Search PubMed⌕ Search

Biomedical subjects

S Tsutsui

Publications and source records attributed to S Tsutsui.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Repeated pulmonary aspiration in the aged demented patients].

We investigated the aged demented inpatients who had repeated aspiration in our hospital during a period of 21 months from July 1997. Subjects are 60 patients aged from 65 to 94. We investigated the clinical background of the subjects, dividing them into the group with pneumonia and the group without pneumonia, and compared their type of dementia, grade of dementia, underlying diseases, laboratory data, diet, and outcome. We further compared the effect of mucoid diet for pneumonia. The most common underlying diseases were hypertension, cerebrovascular disease, diseases of the digestive system, and malignant tumor. There was no statistically significant difference in the outcome of the two groups. Within the subjects, death due to pneumonia was statistically significantly less in patients who had a mucoid diet. These findings suggested that a mucoid diet is useful for the protection against death caused by aspiration pneumonia.

Aged↗
PubMed1999

Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor.

BACKGROUND & AIMS: Parietal cells express heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF). However, it is unknown whether HB-EGF mediates the trophic action of gastrin. The purpose of this study was to determine whether gastrin modulates the expression of HB-EGF, which mediates the proliferative effects of gastrin on gastric epithelial cells. METHODS: RGM1 cells, a rat gastric epithelial cell line, were transfected with a human gastrin receptor complementary DNA. Gastrin induction of messenger RNAs (mRNAs) for EGF-related polypeptides was assayed by Northern blotting. Processing of cell surface-associated proHB-EGF and secretion of HB-EGF were determined by flow cytometry and Western blotting, respectively. Tyrosine phosphorylation of the EGF receptor was assayed by immunoprecipitation and Western blotting with an antiphosphotyrosine antibody. Cell growth was evaluated by [3H]thymidine incorporation. RESULTS: Gastrin induced expression of HB-EGF mRNA, processing of proHB-EGF, release of HB-EGF into the medium, and tyrosine phosphorylation of the EGF receptor. The growth-stimulatory effects of gastrin were partly inhibited by anti-rat HB-EGF serum and completely blocked by AG1478, an EGF receptor-specific tyrphostin. CONCLUSIONS: The findings suggest that HB-EGF at least partially mediates the proliferative effects of gastrin on gastric epithelial cells.

Animals↗
PubMed1999

Lack of correlation between timing of surgery in relation to the menstrual cycle and prognosis of premenopausal patients with early breast cancer.

In a retrospective cohort of a randomised study of adjuvant endocrine, chemotherapy and chemoendocrine therapy, we investigated the correlation between timing of mastectomy and relapse-free survival (RFS) and overall survival (OS) in 721 premenopausal patients with early breast cancer. The median follow-up was 10.1 years (range: 6.1-19.1 years). We grouped the patients by three kinds of classification according to Badwe, Senie, and Hrushesky. The logrank test after the Kaplan-Meier curves showed that there were no significant differences between the categorised menstrual phase in cycle and RFS or OS, except for RFS using Badwe's classification, where the patients whose timing of operation was in the follicular phase had a better RFS compared with those in the luteal phase. These were confirmed by the Cox proportional hazard model. These results suggest that a positive result might be a chance finding, dependent upon the cut-off levels in the menstrual cycle.

Adult↗
PubMed1999

Esophageal motility and psychiatric factors in functional dyspepsia patients with or without pain.

Subtypes of functional dyspepsia (FD), including refluxlike dyspepsia, ulcerlike dyspepsia, dysmotility-like dyspepsia, and nonspecific dyspepsia, have been described and are widely used clinically. However, these symptom patterns often overlap, and the terms are insufficient for indicating all FD symptoms. In this study, we divided 71 FD patients into two groups: patients with or without pain. Group I, the pain dyspepsia group, included patients in whom the main symptoms were epigastralgia and/or chest pain. Group II, the painless dyspepsia group, included patients without pain, in whom the symptoms were nausea, vomiting, and heartburn. We examined the relationship between esophageal function and psychiatric factors in the test groups and compared them with a control group. Of the FD patients, 19.7% [8 (25%) of 32 group I patients, 6 (15.4%) of 39 group II patients] had esophageal motility disorders, such as nutcracker esophagus and diffuse esophageal spasm. The LES pressure of group I was higher than that of group II by esophageal manometry (P < 0.05). In 17 (53.1%) of 32 group I patients and 31 (79.5%) of 39 group II patients, psychiatric disorders (38.0% had depressive disorder and 21.1% had an anxiety disorder) were diagnosed following DSM III-R criteria. Group II tended to be more depressive than group I (P = 0.0508). Psychological assessment scores, STAI-I and STAI-II, were higher in groups I and II than in the control group (P < 0.001). Long-term distress, anxiety, and depression seem to influence the symptoms of FD patients. Esophageal dysmotility may be an important functional abnormality of FD.

Abdominal Pain↗
PubMed1999

Prognostic impact of second cancer on the survival of early breast cancer patients.

Although numerous reports have been published on the incidence of second cancers after adjuvant therapy for early breast cancer, there have been few studies on the effect of the development of second cancer on overall survival (OS) of the patients. 1857 female patients younger than 80 years of age with operable breast cancer with UICC Stages I, II, and III who entered 3 trials of adjuvant therapy were studied for the detection of recurrence and second cancer. The median follow-up period for surviving patients was 12 years (range, 5-25 years). 384 of recurrence and 119 of second cancers occurred. 465 deaths were recorded, the causes of which were designated to be due to recurrence of breast cancer in 326 patients, second cancers in 57, and due to other causes in 82. Many background factors that were significantly related to recurrence did not influence the incidence of and death by second cancers after mastectomy: age and menopausal status alone were related. The difference in the Kaplan-Meier curves between the event (recurrence and second cancers)-free and relapse-free survivals indicates the incidence of second cancers is a significant event in post-operation course of early breast cancer patients (P=0.0001). The survival curve of patients who were free from recurrence- and second cancer-death is shown to be significantly lower than that of those free from breast cancer-specific death (P=0.0355), suggesting that death by second cancers is significantly influential to the overall survival. According to the Cox regression model using a recurrence or second cancers as time-dependent variables, the diagnosis of a recurrence or second cancer is shown to be highly significant to OS of the patients (hazard ratio: 49.3, and 6.3, respectively). Second cancers are shown to be not statistically significantly influential to the breast cancer specific survival (P=0.0637), nor a recurrence to second cancer specific survival (P=0.2285). In spite of heterogeneous distribution of sites of second primary cancers and their different natural histories, the incidence of second cancer has a significant effect on the postoperative survival of early breast cancer patients. In the survival analysis of early breast cancer patients, we have to estimate the contribution of second cancers to properly evaluate the effect of treatment.

Adult↗
PubMed1999

[A randomized study of adjuvant treatments for operable breast cancer patients stratified by estrogen receptor and menopausal status].

According to estrogen receptor (ER) and menopausal status, operable breast cancer patients were randomized for adjuvant endocrine therapy with tamoxifen (TAM) in premenopausal patients, after oophorectomy (OVEX), chemotherapy, CHEM (mitomycin C+ oral cyclophosphamide), or chemo-endocrine therapy (TAM + CHEM). Some 1579 patients were entered in the trial between 9, 1978 and 12, 1991, with a median follow-up of 10 years. In ER-positive, premenopausal patients there were no significant differences in relapse-free (RFS) or overall survival (OS) among the OVEX + TAM, CHEM, and CHEM + TAM arms. On the contrary, in ER-positive, post-menopausal patients, the chemoendocrine therapy showed a significantly better OS (p = 0.0254) with a trend of better RFS (p = 0.0674), as compared with TAM or CHEM groups. ER-negative, premenopausal patients showed no significant differences in RFS or OS between CHEM and CHEM + TAM arms. In ER-negative, postmenopausal patients, there was a non-significantly better RFS (p = 0.0888) and a significantly better OS (p = 0.0332) in CHEM + TAM group than in the CHEM alone group. These results suggest that ER and menopausal status are important criteria to select early breast cancer patients for adjuvant treatments.

Adult↗
PubMed1999

Overexpression of edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner.

Lysophosphatidic acid (LPA) is one of the major growth factors in ascites from ovarian cancer patients and appears to play an important role in proliferation, survival, and invasion of ovarian cancer cells. Recently, several groups have shown that Edg-2, which belongs to the G-protein coupled receptor family, is a functional LPA receptor. Northern blot analysis showed that most ovarian cancer cell lines express Edg-2. Edg-2 expression was especially high in the cisplatin-resistant and slowly proliferating 2780cp cell line and was almost absent from the cisplatin-sensitive and rapidly proliferating A2780 cell line. We thus assessed whether Edg-2 could contribute to changes in cell viability, cell proliferation, or cisplatin resistance. Stable overexpression of Edg-2 in A2780 cells induced an exogenous LPA-independent decrease in proliferation but did not alter cisplatin sensitivity. The LPA-independent decrease in growth rate induced by overexpression of Edg-2 could be explained, at least in part, by Edg-2-induced apoptosis rather than by effects on cell cycle progression. In agreement with the results in stably transfected A2780 cells, transient expression of Edg-2 in Jurkat T cells also induced apoptosis. When cells were separated from the extracellular matrix, they underwent a specialized form of apoptosis called anoikis, which is particularly important in survival of cells in the circulation during metastasis. A2780 cells engineered to overexpress Edg-2 were particularly sensitive to anoikis. These observations suggest that Edg-2 may be a negative regulator for ovarian epithelial cell growth and metastasis.

Animals↗
PubMed1998

Calphostin C induces expression of amphiregulin mRNA via reactive oxygen species in IEC-6 cells.

Calphostin C, a secondary metabolite of the fungus Cladosporium cladosporioides, is generally used as a specific inhibitor of protein kinase C. It is known that 12-O-tetradecanoyl-13-phorbol acetate (TPA), a protein kinase C activator, induces expression of mRNA for amphiregulin (AR), a member of EGF-related polypeptides, in mammalian epithelial cells. In this work, we determined the effect of calphostin C on AR mRNA expression in IEC-6 cells, a rat intestinal epithelial cell line, and unexpectedly found that this compound enhanced the TPA-induced expression of AR mRNA. Moreover, calphostin C alone induced expression of AR mRNA in a light-dependent manner, and this effect was abrogated by pretreatment with N-acetylcysteine. These results suggest that calphostin C can upregulate expression of AR mRNA via reactive oxygen species.

Acetylcysteine↗
PubMed1998

Relationship between preoperative assessment of organ function and postoperative morbidity in patients with oesophageal cancer.

OBJECTIVE: To find out if strict assessment of organ function preoperatively predicted morbidity and mortality in patients being operated on for oesophageal carcinoma. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 178 patients operated on for oesophageal cancer 1989-1993. INTERVENTIONS: Oesophagectomy and reconstruction (using either stomach or colon) in one stage by a right thoracoabdominal approach in 173, and transhiatal resection in 5 with either poor pulmonary reserve or early lesions. MAIN OUTCOME MEASURES: Correlation between preoperative assessment of organ function and postoperative development of complications. RESULT: 79 patients (44%) developed complications and 6 died (3%). Pulmonary dysfunction preoperatively was significantly associated with the development of all complications (p=0.001) and of postoperative pulmonary complications (p=0.04). No other preoperative assessment correlated significantly with the development of postoperative complications. CONCLUSION: Accurate preoperative assessment of pulmonary function is a valuable indicator of postoperative morbidity.

Aged↗
PubMed1997

Role of heparin-binding EGF-related peptides in proliferation and apoptosis of activated ras-stimulated intestinal epithelial cells.

The ras mutation is a common and critical step in carcinogenesis. Autocrine growth factors are also known to play an important role in cancer cell growth and transformation. However, the contribution of autocrine growth factors in regulation of proliferation and apoptosis of activated ras-stimulated intestinal epithelium is not fully understood. Therefore, we constructed activated ras-transfected intestinal epithelial cell clones (IEC-ras) to examine the role of epidermal growth factor (EGF)-related peptides in the behavior of IEC-ras. Overexpression of EGF family growth factors (transforming growth factor alpha, heparin-binding EGF-like growth factor, amphiregulin and betacellulin) and stronger phosphorylation of the EGF receptor was observed in IEC-ras compared with control cells. IEC-ras proliferated more rapidly than control cells, and a specific EGF receptor kinase inhibitor, AG 1478, abolished the increased proliferation of IEC-ras. Heparitinase and chlorate also prevented increased proliferation of IEC-ras. Additionally, IEC-ras expressed more bcl-2 and was more resistant to apoptosis induction by UV radiation and mitomycin C. AG 1478 suppressed bcl-2 expression and inhibited resistance to apoptosis of IEC-ras. Heparitinase and chlorate had effects similar to those of AG 1478. Our data indicate that heparin-binding EGF family growth factors play an important role in both increased proliferation and resistance to apoptosis of ras-stimulated intestinal epithelial cells.

Amphiregulin↗
PubMed1997

Induction of heparin binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach.

The present study was designed to investigate whether heparin-binding epidermal growth factor-like growth factor and its related peptides are expressed in response to gastrin in rat stomach. Rat gastrin-17I (2.5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-740,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-Dawley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene expression was estimated using a ribonuclease protection assay. The level of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNA were significantly increased within 3 hours following gastrin infusion and reached maximum levels 6 and 12 hours later, respectively. Continuous infusion of gastrin significantly increased oxyntic mucosal proliferation. Gastrin receptor antagonist significantly inhibited gastrin-induced heparin-binding epidermal growth factor-like growth factor and amphiregulin gene expression and gastrin-induced oxyntic mucosal proliferation. These findings indicate that heparin-binding epidermal growth factor-like growth factor and amphiregulin genes are induced by gastrin and that they play a role in the trophic action of gastrin on oxyntic mucosa.

Amphiregulin↗
PubMed1997

Galactosamine-induced apoptosis in the primary mouse hepatocyte cultures.

Galactosamine (GalN)-induced apoptosis was investigated in cultured hepatocytes from mice. The percentage of fragmented DNA measured by the ELISA method increased in a concentration-dependent manner from the very early stage, i.e. 0.5 hrs, after GalN-exposure. In addition, a ladder-like fragmentation pattern by agarose gel electrophoresis appeared first at 3 hr-exposure to 20 mM GalN, at 6 hr-exposure to 10 mM GalN and at 12 hr-exposure to 5 mM GalN, respectively. On the other hand, cytotoxicity indicated by leakage of lactate dehydrogenase from cultured hepatocytes to culture medium was first detected at 24 hrs after GalN-treatment. Morphologically, formation of blebs and apoptotic bodies was observed from 12 hr-exposure to 20 mM GalN and from 24 hr-exposure to 10 mM GalN, respectively. Thus GalN could induce apoptosis in primary hepatocyte cultures from mice.

Animals↗
PubMed1997

Hair follicles of young Wistar strain hairless rats: a histological study.

The histological changes in hair follicles in hairless rats derived from the Wistar strain (hW, hairless Wistar) were examined from birth to maturity and compared with those of age-matched normal Wistar rats. In the 1st hair cycle, the hair follicles of hW rats were shorter and less well developed than those of Wistar rats. In early anagen, eosinophilic bodies were observed in some hair follicles which showed immature histological features. By using Tdt-mediated dUTP nick end labelling (TUNEL) method and electron microscopic examination, these bodies were confirmed to be apoptotic bodies. These follicles seemed to disappear by abnormal regression. In late anagen phase, the follicles in which the apoptosis did not occur showed enlarged hair roots with hypertrophy of the inner root sheath. Subsequently, when the follicles in normal Wistar rats synchronously regressed in the catagen phase, most of the follicles in hW rats similarly entered the catagen phase, but a few follicles did not regress completely and showed aberrant hair root enlargement. Finally, both types of follicle in hW rats formed follicular cysts. These abnormalities in follicle development (abnormal follicular regression and follicular cyst formation) appear to be associated with the hairlessness in this rat strain.

Animals↗
PubMed1997

Replication of feline syncytial virus in feline T-lymphoblastoid cells and induction of apoptosis in the cells.

Feline syncytial virus (FSV) was isolated from feline peripheral blood mononuclear cells of FSV-seropositive cats. When the susceptibility of feline T-lymphocytes to FSV was examined using three strains of FSV, FSV antigens were detected in the FSV-infected T-lymphoblastoid cells. Further, a diversity of biological properties, including replication kinetics and syncytia formation, was noted among the strains, and condensation of chromatin and the fragmentation of cellular DNA were observed in the infected cells. From these data, we conclude that FSV is lymphotropic and can induce apoptosis in the lymphocytes.

Animals↗
PubMed1997

Forking genetic algorithms: GAs with search space division schemes.

In this article, we propose a new type of genetic algorithm (GA), the forking GA (fGA), which divides the whole search space into subspaces, depending on the convergence status of the population and the solutions obtained so far. The fGA is intended to deal with multimodal problems that are difficult to solve using conventional GAs. We use a multipopulation scheme that includes one parent population that explores one subspace and one or more child populations exploiting the other subspace. We consider two types of fGAs, depending on the method used to divide the search space. One is the genotypic fGA (g-fGA), which defines the search subspace for each subpopulation, depending on the salient schema within the genotypic search space. The other is the phenotypic fGA (p-fGA), which defines a search subspace by a neighborhood hypercube around the current best individual in the phenotypic feature space. Empirical results on complex function optimization problems show that both the g-fGA and p-fGA perform well compared to conventional GAs. Two additional utilities of the p-fGA are also studied briefly.

Algorithms↗
PubMed1997

Apoptosis of murine hepatocytes induced by high doses of galactosamine.

Apoptosis induced by high doses of Galactosamine (GalN) was investigated in mice hepatocytes in vivo. In mice intraperitoneally (i.p.) treated with GalN 3 g/kg, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells were first observed at 6 hr postadministration (PA). Both acidophilic bodies in hematoxylin and eosin (HE)-stained sections and TUNEL-positive cells were markedly found at 24 hr PA. At 48 hr PA, cellular degeneration and necrosis of hepatocytes were prominently observed, and TUNEL-positive cells were scarcely found. In the mice ip treated with GalN 1.5 g/kg, the lesion was milder than that in those treated with GalN 3 g/kg. Acidophilic bodies and TUNEL-positive cells were scarcely found at 24 hr PA, whereas they were markedly seen at 48 hr PA. In addition, a ladder-like DNA fragmentation pattern by agarose gel electrophoresis was observed most remarkably at 24 hr PA with GalN 3 g/kg and at 48 hr PA with GalN 1.5 g/kg, and less distinctly at 48 hr PA with GalN 3 g/kg. On the other hand, sGOT and sGPT activities increased prominently at 48 hr PA with GalN 3 g/kg. These results suggest that the cell death induced by high dose of GalN may be caused by apoptosis, and subsequently by necrosis in vivo.

Alanine Transaminase↗