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Biomedical subjects

Y Morishima

Publications and source records attributed to Y Morishima.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1995

Inhibition by nitroglycerin of canine platelet aggregation and cyclic flow reductions in stenosed coronary arteries.

The aim of this study was to investigate the hypothesis that the action of nitroglycerin on acute coronary arterial diseases is due to the inhibition of platelet aggregation. Anesthetized open chest beagle dogs under artificial respiration were used. Cyclic flow reductions were induced by partial occlusion of the left anterior descending coronary artery at the site of endothelial injury. Nitroglycerin (20 mu g/kg followed by 3 mu g/kg/min, i.v.) attenuated the frequency and severity of cyclic flow reductions but did not recover the reduced coronary blood flow to baseline. Nitroglycerin completely abolished cyclic flow reductions in 3 of 7 animals. In other animals, intravenous injection of the same dose of nitroglycerin inhibited ex vivo platelet aggregation evoked by adenosine diphosphate (ADP, 10 mu M). However, nitroglycerin failed to suppress the platelet aggregation induced by a combination of ADP (1 mu M) with 5-hydroxytryptamine (5-HT, 1 mu M). In other experiments, diltiazem (calcium antagonist; 0.1 mg/kg, i.v.) did not affect cyclic flow reductions, and DP-1904 (inhibitor of thromboxane A2 synthetase; 1 mg/kg, i.v.) completely abolished cyclic flow reductions in 6 of 7 animals. These results indicate that nitroglycerin can inhibit cyclic flow reductions in part by attenuating the action of ADP on platelet aggregation, and that nitroglycerin is less potent than thromboxane A2 synthetase inhibitor in this model.

Animals↗
PubMed1994

Cataloging of the genes expressed in human keratinocytes: analysis of 607 randomly isolated cDNA sequences.

The partial nucleotide sequences of 607 cDNAs randomly isolated from a cDNA library of cultured human epidermal keratinocytes were determined by single pass sequencing. Homology search of the sequences to the non-redundant nucleotide databases revealed that 27% of the cDNAs matched registered human-or non-human genes encoding not only keratinocyte specific genes, but also a variety of functional proteins, the expression of which had not been identified in keratinocytes. Non-matching cDNAs covering 49% of the cDNAs were not homologous even to ESTs from other organs, suggesting that these cDNAs include novel genes expressed in the cells. The large scale sequencing of keratinocyte cDNAs provides a useful molecular source for research into biology and diseases of the skin.

Animals↗
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

The involvement of polyamines in the activation of vitamin D receptor from porcine intestinal mucosa.

In the intracellular process of the action of calcitriol, vitamin D receptor is thought to undergo some kind of physiochemical change, called activation, before the receptor binds to the vitamin D response element of the gene. In this paper, the effects of polyamines and their analogues on the sedimentation properties of vitamin D receptor prepared from porcine intestinal mucosa, and on DNA binding activity of the receptor, were studied. In sucrose density gradient analysis, polyamines decreased the sedimentation coefficient of vitamin D receptor in a dose-dependent fashion. Polyamines increased DNA binding activity of vitamin D receptor dose-dependently. These findings show that polyamines can activate vitamin D receptor in vitro. Among naturally existing polyamines, spermidine and spermine, but not putrescine, were effective within their physiological intracellular concentrations, suggesting that both spermidine and spermine can activate vitamin D receptor in vivo as well. Sucrose density gradient analysis using various kinds of polyamine analogues having various numbers of cations showed that the number of cation of polyamines is important for the efficiency to change the sedimentation coefficient of vitamin D receptor, and that the distance between two cationic charges does not play an important role.

Animals↗
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

Long persistent bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia without clinical relapse: a study of 64 patients.

We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had > or = 1 negative PCR result < or = 1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had > or = 1 positive PCR result > or = 1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the t-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P < .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.

Adolescent↗
PubMed1993

Impairment of cefdinir absorption by iron ion.

The effect of iron ion on the absorption of cefdinir, a new oral cephalosporin derivative, was evaluated in healthy male volunteers in a randomized three-way crossover study. The subjects received 200 mg cefdinir alone, 200 mg cefdinir and two tablets of iron ion concomitantly, and two tablets of iron ion preparation 3 hours after 200 mg cefdinir administration. The area under the concentration curve [AUC(0-12)] of cefdinir with concurrent iron was significantly smaller than that with cefdinir alone (mean +/- SD, 0.78 +/- 0.38 versus 10.3 +/- 1.35 micrograms.hr/ml). While there were no differences in AUC(0-3) between drug alone and drug with iron 3 hours later, the AUC(3-12) with delayed iron was significantly smaller than that of cefdinir alone (4.60 +/- 1.54 versus 8.03 +/- 1.72 micrograms.hr/ml). These findings suggest that the mechanism of interaction between cefdinir and iron ion preparation is the formation of a chelation complex and that this complex probably restricts gastrointestinal absorption.

Adult↗
PubMed1993

Combined effect of the 5-HT2 receptor antagonist DV-7028 and aspirin or heparin on coronary cyclic flow reductions in dogs.

OBJECTIVE: The aim was to study the combined effect of DV-7028, a selective 5-hydroxytryptamine2 receptor antagonist, and aspirin or heparin on cyclic flow reductions in the canine coronary artery. METHODS: Anaesthetised open chest beagle dogs under artificial respiration were used. Cyclic flow reductions were induced by partial occlusion of the left anterior descending coronary artery at the site of endothelial injury. After induction of cyclic flow reductions, test drugs were given to the animals intravenously. RESULTS: DV-7028 (0.1 mg.kg-1) reduced the frequency of cyclic flow reductions by 77% and improved the nadir of coronary blood flow velocity that indicated the severity of cyclic flow reductions. Also, aspirin (1 or 3 mg.kg-1) or heparin (200 U.kg-1) attenuated the cyclic flow reductions. In experiments with drug combinations, DV-7028 was given to animals that had already received aspirin (1 mg.kg-1) or heparin (200 U.kg-1). DV-7028 (0.1 mg.kg-1) completely abolished the cyclic flow reductions remaining after aspirin treatment in three of four animals. Heparin inhibited the cyclic flow reductions in one of five animals and the addition of DV-7028 abolished the remaining cyclic flow reductions in the other four animals. After combined injection of DV-7028 with aspirin or heparin, the coronary blood flow with cyclical reductions returned to the baseline. CONCLUSIONS: The 5-HT2 receptor antagonist DV-7028 can inhibit the cyclic flow reductions that are resistant to aspirin or heparin. The combined regimen of DV-7028 and aspirin or heparin in treatment of acute coronary stenosis is more effective than that of aspirin or heparin alone.

Animals↗
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↗
PubMed1993

Hemodynamic effects of lipo-PGE1 on peripheral artery in patients with diabetic neuropathy: evaluated by two-dimensional color Doppler echography.

Twenty non-insulin-dependent diabetic patients were studied to evaluate the hemodynamic effects of lipo-PGE1 (prostaglandin E1 incorporated in lipid microspheres). Improvement of diabetic neuropathy was assessed on the basis of subjective symptoms such as pain, coldness, numbness and dysethesia (subjective) after intravenous administration of lipo-PGE1. After lipo-PGE1 treatment, the subjective symptoms were markedly improved. Hemodynamic effects of this drug on the dorsalis pedis artery were examined using new real-time two-dimensional color Doppler echography. After administration of lipo-PGE1, the cross-sectional area of the dorsalis pedis artery significantly increased from 2.6 +/- 0.2 mm2 to 3.5 +/- 0.2 mm2 (P < 0.01). Moreover, the blood flow index significantly increased from 40 +/- 7 to 61 +/- 11 (P < 0.05). The results of this study suggest that lipo-PGE1 may serve as a useful drug in improving diabetic neuropathy.

Adult↗
PubMed1993

New xenografts of human megakaryoblastic cell line (MEG-01) for evaluating anti-tumor agents.

A human megakaryoblastic cell line (MEG-01) was successfully transplanted into athymic nude mice. MEG-01 cells (5 x 10(7)) were inoculated subcutaneously in KSN-nu/nu mice, none of which were pretreated with irradiation or chemotherapeutic agents. All mice developed solid tumors at the site of injection after incubation for 10-14 days reaching a size of 200-400 mm2 (product of cross-sectional diameters) after 30 days. These tumors, designated as MEG-01/nu, were transplanted into other nude mice. The transplanted tumors infiltrated the liver and spleen, and leukemic megakaryoblastic cells appeared in the blood of some transplanted mice. Cells resuspended from MEG-01/nu tumors exhibited almost the same megakaryocytic characteristics as the original MEG-01 cells, and underwent in vitro differentiation to a mature form of megakaryocyte upon addition of phorbol diesters. MEG-01/nu was evaluated for sensitivity to cytosine arabinoside, vincristine, and daunorubicin in vitro and in vivo. Daunorubicin exhibited significant anti-tumor activity against MEG-01/nu in vivo, while cytosine arabinoside did so in vitro. Vincristine showed no activity against these cells. This cell line may provide a useful model for testing the in vivo efficacy of anti-tumor agents and immunotoxins, and for studying the pathophysiological mechanisms of human megakaryoblastic leukemia.

Animals↗
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↗