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M Sada

Publications and source records attributed to M Sada.

At least 19 recordsLinked to original sources
PubMed2003

Genetic analysis on HLA loci in Japanese patients with abdominal aortic aneurysm.

PURPOSE: autoimmunity has been proposed as one of the pathogenesis of abdominal aortic aneurysm (AAA). There is also a likelihood that when aorto-iliac occlusive disease (AIOD) coexists with AAA, some other occlusive atherosclerotic diseases, such as ischemic heart disease and cerebrovascular disease, may develop, leading to a very poor long-term prognosis. Previous studies using serological HLA typing showed that HLA-DR15 was a risk factor for AAA. In this study, we performed HLA-DNA typing by PCR to clarify the relationship between AAA and HLA genotypes in Japanese patients with AAA. In addition, we analyzed whether HLA genotypes are involved in the pathogenesis of AIOD. RESULTS: we examined 78 HLA genotypes of class I (HLA-A and -B) and class II (HLA-DR) and found that 60.4 and 30.4% of 49 AAA patients had HLA-A2 and HLA-B61, respectively. These frequencies were significantly higher than those in control individuals (HLA-A2, p < 0.05; HLA-B61, p < 0.005). We also found that 55.6% of nine AAA patients with AIOD had both HLA-B52 and HLA-DR B1*1502. In contrast, only 10.0% each of 40 AAA patients without AIOD showed HLA-B53 or HLA-DR B1*1502. CONCLUSIONS: this study showed that HLA A-2 and HLA B-61, but not HLA DR-15, were important genetic risk factors for the development of AAA among the Japanese population. We also found high frequencies of HLA-B52 and HLA-DR B1*1502 in the AAA patients with AIOD than in those without, although this must be confirmed using a larger number of AAA patients with AIOD.

Aged↗
PubMed2002

Susceptibility locus for non-obstructive azoospermia is localized within the HLA-DR/DQ subregion: primary role of DQB1*0604.

Non-obstructive azoospermia is a male infertility characterized by no or little sperm in semen as a result of a congenital dysfunction in spermatogenesis. Previous studies have reported a higher prevalence of particular human leukocyte antigen (HLA) antigens in non-obstructive azoospermia. As the expression of the RING3 gene located in the HLA class II region was predominant in the testis, mainly around spermatids and pachytene spermatocytes, it is tempting to speculate that RING3 is one of the strong candidate genes responsible for the pathogenesis of the disease. In this study, the genetic polymorphism in the RING3 gene was investigated by the direct sequencing technique. As a result, a total of 14 single nucleotide polymorphisms were identified. Among them, six were localized in the coding region but none of them was accompanied by an amino-acid substitution. No significant difference in the allelic distribution at these 14 polymorphic sites was observed between the patients and healthy controls, suggesting that the susceptible gene for non-obstructive azoospermia is not the RING3 gene. Then, in order to map the susceptibility locus for non-obstructive azoospermia precisely within the HLA region, 11 polymorphic microsatellite markers distributed from the SACM2L gene just outside the HLA class II region (187 kb telomeric of the DPB1 gene) to the OTF3 gene in the HLA class I region were subjected to association analysis in the patients. Statistical analysis of distribution in the allelic frequency at each microsatellite locus demonstrated that the pathogenic gene for non-obstructive azoospermia is located within the HLA-DR/DQ subregion. In fact, DRB1*1302 and DQB1*0604 were found to be strongly associated with non-obstructive azoospermia by polymerase chain reaction-based DNA typing. Further, haplotype analysis suggested that the DQB1*0604 allele may play a decisive role in the pathogenesis of non-obstructive azoospermia.

Alleles↗
PubMed2001

Susceptibility to vesicoureteral reflux in Japanese is linked to HLA-DR antigen.

OBJECTIVES: To determine whether vesicoureteral reflux is associated with the human leukocyte antigen (HLA) genes. METHODS: We evaluated 40 Japanese patients (27 males and 13 females) with reflux. HLA-DR low-resolution genotyping and high-resolution typing of HLA-DRB1 alleles were performed. The frequencies of the HLAs and alleles were calculated and compared with those previously reported in 493 healthy Japanese. RESULTS: Low-resolution typing showed that the frequency of the HLA-DR11 antigen was significantly higher in the patients with reflux than in the control group. High-resolution typing revealed that the frequencies of HLA-DRB1*1101 and 1502 alleles were significantly higher in the patients with reflux than in the control group. In the patients with and without renal scarring, the frequencies of the HLA-DR11 antigens and HLA-DRB1*1101 alleles were significantly lower in those with renal scarring. In the patients with and without the chief complaint of urinary tract infection symptoms, the frequencies of HLA-DR13 antigens and HLA-DRB1*1302 alleles were significantly lower in those with that chief complaint. CONCLUSIONS: The susceptibility to reflux is, in part, controlled by HLA genes themselves or an unknown gene or genes, the locus for which is located close to the DRB1 gene. The lack of a HLA-DRB1*1101 allele and DRB1*1302 allele in patients with reflux might be connected with renal scarring and urinary tract infection, respectively.

Adolescent↗
PubMed2001

cDNA cloning and genetic polymorphism of the swine major histocompatibility complex (SLA) class II DMA gene.

cDNA clones corresponding to the swine histocompatibility complex (SLA: swine leucocyte antigen)-DM alpha chain were isolated using the polymerase chain reaction (PCR) products from the third exon in the human HLA-DMA gene as a probe. Amino acid comparative analysis revealed that these clones were more closely related to the bovine and human DMA genes than to the other swine class II genes alpha chain genes, DRA, DQA and DOA. These results suggest that the SLA-DMA gene is expressed and may function, like HLA-DM, as an important modulator in class II restricted antigen processing in swine. Furthermore, based on the sequences and PCR-restriction fragment length polymorphism (PCR-RFLP) patterns in the SLA-DMA gene, no allelic variation was recognized in the second exon, but five allelic variations were recognized in the third exon in five different breeds of swine. These DMA alleles were defined by variation at four nucleotide positions. Two of these alleles resulted in an amino acid substitution. These results suggest that SLA-DMA has little polymorphism as observed in HLA-DMA and mouse H2-Ma.

Alleles↗
PubMed2000

On the MICA deleted-MICB null, HLA-B*4801 haplotype.

A 100-kb deletion including the MICA gene was recently reported in the HLA-B48 (B*4801)-associated haplotype in Japanese. Interestingly, this MICA deletion is accompanied by a MICB null allele, MICB0107N. In order to further investigate the universality of the apparent tight linkage between these two events, we present data on high-resolution deletion mapping of eight HLA-B48-homozygous individuals. Among these, five carried the MICA deletion linked to MICB0107N, as originally reported. Conversely, the remaining three possessed an intact MICA gene of MICA008 or MICA010 allelic variant associated this time with a putative expressed MICB allele, MICB0102. These results may imply that the expression of both MICA and MICB molecules is indispensable to viability through a yet-to-be understood mutual interaction in immune surveillance.

Alleles↗
PubMed2000

Fracture of hamate hook--diagnosis by the hamate hook lateral view.

Ten intact wrist joints were examined to evaluate the hamate hook visualisation by a hamate hook lateral radiographic view. Results of the study indicated that this 30 degrees -tilted lateral wrist radiographic projection with palmar abduction of the thumb clearly revealed the hamate hook from its base to the tip in the first web space away from the metacarpal bases and carpal bones. This radiographic technique was applied on patients who experienced pain at the hypothenar eminence. Fracture can be detected at the hamate hook in two cases and bilateral bipartite hamulus in one case. This specific supplementary projection is recommended in patients with the relevant physical signs.

Adolescent↗
PubMed2000

HLA-DRB genotypes in Japanese patients with renal cell carcinoma.

OBJECTIVES: Several clinical features, such as the spontaneous regression of some renal cell carcinoma (RCC) metastases after nephrectomy, suggest immune involvement in tumor destruction. PATIENTS AND METHODS: We investigated the role of genetic variation at the HLA class II loci in RCC by analyzing the HLA-DR antigen and HLA-DRB1, DRB3, DRB4 and DRB5 alleles in 55 patients using the polymerase chain rection. RESULTS: No statistically significant differences were observed in the frequency of the HLA-DR antigen or HLA-DRB3, DRB4, or DRB5 genes between the patients and a healthy control group. On the other hand, the HLA-DRB1*0403 and *1202 alleles were significantly more frequent in the patients than in the controls (p < 0.001 and p < 0.01, respectively). CONCLUSION: RCC might be linked to these two alleles in Japanese patients.

Adult↗
PubMed1999

Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset Type I (insulin-dependent) diabetes mellitus.

AIMS/HYPOTHESIS: To determine whether the clinical heterogeneity observed in the development of Type I (insulin-dependent) diabetes mellitus correlates with immunohistochemical differences observed at diagnosis. METHODS: Patients (n = 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I), underwent pancreatic biopsy for immunohistological analysis. These patients were divided into two groups based on the presence or absence of islet immunological abnormalities (insulitis or hyperexpression of MHC class I antigens or both). The patients were also HLA typed and tested for islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD-Ab). All patients were followed monthly for 2 years and their fasting plasma glucose, haemoglobin A1c and daily insulin doses were recorded. The clinical course of patients with islet immunological abnormalities was compared with that of patients without those abnormalities. RESULTS: Patients with and without islet immunological abnormalities did not differ with regard to HLA type or islet cell antibodies. Antibodies to glutamic acid decarboxylase correlated with the presence of insulitis and MHC class I hyperexpression. These local immunological abnormalities were also associated with higher haemoglobin A1c values (p < 0.05) and a trend towards greater insulin requirements. Further, patients with the islet abnormalities had higher fasting plasma glucose concentrations 2 years after the biopsy than at the time of the biopsy (p < 0.05). CONCLUSION/INTERPRETATION: The heterogeneous clinical course observed following diagnosis in patients with Type I diabetes correlates with islet immunological abnormalities. Insulitis and hyperexpression of MHC class I correlate with deteriorating glycaemic control.

Adolescent↗
PubMed1999

Relationship between HLA-DR antigen and HLA-DRB1 alleles and prostate cancer in Japanese men.

PURPOSE: Human leukocyte antigens (HLA) are cell surface glycoproteins playing a key role in the immune system. In some cancers, changes in major histocompatibility complex (MHC) class I and II expression, usually a reduction or loss of these molecules, appear to provide a mechanism whereby tumour cells may escape host immunity. We investigated the relationship between HLA, especially class II, molecules and prostate cancer in Japanese men using molecular techniques. MATERIALS AND METHODS: HLA class II typing was performed by the polymerase chain reaction-sequence specific primer (PCR-SSP) method of analysis and/or a commercial rapid assay based on the PCR followed by reverse dot-blot hybridization of the PCR products (Inno-LiPA assay). Allele frequencies were calculated. HLA allele frequencies reported in 1216 healthy Japanese individuals were used as the control data. Differences in allele frequency between subjects and the control group were analyzed by the chi-square test. The relationship between HLA antigens/alleles and prostate cancer is expressed in terms of relative risk (RR). RESULTS: The frequencies of HLA-DR4 were significantly higher in Japanese men with prostate cancer than in the healthy control group (gene frequency 36.2% vs. 26.3% in control, p<0.05), although the relative risk of prostate cancer was less than 2. Furthermore, the frequencies of HLA-DRB1-0406, 0410 and 1405 allele were significantly higher in the prostate cancer group than in the control group (allele frequency was 7.3%, 4.5% and 5.4% vs. 3.03%, 1.79% and 2.22%, p<0.05, respectively). RR of those HLA-DRB1 allele for prostate cancer was 2.6 in each allele. CONCLUSIONS: HLA molecules may be useful for the early detection of prostate cancer as a risk factor, and also for recognizing cancer activity by using them as a marker helpful in the choice of appropriate treatment by predicting prognosis.

Alleles↗
PubMed1999

A case of adenocarcinoma of the small intestine in a Japanese patient with Crohn disease: a report with immunohistochemical and oncogenic analyses.

We report a rare case of Crohn disease accompanied by a small-bowel carcinoma that developed in a 54-year-old Japanese man. The ulcerating tumor, which histologically proved to be a poorly differentiated adenocarcinoma and dysplasia surrounding the carcinoma, was located in the diseased ileum. The Ki-67 immunoreactive epithelial cells were increased in regenerative mucosa as compared with values for normal mucosa. The Ki-67- and p53-positive cells were increased in dysplasia and carcinoma as compared with values for regenerative or normal mucosa. In contrast, the p21(WAF1/CIP1) immunoreactive cells were decreased in this order. Intense DCC (deleted in colorectal cancer) expression was constantly shown among normal, regenerative, dysplastic and cancerous tissues. No bcl-2 expression and c-Ki-ras mutations were apparent. In conclusion, enhanced epithelial cell proliferation, p53 overexpression, and decrease of p21(WAF1/CIP1) expression may predispose the small-bowel mucosa to dysplasia and carcinoma development in Crohn disease.

Adenocarcinoma↗
PubMed1999

Cell kinetics, p53 and bcl-2 expression, and c-Ki-ras mutations in flat-elevated tubulovillous adenomas and adenocarcinomas of the colorectum: comparison with polypoid lesions.

BACKGROUND: Flat(-elevated) tubulovillous adenomas and adenocarcinomas of the colorectum constitute a specific type of neoplasm with superficial spreading growth. To establish their characteristics, a comparative investigation of a series of tumors was performed. METHODS: A total of 56 flat tubulovillous tumors (39 adenomas, 17 invasive carcinomas) and 154 polypoid tubular or villous tumors (77 adenomas, 77 invasive carcinomas) were comparatively assessed for cell kinetics and molecular alterations. RESULTS: Ki-67 labeling and p53 expression for both types of tumors increased along with degree of dysplasia or invasion, whereas bcl-2 expression showed an inverse decrease. However, apoptotic activity was invariably low in the flat tubulovillous tumors, as compared with the polypoid tumors, in which increase was apparent with tumor progression. The flat tubulovillous tumors also showed a higher frequency of c-Ki-ras mutations (92.9%) than the polypoid tubular tumors (40.0%). CONCLUSIONS: The flat tubulovillous tumor can be considered a distinct entity, with characteristics different from the polypoid counterpart.

Adenocarcinoma↗
PubMed1999

[Usefulness of endoscopic polypectomy in early colorectal cancer].

This study was carried out to clarify the usefulness of endoscopic polypectomy in early colorectal cancer. Six hundred and sixty-four patients with polypectomized early colorectal cancer were compared with 89 who underwent surgical resection. Among the polypectomized patients, 361 had pedunculated (Ip)-type, 255 semi-pedunculated (Isp)-type, and 48 sessile (Is)-type cancer. The early colorectal cancer was submucosal-invasive cancer (sm cancer) in 16.1% of Ip, 19.2% of I sp, and 22.9% of Is patients. Among the surgically resected patients, sm cancer was present in 41.2% of Ip. 62.1% of I sp. and 58.1% of Is patient in. The percentage of sm cancer and the tumor size surgically resected patients were greater than in polypectomized patients. Local recurrence and distant metastases were investigated after endoscopic polypectomy during follow-up. Two cases (0.4%) of local recurrence were detected after polypectomy among 555 patients with mucosal cancer. Twenty-three (19.8%) of 116 patients with sm cancer underwent surgical resection after polypectomy due to cancer invasion into the vessels and/or extension to the resected margin recognized in polypectomized specimens. Only one case (0.9%) of local recurrence and no distant metastases were detected after polypectomy in 116 patients with sm cancer. Endoscopic polypectomy is very useful as a minimally invasive surgical technique in the protruding type of early colorectal cancer.

Colonoscopy↗
PubMed1998

TACHY: an expert system for the management of supraventricular tachycardia in the elderly.

PURPOSE: Many physicians find the management of supraventricular tachyarrhythmia (SVT) in the elderly complex and challenging. With the use of artificial intelligence theory, we developed an interactive computer expert system, TACHY, to recommend therapies and warn physicians of potential therapeutic side effects. METHODS: We developed a knowledge base that stores guidelines for the management of SVT in the elderly. After the diagnosis of current SVT was input into the computer, TACHY generated a list of therapeutic options as hypotheses. TACHY then prompted the user to provide current patient-specific clinical information, and the optimal therapeutic option was then selected. Potential therapeutic side effects were also displayed. TACHY was tested in a retrospective and a prospective study. The retrospective study, comprising 96 patients with 126 episodes of SVT, was performed to determine the concordance of therapy between TACHY and cardiologists. A prospective study in 18 patients with 26 episodes of SVT was also performed to validate TACHY's recommendations in restoring sinus rhythm. RESULTS: In the retrospective study the concordance between TACHY and the cardiologist's first therapeutic option was 95.9% (121 of 126 episodes). In the prospective study sinus rhythm was restored in 18 (69%) of 26 episodes of SVT by the first therapeutic option recommended by TACHY. In the remaining eight episodes use of the second or third suggestion of TACHY was successful in controlling the ventricular response to SVT. No adverse reaction to the therapeutic options suggested by TACHY occurred. CONCLUSION: TACHY, a knowledge-based computer expert system that simulates human decision making, produced promising results in the management of SVT in the elderly.

Aged↗
PubMed1998

Susceptibility to idiopathic azoospermia in Japanese men is linked to HLA class I antigen.

PURPOSE: Approximately 15 to 20% of infertile men have azoospermia. In the Y chromosome a deletion, termed the azoospermic factor, has been found in some cases of idiopathic azoospermia. We investigate the relationship of factors in autosomal chromosomes (HLA class I antigens) to spermatogenesis failure in idiopathic azoospermia. MATERIALS AND METHODS: We evaluated 65 infertile Japanese men with idiopathic azoospermia. The frequency of the HLA allele reported in 1,216 healthy Japanese men was used as a control. HLA class I typing was performed by the National Institutes of Health standard serological method or polymerase chain reaction-sequence specific primer analysis. Allele frequencies were calculated. We determined statistical significance in the frequency of each allele in patients and controls using the chi-square test. The relationship of HLA antigens to idiopathic azoospermia was expressed as relative risk. RESULTS: In Japanese men with idiopathic azoospermia the frequency of HLA-A33, B13 and B44 was significantly increased compared with controls. The relative risk of HLA-B44 was 8.4, an extremely high value compared with that of other diseases and HLA antigens. CONCLUSIONS: We suggest that HLA class I antigens are important genetic markers that represent a risk factor for idiopathic azoospermia.

Alleles↗