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Biomedical subjects

T Tsukamoto

Publications and source records attributed to T Tsukamoto.

At least 199 records · Page 11Linked to original sources
PubMed1998

5-HT2A receptor gene promoter polymorphism--1438G/A and mood disorders.

A 5-HT2A receptor promoter polymorphism, -1438G/A, was reported to be significantly increased in patients with anorexia nervosa when compared with controls. In practice, many patients with anorexia nervosa suffer from mood disorders. Furthermore, 5-HT2A receptors are thought to play a role in the etiologies of mood disorders. Thus, we studied the polymorphism in 95 Japanese patients with mood disorders and 106 healthy Japanese controls. The allele frequency for the -1438G/A polymorphism did not differ between the patients and controls. In addition, the genotype frequencies did not differ according to the subdiagnosis, age of onset, family history of psychiatric illness or suicide attempts.

Adult↗
PubMed1998

Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy (NALD), are autosomal recessive diseases caused by defects in peroxisome assembly, for which at least 10 complementation groups have been reported. We have isolated a human PEX1 cDNA (HsPEX1) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO) cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged "enhanced" green fluorescent protein. This cDNA encodes a hydrophilic protein (Pex1p) comprising 1,283 amino acids, with high homology to the AAA-type ATPase family. A stable transformant of ZP107 with HsPEX1 was morphologically and biochemically restored for peroxisome biogenesis. HsPEX1 expression restored peroxisomal protein import in fibroblasts from three patients with ZS and NALD of complementation group I (CG-I), which is the highest-incidence PBD. A CG-I ZS patient (PBDE-04) possessed compound heterozygous, inactivating mutations: a missense point mutation resulting in Leu-664 --> Pro and a deletion of the sequence from Gly-634 to His-690 presumably caused by missplicing (splice site mutation). Both PBDE-04 PEX1 cDNAs were defective in peroxisome-restoring activity when expressed in the patient fibroblasts as well as in ZP107 cells. These results demonstrate that PEX1 is the causative gene for CG-I peroxisomal disorders.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1998

Peroxisome biogenesis disorders: identification of a new complementation group distinct from peroxisome-deficient CHO mutants and not complemented by human PEX 13.

Ten complementation groups of generalized peroxisome biogenesis disorders (PBD), (excluding rhizomelic chondrodysplasia punctata) have been identified using complementation analysis. Four of the genes involved have been identified using two different methods of (1) genetic functional complementation of peroxisome deficient CHO cell mutants and (2) homology searches for human dbEST, based on yeast genes involved in peroxisome biogenesis (PEX genes). We report here the first identification of a new complementation group which is genetically different from peroxisome deficient CHO mutants. There were no complementations by the human PEX 13 gene. The nature of the related gene is being investigated.

Animals↗
PubMed1998

Cloning and characterization of two human cDNAs encoding the mRNA capping enzyme.

Previous studies demonstrated that the mammalian mRNA capping enzyme is a bifunctional enzyme containing RNA 5'-triphosphatase and mRNA guanylyl-transferase activities in a single polypeptide. In yeast, both the above activities are separated into two different subunits, alpha and beta, the genes for which we have cloned recently. It is thus interesting to compare the structural and functional relationships between the mammalian and yeast capping enzymes. Here we isolated two human cDNAs encoding mRNA capping enzymes termed hCAP1a and hCAP1b which encode 597 and 541 amino acids, respectively. They are different only at the region coding for the C-terminal portion of the enzyme. Comparison of the deduced amino acid sequences with other cellular and viral capping enzymes showed that all the regions conserved among mRNA guanylyltransferases are observed in our clones except one conserved C-terminal region which was absent in the hCAP1b protein. The purified recombinant hCAP1a gene product, hCAP1a, exhibited both RNA 5'-triphosphatase and mRNA guanylyltransferase activities. Deletion mutant analysis of hCAP1a showed that the N-terminal 213 amino acid fragment containing a tyrosine specific protein phosphatase motif catalyzed the RNA 5'-triphosphatase activity and the C-terminal 369 amino acid fragment exhibited the mRNA guanylyltransferase activity. On the other hand, hCAP1b showed RNA 5'-triphosphatase activity, but neither enzyme-GMP covalent complex formation nor cap structure formation was detected.

Amino Acid Sequence↗
PubMed1998

Size Dependence of Polymer Composition in the Surface Layer of Poly(acrylamide-co-acrylic acid) Hydrogel Microspheres

Poly(acrylamide-co-acrylic acid) hydrogel microspheres of four different average sizes were prepared using a membrane emulsification technique. These four kinds of microspheres had average diameters of 1.35, 2.33, 3.09, and 7.43 &mgr;m in distilled water and were all fairly monodisperse. Their surface properties were studied by measuring the electrophoretic mobility of the microspheres. The mobility values were negative at pH 7.4 with the ionic strengths between 0.005 and 0.154 at 25°C. More negative mobility values were obtained with smaller microspheres than the larger ones. By analyzing the data with an electrokinetic theory for "soft" surfaces, it was found that smaller microspheres have higher surface charge density than the larger ones, although all kinds of microspheres were prepared from monomer solutions with the same monomer composition. The observed size dependence of the electrophoretic mobility suggests that copolymerization of acrylamide monomers and acrylic acid monomers does not proceed homogeneously within a microsphere. That is, charged acrylic acid monomers have a tendency to be localized in the microsphere core region, whereby the surface region of microspheres becomes poor in charges, reducing the mobility of larger microspheres. This is not the case for smaller microspheres, so that their mobility becomes more negative. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗
PubMed1998

Clinicopathologic and genetic features of nonfamilial colorectal carcinomas with DNA replication errors.

BACKGROUND: DNA replication errors (RERs) are closely associated with hereditary nonpolyposis colorectal carcinoma (HNPCC). Recently, alterations in DNA mismatch repair genes, including hMSH2, hMLH1, and hPMS2, have been implicated in the pathogenesis of HNPCC: Several studies have demonstrated RER in 13-17% of nonfamilial colorectal carcinomas. It is unclear, however, as to whether or not these RER positive nonfamilial colorectal carcinomas are incomplete forms of HNPCC or are caused by incidental alterations of DNA mismatch repair genes. Consequently, the authors studied the characteristics of RER positive nonfamilial colorectal carcinomas, placing particular emphasis on hMSH2 and hMLH1 gene mutations. METHODS: Fresh or frozen samples of 103 nonfamilial colorectal carcinomas were examined for RERs using the polymerase chain reaction (PCR) and specific microsatellite primers. The authors also identified mutations of the hMSH2 and hMLH1 genes in RER positive samples by a PCR single strand conformational polymorphism analysis followed by direct nucleotide sequencing. RESULTS: The incidence of RER was 15.7% (17/103) in nonfamilial colorectal carcinomas, and only 1 case, which was found in the ascending colon, showed a somatic mutation at exon 12 in the hMSH2 gene. Neither germline nor somatic mutations of the hMSH2 or hMLH1 genes could be found in any of the remaining RER positive tumors. RER positive nonfamilial carcinomas tended to be located more frequently in the right colon. There was no increased prevalence in young patients, and the clinicopathologic characteristics of HNPCC were absent in the patients with RER positive nonfamilial colorectal carcinoma. CONCLUSIONS: Based on these findings, the carcinogenesis of RER positive nonfamilial colorectal carcinoma is considered different from that of HNPCC:

Adaptor Proteins, Signal Transducing↗
PubMed1998

A new prognostic factor for colorectal carcinoma, thymidylate synthase, and its therapeutic significance.

BACKGROUND: Expression of thymidylate synthase (TS) has been studied as a mechanism of drug resistance and a prognostic factor for various cancers. METHODS: The relation between TS expression in surgically resected specimens and patient survival was examined in 86 patients with colorectal carcinoma (58 of whom received adjuvant chemotherapy and 28 who did not) who had been followed for 10 years. Immunohistochemical demonstration of the protein was achieved using an anti-TS polyclonal antibody. RESULTS: In the 58 patients who received chemotherapy, the overall 10-year survival rate was 77.8% for patients with TS positive tumors and 89.4% for patients with TS negative tumors (difference not significant). However, in the 28 patients who did not receive chemotherapy, these figures were only 42.9% and 85.7%, respectively (P < 0.05). Multivariate analysis also revealed TS expression to be a significant variable for predicting postoperative survival (P < 0.05). CONCLUSIONS: TS expression can be used as an independent prognostic factor for patients with colorectal carcinoma. Patients with TS positive tumors have a poorer prognosis than those with TS negative lesions and therefore should receive special consideration with regard to chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1998

Magnetic resonance imaging of the male pelvic floor: the anatomical configuration and dynamic movement in healthy men.

The male pelvic organs and the rhabdosphincter were visualized using magnetic resonance imaging (MRI) in five young male volunteers (mean age, 25.6 years). The prostate was crescent-shaped in three subjects and doughnut-shaped in two subjects. The external urethral sphincter (EUS) was located anterior to and lateral to the urethra but was rare on the rectal side. The membranous urethral length measured 28-35 mm (average, 31.0 mm). The pubourethral portion of the levator ani embraced the urinary bladder, the prostate, and the membranous urethra, and the most distal portion of the levator was thickened. During anal contraction, the EUS became thinner on both coronal and sagittal images and the levator was approximated closer to the urethra. Consequently, the prostate and the bladder base were elevated and the membranous urethra was elongated by 0-12mm (average, 5.6 mm). On sagittal images, the prostate, the membranous urethra, and the rectum were pulled closer to the pubic bone by anal contraction and the retropubic area became narrower. This study clearly demonstrated that MRI was useful in examining the anatomical configuration of the male pelvic floor and its dynamic movement during anal contraction.

Adult↗
PubMed1998

Significance of microsatellite instability in different types of early-stage nonfamilial colorectal carcinomas.

PURPOSE: The aim of this study was to investigate the genetic alterations of early-stage nonfamilial colorectal carcinomas regarding microsatellite instability, with special reference to the shape of the tumors and the site of the lesions. METHODS: Formalin-fixed, paraffin-embedded specimens of 44 early-stage nonfamilial colorectal carcinomas were examined for microsatellite instability with use of polymerase chain reaction. RESULTS: The 44 carcinomas consisted of 16 flat carcinomas and 28 polypoid carcinomas. Nineteen carcinomas were located in the proximal colon (9 flat type and 10 polypoid type), whereas 25 were in the distal colon and rectum (7 flat type and 18 polypoid type). Ten (22.7 percent) of the 44 carcinomas had at least one positive locus, whereas five (11.4 percent) of them had two or more positive loci. In the proximal colon the percentage of flat carcinomas with at least one positive locus was significantly greater than that of the polypoid carcinomas (4/9 (44 percent) vs. 0/10; P = 0.04). Six patients had synchronous or metachronous colorectal carcinomas or both. They harbored microsatellite instability more frequently than patients with single colorectal carcinomas, and the differences were statistically significant (P < 0.02). CONCLUSIONS: These data suggest that in nonfamilial carcinomas in the proximal colon, the genetic pathway in flat carcinomas may be different from that in polypoid carcinomas.

Adult↗
PubMed1998

Expression of sucrase and intestinal-type alkaline phosphatase in colorectal carcinomas in rats treated with methylazoxymethanol acetate.

In this study the small-intestine phenotype in rat colonic tumors was investigated in terms of sucrase and intestinal-type alkaline phosphatase (I-ALP) activity. F344 rats were given intraperitoneal injections of methylazoxymethanol acetate at a dose level of 25 mg/kg body weight once a week for 8 weeks and were killed 40 weeks after the first injection. Sucrase and I-ALP activities in proximal and distal colon adenocarcinomas were significantly higher than those in the normal colon epithelium. In the jejunum, by contrast, normal tissue had significantly higher levels than tumors. Immunohistochemical staining of I-ALP was also strong in striated cell borders of colon adenocarcinoma cells. These data suggest that, whereas absorptive cells of the small intestine lose their own traits with tumor development, colonocytes acquire phenotypic features of the small intestine. Intestinal enzymes associated with the striated-cell border, such as sucrase and I-ALP, may be useful markers for malignant phenotypic expression in colonocytes.

Adenocarcinoma↗
PubMed1998

Changes and results of surgical strategies for hepatocellular carcinoma: results of a 15-year study on 452 consecutive patients.

In an attempt to define better surgical strategies for patients with hepatocellular carcinoma (HCC), we conducted a retrospective analysis of 452 patients who underwent hepatic resection at our institute during a period of 15 years. The patients were divided into two groups: group A, comprising 188 patients who underwent hepatic resection before 1988, and group B, comprising 264 patients after 1989. These groups were compared clinicopathologically. The percentage of patients with Child's A disease but without cirrhosis, in group A was lower. The diameter of the resected tumor was larger in group A, and major hepatic resections and curative operations were more frequently performed in group A. In group B, there was less blood loss, the specimen weighed less, and the hospital mortality was lower. Although the tumor-free survival rates were similar between the two groups, the survival rate in group B was significantly better. While even minor hepatic resection accompanied by a lower rate of surgical margin-free surgery has contributed to making hepatic resection safer, it has not improved the tumor-free survival rate. Conversely, recent advances in imaging modalities used during follow-up for the early detection of recurrence and for planning multimodality treatment have contributed to increasing the survival rate.

Carcinoma, Hepatocellular↗
PubMed1998

The correction of type 2 stress incontinence with a polytetrafluoroethylene patch sling: 5-year mean followup.

PURPOSE: The durability of pubovaginal sling procedure for type 2 stress urinary incontinence was evaluated by a questionnaire survey. MATERIALS AND METHODS: From 1989 to 1996, 48 patients with type 2 stress urinary incontinence were treated with a polytetrafluoroethylene patch sling. Tightness of the sling was adjusted by setting the posterior urethrovesical angle at about 90 degrees under ultrasound monitoring. Study inclusion criteria were no urine leakage for at least 24 months confirmed by questionnaire and no recurrent urinary incontinence during followup. RESULTS: We received answers from 39 patients (81.3%), of whom 1 was excluded from study due to less than 24-month followup (18 months) without urine leakage. Of the 38 patients 32 (84.2%) reported no leakage of urine, 4 (10.5%) were subjectively improved, 2 (5.3%) were the same and none was worse, for an overall cure or improved rate of 94.7%. Followup of the 32 patients maintaining urinary continence averaged 65.9 +/- 29.4 months. Of the patients 6 (15.8%) had slight pelvic pain, 4 (10.5%) always and 10 (26.3%) sometimes had to strain to void, and 14 (36.8%) complained pollakisuria. Urge incontinence coexisted in 5 of 6 patients reporting improved or the same status. Of all patients 31 (81.6%) were satisfied with the decision to undergo the operation. CONCLUSIONS: Durability and safety of our procedure for stress urinary incontinence were confirmed by the survey questionnaire. Most of the patients complained of no or little difficulty voiding.

Adult↗
PubMed1998

Health-related quality of life associated with lower urinary tract symptoms in four countries.

OBJECTIVES: To describe health-related quality of life (HRQL) associated with lower urinary tract symptoms (LUTS) assessed by validated questionnaires in four countries. METHODS: More than 6000 men, recruited by using community- or population-based sampling in four countries, completed questionnaires soliciting information about urinary symptom frequency, bother, degree of interference with daily activities, and other measures of HRQL. RESULTS: In all countries, disease-specific HRQL worsened with increasing age. Adjusting for age, most disease-specific HRQL measures were significantly worse with increasing symptom severity. The correlation between symptoms and HRQL was strongest in countries with higher prevalence of symptoms, such as Japan or the United States, and less pronounced in countries with lower prevalence (France, Scotland), possibly reflecting the lower variability in scores. CONCLUSIONS: HRQL measures are worse in older men, and increased urinary symptom severity is associated with worse disease-specific HRQL in all countries, despite potential cross-cultural differences in disease prevalence, medication use, perceptions, or willingness to report symptoms or worse HRQL. This cross-cultural consistency suggests that an assessment of symptom bother or interference with daily activities may be useful in patient evaluation.

Adult↗
PubMed1998

Detection of adrenal and retroperitoneal masses in a general health examination system.

OBJECTIVES: To investigate the detection rate of adrenal and retroperitoneal masses other than kidney diseases in a general health examination system. METHODS: From May 1991 through February 1996, 41,357 subjects participated in the general health examination system in our hospital. Approximately 80% of participants were 40 to 59 years old. For all participants, transabdominal ultrasound (US) was performed by five expert examiners using an Aloka SSD-650 with a 3.5-MHz convex-type transducer. When US revealed abnormal lesions on the adrenal gland and in the retroperitoneal space, we recommended that participants be examined with computed tomography (CT), with a slice width of 5 mm. RESULTS: Forty-three participants (0.1%) had abnormal findings on US. Of the 28 of those who underwent CT examination to confirm the lesions, 12 had adrenal and retroperitoneal masses. The detection rate was 0.029% of total participants and 42.9% of those who underwent CT examination. Clinical diagnoses were primary aldosteronism (1), preclinical Cushing syndrome (2), nonfunctioning adrenocortical tumor (5), pheochromocytoma (1), ganglioneuroma (1), adrenal cyst (1), and retroperitoneal neurinoma (1). False-positive results were dominant on the left side of the body (right 3, left 13). A deformed or accessory spleen (3), a cyst on the upper pole of the kidney (2), bowel air (2), and a pancreatic cyst (1) were misdiagnosed as adrenal lesions on US. CONCLUSIONS: The low detection rate of adrenal and retroperitoneal masses by US does not support screening for the diseases in healthy subjects. However, if it is done as part of a general health examination, examiners should attentively observe not only the kidneys but also the adrenal gland and retroperitoneal space because clinically important diseases may be detected.

Adrenal Gland Neoplasms↗
PubMed1998

Evaluation of the alleviative action of neurotropin for penile pain associated with intracavernous injection of prostaglandin E1 assessed using the visual analogue scale.

We examined whether penile pain associated with intracavernous injection of PGE1 could be alleviated with a intracavernous injection of neurotropin, a non-protein, bioactive agent extracted from skin tissue with inflammation elicited by the Vaccinia virus. Twenty-three patients with erectile dysfunction were enrolled in this study. They were divided into two groups. The first group was allocated 20 micrograms of PGE1 alone first, followed by PGE1 plus 1.5 ml of neurotropin after two weeks. The second group was allocated PGE1 plus 1.5 ml of neurotropin first, followed by PGE1 alone after two weeks. Pain was evaluated by the visual analogue scale (VAS). In the 17 patients reporting discomfort, pain scores for PGE1 injection with neurotropin were significantly lower than those without neurotropin. No patients showed local or systemic complications that might be related to neurotropin. From these data we conclude that neurotropin may be an effective and safe drug for penile pain associated with PGE1 intracavernous injection.

Adult↗