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Biomedical subjects

C Chu

Publications and source records attributed to C Chu.

At least 73 records · Page 4Linked to original sources
PubMed1994

Hepatic beta-oxidation of 3-phenylpropionic acid and the stereospecific dehydration of (R)- and (S)-3-hydroxy-3-phenylpropionyl-CoA by different enoyl-CoA hydratases.

The hepatic beta-oxidation of 3-phenylpropionic acid (PPA) was studied by the use of subcellular fractions and purified enzymes with the aim of characterizing intermediates and the subcellular location of this pathway. Respiration measurements with coupled rat liver mitochondria indicate that PPA is efficiently metabolized by mitochondrial beta-oxidation. In contrast, the peroxisomal beta-oxidation of this compound is at best a very slow process, as evidenced by the low activity of peroxisomal acyl-CoA oxidase toward 3-phenylpropionyl-CoA. In mitochondria, 3-phenylpropionyl-CoA is effectively dehydrogenated to cinnamoyl-CoA, which is only slowly converted to benzoylacetyl-CoA due to the unfavorable equilibrium of the hydration of cinnamoyl-CoA to 3-hydroxy-3-phenylpropionyl-CoA. Benzoylacetyl-CoA is a substrate of 3-ketoacyl-CoA thiolase. The dehydration of 3-hydroxy-3-phenylpropionyl-CoA to cinnamoyl-CoA forms the basis for a sensitive and stereospecific assay of enoyl-CoA hydratases. The progress of this reaction, which proceeds to near completion, can be measured spectrophotometrically at 308 nm. Soluble mitochondrial and peroxisomal enoyl-CoA hydratases only act on the (R,L) isomer, whereas the peroxisomal D-3-hydroxyacyl-CoA dehydratase is specific for the (S,D) isomer. Both substrates can be easily prepared from the commercially available enantiomeric acids. It is concluded that PPA, a key compound in Knopp's classical study that led him to formulate the principle of beta-oxidation, is overwhelmingly, if not completely, degraded by mitochondrial beta-oxidation.

Acyl Coenzyme A↗
PubMed1994

Reproductive health research in China: the Ford Foundation initiatives.

Increasing demographic and epidemiological evidence shows that maternal health problems are widespread and are linked to social, cultural, and economic factors, in particular, to women's status in society. Thus, there is an urgent need to expand existing knowledge about these influences on reproductive health and to empower women to gain control over them. To this end, there is a need for a comprehensive, interdisciplinary approach with an emphasis on social science research and training. The Ford Foundation, after an extensive review of its work in population and development, embarked on a new, ten-year, comprehensive reproductive health program for the 1990s. This paper describes one component of that program, a partnership with the All China Women's Federation to sponsor a series of reproductive health research activities. It examines the development and evaluates the positive and negative outcomes of the project, which commenced in 1991, from the perspective of a consultant involved in the process. So far, the project has generated interest in reproductive health in at least twenty-one Chinese provinces and has fostered a real partnership between the sponsoring and the collaborating agency. Based on the immediate outcomes of a research competition designed to identify research projects and investigators, of participant evaluation of the methodology training course, and of the strategies aimed at building capabilities and strengthening institutions in order to ensure future success, I conclude that the Ford Foundation's reproductive health initiative in China is a worthwhile and sustainable project.

China↗
PubMed1994

Resource intensity weighing and case mix grouping: assumptions and implications for health service performance evaluation.

The use of Resource Intensity Weights (RIWs*) for equity funding and utilization management assumes validity of the cost estimates, reliability of the patient categorization scheme, equivalence of the bases for cost comparison, and equity of the subsequent resource distribution. This paper examines these assumptions, and concludes that caution must be taken when using the current RIWs and Case Mix Groups (CMGs*) for resource allocation and performance evaluation purposes. RIW has represented a milestone in the history of Canadian health care product costing and management. It would be prudent for health care professionals at the operational level to provide structured and continuing feedback that can contribute to the validation and refinement of these valuable management tools.

Diagnosis-Related Groups↗
PubMed1994

Compensatory and maladaptive responses to cardiac dysfunction.

The past few years have witnessed an extraordinary number of important developments in the study of compensatory and maladaptive responses to cardiac dysfunction. It now seems clear that the process whereby the heart remodels in response to left ventricular injury is of paramount importance in the expression of clinical heart failure. There have been parallel attempts by basic scientists and clinical investigators to understand better the fundamental biologic processes that underlie remodeling and to assess numerous new treatments--especially angiotensin-converting enzyme inhibitors. A general consensus seems to be emerging that holds that the response of the heart to acute injury includes a number of highly compensatory and adaptive mechanisms that ultimately become maladaptive and contribute to cardiomegaly and severe congestive heart failure. Such mechanisms undoubtedly include local and systemic release of cytokines, peptides, and neurohormones, and altered loading conditions leading to unusual mechanical forces on cardiac myocytes and other cells of the heart. At the organ level there is hypertrophy, dilatation and growth of the interstitium. Preliminary evidence also suggests there may be some "remodeling" at the cardiac myocyte level. Reduction in peripheral vasodilator reserve is seen in experimental animal models of heart failure. Patients with heart failure also develop an endothelial-dependent form of peripheral vascular dysfunction expressed clinically as an attenuated ability to dilate in response to such stimuli as acetylcholine. The transition point whereby these myocardial and peripheral vascular abnormalities become clearly dysfunctional and contribute toward the full clinical expression of heart failure remains to be further investigated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Ectopic expression of cyclin D1 prevents activation of gene transcription by myogenic basic helix-loop-helix regulators.

Activation of muscle gene transcription in differentiating skeletal myoblasts requires their withdrawal from the cell cycle. The effects of ectopic cyclin expression on activation of muscle gene transcription by myogenic basic helix-loop-helix (bHLH) regulators were investigated. Ectopic expression of cyclin D1, but not cyclins A, B1, B2, C, D3, and E, inhibited transcriptional activation of muscle gene reporter constructs by myogenic bHLH regulators in a dose-dependent manner. Ectopic expression of cyclin D1 inhibited the activity of a myogenic bHLH regulator mutant lacking the basic region protein kinase C site, indicating that phosphorylation of this site is not relevant to the mechanism of inhibition. Analysis of cyclin D1 mutants revealed that the C-terminal acidic region was required for inhibition of myogenic bHLH regulator activity, whereas an intact N-terminal pRb binding motif was not essential. Together, these results implicate expression of cyclin D1 as a central determinant of a putatively novel mechanism that links positive control of cell cycle progression to negative regulation of genes expressed in differentiated myocytes.

Animals↗
PubMed1993

Binding of the O-antigen of Shigella dysenteriae type 1 and 26 related synthetic fragments to a monoclonal IgM antibody.

Shigella dysenteriae type 1 possesses an O-antigen whose repeating unit is -->3)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-D-Galp -(1-->3)-alpha-D- GlcpNAc-(1-->, where Rhap is rhamnopyranosyl, Galp is galactopyranosyl, and Glcp is glucopyranosyl. Using ligand-induced protein fluorescence change, we have measured the affinities of a monoclonal murine IgM for 26 fragments of, or related to, the structure of the O-polysaccharide and of the IgM Fab for the intact O-specific bacterial polysaccharide. Synthetic saccharides used were methyl glycosides to ensure an anomerically defined pyranosyl ring conformation. The galactosyl residue is the only monosaccharide of the antigenic epitope that shows quantifiable binding: approximately 3.0 kcal/mol of binding free energy, depending on the structure and conformation of the fragment it is a part of. Addition of an alpha-(1-->2)-linked rhamnosyl residue increases the free energy of binding significantly. We propose this rhamnopyranosyl-alpha-(1-->2)-galactopyranosyl disaccharide to be the basic determinant of the Shigella O-polysaccharide. Further extension (by linkages as in the natural antigen) of this oligosaccharidic ligand toward the upstream end (in an oligo- (or poly-)saccharide, such as A-->B-->C-->D-->E-->m, where A, B, C, D, and E are sugars and m is any moiety, such as methyl, we define A as the glycosyl- or upstream terminus, and E as the glycoside- or downstream terminus) by rhamnosyl and N-acetylglucosaminyl moieties improves the binding only minimally. The antibody is quite specific for the rhamnosyl-alpha-(1-->2)-galactosyl sequence but less so for the nature of the attachment to the galactosyl residue on the downstream side. Measurements using IgM Fab and the intact O-specific polysaccharide show that the antibody can bind internal segments on the antigen chain. The free energy of binding of this antibody for the disaccharide determinant varies from -delta G of 4.7 to 5.1 kcal/mol, depending on its flanking residues.

Animals↗
PubMed1993

Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids.

The theoretic basis for developing conjugate vaccines, to induce immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the prevention of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific polysaccharides (O-SPs) of Shigella dysenteriae type 1, S. flexneri type 2a, and S. sonnei were covalently bound to carrier proteins. Alone, the O-SPs were not immunogenic in mice. Conjugates of these O-SPs, injected into young outbred mice subcutaneously as saline solutions containing 2.5 micrograms of saccharide, elicited serum IgG and IgM antibodies with booster responses; adsorption onto alum enhanced their immunogenicity. Injection of 25 micrograms of these conjugates into adult volunteers elicited mild local reactions only. Each conjugate induced a significant rise of the geometric mean serum IgG, IgM, and IgA LPS antibody levels. A second injection 6 weeks later did not elicit booster responses, and adsorption of the conjugates onto alum did not enhance their immunogenicity. Conjugate-induced levels of IgA, but not IgG or IgM, declined to preimmunization levels at day 56. The levels of postimmunization antibodies of the three immunoglobulin classes were similar to or higher than those of recruits in the Israel Defense Force following shigellosis caused by S. flexneri type 2a or S. sonnei. These data provide the basis for evaluating these conjugates to prevent shigellosis.

Adolescent↗
PubMed1992

Hypothesis for vaccine development: protective immunity to enteric diseases caused by nontyphoidal salmonellae and shigellae may be conferred by serum IgG antibodies to the O-specific polysaccharide of their lipopolysaccharides.

Immunoprophylaxis for bacterial enteric diseases is hindered because the protective immune mechanism(s) against nontyphoidal salmonellae or shigellae in humans are not established. On the basis of the similarities between the clinical signs, epidemiology, pathogenesis, and pathology of as well as protective immunity to salmonellae and shigellae, we propose that serum IgG antibodies to the O-specific polysaccharide (O-SP) of their lipopolysaccharides (LPSs) will confer protective immunity to these two pathogens. Critical to this notion is that (1) the virulence of these two pathogens requires full expression of their LPS; (2) active or passive immunization with serum IgG O-SP antibodies confers protection of mice against Salmonella typhimurium (there are no comparable data for humans); and (3) in humans, convalescence from shigellosis confers type (O-SP) -specific protective immunity, and indirect evidence shows a correlation between the level of serum LPS antibodies and resistance to shigellosis. We designed conjugate vaccines to elicit high levels of long-lived serum IgG O-SP antibodies to nontyphoidal salmonellae and shigellae to test this hypothesis.

Animals↗
PubMed1992

Dietary calcium modifies concentrations of lead and other metals and renal calbindin in rats.

We studied the effects of dietary calcium on kidney, femur, testis, liver, heart and brain concentrations of lead, magnesium, iron, copper, calcium and zinc in rats exposed to lead for 1 y. Renal levels of the 28,000 Da, vitamin D-dependent, calcium-binding protein calbindin-D28K were also measured. Seventy-two weanling male Sprague-Dawley rats were randomly assigned to one of nine treatment groups. Rats were fed diets containing 0.1, 0.5 or 2.5% Ca for 52 wk and were simultaneously given either 0, 50 or 100 mg lead/L in their drinking water. Rats fed the 0.1% Ca diet had organ lead concentrations that were two- to 20-fold greater than the corresponding animals fed 0.5% Ca. Rats fed diets containing 2.5% Ca had the lowest organ lead concentrations. Despite substantial effects of diet Ca on organ lead concentrations, Ca did not significantly influence concentrations of most other divalent metals studied with the exception of kidney calcium and magnesium, testis iron, plasma ionic calcium and magnesium, and several femur metals. Kidney calcium concentrations were lower in rats fed 2.5% Ca diets than in those fed 0.1 or 0.5% Ca diets. For rats not given lead, renal calbindin concentrations were highest in rats fed 0.1% Ca, and lowest in rats fed 2.5% Ca. Lead inhibited an increase in renal calbindin in the rats fed 0.1% Ca, but paradoxically increased renal calbindin levels in animals fed 2.5% Ca.

Administration, Oral↗
PubMed1992

Ethylene-Induced Polyamine Accumulation in Rice (Oryza sativa L.) Coleoptiles.

Effects of ethylene on free polyamine biosynthesis in rice (Oryza sativa L. cv Taichung Native 1) coleoptiles were investigated in sealed and aerobic conditions. In sealed conditions, putrescine increased significantly and coincided with ethylene accumulation. Application of ethylene in sealed containers promoted putrescine accumulation over that in sealed controls. This ethylene-enhanced putrescine accumulation was inhibited by the ethylene action inhibitor 2,5-norbornadiene at 4000 muL/L. In aerobic conditions, ethylene and 1-aminocyclopropane-1-carboxylic acid also induced putrescine accumulation. Activity of arginine decarboxylase (EC 4.1.1.19) and S-adenosylmethionine decarboxylase (EC 4.1.1.50) increased on exposure to ethylene in aerobic conditions. Ornithine decarboxylase (EC 4.1.1.17) activity, however, remained unchanged. The ethylene-induced putrescine accumulation was inhibited by 5 x 10(-4)m alpha-difluromethylarginine, but not by 5 x 10(-4)m alpha-difluromethylornithine. Apparently, arginine decarboxylase, not ornithine decarboxylase, mediates the ethylene-induced putrescine accumulation. The increased S-adenosylmethioinine decarboxylase activity, however, did not result in a significant spermidine/spermine accumulation. In ethylene-treated coleoptiles, the accumulation of putrescine paralleled the increase of coleoptile length in both sealed and aerobic conditions. alpha-difluromethylarginine inhibited ethylene induced putrescine accumulation and coleoptile elongation. It seems that putrescine biosynthesis might be involved in the ethylene-induced elongation of rice coleoptiles.

Journal Article↗
PubMed1991

Plant thioredoxin h: an animal-like thioredoxin occurring in multiple cell compartments.

Thioredoxin h has been purified to electrophoretic homogeneity from spinach roots using a procedure devised for leaves. The root thioredoxin (h2 form) differed from chloroplast and animal thioredoxins in showing an atypical active site (Cys-Ala-Pro-Cys) but otherwise resembled animal thioredoxin in structure. Sequence data for a total of 72 residues of spinach root thioredoxin h2 (about 69% of the primary structure) showed 43-44% identity with rabbit and rat thioredoxin. Analysis of cell fractions from the endosperm of germinating castor beans revealed that thioredoxin h occurs in the cytosol, endoplasmic reticulum, and mitochondria. The present findings demonstrate a similarity between plant thioredoxin h and animal thioredoxins in structure and intracellular location and raise the question of whether these proteins have similar functions.

Amino Acid Sequence↗
PubMed1991

Extended nucleotide sequence of the switch region of the murine gene encoding immunoglobulin E.

The nucleotide sequence of the switch region (S epsilon) of the gene encoding murine IgE was determined from a germline DNA clone. The sequence extends 1.7 kb 5' to the previously published S epsilon sequence. Another 33 repeat units were located by comparison to the S epsilon consensus sequence. Therefore, the complete S epsilon repetitive sequence consists of 53 repeat units contained in a region about 2.5 kb long.

Animals↗
PubMed1991

Interleukin-6 localisation in the synovial membrane in rheumatoid arthritis.

Polyclonal antibodies were raised in rabbits against Interleukin-6 (IL-6) by immunisation with a synthetic peptide of identical sequence to the amino terminal 12 amino acids of human IL-6. These antibodies reacted with recombinant IL-6 by ELISA and stained the cytoplasm of the IL-6 secreting bladder tumour cell line T24. Staining was abolished by prior incubation of the antibody with the IL-6 peptide. F(ab')2 fragments made by pepsin digestion of the IgG were immunopurified, labelled with biotin and retained activity in the biochemical and histological assays. Sections of synovial membrane from patients with rheumatoid arthritis (RA) were stained with these antibodies, using an immunoperoxidase technique, and cells containing IL-6 were domonstrated in the thickened synovial lining layer and also in a perivascular distribution in the deeper synovium. In osteoarthritis there were fewer cells in the lining layer and hence localisation appeared similar in both the interstitial area and lining layer. Double-staining techniques with mouse monoclonal antibodies against cell subset markers in five RA synovial membranes showed that up to 13% of T-cells and 19% of antibody-producing cells stained for IL-6. However, up to 70% of the macrophages contained IL-6 and these were found in close proximity to Ig-producing plasma cells. This study showed that macrophages were the major cells of the immune system in which IL-6 could be localised in RA, and suggests a role for locally produced IL-6 in the stimulation of rheumatoid factor production.

Amino Acids↗
PubMed1991

Calcium binding protein (calbindin-D28k) and glutamate decarboxylase gene expression after kindling induced seizures.

In order to determine whether calcium binding protein (calbindin-D28k or CaBP) and glutamate decarboxylase (GAD) may be involved in the process underlying the generation of seizure activity, changes in CaBP protein and mRNA and in GAD mRNA were examined in the kindling model of epilepsy. Following amygdaloid (AK) and commissure (CK) kindling significant decreases in the concentration of CaBP of 20% and 30%, respectively, were specifically observed in the hippocampal formation. However, using a cDNA specific to mammalian CaBP, Northern analysis of poly(A+) RNA and slot blot analysis of total RNA revealed no changes in the levels of CaBP mRNA in hippocampus, subcortical area (including amygdala, substantia nigra and striatum) or cerebellum of rats sacrificed 30 min, 1 h, 6 h or 24 h after the last kindled seizure. Similarly when these blots were reprobed with a cDNA specific to mammalian GAD, no changes in GAD gene expression were observed. However, fos gene expression was markedly enhanced at 1 h after seizure. We also tested whether changes in CaBP or GAD mRNA could be detected at any of the various stages of the kindling process. Slot blot analysis of cortex, subcortical structures and hippocampus revealed no changes in CaBP or GAD mRNA during the course of commissure kindling. In situ hybridization studies with GAD and CaBP 35S-labeled antisense probes also indicated no obvious changes upon visual analysis of autoradiographs. However, when silver grains were counted, significant changes in GAD mRNA in individual cells in hippocampus and substantia nigra were noted after kindling induced epilepsy. Our results indicate that, unlike fos gene expression, prominent alterations in GAD and CaBP mRNA in gross brain regions (as measured by slot blot and Northern blot analyses) are not observed in the kindling process. However, our in situ hybridization studies suggest that changes in GAD mRNA in individual cells may be involved in the process underlying kindling induced seizure activity.

Animals↗
PubMed1991

Evidence for calcium-reducing and excito-protective roles for the calcium-binding protein calbindin-D28k in cultured hippocampal neurons.

Neuronal systems for calcium homeostasis are crucial for neuronal development and function and may also contribute to selective neuronal vulnerability in adverse conditions such as exposure to excitatory amino acids or anoxia, and in neurodegenerative diseases. Previous work demonstrated the presence and differential distribution of calcium-binding proteins in the CNS. We now report that a subpopulation of neurons in dissociated cell cultures of embryonic rat hippocampus expresses calbindin-D28k (Mr 28,000 calcium-binding protein) immunoreactivity and that these neurons are relatively resistant to neurotoxicity induced by either glutamate or calcium ionophore. Direct comparisons of dynamic aspects of intracellular calcium levels and calbindin-D28k immunoreactivity in the same neurons revealed that calbindin-D28k-positive neurons were better able to reduce free intracellular calcium levels than calbindin-D28k-negative neurons. These findings indicate that the differential expression of calbindin-D28k in hippocampal neurons occurs early in development and may be one determinant of selective neuronal vulnerability to excitotoxic insults.

Animals↗
PubMed1991

Photosynthetic and photorespiratory characteristics of flaveria species.

The genus Flaveria shows evidence of evolution in the mechanism of photosynthesis as its 21 species include C(3), C(3)-C(4), C(4)-like, and C(4) plants. In this study, several physiological and biochemical parameters of photosynthesis and photorespiration were measured in 18 Flaveria species representing all the photosynthetic types. The 10 species classified as C(3)-C(4) intermediates showed an inverse continuum in level of photorespiration and development of the C(4) syndrome. This ranges from F. sonorensis with relatively high apparent photorespiration and lacking C(4) photosynthesis to F. Among the intermediates, the photosynthetic CO(2) compensation points at 30 degrees C and 1150 micromoles quanta per square meter per second varied from 9 to 29 microbars. The values for the three C(4)-like species varied from 3 to 6 microbars, similar to those measured for the C(4) species. The activities of the photorespiratory enzymes glycolate oxidase, hydroxypyruvate reductase, and serine hydroxymethyltransferase decreased progressively from C(3) to C(3)-C(4) to C(4)-like and C(4) species. On the other hand, most intermediates had higher levels of phosphenolpyruvate carboxylase and NADP-malic enzyme than C(3) species, but generally lower activities compared to C(4)-like and C(4) species. The levels of these C(4) enzymes are correlated with the degree of C(4) photosynthesis, based on the initial products of photosynthesis. Another indication of development of the C(4) syndrome in C(3)-C(4)Flaveria species was their intermediate chlorophyll a/b ratios. The chlorophyll a/b ratios of the various Flaveria species are highly correlated with the degree of C(4) photosynthesis suggesting that the photochemical machinery is progressively altered during evolution in order to meet the specific energy requirements for operating the C(4) pathway. In the progression from C(3) to C(4) species in Flaveria, the CO(2) compensation point decreased more rapidly than did the decrease in O(2) inhibition of photosynthesis or the increase in the degree of C(4) photosynthesis. These results suggest that the reduction in photorespiration during evolution occurred initially by refixation of photorespired CO(2) and prior to substantive reduction in O(2) inhibition and development of the C(4) syndrome. However, further reduction in O(2) inhibition in some intermediates and C(4)-like species is considered primarily due to the development of the C(4) syndrome. Thus, the evolution of C(3)-C(4) intermediate photosynthesis likely occurred in response to environmental conditions which limit the intercellular CO(2) concentration first via refixation of photorespired CO(2), followed by development of the C(4) syndrome.

Journal Article↗