Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 19 recordsLinked to original sources

PubMed2026

[Intestinal microbiota alterations after digestive tract reconstruction surgery and their impacts on host physiology].

The gut microbiota, acknowledged as the human body's 'second genome', plays a pivotal role in maintaining health. Digestive tract reconstruction surgery profoundly alters the anatomical structure and physiological environment of the gastrointestinal tract, thereby inducing significant shifts in the intestinal microbiota. These microbial changes subsequently influence host physiological functions through metabolic, immune, neuroendocrine, and other pathways. For instance, Roux-en-Y gastric bypass surgery enriches short-chain fatty acid(SCFA)-producing Bacteroides, improving systemic insulin sensitivity. Conversely, pancreaticoduodenectomy leads to a marked enrichment of potential pathobionts such as Klebsiella and Clostridium, which may elevate the risk of infections and tumor recurrence. This review comprehensively summarizes the characteristic changes in the gut microbiota following various digestive tract reconstruction procedures and discusses their multifaceted impacts on host physiology, aiming to provide insights for future experimental research and clinical practice.

Humans↗

PubMed1992

Influence of specific gamma-carboxyglutamic acid residues on the integrity of the calcium-dependent conformation of human protein C.

The concentration of Ca2+ that produced 50% of the saturable intrinsic fluorescence change (C50) of wild-type (wt) recombinant (r) human protein C (PC) was 0.40 mM. The C50 for Ca2+ increased < 2.5-fold for the following r-PC variants (Gla is gamma-carboxyglutamic acid): [Gla6-->Asp]r-PC, [Gla7-->Asp]r-PC, [Gla14-->Asp]r-PC, [Gla19-->Asp]r-PC, or [Gla25-->Asp]r-PC, and approximately 4-6-fold for [Gla20-->Asp]r-PC and [Gla29-->Asp]r-PC. Much more dramatic increases in the C50 for Ca2+ were observed for [Gla16-->Asp]r-PC (> 75-fold) and [Gla26-->Asp]r-PC (ca. 30-fold). A substantially larger maximum fluorescence change (> 3-fold) as compared to that for wtr-PC, was also found in the case of the Ca2+/[Gla16-->Asp]r-PC complex, suggesting that the final Ca(2+)-induced conformation for this variant is dissimilar to that for wtr-PC and the above mutants. When a mutation was constructed at Arg15 ([Arg15-->Leu]r-PC), a residue conserved in all Gla-containing coagulation proteins, no fluorescence alteration occurred upon addition of Ca2+. The C50 for Ca2+ for promotion of the binding of the Ca(2+)-dependent, Gla-domain-directed, conformational monoclonal antibodies, JTC-1 and JTC-3, to wtr-PC was 3.0 and 4.0 mM, respectively. A similar C50 value was found for [Gla25-->Asp]r-PC. In the case of each antibody, approximately 4-6-fold higher C50 values for Ca2+ were found for the mutants; [Gla14-->Asp]r-PC, [Gla19-->Asp]r-PC, and [Gla29-->Asp]r-PC. Ca2+ did not promote binding of either of these antibodies to the following variants; [Gla6-->Asp]r-PC, [Gla7-->Asp] r-PC, [Arg15-->Leu]r-PC, [Gla16-->Asp]r-PC, [Gla20-->Asp]r-PC, and [Gla26-->Asp]r-PC. The results of this study suggest that adoption of the Ca(2+)-dependent conformation of PC is greatly dependent upon the presence of specific essential Gla residues, particularly those, namely Gla16 and Gla26, shown in the crystal structure of the prothrombin Gla domain/Ca2+ complex to be involved with coordination of Ca2+ ions not exposed to the surface. Of similar importance is Arg15. On the other hand, Gla residues at positions 14 and 19 are much less important in directing this same conformation. This finding is readily reconciled with the above crystal structure, which shows that these latter 2 residues are mainly responsible for coordination of a surface-exposed Ca2+ that is present at the end of the Ca(2+)-ion channel.

1-Carboxyglutamic Acid↗

PubMed1992

Characterization of a Ca2+ binding and regulatory site in the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum.

A region in the skeletal muscle ryanodine receptor between amino acids 4014 and 4765 was expressed as a trpE fusion protein. Overlay studies revealed that this region bound Ca2+ and ruthenium red, an indicator of Ca(2+)-binding sites. Ca2+ binding was mapped to subregion 13b between amino acids 4246 and 4377, encompassing a predicted high affinity Ca(2+)-binding site, and to subregion 13c between amino acids 4364 and 4529, encompassing two predicted high affinity Ca(2+)-binding sites. Ca2+ binding was then mapped to three shorter sequences, 22(13b1), 36(13c1), and 35(13c2), amino acids long, each encompassing one of the three predicted Ca(2+)-binding sites. Site-directed polyclonal antibodies were raised against these three short sequences and purified on antigen affinity columns. The antibody against sequence 13c2, lying between residues 4478 and 4512, specifically recognized both denatured and native forms of the ryanodine receptor, suggesting that at least part of the 35 amino acid sequence containing the Ca(2+)-binding site is surface-exposed. The affinity purified antibody increased the Ca2+ sensitivity of ryanodine receptor channels incorporated into planar lipid bilayers, resulting in increased open probability and opening time without altering channel conductance. The antibody-activated channel was still modulated by Ca2+, Mg2+, ATP, ryanodine, and ruthenium red. These observations suggest that sequence 13c2 may be involved in Ca(2+)-induced Ca2+ release.

Animals↗

PubMed1992

Copper-mediated regulation of cytochrome c553 and plastocyanin in the cyanobacterium Synechocystis 6803.

In certain cyanobacteria and algae, cytochrome c553 or plastocyanin can serve to carry electrons from the cytochrome bf complex to photosystem I. The availability of copper in the growth medium regulates which protein is present. To investigate copper induced control of gene expression we isolated these proteins from the cyanobacterium Synechocystis 6803. Using immunodetection and optical spectroscopy, the steady state levels of cytochrome c553 and plastocyanin were measured in cells grown at different copper concentrations. The results show that in cells grown in 20-30 nM copper, cytochrome c553 was present, whereas plastocyanin was not detected. The opposite behavior was observed in cells grown in the presence of 1 microM copper; plastocyanin was present, whereas cytochrome c553 could not be detected. Both proteins were present in cells grown in 0.3 microM copper. Northern analysis of total RNA, probed with a gene fragment for cytochrome c553 or the plastocyanin gene, showed that cells grown in the presence of 20-30 nM copper have message for cytochrome c553, but not for plastocyanin, whereas cells grown in 1 microM copper have message for plastocyanin, but not for cytochrome c553. These results demonstrate that copper regulates expression of both of the genes encoding cytochrome c553 and plastocyanin prior to translation in Synechocystis 6803.

Copper↗

PubMed1992

Induction by bufalin of differentiation of human leukemia cells HL60, U937, and ML1 toward macrophage/monocyte-like cells and its potent synergistic effect on the differentiation of human leukemia cells in combination with other inducers.

We have recently demonstrated that bufalin is a new potent inducer of the differentiation of human myeloid leukemia cells. The present work was carried out to examine further the effect of bufalin on the growth and characteristics of human leukemia-derived cell lines U937, ML1, and HL60. At concentrations of 5-10 nM, bufalin decreased the growth of ML1 cells preferentially at the G2 phase and U937 cells at the S and G2 phases of the cell cycle. Bufalin, under these conditions, induced the differentiation of U937, ML1, and HL60 cells to monocyte/macrophage-like cells by measuring the expression of various differentiation markers, as assessed by morphology and histochemistry, and ability to phagocytose latex particles, to reduce nitroblue tetrazolium, and to develop Fc receptors. U937 and ML1 cells started to differentiate at 4 and 6 h, respectively, after treatment with 10 nM bufalin and showed maximum differentiation 72 h later. At present, a mechanism for the bufalin-mediated induction of the differentiation of these human leukemia cells remains to be determined. The combination of bufalin with all-trans retinoic acid, 1 alpha,25-dihydroxyvitamin D3, 4'-demethylepipodophyllotoxin ethylidene-beta-D-glucoside (VP16), or human gamma-interferon synergistically induced the differentiation of HL60 and U937 cells. A similar effect on ML1 cells was observed with the combination of bufalin with VP16 or human rTNF-alpha. These results suggest that bufalin in combination with VP16, all-trans retinoic acid, 1 alpha,25-dihydroxyvitamin D3, rTNF-alpha, or gamma-interferon may be very useful in the differentiation of human leukemia.

Antineoplastic Agents↗

PubMed1992

Cigarette smoking and other risk factors for progression of precancerous stomach lesions.

BACKGROUND: Stomach cancer is generally thought to evolve through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. PURPOSE: Our purpose was to assess risk factors for intestinal metaplasia and gastric dysplasia arising from chronic atrophic gastritis in a general population at high risk for stomach cancer. METHODS: A population-based gastroscopic screening of more than 3000 residents was conducted in a county in China with one of the world's highest rates of stomach cancer. Information on the lifestyle and other characteristics of the participants was obtained by interview, and responses were compared between those in whom the most advanced gastric lesion was dysplasia or intestinal metaplasia versus those with chronic atrophic gastritis. RESULTS: Cigarette smoking was found to nearly double the risk of transition to dysplasia and to be a mild risk factor for intestinal metaplasia. Smoking accounted almost entirely for the 55% higher prevalence of dysplasia among men than among women. Risk of transition to dysplasia had a weak association with several dietary factors and was increased among those participants with a family history of stomach cancer and with blood type A. CONCLUSIONS: The findings provide strong evidence for a role of tobacco consumption and offer clues to other environmental and genetic factors involved in the process of gastric carcinogenesis.

Adult↗

PubMed1992

Role of individual gamma-carboxyglutamic acid residues of activated human protein C in defining its in vitro anticoagulant activity.

To evaluate the contributions of individual gamma-carboxyglutamic acid (gla) residues to the overall Ca(2+)-dependent anticoagulant activity of activated human protein C (APC), we used recombinant (r) DNA technology to generate protein C (PC) variants in which each of the gla precursor glutamic acid (E) residues (positions 6, 7, 14, 16, 19, 20, 25, 26, and 29) was separately altered to aspartic acid (D). In one case, a gla26V mutation ([gla26V]r-PC) was constructed because a patient with this particular substitution in coagulation factor IX had been previously identified. Two additional r-PC mutants were generated, viz, an r-PC variant containing a substitution at arginine (R) 15 ([R15]r-PC), because this particular R residue is conserved in all gla-containing blood coagulation proteins, as well as a variant r-PC with substitution of an E at position 32 ([F31L, Q32E]r-PC), because gla residues are found in other proteins at this sequence location. This latter protein did undergo gamma-carboxylation at the newly inserted E32 position. For each of the 11 recombinant variants, a subpopulation of PC molecules that were gamma-carboxylated at all nonmutated gla-precursor E residues has been purified by anion exchange chromatography and, where necessary, affinity chromatography on an antihuman PC column. The r-PC muteins were converted to their respective r-APC forms and assayed for their amidolytic activities and Ca(2+)-dependent anticoagulant properties. While no significant differences were found between wild-type (wt) r-APC and r-APC mutants in the amidolytic assays, lack of a single gla residue at any of the following locations, viz, 7, 16, 20, or 26, led to virtual complete disappearance of the Ca(2+)-dependent anticoagulant activity of the relevant r-APC mutant, as compared with its wt counterpart. On the other hand, single eliminations of any of the gla residues located at positions 6, 14, or 19 of r-APC resulted in variant recombinant molecules with substantial anticoagulant activity (80% to 92%), relative to wtr-APC. Mutation of gla residues at positions 25 and 29 resulted in r-APC variants with significant but low (24% and 9% of wtr-APC, respectively) levels of anticoagulant activity. The variant, [R15L]r-APC, possessed only 19% of the anticoagulant activity of wrt-APC, while inclusion of gla at position 32 in the variant, [F31L, Q32gla]r-APC, resulted in a recombinant enzyme with an anticoagulant activity equivalent to that of wtr-APC.

1-Carboxyglutamic Acid↗

PubMed1992

Effect of glycolipids on the phase behavior and dynamic properties of phospholipid liposomes.

The glycolipids of Acholeplasma laidlawii AIH089 membranes were identified and purified. The effect of monoglucosyldiacylglycerol (MGDG) and diglucosyldiacylglycerol (DGDG) on the thermotropic behavior of multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG) has been investigated by high sensitivity differential scanning calorimetry. The main transition peaks were broadened, the enthalpies were decreased. DGDG caused the decrease in the transition temperatures of DPPC, DPPG liposomes by 3.08 degrees C, 4.18 degrees C, respectively. MGDG did not cause the alteration of the transition temperature of DPPC liposomes but caused the decrease of the transition temperatures of DPPG liposomes by 2.20 degrees C. ESR experiments indicate that MGDG decreased the rotational correlation time of DPPC and DPPG liposomes.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1992

Elevated expression of monocyte chemoattractant protein 1 by vascular smooth muscle cells in hypercholesterolemic primates.

Atherosclerosis is marked by an overt inflammatory infiltrate, with enhanced recruitment of monocytes/macrophages observed in both human and experimental atherosclerosis. We previously determined that monocyte chemoattractant protein 1 (MCP-1) accounts for virtually all of the chemotactic activity produced by vascular (aortic) smooth muscle cells in culture. We now report that arteries from a primate model of atherosclerosis with dietary-induced hypercholesterolemia exhibit increased levels of MCP-1 mRNA expression in vivo, whereas their normal counterparts demonstrate minimal MCP-1 expression. Furthermore, immunohistochemistry and in situ hybridization clearly indicate that the expression of MCP-1 protein and mRNA is in the smooth muscle cells of the medial layer of the artery and in monocyte-like and smooth muscle-like cells found in the overlying intimal lesion. These studies indicate that one of the responses to dietary hypercholesterolemia is the expression of MCP-1 by vascular smooth muscle cells. This expression, when augmented with other cellular and molecular factors, could significantly contribute to the recruitment of monocytes/macrophages to the vessel wall.

Animals↗

PubMed1992

Development of glutathione S-transferase placental form (GST-P) stained foci during hamster buccal pouch mucosa carcinogenesis.

The expression of the placental form of glutathione S-transferase (GST-P) using anti-rat liver GST-P antibody was investigated in hamster buccal pouch mucosa (HBPM) treated with 0.5% dimethylbenz[a]anthracene (DMBA) biweekly for 12 weeks. This preliminary study showed that the anti-rat liver GST-P antibody is applicable to the HBPM model and that DMBA treatment induced GST-P positive foci. These foci are randomly distributed and frequently involved the hyperplastic and dysplastic segments of the epithelium, as well as squamous cell carcinoma. Further study is needed to explore the kinetics of these GST-P positive foci.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Whole genome amplification from a single cell: implications for genetic analysis.

We have developed an in vitro method for amplifying a large fraction of the DNA sequences present in a single haploid cell by repeated primer extensions using a mixture of 15-base random oligonucleotides. We studied 12 genetic loci and estimate that the probability of amplifying any sequence in the genome to a minimum of 30 copies is not less than 0.78 (95% confidence). Whole genome amplification beginning with a single cell, or other samples with very small amounts of DNA, has significant implications for multipoint mapping by sperm or oocyte typing and possibly for genetic disease diagnosis, forensics, and the analysis of ancient DNA samples.

Base Sequence↗

PubMed1992

The gene and cDNA for the human high affinity immunoglobulin E receptor beta chain and expression of the complete human receptor.

The high affinity IgE receptor (Fc epsilon RI) is a tetrameric hetero-oligomer composed of an alpha chain, a beta chain, and two disulfide-linked gamma chains. The beta chain contains four transmembrane (TM) segments and long cytoplasmic domains that are thought to play an important role in intracellular signaling. We now report the structural characterization and the sequence of the complete human beta gene and cDNA. The gene spans approximately 10 kilobases and contains seven exons. There is a single transcription initiation site preceded by a TATA box. The first exon codes for the 5'-untranslated region and a portion of the N-terminal cytoplasmic tail. TM-1 is encoded in exons 2 and 3, TM-2 in exons 3 and 4, TM-3 in exon 5, and TM-4 in exon 6. The seventh and final exon encodes the end of the C-terminal cytoplasmic tail and the 3'-untranslated sequence. The human beta gene appears to be a single copy gene. Two corresponding transcripts, detected as a doublet around 3.9 kilobases, are present in cells of mast cell and basophil lineage from different individuals, but not in the other hematopoietic cells tested here. The human beta protein is homologous to rodent beta. The consensus amino acid sequences of human, mouse, and rat beta show 69% identical residues. Analysis of the surface expression of transfected receptors indicates that human alpha gamma and alpha beta gamma complexes are expressed with comparable efficiency. Human beta interacts with human alpha more efficiently than does rat beta, and both rat and mouse beta interact with their corresponding alpha more efficiently than does human beta, demonstrating a species specificity of the alpha/beta interaction.

Amino Acid Sequence↗

PubMed1992

Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge.

To investigate the role of CD8+ T lymphocytes in recovery from influenza pneumonia, we used transgenic mice either homozygous (-/-) or heterozygous (+/-) for beta 2-microglobulin (beta 2-M) gene disruption. These mice lack major histocompatibility complex-restricted class I (CD8+) T cells. We found that after challenge with a nonlethal influenza virus, the beta 2-M (-/-) mice had significantly delayed pulmonary viral clearance. Furthermore, after challenge with a more virulent influenza virus, the beta 2-M (-/-) mice had a significantly higher mortality rate than did control mice. Thus, CD8+ T cells are important in recovery from virulent influenza infections, but other host defense mechanisms can clear the respiratory tract of more benign infections.

Animals↗

PubMed1992

Prefabrication of free flaps using the omentum in rats.

The omentum used as a vascular carrier is a new experimental model for prefabrication of free flaps in the rat. A 2.5 x 4 cm patch of omentum with gastroepiploic vessels and its rich vascular arcades was transferred under a bipedicled 2.5 x 6 cm right abdominal panniculocutaneous flap. At subsequent time intervals (postoperative days 0, 3, 5, 7, and 14), the skin pedicles were divided and the skin flap was raised as a composite island flap vascularized only by the underlying omental patch. The composite flap was then sutured back in place. Prefabricated flaps examined postoperatively demonstrated a dye fluorescence index (DFI) of 4.60% +/- 2.82% and 1.67% +/- 4.08% flap survival (FS) in the day 0 group; in the day 3 group, 9.83% +/- 1.47% of DFI and 15.00% +/- 10.35% of FS; in the day 5 group, 28.39% +/- 5.25% of DFI and 86.0% +/- 12.74% of FS (P less than 0.05); in the day 7 group, 38.19% +/- 7.52% of DFI and 98.13% +/- 3.72% of FS (P less than 0.05); and, in the day 14 group, 49.55% +/- 6.70% of DFI and 100% of FS (P less than 0.05). India-ink injection and histologic examination confirmed revascularization of the overlying skin by day 5.

Animals↗

PubMed1992

Immunocytochemical staining with antibodies against protein kinase C and its isozymes in the turtle retina.

An LM immunocytochemical study has investigated the patterns of staining in turtle retina with monoclonal antibodies to the alpha, beta and gamma isozymes of protein kinase C. The protein kinase C-gamma antibody reveals cells in the ganglion cell layer, occasional amacrine cells and faint banding in strata 2 and 4 of the inner plexiform layer. The protein kinase C-beta antibody stains primarily amacrine cells that have dendrites running in strata 2, in 4 close to the 3/4 border and on the 4/5 border of the inner plexiform layer. Protein kinase C-alpha immunoreactivity is seen in a population of bipolar cells. The latter are characterized by stained axon terminals in strata 3 and 4 of the inner plexiform layer. A type of amacrine cell, different from those seen with the other antibodies, is also immunoreactive to protein kinase C-alpha. EM immunocytochemistry (using a polyclonal antibody) reveals protein kinase C immunoreactivity in photoreceptor cells, bipolar cells, amacrine cells and ganglion cells. In photoreceptors protein kinase C immunoreactivity occurs as patchy staining associated with vesicles and the plasmalemma in pedicles and telodendria. Some varieties of bipolar cell display protein kinase C reaction product throughout the entire cell. Their dendrites contact photoreceptor pedicles at wide-cleft basal junctions and ribbon and non-ribbon related narrow cleft junctions. A few lateral elements per cone or rod pedicle are always protein kinase C-immunoreactive. Amacrine and ganglion cells typically show small clumps of protein kinase C immunoreactivity around vesicles and close to the postsynaptic membranes. Synaptic boutons of some varieties of amacrine cell stain more uniformly. Protein kinase C-immunoreactive bipolar cells are most commonly presynaptic in stratum 4 of the inner plexiform layer, while protein kinase C-immunoreactive amacrine cells are both pre- and postsynaptic throughout strata 1, 2, 3 and 4. Stratum 5 appears to be almost devoid of protein kinase C-immunoreactive neural profiles.

Animals↗

PubMed1992

[Histochemical study of estrogen and progesterone receptors in cervical carcinoma].

Estrogen and progesterone receptors were determined in 56 cases of primary cervical carcinoma tissue by histochemical methods. 42.86% of the 56 cases were ER positive and 46.43% PR positive. No correlation was found between ER and PR status and age, menopausal status of the patient and clinical stage. Adenocarcinoma had significantly higher ER and PR positive rate than squamous carcinoma. Highly differentiated carcinoma had higher ER and PR positive rate than middle- and dedifferentiated carcinoma. A positive correlation between ER and PR and cellular infiltration of stroma and peritumoral reaction of fibrin was found. The patients with ER and PR positive had a significantly higher 5-year survival. ER and PR may be used as prognostic factors in cervical carcinoma.

Adenocarcinoma↗

PubMed1992

The structure-activity relationship of skin carcinogenicity of aromatic hydrocarbons and heterocycles.

From a study of 239 aromatic and heteroaromatic compounds causing skin cancer in mice, a quantitative structure-activity relationship has been derived. Carcinogenicity depends heavily on the relative hydrophobicity of the chemicals as defined by octanol/water partition coefficients (log P). It is also correlated with the energy of the highest occupied molecular orbital and the presence of substituents on the L and K regions of the carcinogen. The results are discussed in terms of the bay region concept for carcinogenic activity.

Animals↗

PubMed1992

Expression of the polymeric immunoglobulin receptor by cultured aged rat hepatocytes.

The Fischer rat shows an age-related loss of both hepatic blood to bile transport and secretory component-specific binding sites for polymeric immunoglobulin (Ig) A. This age-related loss of hepatic IgA receptor function is also shown by cultured hepatocytes. It is reported here that compared with young cells, binding and uptake of 125I-polymeric IgA by cultured hepatocytes was markedly reduced in cells from senescent animals. In addition, cells from old animals showed markedly diminished secretion of secretory component determined by enzyme-linked immunosorbent assay and expression of polymeric immunoglobulin receptor determined by incorporation of 35S-labeled amino acid and fluorography. It is suggested that the age-related decrease in IgA receptor-mediated transport from serum to bile results, at least in part, from decreased expression and secretion of total hepatic secretory component.

Aging↗