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Biomedical subjects

L Lin

Publications and source records attributed to L Lin.

At least 181 records · Page 10Linked to original sources
PubMed1998

The effects of a high fat diet on leptin mRNA, serum leptin and the response to leptin are not altered in a rat strain susceptible to high fat diet-induced obesity.

Osborne-Mendel (OM) and S5B/Pl rats differ in their sensitivity to develop obesity when fed a high fat (HF) diet; OM rats become obese, whereas S5B/Pl rats remain thin. We have investigated the possibilities that either an impaired leptin response or resistance to leptin action underlies the sensitivity to this form of obesity in OM rats. In Experiment 1, OM and S5B/Pl rats fed a nonpurified diet were killed at d 0 or were fed either a HF (56% fat energy) or a low fat (LF, 10% fat energy) diet for 2 or 7 d. The HF diet increased serum leptin significantly by d 2 to levels that were similar in both rat strains. At 7 d, leptin levels were lower than at d 2 but remained higher than levels in the d 0 control groups. The leptin mRNA:18S RNA ratio in epididymal adipose tissue increased to higher levels in HF-fed OM rats than in S5B/Pl rats fed that diet. However, although the LF diet had no effect in S5B/Pl rats, it increased leptin mRNA levels in epididymal adipose tissue of OM rats compared with the controls fed the nonpurified diet. In Experiment 2, OM and S5B/Pl rats were fed HF or LF diets for 5 wk. At that time, their feeding response to a range of leptin doses (0, 1, 5 or 10 microgram) given intracerebroventricularly was tested after overnight food deprivation. There was a similar dose-dependent reduction in energy intake in response to leptin in both OM and S5B/Pl rats. These responses were independent of the diet. The data suggest that the susceptibility of OM rats to HF diet-induced obesity is not related to either a loss of central sensitivity to leptin or a failure to enhance leptin production acutely, although the failure to maintain chronically increased levels of serum leptin could contribute to the obesity.

Adipose Tissue↗
PubMed1998

The dose-effect relationships between torture and psychiatric symptoms in Vietnamese ex-political detainees and a comparison group.

The purpose of this study was to determine in Vietnamese ex-political detainees newly arrived into the United States a) the prevalence of torture and psychiatric symptoms and b) the dose-effect relationships between cumulative torture experience and the psychiatric symptoms of posttraumatic stress disorder (PTSD) and major depression. The study population included Vietnamese ex-political detainees (N = 51) and a comparison group (N = 22). All respondents received culturally validated instruments with known psychometric properties including Vietnamese versions of the Hopkins Symptom Checklist-25 and the Harvard Trauma Questionnaire. The ex-political detainees, in contrast to the comparison group, had experienced more torture events (12.2 SD = 4.2 vs. 2.6 SD = 3.1) and had higher rates of PTSD (90% vs. 79%) and depression (49% vs. 15%). Dose-effect relationships between cumulative torture experience and psychiatric symptoms were positive with the PTSD subcategory of "increased arousal" revealing the strongest association. These findings provide evidence that torture is associated with psychiatric morbidity in Vietnamese refugees. The demonstration of significant dose-effect responses supports the hypothesis that torture is a major risk factor in the etiology of major depression and PTSD. The generalizability of these results to other torture survivor groups is unknown. The interaction between torture and other pre- and post-migration risk factors over time in different cultural settings still needs to be examined.

Adult↗
PubMed1998

Diversity of HLA-B61 alleles and haplotypes in East Asians and Spanish Gypsies.

The distribution of HLA-B61 alleles and their association with HLA-C and DRB1 alleles were investigated in six East Asian populations (South Korean, Chinese Korean, Man (Manchu), Northern Han, Mongolian and Buryat) and Spanish Gypsies and compared to our previous report on the Japanese population. The alleles were identified using a group-specific polymerase chain reaction (PCR) and genomic DNA followed by hybridization with sequence-specific oligonucleotide probes (SSOP). Both HLA-B*4002 and B*4006 were commonly detected in the South Korean, Chinese Korean, Man, Northern Han and Japanese populations, while HLA-B*4002 was predominant in the Mongolian and Buryat populations. Strong associations of B*4002 with Cw*0304 and of B*4006 with Cw*0801 were commonly observed in these East Asian populations. In contrast, in Spanish Gypsies, only HLA-B*4006 was found and the allele exhibited a strong association with Cw*1502. HLA-B*4003 was also identified in the South Korean, Chinese Korean, Northern Han, Mongolian and Japanese populations at relatively low frequencies, and exhibited an association with Cw*0304. Moreover, the association of these B61 alleles with the DRB1 alleles revealed considerable diversity among the different populations. HLA-B*4004 and B*4009 were not observed in these populations. Consequently, the frequencies of the B61 alleles varied among the different East Asian populations, but the individual B61 alleles were carried by specific haplotypes often regardless of the ethnic differences.

Alleles↗
PubMed1998

Microsatellite single nucleotide polymorphisms in the HLA-DQ region.

Sequencing studies were performed in three previously described microsatellite and minisatellite markers located within the HLA-DQ region, DQCAR, DQCARII and G51152. Multiple nucleotide substitutions that did not change size polymorphisms were observed in all three markers. In all loci, the number of core repeats did not correlate with neighboring DQ allele sequence motifs while single nucleotide changes within or flanking the microsatellite sequence did. This result indicates higher mutation rates for microsatellite expansions/contractions than for nucleotide substitutions in these loci. Further analysis indicated an almost complete phylogenetic correspondence between DQCAR single nucleotide polymorphisms (SNPs) and DQB1 sequences on one side (1.0-1.5 kb apart) and a complete relationship between DQCARII and DQA1 sequences on the other (4.5 kb apart). In contrast, G51152 sequences did not correspond perfectly with DQB1 allelic sequences, thus suggesting the existence of several ancestral crossovers between this marker and DQB1 (20-25 kb). Sequencing microsatellites might be useful in disease mapping studies by increasing marker informativeness and by helping in the interpretation of association study results. It is also proposed that SNPs within the flanking region of CA repeats could be used to develop biallelic markers from already available mapped microsatellite markers.

Alleles↗
PubMed1998

Infection of epithelial cells by pathogenic neisseriae reduces the levels of multiple lysosomal constituents.

Members of our group reported recently that neisseria infection of human epithelial cells results in accelerated degradation of the major lysosomal integral membrane protein LAMP1 and that this is due to hydrolysis of this glycoprotein at its immunoglobulin A1 (IgA1)-like hinge by the neisseria type 2 IgA1 protease (L. Lin et al., Mol. Microbiol. 24:1083-1094, 1997). We also reported that the IgA1 protease plays a major role in the ability of the pathogenic neisseriae to survive within epithelial cells and hypothesized that this is due to alteration of lysosomes as a result of protease-mediated LAMP1 degradation. In this study, we tested the hypothesis that neisseria infection leads to multiple changes in lysosomes. Here, we report that neisseria infection also reduces the levels of three other lysosomal markers: LAMP2, lysosomal acid phosphatase (LAP), and CD63. In contrast, neither the epidermal growth factor receptor level nor the beta-tubulin level is affected. A detailed examination of LAMP2 indicated that the reduced LAMP2 levels are not the result of an altered biosynthetic rate or of cleavage by the IgA1 protease. Nevertheless, the protease plays a role in reducing LAMP2 and LAP activity levels, as these are partially restored in cells infected with an iga mutant. We conclude that neisseria infection results in multiple changes to the lysosomes of infected epithelial cells and that these changes are likely an indirect result of IgA1 protease-mediated cleavage of LAMP1.

Acid Phosphatase↗
PubMed1998

Chronic ingestion of dietary fat is a prerequisite for inhibition of feeding by enterostatin.

Enterostatin (Ent), the activation pentapeptide from procolipase, inhibits the intake of dietary fat. The selectivity of the response to fat suggests that the rat must recognize a permissive signal related to dietary fat for the Ent biological response. To investigate the nature of this signal, we studied the effects of Ent in rats that were adapted to either a high-fat (HF) or high-carbohydrate/low-fat (HC) diet and then naively exposed to either HF or HC diets. Ent (1 nmol) was injected into the lateral ventricle of overnight-fasted rats, and food intake was measured. Rats adapted to HF diet and tested with HC diet responded to Ent, but rats adapted to HC diet and tested with HF did not respond to Ent. The groups were maintained on their new test diets for up to 21 days and tested again for their response to Ent at 3, 7, 14, and 21 days. Ent response did not appear in HC-adapted rats switched to HF diet before 21 days. Conversely, the HF-adapted rats, which responded to Ent when tested with HC diet for the first time, did not respond at any subsequent testing time. The data suggest that chronic ingestion of dietary fat is required for Ent action and that chronic consumption of fat initiates a postingestion metabolic, endocrine, or neurochemical change that is required for the biological response to Ent.

Acclimatization↗
PubMed1998

Construction of phosphorylatable chimeric monoclonal antibody CC49.

Phosphorylation sites were introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting synthetic fragments encoding two and six phosphorylation sites into an expression vector, pdHL7. The phosphorylation sites were created by using the predicted consensus sequences for phosphorylation by the cAMP-dependent protein kinase to the carboxyl terminus of the heavy chain constant region of the MAb-chCC49. The resultant modified antibodies (MAb-chCC49K1 and MAb-chCC49-6P) were expressed in NS0 cells and purified. The MAb-chCC49K1 protein contains two phosphorylation sites per heavy chain whereas the MAb-chCC49-6P protein contains six sites per heavy chain. Both MAb-chCC49K1 and MAb-chCC49-6P proteins can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with [gamma-32P]ATP to high specific activity. The 32P-labeled MAb-chCC49K1 and MAb-chCC49-6P proteins bind to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into a monoclonal antibody provides a reagent for the diagnosis and treatment of cancer. The use of multiple phosphorylation sites provides antibodies with very high specific radioactivity and demonstrates that cassettes of phosphorylation sites can be introduced into proteins without altering their functional activity.

Amino Acid Sequence↗
PubMed1998

Construction of phosphorylatable chimeric monoclonal antibody CC49 with a tyrosine srC kinase recognition site.

A phosphorylation site for a tyrosine kinase was introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting a synthetic fragment (Tyr) encoding one tyrosine kinase phosphorylation site into an expression vector. The phosphorylation site was created by incorporating the predicted consensus sequences for phosphorylation by the tyrosine kinase at the carboxyl terminus of the heavy chain constant region of the MAb-chCC49. The resultant modified MAb-chCC49 (MAb-chCC49Tyr) was expressed and purified. The MAb-chCC49Tyr protein can be phosphorylated by the tyrosine Src kinase with [gamma-32P]ATP to high radiospecific activity. The 32P-labeled MAb-chCC49Tyr protein binds to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into monoclonal antibodies (MAb) provides a new reagent for the diagnosis and treatment of cancer. This demonstrates that, as was described for the cAMP-dependent protein kinase site, a tyrosine phosphorylation site can also be used to introduce phosphorylation sites into proteins.

Amino Acid Sequence↗
PubMed1998

Inhibitory effects of cytokines on ovarian and endometrial carcinoma cells in vitro with special reference to induction of specific transcriptional regulators.

In the present study, we have investigated the effects of interferons-alpha (IFN-alpha) and -gamma (IFN-gamma), interleukin-10 (IL-10) and -13 (IL-13), transforming growth factor-beta1 (TGF-beta1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) on cell proliferation and induction of transcription factors AP-1 and NF-kappaB in UM-EC-3 human endometrial adenocarcinoma cells and UT-OC-5 ovarian carcinoma cells in vitro. In addition, cellular DNA was extracted to study if any of these factors is able to induce apoptosis. In UM-EC-3 cell line DNA synthesis was inhibited by GM-CSF, IL-10, IL-13, TGF-beta1, IFN-alpha, and IFN-gamma after 48 and 72 h in culture, whereas TNF-alpha had no significant effect on cell proliferation in any of the experiments. The inhibition of DNA synthesis was similarly observed in UT-OC-5 ovarian carcinoma cells by IL-10, TNF-alpha, and IFN-gamma after 48 and 72 h, whereas IFN-alpha had no statistically significant effect. An inhibitory effect of GM-CSF was observed only after 48 h and TGF-beta after 72 h in culture, respectively. Transcription factors AP-1 and NF-kappaB were both constitutively active in UM-EC-3 and UT-OC-5 cells. The binding activity of AP-1 was found to be stimulated by all growth-inhibitory cytokines studied in both cell lines, whereas the specific binding activity of NF-kappaB was affected moderately only by TNF-alpha in UT-OC-5 ovarian carcinoma cells. No signs of DNA fragmentation typical of apoptosis were observed in any of these studies.

Adenocarcinoma↗
PubMed1998

[The expressions of p16, CDK4 and PCNA proteins in trophoblastic tumors].

OBJECTIVE: To evaluate the relationship between the regulatory factors in G1 phase of cell cycle and the cacrinogenesis of the trophoblastic cells. METHODS: The expressions of p16, cyclin-dependent kinase 4 (CDK4), proliferation cell nuclear antigen (PCNA) proteins in 18 cases of trophoblastic tumors, 30 cases of hydatidiform mole and 30 cases of normal villi were studied by immunohistochemical methods. RESULTS: The expressions of p16 protein between malignant trophoblastic tumors and normal villi were significantly different (P < 0.05). PCNA positive rate in p16 positive samples were markedly lower than that in negative samples (P < 0.05). The expressions of CDK4 among normal villi, hydatiform mole and trophoblastic tumors were not significantly different. Patients with positive p16 expression had a higher 3 year survival rate. CONCLUSION: p16 protein may inhibit trophoblastic cells proliferation, and p16 gene mutation may be an important factor in carcinogenesis of trophoblastic cells and proliferation out of control. P16 protein expression examination is helpful in prediction of patients prognosis.

Choriocarcinoma↗
PubMed1998

[The clinic significance of serum hyaluronate and tumor necrosis factor alpha levels in liver diseases].

Serum levels of hyaluronic acid (HA) and tumor necrosis factor alpha (TNF alpha) in 94 patients with various liver diseases and 31 healthy controls were studied by RIA, Serum TNF alpha in hepatitis, liver cirrhosis (LC) and primary hepatic carcinoma (PHC) was higher than that of the control. Serum HA in chronic hepatitis, LC and PHC was higher than that in the control. The serum level of HA showed a positive correlation with the serum level of TNF alpha. It is considered that the increase of serum HA indicates an early fibrogenic tendency in patients with liver diseases. TNF alpha is involved in the formation of hepatic fibrosis.

Hepatitis, Chronic↗
PubMed1998

[Surgical management of closed injury of mitral valve: report of four cases].

OBJECTIVE: To show the experience in dealing with mitral valve injury caused by trauma. METHODS: Four cases of closed injury of mitral valve were treated. RESULTS: Two of the four patients presented ruptured chordae of mitral valve and were cured with annutoplasty plus repair of the chordae and mitral valve replacement respectively. One presented tearing of mitral valve leaf and pseudoaneurysm of the femoral artery, which were complicated by infective endocarditis. The patient was cured with emergency operation to repair the lesions and remove pseudoaneurysm and neoplasm in the mitral valve. Another patient, who received mitral valve replacement 8 years before, presented ruptured valve-hook of the prosthesis and died of acute heart failure without prompt operation. The diagnosis was confirmed by autopsy. CONCLUSIONS: The disease is easy to misdiagnose and once the diagnosis is established surgical intervention should be performed early. Emergency operation is necessary if acute heart failure occurs or infective endocarditis is complicated.

Adult↗
PubMed1998

[Studies on chemical constituents of Tinospora hainanesis].

Tinospora hainanesis is a new species of Menispermaceae plant. It is used as folk remedy for joint pain and physical injury. Five compounds were isolated from the vine stalk of Tinospora hainanesis. By spectral analysis and chemical methods, the structures of the compounds were identified as makisterone A (I), 2,3-dimethoxy-9,10-dihydroxy-N-methyltetrahydroproto-berberine quaternary salt (II), palmatine (III), beta-amyrin (IV) and docosyl ferulate (V). II is a new quaternary alkaloid named as haitinosporine. I, IV and V were isolated for the first time from the plants of Tinospora genus.

Berberine Alkaloids↗
PubMed1998

[Study on a new type of endoscope based on micro motor].

The application of Micro Electro Mechanical System (MEMS) on the fields of biomedical engineering is a newly technological field. Applying a micro motor, whose diameter is only 2 mm, as driving device of this system, this paper presented a new type of medical endoscope whose front tip of diagnosing tube could work automatically.

Endoscopes↗
PubMed1998

Betaseron.

Betaseron, an analogue of human beta-interferon where serine was genetically engineered to substitute for cysteine at position 17, is produced in E. coli. The molecule is a small polypeptide of 165 amino acids with a single disulphide bond, and is non-glycosylated. The site-specific substitution was made to obtain a product that is more stable upon storage. Similar to native IFN-beta, Betaseron is hydrophobic in nature and has been shown to have the same panel of biological activities which includes antiviral activity against a variety of viruses, inhibition of cell growth, activation of natural killer cells, and binding to interferon receptors on the cell surface. Betaseron has been tested in a wide variety of clinical settings since 1983. The pivotal trial for the treatment of relapsing-remitting multiple sclerosis began in 1988. A PLA was filed for this indication in 1992 by Berlex and Chiron, and FDA approval was received in 1993. Betaseron is synthesized in E. coli and deposited as inclusion bodies. The manufacturing process involves solubilization and reduction of the insoluble protein, followed by purification by organic extraction, cystine oxidation and size exclusion chromatographic steps. The purified Betaseron is formulated with human serum albumin to maintain solubility at neutral pH. The complete primary sequence of Betaseron was verified by amino and carboxy-terminal sequence analysis, peptide mapping, amino acid analysis and fragment analysis after chemical cleavages. Overlapping amino acid sequence information confirmed that the amino acid sequence is the same as predicted by the DNA sequence. The amino-terminal methionine of Betaseron is removed after synthesis in E. coli. An intramolecular disulphide bond between Cys 31 and Cys 141 formed during the manufacturing process is routinely confirmed by peptide map analysis. The purity of Betaseron is assessed using a panel of analytical methods including non-reducing and reducing SDS-PAGE and reversed phase HPLC analysis where minor product-related components can be identified. These minor species were characterized with respect to their biological and biochemical properties, and identified using a variety of approaches including construction of additional, beta-interferon analogs. There is significant redundancy in the release testing of Betaseron. The amount of characterization information available on this relatively simple molecule along with the extensive manufacturing experience would suggest that some redundant testing could be eliminated for this well-characterized protein.

Amino Acid Sequence↗
PubMed1997

Identification of the mouse homologue of human discs large and rat SAP97 genes.

The human homologue of the Drosophila discs large (dlg) tumor suppressor gene encodes a 926 amino acid protein, hDlg, which is a member of the MAGUK (Membrane Associated GUanylate Kinase homologues) family of proteins. To facilitate the development of murine model system for functional studies in vivo, the primary structure of the mouse homologue of hDlg has been determined. Dlgh1 encodes a approximately 5.5 kb transcript that is ubiquitously expressed in murine tissues. Mouse mDlg is a 927 amino acid protein that is 95% identical to hDlg and 94% identical to rat synapse associated protein, SAP97. The unusually high conservation of the primary structure of murine and human Dlg proteins across their distinct protein domains suggests a conserved function in vivo.

Adaptor Proteins, Signal Transducing↗