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Biomedical subjects

H Zhu

Publications and source records attributed to H Zhu.

At least 397 records · Page 22Linked to original sources

[Change of serum lipid, apolipoprotein during cholesterol gallstone formation in rabbit model].

In order to study the formation of cholesterol gallstone through rabbit model which was induced by high cholesterol diet (HCD), we investigated the rabbits' serum lipoprotein cholesterols and apolipoprotein (apo) at 1 week (1w), 2 weeks (2w), 3 weeks (3w) and 4 weeks (4w) in comparison with those of a control group respectively. The results were as follows: (1) of 10 rabbits subjected to experiment, 4, 6, and 7 rabbits were found to have induced-cholesterol gallstones in the 2w, 3w and 4w groups respectively. (2) The serum concentrations of total cholesterol (TC), triglyceride (TG), phospholipid (PL), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein chloesterol (VLDL) increased significantly (1w, 2w, 3w and 4w groups vs control group, P < 0.05), especially in the 3w and 4w groups; the surum concentrations of high density lipoprotein cholesterol and its subfractions (HDL-C, HDL2-C, HDL3-C) decreased slightly (vs control group, P > 0.05). (3) The serum contents of apoB100, apoC II and apoC III increased significantly (vs control group, P < 0.05), especially in the 3w and 4w groups; the serum apoA I reduced gradually in 1w, 2w and 3w groups, and decreased greatly in 4w group (vs control group, P < 0.05). The results demonstrated that owing to the intake of high cholestrol diet with the passage of time, the increased concentrations of serum VLDL-C, apoB, apoC II and apoC III possibly caused an enhanced secretion of biliary cholesterol into bile; that the decreased serum apoA I level might reduce the secretion of anti-nucleating factor into bile. All of these factors and changes may play important roles during the formation of cholesterol gallstones.

Animals↗

[The expression of mutant p53 (mp53) protein in rat hepatic preneoplastic lesions induced by diethylnitrosamine (DEN)].

OBJECTIVE: To study p53 genes related to hepatocarcinogenesis. METHODS: Using immunohistochemistry techniques, the relation between expression of mp53 protein, placental glutathione S-transferase (GST-P) and the cell proliferative activity was investigated in rat hepatic preneoplastic lesions induced by DEN and the control liver. RESULTS: Two of five rats with hepatic prenoplastic lesions had mp53 protein expression which was seen only in a portion of large-sized hyperplastic nodules (HN) or GST-P positive foci at 5th week. The bromodeoxyuridine labeling indeX (BrdU-LI) in p53-positive HN or GST-P foci was significantly higher than that of p53-negative HN or GST-P-negative foci respectively (P < 0.05). CONCLUSIONS: Mutation of p53 gene occurs in the early stage of hepatocarcinogenesis, and is responsible for the hepatocellular proliferations and hepatocarcinogenesis, and might become an additional tumor marker.

Animals↗

Chinese dietary composition and intakes of elements and radionuclides by ingestion.

As update and complement of Chinese Total Diet Study in 1990, a renewing study was conducted during 1992-1993 according to regulated procedure. Contents of 32 elements, including 19 newly determined, in 12 categories of food from 12 provinces were analyzed by NAA or AAS technique and the daily intakes of Chinese adult man were estimated and hygienically evaluated. Meanwhile, a typical survey on dietary composition and intake for difference among 4 age groups and between Spring and Autumn was surveyed too. The results provide important basis for decision for further improvement of Chinese diet from hygienic view point and compilation of physiological characteristics of Chinese Reference Man. At the end of this article, the estimated nationwide average intakes for adult man are compared with those for current ICRP Reference Man.

Adolescent↗

[Clinical study on reversal of multidrug resistance in refractory and relapsed acute leukemias by cyclosporin A].

OBJECTIVE: To explore the clinical implication of reversal of multidrug resistance (MDR) by cyclosporin A (CsA) in refractory and relapsed acute leukemias. METHODS: The expression of p170 was assayed by immunocytochemical method (Avidin-Biotin Complex, ABC) using a monoclonal antibody JSB-1 against P-170. The P-170 positive cases were randomly divided into two groups:trial group (with CsA as revertant) and control group (without CsA), and the blood concentration of CsA was detected by HPLC. RESULTS: The complete remission rates were 53% and 20% in trial and control group, respectively (P<0.05), and the reversing effect was positively correlated with blood concentration of CsA. CONCLUSION: CsA might be a safe and effective revertant, and can be applied in the treatment of refractory and relapsed acute leukemia.

ATP Binding Cassette Transporter, Subfamily B↗

Potential and limitations of radioimmunodetection and radioimmunotherapy with monoclonal antibodies.

UNLABELLED: Recently, we developed a physiologically based pharmacokinetic model capable of predicting antibody biodistribution in humans by scaling up from mice. By applying this model to anticarcinoembryonic antigen murine antibody ZCE025, we address several critical issues in radioimmunodetection and radioimmunotherapy, including the optimal antibody doses, the desirable antibody form for cancer detection, the optimal combinations of antibody forms and radionuclides for cancer treatment and the effectiveness of the modality. METHODS: Under the baseline conditions of a standard 70-kg man with a 20-g tumor embedded in the liver, the model was used to: (a) estimate absorbed doses in tumor and normal tissues, (b) determine dose-dependent antibody uptake in the tumor, (c) simulate tumor-to-background antibody concentration ratio and (d) calculate therapeutic ratios for different antibody forms and radionuclides. Sensitivity analysis further enabled us to determine antibody delivery barriers and to assess the modality under average and favorable tumor physiological conditions. RESULTS: By using ZCE025 under the baseline conditions, the model found that Fab was the most suitable form for cancer diagnosis, while 131l combined with F(ab')2 provided the highest tumor-to-bone marrow therapeutic ratio for cancer treatment. Sensitivity analysis showed that antibody permeability was the major barrier for antibody accretion in tumors. It also demonstrated that normal tissue antigen expression at a level lower than in the tumor had little effect on the therapeutic ratio. CONCLUSION: The model demonstrates that: (a) for radioimmunodetection, the most effective antibody form (Fab for ZCE025) was the lower mol weight form, yet not sensitive enough for hepatic metastasis detection; and (b) for radioimmunotherapy, a relatively fast-clearing antibody form (F(ab')2 for ZCE025) in combination with long half-life beta(-)-emitters was optimal, yet inadequate as the sole therapeutic modality for solid tumors.

Animals↗

Effect of different diets on oral bacteria and caries activity in Sprague-Dawley rats.

The conventional rat model of dental caries has been used extensively to measure the contribution of various inoculated bacteria or diets to dental caries production. Only limited information is available on the effect of different diets on the oral bacterial community as a whole. In the present study, using selective and non-selective media, the oral bacterial populations of 21-day-old Sprague-Dawley rats fed diets with commercial rat and mouse cubes (control), high-starch (56%) and sucrose (56%) diets for 21 days were investigated. The high-starch diet did not significantly change the proportion of oral bacteria compared with the control group; the high-sucrose diet significantly enhanced the total cultivable bacteria, particularly Actinomyces naeslundii, Streptococcus rattus and Streptococcus suis-like bacteria. The order of diets with respect to the production of dental caries was sucrose > starch > normal. Thus the high-sucrose diet changed the oral bacterial population of Sprague-Dawley rats and these changes were reflected in the increased level of dental caries.

Actinomyces↗

[Ultrastructural study of tumor infiltrating lymphocyte in tissues of laryngeal squamous cell carcinoma].

By transmission electron microscopy tumor infiltrating lymphocyte (TIL) in laryngeal squamous cell carcinoma tissues of 14 cases was studied. The results showed that the infiltrating lymphocyte in varying degrees eristed in laryngeal squamous cell carcinoma tissues. Most of them were present in a motionless state, and the others showed the feature of activated metrocyte and closely contracted with cancer cells and resulted in distinct morphological changes both the cancer cells and themselves. Therefore, this study provided an important morphological evidence for TIL as killer and inhibiter to the growth of cancer cells.

Carcinoma, Squamous Cell↗

[Studies of malignant transformation of human fetal lung cells induced by organic extract from tap water].

Expression of P53 protein was determined in the process and the end of induction of malignant transformation in human fetal lung cells, with organic extract from tap water in a river of City G, to study its molecular mechanism. Results showed that the water sample of experimental doses could induce formation of cell malignant transformation foci to different extent and had certain toxicity to cells. High expression of P53 protein was observed in cell nuclei 15 days after exposure and before formation of cell transformation foci, or 30 days after exposure and formation of them. It suggests that changes of P53 protein may relate to cell malignant transformation to certain extent, and play some roles in the process of it.

Cell Transformation, Neoplastic↗

[Polymorphism and pologenetic affinities of genotype in pathogenic yeast].

The classification of pathogenic yeast, which is one of the most common reasons of opportunistic infection in human body, will be useful for the epidemiological survey and clinical works. The genotypic polymorphism of intergenus, interspecies and intraspecies in 48 isolates, including Candida, Cryptococcus, Torulopsis, Trichosporon, Saccaromyces had been administered carefully with patterns amplified by RAPD (Randomly amplified polymorphic DNA) in 53 primers. The pologenetic affinities had been evaluated by similarity coefficients obtained from these profiles. The results indicated that there are significant difference among intergenus, interspecies and intraspecies in Candida and related yeast. The similarity coefficients among Candida and Crytococcus, Trichosporon were maintained about 80%. The similarity coefficients among interspecies of Candida ranged from 82%-87%, and ones of intraspecies of different Candida species were more than 90%. The genotypic typing of species except C. guilliermondii seems to be related to morphological classification.

Candida↗

Specific cleavage of alpha-fodrin during Fas- and tumor necrosis factor-induced apoptosis is mediated by an interleukin-1beta-converting enzyme/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease.

Interleukin-1beta-converting enzyme (ICE)/Ced-3 proteases play a critical role in apoptosis. One well characterized substrate of these proteases is the DNA repair enzyme poly(ADP-ribose) polymerase. We report here that alpha-fodrin, an abundant membrane-associated cytoskeletal protein, is cleaved rapidly and specifically during Fas- and tumor necrosis factor-induced apoptosis; this cleavage is mediated by an ICE/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease. Studies in cells treated with these apoptotic stimuli reveal that both fodrin and poly(ADP-ribose) polymerase proteolysis are inhibited by acetyl-Tyr-Val-Ala-Asp chloromethyl ketone and CrmA, specific inhibitors of ICE/Ced-3 proteases. However, fodrin proteolysis can be distinguished from poly(ADP-ribose) polymerase proteolysis by its relative insensitivity to acetyl-Asp-Glu-Val-Asp aldehyde (DEVD-CHO), a selective inhibitor of a subset of ICE/Ced-3 proteases that includes CPP32. DEVD-CHO protects cells from Fas-induced apoptosis but does not prevent fodrin proteolysis, indicating that cleavage of this protein can be uncoupled from apoptotic cell death. Moreover, purified fodrin is cleaved in vitro by CPP32 (but not by ICE) into fragments of the same size observed in vivo during apoptosis. These findings suggest that fodrin proteolysis in vivo may reflect the activity of multiple ICE/Ced-3 proteases whose partial sensitivity to DEVD-CHO reflects a limited contribution from CPP32, or an ICE/Ced-3 protease less sensitive than CPP32 to DEVD-CHO inhibition.

Apoptosis↗

Stoichiometry of subunits and heme content of hemoglobin from the earthworm Lumbricus terrestris.

The extracellular hemoglobin (Hb) of the earthworm, Lumbricus terrestris, has four major O2-binding chains, a, b, c (forming a disulfide-linked trimer), and d ("monomer"). Additional structural chains, "linkers," are required for the assembly of the approximately 200-polypeptide molecule. The proportion of linker chains had been reported to be one-third of the total mass on the basis of densitometry of Coomassie Blue-stained SDS-gels. Reverse-phase high performance liquid chromatography (HPLC), however, gave 16.3% linkers on the basis of both 220-nm absorbance and amino acid analysis (Ownby, D. W., Zhu, H., Schneider, K., Beavis, R. C., Chait, B. C., and Riggs, A. F. (1993) J. Biol. Chem. 268, 13539-13547). The subunit proportions have now been redetermined by SDS capillary electrophoresis as a test of the HPLC results. The electrophoresis, monitored at 214 nm, avoided the use of Coomassie Blue and provided results identical with those obtained by HPLC. Capillary electrophoresis monitored at both 214 and 415 nm was used to show that linker chains do not bind heme. Heme content has been found to be 2.9% by determination of hemin, amino acid analysis and dry weight. Measurement of the rate of hemin loss from oxidized L. terrestris Hb shows that high rates of loss can account for values of heme content significantly below 2.9% (or 0.26% iron).

Animals↗

Assembly of the gigantic hemoglobin of the earthworm Lumbricus terrestris. Roles of subunit equilibria, non-globin linker chains, and valence of the heme iron.

The extracellular hemoglobin of the earthworm Lumbricus terrestris has four major kinds of O2-binding chains: a, b, and c (forming a disulfide-linked trimer), and chain d. Non-heme, non-globin structural chains, "linkers," are also present. Light-scattering techniques have been used to show that the ferrous CO-saturated abc trimer and chain d form an (abcd)4 complex of 285 kDa at neutral pH. Formation of the full-sized 4-MDa molecule requires the addition of linker chains in the proportion of two linkers per (abcd)4 and occurs much more rapidly in the presence of 10 mM calcium. This stoichiometry is supported not only by direct quantitative analysis of the intact hemoglobin but also by the fact that the addition of 50% of the proposed stoichiometric quantity of linkers results in the conversion of 50% of the (abcd)4 to full-sized molecules. Isolated CO-saturated abc trimers self-associate to (abc)2 and higher aggregates up to an apparent limit of (abc)10 approximately 550 kDa. The CO-saturated chain d forms dimers, (d)2, and tetramers, (d)4. Oxidation of the (abcd)4 complex with ferricyanide causes complete dissociation of chain d from the abc trimer, but addition of CN- maintains the (abcd)4 complex. Valence hybrids have also been studied. The ferrous CO-saturated abc trimer and met (ferric) chain d also associate to form (abcd)4, but the met abc trimer and ferrous CO-saturated chain d do not. Oxidation of the abc trimer and chain d to the ferric form causes the formation of a characteristic hemichrome spectrum with a maximum at 565 nm and a shoulder near 530 nm. These results show that interactions between the abc trimer and chain d are strongly dependent on the ligand and valence state of the heme iron. Light-scattering measurements reveal that oxidation of the intact Hb produces a significant drop in molecular mass from 4.1 to 3.6 MDa. Inclusion of CN- prevents this drop. These experiments indicate that oxidation causes the Hb to shed subunits. The observations provide an explanation for the wide variations in the molecular mass of L. terrestris Hb that have been observed previously.

Alcohol Dehydrogenase↗

Identification and characterization of Ich-3, a member of the interleukin-1beta converting enzyme (ICE)/Ced-3 family and an upstream regulator of ICE.

We report here the isolation and characterization of a new member of the ice/ced-3 family of cell death genes, named ich-3. The predicted amino acid sequence of Ich-3 protein shares 54% identity with murine interleukin-1beta converting enzyme (ICE). Overexpression of ich-3 in Rat-1 and HeLa cells induces apoptosis, which can be inhibited by CrmA and Bcl-2. The mRNA and proteins of ich-3 are dramatically induced in vivo upon stimulation with lipopolysaccharide, an inducer of septic shock. The ich-3 gene product can be cleaved by cytotoxic T cells granule serine protease granzyme B, suggesting that Ich-3 may mediate apoptosis induced by granzyme B. Ich-3 does not process proIL-1beta directly but does promote proIL-1beta processing by ICE. These results suggest that Ich-3 may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE.

Amino Acid Sequence↗