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The CD45 antigen is essential for normal antigen receptor-mediated signalling in lymphocytes, and different patterns of splicing of CD45 are associated with distinct functions in lymphocytes. Abnormal CD45 splicing has been recognized in humans, caused by a C77G transversion in the gene encoding CD45 (PTPRC). Recently the C77G polymorphism has been associated with multiple sclerosis and increased susceptibility to HIV-1 infection. These studies suggest that the regulation of CD45 splicing may be critical for the proper function of the immune system. Because of these data we examined the frequency of the C77G allele in African and Asian populations from countries with high or low prevalence of HIV infection. Here we report that the variant CD45 C77G allele is absent in African populations. We further show that populations living in the Pamir mountains of Central Asia have a very high prevalence of the C77G variant.

We have previously demonstrated that compound heterozygous (SAO/G701D) and homozygous (G701D/G701D) mutations of the anion exchanger 1 (AE1) gene, encoding erythroid and kidney AE1 proteins, cause autosomal recessive distal renal tubular acidosis (AR dRTA) in Thai patients. It is thus of interest to examine the prevalence of these mutations in the Thai population. The SAO and G701D mutations were examined in 844 individuals from north, northeast, central, and south Thailand. Other reported mutations including R602H, DeltaV850, and A858D were also examined in some groups of subjects. The SAO mutation was common in the southern Thai population; its heterozygote frequency was 7/206 and estimated allele frequency 1.70%. However, this mutation was not observed in populations of three other regions of Thailand. In contrast, the G701D mutation was not found in the southern population but was observed in the northern, northeastern, and central populations, with heterozygote frequencies of 1/216, 3/205, and 1/217, and estimated allele frequencies of 0.23%, 0.73%, and 0.23%, respectively. The higher allele frequency of the G701D mutation in the northeastern Thai population corresponds to our previous finding that all Thai patients with AR dRTA attributable to homozygous G701D mutation originate from this population. This suggests that the G701D allele that is observed in this region might arise in northeastern Thailand. The presence of patients with compound heterozygous SAO/G701D in southern Thailand and Malaysia and their apparently absence in northeastern Thailand indicate that the G701D allele may have migrated to the southern peninsular region where SAO is common, resulting in pathogenic allelic interaction.

Using PCR-SSOP typing we have deduced the composition and frequency of HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, and -DQB1 alleles present in DR51-, DR52-, and DR53-related haplotypes, in 519 individuals representative of five ethnic Thai populations recruited in central, northeastern and northern Thailand. In total, we have unequivocally detected at varying frequencies, 17 DR51-related haplotypes, 24 DR52 haplotypes, and 12 DR53 haplotypes in the study groups. We document evidence of north-south gradients of DR51-related haplotypes, whereby the overall frequency of DR51-containing haplotypes is relatively more common in the northern Thai groups. Similarly, within DR53-related haplotypes the frequency of DRB1∗0901-containing haplotypes increases in the more northerly groups, and an inverse effect was observed with DRB1∗0701-containing haplotypes that were relatively more common in the northeastern and central Thais. We have also compared the class II haplotype profiles of the Thais with the equivalent profiles reported in other non-Thai ethnic groups from mainland and insular SE Asia. One DR51-related haplotype DRB1∗1502x, DRB5∗0102x, DQA1∗0101/4, DQB1∗0501, would appear to be characteristic of Thai populations, as it was the most common DR2 haplotype in all five study groups and is also prevalent in other mainland southeast Asians, but is much less evident in the more northern populations of eastern Asia or China.

We performed a placebo-controlled study to evaluate the effects of immunomodulatory treatment with thalidomide on HIV levels, TNF-alpha levels, and immune status of 31 HIV-infected individuals, after temporary suppression of viral replication with antiretroviral drugs. Treatment with a combination of zidovudine and lamivudine (ZDV/LMV) for 14 days resulted in a median decline in plasma viremia of 1.94 log10 RNA equivalents/ml. After discontinuation of ZDV/LMV, thalidomide therapy (200 mg/day for 4 weeks) did not retard the prompt return of HIV titers to the pretreatment levels, and had no effect on plasma levels of TNF-alpha. In contrast, thalidomide treatment resulted in significant immune stimulation. We observed increased levels of plasma soluble IL-2 receptor, soluble CD8 antigen, and IL-12 (p0.01 for all parameters), as well as increased cutaneous delayed-type hypersensitivity reactions to recall antigens (p0.01) in thalidomide-treated patients. These changes were associated with a median increase in HIV titer of 0.2 log10 RNA equivalents/ml in the thalidomide-treated group (p0.05), which resolved after stopping the drug. Further studies were performed in vitro to elucidate the mechanism of thalidomide-induced immune stimulation. When purified T cells from HIV-infected individuals were stimulated by immobilized anti-CD3 in the presence of thalidomide, a costimulatory effect of the drug was observed, resulting in increased production of IL-2 and IFN-gamma, and increased T cell-proliferative responses. Further experiments showed that thalidomide increased IL-12 production by antigen-presenting cells in a T cell-dependent manner. Our findings suggest a potential application for thalidomide as a novel immune adjuvant in HIV disease.

Warfarin has been widely used for the prevention and treatment of thromboembolism. Warfarin therapy depends on interaction between physiological, environmental, and genetic factors. Vitamin K epoxide reductase (VKORC1) and cytochrome P450 2C9 (CYP2C9) enzyme conjointly determine the warfarin maintenance dose. The prevalence of CYP2C9 and VKORC1 variants varies among ethnic groups. The purpose of the present study was to investigate the prevalence of CYP2C and VKORC1 in the Northern Thai population.Patients with valvular heart disease who regularly took a steady maintenance warfarin dose for at least one month were recruited into the present study. Patients who had taken amiodarone or an anti-inflammatory drug were excluded Clinical data were obtained from medical records. Five milliliters of whole blood was drawn from each patient for gene analysis and prothrombin time with international normalized ratio (INR) measurement.From 242 patients, CYP2C9 *1/*1 was found in 230 patients (95%) and CYP2C9 *1/*3 was found in 12 patients (5%). Neither mutant CYP2C9*2 allele nor individuals homozygous for CYP2C9*3 were observed. Regarding VKORC1, haplotype AB was found in 83 patients (34.3%) and haplotype AA was found in 154 patients (63.6%). Haplotype BB (wild type) was found in five patients (2.1%).The prevalence of CYP2C9 *1/*1 is high while the prevalence of CYP2C9*2 and CYP2C9*3 is very low. VKORC1 haplotype AA is the most common among the Northern Thai population. Further study regarding pharmacogenetic and non-genetic factors to develop warfarin-dosing algorithm is warranted

In sub-Saharan Africa, the Pacific, and particularly Asia, hepatitis B virus (HBV) infection is highly endemic, the most common route of transmission is perinatal. To minimize the number of horizontal transmissions, we determined the prevalence of HBV genotypes among children in northern Thailand. From a survey of 1,231 schoolchildren in Chiang Mai during 1998 to 2000, 55 (4.5%) were found positive for HBsAg. Fifty-three HBsAg-positive samples were available for this study. These came from 28 girls (52.8%) and 25 boys (47.2%), age 5-16 years, with a mean age of 12.8 (+/-2.6) years. The laboratory method was based on a multiplex-PCR for the detection of 6 HBV genotypes (A-F). Among 53 HBsAg positive cases, 48 (90.6%) were genotype C, followed by 4 cases of genotype B (7.5%), and 1 case (1.9%) with mixed infection with genotypes B and C. The high prevalence of HBV genotype C follow by genotype B is similar to that found among blood donors in northern Thailand and the nationwide epidemiological survey conducted in 2004. Perinatal transmission may play an important role in the spread of the virus in this area, as in other Asian countries, where genotypes C and B are highly prevalent.

CD45 is crucial for normal lymphocyte signalling, and altered CD45 expression has major effects on immune function. Both mice and humans lacking CD45 expression are severely immunodeficient, and single-nucleotide polymorphisms in the CD45 gene that cause altered splicing have been associated with autoimmune and infectious diseases. Recently, we identified an exon 6 A138G polymorphism resulting in an increased proportion of activated CD45RO T cells and altered immune function. Here we report a significantly reduced frequency of the 138G allele in hepatitis C Japanese patients and a possibly reduced frequency in type I diabetes. The allele is widely distributed in the Far East and India, indicating that it may have a significant effect on disease burden in a large part of the human population.

A randomized double blind placebo controlled trial to determine the efficacy and safety of combined-herbs (SH) given with zidovudine (ZDV) and zalcitabine (ddC) for the treatment of HIV infection in Thai adults was conducted in 3 hospitals in northern Thailand during 2002 to 2003. The eligible subjects were HIV-infected Thai adults who had never received anti-retrovirals, had a Karnofski Performance Score (KPS) ofor = 70, and had no opportunistic infections. The subjects were randomized to receive either a combination of ZDV 200 mg three times per day, ddC 0.75 mg three times per day, and SH 2.5 g three times per day or a combination of ZDV 200 mg three times per day, ddC 0.75 mg three times per day, and placebo 2.5 g three times per day for 24 weeks. The main outcome measures were HIV-RNA, CD4 cells, and blood chemistry profiles prior to the treatment and then every 4 weeks for 24 weeks. The baseline characteristics of 60 evaluable subjects, 40 in the SH group and 20 in the placebo group, were not significantly different. HIV RNA at week 4 and thereafter was significantly decreased from the baseline value in both groups (p0.001). However, the decline in HIV RNA in the SH group was significantly more than that in the placebo group. The CD4 cells in the SH group at week 12 and thereafter were significantly increased from the baseline value. Serious adverse events in the two groups were not observed. It is concluded that an addition of SH herbs to two nucleoside reverse transcriptase inhibitors has greater antiviral activity than antiretrovirals only. The SH herbs may be an alternative for the third anti-retroviral agent in the triple drug regimen for the treatment of HIV infected patients in countries with limited resources.

Title Short Communication Seroprevalence of hepatitis D virus infection among HBsAg carriers in northern Thailand Author(s) Jutavijittum, Prapan; Jiviriyawat, Yupa; Yousukh, Amnat; Kunachiwa, Warunee; Hayashi, Shigeki; Toriyama, Kan Citation 日本熱帯医学会雑誌, vol.30(3), pp.319-320; 2002 Issue Date 2002-09-15 URL http://hdl.handle.net/10069/22439 Right Japanese Society of Tropical Medicine NAOSITE: Nagasaki University's Academic Output SITE