Biomedical subjects

M Yin

Publications and source records attributed to M Yin.

At least 55 records · Page 3Linked to original sources

PubMed1999

Dietary glycine and renal denervation prevents cyclosporin A-induced hydroxyl radical production in rat kidney.

Cyclosporin A (CsA) nephrotoxicity is associated with renal hypoxia and increases in free radicals in the urine. This study was designed to elucidate the mechanism of radical production caused by CsA. Pretreatment of rats with CsA (25 mg/kg, i.g.) for 5 days decreased glomerular filtration rates by 65%, an effect largely prevented by both dietary glycine (5%) or renal denervation. CsA dissolved in olive oil produced a 6-line alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN)/free radical signal in the urine, which partitioned predominantly into the aqueous phase after chloroform extraction (i.e., it is water soluble). Dimethyl sulfoxide (DMSO) is attacked by the hydroxyl radical to produce a methyl radical; administration of CsA with [(12)C]DMSO produced two radical species in urine, one with hyperfine coupling constants similar to the 4-POBN/methyl radical adduct found in aqueous solution. CsA given with [(13)C]DMSO produced a 12-line spectrum, confirming the formation of hydroxyl radicals. The methyl radical produced by the hydroxyl radical represented 62% of radicals detected in urine but only 15% in bile. Therefore, hydroxyl radicals are produced largely in the kidney. Free radicals in urine were increased about 5-fold by CsA, an effect completely blocked by the inhibitory neurotransmitter, glycine, or by renal denervation. CsA infusion for 30 min increased efferent renal nerve activity 2-fold, and dietary glycine (5%) totally blocked this phenomenon. Taken together, these data are consistent with the hypothesis that CsA increases hydroxyl radical formation by increasing renal nerve activity resulting in vasoconstriction and hypoxia-reoxygenation. Glycine blunts the effect of CsA on the renal nerve, which explains, in part, prevention of nephrotoxicity.

Animals↗

PubMed1999

CYP2E1 is not involved in early alcohol-induced liver injury.

The continuous intragastric enteral feeding protocol in the rat was a major development in alcohol-induced liver injury (ALI) research. Much of what has been learned to date involves inhibitors or nutritional manipulations that may not be specific. Knockout technology avoids these potential problems. Therefore, we used long-term intragastric cannulation in mice to study early ALI. Reactive oxygen species are involved in mechanisms of early ALI; however, their key source remains unclear. Cytochrome P-450 (CYP)2E1 is induced predominantly in hepatocytes by ethanol and could be one source of reactive oxygen species leading to liver injury. We aimed to determine if CYP2E1 was involved in ALI by adapting the enteral alcohol (EA) feeding model to CYP2E1 knockout (-/-) mice. Female CYP2E1 wild-type (+/+) or -/- mice were given a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin as control continuously for 4 wk. All mice gained weight steadily over 4 wk, and there were no significant differences between groups. There were also no differences in ethanol elimination rates between CYP2E1 +/+ and -/- mice after acute ethanol administration to naive mice or mice receiving EA for 4 wk. However, EA stimulated rates 1.4-fold in both groups. EA elevated serum aspartate aminotransferase levels threefold to similar levels over control in both CYP2E1 +/+ and -/- mice. Liver histology was normal in control groups. In contrast, mice given ethanol developed mild steatosis, slight inflammation, and necrosis; however, there were no differences between the CYP2E1 +/+ and -/- groups. Chronic EA induced other CYP families (CYP3A, CYP2A12, CYP1A, and CYP2B) to the same extent in CYP2E1 +/+ and -/- mice. Furthermore, POBN radical adducts were also similar in both groups. Data presented here are consistent with the hypothesis that oxidants from CYP2E1 play only a small role in mechanisms of early ALI in mice. Moreover, this new mouse model illustrates the utility of knockout technology in ALI research.

Animals↗

PubMed1999

[Development of plasmid-based transgenic mice carrying with target gene xylE].

OBJECTIVE: To develop a transgenic mouse model carrying with plasmid pUC118NX integrated into its genomic DNA for detecting mutagenesis. METHODS: DNA of plasmid UC118NX in target gene xy1E was injected microscopically into male protonucleus of 376 mouse spermatova, and 225 survival spermatova were transferred into the oviducts in both sides of 11 pseudopregnant female mice to develop their offspring. The genomic DNA in survival young mice were analyzed with polymerase chain reaction (PCR)-Southern blot, plasmid transformation test and endonuclease-digestion. RESULTS: Seven pseudopregnant mice got pregnant, and 29 offspring were delivered and 25 survived of which 18 were identified with positive for PCR-Southern blot (72%). The two stout male mice with intact integration of plasmid pUC118NX in their genome were finally chosen as founders to detect gene mutation in vivo and establish transgenic mouse lineages. CONCLUSION: Transgenic C57BL/6J mice integrated with plasmid pUC118NX into their genomic DNA have been successfully developed.

Animals↗

PubMed1999

[Inhibitory effects of recombinant human neurotrophin-4/5 protein on neurotoxicity caused by arsenic trioxide].

OBJECTIVE: To study preliminarily the inhibitory effects of recombinant human neurotrophin (hNT)-4/5 protein on neurotoxicity caused by arsenic trioxide (As(2)O(3)). METHODS: Nerve cells of the chicken embryonic forebrain and PC12 cells were co-cultured with recombinant hNT-4/5 protein and As(2)O(3) (0 - 16 micromol/L) for 24 and 48 hours, respectively, to observe the survival of nerve cells and the outgrowth of PC12 cells, with clone expression and recombination techniques. RESULTS: There was significant difference in survival rate of nerve cells between the experimental and control groups (P < 0.01) after co-culture for 48 hours, and survival rate and number of neuron outgrowth increased with the concentration of hNT-4/5 protein. CONCLUSION: Recombinant hNT-4/5 protein could inhibit neurotoxicity caused by As(2)O(3), which provided a basis to find an anti-toxic factor in the environment by genetic engineering.

Animals↗

PubMed1999

[Clinical manifestations and CT diagnosis of non-allergic fungal sinusitis].

OBJECTIVE: The diagnose of fungal sinusitis, especially complicated by bone destructive, and its differential diagnosis from malignant tumour of nasal sinus were studied. METHOD: Five cases were diagnosed with CT; nasal sinus microsurgery was done in 4 cases and sinusotomy in one case. None of them were treated by antifungal agents. RESULT: Fungal filaments were postoperatively shown in 5 pathological reports, fungal spores in some cases. No recurrence and complications occurred as followed from 6 months to 3 years. CONCLUSION: It is not easy to differentiate fungal sinusitis from malignant tumour of nasal sinus, sometimes, but CT has demonstrated its importance of diagnostic value.

Adult↗

PubMed1999

[Epidemiological survey on orchard pollinosis].

OBJECTIVE: To investigate the prevalence of Orchard Pollinosis in China. METHOD: From 1995 to 1998, an epidemiological survey on orchard pollinosis was carried on among 1,660 primary and middle school students and 2,167 university students, including questionnaire investigation, nasal inspection and scratch test. From April to June of 1998, a clinical investigation of orchard pollinosis was adopted among 30 patients of allergic rhinitis including scratch test and nasal mucosa test. RESULT: 1. The total positive rate of orchard pollen scratch test was 6.7%, and the prevalence of orchard pollinosis was 0.37%. 2. 5 cases (16.7%) were hypersensitive to orchard pollen clinically in allergen test. CONCLUSION: Orchard pollinosis is one kind of important pollinosis and should be paid high attention to.

Adolescent↗

PubMed1998

Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage.

Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance of a blastocoel cavity. Throughout development, they increase in size and number and are especially abundant in epidermis and heart muscle. Desmosomes mediate cell-cell adhesion through desmosomal cadherins, which differ from classical cadherins in their attachments to intermediate filaments (IFs), rather than actin filaments. Of the proteins implicated in making this IF connection, only desmoplakin (DP) is both exclusive to and ubiquitous among desmosomes. To explore its function and importance to tissue integrity, we ablated the desmoplakin gene. Homozygous -/- mutant embryos proceeded through implantation, but did not survive beyond E6.5. Surprisingly, analysis of these embryos revealed a critical role for desmoplakin not only in anchoring IFs to desmosomes, but also in desmosome assembly and/or stabilization. This finding not only unveiled a new function for desmoplakin, but also provided the first opportunity to explore desmosome function during embryogenesis. While a blastocoel cavity formed and epithelial cell polarity was at least partially established in the DP (-/-) embryos, the paucity of desmosomal cell-cell junctions severely affected the modeling of tissue architecture and shaping of the early embryo.

Animals↗

PubMed1998

Human SLUG gene organization, expression, and chromosome map location on 8q.

SLUG is a member of the snail family of zinc finger proteins. It is involved in epithelial to mesenchyme cell transition during neurulation and plays a role in limb bud development. We have isolated and described the human SLUG gene by sequencing a region spanning 4034 bp. The human SLUG gene contains three exons. The SLUG transcript is 2.2 kb and is found in placenta and adult heart, pancreas, liver, kidney, and skeletal muscle, and it codes for a protein of 268 amino acids and 29.989 kDa. This protein contains five zinc finger regions. The human SLUG protein is 95, 93, and 88% homologous to mouse, chicken, and Xenopus slug, respectively, but shows only 47% homology to mouse Snail. The zinc finger region is 100% identical between human and mouse Slug. Slug maps to the long arm of chromosome 8, closely linked to D8S2090 between D8S519 and D8S1098.

Amino Acid Sequence↗

PubMed1998

Cytomegalovirus infection enhances the neointima formation in rat aortic allografts: effect of major histocompatibility complex class I and class II antigen differences.

BACKGROUND: The development of chronic rejection has emerged as a major cause of long-term graft failure. Previous studies have demonstrated that cytomegalovirus (CMV) infection is associated with an increased incidence of chronic allograft rejection in renal, cardiac, and aortic allografts. This study was designed to investigate the effects of the major histocompatibility complex (MHC) class I or class II mismatches on CMV-enhanced chronic rejection. METHODS: Aortic transplantation was performed between different inbred rat strain combinations; the Lewis to RP combination was class I-mismatched and Wag/Rij to RP class II-mismatched. At 7, 28, and 90 days after transplantation, the intensity of chronic rejection in mismatched grafts with or without CMV infection was evaluated using histological and immunohistological analysis. RESULTS: The results of this study demonstrated that CMV infection led to an increased influx of monocytes/ macrophages in class I-mismatched grafts at 1 week after transplantation and enhanced infiltration of T lymphocytes in class II-mismatched grafts at 4 weeks. Although more vascular lesions were observed in the class II-mismatched combinations, an intensified neointima formation by CMV infection was observed only in the MHC class I-mismatched allografts. CONCLUSIONS: CMV infection may increase neointima formation of allografts when an MHC class I disparity between donor and recipient is present. This may be associated with the increased perivascular influx of monocytes/macrophages observed in CMV-infected animals early after transplantation.

Animals↗

PubMed1998

Tumor necrosis factor-alpha stimulates the maturation of sterol regulatory element binding protein-1 in human hepatocytes through the action of neutral sphingomyelinase.

The mechanism by which genes involved in cholesterol biosynthesis and import are preferentially up-regulated in response to sterol depletion was elucidated with the cloning of sterol regulatory element binding protein-1 (SREBP-1). SREBP-1 is a transcription factor whose entry into the nucleus is gated by sterol-regulated proteolysis. We have investigated the role of tumor necrosis factor-alpha (TNF-alpha) as a mediator of SREBP-1 maturation in human hepatocytes. TNF-alpha is capable of inducing SREBP-1 maturation in a time- and dose-dependent manner that is consistent with the kinetics of TNF-alpha-mediated activation of neutral sphingomyelinase (N-SMase). Antibodies to N-SMase inhibit TNF-alpha-induced SREBP-1 maturation suggesting that N-SMase is a necessary component of this signal transduction pathway. Ceramide, a product of sphingomyelin hydrolysis, is also capable of inducing SREBP-1 maturation. The mature form of SREBP-1 generated by TNF-alpha, sphingomyelinase or ceramide treatment translocates to the nucleus and binds the sterol regulatory element. This promotes transcription of the gene upstream of the sterol regulatory element. A unique finding of our studies is that ceramide stimulated SREBP-1 maturation even in the presence of cholesterol and 25-hydroxycholesterol both of which are known suppressors of SREBP-1 maturation. Our findings indicate that ceramide-mediated maturation of SREBP-1 maturation is a novel sterol-independent mechanism by which cholesterol homeostasis may be regulated.

Antibodies↗

PubMed1998

Computer-generated time lines for visualizing and editing epidemiological and biomedical data.

Most biomedical data have a temporal dimension. Time-line displays spatialize this dimension and help the viewer comprehend large sets of complex data. If we add ways for users to selectively expand the details of data visible on a time line, even more information can be organized and accessed. Design issues for this kind of display include: how to display time scales that are often wider than the physical display space; how to display events with brief duration; how to display data for two or more events that overlap in time; how to manage the display of data details; how to allow database editing from a time line; and how to facilitate time-based analytical techniques. We describe a time-line display system that addresses each of these issues, and show how it can be used to organize data for an epidemiological study of parental radiation exposure and childhood leukemia. We also suggest further refinements of the time line technique for other biomedical applications.

Child↗

PubMed1998

Fibroblast growth factor 2 control of vascular tone.

Vascular tone control is essential in blood pressure regulation, shock, ischemia-reperfusion, inflammation, vessel injury/repair, wound healing, temperature regulation, digestion, exercise physiology, and metabolism. Here we show that a well-known growth factor, FGF2, long thought to be involved in many developmental and homeostatic processes, including growth of the tissue layers of vessel walls, functions in vascular tone control. Fgf2 knockout mice are morphologically normal and display decreased vascular smooth muscle contractility, low blood pressure and thrombocytosis. Following intra-arterial mechanical injury, FGF2-deficient vessels undergo a normal hyperplastic response. These results force us to reconsider the function of FGF2 in vascular development and homeostasis in terms of vascular tone control.

Animals↗

PubMed1998

Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations.

Thirty-two unrelated patients with features of Saethre-Chotzen syndrome, a common autosomal dominant condition of craniosynostosis and limb anomalies, were screened for mutations in TWIST, FGFR2, and FGFR3. Nine novel and three recurrent TWIST mutations were found in 12 families. Seven families were found to have the FGFR3 P250R mutation, and one individual was found to have an FGFR2 VV269-270 deletion. To date, our detection rate for TWIST or FGFR mutations is 68% in our Saethre-Chotzen syndrome patients, including our five patients elsewhere reported with TWIST mutations. More than 35 different TWIST mutations are now known in the literature. The most common phenotypic features, present in more than a third of our patients with TWIST mutations, are coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, ptosis, hypertelorism, broad great toes, and clinodactyly. Significant intra- and interfamilial phenotypic variability is present for either TWIST mutations or FGFR mutations. The overlap in clinical features and the presence, in the same genes, of mutations for more than one craniosynostotic condition-such as Saethre-Chotzen, Crouzon, and Pfeiffer syndromes-support the hypothesis that TWIST and FGFRs are components of the same molecular pathway involved in the modulation of craniofacial and limb development in humans.

Acrocephalosyndactylia↗

PubMed1998

Effects of chronic ethanol consumption on cytokine regulation of liver regeneration.

Ethanol ingestion may interrupt the proregenerative signal transduction that is initiated by injury-related cytokines such as tumor necrosis factor (TNF)-alpha and TNF-alpha- inducible cytokines including interleukin (IL)-6. To test this theory, liver regeneration, TNF-alpha and IL-6 expression, and cytokine-regulated prereplicative events were compared in ethanol-fed rats and isocalorically fed controls after 70% partial hepatectomy (PH). Ethanol feeding inhibits hepatocyte replication and recovery of liver mass after PH but generally promotes induction of both cytokines in the liver and extrahepatic tissues (i.e., white adipose tissue). Cytokine-regulated events that occur early in the prereplicative period are influenced differentially. TNF-alpha-dependent increases in hepatic nuclear factor-kappaB (NF-kappaB) p50 and p65 expression and DNA binding activity are prevented, whereas IL-6-dependent inductions of hepatic Stat-3 phosphorylation and DNA binding activity occur normally. In contrast, events (e.g., induction of cyclin D1, cdk-1, cyclin D3, and p53 mRNA) that occur at the end of the prereplicative period are uniformly inhibited. These findings indicate that chronic ethanol ingestion arrests the regenerative process during the prereplicative period and demonstrate that increased TNF-alpha, IL-6 and Stat-3 are not sufficient to assure hepatocyte proliferation after PH.

Adipose Tissue↗

PubMed1998

Cyclosporin A increases hypoxia and free radical production in rat kidneys: prevention by dietary glycine.

The major side effect of cyclosporin A is severe nephrotoxicity. It is likely that cyclosporin A causes vasoconstriction leading to hypoxia-reperfusion injury; therefore, these experiments were designed to attempt to obtain physical evidence for hypoxia and free radical production in kidney following cyclosporin A. Rats were treated daily with cyclosporin A (25 mg/kg ig) for 5 days, and pimonidazole, a hypoxia marker, was injected 2 h after the last dose of cyclosporin A. A dose of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) was injected 3 h after cyclosporin A to trap free radicals. Cyclosporin A doubled serum creatinine and decreased glomerular filtration rates by 65% as expected. Pimonidazole adduct binding in the kidney was increased nearly threefold by cyclosporin A, providing physical evidence for tissue hypoxia. Moreover, cyclosporin A increased 4-POBN/radical adducts nearly sixfold in the urine but did not alter levels in the serum. Glycine, which causes vasodilatation and prevents cyclosporin A toxicity, minimized hypoxia and blocked free radical production; however, it did not alter cyclosporin A blood levels. These results demonstrate for the first time that cyclosporin A causes hypoxia and increases production of a new free radical species exclusively in the kidney. Therefore, it is concluded that cyclosporin A causes renal injury by mechanisms involving hypoxia-reoxygenation, effects which can be prevented effectively by dietary glycine.

Animals↗

PubMed1998

Glycine accelerates recovery from alcohol-induced liver injury.

Glycine prevents hepatic damage caused by hypoxia-reoxygenation, diminishes mortality due to endotoxin and minimizes alcoholic liver injury by decreasing blood ethanol. Our purpose was to investigate the effect of dietary glycine during recovery from early alcohol-induced injury, using a model that mimics the clinical presentation and histopathology with alcoholics. Male Wistar rats were exposed to ethanol continuously for 6 wk via intragastric feeding that resulted in typical histology of alcoholic liver injury, including steatosis, inflammation, necrosis and increased serum levels of aspartate aminotransferase and alanine aminotransferase. After cessation of ethanol, one group of rats received a control diet, the other a glycine-containing diet for 2 wk. During this period, all parameters studied tended to return to baseline values. However, serum aspartate aminotransferase and alanine aminotransferase recovered about 30% more rapidly in rats fed glycine. Further, the hepatic pathology score was also significantly lower in the glycine group than in controls (0.5 vs. 2.6). After 1 wk, steatosis was reduced significantly more in the glycine group (5. 6%) than in controls (8.9%). Glycine also diminished numbers of infiltrating leukocytes and necrotic cells significantly more than in controls. This beneficial effect of glycine may be partly explained by the fact that glycine increased influx of chloride into Kupffer cells leading to diminished tumor necrosis factor-alpha production. These results indicate that a glycine containing diet expedites the process of recovery from ethanol-induced liver injury and may lead to its clinical application in alcoholic hepatitis.

Alanine Transaminase↗

PubMed1998

The role of gut-derived bacterial toxins and free radicals in alcohol-induced liver injury.

Previous research from this laboratory using a continuous enteral ethanol (EtOH) administration model demonstrated that Kupffer cells are pivotal in the development of EtOH-induced liver injury. When Kupffer cells were destroyed using gadolinium chloride (GdCl3) or the gut was sterilized with polymyxin B and neomycin, early inflammation due to EtOH was blocked. Anti-tumour necrosis factor (TNF)-alpha antibody markedly decreased EtOH-induced liver injury and increased TNF-mRNA. These findings led to the hypothesis that EtOH-induced liver injury involves increases in circulating endotoxin leading to activation of Kupffer cells. Pimonidazole, a nitro-imidazole marker, was used to detect hypoxia in downstream pericentral regions of the lobule. Following one large dose of EtOH or chronic enteral EtOH for 1 month, pimonidazole binding was increased significantly in pericentral regions of the liver lobule, which was diminished with GdCl3. Enteral EtOH increased free radical generation detected with electron spin resonance (ESR). These radical species had coupling constants matching alpha-hydroxyethyl radical and were shown conclusively to arise from EtOH based on a doubling of the ESR lines when 13C-EtOH was given. Alpha-hydroxyethyl radical production was also blocked by the destruction of Kupffer cells with GdCl3. It is known that females develop more severe EtOH-induced liver injury more rapidly and with less EtOH than males. Female rats on the enteral protocol exhibited more rapid injury and more widespread fatty changes over a larger portion of the liver lobule than males. Plasma endotoxin, ICAM-1, free radical adducts, infiltrating neutrophils and transcription factor NFkappaB were approximately two-fold greater in livers from females than males after 4 weeks of enteral EtOH treatment. Furthermore, oestrogen treatment increased the sensitivity of Kupffer cells to endotoxin. These data are consistent with the hypothesis that Kupffer cells participate in important gender differences in liver injury caused by ethanol.

Animals↗

PubMed1997

Chronic enteral ethanol treatment causes hypoxia in rat liver tissue in vivo.

It is known that ethanol increases oxygen consumption in in vitro liver models, which could lead to hypoxia. Although it was shown recently that one large dose of ethanol caused hypoxia in rat liver in vivo, whether ethanol produces hypoxia in a clinically relevant chronic model remains unclear. In the present study, therefore, the effect of chronic ethanol on hypoxia was investigated in vivo using the 2-nitroimidazole hypoxia marker, pimonidazole. Male Wistar rats (300-325 g) were exposed to enteral ethanol continuously for 4 weeks. In this model, rats develop steatosis, inflammation, and necrosis characteristic of early stages of clinical alcoholic liver disease in humans. One hour before they were killed, rats were injected with pimonidazole (120 mg/kg intravenously), and livers were surgically isolated, removed, and fixed. Protein-bound pimonidazole adducts were identified on formalin-fixed, paraffin-embedded tissue with immunohistochemistry. Ethanol administration for 4 weeks significantly increased serum aspartate transaminase levels and hepatic pathology scores for steatosis, inflammation, and necrosis, as expected. Ethanol treatment significantly increased both the extent and number of cells that stained positive for pimonidazole compared with control animals given an enteral diet without ethanol. Quantitative image-analysis of pimonidazole binding showed that 4 weeks of ethanol administration nearly doubled the pimonidazole-positive area in tissue. Ethanol also increased pimonidazole binding significantly at 7 days, long before inflammation and necrosis could be detected. These results indicate that chronic ethanol causes hypoxia at the cellular level in rat liver in vivo and lend support to the hypothesis that hypoxia is involved in mechanisms of early alcoholic liver injury.

Animals↗