Biomedical subjects

N Iwai

Publications and source records attributed to N Iwai.

At least 55 records · Page 3Linked to original sources

PubMed2000

Arteriovenous malformation of the penis in an infant.

Arteriovenous malformations (AVMs) are common benign lesions in infancy, although they are rare in the genitourinary region. The authors report on a 2-year-old boy with a penile AVM. At presentation, there was venous dilatation and tortuosity of the prepuce without ulceration, which had been recognized at 1 year of age. Left internal iliac arteriography showed early venous filling leading to the diagnosis of AVM. Surgical excision was performed at age 2. The postoperative course was uneventful. At the 6-month follow-up, there was no evidence of recurrence. This is the first report of a penile AVM that was successfully treated by surgical excision.

Arteriovenous Malformations↗

PubMed2000

Congenital anomalies in mice induced by etretinate.

We report on the experimental induction of anorectal malformations (ARM) and other internal and external malformations in mouse fetuses induced by maternal administration of etretinate, a long-acting vitamin A analogue. The teratogen was administered to pregnant mice between the 7th and 10th gestational days (E7 and E10). The mice of the control group were given pure sesame oil on E9. We examined survival rates, crown-rump length, and the incidence of internal and external malformations, with particular attention to ARM, in each group. All mice in the E8 group exhibited rectovesical fistula, hydronephrosis, and spina bifida. All males and females in the E9 group given 60 mg/kg of etretinate developed rectoprostatic urethral fistula and rectocloacal fistula, respectively. The E10 group, given 60 mg/kg of etretinate displayed cleft palate (63.6%), forelimb malformation (68.2%), and a short club-shaped tail (100%). The fetuses had more severe types of ARM when etretinate had been administered on an earlier gestational day. The E9 group is a useful model for anorectal malformation, whereas the E8 group is a model for hydronephrosis and spina bifida.

Abnormalities, Drug-Induced↗

PubMed2000

Genetic mapping of quantitative trait loci influencing left ventricular mass in rats.

High blood pressure is the leading cause of left ventricular hypertrophy (LVH); however, not all hypertensive patients develop LVH. Genetic factors are important in the development of LVH. With the use of F2 male rats from spontaneously hypertensive rats and Lewis rats, we performed a study to identify the quantitative trait loci (QTL) that influence left ventricular mass (LVM). Mean arterial pressure (MAP) was measured by the direct intra-arterial method in conscious animals, and LVM was determined at 24 wk of age. QTL analysis was done using 160 microsatellite markers for a genome-wide scan. Two loci that influenced body weight-adjusted LVM with logarithm of the odds scores >3.4 were found. One locus on chromosome 17 influenced LVM independently of MAP. Another locus on chromosome 7 influenced LVM and MAP. These findings indicate not only the existence of a gene on chromosome 7 that influences LVM in a manner dependent on blood pressure but also the existence of a gene on chromosome 17 that influences LVM independently of blood pressure.

Animals↗

PubMed2000

Leisure-time physical activity and related lifestyle characteristics among middle-aged Japanese. Japan Lifestyle Monitoring Study Group.

The present study describes leisure-time physical activity status and related lifestyle factors in middle-aged Japanese. Data were obtained from 1,893 (905 men, 988 women) participants aged 40-69 years who had either been selected from a public registry or who had visited a healthcare facility. Subjects responded to a self-administered questionnaire and were interviewed using an assessment method for leisure-time and on-the-job physical activity within the last 12 months by trained interviewers. According to the leisure-time physical activity score, men and urban residents tended to engage in more leisure-time physical activity than did women and rural residents, respectively. Leisure-time physical activity tended to be inversely associated with on-the-job physical activity in all cases aside from women in urban regions, and also to be associated with higher levels of education in rural regions. Subjects engaging in more leisure-time physical activity had higher odds ratios of certain lifestyle factors, indicating a healthy lifestyle that included a variety of foods in their diet and a subjective sense of wellness in both men and women, in addition to non-smoking and drinking milk in men. These results suggested that leisure-time physical activity is influenced by socio-environmental factors, and that it is accompanied by other healthy behavior.

Adult↗

PubMed2000

[Alpha-adducin gene].

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Calmodulin-Binding Proteins↗

PubMed2000

[Sa gene].

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Animals↗

PubMed1999

Human prostacyclin synthase gene and hypertension : the Suita Study.

BACKGROUND: Prostacyclin (prostaglandin I(2)) is a strong vasodilator that inhibits the growth of vascular smooth muscle cells and is also the most potent endogenous inhibitor of platelet aggregation. Therefore, it has been considered to play an important roles in cardiovascular disease. On the basis of the hypothesis that variations of the prostacyclin synthase gene may also play an important role in human cardiovascular disease, we performed a screening for variations in the human prostacyclin synthase gene. METHODS AND RESULTS: We have detected a repeat polymorphism in the promoter region of the human prostacyclin synthase gene. The number of 9-bp (CCGCCAGCC) repeats in the promoter region, which encodes a tandem repeat of Sp1 transcriptional binding sites, varied between 3 and 7 in Japanese subjects. Luciferase reporter analysis indicated that the alleles of 3 and 4 repeats (R3 and R4, respectively) had less promoter activity in cultured human umbilical vein endothelial cells. We then investigated the possible association of this repeat polymorphism with blood pressure in a large population-based sample (the Suita Study), which consisted of 4971 Japanese participants. Multivariate models indicated that participants with the R3R3, R3R4, or R4R4 genotype (SS genotype, n=80) had significantly higher systolic pressure (P=0.0133) and pulse pressure (P=0.0005). The odds ratio of hypertension (140/90 mm Hg) for the SS genotype was 1.942 (95% confidence interval 3.20 to 1.19, P=0.0084). CONCLUSIONS: Repeat polymorphism of the human prostacyclin synthase gene seems to be a risk factor for higher pulse pressure and is consequently a risk factor for systolic hypertension in the Japanese population.

Adult↗

PubMed1999

Chromosomal mapping of quantitative trait loci that influence renal hemodynamic functions.

BACKGROUND: Impaired renal hemodynamic function has been suspected to be responsible for hypertension in the spontaneously hypertensive rat (SHR). METHODS AND RESULTS: We measured renal hemodynamic functions, including the glomerular filtration rate, renal plasma flow, and renal vascular resistance, in an F2 rat population derived from spontaneously hypertensive and Wistar-Kyoto (WKY) rats and performed a genome-wide screening to map quantitative trait loci that influence these functions to gain insight into the relationship between renal hemodynamic functions and blood pressure control. The D1 Mit7 locus was identified as a major locus that influenced renal hemodynamic functions, and we transferred the SHR chromosomal segment around the D1 Mit7 locus into the WKY strain. The congenic rats exhibited impaired renal hemodynamic functions. The systolic blood pressure of the congenic rats was significantly higher than that of age-matched WKY rats, but only at nighttime. No significant differences in systolic blood pressure during daytime or diastolic blood pressure were observed between the 2 strains. CONCLUSIONS: We have identified a chromosome segment that influences renal hemodynamic function. The SHR chromosome segment around the D1 Mit7 locus had significant, but not dramatic, effects in increasing blood pressure in the WKY genetic background. However, further studies will be necessary to determine the significance of this locus in SHR hypertension.

Animals↗

PubMed1999

Molecular cloning and genomic organization of mouse homologue of Drosophila germ cell-less and its expression in germ lineage cells.

Primordial germ cells (PGCs) are founder cells of all gametes. A number of genes which control PGCs development have been identified in invertebrates, whereas such genes are by and large unelucidated in mammals. Here we describe cloning, genomic structure and expression of mouse homologue of germ cell-less (gcl) gene which is required for PGCs formation in Drosophila. The mouse gcl shows 34% identity compared with Drosophila gcl protein and contains BTB/POZ domain. The gcl gene consists of 14 exons and spans more than 50 kb. The CpG islands are found around exon 1 of the gene. Putative promoter region contains potential binding sites for various transcription factors. Northern blot analysis showed that its mRNA is highly expressed in adult testis with lower expression in ovary, ES (embryonic stem) cells, and various other organs. In situ hybridization analysis revealed strong expression of the gcl gene in the pachytene stage spermatocytes. The expression was also observed in post-migratory PGCs, but was not apparent in migratory and pre-migratory PGCs. Further studies including gene disruption analysis would provide an important insight into mammalian germ lineage development.

Aging↗

PubMed1999

D allele of the angiotensin-converting enzyme gene is a risk factor for secondary cardiac events after myocardial infarction.

We retrospectively examined the relationship between the genotype of the angiotensin-converting enzyme (ACE) gene or the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, and the secondary cardiac events after myocardial infarction. The study population consisted of 176 patients (ACE genotype: deletion homozygote (DD)=20, insertion/deletion heterozygote (ID)=91, insertion homozygote (II)=65; MTHFR genotype: valine homozygote (VV)=37, valine/alanine heterozygote (VA)=71, alanine homozygote (AA)=68) with acute or recent myocardial infarction at the start of the follow-up. We defined the occurrence of cardiac death, recurrent myocardial infarction, or admission due to unstable angina as the endpoint. Cardiac events related coronary intervention were excluded from the endpoints. During the follow-up (1903+/-1414 days), four patients had cardiac death, 12 patients had recurrent myocardial infarction and 13 patients had admission due to unstable angina. A Cox analysis revealed that the endpoints were significantly associated with diabetes mellitus (RR=4.423), total cholesterol level (RR=1.025) and the genotype of the ACE gene (RR=4.490). The ID or DD genotype of the ACE gene was associated with higher occurrence of the endopoints. The MTFHR gene was not associated with the endopoint. The present results suggest that the presence of the deletion allele of the ACE gene may be a risk factor for secondary cardiac events after myocardial infarction.

Alleles↗

PubMed1999

Variant of the beta3-adrenergic receptor gene and coronary atherosclerosis in Japanese subjects.

In the present study, we assessed the significance of the Trp64Arg mutation in the beta3-adrenergic receptor gene in 428 Japanese subjects, including 198 subjects who underwent coronary angiography for possible ischemic heart diseases (IHD group) and 230 non-IHD subjects (control group). We conclude that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene did not appear to have any pathophysiological significance in Japanese subjects.

Arginine↗

PubMed1999

Mucosal cell proliferation activity of the gallbladder in children with anomalous arrangement of the pancreaticobiliary duct.

Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is an anatomical maljunction of the bile duct and the pancreatic duct that is frequently associated with gallbladder carcinoma. In patients with AAPBD, it has been postulated that pancreatic juice regurgitates into the biliary tree, and the mixture of refluxed pancreatic juice and stagnant bile juice acts as an irritant factor to the biliary tract epithelium, leading to chronic inflammation and metaplasia. Eventually these mucosal changes may progress to invasive carcinoma. We reviewed clinicopathologic studies on epithelial changes of the gallbladder in patients with AAPBD to clarify the implications relevant to carcinogenesis. Conventional histological studies have shown that the most characteristic change observed in the gallbladder of children with this anomaly was epithelial hyperplasia. Furthermore, the incidence of mucosal hyperplasia was significantly increased in the gallbladder of children in whom the pancreatic duct joined the common bile duct (P-C type) compared with the incidence in children in whom the common bile duct joined the pancreatic duct (C-P type). In addition, cell kinetic studies have demonstrated increased cellular proliferative activity of the gallbladder in children with AAPBD. Cell proliferative activity was significantly elevated in children with the P-C type of AAPBD compared with that in children with the C-P type of anomaly. In conclusion, AAPBD may yield increased cell proliferation in the gallbladder of patients with this anomaly in early childhood, resulting in epithelial hyperplasia. Although it remains unknown which agents are responsible for promoting the activation of cellular function, it seems that bile acids and refluxed pancreatic proteases are likely play a role in such promotion. Further investigations are needed to elucidate the mechanism of increased cellular function.

Adenocarcinoma↗

PubMed1999

Mutational analysis of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung's disease.

BACKGROUND/PURPOSE: Germline mutations of the RET proto-oncogene (RET; 10q11.2) have been reported in multiple endocrine neoplasia type 2A (MEN 2A) and Hirschsprung's disease. The authors investigated a Japanese kindred in which MEN 2A and Hirschsprung's disease frequently have been found. METHODS: The pedigree consisted of 28 members (11 boys and 17 girls) spanning 4 generations, of whom, 8 were affected with MEN 2A or Hirschsprung's disease. RESULTS: Direct sequence DNA analysis of the RET proto-oncogene showed a heterozygosity for a G to C transition at the second nucleotide of codon 620 (exon 10) in the patients, resulting in the replacement of cysteine by a serine residue in the affected Ret protein. This family added a novel RET missense mutation (C620S) predisposing to the association of MEN 2A and Hirschsprung's disease. CONCLUSION: Detection of the mutated RET gene carriers may be used for genetic counseling of potential risk for Hirschsprung's disease as well as MEN 2A in the affected families.

Codon↗

PubMed1999

Endosonographic study of anal sphincters in patients after surgery for Hirschsprung's disease.

PURPOSE: This study was performed to evaluate the relationship between endosonographic findings of anal sphincters and anorectal function in patients after surgery for Hirschsprung's disease. In addition, whether internal sphincterotomy or sphincterectomy was accomplished was examined in each procedure by anal endosonography. METHODS: Fifteen patients, aged 11 to 20 years, were examined. Nine patients underwent modified Duhamel's operation, three underwent Rehbein's operation with anorectal myectomy, and three underwent modified Martin's operation. All 15 patients were examined by anal endosonography using a sonographic scanner (Aloka SSD 2000) with a 7.5-MHz radial rotating endoprobe, clinical bowel assessment, and manometric study. RESULTS: After the modified Duhamel operation, anal endosonography showed an interruption of the external anal sphincter (EAS) in eight of the nine patients, as a high, mixed, or low echoic lesion in the hyperechoic band correlated to the EAS. The locations of the interruption were wide in patients with mild constipation. An interruption of the internal anal sphincter (IAS) was observed in all nine patients, as a hyperechoic lesion in the hypoechoic band correlated to IAS, which indicated internal sphincterotomy. After Rehbein's operation with anorectal myectomy, an interruption of EAS was observed in all three patients as a high or low echoic lesion in the hyperechoic band. An interruption of IAS was observed in all three patients. After the modified Martin's operation, an interruption of EAS was observed in two of the three patients as a high or low echoic lesion in the hyperechoic band. An interruption of IAS was observed in all three patients. CONCLUSION: Anal endosonography showed detailed distributions of EAS and IAS in patients after surgery for Hirschsprung's disease and complete internal sphincterotomy or sphincterectomy after these operations.

Adolescent↗

PubMed1999

Cellular activity in the gallbladder of children with anomalous arrangement of the pancreaticobiliary duct.

BACKGROUND/PURPOSE: Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is closely related to congenital biliary dilatation and frequently associated with biliary tract malignancy. To examine the mechanism of biliary tract carcinogenesis in patients with AAPBD, we investigated histologically the early changes in cell proliferative kinetics of the gallbladder mucosa of children with AAPBD. METHODS: Twenty-three specimens of gallbladder were obtained from 23 children with AAPBD, and six control specimens were obtained from pediatric patients. All specimens were fixed routinely and paraffin embedded and examined histologically with H&E staining and immunohistochemically with monoclonal antibody Ki-67(MIB-1), which reacts with a human nuclear antigen associated with cell proliferation. Ki-67 labeling index (Ki-67 LI) was obtained by counting the numbers of Ki-67-positive cells per 1,000 gallbladder epithelial cells. RESULTS: Significant differences in Ki-67 LI were noted between children with and without AAPBD. Furthermore, Ki-67 LI and the incidence of epithelial hyperplasia of gallbladder were significantly higher in children with AAPBD in whom the major pancreatic duct joined the common bile duct (P-C type) than in those in whom the common bile duct joined the major pancreatic duct (C-P type). CONCLUSIONS: Cellular proliferative activity was increased in children with AAPBD, especially those with the P-C-type anomaly. These results suggest that the early mucosal changes of the gallbladder occurred in early childhood of patients with AAPBD and might be associated with gallbladder cancer. Early diagnosis and early surgical division of the biliary tract and pancreatic duct is recommended for children with AAPBD.

Adolescent↗

PubMed1999

Autocrine growth loops dependent on peptidyl alpha-amidating enzyme as targets for novel tumor cell growth inhibitors.

Many small cell lung tumors are dependent in vitro and in vivo on autocrine growth loops. The prototypical small cell lung cancer autocrine growth factor, gastrin-releasing peptide (GRP), is one of many peptide hormones which require post-translational carboxy-terminal alpha-amidation for bioactivity. We have reported that neuroendocrine human lung tumor cell lines express the bifunctional enzyme PAM which catalyzes the biosynthesis of alpha-amidated peptides in a two-step process, and have recently shown that non-small cell lung cancer cell lines and tumors, generally considered to be non-endocrine in nature, also express PAM. We have also shown that two chemical classes of PAM inhibitors, substrate analogues and specific copper chelators, inhibit amidating enzyme activity in cell-free extracts. Here we demonstrate in vitro growth inhibition of lung cancer tumor cell lines by both these classes of PAM inhibitors using the MTT assay and the clonogenic assay. Growth inhibition in a small cell lung cancer cell line can be overcome by exogenous addition of synthetic alpha-amidated GRP. Similar growth-suppressive effects are seen in cell lines stably transfected with a vector expressing antisense PAM RNA. These data support the mechanism of inhibition for a new type of chemotherapeutic/intervention agent, directed at synthesis and activation of peptide growth factors, and support our postulate that alpha-amidated peptide hormones are a common component in lung tumor autocrine growth biology which can be inhibited by targeting the biochemical mechanisms necessary for growth factor synthesis.

Anti-Bacterial Agents↗

PubMed1999

Antenatal diagnosis of biliary atresia (noncorrectable cyst type): a case report.

At 32 weeks of gestation a cystic mass was identified in the hepatic hilum of a fetus by maternal sonography. Laparotomy was performed at 39 days of life after a diagnosis of correctable type of biliary atresia (Type I). A cystically dilated extrahepatic duct, in which the proximal and distal sides of the common bile duct were occluded (Type III with cyst, noncorrectable type), was identified by operative cholangiography. A standard Kasai operation was performed, and 1 year after operation the patient was doing well and was jaundice-free. From this experience in routine maternal sonography, a cystic mass in the hepatic hilum may also suggest Type III biliary atresia with a cyst.

Biliary Atresia↗

PubMed1999

Variation of the factor VII gene and ischemic heart disease in Japanese subjects.

BACKGROUND: Polymorphisms of the 5' region (5'FT), an intronic mutation (IVS7), and the 353Arg-Gln (R353Q) substitution of the factor VII gene have been reported to be associated with the plasma level of factor VII. Greater than normal levels of factor VII have also been reported to be associated with atherothrombotic events. However, the significance of factor VII gene polymorphism in the pathogenesis of ischemic heart diseases (IHD) has not been confirmed. OBJECTIVE: To determine whether these three factor VII gene polymorphisms are associated with levels of factor VII in Japanese subjects, and whether these three polymorphisms of the factor VII gene are associated with the risk of myocardial infarction. METHODS: We studied three polymorphisms of the factor VII gene, 5'FT, IVS7, and R353Q polymorphisms, for 493 Japanese subjects consisting of 285 subjects without clinical evidence of ischemic heart disease (non-IHD group) and 208 myocardial infarction patients (myocardial infarction group). We also assessed the plasma levels of factor VII antigen (FVIIag) in 103 subjects in the non-IHD group. RESULTS: Multiple regression analysis revealed that the level of FVIIag was significantly associated with age, body mass index, cholesterol level and a polymorphism of the factor VII gene (5'FT). Logistic analysis of 493 subjects revealed that cholesterol level [P = 0.0036, odds ratio 1.010, 95% confidence interval (CI) 1.003-1.017], smoking (P = 0.0001, odds ratio 5.522, (95% CI 2.684-11.364) and diabetes mellitus (P = 0.0001, odds ratio 6.450, (95% CI 2.953-14.088) were risk factors for myocardial infarction. However, the three polymorphisms of factor VII gene were not associated with risk of myocardial infarction. CONCLUSION: The polymorphisms of the factor VII gene influenced the levels of factor VII but were not significantly associated with risk of myocardial infarction in Japanese subjects.

Alleles↗