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Biomedical subjects

Y Morishima

Publications and source records attributed to Y Morishima.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese.

To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan.

Adolescent↗
PubMed1994

A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group.

We conducted a prospective, double-blind controlled study to determine the efficacy of a recombinant granulocyte colony-stimulating factor (G-CSF, 200 microgram/m2) starting daily from 2 days before an induction therapy until neutrophils recovered to above 1,500/microL or until 35 days after the therapy in 58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty-eight patients in the G-CSF group showed significantly faster recovery of neutrophils (P < .001) than 30 patients in the placebo group. The incidence of febrile episodes and of documented infections was almost the same in both groups. However, among 39 patients who did not show any infectious episodes during the 2-week period after the start of chemotherapy, the incidence of documented infections after the third week tended to be lower in the G-CSF group, but not statistically significantly. There was no evidence that G-CSF stimulated the growth of AML cells in the bone marrow during the 2-day period before the chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5-week period after the therapy. Fifty percent of patients in the G-CSF group and 37% in the placebo group had complete remission (CR). Although the rate was higher in the G-CSF group, the difference was not statistically significant (P = .306). There was no difference between the two groups in event-free survival of all patients and in disease-free survival of patients who had achieved CR.

Adolescent↗
PubMed1994

[Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank].

One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.

Adolescent↗
PubMed1994

[Coordination of unrelated bone marrow donors in the Tokai Bone Marrow Bank--psychological reactions of donors to donation].

The Tokai Bone Marrow Bank was established in 1989 and coordinated 1,415 patients with 3,000 HLA-A, B-typed donors. Of the 1,415 patients, 757 patients had HLA-A, B-identical donors, 206 patients had HLA-DR-identical donors, and 80 patients had MLC-compatible donors. Finally, 55 unrelated donor bone marrow transplantations were done. The most frequent reason of interruption in coordination was disagreement of donor's family. We sent several questions by mail around 1 month after the donation to 55 donors to analyze the psychological reactions of unrelated bone marrow donors to donation. Donors were generally quite positive about the donation. 92% of the donors felt it was worthwhile and no one felt it was not at all worthwhile. 73% of the donors would be willing to donate again in the future. 79% of donors would like to know the clinical course of the patient after the bone marrow transplantation. We hope that these results may be helpful in the development of the Japan Marrow Donor Program.

Bone Marrow↗
PubMed1993

Autologous BMT in high risk patients with CALLA-positive ALL: possible efficacy of ex vivo marrow leukemia cell purging with monoclonal antibodies and complement.

Autologous BMT (auto-BMT) has been conducted for 17 high-risk common ALL antigen (CALLA)-positive non-T cell type ALL patients. Ex vivo purging of leukemia cells from infused BM cells was performed using complement and three kinds of mouse monoclonal antibodies reactive to CALLA-positive leukemia cells: NL-1 (IgG2a), NL-22 (IgM), and HL-47 (IgM). Minimal residual leukemia cells in BM were examined by PCR method in Philadelphia chromosome (Ph1)-positive ALL cases. BCR/ABL chimeric transcript, which was positive in BM samples before purging, was shown to be absent after ex vivo purging in all three cases tested. Among four Ph1-positive cases transplanted in first CR, three cases survived in CR remission 77, 29 and 26 months after BMT, and one case died without relapse 4 months after BMT. The other four Ph1-negative cases transplanted in the first CR also remained in CR except one who relapsed. The results of minimal residual leukemia cell studies and clinical data indicate the effectiveness of our ex vivo leukemia cell purging method and auto-BMT in the early stage of CR for patients with high risk ALL.

Adolescent↗
PubMed1992

Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation.

Minimal residual disease (MRD) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients received BMT at the time of hematologic and cytogenetic remission. However, MRD was detected in 8 of 10 patients evaluated. Seven patients, including three who had MRD before BMT, continue to have a disease-free survival 5 to 64 months after BMT. Twenty-one specimens obtained from these patients at various times after BMT did not show MRD. In three patients, MRD detected just before BMT seems to be eradicated by BMT protocol. The other eight patients developed cytogenetic or hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus, this technique for the detection of MRD appears to be useful for the more precise assessment of various antileukemia therapies and for early detection of leukemia recurrence.

Adolescent↗
PubMed1992

Biological potency of a fluorinated vitamin D analogue in hypoparathyroidism.

Several in vivo experiments have revealed that a synthesized fluorinated analogue of vitamin D, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3) has a higher and longer-lasting biological activity than 1,25(OH)2D3 in calcium regulating actions. We evaluated the biological potency and the availability for clinical use of this compound in hypocalcemia associated with hypoparathyroidism. In an experimental setting, daily administration of 650 pmol/kg of 26,27-F6-1,25(OH)2D3 showed an equivalent effect to that of 3250 pmol/kg of 1,25(OH)2D3 in elevating whole blood ionized calcium levels in parathyroidectomized rats. Furthermore, an additional clinical study demonstrated that 0.5-1.5 micrograms/day of 26,27-F6-1,25(OH)2D3 were considered adequate maintenance doses in various types of hypoparathyroidism and that changes of medication to the same doses of 1,25(OH)2D3 resulted in prompt decline of urinary calcium excretion and of whole blood ionized calcium levels, and in recurrence of symptoms related to hypocalcemia. Although the mechanism responsible for the high potency of this analogue remains unclear, our experience confirms that 26,27-F6-1,25(OH)2D3 has higher biological activities in bone calcium mobilization and is more potent than 1,25(OH)2D3 in correcting hypocalcemia of hypoparathyroidism in a hospital setting.

Animals↗
PubMed1992

Syntheses and 5-HT2 antagonist activity of bicyclic 1,2,4-triazol-3(2H)-one and 1,3,5-triazine-2,4(3H)-dione derivatives.

A series of bicyclic 1,2,4-triazol-3(2H)-one and 1,3,5-triazine-2,4(3H)-dione derivatives with a 4-[bis(4-fluoro-phenyl)methylene]piperidine or 4-(4-fluorobenzoyl)piperidine group has been prepared and tested for 5-HT2 and alpha 1 receptor antagonist activity. Among the compounds prepared, 2-[2-[4-[bis(4-fluorophenyl)methylene]-piperidin-1-yl]ethyl]- 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (7b) had the most potent 5-HT2 antagonist activity, which was greater than ritanserin (2), while 7b did not show alpha 1 antagonist activity in vivo. The central 5-HT2 receptor antagonism was approximately 1/30 that of 2 when tested for the ability to block head twitches induced by 5-hydroxytryptophan. Compound 21b, 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6,7,8,9-tetrahydro- 2H- pyrido[1,2-a]-1,3,5-triazine-2,4(3H)-dione also displayed potent 5-HT2 antagonist activity. The compound had moderate alpha 1 receptor antagonism, and the potency inhibiting head twitches was about one-third that of ketanserin (1). These results indicate that 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrimidin-3(2H)-one and 6,7,8,9-tetrahydro-2H-pyrido-[1,2-a]-1,3,5-triazine-2,4(3H)-dione ring systems are useful components of 5-HT2 antagonists.

Animals↗
PubMed1992

Clinical characteristics of chronic cutaneous graft-versus-host disease in Japanese leukemia patients after bone marrow transplantation: low incidence and mild manifestations of skin lesions.

We investigated the incidence of chronic graft-versus-host disease (GVHD) and skin and oral lesions in chronic GVHD in 90 Japanese leukemia patients surviving over 100 days after bone marrow transplantation (BMT) from HLA-compatible siblings. The clinical characteristics of chronic cutaneous GVHD occurring in eight of these patients are summarized. There were some differences from previous reports in the USA and Europe. The incidence (8/29: 28%) of skin lesions in chronic GVHD was low in contrast to the previously reported high incidence (79-90%). Cutaneous manifestations in six out of eight patients with chronic GVHD tended to be mild, and lichen-planus-like eruptions in the skin and scleroderma-like lesions, which are well known as representative cutaneous manifestations of chronic GVHD, were rare. Furthermore, our statistical analysis indicated that there was no relationship between pretransplant total body irradiation and GVHD prophylaxis or acute GVHD and the onset of chronic cutaneous GVHD. The present study suggests that the differences from previous reports in the USA and Europe concerning chronic cutaneous GVHD may be attributable to differing genetic backgrounds in Japanese and western populations.

Acute Disease↗
PubMed1992

Bone marrow transplantation for chronic myelogenous leukemia in blastic phase using a phenotypically identical unrelated volunteer donor. Nagoya Bone Marrow Transplantation Group (NBMTG), Tokai Marrow Donor Bank (TMDB).

A 26-year-old male with chronic myelogenous leukemia in lymphoid blast crisis received a bone marrow transplant (BMT) from a phenotypically identical, mixed lymphocyte reaction (MLR)-weakly positive unrelated male volunteer donor. The volunteer was obtained from the Tokai Marrow Donor Bank (TMDB), which was established in Japan in 1989. This donor was selected from volunteer donors who were identical with our patient at the HLA-A,B loci, followed by matching at HLA-DQ, DR loci. On MLR testing, the donor's cells showed no response, but the patient's cells showed a low response to the donor's cells (relative response index 0.29). The patient showed rapid hemopoietic engraftment. He developed acute graft-versus-host disease (GVHD) with vesicle formation on palms and soles and mild liver damage, which were successfully treated with intravenous prednisolone 1 mg/kg per day. Although he also suffered from interstitial pneumonitis on day 64 and localized varicella-zoster infection on day 87, and has suffered from moderate stomatitis and dry skin characteristic of chronic GVHD, he is currently 22 months post-transplant with hematological remission and has a normal daily social life.

Adult↗
PubMed1992

Randomized study of individualized induction therapy with or without VCR, and of maintenance of 4 or 12 courses in adult AML: JALSG-AML87. Japan Adult Leukemia Study Group (JALSG).

We asked 2 questions in this study. First was the additional effect of VCR in induction therapy, and the second was the duration of maintenance therapy. Adult AML were treated by an individualized response-oriented induction therapy with behenoyl Ara-C 200 mg/m2 daily + 6MP 70 mg/m2 daily + prednisolone 40 mg/m2 on days 1-4 + DNA 40 mg/m2 on days 1-3 and additionally on days 7, 8, 11, 12 (for M3, DNR 50 mg/m2 daily) (BHAC-DMP) until bone marrow became severely hypoplastic with less than 5% of blasts. Patients were randomized to BHAC-DMP or BHAC-DMP + VCR 0.35 mg/m2 on days 1-4. After obtaining CR, 3 courses of intensive consolidation therapy were given together with I.T. MTX+Ara-C+PSL. Maintenance intensification therapy was randomized to either 4 or 12 courses given every 2 months. Patients of age greater than or equal to 60 received about 2/3 reduced doses. From June 1987 to Sept. 1989, 265 consecutive adult AML were registered from 19 institutions and 258 were evaluable. Age ranged from 15 to 79 (med., 48). Out of 258, 200 (77.5%) achieved CR (80% in 209 of age less than 60 and 65% in 49 of age greater than or equal to 60). Unexpectedly, addition of VCR reduced the high CR rate of BHAC-DMP significantly (84% to 70%, p = 0.007). At the median follow-up of 37 mo., overall survival is 37%, and event-free survival (EVS) 27%. Survival, continuing CR and disease-free survival (DFS) rates of 200 CR cases are 45%, 40% and 35%, respectively. Patients received 12 courses of maintenance therapy showed better DFS (P = 0.0555). The VCR group had significantly worse EFS. By multivariate analysis, significant prognostic factors for the achievement of CR were age less than 60, PS 0-2 and no addition of VCR. Significant factors for longer DFS were induction of CR by one course, FAB M3 or M5 and age less than 50. The present multi-institutional study confirmed the high CR rates of the response-oriented individualized therapy reported from several centers in Japan, but failed to support an additional effect of VCR reported from one center.

Acute Disease↗
PubMed1991

Prevention by DV-7028, a selective 5-HT2 receptor antagonist, of the formation of coronary thrombi in dogs.

STUDY OBJECTIVE: The aim was to determine the role of 5-HT derived from activated platelets in the formation of intracoronary thrombi in dogs. DESIGN: 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. The effects of intravenous DV-7028, a selective 5-HT2 receptor antagonist (bolus of 0.1 mg.kg-1, followed by 0.3 mg.kg-1.h-1 by infusion), and intravenous aspirin (1 mg.kg-1, followed by 3 mg.kg-1.h-1) in this experimental thrombus model were examined. SUBJECTS: 43 dogs of either sex were used. In experiment A, DV-7028 (n = 12) or saline (n = 11) was given. In experiment B, aspirin (n = 10) or saline (n = 10) was given. MEASUREMENTS AND MAIN RESULTS: DV-7028 significantly reduced the formation of coronary thrombi by 51% and attenuated the decrease in coronary blood flow without affecting systemic blood pressure and heart rate. There was a significant relationship between the thrombus weight and the decrease in coronary blood flow (p less than 0.005). Aspirin failed to prevent the formation of coronary thrombi. CONCLUSION: The results suggest that 5-HT is involved in the platelet thrombosis and that inhibitory effect of DV-7028, a 5-HT2 receptor antagonist, on coronary thrombus formation was superior to that of aspirin.

Animals↗