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Biomedical subjects

M Watanabe

Publications and source records attributed to M Watanabe.

At least 73 records · Page 4Linked to original sources
PubMed2005

In vivo induction of human cytochrome P450 3A4 by rifabutin in chimeric mice with humanized liver.

The induction of human cytochrome P450 enzymes (CYPs) often poses a serious problem in clinical practice. The induction of CYP3A leads to a decrease in the pharmacological potency of drugs, since many drugs are substrates of CYP3A. The present study examined the in vivo induction potency of human CYP3A in chimeric mice with humanized liver, recently established in Japan, by a specific inducer of human CYP3A enzyme activity in this experimental condition, rifabutin, which is an analogue of rifampicin. The chimeric mice were treated intraperitoneally daily for 4 days with rifabutin (50 mg kg(-1) day(-1)). The mRNA, protein and enzyme activity in liver of the chimeric mice were measured by reverse-transcriptase polymerase chain reaction, Western blot analysis and high-performance liquid chromatography, respectively. In the chimeric mice, the human CYP3A4 mRNA expression, CYP3A4 protein content, testosterone 6ss-hydroxylase activity and dexamethasone 6-hydroxylase activity were increased 7.4-, 3.0-, 2.4- and 1.9-fold, respectively, by treatment with rifabutin. The mRNA expression of other human CYPs, transporters and nuclear receptors was not significantly changed by rifabutin. On the other hand, rifabutin was demonstrated not to increase the murine Cyp3a enzyme activities in the control mice. It was demonstrated that human CYP3A4 expressed in the chimeric mice with humanized liver was induced by rifabutin, suggesting that human CYP3A4 in the chimeric mice had induction potency. This chimeric mouse model may be a useful animal model to estimate and predict the in vivo induction of CYPs in human.

Animals↗
PubMed2005

Randomized, double-blind, placebo-controlled crossover trial of famotidine in patients with functional dyspepsia.

BACKGROUND: Histamine 2-receptor antagonists were used as a first therapy against functional dyspepsia. However, few clinical studies with famotidine for functional dyspepsia have been reported. AIM: To evaluate the effectiveness of famotidine for functional dyspepsia patients. METHODS: A multicentre, randomized, double-blind, placebo-controlled crossover trail was conducted. Patients diagnosed with functional dyspepsia by the Roma II criteria were included. Subjects were randomized into two groups, and received either famotidine or placebo as the first 4 weeks medication. After a 1-week washout period, they were switched to the other regimen for another 4 weeks. Evaluation was made prior to the start of study, upon completion of the first drug cycle, and the second drug cycle, by Gastrointestinal Symptoms Rating Scale for the seriousness of abdominal symptoms, and by Short Form-36 for the level of quality of life. RESULTS: Nineteen of 21 enrolled patients successfully completed this study. Significant improvement in Gastrointestinal Symptoms Rating Scale scores was observed in abdominal pain (P = 0.007), indigestion and reflux syndrome after famotidine treatment. Also quality of life scores showed significant improvement in body pain, vitality and general health perceptions after famotidine treatment. There was no improvement of symptoms and quality of life scores after administration of placebo. CONCLUSIONS: Famotidine was effective for improving symptoms and quality of life in functional dyspepsia patients.

Adult↗
PubMed2005

Clinical investigation: increased serum stromal derived factor 1 alpha levels in pulmonary tuberculosis.

Pulmonary tuberculosis, a granulomatous disease, has few serological markers for its activity. Recently, an increased plasma level of stromal derived factor 1 alpha (SDF-1alpha), which can induce strong chemotaxis of cells through its receptor CXCR4, was detected in patients with tuberculosis. In this study we investigated serum SDF-1alpha levels and CXCR4 expression on peripheral blood mononuclear cells (PBMCs). Fifty-five active tuberculosis patients, 30 resolved tuberculosis patients, 27 acute bronchitis patients and 8 healthy volunteers were examined. Histological expression of SDF-1alpha in the tuberculosis lesion and CXCR4 expression of PBMCs were also analysed. Serum SDF-1alpha levels in active tuberculosis patients were significantly higher than other groups. The sensitivity and specificity for the diagnosis of active tuberculosis was 88.5% and 85.3% (cutoff value = 650 pg/ml), respectively. CXCR4 expression levels on PBMCs showed a significant negative correlation with serum SDF-1alpha levels. Inflammatory cells including multinuclear giant cells in the lesion expressed SDF-1alpha. Measurement of serum SDF-1alpha could be a useful screening marker for the identification of active pulmonary tuberuculosis. We propose that interaction of SDF-1alpha and CXCR4 might be involved in the pathogenesis of pulmonary tuberculosis.

Acute Disease↗
PubMed2005

Primary invasive micropapillary carcinoma of the colon.

AIMS: Invasive micropapillary carcinoma (IMPC) is associated with frequent lymph node metastasis and adverse clinical outcome. IMPC has been reported in breast, urinary bladder, ureter, lung and parotid gland but not in colon. We present the clinicopathological features of three cases of primary IMPC of the colon with a review of the literature. METHODS AND RESULTS: The patients (one man and two women) were 53, 67 and 68 years old, respectively. The size of the tumour ranged from 20 to 100 mm in diameter. Histologically, all cases were composed predominantly of papillary tumour cell clusters with spaces in a background of fine fibrocollagenous stroma. One of the tumours (case 1) was nearly completely composed of IMPC, but the other two were associated with foci of adenocarcinoma and concurrent mucinous carcinoma, respectively. MUC1 was positive in all cases, suggestive of reverse cell orientation which is responsible for its unique histological features. CONCLUSIONS: We report three cases of primary IMPC of the colon. Its clinical significance remains undetermined but the presence of this component may represent a poor prognostic factor.

Aged↗
PubMed2005

Effects of defect configuration, size, and remaining teeth on masticatory function in post-maxillectomy patients.

The aim of this study was to investigate the correlation between the masticatory function and the maxillary defect configuration, size, and remaining teeth in post-maxillectomy patients restored with an obturator prosthesis. Fifty consecutive post-maxillectomy patients (mean age 67.0) participated in this study. The subjects consisted of 26 dentate and 24 edentulous patients. Data were collected from the patients' clinical records, diagnostic casts, and a questionnaire on masticatory function to evaluate the defect configuration, size, and the masticatory function scores associated with wearing obturator prostheses. The defect size was evaluated by the ratio of defect area to the horizontal impression area. The defect configuration was assessed according to Aramany's classification and separated into unilateral and bilateral defects. The multiple regression analysis and the Mann-Whitney U-test (P<0.05) were used to assess statistical significance. The Spearman's correlation coefficient by rank test was also used to detect correlation. The following conclusions were made: (i) The presence of teeth in the maxillary dentition and the different type of the defect configuration had significant correlation with the masticatory function score (r=0.616). (ii) The masticatory function scores of the subjects differed significantly with the presence of teeth in the maxillary dentition and the different types of defect configurations (P=0.005, P=0.002, respectively). (iii) There was significant correlation between the masticatory function score and the size of the defect area in the edentulous group (r=-0.648, P=0.001). The presence of teeth, the size and configuration of the defect influenced the masticatory function of post-maxillectomy patients with obturator prostheses.

Adult↗
PubMed2005

Characteristic sequence changes of hepatitis C virus genotype 2b associated with sustained biochemical response to IFN therapy.

In hepatitis C virus (HCV) genotype 2b infection, viral eradication (sustained viral response; sVR) is obtained in about 40% by interferon monotherapy, whereas a considerable proportion of non-sVR patients exhibit sustained biochemical response (sBR) showing normal biochemical values despite persistent viraemia. However, the mechanism of sBR has not yet been established. In this study, we analysed serial changes in full-length sequences of HCV genotype 2b before and after interferon (IFN) therapy in five patients with sBR and five with no response (NR; persistent viraemia and abnormal biochemical values after IFN therapy). The overall substitution rate of amino acids in the full-length HCV genome was higher in the sBR group than in the NR group [2.22 +/- 0.48 (10(-3) changes/site/year) vs 1.04 +/- 0.30: P = 0.002]. When the genetic changes were analysed for individual HCV proteins, the sBR group had significantly higher substitution rates of amino acid in NS4A [8.82 +/- 2.80 (10(-3) changes/site/year) vs 0: P = 0.001]. These amino acid changes in sBR were mainly located in the binding motifs of HLA class I molecules including those frequently found in the Japanese population. These results demonstrated that the greater amino acid changes of HCV arising during interferon therapy are associated with the establishment of sBR. Although functional significance of these changes awaits further investigation, the finding that amino acid changes in NS4A in sBR patients are mainly located in the HLA class I binding motifs illustrated the potential roles of the escape mutations of HCV genome from CTLs in the decreasing activities of hepatitis in sBR.

Adult↗
PubMed2005

Viral load change and sequential evolution of entire hepatitis C virus genome in Irish recipients of single source-contaminated anti-D immunoglobulin*.

In hepatitis C virus (HCV) infection, serum viral load is important in the prediction of therapeutic efficacy. However, factors that affect the viral load remain poorly understood. To identify viral genomic elements responsible for the viral load, we investigated samples from a population of Irish women who were iatrogenically infected from a single HCV source by administration of HCV 1b-contaminated anti-D immune globulin between 1977 and 1978 (Kenny-Walsh, N Engl J Med 1999; 340: 1228). About 15 patients were divided into two groups, viral load increasing group (11 patients) and decreasing group (4 patients). Pairs of sera were collected from each patient at interval between 1.1 and 5.8 years. Full-length sequences of HCV genome were determined, and analyzed for changes in each patient. Sliding window analysis showed that the decreasing group had significantly higher mutation rates in a short segment of NS5B region that may affect the activity of RNA-dependent RNA polymerase. By comparing each coding regions, significantly higher mutation numbers were accumulated in NS5A region in the increasing group than the decreasing group (0.92 vs 0.16 nucleotides/site/year, P = 0.021). The mutation in certain positions of the HCV genome may be determinant factors of the viral load in a relatively homogeneous patient population.

Amino Acid Sequence↗
PubMed2005

Long-term outcome of per anum intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer.

OBJECTIVE: The authors have performed per anum intersphincteric rectal dissection. With direct coloanal anastomosis for cases of lower rectal cancer in which the distal surgical margin is difficult to secure by the double stapling technique. The aim of this study was to evaluate the long-term outcome and to clarify the surgical indications for this operation. PATIENTS AND METHODS: Between 1993 and 2002, 31 patients underwent per anum intersphincteric rectal dissection with direct coloanal anastomosis. Of these, two patients (one stage 0 and one stage IV) were excluded from the analysis of oncological outcome. The remaining 29 patients formed the basis of this study. The median follow-up was 57 months (range 6-106 months). RESULTS: Local recurrence and distant metastasis developed in 9 and 3 patients, respectively. Local recurrence rate for pT1 was significantly lower than that for pT2/T3 disease. The local recurrence rate cases with tumours less than 3 cm was significantly lower than that for tumours sized 3 cm or more. The distant metastasis rate for cases with lymph node metastasis was significantly higher than that for cases without lymph node metastasis. There was an association between distant metastasis and TNM or pT stage. The overall survival rates for stage I, II and III were 85%, 80% and 89%, respectively. No significant difference was seen in total Cleveland Clinic incontinence score between per anum intersphincteric rectal dissection with direct coloanal anastomosis and the double stapling technique. CONCLUSION: The surgical indications of this operation should be limited to patients with T1 rectal cancer or tumours less than 3 cm.

Adult↗
PubMed2005

Interspecific structural differences in nucleosome as revealed by heteroimmunization in mice with human nucleosome.

Although mounting evidence suggests the association of anti-nucleosome (NS) antibodies with lupus nephropathy in humans, the influence of interspecific differences in NS structure on the diagnosis has not been studied fully. Thus, we investigated the interspecific differences in NS structure by immunizing normal BALB/c mice with human nucleosomes (hNS). We purified hNS and mouse nucleosomes (mNS) from individual established cell lines. Purified NS was of high-pressure liquid chromatography grade and contained less than 1% dinucleosome, if any. Immune responses to NS were tested by an enzyme-linked immunosorbent assay. Of 6 mice, 2 responded to both hNS and mNS. However, antibodies produced in individual mice had higher affinity to mNS than to hNS. IgG response to hNS was IgG1 and IgG2b in subclass, whereas that to mNS was restricted to IgG1. Coincident with this response difference, agarose gel electrophoresis showed a mobility difference between hNS and mNS: the former was slower than the latter. In conclusion, immunodifferentiation in vivo in mice of autologous from heterologous NS together with their mobility difference in agarose gel suggest the presence of interspecific differences in NS. In humans, 2 out of 14 randomly tested patients with systemic lupus erythematosus preferred hNS over mNS; the IgG subclass in one was IgG1, and in the other IgG4. Taken together, interspecific differences in NS will provide a new area of study not only in biochemistry but also in immunology and/or autoimmunity.

Animals↗
PubMed2004

Dissecting aneurysm of the posterior communicating artery.

A 36-year-old male presented with an extremely rare dissecting aneurysm of the posterior communicating artery manifesting as severe occipital headache. Magnetic resonance (MR) imaging revealed a partially thrombosed aneurysm of the right posterior communicating artery and angiography showed the pearl and string sign. Three months later, repeat angiography showed that the aneurysm was completely thrombosed and the posterior communicating artery was occluded. Magnetic resonance (MR) imaging showed an intimal flap. These neuroradiological findings demonstrated that the aneurysm was a dissecting aneurysm of the right posterior communicating artery. He was discharged with no neurological deficit.

Adult↗
PubMed2004

Electrophysiology and anatomy of embryonic rabbit hearts before and after septation.

Mechanisms of cardiac pacemaking and conduction system (CPCS) development are difficult to study, in part because of the absence of models that are physiologically similar to humans in which we can label the entire CPCS. Investigations of the adult rabbit heart have provided insight into normal and abnormal cardiac conduction. The adult and the embryonic rabbit have an endogenous marker of the entire cardiac conduction system, neurofilament 160 (NF-160). Previous work suggested that ventricular septation correlates with critical phases in avian CPCS development, in contrast to the mouse CPCS. Combining high-resolution optical mapping with immunohistochemical analysis of the embryonic rabbit heart, we investigated the significance of ventricular septation in patterning the rabbit embryonic conduction system. We hypothesized that 1) completion of ventricular septation does not correlate with changes in the ventricular activation sequence in rabbit embryos and 2) CPCS anatomy determines the activation sequence of the embryonic heart. We found that preseptated (days 11-13, n = 13) and postseptated (day 15, n = 5) hearts had similar "apex-to-base" ventricular excitation. PR intervals were not significantly different in either group. CPCS anatomy revealed continuity of the NF-160-positive tract connecting the presumptive sinoatrial node, atrioventricular (AV) junction, and ventricular conduction system. The presence of collagen in the AV junction coincided with the appearance of an AV interval. We conclude that the apex-to-base ventricular activation sequence in the rabbit embryo is present before completion of ventricular septation. CPCS anatomy reflects global cardiac activation as demonstrated by high-resolution optical mapping.

Animals↗
PubMed2004

Atypical teratoid/rhabdoid tumour with leptomeningeal dissemination in an adult.

A 22-year-old man presented with a rare case of atypical teratoid/rhabdoid tumour (AT/RT). Magnetic resonance imaging showed a left cerebellar mass with leptomeningeal dissemination. Partial resection was performed. Histological examination revealed AT/RT. Postoperatively, whole neuraxis and local irradiation were performed. Three-drug chemotherapy with ifosfamide, cisplatin, and etoposide, and adjuvant intrathecal administration of methotrexate were repeated. Near complete response was achieved, and no tumour recurrence/progression has been noticed during the follow up of 24 months. Intensive radiochemotherapy can successfully control AT/RT, even with leptomeningeal dissemination.

Adult↗
PubMed2004

Identification and characterization of novel developmentally regulated neural-specific proteins, BRINP family.

Processes of neuronal differentiation involve activation of a set of neuronal specific genes and cessation of cell proliferation in postmitotic neurons. Previous studies revealed that bone morphogenetic protein (BMP) and retinoic acid (RA) play important roles in the differentiation of peripheral sympathetic neurons such as the synergistic induction of responsiveness to specific neurotrophic factors. In the present study, while trying to clarify the mechanism of the BMP/RA-actions, we identified a novel neural-specific protein, BMP/RA-inducible neural-specific protein-1 (BRINP1) which shows no similarity to other known proteins. Subsequently, two homologous proteins, BRINP2 and BRINP3, making up the BRINP family, are identified. Individual BRINP genes have distinct regulatory mechanisms of expression within the nervous system. In rodent brain, BRINP1 is expressed from earlier developmental stage, i.e. E9.5, and widely expressed in various neuronal layers and nuclei of the adult animal, while BRINP2 and BRINP3 were detectable from E11.5 and expressed in rather limited regions in a complementary manner. During the course of perinatal development of sympathetic neurons, BRINP1 is induced from earlier embryonic stage and further increased toward adult stage, while BRINP3 expressed from earlier stage is replaced by BRINP2 expression which increases postnatally in accordance with the action of BMP2 and RA. Furthermore, when expressed in nonneuronal cells, all three BRINP family proteins suppressed the cell cycle progression. Possible physiological functions of BRINP family members in the development of the nervous system are discussed.

Amino Acid Sequence↗
PubMed2004

Differential gene-expression profiles associated with gastric adenoma.

Gastric adenomas may eventually progress to adenocarcinomas at varying rates. The purpose of the present study was to identify gene-expression profiles linked to the heterogeneous nature of gastric adenoma as compared to adenocarcinoma. Suppression subtractive hybridisation analysis was performed to extract relevant genes from two cases of low- and high-grade gastric adenomas. The identified genes were quantified by RT-PCR in 14 low-grade adenoma, nine high-grade adenoma and nine adenocarcinoma samples, followed by hierarchical clustering analysis to separate tumours into groups according to their gene-expression profiles. Nine genes previously implicated in carcinogenesis in a variety of organs, including three genes related to gastric adenocarcinoma, were identified. The overexpression of these genes in gastric adenoma has not been reported previously. The clustering analysis of these nine genes across 32 cases identified three groups, one of which consisted primarily of adenocarcinomas, whereas the other two groups consisted of adenomas. One group of adenomas, characterised by larger tumour size, exhibited gene-expression profiles of an intestinal cell lineage implicated in the pathogenesis of an intestinal-type gastric adenocarcinoma. Another adenoma group consisting of low-grade adenomas with smaller tumour size exhibited a unique expression profile. In conclusion, clustering analysis of expression profiles using a limited number of genes may serve as molecular markers for gastric adenoma with different biological properties. Although the prognostic values of these gene-expression profiles need to be evaluated in further follow-up study of adenoma cases, these findings add new insights to (a) our understanding of the pathogenesis of gastric tumours, (b) the development of specific tumour markers for clinical practice, and (c) the design of novel therapeutic targets.

Adenocarcinoma↗
PubMed2004

Dioxins and related compounds in human breast milk collected around open dumping sites in Asian developing countries: bovine milk as a potential source.

In this study, concentrations of dioxins and related compounds (DRCs)--such as polychlorinated dibenzo- p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls--were found in human breast milk from women living near dumping sites of municipal waste and reference sites in India, Cambodia, Vietnam, and the Philippines during 1999 to 2000. DRCs were detected in all human breast milk samples analyzed, demonstrating that residents in these Asian developing countries have been exposed to these contaminants. In India, the concentrations of DRCs in human breast milk from women living near the investigated dumping site were notably higher than those from women living near reference sites and from women in other Asian developing countries. Toxic equivalent quantity (TEQ) levels of DRCs were comparable with or higher than those reported in the general populations of developed countries since 1990. In contrast, levels of these contaminants in human breast milk in women from Cambodia and Vietnam were not significantly different between milk from women living near the dumping and reference sites. These results indicate that significant pollution sources for DRCs are present in Indian dumping sites and that residents there have been exposed to relatively higher levels of these contaminants. TEQ levels in human breast milk from the dumping site in India tended to decrease with an increase in the number of previous deliveries by mothers, whereas no significant relationship was observed in Cambodia, Vietnam, or the Philippines. This suggests that mothers who have been exposed to relatively high levels of DRCs transfer greater amounts of these contaminants to the first infant than later ones through breast-feeding, which in turn implies that the first children of these mothers might be at higher risk from DRCs. When the residue levels of DRCs in bovine milk collected from the Indian dumping site and reference sites were examined, TEQ levels in bovine milk from the dumping site were higher than those from reference sites. This result suggests that bovine milk is a potential source of DRCs for residents living near the dumping site in India. To our knowledge, this is the first comprehensive study on exposure to DRCs of residents living in proximity to open dumping sites of municipal waste in Asian developing countries.

Adolescent↗
PubMed2004

Magnetic resonance and biochemical studies during pentylenetetrazole-kindling development: the relationship between nitric oxide, neuronal nitric oxide synthase and seizures.

The major aim of this study was to elucidate the role of nitric oxide (NO) in the development of pentylenetetrazole (PTZ)-kindling as an animal model of primary generalized epilepsy. The daily administration of PTZ is associated with an increase in the amount of neuronal nitric oxide synthase (nNOS). NO generation was measured directly by in vivo and ex vivo electron paramagnetic resonance on rodents undergoing progressive convulsions. We found that primary generalized epilepsy is caused by NO induction during the persistent up-regulation of nNOS expression, but that NO induction is not associated with severe generalized seizures following long-term kindling phenomena after PTZ withdrawal. Morphological changes in the brain structure of rats were measured by magnetic resonance imaging during epileptic convulsions induced by repetitive administration of PTZ. Cerebellum volume for kindled rats decreased 20% but not in rats treated with the nNOS inhibitor, 3Br-7NI, suggesting that generation of NO in the cerebellum is related to decrease in cerebellum volume following PTZ-kindling.

Analysis of Variance↗
PubMed2004

Analysis of retrograde ejaculation using color Doppler ultrasonography before and after transurethral collagen injection.

Transurethral bladder neck collagen injection therapy was performed in a patient with retrograde ejaculation. The phenomenon of retrograde ejaculation and its correction after the therapy were clearly demonstrated by color Doppler ultrasonography. To our knowledge this is the first report showing successful observation of retrograde ejaculation using color Doppler ultrasonography.

Adult↗