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1.
Case Rep Rheumatol ; 2019: 9053747, 2019.
Article in English | MEDLINE | ID: mdl-31565459

ABSTRACT

In children, acute pancreatitis has been reported in IgA vasculitis, Kawasaki disease, systemic lupus erythematosus-associated vasculitis, and juvenile dermatomyositis-associated vasculitis. However, its frequency in these vasculitides has been shown to be low. In other childhood-onset vasculitides, acute pancreatitis is seldom reported. The patient was a 5-year-old Japanese boy who suddenly presented with gastrointestinal (GI) bleeding. Therapy with antiulcer drugs successfully stopped bleeding, but subsequently, high fever, leukocytosis, and hypoxia appeared. He died 12 days after he presented with GI bleeding. An autopsy unexpectedly revealed that necrotizing vasculitis with marked eosinophilic and histiocytic infiltration of the pancreas led to acute pancreatitis, and gastric ulcer with eosinophilic infiltration was shown to be the origin of GI bleeding. In addition, eosinophilic infiltration was found in the small intestine, lungs, and bone marrow. Necrotizing vasculitis with eosinophilic and histiocytic infiltration of the pancreas, eosinophilic infiltration of the airway wall, and eosinophilic gastroenteritis with gastric ulcer were histologically confirmed, suggesting that the present case may be an early stage of eosinophilic granulomatosis with polyangiitis- (EGPA-) like vasculitis. To our knowledge, this might be the first reported case of EGPA-like vasculitis presenting with acute pancreatitis in a child.

2.
J Am Chem Soc ; 140(4): 1415-1422, 2018 01 31.
Article in English | MEDLINE | ID: mdl-29325412

ABSTRACT

Heterogeneous photocatalysis is vital in solving energy and environmental issues that this society is confronted with. Although photocatalysts are often operated in the presence of water, it has not been yet clarified how the interaction with water itself affects charge dynamics in photocatalysts. Using water-coverage-controlled steady and transient infrared absorption spectroscopy and large-model (∼800 atoms) ab initio calculations, we clarify that water enhances hole trapping at the surface of TiO2 nanospheres but not of well-faceted nanoparticles. This water-assisted effect unique to the nanospheres originates from water adsorption as a ligand at a low-coordinated Ti-OH site or through robust hydrogen bonding directly to the terminal OH at the highly curved nanosphere surface. Thus, the interaction with water at the surface of nanospheres can promote photocatalytic reactions of both oxidation and reduction by elongating photogenerated carrier lifetimes. This morphology-dependent water-assisted effect provides a novel and rational basis for designing and engineering nanophotocatalyst morphology to improve photocatalytic performances.

3.
J Gen Virol ; 98(12): 2955-2967, 2017 12.
Article in English | MEDLINE | ID: mdl-29160199

ABSTRACT

Dengue virus (DENV) is one of the major infectious diseases in tropical regions and approximately half of the world population is at risk of infection. Vaccines would offer an effective control measure against this disease. We previously reported on the utility of marmosets as an animal model for studying primary and secondary dengue infections. Infected marmosets consistently develop viraemia and antibody kinetics that reflect those of patients with dengue. Thus, it is important to determine the utility of marmosets as an animal model for demonstrating vaccine efficacy. In this study, marmosets were inoculated with candidate vaccine and parent strains and challenged with a clinical DENV strain. The viraemia and antibody kinetics in these marmosets were determined. Marmosets consistently develop lower viraemia with an attenuated vaccine strain. During secondary challenge, the IgM response was delayed, whereas the IgG levels rose rapidly, indicating a secondary antibody response. The neutralizing activities against the homotypic serotype were high; all marmosets were protected against viraemia following secondary inoculation. The viraemia markers and antibody responses were consistent with those of human DENV infection and vaccinees. These results demonstrate the utility of marmosets as an animal model for the study of vaccine efficacy.


Subject(s)
Callithrix , Dengue Vaccines/immunology , Dengue Virus/immunology , Dengue/prevention & control , Disease Models, Animal , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibody Formation , Blood/virology , Dengue Vaccines/administration & dosage , Dengue Virus/isolation & purification , Immunoglobulin G/blood , Immunoglobulin M/blood , Monkey Diseases , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology , Viremia/prevention & control
4.
Pediatr Diabetes ; 18(7): 532-539, 2017 Nov.
Article in English | MEDLINE | ID: mdl-27681997

ABSTRACT

BACKGROUND: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM). OBJECTIVES: To elucidate the characteristics of Japanese patients with KATP-NDM. METHODS: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM. Clinical data were collected from the medical charts. RESULTS: Sixteen patients had mutations in KCNJ11 and nine in ABCC8. Eight novel mutations were identified; two in KCNJ11 (V64M, R201G) and six in ABCC8 (R216C, G832C, F1176L, A1263V, I196N, T229N). Interestingly, V64M caused DEND (developmental delay, epilepsy, neonatal diabetes) syndrome in our patient, while mutation of the same residue (V64G) had been reported to cause congenital hyperinsulinism. Mutations in ABCC8 were associated with TNDM (4/9) or isolated PNDM (5/9), whereas those in KCNJ11 were associated with more severe phenotypes, including DEND (3/16), iDEND (intermediate DEND, 4/16), or isolated PNDM (6/16). Switching from insulin to glibenclamide monotherapy was successful in 87.5% of the patients. Neurological improvement was observed in two patients, one with DEND (T293N) and one with iDEND (R50P) syndrome. Three others with iDEND mutations (R201C, G53D, and V59M) remained neurologically normal at 5, 1, and 4 years of age, respectively, with early introduction of sulfonylurea. CONCLUSION: Overall, clinical presentation of KATP-NDM in Japanese patients was similar to those of other populations. Early introduction of sulfonylurea appeared beneficial in ameliorating neurological symptoms.


Subject(s)
Diabetes Mellitus/genetics , Genetic Predisposition to Disease , Mutation , Potassium Channels, Inwardly Rectifying/genetics , Sulfonylurea Receptors/genetics , Amino Acid Substitution , Congenital Hyperinsulinism/blood , Congenital Hyperinsulinism/drug therapy , Congenital Hyperinsulinism/genetics , Congenital Hyperinsulinism/physiopathology , DNA Mutational Analysis , Diabetes Mellitus/blood , Diabetes Mellitus/drug therapy , Diabetes Mellitus/physiopathology , Drug Monitoring , Drug Resistance , Epilepsy/blood , Epilepsy/drug therapy , Epilepsy/genetics , Epilepsy/physiopathology , Female , Genetic Association Studies , Glyburide/therapeutic use , Humans , Hyperglycemia/prevention & control , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Infant , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/drug therapy , Infant, Newborn, Diseases/genetics , Infant, Newborn, Diseases/physiopathology , Insulin/therapeutic use , Japan , Male , Potassium Channels, Inwardly Rectifying/chemistry , Psychomotor Disorders/blood , Psychomotor Disorders/drug therapy , Psychomotor Disorders/genetics , Psychomotor Disorders/physiopathology , Severity of Illness Index , Sulfonylurea Receptors/chemistry
5.
Nano Lett ; 16(2): 1323-7, 2016 Feb 10.
Article in English | MEDLINE | ID: mdl-26806190

ABSTRACT

Charge carrier trapping plays a vital role in heterogeneous photocatalytic water splitting because it strongly affects the dynamics of photogenerated charges and hence the photoconversion efficiency. Although hole trapping by water at water/photocatalyst interface is the first step of oxygen evolution in water splitting, little has been known on how water adsorbate itself is involved in hole trapping dynamics. To clarify this point, we have performed infrared transient and steady-state absorption spectroscopy of anatase TiO2 nanoparticles as a function of the number of water adsorbate layers. Here, we demonstrate that water molecules reversibly adsorbed in the first layer on TiO2 nanoparticles are capable to trap photogenerated holes, while water in the second layer hydrogen bonding to the first-layer water makes hole trapping less effective.

6.
Arch Virol ; 160(3): 765-75, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25604524

ABSTRACT

Japanese encephalitis (JE) is the most important form of viral encephalitis in Asia. The critical factors determining mortality and severity of JE virus (JEV) infection remain unclear. We identified brain-infiltrating T cells associated with a fatal outcome of JEV infection in mice. Dying mice were defined as those that lost more than 25 % of their body weight by day 13 and died by day 21, while surviving mice were defined as those that lost less than 10 % by day 13, based on the result of the survival time course study. Two groups of five mice that demonstrated brain virus titers of >1 × 10(6) pfu/g were randomly selected from the dying and surviving groups and used in the analyses. Cytokine patterns in brains were first examined, revealing a higher ratio of Th1-related cytokine genes in dying mice. The expression levels of CD3, CD8, CD25, and CD69 increased in JEV-infected mice relative to mock-infected mice. However, expression levels of these cell-surface markers did not differ between the two groups. T-cell receptor (TCR) usage and complementary determining region 3 (CDR3) sequences were analyzed in the brain-infiltrating T cells. T cells expressing VA8-1, VA10-1, and VB2-1 increased in both groups. However, the dominant T-cell clones as defined by CDR3 amino acid sequence differed between the two groups. The results indicate that the outcome of JEV infection, death or survival, was determined by qualitative differences in infiltrating T-cell clones with unique CDR3 amino acid sequences.


Subject(s)
Brain/immunology , Encephalitis Virus, Japanese/immunology , Encephalitis, Japanese/immunology , Encephalitis, Japanese/mortality , T-Lymphocyte Subsets/immunology , Animals , Body Weight , Brain/virology , Complementarity Determining Regions/genetics , Disease Models, Animal , Mice , Receptors, Antigen, T-Cell/genetics , Survival Analysis
7.
Am J Trop Med Hyg ; 92(2): 370-6, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25548383

ABSTRACT

Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells.


Subject(s)
Antigen-Antibody Complex/immunology , Dengue Virus/immunology , Dengue/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Callithrix/immunology , Callithrix/virology , Cross Reactions/immunology , Immunization, Passive , Receptors, IgG/immunology , Reverse Transcriptase Polymerase Chain Reaction , Viral Plaque Assay , Viremia/virology
8.
PLoS One ; 9(11): e112286, 2014.
Article in English | MEDLINE | ID: mdl-25397968

ABSTRACT

OBJECTIVE: Individuals with very low birth weight (VLBW; <1500 g) are known to be predisposed to both short final height and cardiometabolic disorders. However, associations between final height and cardiometabolic outcomes including glucose metabolism in VLBW individuals in young adulthood are not fully investigated. METHODS: We investigated glucose metabolism and other cardiometabolic outcomes such as lipid profiles, blood pressure, renal function, urinary albumin, and thyroid function in young adults with VLBW born between 1980 and 1990. Short stature was defined as a final height <10th percentile. Glucose intolerance [diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG)] was determined using 75-g oral glucose tolerance tests. Associations between final height and cardiometabolic outcomes were examined using logistic or multiple linear regression. RESULTS: A total of 628 VLBW individuals were screened and 111 young adults with VLBW (19-30 years) participated in the study. Of the participants, 40 subjects (36%) had short stature with a final height <10th percentile. Eight subjects (7.2%) had glucose intolerance (1, diabetes; 6, IGT; 1, IFG). Short stature was correlated with glucose intolerance (odds ratio 11.1; 95% CI 1.92, 99.7; P = 0.006). Final height was inversely associated with the homeostatic model assessment (HOMA) of insulin resistance, HOMA-ß, insulinogenic index, and total/LDL-cholesterol. The associations of final height with insulin sensitivity and lipid profiles remained after adjustment for target height and age at puberty onset. CONCLUSIONS: Shorter final height was associated with less favorable metabolic profiles in young adults with VLBW, and may be partly mediated by reduced insulin sensitivity. These associations were independent of target height or age at puberty onset.


Subject(s)
Body Height/physiology , Infant, Very Low Birth Weight/physiology , Myocardium/metabolism , Adult , Age Factors , Female , Humans , Infant, Small for Gestational Age/physiology , Male , Puberty/physiology , Thyroid Function Tests , Young Adult
9.
Sci Rep ; 4: 5344, 2014 Jun 18.
Article in English | MEDLINE | ID: mdl-24938868

ABSTRACT

Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease. Here, we investigated the roles of the TNF-α, IL-10 and other cytokines in appropriate KO mice following infection with Oshima and Sofjin strains of TBEV. Following infection with the Oshima strain, mortality rates were significantly increased in TNF-α KO and IL-10 KO mice compared with wild type (WT) mice. These results suggested that TNF-α and IL-10 play protective roles against fatal infection due to Oshima strain infection. However, viral loads and proinflammatory cytokine levels in the brain of TNF-α KO andIL-10 KO mice were not significantly different compared with those of WT mice. On the other hand, all WT, TNF-α KO and IL-10 KO mice died following infection with Sofjin strain. Interestingly, Sofjin-infected mice did not exhibit an up-regulated mRNA level of IL-2 in the spleen in all groups of mice, whereas Oshima-infected mice showed significantly increased level of IL-2 compared with mock-infected mice. From these results, we suggest that TNF-α, IL-10 and IL-2 are key factors for disease remission from fatal encephalitis due to infection with Oshima strain of TBEV.


Subject(s)
Encephalitis, Tick-Borne/genetics , Interleukin-10/genetics , Interleukin-2/genetics , Tumor Necrosis Factor-alpha/genetics , Animals , Brain/metabolism , Brain/pathology , Brain/virology , Cells, Cultured , Cytokines/genetics , Encephalitis Viruses, Tick-Borne/classification , Encephalitis Viruses, Tick-Borne/physiology , Encephalitis, Tick-Borne/mortality , Encephalitis, Tick-Borne/virology , Gene Expression , Host-Pathogen Interactions , Inflammation Mediators/metabolism , Mice, Inbred C57BL , Mice, Knockout , Protective Agents/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Species Specificity , Survival Rate , Time Factors , Viral Load
10.
PLoS One ; 8(8): e71643, 2013.
Article in English | MEDLINE | ID: mdl-23940775

ABSTRACT

Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis. However, the mechanism of severe encephalitis has not been fully elucidated. In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection. Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome. Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases. However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection. Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice. However, exaggerated inflammatory responses were observed in the CNS of TNF-α KO mice. Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice. Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease. Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease. In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis.


Subject(s)
Brain/immunology , Encephalitis Virus, Japanese/immunology , Encephalitis, Japanese/genetics , Encephalitis, Japanese/immunology , Tumor Necrosis Factor-alpha/physiology , Animals , Brain/metabolism , Brain/virology , Cells, Cultured , Cricetinae , Encephalitis, Japanese/epidemiology , Incidence , Mice , Mice, Inbred C57BL , Mice, Knockout , Severity of Illness Index , Thymus Gland/immunology , Thymus Gland/virology , Tumor Necrosis Factor-alpha/genetics , Viral Load
11.
PLoS One ; 8(2): e56296, 2013.
Article in English | MEDLINE | ID: mdl-23451040

ABSTRACT

The common marmoset (Callithrix jacchus) is considered a novel experimental animal model of non-human primates. However, due to antibody unavailability, immunological and pathological studies have not been adequately conducted in various disease models of common marmoset. Quantitative real-time PCR (qPCR) is a powerful tool to examine gene expression levels. Recent reports have shown that selection of internal reference housekeeping genes are required for accurate normalization of gene expression. To develop a reliable qPCR method in common marmoset, we used geNorm applets to evaluate the expression stability of eight candidate reference genes (GAPDH, ACTB, rRNA, B2M, UBC, HPRT, SDHA and TBP) in various tissues from laboratory common marmosets. geNorm analysis showed that GAPDH, ACTB, SDHA and TBP were generally ranked high in stability followed by UBC. In contrast, HPRT, rRNA and B2M exhibited lower expression stability than other genes in most tissues analyzed. Furthermore, by using the improved qPCR with selected reference genes, we analyzed the expression levels of CD antigens (CD3ε, CD4, CD8α and CD20) and cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12ß, IL-13, IFN-γ and TNF-α) in peripheral blood leukocytes and compared them between common marmosets and humans. The expression levels of CD4 and IL-4 were lower in common marmosets than in humans whereas those of IL-10, IL-12ß and IFN-γ were higher in the common marmoset. The ratio of Th1-related gene expression level to that of Th2-related genes was inverted in common marmosets. We confirmed the inverted ratio of CD4 to CD8 in common marmosets by flow cytometric analysis. Therefore, the difference in Th1/Th2 balance between common marmosets and humans may affect host defense and/or disease susceptibility, which should be carefully considered when using common marmoset as an experimental model for biomedical research.


Subject(s)
Callithrix/genetics , Transcriptome/genetics , Animals , Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/genetics , Interleukin-10/genetics , Interleukin-13/genetics , Interleukin-2/genetics , Interleukin-4/genetics , Interleukin-5/genetics , Interleukin-6/genetics , Real-Time Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/genetics
12.
J Immunol Methods ; 384(1-2): 81-91, 2012 Oct 31.
Article in English | MEDLINE | ID: mdl-22841578

ABSTRACT

The common marmoset, Callithrix jacchus, is one of the smallest primates and is increasingly used for an experimental nonhuman primate model in many research fields. Analysis of T cell receptor (TCR) repertoires is a powerful tool to investigate T cell immunity in terms of antigen specificity and variability of TCR expression. However, monoclonal antibodies specific for many TCR Vα or Vß chains have not been created. We have recently identified a large number of TCRα chain variable (TRAV) and TCRß chain variable (TRBV) sequences from a cDNA library of common marmosets. The purpose of this study is to develop a new method for analysis of TCR repertoires in the common marmoset using this sequence information. This method is based on a microplate hybridization technique using 32 TRAV-specific and 32 TRBV-specific oligoprobes following an adaptor-ligation PCR. This enables the easy quantitation of the respective TRAV and TRBV expression levels. No cross-hybridization among specific-oligoprobes and very low variances in repeated measures of the same samples was found, demonstrating high specificity and reproducibility. Furthermore, this method was validated by an antihuman Vß23 antibody which specifically bound to marmoset Vß23. Using this method, we analyzed TCR repertoires from various tissue samples (PBMCs, spleen, lymph node and thymus) and isolated T cell subpopulations (CD4+CD8+, CD4+CD8− and CD4−CD8+) from the thymus of 10 common marmosets. Neither tissue-specific nor T cell subpopulation-specific differences was found in TRAV and TRBV repertoires. These results suggest that, unlike mice, TCR repertoires in the common marmoset are not affected by endogenous superantigens and are conserved among individuals, among tissues, and among T cell subpopulations. Thus, TCR repertoire analysis with high specificity and reproducibility is a very useful technique, with the potential to replace flow cytometric analysis using a panel of TRV-specific antibodies, many of which remain unavailable.


Subject(s)
Callithrix/genetics , Nucleic Acid Hybridization/methods , Polymerase Chain Reaction/methods , Receptors, Antigen, T-Cell, alpha-beta/genetics , Animals , Callithrix/immunology , Female , Gene Library , Leukocytes, Mononuclear/metabolism , Lymph Nodes/cytology , Lymph Nodes/metabolism , Male , Oligonucleotide Probes/genetics , Receptors, Antigen, T-Cell, alpha-beta/immunology , Reproducibility of Results , Spleen/cytology , Spleen/metabolism , T-Lymphocytes/metabolism , Thymus Gland/cytology , Thymus Gland/metabolism
13.
BMJ Open ; 2(1): e000327, 2012.
Article in English | MEDLINE | ID: mdl-22307095

ABSTRACT

OBJECTIVES: To investigate glucose regulation in young adults with very low birth weight (VLBW; <1500 g) in an Asian population. DESIGN: Cross-sectional observational study. SETTING: A general hospital in Hamamatsu, Japan. PARTICIPANTS: 111 young adults (42 men and 69 women; aged 19-30 years) born with VLBW between 1980 and 1990. Participants underwent standard 75 g oral glucose tolerance test (OGTT). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were glucose and insulin levels during OGTT and risk factors for a category of hyperglycaemia defined as follows: diabetes mellitus, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and non-diabetes/IGT/IFG with elevated 1 h glucose levels (>8.6 mmol/l). The secondary outcomes were the pancreatic ß cell function (insulinogenic index and homeostasis model of assessment for beta cell (HOMA-ß)) and insulin resistance (homeostasis model of assessment for insulin resistance (HOMA-IR)). RESULTS: Of 111 young adults with VLBW, 21 subjects (19%) had hyperglycaemia: one had type 2 diabetes, six had IGT, one had IFG and 13 had non-diabetes/IGT/IFG with elevated 1 h glucose levels. In logistic regression analysis, male gender was an independent risk factor associated with hyperglycaemia (OR 3.34, 95% CI 1.08 to 10.3, p=0.036). Male subjects had significantly higher levels of glucose and lower levels of insulin during OGTT than female subjects (p<0.001 for glucose and p=0.005 for insulin by repeated measures analysis of variance). Pancreatic ß cell function was lower in men (insulinogenic index: p=0.002; HOMA-ß: p=0.001), although no gender difference was found in insulin resistance (HOMA-IR: p=0.477). In male subjects, logistic regression analysis showed that small for gestational age was an independent risk factor associated with hyperglycaemia (OR 33.3, 95% CI 1.67 to 662.6, p=0.022). CONCLUSIONS: 19% of individuals with VLBW already had hyperglycaemia in young adulthood, and male gender was a significant independent risk factor of hyperglycaemia. In male young adults with VLBW, small for gestational age was associated with hyperglycaemia.

15.
J Immunol ; 187(8): 3919-30, 2011 Oct 15.
Article in English | MEDLINE | ID: mdl-21908734

ABSTRACT

It has been reported that brain-infiltrating T lymphocytes play critical roles in the clearance of West Nile virus (WNV) from the brains of mice. We characterized brain-infiltrating T lymphocytes by analyzing the TCR α- and ß-chain repertoires, T cell clonality, and CDR3 sequences. CD3(+)CD8(+) T cells were localized in the WNV-infected brains. The expression of CD3, CD8, CD25, CD69, perforin, and granzymes positively correlated with viral RNA levels, and high levels of expression of IFN-γ, TNF-α, and IL-2 were detected in the brains, suggesting that Th1-like cytotoxic CD8(+) T cells are expanded in the brains in response to WNV infection. The brain-infiltrating T lymphocytes dominantly used TCR genes, VA1-1, VA2-1, VB5-2, and VB8-2, and exhibited a highly oligoclonal TCR repertoire. Interestingly, the brain-infiltrating T lymphocytes had different patterns of TCR repertoire usages among WNV-, Japanese encephalitis virus-, and tick-borne encephalitis virus-infected mice. Moreover, CD8(+) T cells isolated from the brains of WNV-infected mice produced IFN-γ and TNF-α after in vitro stimulation with peritoneal cells infected with WNV, but not with Japanese encephalitis virus. The results suggest that the infiltrating CD8(+) T cells were WNV-specific, but not cross-reactive among flaviviruses. T cells from the WNV-infected brains exhibited identical or similar CDR3 sequences in TCRα among tested mice, but somewhat diverse sequences in TCRß. The results indicate that WNV-specific CD3(+)CD8(+) T cells expanding in the infected brains are highly oligoclonal, and they suggest that TCR α-chains play a dominant and critical role in Ag specificity of WNV-specific T cells.


Subject(s)
Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology , West Nile Fever/immunology , West Nile Fever/virology , West Nile virus/immunology , Animals , Antigens, CD/analysis , Antigens, CD/biosynthesis , Antigens, CD/immunology , Clone Cells , DNA, Viral/genetics , DNA, Viral/isolation & purification , Disease Models, Animal , Female , Genes, T-Cell Receptor , Immunohistochemistry , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Reverse Transcriptase Polymerase Chain Reaction , West Nile Fever/genetics , West Nile virus/genetics
16.
Brain Dev ; 32(3): 258-62, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19243903

ABSTRACT

We report two sibling cases of pontocerebellar hypoplasia type 1 (PCH-1), which showed severe generalized hypotonia, psychomotor delay, and visual impairment. Magnetic resonance imaging in the neonatal period revealed delayed gyration compared to the postconceptional ages in both cases. The elder brother died with pneumonia at 10months of age, and the younger brother survived to over 6years of age. Repeated neuroimaging in the younger brother revealed improvement of the delayed gyration and progressive atrophy, not only in the pons and cerebellum, but also in the cerebrum. To the best of our knowledge, this is the first report of delayed gyration in PCH-1.


Subject(s)
Abnormalities, Multiple/pathology , Olivopontocerebellar Atrophies/complications , Olivopontocerebellar Atrophies/pathology , Brain/abnormalities , Brain/pathology , Child , Chromosome Mapping/methods , Evoked Potentials, Auditory, Brain Stem/physiology , Humans , Infant , Magnetic Resonance Imaging/methods , Male , Siblings
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