg). MC903 was found to inhibit cell proliferation and induce cell differentiation in a liquid culture system at concentrations comparable to those of 1,25(OH)2 D3. Colony formation assay showed that MC903 or 1,25(OH)2 D3 markedly diminished the colony-forming ability of HIMeg cells at concentrations of 10(-6) M to 10(-10) M. Cell cycle analysis demonstrated that, as seen with 1,25(OH)2 D3, MC903 also altered the cell cycle distribution; the fraction of cells in G0 + G1 increased while those in S and G2 + M decreased. It can be concluded from these findings that 1,25(OH)2 D3 and its analogue MC903 have approximately equipotent effects on cells of megakaryoblastic lineage and are potentially useful in studying the cellular processes that are responsible for megakaryocytopoiesis.

Calcitriol↗

Study on induction of differentiation of a human megakaryoblastic leukemia cell line (HIMeg) by 1,25-dihydroxyvitamin D3.

It is reported that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a physiological factor, has an inductive effect on the differentiation of a novel human megakaryoblastic leukemia cell line (HIMeg) in vitro. At the concentrations ranging from 10(-9) to 10(-6) mol/L, 1,25(OH)2D3 showed inhibition of proliferation on HIMeg cells which was demonstrated by count of survival cells and cloning efficiency. Meanwhile, using light/electron microscopy, stain of cytochemistry (including immunoenzymatic technique) and flow cytometry, we found that HIMeg cells could be further induced into more mature cells in megakaryocytic lineage confirmed by a series of evidence, including the changes of cell morphology/structure and cytochemistry, increased expression of differentiation antigens on the cell surface, and polyploidization. So, it is possible for 1,25(OH)2D3 to promote the differentiation of the cells in megakaryocytic lineage in vivo and to be used to treat acute megakaryoblastic leukemia and other diseases with malignant megakaryocytosis.

Calcitriol↗

Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease.

Of 19 unselected patients with the diagnosis of amyotrophic lateral sclerosis (ALS) living in Suffolk County, New York (an area of high Lyme disease prevalence), 9 had serologic evidence of exposure to Borrelia burgdorferi; 4 of 38 matched controls were seropositive. Eight of 9 seropositive patients were male (8 of 12 male patients vs 2 of 24 controls). Rates of seropositivity were lower among patients with ALS from nonendemic areas. All patients had typical ALS; none had typical Lyme disease. Cerebrospinal fluid was examined in 24 ALS patients--3 (all with severe bulbar involvement) appeared to have intrathecal synthesis of anti-B burgdorferi antibody. Following therapy with antibiotics, 3 patients with predominantly lower motor neuron abnormalities appeared to improve, 3 with severe bulbar dysfunction deteriorated rapidly, and all others appeared unaffected. There appears to be a statistically significant association between ALS and immunoreactivity to B burgdorferi, at least among men living in hyperendemic areas.

Adult↗

Comparison of non-collagenous type IV collagen subunits in human glomerular basement membrane, alveolar basement membrane, and placenta.

This study examines the similarities and differences in the noncollagenous domain (NC1) of type IV collagen from human glomerular basement membrane (hGBM), alveolar basement membrane (hABM), and placenta (hPBM). Following collagenase digestion, NC1 domain was isolated on Bio-Gel A-0.5m or by cation exchange chromatography on S-Sepharose. NC1 from each source was characterized by SDS PAGE, and two dimension NEPHGE/SDS PAGE. Immunoblotting and ELISA inhibition was performed using antibody probes specific for M28 , M28+, M26 and M24 monomer subunits of human NC1. It was observed that all NC1 subunits were present in hGBM and hABM derived material, however M28 and M28+ monomers were absent in hPBM NC1. These findings indicate that while alpha 1(IV) and alpha 2(IV) collagen chains are present in hGBM, hABM and hPBM, alpha 3(IV) and alpha 4(IV) collagen chains are only found in hGBM and hABM but are absent in hPBM. It can now be appreciated that heterogeneity of alpha (IV) chain composition exists in basement membranes from various organs.

Basement Membrane↗

Long-term effects of manipulations of dietary omega-3 fatty acids on clinical control and in vitro uptake of glucose and lipids in diabetic rats.

The intestinal absorption of nutrients is increased in diabetic rats fed chow, yet short-term (two week) studies have demonstrated reduced and near-normal intestinal nutrient absorption in diabetic rats fed a diet high in polyunsaturated fatty acids. In this study we undertook to establish the effect of 10 weeks' feeding of isocaloric semisynthetic diets with high or low ratios of saturated (S)-to-omega-3 polyunsaturated (P) fatty acids ("fish oil") when given to streptozotocin diabetic rats. The fasting plasma glucose concentration was approximately 10% lower in diabetic rats fed P as compared with S, although the oral and intravenous glucose tolerance tests and the time-course of the oral and intravenous glucose-stimulated immunoreactive insulin levels were similar in P and S, as also were the levels of the hemoglobin A1C. The fasting plasma triglyceride concentrations were similar in P and S, but the fasting plasma cholesterol concentrations were approximately 20% lower in diabetic rats fed P as compared with S. Feeding P to diabetic animals was associated with a heavier intestine, which was comprised of a greater proportion of mucosal than submucosal tissue. The enhanced jejunal uptake of fatty acids 18:0 (stearic) and 18:2 (linoleic) as well as cholesterol observed in diabetic as compared with non-diabetic animals fed S was not observed in those fed P. The enhanced uptake of glucose in diabetic rats was also influenced by diet, with a lower rate for jejunal and ileal uptake of glucose in diabetic rats fed P than in those fed S.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recurrent outbreaks of giardiasis in a child day care center, Wisconsin.

In the 19-month period September 1983-March 1985, three outbreaks of giardiasis occurred in one large child day care center. Control measures instituted during each outbreak included case finding; pharmacologic treatment and follow-up testing of stool specimens for cases of giardia infection in day care children and staff, and their household contacts; facilitating and stressing personal and environmental hygiene, including altering diapering practices and teaching appropriate hand washing techniques. In the first, second, and third outbreaks, overall attack rates (stool analysis positive for Giardia lamblia) were determined for those persons with greater than or equal to 2 stool specimens submitted; attack rates in children were 47, 17, and 37 per cent, respectively; for tested staff, the rates were 35, 13, and 9 per cent; and for tested household contacts were 18, 9, and 5 per cent. Attack rates were highest for ambulatory diapered children, children attending the day care center greater than or equal to 40 hours per week, and children who were infected with G. lamblia in the most recent previous outbreak. Despite extensive efforts to identify cases, a cure rate of greater than 90 per cent in treated cases, and improvements in personal and environmental hygiene practices, G. lamblia infections recurred in outbreak proportions.

Child Day Care Centers↗

Adolescents' willingness to use a school-based clinic in view of expressed health concerns.

A health needs assessment was developed to facilitate implementation of a comprehensive school-based adolescent clinic. Students were asked about their willingness to use a school-based clinic for certain health and emotional problems. Six hundred students in grades 9 through 12 completed anonymous self-administered questionnaires. Twenty-eight percent of respondents reported recently feeling depressed; 12% reported a prior suicide attempt. Twenty-five percent of students felt they were overweight. Of 56% who had experienced intercourse at least once, only one third had ever used birth control. Twenty-one percent smoked cigarettes and 27% marijuana, 24% used other drugs, and 38% used alcohol. Students who reported depression and past suicide attempts were significantly (p less than or equal to 0.001) more willing to use the clinic for counseling needs than students not so reporting. Those with perceived weight problems reported more willingness to use a school clinic for nutrition information than those who did not feel overweight. Currently sexually active students were also more willing (p less than or equal to 0.001) than nonsexually active students to use the clinic for sexuality information and sexually transmitted disease screens. Respondents who used drugs, alcohol, or cigarettes, however, were no more willing than nonsubstance-using peers to use clinic services for relevant health information.

Adolescent↗

Use of haplotype analysis in the beta-globin gene cluster to discover beta-thalassemia mutations.

DNA polymorphisms have been of great value in defining a small number of common sequences in the beta-globin gene cluster and a region within which recombination may be restricted. Moreover, they have led to a screening procedure that not only has been of great value for the molecular characterization of beta-thalassemia mutations but also has implications for the characterization of other single-gene disorders.

Base Sequence↗