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Biomedical subjects

L Lin

Publications and source records attributed to L Lin.

At least 109 records · Page 6Linked to original sources
PubMed1997

Cloning and characterization of the Neisseria meningitidis rfaC gene encoding alpha-1,5 heptosyltransferase I.

We cloned and characterized the Neisseria meningitidis rfaC gene which encodes an enzyme, alpha-1,5 heptosyltransferase I, involved in the synthesis of the deep-core of the lipooligosaccharide. The N. meningitidis rfaC mutant, obtained by an allelic exchange, produced lipooligosaccharide which migrated faster in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the lipooligosaccharide isolated from the wild-type N. meningitidis. The N. meningitidis rfaC mutant was not affected by growth in a rich microbiological medium and did not show any defect in adhesion to epithelial cell lines. Conversely, the rfaC mutant was attenuated in the infant rat model of meningococcemia, thus confirming the importance of intact lipooligosaccharide in the virulence of N. meningitidis.

Amino Acid Sequence↗
PubMed1997

A point mutation in the glucose-dependent insulinotropic peptide receptor confers constitutive activity.

The glucose-dependent insulinotropic peptide receptor (GIP-R) is a member of the secretin and parathyroid hormone (PTH) family of seven transmembrane-spanning receptors. Point mutations of a histidine at the junction between the first intracellular loop and the second membrane-spanning domain and a threonine in the sixth membrane-spanning domain of the human PTH-receptor have been reported to be associated with constitutive activation of the PTH receptor in Jansen-type metaphyseal chondrodysplasia. In this study, we explored whether such mutations in the GIP-R might similarly induce constitutive, ligand-independent activation of the receptor. Single amino acid substitutions in the GIP receptor were made by site-directed mutagenesis and receptor binding and cAMP levels were measured in transfected human embryonal kidney cell line (L293). Mutation of the threonine at position 340 in the sixth transmembrane spanning domain to proline (T340P) led to agonist-independent constitutive activity and exhibited a four-fold increase in basal cAMP level as compared to the wild-type GIP-R. The increase in cAMP level in T340P mutant was proportional to the amount of transfected plasmid and corresponded to the receptor number on the cell surface. Despite its high basal cAMP level, the T340P mutant could be further stimulated by GIP, with maximal cAMP generation comparable to the wild-type receptor. The change of amino acid histidine at position 169 to arginine (H169R), however, behaved like the wild type receptor and did not possess constitutive activity. These results illustrate that a point mutation of threonine to proline at position 340 results in constitutive activation of the GIP receptor, without affecting its sensitivity to agonist stimulation.

Amino Acid Sequence↗
PubMed1997

Comparisons of the effects of enterostatin on food intake and gastric emptying in rats.

The effects of central and peripheral administration of enterostatin (ENT) on food intake and gastric emptying of a non-nutrient liquid meal have been studied in rats. Intraperitoneal and intragastric administration of ENT at a dose of 120 nmol suppressed the intake of a high-fat diet but failed to inhibit gastric emptying in Sprague-Dawley (SD) rats. Intracerebroventricular (i.c.v.) ENT (1 nmol) reduced intake of a high-fate diet in Osborne-Mendel (OM) and SD rats but not in S5B/Pl rats, whereas it decreased gastric emptying in S5B/P1 and SD rats but not in OM rats. The data suggest that although central ENT may reduce gastric emptying rate, this effect is not related to the inhibitory effect of ENT on food intake.

Animals↗
PubMed1997

Termination and suppression of idiopathic left ventricular tachycardia by diltiazem.

Idiopathic left ventricular tachycardia is known to be responsive to verapamil in many cases. However, the role of other calcium-channel blockers, such as diltiazem, in treating this specific type of ventricular tachycardia is unknown. We report a case of idiopathic left ventricular tachycardia in a patient with a structurally normal heart, which was terminated and suppressed in the electrophysiology laboratory by a single dose of diltiazem intravenously, and was subsequently suppressed long-term with sustained-release diltiazem. Our finding suggests that idiopathic left ventricular tachycardia may be managed effectively with diltiazem in both the acute and chronic settings.

Adult↗
PubMed1997

Sequence-based association analysis of HLA class I and II alleles in Japanese supports conservation of common haplotypes.

Alleles of HLA-A, B, C, DRB1, DQB1, and DPB1 loci were fully determined in 117 healthy Japanese. A*2402, A*3303, A*1101, A*0201, B*4403, B*5201, Cw*0102, Cw*1403, Cw*0304, Cw*0702, Cw*0801, and Cw*1202 showed frequencies of over 10%. Multi-locus haplotype frequencies were estimated by the maximum likelihood method. Strength of association between C and B loci was comparable with that between DRB1 and DQB1 loci. Alleles unidentified by a serological method and having very similar nucleotide sequences (A2: A*0201, A*0206, A*0207, B61: B*4002, B*4006) were carried by different haplotypes. Several frequent five-locus haplotypes were identified including A*3303-Cw*1403-B*4403-DRB1(*)1302-DQB1(*)0604, and A*2402-Cw*1202-B*5201-DRB1(*)1502-DQB1(*)0601. These sequence-based haplotypes corresponded to serology-based common haplotypes which have already been described in Japanese. These findings indicate that common HLA haplotypes consist of particular sets of HLA alleles and that these haplotypes have been conserved through recent human evolution.

Alleles↗
PubMed1997

Chronic ICV enterostatin preferentially reduced fat intake and lowered body weight.

The pancreatic peptide enterostatin will acutely reduce fat intake in rats provided a choice of diets. Chronic ICV infusions of enterostatin suppress the intake of high fat diet. However, the effects of chronic ICV enterostatin on diet choice has not previously been studied. To investigate this, enterostatin (0.5 microgram/h) or artificial cerebrospinal fluid (CSF) was infused for 9 days into the lateral ventricle of rats adapted to a two-choice high-fat (HF) and low-fat (LF) diet regime. Enterostatin reduced intake of HF diet with the maximum depression at day 4, but there was no compensatory increase in LF intake. The body weight of enterostatin-infused rats declined. This was associated with a reduction in fat pad and liver weights compared to the CSF-infused control rats. Serum triglycerides and insulin were decreased and corticosterone was elevated in enterostatin-infused rats. The data show that enterostatin will chronically reduce fat intake and body weight and suggest that enterostatin may attenuate the appetite for fat.

Animals↗
PubMed1997

Enterostatin actions in the amygdala and PVN to suppress feeding in the rat.

The pentapeptide enterostatin (ENT) inhibits feeding after injection into the cerebral ventricles. To localize the central sites of action of ENT, the peptide (0.01 to 3.3 nM) was microinjected into several brain regions and the intake of a high fat diet was measured. The results show that ENT injection in the paraventricular nucleus (PVN) or the amygdala (AMYG) produced a bi-phasic dose related feeding response, low doses of ENT inhibited feeding while higher dose had no effect. The effective dose to inhibit feeding in the AMYG was 10 fold lower than that in the PVN. No changes in food intake were observed after ENT injection into the ventromedial hypothalamus and nucleus tractus solitarius. The data provide further support that there are targets in the CNS for ENT and suggest that central ENT function is site specific.

Adaptation, Physiological↗
PubMed1997

Japanese population does not manifest significant association between low NK activity and HLA-B(C) locus homozygosity.

It was reported previously that natural killer (NK) activity is controlled by the HLA-B(C) region and that individuals homozygous for HLA-B(C) or homozygous for the NKB complementation groups, which are mapped to the HLA-B(C) region, have fewer circulating NK cells and lower NK activity than do individuals heterozygous for these alleles. Those studies had used subjects in the United States. In the present study, we investigated the NK activity, NK subpopulation, and HLA types of 65 healthy Japanese individuals in Japan, most of whom have a quite different HLA-B(C) type than did subjects in the earlier study. Among 13 individuals having low NK activity, only two were HLA-B(C) homozygous and the rest were heterozygous. No obvious relation between low NK activity and specific HLA-B(C) allele was found. Seven of the nine HLA-B(C) homozygotes had medium or high NK activity. No significant differences were detected in either the NK activity or in the NK subset frequencies (circulating NK cell number) between HLA-B(C) homozygous and heterozygous individuals. These results indicate that HLA-B(C) homozygosity does not always induce low NK activity and that other factors also may influence NK activities.

Adult↗
PubMed1997

The validity of posttraumatic stress disorder among Vietnamese refugees.

The aim of this study was to examine the validity of posttraumatic stress disorder (PTSD) among Vietnamese refugees. The study population included 74 Vietnamese refugees who had resettled in the metropolitan Boston area. The previously validated Harvard Trauma Questionnaire was used to assess traumatic events and trauma-related symptoms. The number of traumatic events experienced was positively correlated with the severity of PTSD-related symptoms in this population. Internal consistency estimates and principal components analysis provided results that generally supported DSM-IV symptom dimensions of arousal, avoidance, and reexperiencing. However, the emergence of two separate dimensions of avoidance reflected the important contribution of depression to the traumatic response.

Adult↗
PubMed1997

The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells.

Infection of human epithelial cells by Neisseria meningitidis (MC) and Neisseria gonorrhoeae (GC) increases the rate of degradation of LAMP1, a major integral membrane glycoprotein of late endosomes and lysosomes. Several lines of evidence indicate that the neisserial IgA1 protease is directly responsible for this LAMP1 degradation. LAMP1 contains an IgA1-like hinge region with potential cleavage sites for the neisserial type 1 and type 2 IgA1 proteases. Neisserial type 2 IgA1 protease cleaves purified LAMP1 in vitro. Unlike its wild-type isogenic parent, an iga mutant of N. gonorrhoeae cannot affect LAMP1 turnover and its growth in epithelial cells is dramatically reduced. Thus, IgA1 protease cleavage of LAMP1 promotes intracellular survival of pathogenic Neisseria spp.

Animals↗
PubMed1997

Photochemical inactivation of viruses and bacteria in platelet concentrates by use of a novel psoralen and long-wavelength ultraviolet light.

BACKGROUND: A photochemical treatment process has been developed for the inactivation of viruses and bacteria in platelet concentrates. This process is based on the photochemical reaction of a novel psoralen, S-59, with nucleic acids upon illumination with long-wavelength ultraviolet light (UVA, 320-400 nm). STUDY DESIGN AND METHODS: High levels of pathogens were added to single-donor platelet concentrates containing 3 to 5 x 10(11) platelets in 300 mL of 35-percent autologous plasma and 65-percent platelet additive solution. After treatment with S-59 (150 microM) and UVA (0-3 J/cm2), the infectivity of each pathogen was measured with established biologic assays. In vitro platelet function after photochemical treatment was evaluated during 7 days of storage by using a panel of 14 assays. The in vivo recovery and life span of photochemically treated platelets were evaluated after 24 hours of storage in a primate transfusion model. RESULTS: The following levels of pathogen inactivation were achieved: >10(6.7) plaque-forming units (PFU) per mL of cell-free human immunodeficiency virus (HIV), >10(6.6) PFU per mL of cell-associated HIV, >10(6.8) infectious dose (ID50) per mL of duck hepatitis B virus (a model for hepatitis B virus), >10(6.5) PFU per mL of bovine viral diarrhea virus (a model for hepatitis C virus), >10(6.6) colony-forming units of Staphylococcus epidermidis, and >10(5.6) colony-forming units of Klebsiella pneumoniae. Expression of integrated HIV was inhibited by 0.1 microM S-59 and 1 J per cm2 of UVA. In vitro and in vivo platelet function were adequately maintained after antiviral and antibacterial treatment. CONCLUSION: Photochemical treatment of platelet concentrates offers the potential for reducing transfusion-related viral and bacterial diseases.

Animals↗
PubMed1997

Promotion of proliferation of murine BALB/C3T3 fibroblasts mediated by nitric oxide at lower concentrations.

This study showed that nitric oxide (NO)-generating S-nitrosothiols, S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO), increased proliferation of BALB/c 3T3 (clone A31-1-1) fibroblasts in vitro. Treatment with SNAP at a relatively low concentration (0.005-0.02 mM) induced an increase in cell number compared to control. SNAP (0.005-0.02 mM) and GSNO (0.025-0.05 mM) both showed an increase of [3H]thymidine incorporation in exponentially growing cells in a dose-dependent manner. The maximal effect was observed at about 40 and 90% above control at 0.02 mM and 0.05 mM, respectively. The increase induced by 0.02 mM SNAP was abolished by the addition of 0.01 mM oxyhemoglobin, a scavenger of NO. [3H]Thymidine incorporation in stationary cells was also increased by SNAP. In addition, 0.02 mM SNAP produced a 1.8-3.2-fold increase of thymidine kinase activity in exponentially growing cells.

3T3 Cells↗
PubMed1997

Extensive HLA class II studies in 58 non-DRB1*15 (DR2) narcoleptic patients with cataplexy.

Narcolepsy is a sleep disorder that has been shown to be tightly associated with HLA DR15 (DR2). In this study, 58 non-DR15 patients with narcolepsy-cataplexy were typed at the HLA DRB1, DQA1 and DQB1 loci. Subjects included both sporadic cases and narcoleptic probands from multiplex families. Additional markers studied in the class II region were the promoters of the DQA1 and DQB1 genes, two CA repeat polymorphisms (DQCAR and DQCARII) located between the DQA1 and DQB1 genes, three CA repeat markers (G51152, T16CAR and G411624R) located between DQB1 and DQB3 and polymorphisms at the DQB2 locus. Twenty-one (36%) of these 58 non-DR15 narcoleptic patients were DQA1*0102 and DQB1*0602, a DQ1 subtype normally associated with DRB1*15 in DR2-positive narcoleptic subjects. Additional microsatellite and DQA1 promoter diversity was found in some of these non-DR15 but DQB1*0602-positive haplotypes but the known allele specific codons of DQA1*0102 and DQB1*0602 were maintained in all 21 cases. The 37 non-DQA1*0102/DQB1*0602 subjects did not share any particular HLA DR or DQ alleles. We conclude that HLA DQA1*0102 and DQB1*0602 are the most likely primary candidate susceptibility genes for narcolepsy in the HLA class II region.

Cataplexy↗
PubMed1997

Five HLA-B22 group alleles in Japanese.

HLA-B22-group alleles in Japanese were identified using PCR-single-strand conformation polymorphism (SSCP) and sequence analyses. We analyzed genomic DNAs obtained from Japanese individuals positive for HLA-B22 group antigens (HLA-B54, B55, B56) including two locally proposed splits (B55.2, and B22N). In the SSCP analysis of both exons 2 and 3, we discriminated five different B22-group alleles. Each allelic pattern corresponded to each serological split antigen. Direct sequencing analysis of exon 2 and exon 3 showed that alleles encoding B54, B55.1 and B56 antigens in Japanese are encoded by B*5401, B*5502 and B*5601, respectively, and those encoding B55.2 and B22N antigens are previously unidentified alleles, B*5504 and B*5603, respectively. Full-length cDNA sequencing showed that the B*5603 sequence is identical to those of B*5501, B*5502, B*5601, and B*5602 in exons 1 to 2 except for a synonymous substitution at nucleotide position 165 in exon 2. On the other hand, the sequence of exons 3 to 7 was identical to those of some B15 and B46 alleles, suggesting that B*5603 was generated by a recombination event between one of the B55 and B56 alleles and one of the B15 and B46 alleles in intron 2. As for B*5504, the entire exon 1 to 7 sequence is identical to that of B*5502 except that the 5'-half of the exon 3 sequence is identical to those of some B7, B27, B40 and B48 alleles, suggesting that an event such as gene conversion, segmental exchange, or double recombination occurred in this region.

Alleles↗
PubMed1997

DQ microsatellite association studies in three ethnic groups.

Polymorphism at the level of three microsatellite markers (DQCAR, DQCARII, G51152) located in the HLA-DQ region was characterized in 78 10th International Histocompatibility Workshop B-cell lines, 718 random Japanese Asians, 99 Norwegian Caucasians and 95 New Guinean Aborigines with established HLA-DRB1, -DQA1 and -DQB1 typing. DQCAR, DQCARII, and G51152 result in 13, 13, and 11 alleles respectively. All three markers were in tight linkage disequilibrium with HLA-DRB1, -DQA1 and -DQB1. DRB1, DQA1, DQCARII, DQCAR, DQB1, and G51152 haplotypes could be defined for all subjects. In fact, DQ microsatellite typing data could predict DQA1 and DQB1 genotypes with high accuracy and may be used as a simple first pass HLA-DQ typing method. The haplotype data was also used to determine recombination in the DRB1-DQA1 (about 80 kb), DQA1-DQCARII (about 4.5 kb), DQCARII-DQCAR (about 7.5 kb), DQCAR-DQB1 (about 1-1.5 kb) and DQB1-G51152 (about 20-25 kb) genomic segments and the relative rate of slippage microsatellite mutations for DQCAR, DQCARII, and G51152. This led us to conclude that recombination is more frequent in the DRB1-DQA1 and DQCAR-DQCARII segments, thus suggesting cross-overs within small genomic segments are not proportional to genetic distance. We also observed that DQCAR had a higher mutation rate than DQCARII or G51152 and that 1 or 2 CA slippage mutations were arising more frequently from large size microsatellite alleles.

DNA, Satellite↗
PubMed1997

The validity of screening for post-traumatic stress disorder and major depression among Vietnamese former political prisoners.

The aim of this study was to investigate the validity of the Harvard Trauma Questionnaire (HTQ) and the depression sub-scale of the Hopkins Symptom Checklist-25 (HSCL-25) in screening for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) among Vietnamese former political prisoners (POWs). The study population included Vietnamese POWs (n = 51) who migrated to the Boston metropolitan area between January 1990 and July 1992 under the Special Released Re-education Center Detainees Resettlement Program. The criterion validity of the HTQ in assessing PTSD and of the depression sub-scale of the HSCL-25 in assessing MDD is supported by the results. Consideration of an appropriate cut-off score should include examination of the utility of a given screening instrument for PTSD or MDD within different settings, such as refugee camps vs. countries of third asylum.

Adult↗