Biomedical subjects

Wei Hou

Publications and source records attributed to Wei Hou.

36 records · Page 2Linked to original sources

PubMed2005

Immunogenicity, safety, and protective efficacy of an inactivated SARS-associated coronavirus vaccine in rhesus monkeys.

An inactivated vaccine for severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was evaluated in rhesus monkeys. The monkeys were inoculated intramuscularly (i.m.) with 0.5, 5, 50, or 5000 microg of vaccine, or PBS as control, and boosted on day 7. After 3 weeks, they were challenged with the NS-1 strain of SARS-CoV. The humoral and mucosal immune responses, clinical signs, chemical indices and viremia were monitored following the immunization and challenge. The control animals who received PBS developed atypical SAR-CoV infection after viral challenge, according to clinical, virological and pathological findings. No systematic side effects were observed in vaccinated animals post-immunization, even in at the high dose of 5000 microg. The 50 microg dosage of vaccine elicited SARS-CoV specific immune responses against viral infection as compared to the partial immunity elicited by 0.5 and 5 microg doses. The results show that this inactivated vaccine can induce effective concomitant humoral and mucosal immunity against SARS-CoV infection, is safe in monkeys, and the vaccine maybe a good candidate for clinical trials.

Animals↗

PubMed2005

A general model for detecting genetic determinants underlying longitudinal traits with unequally spaced measurements and nonstationary covariance structure.

A mixture model for determining quantitative trait loci (QTL) affecting growth trajectories has been proposed in the literature. In this article, we extend this model to a more general situation in which longitudinal traits for each subject are measured at unequally spaced time intervals, different subjects have different measurement patterns, and the residual correlation within subjects is nonstationary. We derive an EM-simplex hybrid algorithm to estimate the allele frequencies, Hardy-Weinberg disequilibrium, and linkage disequilibrium between QTL in the original population and parameters contained in the growth equation and in the covariance structure. A worked example of head circumference growth in 145 children is used to validate our extended model. A simulation study is performed to examine the statistical properties of the parameter estimation obtained from this example. Finally, we discuss the implications and extensions of our model for detecting QTL that affect growth trajectories.

Algorithms↗

PubMed2005

Outcome from a prospective, longitudinal study of prenatal cocaine use: preschool development at 3 years of age.

OBJECTIVE: To determine the effects of prenatal cocaine exposure on child development. METHODS: This prospective, longitudinal study recruited 154 pregnant cocaine users who were matched on race, parity, socioeconomic status, and perinatal risk to 154 noncocaine users. Drug use status was determined by maternal history and urine screening. At 3 years of age, the child subjects were assessed by an evaluator blinded to maternal drug use history. During a home visit at age 3, caregiver, family, and home assessments were administered. RESULTS: Structural equation modeling showed a direct effect of the amount of prenatal cocaine exposure on the adjusted birth head circumference which in turn directly affected preschool development. CONCLUSIONS: We could not demonstrate a direct effect of prenatal cocaine exposure on preschool development, a result that is consistent with that of earlier work and now extending findings to age 3. However, cocaine continued to exert an indirect effect on development through its direct effect on the head circumference at birth.

Child, Preschool↗

PubMed2005

Use and persistence of pharmacotherapy for elementary school students with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to describe rates of attention-deficit/hyperactivity disorder (ADHD) medication treatment and relevant school services use during a 2-year period, and to examine independent predictors of these interventions. METHOD: Parent and child interviews (n = 266) and follow-up 12-month telephone surveys (n = 220) were conducted among a high-risk sample, selected from a districtwide, stratified, random sample of elementary-school students screened for ADHD risk. Medication treatment status and school services use were assessed from multiple sources, and their predictors were identified by logistic regression modeling, adjusting for sociodemographic and parental characteristics, as well as clinical-need variables. RESULTS: Approximately one third (35%) of the children received ADHD medications during a 2-year period, and of those treated at Time 2, approximately one third (36%) were no longer on medications at Time 3. Boys were more than twice as likely to receive ADHD medication as girls. Approximately one quarter (28%) of the children accessed school services and continued their use over 2 years. African-American youths were more likely to receive school services than were Caucasian children. CONCLUSIONS: In this elementary school-district high-risk sample, care for ADHD was remarkable for underuse and attrition of medication treatment, as well as poor linkage to relevant school services. Interventions to improve ADHD care should include supports to access and sustain medication treatment, as well as link with school services, especially for girls.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

CTLA-4 gene polymorphisms in Chinese patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by chronic inflammation of the colon and rectum as a result of an exaggerated T-cell response. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a T cell-restricted surface molecule induced with TCR or CD28 activation. There is evidence for genetic involvement of CTLA-4 in several autoimmune diseases, with the focus on the possible role of genetic variation of the CTLA-4 locus. The aim of this study was to investigate CTLA-4 gene polymorphisms in patients with UC in a Chinese population with Han nationality. METHODS: The C-318T polymorphism in the promoter region and A+49G polymorphism in exon 1 of the CTLA-4 gene were studied by a polymerase chain reaction-sequence-specific primer method. We studied 82 unrelated patients with UC and 204 healthy controls in a Chinese population with Han nationality. RESULTS: The frequency of the haplotype 2,3 (-318C+49G/-318T+49A) was 26% in patients with UC and 41% in healthy controls (Fisher exact test P = 0.0147, odds ratio = 0.4918, 95% confidence interval: 0.2784 - 0.8688), but this significance disappeared when Bonferoni correction was applied. No other significant differences in the distribution of allele and genotype frequencies were observed between C-318T and A+49G gene polymorphisms and UC in the Chinese Han population. CONCLUSION: The C-318T and A+49G polymorphisms of the CTLA-4 gene were not associated with UC in Chinese Han patients.

Adolescent↗

PubMed2005

Targeted therapy of human laryngeal squamous cell carcinoma in vitro by antisense oligonucleotides directed against telomerase reverse transcriptase mRNA.

A number of different approaches have been developed to inhibit telomerase activity in human cancer cells. In this study, the effect of antisense oligonucleotides (ODNs) by targeting human telomerase reverse transcriptase (hTERT) mRNA in a laryngeal cancer cell line (Hep-2) was investigated. A 20mer antisense oligodeoxynucleotide targeting the most open part of hTERT mRNA (anti-hTERT) and a mismatched control sequence were synthesized. Cells were treated daily with oligonucleotides for up to 72 hours. hTERT mRNA expression was measured by the reverse transcription polymerase chain reaction (RT-PCR) assay; telomerase activity by the telomerase PCR ELISA assay kit (TRAP; Boehringer Mannheim, GmbH, Mannheim, Germany). Cell viability after administration of ODNs was determined using the MTT assay. Morphological changes were examined by haematoxylin and eosin staining. The cell cycle was analyzed using flow cytometry. It was found that antisense treatment induced a decrease in hTERT mRNA expression, telomerase activity, cell growth rate, cell viability, and an increase in apoptosis. The results suggest that inhibition of telomerase activity in Hep-2 cells by short-term antisense treatment against the mRNA of hTERT results in apoptotic cell death. The treatment with anti-hTERT may be useful as a treatment modality for laryngeal squamous carcinoma.

Apoptosis↗

PubMed2005

Character of HBV (hepatitis B virus) polymerase gene rtM204V/I and rtL180M mutation in patients with lamivudine resistance.

OBJECTIVES: To investigate the relationship between HBV (hepatitis B virus) polymerase gene 180 and 204 sites mutation and lamivudine resistance. METHODS: One hundred forty-one patients with lamivudine resistance after lamivudine treatment and 60 chronic hepatitis B patients without lamivudine treatment were enrolled in this study. The serum HBV DNA mutation was analyzed by sequence detection via polymerase chain reaction (PCR). The sequences of the same patient were analyzed before and after lamivudine treatment. RESULTS: One hundred and nine lamivudine resistance patients had HBV YMDD (tyrosine-methionine-aspartate-aspartate) mutation. Among them, 45 patients had rtL180M/M204V mutation (41.28%), 28 patients had rtL180M/M204I mutation (25.70%) and 36 patients had rtM204I mutation (33.02%). There were 6 patients with rtL180M mutation in 32 lamivudine resistance patients. Sixty chronic hepatitis patients without lamivudine treatment had no mutations. CONCLUSIONS: HBV mutations, which play an important role in lamivudine resistance usually locate at polymerase gene 204 site; 180 site mutation was also observed in these patients. Evaluation of the anti-virus therapy by surveillance of the two sites mutations is of importance.

China↗

PubMed2005

Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy.

OBJECTIVE: To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartate-aspartate (YMDD) mutation after lamivudine therapy. METHODS: This investigation was a retrospective study of 63 CHB patients with YMDD mutation during lamivudine therapy. Clinical data, including period and types of YMDD mutation; hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) levels before and after YMDD mutation were measured. YMDD mutation in the HBV DNA polymerase gene was determined using polymerase chain reaction (PCR) and direct sequencing. HBV DNA quantification was determined using real-time PCR. Relevant serum markers of HBV were measured. The follow-up period was 12 months after YMDD mutation. RESULTS: YMDD mutation occurred 7-44 months (median, 21.5 months) after the start of lamivudine therapy. The majority of the cases (42/63, 66.6%) had YMDD mutants detected between 12 and 24 months. Four types of YMDD mutation were observed in this study, rtL180M/M204V mutation was the predominant type (26/63, 41.3%). A proportion of patients (16/63, 25.4%; 12/63, 19.1%) had higher HBV DNA levels and ALT levels (after mutation vs before mutation), respectively. CONCLUSION: The majority of patients with YMDD mutants had similar or lower HBV DNA levels and ALT levels compared with baseline values. This subset of patients might have benefited from the continued lamivudine therapy. The patients with increased ALT and HBV DNA levels (breakthrough hepatitis) should benefit from the addition of a newer nucleotide analogue (e.g. adefovir).

Adolescent↗

PubMed2005

Effect of IFNalpha-2a on Fas expression and apoptosis rate of peripheral blood cytotoxic T cells in patients with hepatitis B.

BACKGROUND: Interferon(IFN) with antiviral and immunomodulatory activities is one of the most important therapeutic agents for the treatment of chronic hepatitis. The apoptotic effect of IFN is influenced by cell type and the types of IFN, which suppresses proliferation and induces apoptosis in some cell types while inhibiting apoptosis in others. The aim of this study was to explore the effect of IFNalpha-2a on Fas expression and the apoptosis rate of peripheral blood cytotoxic T cells(CTLs) in patients with hepatitis B. METHODS: Peripheral blood mononuclear cells were isolated from 26 patients with hepatitis B including 16 patients with chronic hepatitis B and 10 patients with chronic severe hepatitis B. Fas expression and apoptosis rate of CTLs were analyzed with flow cytometry before and after IFNalpha-2a treatment. RESULTS: Before IFNalpha-2a treatment, Fas expression and apoptosis rate of CTLs from patients with chronic hepatitis B were significantly higher than those from patients with chronic severe hepatitis B and healthy controls respectively. No significant difference was observed between Fas expression and apoptosis rate of CTLs from patients with chronic severe hepatitis B and healthy controls. After IFNalpha-2a treatment, Fas expression and apoptosis rate of CTLs from different groups were compared with those before IFNalpha-2a treatment, showing no significant difference despite alternation of different degree. CONCLUSIONS: Activation induced cell death (AICD) exists in peripheral blood CTLs from patients with hepatitis B. No effect of IFNalpha-2a exerts on Fas expression and apoptosis rate of Fas in patients with hepatitis B.

Adult↗

PubMed2005

HBV genotype characterization and distribution in patients with HBV-related liver diseases in Zhejiang Province, P.R. China: possible association of co-infection with disease prevalence and severity.

BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P<0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and 3 (17.7%) and (ii) hepatocellular carcinoma (HCC) 2 (28.6%), 5 (71.4%) and 0 (0.0%) respectively revealed a marked association of C genotype with liver disease; however, the association was statistically insignificant (P>0.05). Differences in positive rate of HBeAg for the three genotypes B, 16 (30.8%), C, 27 (51.9%), and mixed B/C, 9 (17.3%) were significant (P<0.05), with genotype C showing predominance. CONCLUSIONS: These findings show an interesting distribution of HBV A-D genotypes in Zhejiang Province. Furthermore, our results indicate a novel and markedly high prevalence of mixed B/C genotype infections in subjects with severe CH and LC, and a possible association of mixed B/C infections with the severity of liver diseases in this region of Mainland China.

Adult↗

PubMed2005

In vitro cleavage of hepatitis B virus C mRNA by 10-23 DNA enzyme.

BACKGROUND: 10-23 DNA enzyme is one kind of deoxyribozymes for RNA cleavage. The inhibition effects of 10-23 DNA enzyme on the expression of the HBV C gene in HepG2.2.15 cells were demonstrated previously. The aim of this study was to further explore the cleavage activities of 10-23 DNA enzyme targeting at HBV C gene mRNA in vitro. METHODS: 10-23 DNA enzyme named Drz-HBV-C-9 specific to HBV C gene ORF A(1816)UG was designed and synthesized. HBV C gene mRNA was obtained by the in vitro transcription method. Cleavage activities of Drz-HBV-C-9 were observed in vitro. Values of kinetic parameters including Km,Kcat and Kcat/Km were calculated accordingly. RESULTS: Under the certain cleavage conditions, Drz-HBV-C-9 could efficiently cleave target mRNA at specific sites in vitro. Cleavage products of 109nt plus 191nt were obtained. The kinetic parameters, Km, Kcat and Kcat/Km for Drz-HBV-C-9, were 1.4 X 10(-9) mol, 1.6 min-1 and 1.1 X 10(9) mol(-1) x min(-1), respectively. CONCLUSIONS: 10-23 DNA enzyme targeting at HBV C gene mRNA possesses specific cleavage activities in vitro. This would be a potent antiviral strategy with respect to HBV gene therapy.

Antiviral Agents↗

PubMed2003

[Targeted therapy of human laryngeal squamous cell carcinoma in vitro with telomerase catalytic subunit mRNA].

OBJECTIVE: To study the effect of antisense oligonucleotide targeted human telomerase catalytic subunit (hTERT) on Hep-2 cell line. METHOD: Cells were treated daily with oligonucleotide (ODN) directed against hTERT, or control ODN-a mismatched sequence or only Lipofectamine. At 24 h, 48 h, 72 h cell viability after administration of ODNs was determined using the MTT assay. At 72 h, the morpholog alteration of the cells was observed by HE stain. At 72 h, telomerase activity was determined. RESULT: After daily transfection ASODN, some Hep-2 cells begin to stop growing up, but not in the mismatched ODN group or Lipofectamine group. Hep-2 cells treated with antisense against hTERT showed a decrease in telomerase activity. CONCLUSION: hTERT antisense ODN can inhibit telomerase activity and the growth of Hep-2 cells in short term.

DNA-Binding Proteins↗

PubMed2003

[Use of glucocorticoid in treatment of severe acute respiratory syndrome cases].

OBJECTIVE: To explore the effect of glucocorticoid in the treatment for severe acute respiratory syndrome (SARS). METHODS: Clinical data of 70 patients with SARS admitted to Youan Hospital in Beijing during March to May, 2003 were analyzed. RESULTS: (1) Sixty-three of 70 cases of SARS recovered and seven cases died, with a case-fatality ratio of 10%. (2) Average length of hospital stay was 16.9 days for the all 70 cases, and 16.8 days for the 11 cases without glucocorticoid treatment, without statistical significance (F = 1.018, P = 0.39). (3) The other 59 cases were administered with 40 mg to 640 mg of methylprednisolone daily. (4) Average hospital stay was 15 days for the 23 cases with lower dose of 40 mg to 80 mg methylprednisolone daily, 18.5 days for the 27 cases with medium dose of 120 mg to 240 mg daily, and 17.9 days for the nine cases with higher dose of 320 mg to 640 mg daily (F = 1.018, P = 0.39). CONCLUSIONS: Earlier use of glucocorticoid therapy with suitable doses could alleviate their clinical symptoms, improve their clinical courses, and promote the absorbance of infiltration in their lungs on chest-X-ray films for the cases with SARS. However, current clinical data showed that glucocorticoid therapy could not shorten the length of hospitalization for the cases with SARS.

Adolescent↗

PubMed2003

[Clinical features of severe acute respiratory syndrome in forty-one confirmed health care workers].

OBJECTIVE: To investigate the clinical features of severe acute respiratory syndrome (SARS). METHODS: Forty-one medical care workers (aged 23 - 55 years, with a average of 32 years; men/women = 8/32) who were admitted to our hospital and diagnosed with SARS during March and April, 2003 were retrospectively analyzed. RESULTS: Thirteen of all the patients were physicians and the rest were nurses. The disease was mainly transmitted through air droplet in a short distance, and overwork induced tiredness was involved in disease stimulation. Seventy-three percent of the patients presented fever as their first symptom. Ten patients complained inertia and myalgia. One patient showed no clinical symptoms, and bilateral infiltrates was found in his chest X-ray. Among the 41 cases, 6 (15%) were diagnosed as severe type. At the first week, the counts of white blood cells (WBCs), lymphocyte and platelets were (4.4 +/- 1.5) x 10(9)/L, 0.22 +/- 0.12 and (143 +/- 37) x 10(9)/L, which were significantly lower when compared with those at the 2nd to 4th week. Abnormal liver function was found in 27 cases (mostly with elevated serum ALT), with 70% occurred at the 3rd or 4th week. In terms of CT, 30 patients (73%) showed pathological changes in lungs, and bilateral lung involvement was found in 35.59%. Of 36 cases treated with steroids, 86% received middle or low dosage (80 - 240 mg/d). Artificial ventilation was used for twenty-seven patients, and air pipe mechanical ventilation was used for 1 case. Mortality in this study was 5%. CONCLUSIONS: Inertia and myalgia may be the earlier symptoms of health care workers with SARS include, which are parallel to CT manifestations. There is no objective index for the assessment of the severity of the disease at early stage. The medicine associated toxicities may be the main reason of liver lesions. damages. Middle or low dosage of steroid was reasonable to be used as early as possible.

Adult↗

PubMed2002

Her-2/neu expression and gene amplification in gastrinomas: correlations with tumor biology, growth, and aggressiveness.

A proportion of gastrointestinal neuroendocrine tumors are aggressive; however, little is known of molecular determinants of their growth, and molecular studies have identified no useful prognostic factors. Overexpression of HER-2/neu is common in some nonendocrine tumors, frequently correlates with increased tumor aggressiveness, and can be used as a basis of treatment with trastuzumab. Little is known of its expression in malignant pancreatic endocrine tumors. In the present study HER-2/neu gene amplification and expression was determined in 43 gastrinomas from different patients. Results were correlated with clinical, laboratory, and tumor characteristics including tumor growth. HER-2/neu gene amplification was assessed by differential PCR, mRNA levels assessed by quantitative PCR, and protein by immunohistochemistry. Fourteen percent of patients had HER-2/neu gene amplification in tumors compared with levels in their WBCs. HER-2/neu mRNA varied over a 700-fold range. However, only 3% exceeded levels seen in normal pancreas, and immunohistochemistry did not show protein overexpression in any tumor (n = 10). HER-2/neu mRNA levels were significantly higher (P = 0.032) in tumors associated with liver metastases but not with tumor location or size. These results show that HER-2/neu amplification/overexpression does not seem to play a role in the molecular pathogenesis of most gastrinomas, as suggested in a previous study involving small numbers of cases. However, mild gene amplification occurs in a subset, and overexpression is associated with aggressiveness. Therefore, HER-2/neu levels could have prognostic significance as well as identify a patient subset with gastrinomas who might benefit from trastuzumab treatment.

Adolescent↗

PubMed2002

Elucidation of the vasoactive intestinal peptide pharmacophore for VPAC(2) receptors in human and rat and comparison to the pharmacophore for VPAC(1) receptors.

Vasoactive intestinal peptide (VIP) functions as a neurotransmitter involved in a number of physiological and pathological conditions. The actions of VIP are mediated through VPAC(1) and VPAC(2). In contrast to VPAC(1), which has been extensively studied, little is known about the pharmacology of VPAC(2). In this study we investigated the VIP pharmacophore for VPAC(2) by using alanine and D-amino acid scanning. We found significant species differences, and the human VPAC(2) (hVPAC(2)) expressed in Chinese hamster ovary (CHO) cells, which have been used in previous studies, differed significantly from the native hVPAC(2) in Sup T(1) cells and hVPAC(2) expressed in PANC1 cells. There was a close agreement between binding affinities and potencies for VPAC(2) activation. The amino acids whose backbone or side chain orientations were most important for high affinity potency are Asp(3), Phe(6), Thr(7), Tyr(10), Arg(12), Tyr(22), and Leu(23), whereas the side chains of Ser(2), Asp(8), Asn(9), Gln(16), Val(19), Lys(20), Lys(21), Asn(24), and Ser(25) are not essential. Comparison of the VIP pharmacophore between hVPAC(1) and hVPAC(2) demonstrated that the side chains of Thr(7), Tyr(10), Thr(11), and Tyr(22) were much more critical for high affinity for the hVPAC(2) than the hVPAC(1). In contrast, the orientation of the side chain of Asn(24) was more important for high affinity for the hVPAC(1). This study shows that in assessing the pharmacophore of VIP analogs for the VPAC(2), important species differences need to be considered as well as the expression system used. These results of our study should be useful for designing VPAC subtype-selective analogs, simplified analogs, and possibly metabolically stable analogs.

Adenylyl Cyclases↗

PubMed2002

Elucidation of vasoactive intestinal peptide pharmacophore for VPAC(1) receptors in human, rat, and guinea pig.

Vasoactive intestinal peptide (VIP) is a neurotransmitter involved in a number of pathological and physiological processes. VIP is rapidly degraded and simplified stable analogs are needed. VIP's action was extensively studied in rat and guinea pig. However, it is largely unknown whether its pharmacophore in these species resembles human. To address this issue we investigated the VIP pharmacophore for VPAC(1) (the predominant receptor subtype in cancers and widely distributed in normal tissues) by using alanine and D-amino acid scanning. Interaction with rat, guinea pig, and human VPAC(1) was assessed using transfected Chinese hamster ovary (CHO) and PANC1 cells and cells possessing native VPAC(1). Important species differences existed in the VIP pharmacophore. The human VPAC(1) expressed in CHO cells, which were used almost exclusively in previous studies, differed markedly from the native VPAC(1) in T47D cells. The most important amino acids for determining affinity are His(1), Asp(3), Phe(6), Arg(12), Arg(14), and Leu(23). Ser(2), Asp(8), Asn(9), Thr(11), Val(19), Asn(24), Ser(25), Leu(27), and Asn(28) are not essential for high-affinity interaction/activation. [Ala(2,8,9,11,19,24,25,27,28)]VIP, which contained 11 alanines, was synthesized and it was equipotent to VIP at VPAC(1) receptors in all species and was metabolically stable. Our results show in any design of simplified VIP analogs for VPAC(1) it will be important to consider species differences and it is essential to use transfected systems that reflect the native receptor's pharmacophore. Last, with our results a simplified, metabolically stable VIP analog was identified that should be useful as a prototype for design of selective agonists/antagonists that could be useful therapeutically.

Alanine↗

PubMed2000

The relation between HLA-DQA1 genes and genetic susceptibility to duodenal ulcer in Wuhan Hans.

AIM:To study the genetic susceptibility of HLA-DQA1 alleles to duodenal ulcer in Wuhan Hans.METHODS:Seventy patients with duodenal ulcer and fifty healthy controls were examined for HLA-DQA1 genotypes.HLA-DQA1 typing was carried out by digesting the locus specific polymerase chain reaction amplified products with alleles specific restriction enzymes (PCR-RFLP), i.e.,Apal I, Bsaj- I, Hph I, Fok I, Mbo II and Mnl I.RESULTS:The allele frequencies of DQA10301 and DQA1-0102 in patients with duodenal ulcer were significantly higher and lower respectively than those in healthy controls (0.40 vs 0.20, P = 0.003, P(corret) = 0.024) and (0.05 vs 0.14, P = 0.012, but P(corret) > 0.05), respectively.CONCLUSION: DQA1(*)0301 is a susceptible gene for duodenal ulcer in Wuhan Hans, and there are immunogenetic differences in HLA-DQA1 locus between duodenal ulcer patients and healthy controls.

Journal Article↗