Search PubMed⌕ Search

Biomedical subjects

Y Kinoshita

Publications and source records attributed to Y Kinoshita.

At least 73 records · Page 4Linked to original sources

Subcellular distribution of cytokeratin and vimentin in malignant rhabdoid tumor: three-dimensional imaging with confocal laser scanning microscopy and double immunofluorescence.

Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm that mostly occurs in childhood, characterized histologically by rhabdoid cells as shown by eosinophilic intracytoplasmic inclusions. Although it is known that rhabdoid cells co-express cytokeratin (CK) and vimentin, the distribution patterns of these two kinds of intermediate filaments and structural relationship between them are still not known. We investigated the subcellular distribution of CKs 8 and 18 and vimentin in MRT cell lines (Tm87-16, STM91-01, TTC549, and TC289) using confocal laser scanning microscopy and double immunofluorescence, in addition to ultrastructural examination. Vimentin was diffusely expressed in the cytoplasm of MRT cells, focally forming a filamentous network. In contrast, CKs 8 and 18 were partially expressed in the cytoplasm of MRT cells, forming globules or a few vague agglomerates. Three-dimensional images in TC289 cells revealed distinct distribution patterns of cytokeratin and vimentin, showing agglomerates of cytokeratins within the vimentin filament network. We conclude that these globules and agglomerates of CKs 8 and 18 correspond with the characteristic ultrastructural finding, showing cytoplasmic bundles of intermediate filaments concentrated in whorled arrays.

Female↗

Efficacy of ecabet sodium for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole-based regimen.

BACKGROUND: The cytoprotective agent, ecabet sodium, inhibits urease activity and growth of Helicobacter pylori. AIM: To evaluate the efficacy and safety of ecabet sodium-based eradication of H. pylori infection, compared with a lansoprazole-based regimen, in a randomized multicentre study. SUBJECTS AND METHODS: A total of 120 H. pylori-positive patients were assigned to one of two treatment regimens for 2 weeks: ecabet sodium 1 g b.d., amoxicillin 500 mg t.d.s. and clarithromycin 400 mg b.d. (EAC: 60 patients); or lansoprazole 30 mg (o.m.) with the same antimicrobial agents (LAC: 60 patients). Cure of infection was assessed by a 13C-urea breath test 1 month after completion of treatment. RESULTS: One patient in the EAC group and two in the LAC group did not complete therapy because of an adverse event, and three did not undergo the 13C-urea breath test. Cure rates for the intention-to-treat, all-patients-treated and per protocol analysis in the EAC group were 85%, 86% and 88%, respectively, whereas those in the LAC group were 85%, 88% and 91%. There were no significant differences in cure rate or adverse events between the two regimens. CONCLUSIONS: Ecabet sodium in combination with amoxicillin and clarithromycin is as effective as lansoprazole-based eradication therapy for H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Intragastric distribution of Helicobacter pylori during short-term omeprazole therapy: study using Carnoy's fixation and immunohistochemistry for detection of bacteria.

BACKGROUND: There is controversy about the effect of acid-suppressive therapy on Helicobacter pylori density and the severity of histological gastritis in the corpus. AIM: To evaluate the precise distribution of H. pylori, both on the surface mucus cells and in the surface mucus gel layer, by using Carnoy's fixation and immunostaining for the detection of bacteria. METHODS: A total of 19 peptic ulcer patients with H. pylori infection were studied. All patients received a 6-week course of treatment with omeprazole (20 mg/day). Before and after the therapy, H. pylori density in Carnoy-fixed tissue sections was examined immunohistochemically. The effect of omeprazole therapy on the severity of gastritis was also evaluated. RESULTS: H. pylori density and the grade of gastritis significantly decreased in the antrum after omeprazole therapy. In the corpus, however, there were no significant changes in H. pylori density or the severity of gastritis after omeprazole therapy. CONCLUSION: Carnoy's fixation and immunostaining was found to be useful for the detection of H. pylori in the surface mucus gel layer as well as on the surface mucus cells in biopsy tissue sections. By using this method, H. pylori density decreased in the antrum, but remained unchanged in the corpus after a 6-week course of omeprazole therapy.

Acetic Acid↗

S1 proteins C2 and D2 are novel hnRNPs similar to the transcriptional repressor, CArG box motif-binding factor A.

S1 proteins A-D are liberated from thoroughly washed nuclei by mild digestion with DNase I or RNase A, and extracted selectively at pH 4.9 from the reaction supernatants. Here, we characterized the S1 proteins, focusing on protein D2, the most abundant S1 protein in the rat liver, and on protein C2 as well. Using a specific antibody, McAb 351, they were shown to occur in the extranucleolar nucleoplasm, and to be extracted partly in the nuclear soluble fraction. We demonstrate that the S1 proteins in this fraction exist constituting heterogeneous nuclear ribonucleoproteins (hnRNPs), through direct binding to hnRNAs, as revealed by centrifugation on density gradients, immunoprecipitation, and UV cross-linking. In hnRNPs, protein D2 occurred at nuclease-hypersensitive sites and C2 in the structures that gave rise to 40 S RNP particles. By microsequencing, protein D2 was identified with a known protein, CArG box motif-binding factor A (CBF-A), which has been characterized as a transcriptional repressor, and C2 as its isoform protein. In fact, CBF-A expressed from its cDNA was indistinguishable from protein D2 in molecular size and immunoreactivity to McAb 351. Thus, the present results demonstrate that S1 proteins C2 and D2 are novel hnRNP proteins, and suggest that the proteins C2 and D2 act in both transcriptional and post-transcriptional processes in gene expression.

Amino Acid Sequence↗

Role of hiatus hernia and gastric mucosal atrophy in the development of reflux esophagitis in the elderly.

BACKGROUND AND AIMS: The pathogenetic mechanism responsible for the increased prevalence of reflux esophagitis in the elderly remains controversial. The aim of this study was to determine if an increased occurrence of hiatus hernia (HH) and/or a lower rate of gastric mucosal atrophy (GMA) are the main causes of the increased prevalence of reflux esophagitis in elderly patients. METHODS: The prevalence of HH, GMA, and reflux esophagitis was investigated by reviewing the endoscopic films of 2788 consecutive patients examined during a 3-year period. RESULTS: The prevalence of esophagitis in males was higher than in females (11.6% vs 7.6%, P< 0.0005). The prevalence of reflux esophagitis and HH was found to increase with age in females, but not in male patients. The prevalence of reflux esophagitis in hernia-positive patients also increased with age in women, but not in men. Age, male gender, presence of HH, and closed-type of GMA were significant risk factors for the prevalence of esophagitis (P=0.0001, 0.0229, <0.0001, <0.0001, respectively). In addition, the risk ratios of HH and low-grade GMA for reflux esophagitis increased with age, and this tendency was higher in female patients than in males. CONCLUSIONS: Aging, male gender, HH and closed-type GMA are most likely the risk factors of endoscopically proven reflux esophagitis in Japanese patients.

Adult↗

Prevalence of functional dyspepsia and its relationship with Helicobacter pylori infection in a Japanese population.

AIM: To investigate the prevalence of functional dyspepsia and Helicobacter pylori infection and their relationship in a Japanese population. METHODS: Two thousand five hundred people who visited Shimane Institute of Health Science for their annual medical check-up from September 1998 to August 1999 were prospectively enrolled in the study. After routine medical examination, including an upper gastrointestinal study and an ultrasonographic examination, all subjects were asked standard questions to check for the presence of any symptoms that suggested dyspepsia. Helicobacter pylori infection was determined by using a serum IgG antibody concentration with an ELISA. RESULTS: Of the 2,500 persons investigated, 2,263 showed no abnormal finding in any medical examination. The presence or absence of symptoms and H. pylori infection was investigated in these 2,263 cases. Of these, 201 people (8.9%) experienced nausea, fullness and/or early satiety and were diagnosed as having dysmotility-like dyspepsia, while 118 people (5.2%) experienced pain localized to the epigastrium and were diagnosed as having ulcer-like dyspepsia. The frequency of these symptoms had a tendency to decline with age, although this was not statistically significant. In contrast, the rate of H. pylori infection increased with age. There was no significant relationship between H. pylori infection and any type of functional dyspepsia. CONCLUSIONS: Helicobacter pylori infection does not influence the prevalence of the dysmotility-like and ulcer-like dyspeptic symptoms.

Adult↗

Influence of Helicobacter pylori infection and cetraxate on gastric mucosal blood flow during healing of endoscopic mucosal resection-induced ulcers.

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection is known to affect the gastric microcirculation, and cetraxate is reported to accelerate gastric ulcer healing, possibly by augmenting gastric mucosal blood flow (MBF). The aim of this study is to clarify the effect of H. pylori infection and cetraxate on MBF during gastric ulcer healing. METHODS: Forty-two patients who had undergone endoscopic mucosal resection (EMR) were studied. Mucosal blood flow was measured by the use of a laser Doppler flowmeter in the surrounding mucosa and at the ulcer margin, before, 1 day, 1 week and 4 weeks after EMR. Helicobacter pylori infection was confirmed by the use of bacterial culture and histology. After EMR, patients were randomly assigned to receive 30 mg lansoprazole (u.i.d; L-regimen) or 30 mg lansoprazole (u.i.d.) with 200 mg cetraxate (q.i.d; LC-regimen) for 4 weeks. RESULTS: The MBF ratio (MBF at ulcer margin/MBF in surrounding mucosa) 1 week after EMR was significantly lower than that before or 4 weeks after EMR only in H. pylori-positive patients treated with the L-regimen. No such decrease in MBF was observed after 1 week in H. pylori-positive patients treated with the LC-regimen or in H. pylori-negative patients. CONCLUSION: A transient decrease in MBF was detected at the ulcer margin during healing of EMR-induced ulcers in H. pylori-infected patients. Cetraxate seemed to prevent this decrease in MBF.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis.

BACKGROUND AND AIMS: Nocturnal gastric acid breakthrough (NAB) is defined as an intragastric pH < 4.0 lasting more than 1 h during the night in patients taking a proton pump inhibitor (PPI). Gastroesophageal reflux disease (GERD) patients with nocturnal gastroesophageal acid reflux accompanied by NAB are thought to be refractory to PPI treatment. The aim of this study was to endoscopically identify the patients with predominant nocturnal gastroesophageal acid reflux. METHODS: The subjects were 37 patients with erosive reflux esophagitis (Los Angeles classification (LA) grade A, 12; B, 10; C, eight; and D, seven cases) and a control group of 20 patients without esophagitis. The results of ambulatory 24 h gastric and esophageal pH monitoring were compared among different grades of esophagitis. RESULTS: Gastroesophageal reflux during 24 h in patients with high-grade esophagitis was more frequent than for patients with low-grade esophagitis or no esophagitis. Although the length of esophageal acid exposure (percentage time with pH < 4.0) in patients with grade A or without esophagitis was longer in the daytime, that in patients with grades C and D was longer during the night. The reason for the delayed nocturnal acid exposure was the longer nocturnal acid clearance in high-grade reflux esophagitis. CONCLUSIONS: Nocturnal exposure of the esophagus to acid occurs frequently in patients with LA grades C and D esophagitis. Thus, the existence of NAB with resulting nocturnal acid reflux should be considered when the patient with high-grade esophagitis shows resistance to PPI treatment.

Adult↗

Influence of Helicobacter pylori infection on the prevalence of reflux esophagitis in Japanese patients.

BACKGROUND AND AIM: Reflux esophagitis is caused by esophageal motor dysfunction in patients with sufficient gastric acid secretion. Helicobacter pylori causes atrophic gastritis and influences gastric acid secretion. Hiatus hernia (HH) of the esophagus causes motor dysfunction in the lower esophagus. Therefore, this study aimed to test whether H. pylori infection, gastric mucosal atrophy and HH are predictive factors for reflux esophagitis. METHODS: Helicobacter pylori infection was examined in 781 patients by the measurement of serum immunoglobulin (Ig)G antibody, bacteriological culture and histological examination of biopsy specimens. The prevalence of HH, endoscopically identified gastric mucosal atrophy (closed- or open-type) and reflux esophagitis were investigated by reviewing endoscopic films. Investigated patients were divided into three age groups, under 49, 50-69, and over 70 years. The prevalence of esophagitis, H. pylori infection, gastric mucosal atrophy, and HH were compared to identify the possible predictive factors for reflux esophagitis by using logistic regression analysis. RESULTS: Sixty-nine patients with reflux esophagitis were found among the 781 investigated cases. The odds ratios of negative H. pylori infection, endoscopically identified closed-type gastric mucosal atrophy, and HH for the prevalence of reflux esophagitis were 1.342, 1.751 and 5.527, respectively. These results indicated that the presence of H. pylori infection was only a weak negative risk factor, and that HH was the most reliable endoscopic predictive factor for reflux esophagitis. CONCLUSION: Helicobacter pylori infection is a weak negative risk factor for the prevalence of reflux esophagitis, while HH is the most reliable predictive factor.

Aged↗

Expression of intercellular adhesion molecules in epithelioid sarcoma and malignant rhabdoid tumor.

We clinicopathologically evaluated 31 cases of epithelioid sarcoma (ES; 25 'classical' type and six 'proximal variant' type) and six cases of malignant rhabdoid tumor (MRT; three extrarenal and three renal). We also did immunohistochemical studies on 12 classical and three proximal variant cases of ES, and six cases of MRT, to clarify the differences in biological behavior in these tumors. E-cadherin, beta-catenin and CD34 expression was evaluated. We also carried out mutational analysis of exon 3 of the beta-catenin gene by polymerase chain reaction-single-strand conformation polymorphism analysis. In ES, the 5- and 10-year survival rates were 71.1 and 55.3%, respectively. A high mitotic rate (>15/10 high-power fields) was significantly correlated with a poor overall survival rate in ES (P = 0.0248). E-cadherin expression was observed in nine cases (69.2%) of ES and in four cases (66.7%) of MRT. Most of these tumors showed aberrant E-cadherin expression. Seven cases (46.7%) of ES were positive for CD34, although none of the cases of MRT were CD34 positive. Eleven cases (73.3%) of ES were positive for beta-catenin, which was localized to the cellular membrane, whereas all of the cases of MRT were beta-catenin negative. Mutational analysis for the beta-catenin gene was done in nine cases of ES and six cases of MRT, however, genetic alteration was not found. From our results, we conclude that beta-catenin membranous expression could be a useful marker for distinguishing ES, including the proximal variant, from MRT.

Adolescent↗

T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter pylori-infected gastric corpus.

BACKGROUND: Helicobacter pylori infection induces T helper-1 immune responses in inflamed mucosa. However, the role of T cell-mediated cytotoxicity in the induction of epithelial apoptosis is still unclear. The aim of this study was to investigate the involvement of the Fas/Fas ligand (Fas/Fas-L) system in the H. pylori-infected gastric corpus. MATERIALS AND METHODS: Gastric fundic biopsy specimens were taken from patients with and without H. pylori infection. The expression of Fas and Fas-L was examined by immunohistochemistry and RT-PCR. Subsets of gastric infiltrating T cells in the biopsy specimens were studied by immunohistochemistry and flow cytometry. In histological sections, apoptosis was detected by the TUNEL method. We studied the in vitro expression of Fas-L in peripheral T cells after stimulation with H. pylori antigen and interferon-gamma (IFN-gamma). The Fas-mediated in vitro cytotoxicity of activated T cells was assessed by flow cytometry. RESULTS: The numbers of CD4+ and CD8+ T cells were greater in H. pylori-infected subjects. Fas expression was abundantly increased on fundic gland epithelium, and Fas-L was detected on lamina propria mononuclear cells in H. pylori-infected mucosa. TUNEL-positive epithelial cells were also increased in H. pylori-infected subjects. H. pylori antigen and IFN-gamma induced Fas-L mRNA expression in both CD4+ and CD8+ T cells. In cytotoxic assay, activated T cells induced apoptosis in AGS cells, which could be significantly inhibited by neutralizing Fas-L antibody. CONCLUSIONS: T cell-mediated cytotoxicity via Fas/Fas-L signaling may contribute to the induction of apoptosis in gastric epithelial cells during H. pylori infection.

Adult↗

Postoperative cortical venous infarction in tumours firmly adherent to the cortex.

It is sometimes difficult to separate extra-axial tumours from the cortical veins in case of tumours attaching tightly to the cortex and the cortical veins. We present two patients having a postoperative cortical venous infarction. A 59 year old female had convexity meningioma above the motor cortex where abnormal cortical anastomotic veins developed. Transient hemiparesis occurred after total removal of the tumour because of venous infarction and cyst formation resulting from sacrifice of these veins which were tightly adherent to the tumour surface. A 15 year old boy with immature teratoma of the pineal region, showing several draining veins around the vascular-rich tumour, presented transient drowsiness, diplopia and partial impairment of bilateral visual acuity postoperatively because of localised cortical brain and venous damage. It is important to make an effort to preserve main cortical veins during operation as much as possible, even if the tumour adheres to the cortical surface.

Adolescent↗

E-cadherin is essential for gastric epithelial restitution in vitro: a study using the normal rat gastric mucosal cell line RGM1.

The proliferation and migration of epithelial cells appear to have important roles in intercellular adhesion and the regeneration of gastric mucosal lesions. However, the role of E-cadherin, an important intercellular adhesion molecule, in restitution after gastric mucosal damage is unknown. This study was designed to investigate the possible role of E-cadherin in the regeneration of gastric mucosal lesions. Artificial small wounds were made in an RGM1 confluent monolayer sheet, and the healing process was monitored with or without the presence of different concentrations of anti-E-cadherin antibodies. E-cadherin mRNA and protein expression were determined by Northern blot analysis and immunostaining, respectively. Epithelial restitution in anti-E-cadherin antibody-treated monolayers was inhibited as compared with that in the controls without antibody. E-cadherin mRNA and protein expression were up-regulated transiently during the healing process. E-cadherin plays an important role during wound healing of gastric epithelial lesions and is crucial for sheet migration.

Animals↗

Expression of sex steroid hormone receptors in human cornea.

PURPOSE: Previously we reported the occurrence of estrogen receptor alpha (ER beta), estrogen receptor beta (ER beta) and androgen receptor (AR) in mouse corneas. The present study was designed to investigate the occurrence of various sex steroid hormone receptors, including ER alpha, progesterone receptor (PR) and AR, in human corneas. METHODS: We used reverse transcription-polymerase chain reaction (RT-PCR) to look for sex hormone receptor mRNAs (ER alpha, PR and AR) in human corneal epithelial cells obtained at autopsy. Next, using an immunocytochemical technique, we localized these receptors in donor human corneas. RESULTS: mRNAs encoding all receptors tested for were found in corneal epithelial cells obtained from male and female donor eyes. Immunocytochemical examination revealed that the receptors were located in the nuclei of corneal epithelial, stromal, and endothelial cells. CONCLUSIONS: Since receptors for both male and female sex hormones are present in human corneas of both genders, we postulate that the receptors may influence the biological functions of corneal cells through direct interaction with specific hormones.

Aged↗

Expression of c-fos, heat shock protein 70, neurotrophins, and cyclooxygenase-2 mRNA in response to focal cerebral ischemia/reperfusion in rats and their modification by magnesium sulfate.

The marginal area surrounding a region of ischemic brain tissue, designated as the penumbra, is of interest as a potential area for the rescue of neurons from cell death. Despite its clinical importance, relatively little is known about the molecular events leading to changes in brain cells in the penumbra following ischemia. In the first part of this study, we used in situ hybridization to investigate the temporal and spatial expression of c-fos, heat shock protein 70 (HSP70), neurotrophins and inducible cyclooxygenase-2 (COX-2) in the rat brain following a 2-h occlusion of the middle cerebral artery (MCA) with reperfusion. In the penumbra and surrounding cortex, upregulation of c-fos, brain-derived neurotrophic factor (BDNF), and COX-2 mRNAs was observed, while expression of HSP70 mRNA was restricted to the penumbra. This spatial discrepancy of mRNA expression suggests that different mechanisms are involved in the regulation of c-fos/BDNF/COX-2 and HSP70 expression. Intravenous infusion of magnesium sulfate (25 mg/kg) decreased both the infarct volume and upregulation of these mRNAs, suggesting its therapeutic potential.

Animals↗

Clinical relevance of precore and basal core promoter variants of hepatitis B virus during natural hepatitis B e antigen seroconversion may be overstated.

BACKGROUND: Clinical relevance of nucleotide changes in precore and basal core promoters in the hepatitis B virus genome during hepatitis B e antigen seroconversion may be overstated. The authors investigated the existence and changes in the relative proportion of variants to wild virus that occur with seroconversion. METHODS: Sera from 30 school-aged long-term hepatitis B virus carriers, including 11 tested before and after seroconversion during 1 to 8 years of follow-up, were evaluated for variations in nucleotide sequences of the basal core promoter (T1762 and A1764), precore region (A1869), and carboxyl-terminus of the X region of the hepatitis B virus genome using an amplification refractory mutation detection system with mutant-specific primers. RESULTS: All variants were found to already exist before seroconversion at various wild-type/mutant ratios. The positive rates of these variants were not changed with loss of hepatitis B e antigen. Although there was a relative increase in the concentration of these mutants in wild-type/mutant mixed populations, most patients with only a wild-type population maintained the same pattern after loss of hepatitis B e antigen. CONCLUSIONS: Our results indicate that hepatitis B virus exists as a quasi species, and correlations of nucleotide sequences with clinical and serologic findings must be done with caution.

Adolescent↗

Second primary cancers following breast cancer in the Japanese female population.

To assess the risk of developing second primary cancers following breast cancer in Japanese females, we performed a retrospective cohort study of 2786 patients who were newly diagnosed with breast cancer at our hospital between 1970 - 1994, until the end of 1995 (average follow-up period, 8.6 years). The expected number of each second primary cancer was calculated by multiplying the number of appropriate person-years at risk by the corresponding age- and calendar period-specific cancer incidence rates for women obtained from the Osaka Cancer Registry. One hundred and seventeen patients developed a second primary cancer other than subsequent breast cancer, yielding an observed-to-expected ratio (O / E) of 1.3 [95% confidence interval (CI) = 1.1 - 1.6]. The risk for developing a second primary cancer was significantly elevated during the first year following the diagnosis of breast cancer, and decreased with the passage of time to unity. A significantly increased risk was noted for the development of ovarian cancer (O / E = 2.4, 95% CI = 1.0 - 4.6), thyroid cancer (O / E = 3.7, 95% CI = 1.5 - 7.6) and non-Hodgkin's lymphoma (NHL) (O / E = 3.5, 95% CI = 1.4 - 7.1) among the breast cancer patients compared with the general population. Patients who received hormonal therapy as the breast cancer treatment showed a significantly increased risk for ovarian cancer (O / E = 5.5, 95% CI = 1.8 - 12.9). Patients who received chemotherapy as the breast cancer treatment had an increased risk for NHL (O / E = 5.0, 95% CI = 1.6 - 11.6). These findings indicate that Japanese female patients with breast cancer had a 30% higher risk of developing a second primary cancer than the general population, the higher risk being manifested in the early period following the diagnosis of breast cancer. Medical surveillance of breast cancer patients for NHL, as well as for ovarian cancer and thyroid cancer, is required.

Adult↗