Biomedical subjects

Hitoshi Kohno

Publications and source records attributed to Hitoshi Kohno.

At least 19 recordsLinked to original sources

PubMed2007

PD-1 gene haplotype is associated with the development of type 1 diabetes mellitus in Japanese children.

Interaction between Programmed cell death-1 (PD-1), a member of costimulatory molecules, and its receptors Programmed cell Death-1 Ligand 1 (PD-L1) and Programmed cell Death-1 Ligand 2 (PD-L2), play an important role in the negative regulation of immune reactions. It was shown that a polymorphism in a regulatory site of the PD-1 gene was associated with susceptibility to several autoimmune diseases in various ethnic groups, whereas the contribution of the PD-1 gene or its ligand genes to the onset of type 1 diabetes (T1D) mellitus in the Japanese population remains unknown. We first screened PD-1, PD-L1, and PD-L2 genes for polymorphisms in the Japanese population, and then investigated the frequencies of polymorphisms in patients with T1D mellitus in comparison with healthy controls. In total, we identified 26 polymorphic sites within these genes, and then 23 polymorphisms with minor allele frequencies greater than 5% were intensively analyzed for genotyping in the patients and the controls. As a result, allele and genotype frequencies of the polymorphism numbers 2, 3, 4, 5, 6, and 8 in the PD-1 gene were different to some extent between the patients and the controls with P < 0.05, which did not reach statistical significance after the correction of multiple comparisons. Allele or genotype frequencies of any SNPs in the PD-L1 or PD-L2 gene did not show differences between the patients and the controls. The frequencies of the estimated haplotypes, those of which consisted of polymorphism numbers 2, 3, 4, 5, 6, and 8 in the PD-1, were significantly different between the patients and the controls (P = 0.00095). The in vitro assessment for a transcription activity of each haplotype of the PD-1 gene by luciferase assay did not demonstrate a functional difference between the haplotypes. In conclusion, the genetic evaluation by association study demonstrated that the PD-1 gene was a predisposing gene to the development of T1D mellitus in the Japanese population.

Adolescent↗

PubMed2006

Growth hormone (GH) effects on central fat accumulation in adult Japanese GH deficient patients: 6-month fixed-dose effects persist during second 6-month individualized-dose phase.

Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced abdominal obesity, which is associated with increased risk of cardiovascular complications. We investigated the effects of GH treatment in 27 adult Japanese GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD. Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a double-blind design and the dose was then individualized for each patient according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA) data were evaluated for percentages of trunk fat, total body fat and lean body mass. Serum IGF-I and lipid concentrations were determined at a central laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6 and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day, respectively. With the reductions in dose when individualized between weeks 24 and 48, mean serum IGF-I level was reduced and excessively high values, observed in AO patients on the fixed GH dose, were no longer seen. The decrease from baseline in trunk fat was similar at week 24 (-3.8 +/- 3.3%, p<0.001) and week 48 (-3.1 +/- 3.7%, p<0.001), and the difference between changes was not significant. Total cholesterol was decreased from baseline by -24 +/- 28 mg/dl (p<0.001) at week 24 and -17 +/- 28 mg/dl (p = 0.007) at week 48. Two patients had elevated HbA1c levels: one continued GH treatment after a dose reduction and the other discontinued due to persistent impaired glucose tolerance. Therefore, excessively high IGF-I levels can be avoided by individualized dosing during long-term GH treatment. Individualized dosing maintains the decrease in abdominal fat in adult Japanese GHD patients and should reduce the cardiovascular risk.

Abdominal Fat↗

PubMed2006

Effect of growth hormone treatment on trunk fat accumulation in adult GH-deficient Japanese patients: a randomised, placebo-controlled trial.

OBJECTIVE: Patients with growth hormone deficiency (GHD), both Japanese and Caucasian, have an abnormal body composition with pronounced abdominal obesity. This study aimed to evaluate changes in trunk fat with GH treatment. DESIGN: Double-blind, placebo-controlled study. PATIENTS AND MEASUREMENTS: Sixty-one Japanese adult GH deficient patients (mean age 37 years) were randomised to either GH, titrated to 0.012 mg/kg/day, (n = 30) or placebo (n = 31) for 24 weeks. Body composition, by dual-energy X-ray absorptiometry (DXA), was evaluated at a central laboratory for trunk fat, total body fat and lean body mass. Serum lipid levels were also determined centrally. RESULTS: At baseline, 26 (42.6%) patients had a body mass index (BMI) > or = 25 kg/m(2), the threshold for obesity-related complications for Japanese subjects. Median trunk fat mass (FM) was > or = 9.0 kg for each treatment and gender group, higher than the cut-off for increased age-adjusted risk for cardiovascular complications reported in the normal Japanese population. After 24 weeks of GH treatment, the change in percentage trunk FM was -3.4 +/- 0.6%, versus 0.4 +/- 0.6% with placebo (p < 0.001). Change in total body FM was -2.8 +/- 0.5% with GH and 0.0 +/- 0.5% with placebo, indicating that the decrease in trunk fat was more pronounced than for total body fat. Total and low density lipoprotein (LDL)-cholesterol were both significantly (p < 0.001) decreased compared with placebo. One patient discontinued due to a subdural haematoma and one had GH dose reduced due to hyperglycaemia. CONCLUSIONS: Japanese patients with GHD have abnormal central fat accumulation, which is reduced by GH treatment over 24 weeks. This may reduce cardiovascular risk but the GH dose should be individualised to maintain IGF-I in the normal range.

Abdominal Fat↗

PubMed2005

Metastatic lymph node size and colorectal cancer prognosis.

BACKGROUND: Colorectal cancer patients with lymph node metastasis constitute a heterogeneous population with variable prognoses. In this study, my colleagues and I propose a simpler lymph node (LN) staging system for colorectal cancer. STUDY DESIGN: Four-hundred and twenty-three consecutive colorectal cancer patients were studied. Of these, 36 were excluded because another carcinoma was present. The remaining 387 patients entered the TNM staging analysis. In the survival analysis, 76 patients with distant metastasis were excluded and the remaining 311 patients (LN(-) = 204 and LN(+) = 107) were studied. The diameter of the largest metastatic LN (MLN) was measured on histopathological slides. After examination of various cutpoints and survival outcomes, patients with MLNs were classified into n1 (< or = 9 mm) and n2 (> or = 10 mm) groups, according to size of MLNs (n-stage). RESULTS: Using disease-free survival (DFS) and overall survival (OS) as outcomes, patients were separated into significant prognostic groups by MLN size (univariate, p < 0.0001) (5-year survival, DFS: n0 = 91.5%, n1 = 62.2%, and n2 = 34.4%; OS: n0 = 85.1%, n1 = 63.5%, and n2 = 42.5%) and International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) (N-stage) (univariate, p < 0.0001) (5-year survival, DFS: N0 = 91.5%, N1 = 60.5%, and N2 = 36.8%; OS: N0 = 85.1%, N1 = 65.3%, and N2 = 38.0%). But in patients with fewer than 15 LNs examined (n = 31), only the new nodal stage stratified patients into significant groups (OS: p = 0.003 and DFS: p = 0.001). Only the UICC/AJCC N-stage subcategories were further split into significant prognostic groups by MLN size (UICC/AJCC N1: DFS, p = 0.048 and OS, p = 0.11; N2: DFS, p = 0.04 and OS, p = 0.04). n-stage was an independent important factor both in the DFS and OS in multivariable analysis. CONCLUSIONS: MLN size is a strong prognostic variable in colorectal carcinoma. This new metric may help clinicians treating colorectal cancer patients, but additional studies are required before clinical application.

Adult↗

PubMed2005

Vitamin D deficiency rickets caused by improper lifestyle in Japanese children.

BACKGROUND: Nutritional rickets is considered rare in developed countries. However, reports on vitamin D deficiency rickets caused by improper lifestyle have recently increased. The clinical and laboratory characteristics of patients with vitamin D deficiency rickets treated at Fukuoka Children's Hospital, Fukuoka, Japan, were evaluated to clarify current causes and ways to prevent this disease. METHODS: Clinical records were reviewed, and obtained information and data were summarized. RESULTS: Eight patients with vitamin D deficiency rickets (five boys and three girls) were treated during the past 10 years (January 1992 to December 2001). Two infants were referred to the hospital for hypocalcemia and convulsion, and six toddlers (1-2 years old) for bowlegs. One patient lacked exposure to sunlight, and six had an unbalanced diet. The cause of rickets could not be established in one patient. Anthropometric and laboratory data did not indicate malnutrition. Serum alkaline phosphatase was 2518.3 +/- 1401.7 IU/l, calcium was 8.2 +/- 2.6 mg/dL (including 4.7 mg/dL in one infant and 4.8 mg/dL in another), and phosphorus was 4.9 +/- 1.0 mg/dL. High sensitive parathyroid hormone was 1393.1 +/- 321.7 pg/mL (reference range, 180-560), 1,25-dihydroxyvitamin D was 86.0 +/- 61.5 pg/mL (reference range, 20-70), and 25-hydroxyvitamin D was 11.6 +/- 5.6 ng/mL (reference range, 10-30). The patients recovered with a change to a balanced diet, the promotion of weaning, and/or an increase in sunlight exposure. CONCLUSION: Vitamin D deficiency rickets remains a common condition that is best managed by education and disease prevention.

Alkaline Phosphatase↗

PubMed2005

An individualized GH dose regimen for long-term GH treatment in Japanese patients with adult GH deficiency.

OBJECTIVES: To investigate the effects of growth hormone (GH) treatment, using a dose-adjustment regimen based on serum insulin-like growth factor (IGF)-I concentrations, in adult Japanese hypopituitary patients with GH deficiency. STUDY DESIGN: Japanese patients who had initially been administered GH (n = 31) or placebo (n = 28) in a 24-week double-blind study received individualized GH treatment in an open-label study for 48 weeks. Body composition from dual-energy X-ray absorptiometry (DXA) and serum IGF-I, IGF-binding protein 3 (IGFBP-3) and lipid levels were determined centrally. RESULTS: Significant increases in lean body mass (4.5%) and decreases in fat mass (-10.5%) were observed in the group that received individualized GH doses in the present open-label study following placebo in the double-blind study. This was comparable with the changes observed in these parameters (4.7 and -9.2%, respectively) with fixed-dose GH treatment in the double-blind study; this latter group maintained these improvements throughout the open-label study. Individualized dose adjustment allowed for more moderate dose increases than the fixed-dose titration method. Individualized dosing also resulted in a lower mean dose for adult-onset compared with childhood-onset GH-deficient patients (0.032+/-0.019 versus 0.061+/-0.023 mg/kg per week for patients treated with GH for 48 weeks in the open-label study following placebo in the double-blind study). Dosing patterns in the two groups were paralleled by the changes in IGF-I and IGFBP-3. The incidence of oedema and cases with high IGF-I level were less frequent under the IGF-I controlled regimen compared with those during the fixed-dose titration method. CONCLUSION: Individualized GH administration based on IGF-I levels was safe and effective. This regimen demonstrated differences in dose requirements between adult- and childhood-onset patients. An individualized dose regimen is recommended in adult Japanese GH-deficient patients.

Adult↗

PubMed2004

Prognostic impact of hypoxia-inducible factors 1alpha and 2alpha in colorectal cancer patients: correlation with tumor angiogenesis and cyclooxygenase-2 expression.

PURPOSE: Angiogenesis plays an important role in a multitude of biological processes including those of tumorigenesis and cancer progression. Hypoxia is the prime driving factor for tumor angiogenesis and the family of hypoxia-inducible factors (HIFs) plays a pivotal role in this process. The role of HIF in tumor angiogenesis has been underscored in different carcinomas but yet to be reported for colorectal carcinomas. EXPERIMENTAL DESIGN: In this study, we examined HIF [HIF-1alpha (HIF1) and HIF-2alpha (HIF2)] expression in 87 curatively resected colorectal carcinoma samples, and the results were correlated with clinicopathological factors, microvessel density, cyclooxygenase 2 expression, and patient prognosis. RESULTS: HIF1 (44.8%) was more frequently expressed than HIF2 (29.9%). Most of the clinicopathological factors representing the tumor aggressiveness were significantly correlated with overexpression of HIF2 but not with HIF1 expression. HIF2 expression had direct correlation with microvessel density and cyclooxygenase 2 expression. and, in contrast, HIF1 expression had a weak but significant inverse correlation in T1 and T2 tumors only. HIF2 expression alone and the combined expression of HIF1 and HIF2 had significant impact on patient survival. In the multivariate analysis, however, only the combined expression of HIF1 and HIF2 remained independently significant. CONCLUSIONS: Taken together, our results suggest that HIF2 expression may play an important role in angiogenesis and that the combined expression of HIF1 and HIF2 may play an important role in tumor progression and prognosis of colorectal carcinomas. Therefore, HIF expression could be a useful target for therapeutic intervention.

Adult↗

PubMed2004

Identification of a novel type 1 diabetes susceptibility gene, T-bet.

The gene encoding interferon (IFN)-gamma, IFNG, is known as one of the candidate susceptibility genes for type 1 diabetes. In addition, cytokines, including IFN-gamma, play important roles in the pathogenesis of type 1 diabetes. Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-gamma. We first screened for polymorphisms in the T-bet gene and detected two microsatellite repeat polymorphisms located in intron 1 and the 3'- flanking region, and two single nucleotide polymorphisms, including a His33Gln substitution within the coding region. By association studies, the Gln-positive phenotype and (CA)14 allele in 3'-flanking region of T-bet were found to be associated with type 1 diabetes in the Japanese population. Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-gamma production in Th1 cells.

Adolescent↗

PubMed2004

Expression of gap junction protein connexin32 in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

BACKGROUND: The gap junction (GJ) plays important roles in the maintenance of tissue homeostasis, the control of cell growth and differentiation, and the prevention of experimental hepatocarcinogenesis. In this study, we examined the relationship between the expression of the GJ protein connexin (Cx) 32 in 24 human hepatocellular carcinomas (HCCs) and 29 non-carcinomatous liver specimens (NCLs) of 31 patients. METHODS: An immunohistochemical study of Cx32 was done in 24 HCCs and 29 NCLs from 31 patients who had undergone hepatic resection. RESULTS: The Cx32 expression decreased gradually as the disease progressed to cirrhosis and HCC. In all Cx32 positive HCCs, the expression was mostly recognized in cytoplasm, not only on the cell membrane. This internalization of Cx32 was also recognized in liver specimens showing hepatitis and cirrhosis, although it was less frequent than in the HCCs. CONCLUSIONS: These findings suggest the possibility that changes in both the amount and the distribution of Cx32 may be implicated in human hepatocarcinogenesis.

Aged↗

PubMed2004

Transforming growth factor-beta1 induced hepatocyte apoptosis--a possible mechanism for growth of colorectal liver metastasis.

The mechanisms of colonization and growth of metastatic liver tumors from colorectal cancers remain obscure. Forty-three resected colorectal metastatic liver tumors with surrounding livers were evaluated for apoptotic index (AI), proliferation index (PI), and immunohistochemical expressions of TGF-beta1. TGF-beta receptor II, Fas, and Fas-ligand. All the parameters were significantly higher in the peri-tumoral livers than in the tumors with the exception of PI, which was significantly high in tumors. Enhanced TGF-beta1 expression was noticed at the interface between the metastatic tumor and the adjacent liver parenchyma. The AIs of hepatocytes in the TGF-beta1-positive areas (8.7 +/- 7.5%, n = 43) were significantly higher when compared with those in the TGF-beta1-negative areas (2.4 +/- 4.5%, n = 42) (p < 0.001). However, the same kind of correlation could not be found in metastatic tumors. The enhanced expression of TGF-beta1 and hepatocyte apoptosis in the peri-tumoral liver parenchyma may suggest that TGF-beta1 plays a substantial role in the development of colorectal liver metastasis.

Aged↗

PubMed2004

Cervical laminoplasty for subaxial lesion in rheumatoid arthritis.

Expansive laminoplasty of the cervical spine was performed for 15 patients with subaxial lesion (SAL) in rheumatoid arthritis (RA) with or without symptomatic occipitocervical pathology. Clinical results were satisfactory, and radiographic evaluation revealed that the range of movement of the cervical spine decreased to 56.3%, spinal alignment was well preserved, and intervertebral slipping advanced only slightly. Therefore, expansive laminoplasty is shown to be clinically effective in decompressing the subaxial spinal cord without the need for fusion of this region, yet it avoids exacerbating or creating significant instability. We found that it can serve as a useful procedure for treating spinal cord compression caused by SAL in RA. For patients with upper cervical instability, laminoplasty with upper cervical fusion appears to be an effective option. In a case in which kyphosis was observed preoperatively, its deformity became worse after laminoplasty. Thus, it may be advisable to consider subaxial fusion in such cases.

Aged↗

PubMed2004

Improved diabetes control by using 'close adjustment algorithms'.

BACKGROUND: Intensive insulin therapy increases the frequency of severe hypoglycemia despite markedly improved glycemic control in patients with type 1 diabetes mellitus. To determine the optimal dose of insulin, the authors designed algorithms based on self-monitored blood glucose levels. METHODS: Each dose of insulin was composed of two components: a basal dose determined on the basis of blood glucose levels over the previous two days and an additional dose determined on the basis of blood glucose level just before insulin injection. The patients were instructed to adjust each dose according to the algorithms. The authors investigated the effects of using algorithms on glycemic control, anthropometric data, body composition, and lipid profile in seven females with type 1 diabetes 12-20 years old. RESULTS: After 3 months, the daily dose of insulin increased significantly from 0.93 +/- 0.18 to 1.16 +/- 0.26 units/kg of body weight, and haemoglobin A(1C) decreased significantly from 8.27 +/- 1.33 to 6.50 +/- 0.64%. Severe hypoglycemia, however, did not occur. Body mass index increased significantly from 21.7 +/- 2.7 to 22.7 +/- 2.9 kg/m(2) with no increase in the percentage of body fat. All lipid-profile data showed a decreasing trend. CONCLUSIONS: Algorithms developed on the basis of self-monitored blood glucose levels are useful in determining the optimal dose of insulin and can improve glycemic control and lipid metabolism.

Algorithms↗

PubMed2004

Two cases of Allgrove syndrome with mutations in the AAAS gene.

Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known as triple A syndrome, is now known to be caused by mutations in the AAAS gene. In the present study, we report two new patients of Allgrove syndrome with mutations in the AAAS gene. Patient 1 was a 22-year-old Japanese woman, born to consanguineous parents. She was confirmed to have adrenal insufficiency at the age of 3 years and 6 months. She developed alacrima and bilateral optic nerve atrophy at the age of 8 years. She had been noticed to have dysphagia. Based on these findings, she was diagnosed as having Allgrove syndrome. Mutation analysis revealed a novel homozygous point mutation in exon 7 of her AAAS gene, changing codon 194 encoding Arg (CGA) to a stop codon (TGA) (R194X). Patient 2 was a 7-year-old Japanese boy, born to consanguineous parents. At the age of 1 year, he was noticed to be unable to produce tears. He was confirmed to have adrenal insufficiency, mental retardation and spastic diplegia at the age of 5 years and 4 months. He was tentatively diagnosed as having Allgrove syndrome, although he has never complained of dysphasia. Mutation analysis revealed a homozygous point mutation in exon 4 of his AAAS gene, changing codon 119 encoding Arg (CGA) to a stop codon (TGA) (R119X). Both of the R119X and R194X mutations are predicted to result in truncated and non-functioning ALADIN proteins, and thus the diagnosis of Allgrove syndrome was confirmed by the mutation analyses. These findings indicate that there exist significant clinical variability and mutational heterogeneities in Japanese patients with this syndrome.

Adrenal Insufficiency↗

PubMed2004

Association study of human MTH1 gene polymorphisms with type 1 diabetes mellitus.

Reactive oxygen species are considered to play a role in the development of diabetes mellitus and its complications. Human MTH1 (mutT homologue 1) has 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase activity, which repairs oxidized forms of dGTP. This enzyme is known to have a thermolabile Met83 variant. We examined whether Val83Met polymorphism of human MTH1 gene is associated with type 1 diabetes mellitus. We recruited 156 type 1 diabetic patients (59 males and 97 females). The polymorphism was analyzed by restriction fragment length polymorphism analysis with Nsi I. The Met/Met genotype at codon 83 was very rare in both control and patient groups. Val/Met genotype tended to be more frequent in the whole type 1 diabetic patients than in controls. When subjects were divided into subgroups according to gender, there were no differences in the genotype and allele frequencies between patients and controls in males. On the other hand, in female type 1 diabetic patients, the Val/Met genotype was more frequent than in female controls (corrected P = 0.102). The Met allele was significantly more frequent in female type 1 diabetic patients than in female controls (corrected P = 0.022). Our results suggested that the Met allele at codon 83 of MTH1 gene might be involved in the development of type 1 diabetes mellitus in the Japanese female population.

Adult↗

PubMed2004

Adult GH deficiency in Japanese patients: effects of GH treatment in a randomised, placebo-controlled trial.

OBJECTIVE: To evaluate the influence of factors intrinsic to the Japanese population on consequences of growth hormone deficiency (GHD) and effects of GH treatment in adult Japanese hypopituitary patients with GHD. STUDY DESIGN: A 24-week, randomised, placebo-controlled, double-blind study in 64 patients in Japan, with GHD onset during adulthood (AO; n=27) or childhood (CO; n=37). Body composition measured by dual-energy X-ray absorptiometry (DXA) was evaluated centrally. Serum IGF-I, IGF binding protein-3 (IGFBP-3) and lipid levels were determined centrally. RESULTS: In contrast to Caucasian patients, there were no significant differences before treatment between AO and CO patients for body mass index (BMI), lean body mass (LBM) and fat mass (FM). Baseline BMI was >/=25 kg/m(2) for 32.8% of patients. For all patients combined, a significant increase in LBM and decrease in FM (P<0.001 for each) was seen with GH treatment. Serum IGF-I and IGFBP-3 were significantly lower at baseline in CO compared with AO patients, similar to Caucasian patients, and were increased in both onsets following GH treatment. Serum total and low-density lipoprotein (LDL)-cholesterol concentrations did not differ between AO and CO patients at baseline and were elevated compared with normal ranges. GH-induced decreases were significant compared with placebo for both total (P=0.036) and LDL-cholesterol (P=0.040). Glycosylated haemoglobin was increased with GH compared with placebo treatment (P=0.016) but remained within the upper limit of normal for all patients at endpoint. CONCLUSIONS: Adult Japanese hypopituitary patients with GHD demonstrated obesity relative to healthy Japanese subjects but the clinical presentation differed from that of Caucasian patients. GH treatment improved body composition and serum cholesterol profiles of adult Japanese hypopituitary patients with GHD.

Adult↗

PubMed2003

A functional polymorphism in the promoter/enhancer region of the FOXP3/Scurfin gene associated with type 1 diabetes.

FOXP3/Scurfin, a member of forkhead/winged-helix proteins, is involved in the regulation of T-cell activation, and essential for normal immune homeostasis. The FOXP3/Scurfin gene is located on chromosome Xp11.23, which includes one of the type 1 diabetes susceptible loci. Therefore, we investigated whether the human FOXP3/Scurfin gene might be a new candidate gene for type 1 diabetes. We first screened the human FOXP3/Scurfin gene for microsatellite and single nucleotide polymorphisms. Next, we performed an association study between the FOXP3/Scurfin gene and type 1 diabetes. Then, the evaluation of promoter/enhancer activity of the intron with (GT)(n) polymorphism was performed by dual luciferase reporter assay. We demonstrated two regions contained microsatellite polymorphisms; one was (GT)(n), located on intron zero and the other (TC)(n) on intron 5, which were under linkage-disequilibrium. The (GT)(15) allele showed a significantly higher frequency in patients with type 1 diabetes than in controls (43.1% vs 32.6%, P=0.0027). The genotype frequencies of (GT)(15)/(GT)(15) in female patients and of (GT)(15) in male patients tended to be higher than those in female ( P=0.064) and male ( P=0.061) controls, respectively. A significant difference in the enhancer activity between (GT)(15) and (GT)(16) dinucleotide repeats was detected. In conclusion, the FOXP3/Scurfin gene appears to confer a significant susceptibility to type 1 diabetes in the Japanese population.

DNA-Binding Proteins↗

PubMed2003

Association study between interleukin-12 receptor beta1/beta2 genes and type 1 diabetes or asthma in the Japanese population.

Interleukin-12 (IL-12) secreted from macrophages or dendritic cells plays an important role in the protection against intracellular pathogens as well as the developmental commitment of T helper 1 cells. IL-12 exerts its biological effects through binding to specific IL-12 receptors (IL-12Rs) termed IL-12Rbeta1 and IL 12Rbeta2. In this paper, we performed association studies between the three reported polymorphisms (Q214R, M365T and G378R) of the IL-12Rbeta1 gene or the newly identified polymorphisms (P238L, IVS9 -7G>A, IVS13 -121G>A, A643T, P779P and c.3283T>G) of the IL-12Rbeta2 gene, and the development of type 1 diabetes or atopic asthma as representative Th1- and Th2- dominant diseases, respectively. The association study of each polymorphism of the IL-12Rbeta1 or IL-12Rbeta2 gene and type 1 diabetes or asthma showed that these IL-12R genes did not contribute to the development of type 1 diabetes or asthma in the Japanese population. Further analysis in individuals with susceptibility to intracellular pathogens may elucidate the importance of the IL-12R genes.

Adolescent↗

PubMed2003

Does fibrin glue reduce lymph leakage (pleural effusion) after extended esophagectomy? Prospective randomized clinical trial.

Fibrin glue has been shown to be effective in improving postoperative chylothorax following various thoracic procedures and in reducing lymphorrhea after axillary dissection. It is unknown, however, whether fibrin glue is effective in reducing lymph leakage (pleural effusion) after esophagectomy. A series of 43 consecutive patients with thoracic esophageal cancer who underwent extended esophagectomy were prospectively randomized to two groups: group A (n = 21), in whom 3 ml of fibrin glue was applied to the dissected mediastinum; and group B (n = 22), in whom fibrin glue was not applied. The time of drain removal and the volume of the thoracic drainage were compared. All data were expressed as the mean +/- standard deviation. There were no significant differences in the clinicopathologic characteristics between the two groups. None of the patients developed chylothorax or died during their hospital stay. The daily volume from the thoracic drain (457 +/- 273 ml) was significantly (p < 0.05) larger on postoperative day (POD) 1 in group A than in group B (298 +/- 158 ml) and tended to be larger (p < 0.10) on PODs 4 and 6 in group A than in group B. The cumulative drainage volume was significantly (p < 0.05) larger on PODs 4 to 6 and POD 9, and it tended to be larger (p < 0.10) on PODs 1, 3, 7, 8, 10, and 11 in group A than in group B, suggesting that the cumulative drainage volume in group A was consistently larger than that in group B. The cumulative numbers of patients with a drain remaining in place were not significantly different for the two groups (p = 0.4683). Three patients in group A, however, had prolonged insertion (> 20 days) of the chest tube. There were no significant differences in the incidence of postoperative chest-related complications. No patients in group A developed viral infectious disease during the long-term follow-up. Application of fibrin glue to the dissected mediastinum seems to induce postoperative lymph leakage and thus be responsible for prolonged chest tube insertion in some patients. Hence the use of fibrin glue cannot be recommended for reducing lymph leakage after esophagectomy.

Adult↗