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Biomedical subjects

Akihiro Matsumoto

Publications and source records attributed to Akihiro Matsumoto.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative analyses of leukemia inhibitory factor in the cerebrospinal fluid in mouse embryos.

Leukemia inhibitory factor contributes to the self-renewal of neural stem cells in the forebrain. Although the existence of endogenous leukemia inhibitory factor in the brain parenchyma has been controversial, the cerebrospinal fluid is known to be another source of leukemia inhibitory factor. No reports of the measurement of leukemia inhibitory factor concentrations in the cerebrospinal fluid, however, exist. In the present study, we determined the leukemia inhibitory factor concentration in cerebrospinal fluid, amniotic fluid, and sera of embryos and dams in mice by enzyme-linked immunosorbent assay. The leukemia inhibitory factor concentrations were found to be constitutively high in the cerebrospinal fluid from embryonic day 11 to embryonic day 17, with a peak on embryonic day 13 and embryonic day 14. These findings correspond to the timing of cortical neuron production in mouse cerebrum.

Age Factors↗
PubMed2006

Rupture and drug release characteristics of multi-reservoir type microspheres with poly(dl-lactide-co-glycolide) and poly(dl-lactide).

For the multi-reservoir type microspheres composed of polylactide (PLA) and poly(dl-lactide-co-glycolide) (PLGA), the influence of inner drug-holding layer/outer layer ratio on drug release profiles was studied. The microspheres were prepared by the O/W type emulsion-solvent evaporation technique, and cisplatin was used as a model drug. The water-uptake and the erosion of each polymer were evaluated to clarify the mechanism of drug release for multi-reservoir type microspheres. The formulations were classified by the influence of the blending ratio on drug-release profiles: the formulations with the drug-release profiles independent of the blending ratio (Typel group) and the formulations with drug-release profiles depending on the blending ratio (type 2 group). The formulations of type 1 group showed the uniform swelling during drug-release test, and provided the drug-release governed by the erosion of the inner drug-holding layer. On the other hand, the formulations of Type2 group showed the rupture of outer layer which was induced by the swelling of inner drug-holding layer, and the microspheres with the low ratio of the PLGA provided the drug-release rate which exceeded the estimate from the erosion profiles. The results of present study revealed that two types of drug-release mechanism exist for multi-reservoir type microspheres.

Chemistry, Pharmaceutical↗
PubMed2006

Characteristics of dioxin emissions at startup and shutdown of MSW incinerators.

Dioxin concentrations from municipal waste incinerators in Japan and elsewhere often show low concentrations that comply with legal limits (in this paper, the term "dioxin" designates WHO-TEQ: PCDD/Fs+dioxin-like PCB). However, such data is usually generated under normal steady state operational conditions, and there has been little investigation of releases occurring during startup and shutdown. It is important, therefore, to ascertain quantitatively emissions in an unsteady state (startup and shutdown) in order to correctly evaluate the relationship between emissions from a facility and the surrounding environment. The present study aimed to examine dioxin emissions of a continuously operated incinerator at startup and shutdown, and estimating the time period of greatest emission, and the processes causing dioxin generation. The startup process was divided into five stages and the shutdown into two; at each stage, dioxins in the flue gas were measured at the boiler outlet and the stack. From the concentration of dioxins and the flue gas volume at each stage, the amount of dioxins at startup and shutdown were calculated, and these were compared with that under steady state conditions. Dioxin concentration at the stack under steady state conditions was a very low level, while those at startup and shutdown were higher. In the case where dioxin concentration under a steady state is a low level like in this study, it is indicated that the total annual dioxin emission from a facility could be attributed to the startup periods.

Air Pollution↗
PubMed2006

Patients with and without loss of hepatitis B virus DNA after hepatitis B e antigen seroconversion have different virological characteristics.

The characteristic differences between patients with and without loss of hepatitis B virus (HBV) DNA after achieving hepatitis B e antigen seroconversion were analyzed by comparing changes in HBV DNA and HBV core-related antigen levels during a period from 3 years before to 3 years after the seroconversion. Of the 24 seroconverters, 6 (inactive replication group) showed continuous loss of HBV DNA in serum after the seroconversion and the remaining 18 did not lose HBV DNA (active replication group). The HBV DNA level was similar between the two groups, while the HBV core-related antigen level was significantly lower in the active replication group than in the inactive replication group before the seroconversion. The levels of both HBV DNA and HBV core-related antigen decreased remarkably around the time of seroconversion in the inactive replication group, while these levels did not change or decreased slightly in the active replication group. After the seroconversion, the HBV DNA level was significantly higher in the active replication group than in the inactive replication group, while the HBV core-related antigen level was similarly low between the two groups. Because the serum level of HBV core-related antigen mainly reflects that of HBe antigen, the low level of HBV core-related antigen seen after seroconversion in both groups might have contributed to the occurrence of seroconversion. The precore and core promoter mutations which cause diminished excretion of hepatitis B e antigen were significantly more frequent in the active replication group than in the inactive replication group. It was therefore considered that the seroconversion was caused mainly by a decrease in viral replication in the inactive replication group, and mainly by a decrease in HBe antigen production in the active replication group.

Adult↗
PubMed2006

Hepatitis B virus RNA is measurable in serum and can be a new marker for monitoring lamivudine therapy.

BACKGROUND: Changes in the serum hepatitis B virus (HBV) RNA level during lamivudine therapy were compared to those in the serum HBV DNA and HBV core-related antigen (HBVcrAg) levels in 24 patients with chronic hepatitis B. METHODS: For measurement of HBV RNA, total nucleic acid was extracted from serum samples and treated with RNase-free DNase I. After cDNA synthesis from extracted RNA, HBV RNA was measured by real-time detection polymerase chain reaction. RESULTS: The peak fraction of HBV RNA in serum samples was consistent with peak fractions of HBV DNA and HBV core protein in a sucrose gradient analysis, indicating that HBV RNA was incorporated into virus particles. All levels of HBV DNA, HBV RNA, and HBVcrAg decreased gradually during lamivudine therapy (P < 0.001 for all). The amount of decrease from the start of lamivudine therapy was significantly higher for HBV DNA than for HBV RNA or HBVcrAg during 6 months of lamivudine therapy (P < 0.001 for all). However, a similar difference was not seen between HBV RNA and HBVcrAg levels during that period. The HBV RNA level was significantly correlated (P < 0.001 for all) with levels of HBV DNA and HBVcrAg both at the beginning and 2 months after the start of lamivudine therapy. CONCLUSIONS: HBV RNA is detectable in serum in a form indicating incorporation into virus particles, and its serum level might serve as a new viral marker with a significance different from that of HBV DNA in lamivudine therapy.

Adult↗
PubMed2006

A case of cholesterol embolism confirmed by skin biopsy and successfully treated with statins and steroids.

Although cholesterol embolism syndrome was recognized as a clinicopathologic entity more than 50 years ago, it is attracting growing attention recently. It is a multisystemic disorder in which cholesterol crystals released from atherosclerotic plaques obstruct small arterioles, resulting in local ischemia and end-organ damage. There are no established treatments, and with the limited treatment options available, it is important to make the diagnosis as early as possible. We present the case of a 68-year-old man with cholesterol embolism who had a few fluttering atheromas in the aorta, as demonstrated by transesophageal ultrasonography. The diagnosis was confirmed by skin biopsy, and treatment with statins and steroids proved effective, as renal failure progressively improved. This case emphasizes the importance of early diagnosis and shows the possible therapeutic effects of statins and steroids for patients with this syndrome.

Aged↗
PubMed2006

The usefulness of ureterorenoscopic examination in evaluation of upper tract disease.

AIM: The objective of the present study was to clarify the indications, usefulness and limitations of ureterorenoscopy. MATERIAL AND METHODS: From January 1998 to June 2004, 72 consecutive patients (48 men and 24 women) with a mean age of 66 years (range, 27-83 years) underwent ureterorenoscopy to diagnose upper urinary tract tumors (UUT). Median follow-up was 24 months (range, 1-73 months). Patients were divided into four subgroups by voided urine cytology and preoperative radiographic findings. Group A (n=11, 15.3%), positive voided urine cytology and positive preoperative radiographic findings; group B (n=5, 6.9%), positive cytology and negative radiographic findings; group C (n=48, 66.7%), negative cytology and positive radiographic findings and group D (n=8, 11.1%), frank hematuria originating from the UUT but negative cytology and negative radiographic findings. We compared the findings of ureterorenoscopic examination and biopsy with the results of retrograde pyelography and cytology of upper tract urine. For each examination, the following diagnostic indices were assessed: sensitivity, specificity, positive-predictive-value (PPV) and negative-predictive-value (NPV) and accuracy. Statistical analysis was performed using McNemar's test. RESULTS: For ureterorenoscopy, sensitivity was 94%, specificity 59%, PPV 72%, NPV 92% and accuracy 76%. For biopsy, sensitivity was 77%, specificity 100%, PPV 100%, NPV 80% and accuracy 88%. Accuracy of ureterorenoscopy tended to be superior to that of retrograde pyelography. Ureterorenoscopy was most useful in the group which consisted of 48 patients (66.7%) with negative voided urine cytology and positive preoperative radiographic findings. This group was the only group in which accuracy of ureterorenoscopic biopsy was superior to that of urine cytology, significantly (P=0.03). CONCLUSION: Results indicated that ureterorenoscopy is most suitable and gives superior accuracy in patients with positive radiographic findings and negative voiding cytology. Ureterorenoscopic biopsy of the upper urinary tract would provide useful information when considering therapeutic strategies, such as nephron-sparing management.

Adult↗
PubMed2006

Laparoscopic findings in patients with nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Laparoscopic observation of the liver is important to diagnose liver conditions accurately. However, the laparoscopic findings of nonalcoholic steatohepatitis (NASH) have not been characterized. The aim of this study was to clarify the laparoscopic characteristics of NASH. METHODS: Twenty-four patients were enrolled. The degrees of hepatomegaly, color and irregularity of the liver surface, and the presence of depressions, patches, and vesicles were investigated. These laparoscopic findings were compared among NASH, alcoholic liver disease (ALD), and autoimmune hepatitis (AIH). RESULTS: Mild hepatomegaly, dullness of the liver edge, increased fat accumulation of the round ligament, and whitish markings were found in most of the patients with NASH. Small depressions were observed in approximately 70% of the patients. As fibrosis developed, the liver surface became whiter and more uneven. Compared with patients with ALD and AIH, increased fat accumulation of the round ligament and dullness of the liver edge were observed more frequently in those with NASH. However, coarse and groove-like depressions were rare in NASH patients. CONCLUSIONS: Several findings, including mild hepatomegaly, increased fat accumulation of the round ligament, rounded liver edge, whitish markings, and small depressions were common in patients with NASH. However, coarse and groove-like depressions were rare. These findings may be helpful for confirming a diagnosis of NASH.

Adult↗
PubMed2006

Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance.

OBJECTIVE: The clinical usefulness of hepatitis B virus core-related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B. PATIENTS: Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow-up period of 19.3 months. RESULTS: The pretreatment positive rate of HBe antigen, or pretreatment levels of HBVcrAg or HBV DNA did not differ between patients with and without lamivudine resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of lamivudine administration; however, the level of HBVcrAg decreased significantly more slowly than that of HBV DNA. The occurrence of lamivudine resistance was significantly less frequent in the 56 patients whose HBV DNA level was less than 2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The cumulative rate of lamivudine resistance was as high as 70% within 2 years in the latter group, while it was only 28% in the former group. Lamivudine resistance did not occur during the follow-up period in the 19 patients whose HBVcrAg level was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of the remaining patients within 2 years. CONCLUSION: These results suggest that measurement of HBV DNA is valuable for identifying patients who are at high risk of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg is valuable for identifying those who are at low risk of lamivudine resistance.

Adult↗
PubMed2006

Useful parameters for distinguishing nonalcoholic steatohepatitis with mild steatosis from cryptogenic chronic hepatitis in the Japanese population.

BACKGROUND/AIMS: As detecting mild steatosis is difficult by abdominal ultrasonography (US), nonalcoholic steatohepatitis (NASH) with mild steatosis may sometimes be confused with cryptogenic chronic hepatitis. We aimed to test this possibility and to isolate factors that may indicate NASH. METHODS: First, 53 Japanese patients diagnosed as having cryptogenic chronic hepatitis by laboratory examination and US were enrolled. These patients were histologically divided into NASH and non-NASH groups, and their clinical features were compared. Second, the diagnostic accuracy of predictors of NASH was examined prospectively. RESULTS: Fifteen patients (28%) were histologically diagnosed as having NASH with mild steatosis. Multivariable analysis revealed that body mass index (BMI) and serum ferritin level were independent predictors of NASH. The best cutoff values to detect NASH were assessed by using receiver-operating characteristic curves: BMI>25.2 kg/m(2) and serum ferritin level >142 ng/ml. When both markers were concomitantly negative, the negative predictive value to detect NASH was 100%. CONCLUSIONS: In cases of mild steatosis, US is not a perfect tool for the accurate diagnosis of NASH. BMI and serum ferritin level are useful discriminators of NASH from cryptogenic chronic hepatitis, and might be helpful markers for diagnosing NASH more accurately in Japanese patients.

Adolescent↗
PubMed2006

Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma with and without Helicobacter pylori infection.

BACKGROUND: The clinical features and clinical course of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear and a treatment strategy has not yet been established. AIM: To clarify the clinical differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were studied. H. pylori infection was present in 41 and absent in 16. Treatment consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response assessment was performed every 3-6 months by esophagogastroduodenoscopy including gathering biopsy samples, endoscopic ultrasonography, clinical examination, and various imaging procedures. The median follow-up period was 37 months. RESULTS: There were no significant differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma patients in terms of sex, age, stage, gross phenotype, affected area of the stomach, or the presence of monoclonality. Complete regression was achieved with antibiotic therapy against H. pylori-negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001). Radiation therapy showed high effectiveness for the local control of H. pylori-negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the transformation of the disease into diffuse large B-cell lymphoma. There was a significant difference in both the overall and cause-specific survival rate between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT lymphoma. However, careful systemic follow-up for distant involvement should be required. Transformation into diffuse large B-cell lymphoma is thought to be the important cause of death in patients with gastric MALT lymphoma.

Adult↗
PubMed2005

Assessment of KL-6 as a tumor marker in patients with hepatocellular carcinoma.

AIM: To investigate the clinical significance of KL-6 as a tumor marker of HCC in two different ethnic groups with chronic liver disease consecutively encountered at outpatient clinics. METHODS: Serum KL-6 was measured by the sandwich enzyme immunoassay method using the KL-6 antibody (Ab) as both the capture and tracer Ab according to the manufacturer's instructions (Eisai, Tokyo, Japan). Assessment of alpha fetoprotein (AFP) and protein induced vitamin K deficiency or absence (PIVKA-II) was performed in both groups using commercially available kits. RESULTS: A significantly higher mean serum KL-6 (556+/-467 U/L) was found in HCC in comparison with non-HCC groups either with (391+/-176 U/L; P<0.001) or without (361+/-161 U/L; P<0.001) liver cirrhosis (LC). Serum KL-6 level did not correlate with either AFP or PIVKA-II serU/Levels. Using receiver operating curve analysis for KL-6 as a predictor for HCC showed that the area under the curve was 0.574 (95%CI = 0.50-0.64) and the KL-6 level that gave the best sensitivity (61%) was found to be 334 U/L but according to the manufacturer's instructions; a cut-off point of 500 U/L was used that showed the highest specificity (80%) in comparison with AFP and PIVKA-II (78% vs 72% respectively). Combining the values of the three markers improved specificity of AFP for HCC diagnosis from 78% for AFP alone; 93% for AFP plus PIVKA-II to 99% for both plus KL-6 value (P<0.001). Mean serum alkaline phosphatase level was significantly higher in KL-6 positive (564+/-475) in comparison with KL-6 negative (505+/-469) HCC patients (P = 0.021), but such a difference was not found among non-HCC corresponding groups. CONCLUSION: KL-6 is suggested as a tumor for HCC. Its positivity may reflect HCC-associated cholestasis and/or local tumor invasion.

Adult↗
PubMed2005

Drug release characteristics of multi-reservoir type microspheres with poly(dl-lactide-co-glycolide) and poly(dl-lactide).

For the multi-reservoir type microspheres composed of poly(dl-lactide-co-glycolide) (PLGA) and poly(dl-lactide) (PLA), the influence of the drug-holding layer and the non-drug-holding layer on drug release profiles was studied. The microspheres with the blend of PLGA and PLA were prepared by the W/O type emulsion-solvent evaporation technique, and cisplatin was used as a model drug. The degree of water uptake and the erosion of each polymer were evaluated to clarify the mechanism of drug release for multi-reservoir type microspheres. The blending of PLA and PLGA provided two types of microspheres in terms of the drug distribution in a microsphere, depending on the ratio of the blend: the microspheres with the drug-holding layer covered by the non-drug layer and the microspheres with the drug on the outer region. The drug release in the early period was governed by the pattern of drug distribution. The drug release rate at a steady state was governed by the erosion of the drug-holding layer. The results of present study indicate that drug release from multi-reservoir type microspheres involves the following process: (a) rapid release of the drug near the surface of microspheres, (b) formation of micropores in the non-drug-holding layer by hydration and erosion, (c) degradation of the drug-holding layer, and (d) diffusion of the drug through micropores.

Antineoplastic Agents↗
PubMed2005

Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: A multicenter retrospective study of 2795 patients.

A retrospective survey of Japanese patients histologically diagnosed with chronic hepatitis B was conducted to determine the effectiveness of lamivudine in preventing hepatocellular carcinoma (HCC). Of the 2795 patients who satisfied criteria for analysis after treatment from any of 30 medical institutions, 657 had received lamivudine and the remaining 2138 had not. A Cox regression model with liver biopsy as the starting point revealed seven factors related to HCC: lamivudine therapy, gender, family clustering of hepatitis B, age at liver biopsy, hepatic fibrosis stage, serum albumin level, and platelet count. In a matched case-controlled study, 377 patients in a lamivudine-treated group and 377 matched patients in a non-treated group were selected based on their propensity scores. The mean follow-up period was 2.7 years in the lamivudine group and 5.3 years in the control group. In the lamivudine group, HCC occurred in four patients (1.1%) with an annual incidence rate of 0.4%/(patient/year), whereas in the control group HCC occurred in 50 patients (13.3%) for a rate of 2.5%/(patient/year). A comparison of the cumulative HCC incidence between the two groups by the Kaplan-Meier method showed a significantly lower incidence of HCC in the lamivudine group (p<0.001). These findings suggest that lamivudine effectively reduces the incidence of HCC in patients with chronic hepatitis B.

Journal Article↗
PubMed2005

Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow.

We investigated the hemodynamic and hormonal responses to a short-term low-intensity resistance exercise (STLIRE) with the reduction of muscle blood flow. Eleven untrained men performed bilateral leg extension exercise under the reduction of muscle blood flow of the proximal end of both legs pressure-applied by a specially designed belt (a banding pressure of 1.3 times higher than resting systolic blood pressure, 160-180 mmHg), named as Kaatsu. The intensity of STLIRE was 20% of one repetition maximum. The subjects performed 30 repetitions, and after a 20-seconds rest, they performed three sets again until exhaustion. The superficial femoral arterial blood flow and hemodynamic parameters were measured by using the ultrasound and impedance cardiography. Serum concentrations of growth hormone (GH), vascular endothelial growth factor (VEGF), noradrenaline (NE), insulin-like growth factor (IGF)-1, ghrelin, and lactate were also measured. Under the conditions with Kaatsu, the arterial flow was reduced to about 30% of the control. STLIRE with Kaatsu significantly increased GH (0.11+/-0.03 to 8.6+/-1.1 ng/ml, P < 0.01), IGF-1 (210+/-40 to 236+/-56 ng/ml, P < 0.01), and VEGF (41+/-13 to 103+/-38 pg/ml, P < 0.05). The increase in GH was related to neither NE nor lactate, but the increase in VEGF was related to that in lactate (r = 0.57, P < 0.05). Ghrelin did not change during the exercise. The maximal heart rate (HR) and blood pressure (BP) in STLIRE with Kaatsu were higher than that without Kaatsu. Stroke volume (SV) was lower due to the decrease of the venous return by Kaatsu, but, total peripheral resistance (TPR) did not change significantly. These results suggest that STLIRE with Kaatsu significantly stimulates the exercise-induced GH, IGF, and VEGF responses with the reduction of cardiac preload during exercise, which may become a unique method for rehabilitation in patients with cardiovascular diseases.

Adaptation, Physiological↗
PubMed2005

Hepatitis B virus DNA-negative dane particles lack core protein but contain a 22-kDa precore protein without C-terminal arginine-rich domain.

DNA-negative Dane particles have been observed in hepatitis B virus (HBV)-infected sera. The capsids of the empty particles are thought to be composed of core protein but have not been studied in detail. In the present study, the protein composition of the particles was examined using new enzyme immunoassays for the HBV core antigen (HBcAg) and for the HBV precore/core proteins (core-related antigens, HBcrAg). HBcrAg were abundant in fractions slightly less dense than HBcAg and HBV DNA. Three times more Dane-like particles were observed in the HBcrAg-rich fraction than in the HBV DNA-rich fraction by electron microscopy. Western blots and mass spectrometry identified the HBcrAg as a 22-kDa precore protein (p22cr) containing the uncleaved signal peptide and lacking the arginine-rich domain that is involved in binding the RNA pregenome or the DNA genome. In sera from 30 HBV-infected patients, HBcAg represented only a median 10.5% of the precore/core proteins in enveloped particles. These data suggest that most of the Dane particles lack viral DNA and core capsid but contain p22cr. This study provides a model for the formation of the DNA-negative Dane particles. The precore proteins, which lack the arginine-rich nucleotide-binding domain, form viral RNA/DNA-negative capsid-like particles and are enveloped and released as empty particles.

Antibodies, Monoclonal↗
PubMed2005

Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis.

BACKGROUND/AIMS: Genetic predisposition to type 1 autoimmune hepatitis (AIH) is linked mainly to HLA-class II genes. The aim of this study is to scan the HLA region for additional genes which may contribute to type 1 AIH susceptibility. METHODS: We performed association analysis using HLA class I and II alleles and 18 polymorphic microsatellite markers distributed throughout the HLA region. We specifically assessed tumor necrosis factor (TNF)-alpha gene polymorphisms. RESULTS: The frequencies of HLA-DRB1*0405, DRB4 and DQB1*0401 alleles were significantly higher in AIH patients. The association study revealed the presence of three segments in the HLA region showing significantly low P (Pc) values. The first segment was located around the HLA-DR/-DQ subregion, the second was around the HLA-B54 allele, and the third was around two microsatellites near the TNF gene cluster. However, stratification analysis for the effect of DRB1*0405 eliminated association of the latter two segments. Haplotype D of the TNF-alpha promoter gene polymorphisms was weakly associated with susceptibility, but was found to be not significant after stratification analysis. CONCLUSIONS: The most influential gene on type 1 AIH pathogenesis in Japanese is the HLA-DRB1. Other genes in the HLA region, including TNF-alpha, have little or no association with type 1 AIH susceptibility.

Adult↗