Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 505 records · Page 28Linked to original sources

PubMed1996

Different carcinogenesis in the gastric remnant after gastrectomy for gastric cancer.

BACKGROUND: The incidence of gastric remnant cancer after surgery for gastric malignancies has been increasing. The interval between previous operations and the diagnosis of gastric remnant cancer, location of cancer development, and histologic type were different from those after surgery for benign diseases. However, very little is known about the reasons for these differences. Patients with gastric cancer already have cancer-related gastric mucosal changes at gastrectomy, and they undergo a wide range of dissection of nerve distribution to the stomach due to lymph node dissection. Therefore, the effects of preliminary administration of a carcinogenic agent and denervation of the gastric mucosa on tumorigenesis in the gastric remnant were investigated. METHODS: Using male Wistar rats, N-methyl-N'-nitro-N-nitroguanidine (MNNG; 50 mg/L) was given in drinking water for 10 weeks. The animals were then assigned into four groups of those undergoing Billroth I (B-I) gastrectomy or Billroth II (B-II) gastrectomy, with and without denervation. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after gastrectomy, the following investigations were performed: histologic examination and periodic acid-Schiff-Alcian blue (PAS-AB) staining of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen (PCNA). RESULTS: In macroscopic findings, the groups undergoing nitrosoguanide (NG) gastrectomy with denervation showed a significant increase in the development of whitish, nodular changes in the gastric body. These changes mainly consisted of intestinal metaplasia in microscopic findings. In the NG gastrectomy group, the cancer developed at a lower rate of incidence at the anastomotic site and in the gastric body (1 of 11 rats and 1 of 11 rats, respectively). Conversely, a higher incidence of cancer development (5 of 13 rats) in the gastric body was observed in the group that underwent NG gastrectomy with denervation. Furthermore, the denervation group showed a significant increase in the PCNA labeling index and a distinct increase in the staining of Alcian blue positive mucin in the mucosa of the gastric body. The cancers that developed in the gastric body showed horizontal growth and were accompanied by intestinal metaplasia. In contrast, the cancers that developed in the gastric stumps showed downward growth, and were always accompanied by adenocystic proliferation, but not intestinal metaplasia. CONCLUSIONS: Different processes of carcinogenesis in the gastric remnant are postulated after the surgery for gastric malignancies. The developed cancer is defined by its location and the gastric mucosal changes that developed at the time of gastrectomy.

Animals↗

PubMed1996

A neural cell-type-specific expression system using recombinant adenovirus vectors.

We demonstrated neural cell-type-specific gene expression using an adenovirus vector, which is useful for delivering foreign genes into quiescent neural cells. We produced eight recombinant replication-defective adenoviruses carrying the lacZ reporter gene driven by various promoters, including those of the L7/PCP2 gene (highly restricted expression in cerebellar Purkinje cells), and the myelin basic protein (in oligodendrocytes) gene. We demonstrated in vitro and in vivo promoter-driven, neural cell-type-specific gene expression by recombinant adenoviruses. The genes were transferred into these recombinant adenoviruses and expressed with high levels of efficiency in vitro and in vivo. In primary culture, the recombinant adenoviruses AdexL7-NL-LacZ and AdexMBP-NL-LacZ appeared to be expressed in a Purkinje cell and oligodendrocyte-specific manner. Introduction of 10(8) pfu of these viruses into the adult rat cerebellum by stereotactic injection yielded neural cell-type-specific expression without apparent toxicity to the animals. Thus, adenovirus vectors are useful for cell-type-specific therapeutic uses and in studies requiring neural cell-type-specific gene expression.

Adenoviruses, Human↗

PubMed1996

Epstein-Barr virus in Hodgkin's disease patients in Japan.

BACKGROUND: The association of Epstein-Barr virus (EBV) and Hodgkin's disease (HD) has been suggested by serologic, epidemiologic, and molecular biologic studies. The high level of EBV association with HD in the developing countries was discussed in relation to the high HD incidence in these areas. Japanese HD shows a distinct peak incidence in older adults. In contrast, Western HD shows a bimodal pattern, the first peak in young adulthood and a second peak in older patients. In the present study, the EBV association with HD in Japan was investigated, and the results were compared with those reported from industrialized and developing countries. METHODS: Fifty-seven patients with HD were studied for the presence or absence of the EBV genome by the polymerase chain reaction and in situ hybridization methods. Seven cases were excluded from the analysis for EBV because of poor preservation of nucleotides in the specimens. RESULTS: EBV genomes were detected in the Reed-Sternberg (R-S) cells of 32 of the 50 patients examined (64%). The EBV association was independently affected by histologic subtype (84% in mixed cellularity and 44% in others), sex (76% in males and 31% in females), and age (76% in patients aged 40 years and older and 38% in patients younger than 40 years of age; P < 0.01). High EBV association is found at the peak in older adults predominantly with mixed cellularity type. Previous studies revealed that the high EBV was associated with the older peak of the bimodal peaks in Western HD, and a unimodal peak in childhood in developing countries. The EBV subtype was predominantly type A, which is identical to the immunocompetent type of HD reported previously. CONCLUSIONS: The results of the current study, together with those reported previously, showed that the presence of the Epstein-Barr virus correlated with mixed cellularity type, age older than 40 years, and male sex.

Adolescent↗

PubMed1996

Effect of fentanyl citrate analgesia on glucose production following trauma in rats.

The postoperative hormonal milieu enhances glucose production. The objectives of this study were to determine whether fentanyl plus pentobarbital anesthesia reduced the excretion of stress hormones and whether this resulted in decreased glucose production following trauma. Male Sprague-Dawley rats were assigned into control and trauma. The trauma group was further subdivided into three groups according to the methods of anesthesia: T-1, pentobarbital (PB) alone; T-2, pentobarbital plus fentanyl (FE); and T-3, given PB during surgery and FE at the end of surgery. Glucose production was measured by a primed constant infusion of 3-3H-glucose. Fentanyl plus pentobarbital anesthesia prevented an increase in corticosterone levels in the plasma compared with in T-1 and T-3, 0.5 hr after the surgery. Fentanyl plus pentobarbital, anesthesia caused reductions of insulin and glucagon levels in the plasma and a decrease in catecholamines excretion in the urine. Glucose production was lower with FE+PB anesthesia than with PB alone (PB: 4.6 +/- 0.1 mg/kg/min vs PB+FE: 3.6 +/- 0.2 mg/kg/min, P < 0.05). However, fentanyl given at the end of surgery did not alter hormonal milieu and glucose production compared with pentobarbital alone. Blocking afferent neural stimuli from the wound and injury during the surgery is one approach to prevent an enhancement of postoperative glucose production.

Analgesia↗

PubMed1996

Difference between normal and WHHL rabbits in susceptibility to the adrenal toxicity of an acyl-CoA:cholesterol acyltransferase inhibitor, FR145237.

The adrenal toxicity of an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, FR145237, was investigated using Japanese White (normal) and low density lipoprotein (LDL) receptor deficient Watanabe heritable hyperlipidemic (WHHL) rabbits. In the normal rabbits, severe necrosis of the cells in the zona fasciculata and reticularis was observed 24 hr after intravenous injection of 3.2 mg/kg of FR145237, whereas no morphological changes could be found in the adrenal cells of the WHHL rabbits in spite of a higher plasma concentration of the drug. Since most of the FR145237 (87%) in the plasma of the WHHL rabbits was recovered in the LDL fraction 1 hr after intravenous injection of the drug (3.2 mg/kg), it was hypothesized that the delivery of the drug to the adrenal cells may be limited by the LDL receptor deficiency. However, the concentration of FR145237 in the adrenal gland of the WHHL rabbits (13.3 microg/g) was identical to that in the normal rabbits (13.6 microg/g). These results suggest that the susceptibility of the adrenal cells of the WHHL rabbits to the toxicity of FR145237 truly differs from that of normal rabbits, and that the WHHL rabbit may be a useful animal model for the investigation of the mechanisms of the adrenal toxicity of ACAT inhibitors.

Adrenal Cortex↗

PubMed1996

The significant effect of HLA-DRB1 matching on acute rejection in kidney transplants.

The object of the present study was to confirm the HLA-DRB1 matching effect on rejection crisis, its severity, and kidney graft survival based on genotyping. Ninety-four renal allografts were included in this study. DNA typing of HLA-DRB1 was performed by the polymerase chain reaction sequence-specific oligonucleotide method. The incidence of acute rejection within 6 months following transplantation, the frequency of OKT3 administration for steroid-resistant rejection, histopathological findings, and graft survival rate were compared between the DRB1-matched (n = 23) and DRB1-mismatched (n = 71) groups. Four acute rejections occurred in the DRB1-matched group (incidence; 17%) and 40 in the DRB1-mismatched group (56%). In the DRB1-matched group, the incidence of acute rejection was significantly less frequent than that of the DRB1-mismatched group (P < 0.005). In the DRB1-matched group, only one patient received OKT3 administration (4%), in contrast to 16 of 71 patients in the DRB1-mismatched group (23%). The use of OKT3 was significantly less frequent in the DRB1-matched group (P < 0.05). Histopathological findings from biopsy specimens showed no constant distribution of pathological grades of acute rejection according to DRB1 matching in the present study. The graft survival rate in the two groups did not differ significantly, but the graft survival rate in the DRB1-mismatched group had a tendency to decrease as the grafts survived longer. In conclusion, the results of the present study confirm that HLA-DRB1 matching has marked beneficial effects on kidney transplants through reduction of the acute rejection rate and decrease of the severity of rejection, and suggest that improvement of graft survival will be obtained through kidney allocation to a DRB1-matched recipient.

Acute Disease↗

PubMed1996

Analysis of results of surgery performed over a 20-year period on 500 patients with cancer of the thoracic esophagus.

This study was conducted to examine the long-term outcome of 500 patients who underwent surgery for cancer of the thoracic esophagus during the past 20 years. Favorable results were obtained with postoperative adjuvant radiation and chemotherapy and there were no surgical deaths in the last 5 years. The mortality rate decreased from 17% prior to 1980 to 5% between 1981 and 1993, this being most probably attributable to the decreased incidence of suture leakage. With respect to changes in surgical techniques, during the initial years we performed intrathoracic anastomosis, after which sternal manubrium resection with anterior mediastinal esophagogastrostomy was carried out. Subsequently, we invented a technique for performing esophagogastrostomy via the posterior mediastinum. The posterior mediastinum was selected as the most physiologic route, based on measurement of tissue oxygen tension. Using blood flow determinations obtained by laser-Doppler velocimetry, we concluded that the effectiveness of thicker gastric tubes was superior to that of thin tubes. Esophagogastrostomy was performed in a shallow field in the cervical region, with the anastomosis ultimately positioned in the superior mediastinum and covered with mediastinal pleura.

Anastomosis, Surgical↗

PubMed1996

Localized right ventricular structural abnormalities in patients with idiopathic ventricular fibrillation: magnetic resonance imaging study.

Lethal arrhythmias, including ventricular tachycardia and ventricular fibrillation, may occur in the absence of apparent morphological abnormalities. However, a recent study using magnetic resonance imaging (MRI) has suggested that localized, minor structural abnormalities of the right ventricle are responsible for right ventricular outflow tract ventricular tachycardia in a number of patients. We demonstrated regional wall thinning and systolic dyskinesia of the right ventricle by MRI in two patients with idiopathic ventricular fibrillation in whom other cardiac imaging modalities failed to show abnormalities. This finding implies that minor structural abnormalities do exist in patients with so-called idiopathic ventricular fibrillation.

Adult↗

PubMed1996

Inhibition of platelet aggregation by endocardial endothelial cells.

We assessed the anti-platelet properties of endocardial endothelial cells (EECs) by measuring platelet aggregation after brief interaction with EECs isolated from the right ventricles of porcine hearts. Platelet aggregation in response to thrombin was significantly inhibited by brief incubation of platelet suspensions over EEC monolayers. Pretreatment of EECs with indomethacin restored platelet reaction but that with L-NAME and hemoglobin (Hb) did not. The PGI2 content of platelet suspensions after interaction with cultured EECs was significantly correlated with the inhibition of platelet aggregation. These results suggest that EECs inhibit platelet aggregation by releasing PGI2.

Animals↗

PubMed1996

Depolarization with high-K+ causes Ca(2+)-independent but partially Cl(-)-dependent glutamate release in rat hippocampal slice cultures.

We studied the neurotoxic glutamate release induced by high-K+ depolarization in rat hippocampal slice cultures. Depolarization with 90 mM K+ for 30 min caused a significant, three-fold increase in glutamate release. This release was not inhibited by removing extracellular Ca2+, but was significantly inhibited by replacement of extracellular Cl- with SO4(2-). These findings suggest that glutamate is released by mechanisms other than conventional vesicular release under the high-K+ condition.

Animals↗

PubMed1996

A nitric oxide-sensitive electrode: requirement of lower oxygen concentration for detecting nitric oxide from the tissue.

In order to directly detect nitric oxide (NO) liberated from isolated tissue, a practical and convenient method using a nitric oxide-sensitive electrode is described. To avoid the nonselective signal caused by ionic substances, the electrode was covered with three layers but remains permeable for gaseous substances. In a solution bubbled with 20% oxygen (pO2, approximately 150 mm Hg), administration of S-nitroso-N-acetyl-d, l-penicillamine (SNAP) at concentrations greater than 10(-7) mol/L elicited an electrode response. Based on a comparison with the chemical determination of NO released from SNAP, the electrode may be able to detect nitric oxide around nmol/L. At least 30 nmol NO per liter in anoxic conditions was reported to be detected by this electrode (Matsui, 1995). In a specially designed small chamber, the electrode was attached on the surface of endothelial side of the isolated aorta of the guinea pig. When carbachol was added to the chamber, the electrode responded when the solution was bubbled with 20% but not with 40% or 95% of oxygen, suggesting a much faster decomposition of nitric oxide in the presence of higher concentrations of oxygen. The electrode response to carbachol was abolished in the presence of NG-monomethyl-L-arginine or nitro arginine. These results suggest that the electrode method described in this manuscript is suitable for detecting nitric oxide liberated from isolated tissues when comparatively low oxygen levels are present in the physiological salt solution.

Animals↗

PubMed1996

Isolation and primary culture of rat cerebral microvascular endothelial cells for studying drug transport in vitro.

To establish the cerebral microvascular endothelial cell (CMEC) culture system for animals commonly utilized in in vivo studies, we developed a method for isolation and culture of rat CMECs, and the model system was used in preliminary in vitro transport experiments. The isolated rat brains were minced. After an incubation with dispase, a fraction of microvessels was obtained by the dextran gradient. The tissue was filtered and dissociated using collagenase/dispase. After the enzyme treatment, the microvessels were layered onto the top of Percoll gradient and centrifuged for purification. Specific enzyme activities of alkaline phosphatase and gamma-glutamyltransferase in the preparations gradually increased as the isolation process progressed. The isolated cells reached confluence after 5-7 days in culture. The cultured cells had Factor VIII-related antigen and an uptake of acetylated-low density lipoprotein labeled with 1,1'-dioctadecyl-3,3, 3',3'-tetramethyl-indocarbocyamine perchlorate (Dil-Ac-LDL). In the transport studies, thawed cells after several months under -80 degrees C were used. The cultured cells after the freezing preservation also had CMEC characteristics, the same as the cells seeded immediately after isolation. The permeability of [14C]-mannitol, an impermeable marker for blood-brain barrier, was considerably reduced when the cell monolayer was present. The transport of [3H]3-O-methyl-D-glucose was significantly inhibited by the unlabeled compound. Furthermore, 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation, significantly diminished the transport of [3H]L-proline. These results indicated that the cell monolayer obtained in the present study could be applicable to drug transport studies through the blood-brain barrier in vitro.

3-O-Methylglucose↗

PubMed1996

Measurement of airborne mite allergen exposure in individual subjects.

To evaluate the extent of personal exposure to airborne mite allergens, subjects were asked to carry a personal air sampler when in their houses. The level of Der 1 allergen trapped by the sampler was measured with a highly sensitive immunoassay. There were great variations in airborne Der 1 exposure in each subject. When used bedding was replaced with new allergen-free bedding, we detected a decrease in the allergen level. The use of new bedding seems to be an effective measure for reducing airborne mite allergen exposure.

Air Pollutants↗

PubMed1996

Reduction of adhesions with fibrin glue after laparoscopic excision of large ovarian endometriomas.

STUDY OBJECTIVE: To evaluate the effect of fibrin glue on the formation of adhesions after laparoscopic excision of endometriomas. DESIGN: Prospective case series. SETTING: Department of Obstetrics and Gynecology at a university-affiliated hospital. PATIENTS: Thirty women with ovarian cysts. INTERVENTIONS: In 10 women (16 cysts) we performed laparoscopic resection of endometriomas leaving the ovarian capsule open. Twenty patients (25 cysts) underwent laparoscopic removal of endometriomas and fibrin glue approximation of the ovarian capsule, as well as coating of serosal defects with the glue. At second-look laparoscopy 4 to 6 months after the initial surgery, postoperative adhesion formation was assessed according to the revised American Fertility Society classification. MEASUREMENTS AND MAIN RESULTS: The mean (+/- SEM) adnexal adhesion score in patients without fibrin glue was 8.6 +/- 2.2 at initial surgery and increased slightly to 12.6 +/- 2.6 at second-look laparoscopy. In patients treated with fibrin glue, the score decreased significantly from 10.9 +/- 1.4 to 7.8 +/- 1.3 (p <0.02). The decrease was most marked in women with endometriomas 5 cm or more in diameter and for those with a preoperative adhesion score of 8 or higher. CONCLUSION: Fibrin glue reduced postoperative adhesions after laparoscopic resection of endometriomas.

Endometriosis↗

PubMed1996

Different biodistribution of 99mTc-labelled chimeric mouse-human monoclonal antibody between athymic mice model and human.

Biodistribution of chimeric mouse/human monoclonal antibody against non-specific cross-reacting antigen (chNCA Ab) was studied in athymic mice and patients with metastatic bone disease. 99mTc-chNCA Ab showed a high labelling efficiency, stability and also a high binding ratio to human granulocytes. Since NCA showed cross-reactivity with carcinoembryonic antigen (CEA), animal experiments showed that 99mTc-chNCA Ab was accumulated in the xenografted tumour which expressed CEA, suggesting the preserved immunoreactivity of labelled materials. In the clinical study, injected 99mTc-chNCA Ab formed a high molecular weight complex immediately after intravenous administration and was trapped mainly in liver. The first-phase plasma half-life was 6.4 +/- 1.1 min. None of the patients showed adverse reaction or human antimurine or anti-chimeric antibody in their serum. 99mTc-chNCA Ab demonstrated remarkably different biodistribution between patients and the animal model and showed different pharmacokinetics from other murine and chimeric Abs reported previously. For safety HPLC analysis should be performed before clinical radioimmunodetection or radioimmunotherapy by incubating radiolabelled MAb with human serum under strict conditions.

Aged↗

PubMed1996

Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells.

In order to investigate the in vivo role of rheumatoid factor (RF), the effects of the administration of human monoclonal (m) IgM-RF and IgG-RF on the development of arthritis in mice were examined. The administration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups receiving RF (RF-enhanced arthritis). Skin ulcers were also observed in some of these RF-enhanced arthritis mice, whereas no such signs were observed in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increased CII-specific IgG antibodies in circulation, and the severity of arthritis correlated with the production of high titres of anti-CII antibodies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immunodeficient (SCID) mice with arthritis developed by the transfer of spleen cells from CII-immunized mice, prolonged the arthritis and enhanced the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients.

Adoptive Transfer↗

PubMed1996

A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C.

Interferon treatment reduces the serum level of hepatitis C virus (HCV) and improves inflammatory activity, but relapse is frequently observed. In an attempt to develop a new therapeutic strategy that may reduce relapse and cure the disease, we evaluated the effect of corticosteroid priming on lymphoblastoid interferon alfa in an open randomized clinical trial. The level of HCV RNA increased significantly during corticosteroid priming (from 5.60 [median] to 21.0 x 10(5) Eq/mL; P = .0004) but decreased to the pretreatment level 4 weeks after cessation of corticosteroid (7.0 x 10(5) Eq/mL; P = .07). Sustained normalization of alanine transaminase (ALT) level and virus clearance, confirmed by negative results for HCV RNA using reverse-transcription nested polymerase chain reaction (PCR), were observed over a period of 6 months in 8 of 19 (42.1%) corticosteroid-primed patients, compared with 6 of 19 patients (31.6%) treated with interferon only. A "rebound" of ALT after the withdrawal of corticosteroid was observed in only 2 of 19 patients primed with corticosteroid, but both showed sustained responses. Multivariate analysis for factors predictive of the sustained response indicated that HCV titers measured immediately before interferon therapy and HCV genotype were statistically significant (P = .006 and P = .025, respectively). Our results indicated that corticosteroid priming has a marginal benefit over treatment with interferon alone and that large-scale clinical trials are necessary to determine whether interferon with corticosteroid priming is more effective than interferon alone.

Adult↗

PubMed1996

Immunohistochemical study of estradiol, epidermal growth factor, transforming growth factor alpha and epidermal growth factor receptor in endometrial neoplasia.

In a total of 113 cases of endometrial neoplasm, we studied the immunohistochemical expression of estradiol (E2), epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and epidermal growth factor receptor (EGFR). Positive immunoreactivity of E2 was found in 61% of the neoplasms. E2 immunoreactivity correlated well with high histologic grade and early clinical stage. Positive immunoreactivity for EGF or EGFR was found in 25.6% or 53.1% of the neoplasms, respectively. However, this was unrelated to histologic grade or clinical stage. On the other hand, TGFalpha immunoreactivity was found in 67% of endometrial neoplasias and was correlated with poor histologic grade and advanced stage. Contingency tables indicated a significant negative association between the status of E2 and that of TGFalpha. Simultaneous expression of E2, EGF and EGFR, or E2, TGFalpha and EGFR was found in 6.8% and 15.9% of endometrial carcinomas, respectively. These results suggest that a predominant number of endometrial carcinomas escape autocrine/paracrine growth regulation by EGF and E2 or TGFalpha and E2, and that TGFalpha may be involved in the progression of endometrial carcinoma.

Adult↗