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Toxoplasma gondii infection was studied in Khon Kaen, northeastern Thailand. Blood specimens were collected from 493 non-pregnant women between 2009 and 2012. Presence of antibodies to T. gondii was determined using the latex agglutination test (cutoff titer 1:32). Thirteen of 493 (2.6%) were found to be seropositive for T. gondii infection. There was no age dependence in the prevalence. The present study reporting a low prevalence of T. gondii infection in northeastern Thailand suggests that the traditional lifestyles and climatic environments may limit the emergence of toxoplasmosis in this region.

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AIMS/BACKGROUND: To investigate how systemic overexpression of IL-4, IL-5 and IFN-gamma affects the severity of experimental conjunctivitis (EC) in mice. METHODS: The tibialis anterior muscle of naive BALB/c mice was electroporated with IL-4, IL-5, IFN-gamma or a control gene, and then the mice blood and conjunctivas were harvested to measure the eosinophil content in these tissues. To evaluate the effects of cytokine gene electroporation on the early-phase reaction (EPR), cytokine gene-electroporated ragweed (RW)-immunised mice were intravenously injected with Evans Blue (EB) and then challenged with RW in eye-drops. Thirty minutes later, their conjunctivas were harvested to extract EB and evaluate the EPR. Additionally, 24 h after RW challenge, conjunctivas were harvested from cytokine gene-electroporated RW-immunised mice, which had not received intravenous injection of EB, to measure conjunctival eosinophilia. RESULTS: Significantly more eosinophils were detected in the blood and conjunctivas of IL-5-electroporated mice in which EC was not induced. The intensity of the EPR was significantly greater in IFN-gamma-electroporated mice. Significantly greater eosinophil infiltration was seen in the conjunctivas of IL-5-electroporated EC-developing mice. CONCLUSIONS: It appears that systemic IL-5 and IFN-gamma play different roles in the development of EC.

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The nonreceptor protein tyrosine kinase c-Abl regulates cell proliferation and survival. Recent studies provide evidence that implicate c-Abl as a mediator for fibrotic responses induced by transforming growth factor-beta (TGF-beta), but the precise mechanisms underlying this novel oncogene function are unknown. Here, we report that when expressed in normal fibroblasts, a constitutively active mutant of Abl that causes chronic myelogenous leukemia (CML) stimulated the expression and transcriptional activity of the early growth response factor 1 (Egr-1). Mouse embryonic fibroblasts (MEFs), lacking c-Abl, were resistant to TGF-beta stimulation. Responsiveness of these MEFs to TGF-beta could be rescued by wild-type c-Abl, but not by a kinase-deficient mutant form of c-Abl. Furthermore, Abl kinase activity was necessary for the induction of Egr-1 by TGF-beta in normal fibroblasts, and Egr-1 was required for stimulation of collagen by Bcr-Abl. Lesional skin fibroblasts in mice with bleomycin-induced fibrosis of skin displayed evidence of c-Abl activation in situ, and elevated phospho-c-Abl correlated with increased local expression of Egr-1. Collectively, these results position Egr-1 downstream of c-Abl in the fibrotic response, delineate a novel Egr-1-dependent intracellular signaling mechanism that underlies the involvement of c-Abl in certain TGF-beta responses, and identify Egr-1 as a target of inhibition by imatinib. Furthermore, the findings show in situ activation of c-Abl paralleling the upregulated tissue expression of Egr-1 that accompanies fibrosis. Pharmacological targeting of c-Abl and its downstream effector pathways may, therefore, represent a novel therapeutic approach to blocking TGF-beta-dependent fibrotic processes.

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BACKGROUND/AIMS: Tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) plays a role in the development of allergic asthma. The study aimed to determine whether TRAIL also participates in the development of experimental allergic conjunctivitis (EC), another allergic disease model. METHODS: EC was induced in BALB/c mice by active immunisation with ragweed (RW) followed by RW challenge. To investigate whether TRAIL in the conjunctiva plays a role in the development of EC, conjunctival TRAIL expression in EC-developing mice was evaluated by immunohistochemistry. Additionally, the effect of subconjunctival injection of recombinant TRAIL on conjunctival inflammation was examined. To investigate whether TRAIL expressed in systemic immunocompetent cells plays a role in the development of EC, anti-TRAIL blocking Ab or anti-TRAIL receptor agonistic Ab was intraperitoneally injected into EC-developing mice, and conjunctival eosinophil infiltration was evaluated. RESULTS: Conjunctival TRAIL expression was not increased by EC induction. Moreover, subconjunctival injection of TRAIL protein in naive mice did not induce conjunctival inflammation. Thus, TRAIL in the conjunctiva is less likely to participate in the development of EC. Systemic treatment with anti-TRAIL blocking Ab in EC-developing mice did not affect the severity of EC. However, systemic treatment during the induction phase of EC with an agonistic Ab for the TRAIL receptor significantly augmented the severity of EC and increased Ag-recall splenocyte IFN-gamma production in vitro. CONCLUSIONS: These results indicate that TRAIL receptor-expressing cells in lymphoid organ participate in the development of EC.

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INTRODUCTION: The reversible nature of deep brain stimulation (DBS) brought renewed interest on surgery to medically intractable mental illnesses. The explosion of anatomical and functional imaging has allowed the development of new potential targets and the understanding of historical targets. METHODS: Fifteen patients undergoing stereotactic surgery for movement disorders, at UCLAs interventional MRI operating-room, were studied with fiber tracking. Stereotactic targets and fiber tracking were determined on MRIs using the Schaltenbrand-Wahren atlas for definition in the iPlan software. Cingulate, subcaudate, BA25/CgWM, amygdala, posterior hypothalamus, orbitofrontal cortex, nucleus accumbens, anterior limb of the internal capsule and dorsomedial thalamus were studied. DTI parameters used ranged from 10 to 20mm for voxel size in the x/y/z planes, fiber length was kept constant at 36 mm, and fractional anisotropy (FA) threshold varied from 0.20 to 0.25. RESULTS: Reliable interconnectivity of targets were determined with DTI and related to PET imaging. Mental illness targets were observed with functional and fiber tract maps. This confirmation yields reliability to DTI imaging in order to determine novel targets and enhance the understanding of areas not well understood. CONCLUSIONS: Currently available imaging techniques, the reversibility of DBS to modulate targets promises to bring a brighter future for surgery of mental illness.

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PURPOSE: To investigate whether inflammatory responses are more severe in uveitic eyes than nonuveitic eyes when acrylic intraocular lens (IOL) is implanted after cataract surgery. METHODS: Clear lens removal (phacoemulsification and aspiration) was conducted and the hydrophobic acrylic IOL (AR40e, AMO) was implanted in adult albino rabbits. Just after the operation, rabbits were divided into two groups. One group (nine rabbits) received intravitreal injection of lipopolysaccharide (LPS, 200 ng/10 microl) into both eyes to induce endotoxin-induced uveitis (EIU) and the other group (nine rabbits) received intravitreal injection of phosphate-buffered saline (PBS, 10 microl) into both eyes as the control. Aqueous humour (AH) and IOLs were harvested 1, 3 , and 7 days after the intravitreal injection. The infiltrating cell number in AH was counted and the protein concentration of AH was measured. IOLs were evaluated morphologically. RESULTS: At 1 day after intravitreal injection, both the infiltrating cell number in AH and protein concentration of AH were significantly higher in the LPS-injected group than in the PBS-injected group. Similarly, more inflammatory cells attached to the surfaces of the IOLs in the LPS-injected group. However, 7 days later, inflammatory reactions subsided and no clear differences in any of the parameters examined were observed between the two groups. CONCLUSIONS: At 7 days after the operation, inflammatory reactions in eyes implanted with the hydrophobic acrylic IOLs were similar in uveitic eyes and nonuveitic eyes. The data suggest that the hydrophobic acrylic IOLs may be suitable for patients with uveitis.

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Epigenetic alterations like DNA methylation and the resulting inactivation of cancer-related genes often contribute to the development of various cancers. To identify the genes that are silenced by aberrant methylation in renal cell carcinoma (RCC), we subjected two RCC lines to methylated CpG island amplification/representational difference analysis. This identified 27 CpG islands. Combined bisulfite restriction analysis of these CpG islands in primary RCC cases revealed that four were methylated in a tumor-specific manner. One of these was identified as the human homeo-box gene B13 (HOXB13) gene, but the remaining three CpG islands were not associated with known genes. The methylation frequencies of HOXB13 in primary RCC samples and lines were 30 and 73%, respectively. The methylation status of HOXB13 correlated with the loss of its expression both in RCC lines and primary tumors, and methyltransferase inhibitor treatment induced the recovery of its expression. Exogenous expression of HOXB13 in RCC cells that lacked endogenous HOXB13 expression suppressed colony formation and induced apoptotic features. Furthermore, HOXB13 methylation correlated positively with tumor grade and microvessel invasion. These results suggest that HOXB13 is a novel candidate tumor suppressor gene in RCC and that its inactivation may play an important role in both RCC tumorigenesis and progression.

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Systemic sclerosis (SSc) is a generalised connective tissue disorder characterised by sclerotic changes in the skin and internal organs. The occurrence of SSc in childhood is rare, with childhood-onset disease representing 3% of all SSc cases, and fewer than 100 such patients have been reported in the world literature to date [1]. We report a case of juvenile SSc with disease onset at the age of 6 months. To our knowledge, this case is the youngest in the world literature.

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Genetic differences among human populations are usually larger for the Y chromosome than for mtDNA. One possible explanation is the higher rate of female versus male migration due to the widespread phenomenon of patrilocality, in which the woman moves to her mate's residence after marriage. To test this hypothesis, we compare mtDNA and Y-chromosome variation in three matrilocal (in which the man moves to his mate's residence after marriage) and three patrilocal groups among the hill tribes of northern Thailand. Genetic diversity in these groups shows a striking correlation with residence pattern, supporting the role of sex-specific migration in influencing human genetic variation.

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Duffy blood group was studied among malaria-endemic Thai and Indonesian populations: Hmong (n = 103), Akha (n = 218), Lisu (n = 44), Bugis (n = 95), Toraja (n = 77), Dani (n = 44), Mee (n = 80) and Irianese (n = 81). Phenotypes were studied by the ordinal indirect Coombs' test and genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) test. DNA analysis was used to type the Duffy blood group system. Deduced allele frequencies of Fya (0.958-1.0) based on the phenotypes were similar to those in other populations in Southeast Asia and Oceania. The study revealed the presence of Fya-antigens showing weak reactivity to antisera as well as a discrepancy between the genotype shown by the PCR-RFLP study and that predicted by the phenotype. The PCR-RFLP study also suggested the presence of an alternative genetic basis for the Fy(a- b-) phenotype, which differs from the African type.

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Smad6 is an inhibitory Smad that is induced by bone morphogenetic proteins (BMPs) and interferes with BMP signaling. We have isolated the mouse Smad6 promoter and identified the regions responsible for transcriptional activation by BMPs. The proximal BMP-responsive element (PBE) in the Smad6 promoter is important for the transcriptional activation by BMPs and contains a 28-base pair GC-rich sequence including four overlapping copies of the GCCGnCGC-like motif, which is a binding site for Drosophila Mad and Medea. We generated a luciferase reporter construct (3GC2-Lux) containing three repeats of the GC-rich sequence derived from the PBE. BMPs and BMP receptors induced transcriptional activation of 3GC2-Lux in various cell types, and this activation was enhanced by cotransfection of BMP-responsive Smads, i.e. Smad1 or Smad5. Moreover, direct DNA binding of BMP-responsive Smads and common-partner Smad4 to the GC-rich sequence of PBE was observed. These results indicate that the expression of Smad6 is regulated by the effects of BMP-activated Smad1/5 on the Smad6 promoter.

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Seroprevalence of antibodies to human T-lymphotropic virus type-1 (HTLV-1) was surveyed among the Thai population by the particle agglutination test and Western blotting test. None of a total of 727 individuals from seven ethnic groups were positive for the specific antibody to HTLV-1. Among hospital based 3,427 subjects in Southern Thailand, one patient with a brain tumor showed positivity in the Western blotting test, however, HTLV-1 proviral genome was not identified by PCR. The present data suggest that HTLV-1 is not endemic in the Thai population and that HTLV-1 is not a major public health problem in Thailand because HTLV-1 rarely causes its associated diseases.

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Screening for a 27-bp deletion in the band 3 protein gene that causes Southeast Asian/Melanesian ovalocytosis (SAO) was carried out using the PCR method among 15 Southeast Asian populations of Thailand (Akha, Hmong, Isaan, Red Karen, White Karen, Black Lahu, Lisu, Manni, Shan, and central Thais) and Indonesia (Bugis, Dayak, Javanese, Madurian, and Toraja). Individuals with the 27-bp deletion were identified only in the Bugis of southern Sulawesi, the Dayak of southern Borneo, and Javanese of central Java. The gene frequency of the 27-bp deletion in the general population was rather low: 0.012 and 0.013 in the Dayak and the Bugis, respectively. This restricted ethnic and geographic distribution of the 27-bp deletion suggests (1) local differentiation in the prevalence of this deletion in a given ethnic group and (2) the presence of molecular heterogeneity of SAO.

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Plasma concentration of insulin-like growth factor type-I (IGF-I) was studied among the Mannis in Thailand to find a possible cause of their short stature. The Mannis are hunting and gathering indigenous tribal peoples living in Asian tropical rain forests. A total of 50 plasma specimens from three different Manni groups in southern Thailand were used in this study. The concentrations of acid-ethanol extract of plasma IGF-I were measured by radio-immunoassay. We found that (1) plasma concentration of IGF-I in the Mannis was low, (2) there was no adolescent spurt in IGF-I levels, and (3) the post adolescent plasma IGF-I level of the Manni was significantly lower than that of age-matched Japanese. Low IGF-I levels among the Mannis may account for their short stature.

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Duffy blood groups were serologically investigated in 434 individuals from Black Lahu (N = 54), Shan (N = 62), Lisu (N = 74), Red Karen (N = 112), White Karen (N = 102) and Manni (N = 30) in Thailand. High frequency of Fya (0.917-1.0) which is comparable with other Mongoloid populations was observed. The presence of weak-Fya antigen was detected in eight individuals of northern ethnic groups.

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