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Objectives: This study was designed to examine the prevalence of endometriosis among female siblings of patients with endometriosis in Japan.Methods: A total of 339 patients with endometriosis were questioned about endometriosis in their sisters. The control group consisted of 284 Japanese healthy fertile women with no history of endometriosis. Similarly, the controls were interviewed about their sisters.Results: We detected sisters with endometriosis in 8.8% of cases and 1.5% of the control population. The relative risk of endometriosis in female siblings was 5.7. However, a significant difference was not seen in age at diagnosis and clinical stage between patients with or without a family history of endometriosis.Conclusions: These data demonstrate a familial tendency for endometriosis and suggest that endometriosis has a genetic factor in the pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Although neonatal disseminated intravascular coagulation (DIC) is associated with high mortality and severe complications, few studies have reported its clinical course. We aimed to describe the characteristics, treatments, and outcomes of neonatal DIC by using a national inpatient database., Methods: Using the Japanese Diagnosis Procedure Combination database, we identified 5533 patients with neonatal DIC who were admitted to neonatal intensive care units between July 2010 and March 2020. We categorized the patients into those with asphyxia (n = 2911) and those without asphyxia (n = 2622). We investigated the patient characteristics, treatments, and outcomes. We further categorized neonates with asphyxia according to its severity., Results: The gestational age of neonates with asphyxia was significantly lower than that of neonates without asphyxia (P < 0.001). Antithrombin was most commonly used for DIC (40%). Neonates with asphyxia were more likely to receive antithrombin (43% vs. 38%; P < 0.001), recombinant human soluble thrombomodulin (28% vs. 20%; P < 0.001), and fresh frozen plasma transfusion (68% vs. 51%; P < 0.001) than those without asphyxia. Neonates with asphyxia had higher in-hospital mortality (17% vs. 10%; P < 0.001), severe bleeding (11% vs. 6.8%; P < 0.001), and hospitalization costs than those without asphyxia. Additionally, neonates with severe asphyxia were more likely to receive several DIC therapies (such as recombinant human soluble thrombomodulin [30% vs. 24%]) and had higher in-hospital mortality (19% vs. 11%) and hospitalization costs than those with mild asphyxia., Conclusions: In this large retrospective study of neonatal DIC, patients with asphyxia received several treatments and demonstrated unfavorable outcomes when compared to those without asphyxia., Competing Interests: Declaration of competing interest Dr. Konishi received grants from Pfizer Co. Ltd., Kanzawa Medical Research Foundation, and Japan Kampo Medicines Manufacturers Association outside the submitted work. There are no other conflicts of interest to disclose., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

We investigated the prevalence of Campylobacter jejuni, Campylobacter coli, Salmonella, enterohemorrhagic Escherichia coli, enterotoxigenic Escherichia coli, Yersinia enterocolitica, and Escherichia albertii in domestic chicken and pork sold at retail stores in Saitama Prefecture, Japan. Campylobacter was detected in 35.7% (60/168) of chicken samples and 7.3% (14/190) of pork samples. C. jejuni and C. coli were predominant in chicken and pork, respectively. Salmonella was found in 58.1% (100/172) of chicken samples and 19.9% (41/206) of pork samples. Moreover, Salmonella Schwarzengrund was the major serovar observed in chicken isolates, whereas S. Typhimurium monophasic variant was in pork isolates. Furthermore, ETEC was found in 0.6% (1/160) of chicken samples and 2.4% (5/206) of pork samples. Y. enterocolitica was absent from all (83/83) chicken samples but was present in 9.3% (18/193) of pork samples, with a prevalence in pork tongues as high as 21.0% (13/62 samples). However, EHEC and E. albertii were not detected in our study. Therefore, the results of this study indicate that chicken was highly contaminated with Campylobacter sp. and Salmonella, and pork was with Y. enterocolitica serotype O3, Campylobacter sp., Salmonella, and ETEC.

In June 2020, a large-scale food poisoning outbreak involving about 3000 elementary and junior high school students occurred in Yashio, Saitama, Japan. A school lunch was the only food stuff ingested by all of the patients. Escherichia coli serotype O7:H4 carrying the astA gene for enteroaggregative E. coli (EAggEC) heat-stable enterotoxin 1 (EAST1) was detected in faecal specimens from the patients, and sample inspection revealed its presence in a seaweed salad and red seaweed (Gigartina tenella) as one of the raw materials. Analysis of the antibiotic sensitivity of the isolates revealed resistance to ampicillin and cefotaxime. All isolates were confirmed to be of the same origin by pulsed-field gel electrophoresis after digestion with the restriction enzyme XbaI, and single nucleotide polymorphism analysis using whole genome sequencing. To our knowledge, this is the first report of a large-scale food poisoning caused by E. coli O7:H4, which lacks well-characterized virulence genes other than astA.

We performed a cross-sectional study on 215 Japanese employees aged 20-68 years to investigate the association between NAFLD and serum phospholipid fatty acid composition. NAFLD was diagnosed by ultrasonography. The fatty acid composition between the control and NAFLD groups was compared, and the inverse probability of treatment weighting (IPTW) was performed to eliminate each confounding effect of sex, smoking status, BMI, insulin resistance, dietary cholesterol, and salt intake. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the NAFLD prediction accuracy of fatty acids. Seventy-one subjects were diagnosed with NAFLD. Their serum phospholipid dihomo-γ-linolenic acid (DGLA) level was significantly higher after adjusting for each variable using IPTW. In the ROC analysis, the ratio of ARA to DGLA had an area under the curve (AUC) of 0.763. By combining the ratio of ARA to DGLA with the ratio of AST to ALT, AUC increased to 0.871. In conclusion, NAFLD subjects in a Japanese working population have higher serum phospholipid DGLA. Results of the IPTW and ROC analysis indicated that serum PL DGLA and the ratio of ARA to DGLA provide diagnosis information on the fatty liver that is different to AST and ALT and improve the accuracy of fatty liver prediction, owning potential value as serum biomarkers., (© 2020 AOCS.)

We explored the frequency of germline and somatic mutations in homologous recombination (HR)-associated genes in major histological types of ovarian cancer. We performed targeted sequencing to assess germline and somatic mutations of 16 HR-associated genes and 4 mismatch repair (MMR) genes among 207 ovarian cancer patients (50 high-grade serous carcinomas (HGSC), 99 clear cell carcinomas (CCC), 39 endometrioid carcinomas (EC), 13 mucinous carcinomas (MC), and 6 low-grade serous carcinomas (LGSC)). Germline or somatic mutations of HR-associated genes were detected in 44% of HGSC, 28% of CCC, 23% of EC, 16% of MC, and 17% of LGSC patients. The profile of HR-associated gene mutations was remarkably different among each histological type. Germline BRCA1/2 mutations were frequently detected in HGSC and were rarely observed in CCC, EC, and MC patients. ATM somatic mutation was more frequently detected in CCC (9%) and EC patients (18%) than in HGSC patients (4%). There was a positive correlation between MMR gene mutations and HR-associated gene mutations (p = 0.0072). Our findings might be useful in selection of ovarian cancer patients that should be treated with PARP inhibitors.

Background: Vaccination against influenza A(H1N1)pdm09 in Japan started in October 2009. Children with asthma are considered as a high-risk group and are recommended to preferentially receive the vaccine., Objective: To identify the clinical effects of vaccination in Japanese children with and without asthma., Methods: We conducted a cross-sectional, questionnaire-based survey to compare vaccination rates, vaccine effectiveness against physician-diagnosed influenza A infection (PDIA), and consecutive asthma exacerbations between children with and without asthma., Results: Of the 460 children included in this study, those with asthma had higher vaccination rates (46.5%, 67/144) than those without asthma (30.4%, 96/316). Influenza A infections were diagnosed in 28 of 163 vaccinated children (17.2%) compared to 164 of 297 unvaccinated children (55.2%, p < 0.001). Comparison of positive influenza diagnosis rates between vaccinated and unvaccinated children with and without asthma showed that unvaccinated children with asthma had an elevated odds ratio (13.235; 95% confidence interval [CI], 5.564-32.134) and that treatment for asthma exacerbations was needed in a larger proportion of unvaccinated children. Vaccine effectiveness against PDIA was 87% (95% CI, 78-93%) overall, 92% (95% CI, 81-96%) in children with asthma and 81% (95% CI, 63-91%) in children without asthma, respectively., Conclusions: The administration of an inactivated, split-virus, non-adjuvanted monovalent A(H1N1)pdm09 vaccine during the pandemic period reduced the number of physician-diagnosed influenza A infections and asthma exacerbations in children with asthma. Therefore, we strongly recommend that high-risk children with a history of asthma receive vaccines during pandemics.

Objective: To assess whether the insulin receptor (INSR) gene contributes to genetic susceptibility to polycystic ovary syndrome (PCOS) in a Japanese population., Study Design: We ex-amined the frequency of the His 1058 C/T single nucleotide polymorphism (SNP) found in exon 17 of the INSR gene in 61 Japanese PCOS patients and 99 Japanese healthy controls. In addition, we analyzed the association between the genotype of this SNP and the clinical phenotypes., Results: The frequency of the C/C genotype was not significantly different between all PCOS patients (47.5%) and controls (35.4%). However, among the lean cases (body mass index < or = 20 kg/m2) the frequency of the C/C genotype was significantly increased (p < 0.05) in PCOS patients (65.0%) as compared with controls (36.6%)., Conclusion: We concluded that the His 1058 C/T polymorphism at the tyrosine kinase domain of the INSR gene had a relationship to the pathogenesis of lean PCOS patients in a Japanese population.

Our previous genome-wide association study has demonstrated that single-nucleotide polymorphisms (SNPs) located in intronic and downstream regions of IL1A (interleukin 1α) were associated with the risk of endometriosis. These SNPs on the genome-wide association study platform could be only surrogates for the true causal variant. Thus, we resequenced all the exons of IL1A in 377 patients with endometriosis and 457 healthy controls. We detected seven rare variants (minor allele frequency <0.01) and four common variants. All the rare variants were not associated with endometriosis. The four common variants (rs17561, rs1304037, rs2856836 and rs3783553) in IL1A were significantly associated with endometriosis (P=0.0024, 0.0024, 0.0014 and 0.0061, respectively). All the four SNPs were within a linkage disequilibrium block. Among them, only rs17561 was nonsynonymous (p.A114S), which has been reported to be associated with susceptibility to ovarian cancer. Taken together, we examined association between rs17561 and endometriosis in an independent validation data set (524 patients and 533 healthy controls) replicating significant association (P=4.0 × 10(-5); odds ratio (OR), 1.91; 95% confidence interval (CI), 1.41-2.61). Meta-analysis by combining results from the two stages strengthened the evidence of association (P=2.5 × 10(-7); OR, 1.90; 95% CI, 1.49-2.43). Our findings demonstrated that the nonsynonymous variant of IL1A might confer genetic susceptibility to endometriosis in Japanese population.

Objective: To report the clinical outcomes of patients with FIGO stage IC epithelial ovarian cancer (EOC) treated by fertility-sparing surgery (FSS)., Methods: A retrospective review was conducted of 18 women who underwent FSS at Niigata University Hospital, Japan, between December 15, 1986, and December 31, 2010., Results: Tumors were mucinous (n=9), clear cell (n=4), endometrioid (n=3), and serous (n=2). Median follow-up was 78.0 months (range, 9.3-181.3 months). Five patients (27.8%) developed tumor recurrence at 7.4-19.2 months after initial surgery. The sites of recurrence were peritoneal lymph nodes (n=2), contralateral ovary (n=1), contralateral ovary and peritoneal cavity (n=1), and brain (n=1). In all, 7 full-term singleton pregnancies were recorded among 5 of the 10 women who attempted to conceive after FSS., Conclusion: Favorable reproductive outcomes were observed following FSS, suggesting that this procedure may be a valid treatment option for women with FIGO stage IC EOC who wish to conceive., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Endometriotic cells display invasive characteristics, despite their benign histological appearance. Recently, the epithelial-mesenchymal transition, in which epithelial cells acquire mesenchymal and migratory properties, has attracted attention as a mechanism of tumor invasion. We aimed to investigate the association between endometriosis and polymorphisms of the E-cadherin gene, a central player in the epithelial-mesenchymal transition, in Japanese women., Methods: Twelve single-nucleotide polymorphisms (SNPs) in the E-cadherin gene were identified by real-time polymerase chain reaction using a TaqMan assay in 511 women with endometriosis (the majority in Stages III and IV) and 498 healthy controls., Results: Allele frequency analysis indicated that there was a marginally higher frequency of the rs4783689 C allele in women with endometriosis compared with controls (corrected P = 0.007; odds ratio = 1.37; 95% confidence interval, 1.14-1.64). No significant associations with endometriosis were found for the other 11 SNPs., Conclusions: Although this study was limited by sample size, the E-cadherin gene polymorphism rs4783689 was marginally associated with endometriosis in the Japanese population, suggesting that E-cadherin might be involved in genetic susceptibility to endometriosis.

Background: There are few cross-sectional and longitudinal studies on identification of the age of onset of obesity. The purpose of the present study was therefore to investigate 30 years of cross-sectional and longitudinal changes in the prevalence of obesity from 1978 to 2007 in Japanese children and adolescents between 5 and 17 years of age, using population-based samples., Methods: Subject data were obtained from the Annual Reports of the School Health Survey published by the Ministry of Education, Culture, Sports, Science and Technology, Japan. Obesity was defined as a body mass index (BMI) at or above the 95th percentile for age and gender based on the reference years from 1979 to 1981 in Japan. The BMI was calculated as weight in kg/(height in m)(2)., Results: Cross-sectional analysis of 5-, 8-, 11-, 14-, and 17-year-olds showed that the prevalence of obesity has gradually decreased since the early 2000s, with the highest prevalence in the late 1990s to early 2000s, except for in 17 year-old boys. Longitudinal studies showed that the critical periods for developing obesity were in late infancy (between 5 and 6 years of age) and in the high school period in boys, and mainly in late infancy in girls., Conclusions: Intervention to prevent obesity should be focused on late infancy in both genders and male adolescents in Japan.

Objective: To examine the possible association of adiponectin (ADIPOQ), adiponectin receptor (ADIPOR1/2) gene polymorphisms with polycystic ovary syndrome (PCOS) and their influence on insulin resistance in Japanese women with PCOS., Study Design: Six single nucleotide polymorphisms (SNPs) in ADIPOQ and ADIPOR1/2 were genotyped in 59 infertile Japanese women with PCOS and 97 healthy Japanese controls. In addition, the association between the genotype and allele frequencies of these SNPs and the clinical phenotypes was analyzed in PCOS patients., Results: There was no significant difference in the genotype and allele frequencies of the 6 SNPs between PCOS patients and controls. In the PCOS group, women with the GG genotype of 45T > G of ADIPOQ had a significantly higher score in the homeostasis model assessment for insulin resistance, fasting blood sugar and insulin level than those with other genotypes. Furthermore, a statistically significant difference in the genotype frequency of 45T > G polymorphism was observed between PCOS subjects with insulin resistance (n = 38) and controls (p = 0.011)., Conclusion: The 6 SNPs of ADIPOQ and ADIPOR1/2 were not associated with a risk of PCOS. However, the 45T > G SNP in the ADIPOQ may be related to insulin resistance in Japanese women with PCOS.

Background: The aim of this study was to clarify the relationship between onset of acute myocardial infarction (AMI) and weather conditions, to determine whether days in which AMI onset is likely can be predicted., Methods and Results: Of the 929 patients admitted to our hospitals in Kagoshima prefecture with AMI, subjects comprised 611 patients. Days of frequent onset (F-days) were defined as days with > or = 3 patients/day admitted for AMI, with days of non-frequent onset (N-days) defined as days with < 3 patients/day. Meteorological factors were measured, and daily differences in all parameters and intraday temperature differences on the onset day, and 1 and 2 days before onset were calculated. F-days were significantly associated with intraday temperature differences on the onset day (10.3 degrees C vs. 7.9 degrees C, p=0.005), 1 day before onset (10.7 degrees C vs. 7.9 degrees C, p=0.002), and 2 days before onset (11.3 degrees C vs. 7.9 degrees C, p=0.0001). A cutoff intraday temperature difference of > or = 9.4 degrees C on 1 and 2 days before onset was predictive of F-days with 89% sensitivity and 87% specificity., Conclusions: Intraday temperature differences offer a powerful predictor of F-days. Onset of AMI can be predicted based on weather conditions over the preceding 1-2 days.

In this study, the efficacy and safety of assisted reproduction techniques with the sperm-washing method and nested PCR assay were evaluated in HIV-1-discordant couples, as many HIV-1-positive people of reproductive age are getting married and wish to have children safely. Twenty-seven HIV-1-discordant couples (husband, positive; wife, negative) were enrolled in this study. The spermatozoa were separated from semen samples by density gradient centrifugation and the swim-up method. HIV-1 RNA and proviral DNA were checked using nested PCR with a detection limit of one copy before fertilization and before embryo transfer. Clinical outcomes were compared with those of matched control couples. Thirty-eight cycles of in vitro fertilization or intracytoplasmic sperm injection were performed in HIV-1-discordant couples, where the pregnancy rates per embryo transfer and per couple were 60.6 and 63.0%, respectively. These rates were significantly higher than those in control couples (P<0.05). Furthermore, all of the females and babies remained HIV-1 negative throughout the study period. Our data strongly suggest that this technique will allow HIV-1-discordant couples to conceive more safely and effectively.

Human intestinal spirochetosis is a common condition in Western countries, but is not well recognized in Japan. To demonstrate the incidence and clinicopathologic findings of human intestinal spirochetosis in Japan, we retrospectively investigated biopsy, and endoscopically or surgically resected specimens of the large intestine. Among a series of 2556 samples, 11 cases of human intestinal spirochetosis were detected (0.4%). Together with additional nine cases sporadically found, 20 cases of human intestinal spirochetosis were subjected to molecular detection of two strains of spirochetes (Brachyspira aalborgi and Brachyspira pilosicoli) by amplifying species-specific portion of 16S ribosomal RNA and NADH oxydase gene by polymerase chain reaction. B. aalborgi was detected in all cases examined, three of which revealed dual infection of both species. Our results suggest that human intestinal spirochetosis infection is relatively rare, and B. aalborgi is the most prevalent species in Japan. Most of human intestinal spirochetosis were asymptomatic, although symptomatic in exceptional cases. In addition, we emphasize a usefulness of immunostaining with anti-Treponema pallidum and anti-Mycobacterium bovis polyclonal antibodies for detecting the spirochetes.

Purpose: To assess the current practice of pediatric MDCT in Japan, with particular reference to age-related dose adjustment., Materials and Methods: During the first three months of 2004, a questionnaire was mailed to 996 institutions, among which listed MDCT users ranged from private hospitals to large university-based hospitals., Results: We received responses from 348 (34.9%) institutions. Fifty-three percent of the respondents had four-detector MDCT units. Approximately 70% of examinations were head and 22% were body. Scanning parameters were determined by full-time radiologists in 40%, and by CT technologists in 28% of respondents. Eighty-nine percent (head CT) and 85% (abdominal CT) of respondents indicated that they changed parameters for children. More than 90% changed tube current for optimization. Change was based on the technologist's experience (56%, head CT; 43%, abdominal CT), and automatic exposure control has been used as a basis of mAs control in 17% of respondents for head CT and in 34% for abdominal CT. Age-related mAs settings for abdominal CT were almost the same as those published in a United States survey., Conclusion: Although Japan has approximately 40% of the world's CT units, optimized pediatric MDCT settings might be moved away from a fixed mA protocol as recommended by the FDA and in conformity with the ALARA (as low as reasonably achievable) concept.

We report the case of a 76-year-old man with hairy cell leukemia (HCL)-Japanese variant who underwent rituximab therapy. HCL proved refractory to treatment with pentostatin and cladribine, and the number of hairy cells in the peripheral blood continued to increase after splenectomy. The patient was treated with rituximab (375 mg/m2 intravenously weekly for 4 cycles), and hairy cells disappeared from the peripheral blood on the day after the first administration. Complete remission continued for 18 months after treatment. Although they produce high response rates in typical HCL, nucleoside analogs are associated with an inferior clinical response in HCL-Japanese variant, and repetitive administration of these agents increases the risk of serious infections. This encouraging result suggests that rituximab therapy should be considered as salvage therapy for refractory HCL-Japanese variant.

Methodology: In 1997, a cooperative nationwide survey of 192 patients diagnosed with severe acute pancreatitis in 1996 was carried out., Results: Alcoholic pancreatitis was the major etiology (46%), and the male-to-female ratio was 2.6:1. Overall, the mortality rate was 27%, which was similar to the rate (30%) in the first nationwide survey of 1,219 patients diagnosed between 1982 and 1986 that was performed in 1987. A marked difference between the surveys was the early mortality rate within 2 weeks: 52% in the 1987 survey and 29% in the current survey. We devised a new stage classification system for acute pancreatitis. Stages 0 and 1 are equivalent to mild and moderate conditions, respectively, in the conventional classification, and stages 2 and higher correspond to severe acute pancreatitis. Severity scores of 2-8 are regarded as stage 2, scores of 9-14, as stage 3, and scores of > or =15, as stage 4. The mortality rates were as follows: 0, stages 0 and 1 at hospitalization; approximately 10%, stage 2; approximately 30-40%, stage 3; and approximately 70-100%, stage 4., Conclusion: We found that stage at hospitalization reflected the prognosis of acute pancreatitis.

The patterns of antibiotic resistance in Helicobacter pylori were assessed in two different regions in Japan. Overall, prevalences of resistance to metronidazole and clarithromycin were 12.4 and 12.9%, respectively. While there was no difference in clarithromycin resistance, the prevalence of metronidazole resistance was significantly higher in Kyoto (23.8%) than in Sapporo (8.1%). From 1996 to 1999, the prevalence of metronidazole resistance did not change but the prevalence of clarithromycin resistance doubled (from 9.1 to 18.7%).

We have characterized HLA and insulin autoantibodies in a Japanese female patient with insulin autoimmune syndrome. Serological HLA typing demonstrated the patient had HLA-DR4, and DNA typing showed she had HLA-DRB1*0401 which has not been reported in patients with insulin autoimmune syndrome in Japan. A single binding affinity of insulin autoantibodies was demonstrated by Scatchard analysis and immunoglobulin class of insulin autoantibodies was exclusively IgG-kappa. HLA-DRB1*0406 is strikingly associated with patients with insulin autoimmune syndrome who have polyclonal insulin autoantibodies. The present report demonstrated the first Japanese patient with insulin autoimmune syndrome carrying HLA-DRB1*0401 who was revealed to have monoclonal insulin autoantibodies. The present results indicate that HLA molecules are the major determinants of polyclonal insulin autoantibodies and monoclonal insulin autoantibodies in insulin autoimmune syndrome., (Copyright 2001 S. Karger AG, Basel)

There is continuing interest in identifying Helicobacter pylori virulence factors that might predict the risk for symptomatic clinical outcomes. It has been proposed that iceA and cagA genes are such markers and can identify patients with peptic ulcers. We compared H. pylori isolates from four countries, looking at the cagA and vacA genotypes, iceA alleles, and presentation of the infection. We used PCR to examine iceA, vacA, and cagA status of 424 H. pylori isolates obtained from patients with different clinical presentations (peptic ulcer, gastric cancer, and atrophic gastritis). The H. pylori isolates examined included 107 strains from Bogota, Colombia, 70 from Houston, Tex., 135 from Seoul, Korea, and 112 from Kyoto, Japan. The predominant genotype differed among countries: the cagA-positive iceA1 vacA s1c-m1 genotype was predominant in Japan and Korea, the cagA-positive iceA2 vacA s1b-m1 genotype was predominant in the United States, and the cagA-positive iceA2 vacA s1a-m1 genotype was predominant in Colombia. There was no association between the iceA, vacA, or cagA status and clinical outcome in patients in the countries studied. iceA status shows considerable geographic differences, and neither iceA nor combinations of iceA, vacA, and cagA were helpful in predicting the clinical presentation of an H. pylori infection.

Background/aim: Hepatocellular carcinoma frequently develops during the advanced stages of chronic hepatitis C. We examined whether interferon prevents the development of hepatocellular carcinoma in chronic hepatitis C patients., Methods: Japanese patients with chronic hepatitis C (n = 1.148; 117 with portal fibrous expansion (F1), 636 with bridging fibrosis (F2), 355 with bridging fibrosis and architectural distortion (F3)) and 40 cirrhotic (F4) patients were treated with interferon. These patients were followed from 1 to 7 years after interferon therapy. Blood tests and image analysis were serially performed to assess response to interferon and to detect hepatocellular carcinoma. Fifty-five cirrhotic type C patients (control F4) not receiving interferon were enrolled in this study., Results: Sustained (SR: 27.5%) and transient (TR: 23.0%) responders totaled 50.5%, while 49.5% did not respond to interferon. SR showed an improvement in disease stage reflected by increased platelet counts. Fifty-two patients (9 F2, 36 F3, and 7 F4) developed hepatocellular carcinoma in the follow-up period; 3 SR, 8 TR, and 41 non-responders (NR). The cumulative incidence of hepatocellular carcinoma in F2 was significantly lower (p = 0.019) in SR compared with NR, but not in SR in F3 and F4 patients. However, the cumulative incidence of hepatocellular carcinoma was significantly decreased in all SR (p = 0.0001) and TR (p = 0.0397) compared with all NR., Conclusion: These results indicate that interferon therapy in chronic hepatitis C patients lowered the rate of progression of hepatocellular carcinoma in sensitive cases but not in patients in an advanced stage.

Background: Mosaicism in vacA alleles with three distinct families of vacA signal sequences (s1a, s1b and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. It was suggested that the vacA s1a genotype was closely associated with duodenal ulcer disease and with high cytotoxin production. The aim of this study was to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, cytotoxin activity, and clinical presentation., Methods: H. pylori from patients with gastritis, peptic ulcer disease, or gastric cancer were characterized by vacA typing by polymerase chain reaction (PCR) and DNA sequencing. In vitro cytotoxin activity was assessed by vacuolation assay using Vero cells as well as with Hela cells., Results: Four hundred ninety-one strains were tested. vacA genotype s1a/m1 was present in more than 95% of strains independent of presentation with gastritis, peptic ulcer, or gastric cancer. No vacA genotype was associated with high average cytotoxin activity. The s2/m2 isolates had low or absent cytotoxin activity. All cagA negative strains (n = 18) were s1a strains and both s2/m2 strains were cagA positive. One strain that was a recombinant of m1 and m2 strains was identified and had low cytotoxin activity. The nucleotide and amino acid sequences between original m1 strains and Japanese m1 strains (new m1 strains) were about 85% and 81%, respectively. Strains with the new m1 genotype had nucleotide and amino acid sequences similarity of more than 96%. There was no difference in cytotoxin activity between strains with the Western type m1 and the new type m1 genotype., Conclusion: In this as in other reported studies ( approximately 1500 patients overall) vacA genotype was strongly but not exclusively associated with the presence of cagA. Overall, the studies did not support a role for vacA genotyping in relation to cytotoxin activity, virulence, histologic finding, or risk of a particular H. pylori disease. vacA genotype s1 is likely to be a surrogate marker for the presence of the cag pathogenicity island.

The CagA protein of Helicobacter pylori is an immunogenic antigen of variable size and unknown function that has been associated with increased virulence as well as two mutually exclusive diseases, duodenal ulcer and gastric carcinoma. The 3' region of the cagA gene contains repeated sequences. To determine whether there are structural changes in the 3' region of cagA that predict outcome of H. pylori infection, we examined 155 cagA gene-positive H. pylori isolates from Japanese patients including 50 patients with simple gastritis, 40 with gastric ulcer, 35 with duodenal ulcer, and 30 with gastric cancer. The 3' region of the cagA gene was amplified by PCR followed by sequencing. CagA proteins were detected by immunoblotting using a polyclonal antibody against recombinant CagA. One hundred forty-five strains yielded PCR products of 642 to 651 bp; 10 strains had products of 756 to 813 bp. The sequence of the 3' region of the cagA gene in Japan differs markedly from the primary sequence of cagA genes from Western isolates. Sequence analysis of the PCR products showed four types of primary gene structure (designated types A, B, C, and D) depending on the type and number of repeats. Six of the seven type C strains were found in patients with gastric cancer (P < 0.01 in comparison to noncancer patients). Comparison of type A and type C strains from patients with gastric cancer showed that type C was associated with higher levels of CagA antibody and more severe degrees of atrophy. Differences in cagA genotype may be useful for molecular epidemiology and may provide a marker for differences in virulence among cagA-positive H. pylori strains.

Early studies suggested that two Helicobacter pylori proteins, CagA and VacA, were virulence factors. Support for that hypothesis has been undermined by geographic differences in prevalence of these antigens. To identify other possible putative virulence factors by establishing a relationship between antigens and different H. pylori diseases, two commercial available immunoblot assay kits, HelicoBlot 2.0 (Genelabs Diagnostics, Singapore) and RIDA Blot Helicobacter (R-Biopharm GmbH, Darmstadt, Germany), were used to investigate the prevalence of various specific antigen seropositivity in 80 H. pylori-infected Japanese (20 each with gastritis, duodenal ulcer, gastric ulcer, or gastric cancer). The production of interleukin-8 (IL-8) in biopsy specimens was also measured by enzyme-linked immunosorbent assay (ELISA). Both assays had 100% sensitivity; specificity was 90% for HB2.0 and 80% for RIDA-BH. With the exception of the 33-35 K antigen, there was no relationship between antigens, endoscopic diagnoses, histological findings, or mucosal IL-8 levels. The 33-35 K antigen was present in 97.5% (39 of 40) patients with gastric or duodenal ulcer compared to 70% (14 of 20) those with chronic gastritis (P < 0.006). The mean IL-8 levels in the corpus was significantly higher in those with antibody to the 33-35 K antigen compared to those without (105.4+/-22 pg/mg vs 10.2+/-8.8 pg/mg) (P=0.015). There was no relationship between other antigens including CagA and production of IL-8. In conclusion, the low-molecular-weight 33-35 K antigen may play an important role in the pathogenesis of H. pylori-related disease.

The present study was aimed to clarify the virologic status, liver histologies, and the results of follow-up liver tests in symptom-free individuals with anti-HCV antibodies and normal liver tests. Forty-nine individuals with normal liver tests and positive second generation anti-HCV antibody assay were entered into this study. Cases with hepatitis C viremia were evaluated for HCV genotype, amount of circulating HCV-RNA, and liver histology and were followed-up for more than one year. Of the forty-nine individuals, 36 had hepatitis C viremia, indicated by polymerase chain reaction (PCR) assay. Liver histology was as follows: 3 had non-specific changes, 25 had chronic persistent hepatitis (CPH), and 8 had chronic active hepatitis (CAH). Twenty-four cases with CPH and CAH developed an elevated AST and/or ALT concentration (> 30 IU/l) between 12 and 32 months of follow-up. The amount of circulating HCV-RNA ranged from 10(2) to 10(7) copies/50 microliters serum. The distribution of HCV genotypes was nearly the same as that for symptomatic CAH. These data suggest that the histological examination and follow-up examination are very important for following symptom-free individuals with hepatitis C viremia because there are some candidates for interferon therapy among them. There are few individuals who will remain healthy among asymptomatic HCV carriers.

To evaluate the efficacy and safety of subcutaneous administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in aplastic anemia (AA), 21 patients were given a daily subcutaneous dose of 200 micrograms/m2 of KRN8601 for 4 weeks. When the blood neutrophil count did not reach 2,000/microliters within 2 weeks, the dose was increased to 400 micrograms/m2. A marked neutrophilic response was obtained in all 9 patients with non-severe AA and in 9 out of the 12 patients with severe AA, yielding a response rate of 85.7%. Adverse effects included lumbago in one patient and elevation of serum enzyme levels in 6 patients, but did not prohibit further treatment. These results suggest that subcutaneous administration of KRN8601 is safe and useful in improving neutropenia in AA.

To evaluate the safety and efficacy of subcutaneous administration of recombinant human granulocyte colony-stimulating factor in the myelodysplastic syndromes (MDS), 20 patients were given a daily dose of 50 micrograms/m2 of KRN8601 for 4 weeks. When the blood neutrophil count did not reach 2,000/microliters within 2 weeks, the dose was increased to 100 micrograms/m2. A marked neutrophilic response was obtained in 17 of the 18 evaluable patients (94.4%), irrespective of the MDS disease type. Five patients showed a platelet increase, 3 of which also showed an erythroid improvement. To maintain neutrophil levels greater than 1,000/microliters, 12 patients were treated with KRN8601 for 4 weeks. A dose of 25 to 50 micrograms/m2 3-4 times a week served to this end in 8 patients and 100 micrograms/m2 three times a week or daily in the remaining 4 patients. One patient with RAEB progressed to acute myeloid leukemia 8 weeks after KRN8601. The treatment was well-tolerated in the majority of patients with no severe toxicities. These results suggest that subcutaneous administration of KRN8601 is safe and useful in the treatment of cytopenias in MDS.

It has recently come to be thought that cases of juvenile polyposis have a natural tendency to develop adenoma and/or carcinoma. Here we present a case of juvenile polyposis coli with adenomatous change in a 21-year-old male, with a review of 34 cases of juvenile polyposis in the Japanese literature, and discuss the pathogenetic development of the polyps and their malignant potential. In this case, focal or entire adenomatous areas were found in large part of the polyps in the resected sigmoid colon and rectum, though these findings had not been recognized in 23 polypectomy specimens from the rectum 10 months prior to the operation. It was suggested that adenomatous change developed quickly in a very short time.

The materials for study were serial upper jaw plaster casts of 58 Japanese (29 boys and 29 girls) aged 3 to 7 years, and 93 Indians (46 boys and 47 girls) aged 5 to 8 years. I observed and measured the palatal rugae, the papilla incisiva and the shape of the hard palate using the method of Yamazaki, following Lysell's and Hauser's. The differences according to population (1-5), palatal findings (6) and sex (7) are summarized as follows. 1. The number of primary rugae of Japanese children were more than those of Indian children, but the number of transverse palatal rugae were the same. 2. There were differences between Japanese and Indian children in the primary rugae shapes, the posterior limit of the rugae zone, the number and position of the secondary rugae and fragmentary rugae. 3. The papilla incisiva of the Japanese children were a little larger than those of the Indians. Generally the papilla incisiva of the two populations were pear-shaped, but the Indians showed more variability. 4. The palatal raphe of the Japanese were wider than those of the Indians. The number of children with no palatal raphe branch was large for Indian children, but small for Japanese. 5. The frontal view of the hard palate of Japanese children was broad and that of Indian children was narrower than the Japanese. The palatal shape of the two populations was almost trapezoid. The occlusal view of the two populations was broad and U-shaped. 6. There were many transverse palatal rugae in the two populations at the left side. The posterior limit of the ruga zone of the left side was shifted further back than the right side. 7. There were no significant differences between sexes for most of the above points.