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Biomedical subjects

Y Morishima

Publications and source records attributed to Y Morishima.

At least 145 records · Page 8Linked to original sources
PubMed1997

Overexpression of cyclin D1 in rat esophageal carcinogenesis model.

Overexpression of cyclin D1 in human esophageal carcinomas has been well documented. The aim of the present study was to assess the expression of cyclin D1 in different types of esophageal epithelial lesions induced by N-nitrosomethylbenzylamine (NMBA) in rats. A total of 30 rats received s.c.-injections, five times/week, of 1.0 mg/kg NMBA for a period of 5 weeks followed by the same dose once per week for another 10 weeks. An additional 15 rats were given saline and used as controls to provide normal epithelium. The tumor incidence was 100% at the termination point of 21 weeks. Seventeen rats (57%) showed nuclear staining for cyclin D1, with a great variation in the intensity, as demonstrated by using an immunohistochemical technique. The cyclin D1 positive indices were in the range of 0% to 60% of the individual cells. Negligible staining was observed for normal esophageal epithelium, with a minimal increase in hyperplastic and dysplastic lesions. A significant elevation of cyclin D1 levels was observed in tumors. However, no significant differences were found between papillomas and carcinomas. The immunohistochemical results were confirmed by western blotting analysis. Tumors, papillomas and carcinomas overexpressing cyclin D1 had elevated proliferating cell nuclear antigen (PCNA) indices (P < 0.05). The correlation coefficient of overexpressions of PCNA and cyclin D1 was r = 0.7 for papillomas, but only r=0.3 for carcinomas. The study thus provides strong evidence of relatively early overexpression of cyclin D1 during tumorigenesis in the present rat esophageal model. Cyclin D1 expression is not simply a direct consequence of increase cell proliferation.

Animals↗
PubMed1997

Somatic hypermutations in the VH segment of immunoglobulin genes of CD5-positive diffuse large B-cell lymphomas.

De novo CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBL) has recently been identified as constituting a homogeneous subgroup with distinct clinicopathologic and genotypic characteristics, but its origin remains to be elucidated. Previous studies by sequence analysis of the variable region of the immunoglobulin heavy chain (VH) have shown that CD5+ B-cell malignancies such as mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia (B-CLL) cells represent pre-germinal center (pre-GC) stage B cells in contrast with the post-GC stage of most DLBLs, which show somatic hypermutations in VH genes. In the present study, we investigated the VH sequence of de novo CD5+ DLBL to clarify whether CD5+ DLBL represents the pre-GC stage, as do other CD5+ B-cell malignancies, or the post-GC stage, as is typical of DLBL. All eight cases (four CD5+ DLBL and four CD5-negative (CD5-) DLBL) examined by us showed somatic hypermutations in the VH segment and two of the CD5- DLBL cases showed intra-clonal diversity, suggesting that CD5+ DLBLs were derived from the same maturation stage as CD5- DLBL, but were distinct from the other indolent CD5+ B-cell lymphomas of B-CLL and MCL. These data suggest that de novo CD5+ DLBLs do not merely lie within a continuous spectrum with B-CLL and MCL, but represent a biologically distinct variant within the diagnostic framework of diffuse large B-cell lymphoma.

Adult↗
PubMed1997

[The effects of preventive regimens for the prophylaxis of infection after bone marrow transplantation].

The effects of regimens on the prevention of infection in 42 adult leukemia patients receiving bone marrow transplantation was analyzed. Standard risk patients (transplantation in 1st remission of acute leukemia and chronic phase of chronic myelogeneous leukemia received marrow from HLA compatible sibling or autologous marrow) showed shorter febrile days than high risk patients (transplantation in more advanced stage of leukemia and transplantation from unrelated donor), 1.33 mean days vs. 4.93 mean days respectively. Poorer intake of non-absorved antibiotics resulted in higher rate of bacterial colonization in stool after transplantation. And that, the degree of gut sterilization correlated with the duration of febrile days during the period of less than 100/microliter peripheral neutrophil count in high risk patients. Thus, prophylactic regimens of infection in bone marrow transplantation should be considered according to the risk of patient, that is, more practical and complete prophylaxis in risk patients and more conventional one in standard risk patients.

Adult↗
PubMed1997

[Inoperable esophageal carcinoma managed by combined chemotherapy (CBDCA, 5-FU and VDS) and radiotherapy].

Eleven inoperable patients with advanced esophageal carcinoma were treated with chemotherapy (carboplatin, 5-FU, vindesine) and concomitant radiotherapy. Two patients (T2) received this treatment due to their poor general condition and refusal of operation, and 9 patients for infiltration of tumor into the adjacent organs (T4). Administration of carboplatin (30 mg/body) and 5-FU (250 mg/body) together with radiotherapy (1.8 Gy/d) for 5 days a week was performed. This chemoradiation therapy was carried out for 5 consecutive weeks. In addition, vindesine (1-3 mg/body) was administered in the 1st and 4th week. After evaluation, endoscopic balloon dilatation was performed in 6 patients with stenosis of the esophagus. The general response rate was 80%. CR was noted in 2 patients of T2 but 1 patient of T4 developed severe leucopenia and immunosuppression, and died of septic MOF. All but the MOF case could take enough food orally following the endoscopic dilatation. The 1-year survival rate in the T4 group (45%) was significantly better than the non-treatment group (0%). In conclusion, this treatment is beneficial for patients with inoperable esophageal carcinoma to obtain a satisfactory QOL and survival rate.

Aged↗
PubMed1997

Antithrombotic and hemorrhagic effects of DX-9065a, a direct and selective factor Xa inhibitor: comparison with a direct thrombin inhibitor and antithrombin III-dependent anticoagulants.

(+)-2S-2-[4-[[(3S)-1-Acetimidoyl-3- pyrrolidinyl]oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate (DX-9065a) is an antithrombin III (AT III)-independent and selective inhibitor of activated blood coagulation factor X (FXa). The aim of the present study was to compare the antithrombotic and hemorrhagic effects of DX-9065a with a direct thrombin inhibitor and AT III-dependent anticoagulants in rat models of thrombosis and bleeding. Rats were administered intravenously DX-9065a (0.1-1 mg/kg/h), argatroban (0.1-1 mg/k/h), low molecular weight heparin (25-100 anti-XaU/kg/h), unfractionated heparin (25-100 anti-XaU/kg/h) or Orgaran (30-300 anti-XaU/kg/h) for 1 h. DX-9065a dose-dependently inhibited both thrombus formation and elevation in plasma thrombin-AT III complex (TAT) level in a copper wire-inserted arteriovenous (AV) shunt model in rats. The dose required for 50% inhibition of thrombus formation was 0.27 mg/kg/h. DX-9065a did not prolong transection bleeding time up to 7.78 mg/kg/h. Argatroban and AT III-dependent anticoagulants also inhibited both thrombus formation and TAT elevation, but prolonged bleeding time at a slightly higher dose than the effective dose. These results suggest that direct and selective inhibition of factor Xa by DX-9065a is preferable for the treatment of thrombosis in the aspect of lack of compromising primary hemostasis.

Animals↗
PubMed1996

Lack of a kinetic interaction between fluconazole and mexiletine.

OBJECTIVE: To investigate the effect of fluconazole on the kinetics of mexiletine. METHODS: Six healthy male volunteers participated in a crossover study. On the 1st day, the subjects received 200 mg mexiletine alone. On days 2-7 they received 200 mg fluconazole orally, and on day 8 they received 200 mg mexiletine and 200 mg fluconazole concomitantly. In a third phase two subjects received 400 mg fluconazole daily. RESULTS: No differences in concentrations were observed between the three phases. The area under the concentration curves (AUC) after administration of mexiletine alone and in combination with fluconazole 200 mg/day were 6.63 and 7.31 micrograms.h.ml-1, respectively. CONCLUSION: These findings suggest that fluconazole does not inhibit mexiletine metabolism.

Adult↗
PubMed1996

Serum thrombopoietin level after allogeneic bone marrow transplantation: possible correlations with platelet recovery, acute graft-versus-host disease and hepatic veno-occlusive disease. Nagoya Bone Marrow Transplantation Group.

Thrombopoietin (TPO) is a growth and differentiation factor for megakaryocytes and platelets. An ELISA was developed for measuring TPO concentrations in human sera. The mean +/- S.D. of TPO level obtained in 29 control subjects was 0.87 +/- 0.35 fmol/ml. We measured the TPO level in 36 patients after allogeneic bone marrow transplantation (BMT) and determined the relationship between blood levels of TPO and changes in the circulating platelet mass. In general, a reciprocal relationship was observed between TPO and platelet count (r = -0.609, P < 0.0001; n = 165). With the decrease in the platelet mass after myeloablative therapy, the TPO level increased proportionally and peaked during the platelet nadir. The peak concentration of TPO ranged from 20-50 fmol/ml. The TPO level decreased with the normalization of the platelet mass. In contrast, the TPO level decreased during acute graft-versus-host disease (GVHD) in several patients. Furthermore, the TPO level was significantly lower in the patients with hepatic veno-occlusive disease (VOD) than in the patients after BMT without GVHD and VOD in the samples of less than 50000/microliters platelets (P < 0.005). These findings suggest that in the patients given allogeneic BMT, TPO has an important role in the physiologic regulation of platelet production and that liver damage due to acute GVHD and VOD may decrease the TPO level.

Acute Disease↗
PubMed1996

Increased contribution by myofibrillar protein to whole-body protein breakdown according to severity of surgical stress.

A study was conducted to clarify the contribution by myofibrillar protein to whole-body protein breakdown in surgically stressed patients. Thirteen patients who underwent esophagectomy (group E) and 22 who underwent gastric or colorectal operation (group GC) were studied. Patients were all male and younger than 65 y old. Whole-body protein breakdown was determined using constant infusion of 15N-glycine. Urinary excretion of total catecholamines and 3-methylhistidine (3-MH) were measured. Amino acid composition of femoral arterial and venous blood was also analyzed. All the patients were fed exclusively by total parenteral nutrition providing 1.5 g protein and 40 kcal.kg-1.d-1 throughout the study. Whole-body protein breakdown increased significantly in group E (P < 0.01) and group GC (P < 0.05) on the 3rd postoperative day. The increase was significantly greater in group E than group GC (P < 0.01). Urinary excretion of 3-MH also increased significantly in group E (P < 0.01) and in group GC (P < 0.01) on the 3rd postoperative day. The increase was also greater in group E than group GC (P < 0.01). The ratio of urinary 3-MH excretion to whole-body breakdown protein (mumol/g), which is a indicator for the contribution of myofibrillar protein to the whole-body protein breakdown, increased significantly from 0.84 +/- 0.30 of preoperative value to 1.79 +/- 0.38 in group E (mean +/- SD; P < 0.01) and 1.42 +/- 0.18 in group GC (P < 0.05) on the 3rd postoperative day. This ratio was significantly higher in group E (P < 0.05). Furthermore, the ratio of myofibrillar to whole-body protein breakdown correlated significantly with urinary excretion of total catecholamines (r = 0.546; P < 0.01). Therefore, the contribution of myofibrillar protein to whole-body protein breakdown increased proportionately with the severity of surgical stress. On the other hand, femoral-arteriovenous differences of BCAA, Ala, Gln, Tyr, and Phe correlated significantly with the urinary excretion of 3-MH. These data suggest that skeletal muscle protein degradation is proportional to the breakdown of total myofibrillar proteins and both correlate with the severity of stress. From these data, it may be suggested that the contribution of skeletal muscle to whole-body protein catabolism is increased postoperatively, and that the increase is correlated with the severity of surgical stress.

Alanine↗
PubMed1996

Analysis of 55 transplantations from unrelated volunteer donors facilitated by Tokai Marrow Donor Bank.

In October, 1989, the Tokai Marrow Donor Bank (TMDB) was established through the cooperation of patients' families, the branches of blood centers of Japanese Red Cross and the hematologists' group in Tokai Area (Aichi, Shizuoka, Gifu and Mie Prefectùres) in Japan to facilitate the procurement of suitable marrow from unrelated volunteer donors for patients lacking related donors. The number of human leukocyte antigen (HLA)-A, B typed donors totaled 3,083 and the number of patients registered for donor search totaled 1,415 by June 1992, when the activities of TMDB were transferred to the newly created Japan Marrow Donor Program (JMDP), and 55 transplanations from unrelated donors facilitated by TMDD were performed.

Adolescent↗
PubMed1996

[Invasive thymoma associated with pure red cell aplasia and lung cancer].

A 71-year-old man was admitted to our hospital with vertigo and general fatigue. Examination of his blood and bone marrow showed pure red cell aplasia. His chest X-ray film revealed an anterior mediastinal mass and a nodular shadow in the right lower lobe. Extended thymothymectomy and right lower lobectomy were done. The mediastinal mass appeared to be an invasive thymoma and the nodular shadow in the right lower lobe proved to be from an adenocarcinoma. The patient was treated with radiation and steroids. Thymoma, pure red cell aplasia, and lung cancer had not recurred and he was alive and well as of 2 years after surgery.

Adenocarcinoma, Papillary↗
PubMed1995

Species differences in anticoagulant and anti-Xa activity of DX-9065a, a highly selective factor Xa inhibitor.

Activation of the blood coagulation cascade results in the formation of factor Xa (FXa) in either its intrinsic or extrinsic pathways, which in turn converts prothrombin to thrombin. We recently described the synthesis and characterization of DX-9065a, a highly selective FXa inhibitor, as an orally active anticoagulant agent (1). Although DX-9065a potently inhibited human FXa (2), a much larger dosage was required to inhibit thrombus formation in a rat thrombosis model (3): The plasma concentration of DX-9065a after administration of a dose which reduced thrombus formation by 50% in rats was in the microM range, or 40 times higher than the Ki value for FXa. From this, several assumptions arise, namely that an unknown mechanism other than FXa inhibition contributes to the antithrombotic effect of DX-9065a, or that the efficacy of DX-9065a differs among species. However, as the anticoagulant effect of DX-9065a was closely consistent with anti-Xa activity in plasma and as DX-9065a inhibited only FXa activity (2), the former assumption could be disregarded. To clarify the latter, we examined the inhibitory effect of DX-9065a on FXa from several animal species and its anticoagulant effect ex vivo in these species. Further, we also compared the anticoagulant effect of DX-9065a in plasma from each species with that of NAPAP, a benzamidine-derived direct thrombin inhibitor (4).

Animals↗
PubMed1995

Chromosomal loci of 50 human keratinocyte cDNAs assigned by fluorescence in situ hybridization.

The chromosomal loci of expressed genes provide useful information for a candidate gene approach to the genes responsible for genetic diseases. A large set of randomly isolated cDNAs catalogued by partial sequencing can serve as a resource for accessing and isolating these disease genes. Using fluorescence in situ hybridization, we examined the chromosomal loci of 217 human keratinocyte-derived cDNAs, with independent novel sequence tags at the 3' end region. Among them, we determined the loci of 50 cDNAs. Single-pass sequencing of these from the 5' ends indicated that 39 cDNAs still can be produced for new genes. These cDNAs with identified chromosomal loci are powerful tools that can be used to help elucidate the genes responsible for hereditary skin disorders.

Chromosome Mapping↗
PubMed1995

Evidence that 5-HT2A receptors are not involved in 5-HT-mediated thermoregulation in mice.

To determine the role of 5-hydroxytryptamine2A (5-HT2A) receptors in 5-HT-mediated thermoregulation in mice, we studied the effects of a 5-HT2A receptor agonist and 5-HT2A receptor antagonists on the body temperature, and the effects of selective 5-HT2A receptor and nonselective 5-HT receptor antagonists on hypothermia induced by 5-hydroxytryptophan (5-HTP). (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A receptor agonist, did not change body temperature in mice at doses of 1 and 5 mg/kg, intraperitoneally (IP), which induced head twitch response. Three 5-HT2A receptor antagonists, ketanserin (1 mg/kg, orally), ritanserin (1 and 10 mg/kg, orally), and DV-7028 (10 mg/kg, orally), also failed to alter body temperature, although these three 5-HT2A receptor antagonists at > or = 1 mg/kg, orally, inhibited head twitch response induced by 5-HTP (200 mg/kg, IP), a precursor of 5-HT. Ketanserin (1 mg/kg, orally), ritanserin (1 and 10 mg/kg, orally), and DV-7028 (10 mg/kg, orally) did not inhibit hypothermia induced by 5-HTP (200 mg/kg, IP). A nonselective 5-HT receptor antagonist, methysergide (1 mg/kg, subcutaneously), attenuated hypothermic response to 5-HTP. These results suggest that in mice, 5-HT2A receptors are unlikely to be involved in 5-HT-mediated thermoregulation.

Analysis of Variance↗
PubMed1995

Failure of aspirin and diltiazem to prevent the formation of acute coronary thrombi in dogs.

The aim of the present study was to determine the efficacy of aspirin and diltiazem in preventing the formation of coronary thrombi in dogs. Canine coronary thrombi were produced by inserting a small catheter filled with collagen powder into the endothelial-injured, partially occluded left anterior descending coronary artery. Neither aspirin (bolus of 30 mg/kg, followed by 100 mg/kg/h by infusion), nor diltiazem (0.1 mg/kg, followed by 0.3 mg/kg/h by infusion) prevented the formation of coronary thrombi. The mortality in aspirin group was significantly higher than that in control and diltiazem groups. These results indicate that aspirin and diltiazem do not inhibit thrombus formation in the canine model of coronary thrombosis.

Animals↗
PubMed1995

[Indication of allogeneic bone marrow transplantation (BMT) from HLA identical sibling in adult acute myeloblastic leukemia--comparative study of BMT and chemotherapy in patients with the first remission state. Nagoya BMT Group. Japan Adult Leukemia Study Group].

The indication of allogeneic bone marrow transplantation (BMT) from HLA identical siblings during the first remission of acute myeloblastic leukemia was discussed according to the results of BMT and chemotherapy study groups. The comparison of disease free survival between both groups was done, after selection biases such as risk factors and time of BMT were adjusted by multivariate analysis or matched-pair analysis. In conclusion, patients with more than one high risk factors for leukemia relapse, that is, high peripheral white blood cell count (PBC) (> 20,000/cmm) at diagnosis or more than two remission induction courses should be considered for BMT, and the indication of treatments for patients with no high risk factors should be determined depending on situations of the disease and patient's intention.

Adult↗
PubMed1995

[A preliminary analysis of unrelated marrow transplantations facilitated by the Japan Marrow Donor Program (JMDP)].

Between January 1993 and June 1994, the JMDP facilitated marrow donations from unrelated donors for 171 patients with malignant and non-malignant disorders. The median age of the patients was 21 years. All patients received marrow from phenotypically HLA -A, -B, -DR identical donors. About half of the patients wrer treated with total body irradiation (TBI)-containing regimens and about 80% of the patients received short-courses methotrexate and cyclosporine for graft-versus-host disease (GVHD) prophylaxis. Eight out of 171 patients, (4.7%) had graft failure and 63 out of 144 patients (44%), who survived for more than 30 days posttransplant, developed grade II to IV acute GVHD. The incidence of chronic GVHD was 47% (extensive form; 27%); most of them were progressive/quiscent type. The incidence of moderate to severe acute GVHD was higher than that observed in sibling transplants. On the other hand, the incidence of chronic GVHD was similar to that observed in sibling transplants. Overall survival at 1.5 years posttransplant was about 50% with no significant differences between diseases. The age correlated significantly with the survival in standard risk leukemia but not in high-risk leukemia. Despite the risk of graft failure and acute GVHD, this preliminary analysis demonstrates that transplantation of marrow from unrelated donors can be an effective treatment for certain hematologic disorders.

Acute Disease↗
PubMed1995

[Effects of insulin-like growth factor-I in burned rats].

Effect of insulin-like growth factor-I (IGF-I) on protein metabolism was investigated in burned rats receiving TPN. Twenty-six male SD rats were divided into two groups. IGF-I was administered to group IGF (IGF-I group, n = 14), but not to group C (Control group, n = 12). Loss of body weight after burn in group IGF was significantly lower than group C (p < 0.01). Cumulative nitrogen balance for 2 postburn days in group IGF was significantly higher than group C (p < 0.01). Rate of whole body protein turnover, synthesis and breakdown increased significantly in group IGF compared with group C. On the other hand, blood glucose was decreased significantly in group IGF (p < 0.05). Water balance made no significant difference between two groups. In group IGF, weight of the spleen, kidney, small intestine and colon increased significantly. Fractional synthesis rate and protein content of mucosa of the small intestine were significantly higher in group IGF than group C. From the histological point of view, mucosal layer was thickened and hyperplastic. Catabolism and surgical diabetes are caused in the surgical stress, and the administration of IGF-I are thought to be effective for improvement of those conditions. And IGF-I has the most remarkable effect on the small intestine of all organs studied in our experiment.

Animals↗