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Biomedical subjects

M Mori

Publications and source records attributed to M Mori.

At least 361 records · Page 20Linked to original sources
PubMed2000

Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis.

Cholestasis is frequently associated with inflammatory bowel disease. Because some cholestasis is resulted from altered hepatocyte tight junctions (TJs) or the canalicular multispecific organic anion transporter, we have investigated the following topics in a rat model of inflammatory bowel disease: (1) alterations in hepatocyte TJs and in the canalicular multispecific organic anion transporter, (2) etiologic factors for cholestasis, and (3) effects of antibiotics on cholestasis. Rats with trinitrobenzene sulfonic acid-induced colitis were studied 24 hours after treatment. Hepatocyte TJs and the canalicular multispecific organic anion transporter were evaluated by immunostaining for TJ-associated proteins, 7H6 and ZO-1, and multidrug resistance protein 2 (mrp2). To investigate etiologic factors causing cholestasis, portal endotoxin and proinflammatory cytokines were examined. The effects of polymyxin B, penicillin G, or metronidazole on immunostaining for 7H6, ZO-1, mrp2, and cholestasis were investigated. (1) Immunostaining for 7H6 and ZO-1 colocalized outlining the bile canaliculi and immunostaining for mrp2 localized on the canalicular membrane in controls. Treatment with trinitrobenzene sulfonic acid induced significant cholestasis and caused translocation of immunostaining for 7H6, but not that for ZO-1, to the cytoplasm and diminished immunostaining for mrp2 on the canaliculus membrane. (2) The levels of portal endotoxin, but not proinflammatory cytokines, was increased. (3) Polymyxin B, but not the other antibiotics, prevented alterations in immunostaining for both 7H6 and mrp2, and cholestasis. We described that both hepatocyte TJs and the canalicular multispecific organic anion transporter were altered and that gut-derived endotoxin levels in the portal blood were increased in this rat colitis model.

Animals↗
PubMed2000

Evidence of oxidative stress in asthma and COPD: potential inhibitory effect of theophylline.

To evaluate the potential inhibitory effect of theophylline on the pulmonary oxidative stress in asthma and chronic obstructive pulmonary disease (COPD), we concomitantly measured the blood levels of theophylline, a non-selective phosphodiesterase (PDE) inhibitor and lipid peroxides as an index of oxidative stress. The plasma levels of lipid peroxides were significantly elevated in patients with asthma (3.48 +/- 0.11 nmol ml(-1); mean +/- SEM; n=21, P<0.01), non- or ex-smoking patients with COPD (3.55 +/- 0.11 nmol ml(-1); n = 20, P<0.01), and current-smoking patients with COPD (3.53 +/- 0.15 nmol ml(-1); n = 15, P<0.01), respectively, as compared to those of non-smoking controls (3.02 +/- 0.08 nmol ml(-1); n = 19). There was a significant negative correlation between the plasma level of lipid peroxides and the forced expiratory volume in 1 sec (FEV1)% of forced vital capacity in these subjects (r = -0.304; n = 75, P < 0.01). In asthmatics, there was a significant negative correlation between the plasma level of lipid peroxides and the serum level of theophylline (r = -0.495; n = 18, P<0.05). These results suggest that there may be increased oxidative stress in patients with asthma and COPD, and indicate that oxidative stress could possibly attribute to the pathophysiology of asthma and COPD in leading to airflow obstruction and that theophylline could potentially inhibit oxidative stress in the process of bronchopulmonary inflammation in asthmatics.

Aged↗
PubMed2000

A dominant negative mutation of transforming growth factor-beta receptor type II gene in microsatellite stable oesophageal carcinoma.

Recent investigations revealed microsatellite instability in colon cancers are associated with mutations of the transforming growth factor-beta receptor type II gene (TGF-beta RII) that encodes a transmembrane protein containing an intracellular serine/threonine kinase domain. Activation of TGF-beta receptor type I (RI) and RII by TGF-beta induces nuclear translocation of Smad proteins including Smad2 and Smad4 that have been originally identified as tumour suppressor genes. We have previously reported six cases with microsatellite instability in 32 oesophageal carcinomas. In this study, we analysed genetic mutations of TGF-beta RII, Smad2 and Smad4 in these oesophageal carcinoma tissues and established 16 cell lines. No genetic mutation was detected in any tissues or cell lines except one tissue sample of microsatellite stable oesophageal carcinoma, that is, a mis-sense mutation of glutamic acid to glutamine at codon 526 (E526Q) in the TGF-beta RII serine/threonine kinase domain. Interestingly, the mutant TGF-beta RII E526Q can completely inhibit TGF-beta-induction of nuclear translocation of Smad4 protein in oesophageal carcinoma cells. This mutation of TGF-beta RII that is not associated with microsatellite instability might make a dominant negative effect on TGF-beta signal transduction in oesophageal carcinoma.

Amino Acid Sequence↗
PubMed2000

Effect of Helicobacter pylori eradication on malignant transformation of gastric adenoma.

BACKGROUND: A nonrandomized trial of Helicobacter pylori eradication was conducted in patients with endoscopically diagnosed gastric adenoma to determine the long-term effect of antimicrobial treatment on progression of the adenoma. METHODS: Of 64 patients with an endoscopically diagnosed gastric adenoma and H pylori infection, 32 were treated with omeprazole and antibiotics to eradicate the infection, and 32 were not. RESULTS: During 2 years of follow-up, 4 (12.5%) of the 32 patients in the untreated group developed an early stage, intestinal-type gastric cancer, whereas no gastric cancer was found in the 32 patients in the treated group. CONCLUSION: H Pylori eradication may inhibit progression of gastric adenoma to carcinoma.

Adenoma↗
PubMed2000

Significance of small distal adenoma for detection of proximal neoplasms in the colorectum.

BACKGROUND: The significance of the small distal tubular adenoma detected by sigmoidoscopy as a predictor of proximal neoplasm remains controversial. The aim of this study was to examine the prevalence of proximal neoplasms in patients with and without distal neoplasms. METHODS: This is a retrospective study of 3131 asymptomatic middle-aged men who underwent total colonoscopy. For 812 men with colorectal neoplasms characteristics of the identified neoplasms were determined. RESULTS: The prevalence of proximal neoplasms in patients with small distal tubular adenoma was 20% (92 of 461), whereas the prevalence of proximal neoplasms in patients without distal neoplasms was 11.5% (301 of 2620). The prevalence of advanced proximal neoplasms in patients with small distal tubular adenoma and without distal neoplasm was 1.3% and 0.8%, respectively. In the 29 patients with advanced proximal neoplasms, only 6 (21%) had a small distal tubular adenoma. CONCLUSIONS: The presence of small distal tubular adenomas may provide a clue to the presence of small proximal tubular adenomas. However, the majority of advanced proximal neoplasms (79%) do not have a synchronous small distal tubular adenoma. (Gastrointest Endosc 2000;52:358-61).

Adenoma↗
PubMed2000

Predictors of coronary artery lesions after intravenous gamma-globulin treatment in Kawasaki disease.

OBJECTIVE: We evaluated the efficacy of intravenous gamma-globulin (IVGG) administration for children with Kawasaki disease to establish whether additional, more advanced therapy is needed in intractable cases. STUDY DESIGN: A total of 193 children with Kawasaki disease were studied retrospectively. Patients were admitted 3 to 7 days after the onset of the disease, and IVGG was administered. Laboratory measurements including white blood cell (WBC), neutrophil, and platelet counts and C-reactive protein (CRP) and albumin concentrations were determined before and 2 to 3 days after IVGG treatment. The progression of coronary artery lesions (CALs) was monitored by serial echocardiography until 30 days after treatment. RESULTS: Of 193 children, 24 (12.2 %) had CALs including transient dilatation. In contrast to the other measurements, the WBC count increased in 21 of 24 (87.5%) children with CALs after IVGG therapy. The patients with increased neutrophil count and CRP concentration after IVGG therapy also had CAL formation at a high rate (78.3% and 66.7%, respectively). Among children with normal coronary arteries, elevations of the WBC and neutrophil counts and CRP concentration were observed after IVGG therapy in only 3, 6, and 8 patients, respectively (specificity: 98.2%, 97.0%, and 95.3%, respectively). Furthermore, multiple logistic regression indicated that these variables were useful predictors of CALs in KD. CONCLUSION: Though the introduction of IVGG therapy has improved the prognosis of Kawasaki disease, approximately 10% of patients still develop CALs. The need for more aggressive therapy in IVGG-resistant cases can be recognized early by increases in the WBC and neutrophil counts and serum CRP concentration after IVGG administration.

Biomarkers↗
PubMed2000

The twilight of "medicine" and the dawn of "health care": reflections on bioethics at the turn of the millennium.

The traditional paradigm of medicine assumes that health is a natural given depending on a body's intrinsic teleology, and that medicine aims at restoring or preserving health, making a physician only an "assistant to nature." I argue that nowadays this paradigm is becoming obsolete, because the concept of health is no longer a "natural given" and interventions on the human body attempt not only to help nature's teleology, but also to change it whenever doing so can satisfy human needs and wants. We should abandon the term "medicine" and adopt the term "health care" to mark such an epoch-making transition, analogous to that marking the passage from "alchemy" to "chemistry."

Bioethics↗
PubMed2000

Early normal menstrual cycle pattern and the development of uterine leiomyomas.

It is unclear if women who develop uterine leiomyomas have had menstrual regularity or irregularity in their reproductive life. This case-control study examines the recalled menstrual cycle patterns throughout the reproductive life among women requiring hysterectomy for myomas. One hundred twenty-two women with myomas and 244 age-matched healthy controls without myomas were enrolled in Japan. The incidence of normal menstrual cycle pattern in their teens among patients with myoma was significantly higher than that among healthy controls (p < 0.01). The subset results for parous women were the same as those for all subjects. The size of the uterus in myoma patients with teenage menstrual regularity was not larger than in those with teenage menstrual irregularity. Women who developed myomas later in life tended to have early normal menstrual cycle pattern. Early menstrual regularity may enhance leiomyoma growth in early reproductive life.

Adult↗
PubMed2000

Haemophilus influenzae infection and Guillain-Barré syndrome.

It has been reported recently that Haemophilus influenzae can elicit an axonal form of Guillain-Barré syndrome. To investigate the incidence and features of H. influenzae-related Guillain-Barré syndrome, anti-H. influenzae antibody titres were measured by enzyme-linked immunosorbent assay (ELISA) in 46 consecutive Japanese patients with Guillain-Barré syndrome, 49 normal controls, 24 patients with multiple sclerosis and 27 patients with amyotrophic lateral sclerosis (ALS). Whole bacteria of non-encapsulated (non-typable) H. influenzae isolated from one of the Guillain-Barré syndrome patients was the antigen used. Elevated anti-H. influenzae antibodies for two or three classes of IgG, IgM and IgA were found in six (13%) Guillain-Barré syndrome patients, but not in the normal controls and patients with multiple sclerosis or ALS. The incidence was significantly higher in patients with Guillain-Barré syndrome than in the normal controls (P = 0.01) and patients with multiple sclerosis or ALS (P = 0.009). Western blot analysis confirmed that the H. influenzae-positive patients' IgG recognized the lipopolysaccharides of H. influenzae. Guillain-Barré syndrome patients with anti-H. influenzae antibodies showed relatively uniform clinical and laboratory features: prodromal respiratory infection, less frequent cranial and sensory nerve involvement, pure motor axonal degeneration on electrophysiology, and positivity for IgG anti-GM1 antibodies. Although the features were similar to those in Guillain-Barré syndrome patients infected by Campylobacter jejuni, the recoveries seemed to be better in patients with H. influenzae-related Guillain-Barré syndrome. It is concluded that a form of Guillain-Barré syndrome occurs after respiratory infection by H. influenzae in the Japanese population. A particular strain of non-typable H. influenzae has a ganglioside GM1-like structure and elicits axonal Guillain-Barré syndrome similar to C. jejuni-related Guillain-Barré syndrome.

Adult↗
PubMed2000

Wild type ApoA-II gene does not rescue senescence-accelerated mouse (SAMP1) from short life span and accelerated mortality.

Biochemical and genetic data suggest that the Apoa2c allele of the apolipoprotein A-II gene causes severe senile amyloidosis (AApoAII) in SAMP1, a mouse model for accelerated senescence. We analyzed the effects of replacement of Apoa2c in SAMP1 mice with non-amyloidogenic Apoa2b on amyloidosis, lipoprotein metabolism, and progression of senescence using a congenic strain, P1.R1-Apoa2b, which has the Apoa2b chromosome region of SAMR1 in the genome of SAMP1. Age-associated amyloid deposition was not observed, but plasma concentrations of apoA-II protein and HDL-cholesterol decreased with age in P1.R1-Apoa2b. P1.R1-Apoa2b showed lower scores of senescence than did SAMP1. However, the life span and mortality rate doubling time were similar in P1.R1-Apoa2b and SAMP1. These results suggest that replacement of Apoa2c with non-amyloidogenic Apoa2b does not rescue SAMP1 mice from a short life span and accelerated mortality.

Aging↗
PubMed2000

Mechanisms of umami taste preference and aversion in rats.

The influence of glutamate intake on growth and appetite, and the mechanisms of preference and aversion for monosodium L-glutamate (MSG) solutions were investigated in rats. Food intake, but not weight gain, was reduced significantly in rats fed a glutamate + glutamine (Glx)-deficient diet compared with those fed a control diet. Increase in the voluntary intake of Glx solutions was more rapid in rats fed the Glx-deficient diet. The preference and aversion for MSG solutions were distinctly different in 14 rat strains tested. Brown-Norway rats showed a strong preference for 60 mmol/L MSG and did not show aversive behavior toward solutions containing up to 600 mmol/L MSG. Sprague-Dawley (SD) rats showed a moderate preference for 60 mmol/L MSG and a weak aversion for MSG concentrations higher than 240 mmol/L; Long-Evans Agouti rats showed a moderate preference for 60 mmol/L MSG and a marked aversion for MSG concentrations higher than 120 mmol/L. Aversion was not due to nonspecific hyperosmotic effects. After section of gastric branches of the vagus nerve, MSG became aversive to SD rats. Aversion to 240 mmol/L MSG was reduced by 23-39% when combined with proline, alanine, glycine and glucose. These results show that the preference and aversion for MSG are determined by genetic factors, as well as vagus nerve function, and that the aversion to high MSG concentrations is reduced by the presence of other glucogenic amino acids and sugars.

Amino Acids↗
PubMed2000

Circadian release of hypothalamic norepinephrine in rats in vivo is depressed during early L-lysine deficiency.

Rats rapidly recognize an amino acid-deficient diet, presumably via central mechanisms that involve hypothalamic circuits. We evaluated the effects of a deficiency of the essential amino acid, L-lysine, on the ventromedial hypothalamus (VMH) norepinephrine (NE) circadian release in free-moving, nonstressed rats. A dialysis probe was implanted into the VMH of male Wistar rats. Continuous microdialysis measurement was done during the first 26 h of L-lysine (Lys) deficiency in rats that had free access to food and fluid. The dark phase was from 1900 to 0700 h. Rats were divided into six groups according to their food and fluid intakes. They were fed either normal (Lys sufficient) or Lys deficient powdered food and provided with distilled water, glycine (Gly, 400 mmol/L) or Lys solution (400 mmol/L). In control rats, VMH NE release showed a diurnal pattern, with the lowest levels measured at the onset of the dark phase. In Lys-deficient rats, the release was significantly depressed from the early morning (0500 h) compared with Lys-sufficient rats, without any differences in food and fluid intakes. A normal pattern of VMH NE was restored by the provision of 400 mmol/L Lys solution to deficient rats. The results suggest that the VMH NE release is involved in the early integration of signals about amino acid deficiency.

Analysis of Variance↗
PubMed2000

A phase II study of combined chemoradiotherapy for limited disease-small-cell lung cancer.

A study to evaluate the efficacy of cisplatin, doxorubicin, and etoposide chemotherapy with combined radiotherapy was undertaken in 26 patients with limited disease-small-cell lung cancer. Patients were treated with cisplatin (80 mg/m2) intravenously (i.v.) on day 1, doxorubicin (30 mg/m2) i.v. on day 1, and etoposide (80 mg/m2) i.v. on days 1, 3, and 5, every 4 weeks for four cycles. Thoracic irradiation of 40 Gy in 20 fractions was delivered during 4 weeks to the primary site starting on day 8 of the second cycle of chemotherapy. The objective response rate was 100%. A complete response was observed in 10 patients (38%). The median survival time was 23 months, and the 3-year survival rate was 42%. Seven patients (27%) continued to survive at least 8 years and remain free from disease. Grade III/IV leukopenia was observed in 25 patients (96%). Grade III/IV thrombocytopenia developed in 19 patients (73%). Grade III/IV esophagitis was not seen. Interstitial pneumonitis occurred in two patients. This regimen is effective and has acceptable toxicity for use in the treatment of limited disease-small-cell lung cancer.

Aged↗
PubMed2000

L-myc restriction fragment length polymorphism in Japanese patients with esophageal cancer.

L-myc polymorphism is a representative genetic trait related to an individual's susceptibility to several cancers. However, there have been no reports concerning the association between esophageal cancer and L-myc polymorphism. To analyze the distribution of polymorphism in Japanese patients with esophageal cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used. Based on an analysis of 65 Japanese patients with esophageal cancer and 107 healthy control subjects, a significant difference was observed in either the distribution of genotypes (P=0.012) or of allele frequencies between the two groups (P=0.004). The relative risk of esophageal cancer for genotypes including the shorter allele was 2.9 compared to the longer allele homozygote. Furthermore, the patients with S-allele had a tendency for poor prognosis among those with three genotypes. A significant difference between the distribution of genotypes and the incidence of lymph node metastasis was found based on the clinicopathological features of the cancers. These results suggest that L-myc polymorphism may be implicated as a genetic trait affecting an individual's susceptibility to esophageal cancer, at least among Japanese patients.

Esophageal Neoplasms↗
PubMed2000

Expression of SART3 tumor-rejection antigen in gastric cancers.

We previously reported SART3 as a tumor-rejection antigen recognized by histocompatibility leukocyte antigen (HLA)-A24-restricted cytotoxic T lymphocytes (CTLs). In this study, we investigated the expression of the SART3 antigen in gastric cancers, as a candidate for use in specific immunotherapy. The SART3 antigen was detected in 9 of 10 (90%) gastric cancer cell lines, 35 of 52 (67.3%) gastric cancer tissues, and 0 of 20 non-tumorous gastric tissues. SART3-derived peptides corresponding to positions 109- 118 and 315-323 induced HLA-A24-restricted and tumor-specific CTLs from peripheral blood mononuclear cells (PBMCs) of gastric cancer patients. These peptide-induced CTLs recognized HLA-A24(+) SART3(+) gastric cancer cells, but not HLA-A24(+) SART3(-) or HLA-A24(-) SART3(+) gastric cancer cells. Therefore, the SART3 peptides could be useful in specific immunotherapy of gastric cancer patients.

Adenocarcinoma↗