[Recent progress of bone marrow transplantation].
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Animals↗
Biomedical subjects
Y Morishima
Publications and source records attributed to Y Morishima.
[T cell depletion for allogeneic bone marrow transplantation].
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Animals↗
[Unrelated bone marrow transplantation b. Bone Marrow Donor Registry. Nagoya Bone Marrow Transplantation Group].
Tokai Bone Marrow Donor Registry was established to facilitate unrelated bone marrow transplantations in Japan. Although the basic structure was constructed, the number of donors must be expanded and financial problems must be solved. More bone marrow donor registries are likely to be established in the near future throughout Japan, and those will be anticipated to become a nationwide bone marrow donor registry. The HLA identity between unrelated individuals is unique in that it is only phenotypically identical and not genotypically identical. Therefore, for the HLA matching, not only serological typing of donors and recipients but molecular and biochemical methods would be employed to facilitate the analysis of the degree of the HLA identity to be more precise. Those methods include HLA-DP DNA typing and IEF analysis of HLA-class 1 antigens.
Bone Marrow Transplantation↗
Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group.
Japanese patients with leukemia who received bone marrow from human leukocyte antigen (HLA)-compatible siblings had a low incidence of acute graft-versus-host disease (GVHD). Twenty-five (21%) of 120 patients developed moderate (grade II) to severe (grades III to IV) acute GVHD. Severe GVHD was only seen in patients older than 20 years of age. It is also notable that only 2 (5%) of 39 patients who received the combination of methotrexate and cyclosporine (MTX/CSP) for the prevention of GVHD developed grade II acute GVHD, and none developed grades III to IV acute GVHD. Thirteen (30%) of 44 patients receiving MTX alone and 10 (27%) of 37 patients receiving CSP alone developed grades II to IV acute GVHD. Multivariate life-table analysis indicated that the prophylaxis by MTX/CSP was the risk factor for the low incidence of grades II to IV acute GVHD. Compared with the reported incidence of acute GVHD in the patients of the United States, lower incidence of acute GVHD in Japanese BMT patients might be attributable to a lesser degree of genetic diversity in histocompatibility antigens among Japanese.
Acute Disease↗
Increased P-glycoprotein expression and multidrug-resistant gene (mdr1) amplification are infrequently found in fresh acute leukemia cells. Sequential analysis of 15 cases at initial presentation and relapsed stage.
Using a DNA probe of mdr1 and an anti-P-glycoprotein monoclonal antibody (MRK16), the authors investigated 19 cases of adult acute leukemia patients (one M1, six M2, three M3, one M4, three M5, two L1, and three L2), comparing leukemia cells at the initial presentation (I) with those at the relapsed stage (R). By Southern hybridization analysis mdr1 DNA levels were not amplified in 32 samples from 19 patients (I: 14, R: 18). By Northern hybridization analysis mdr1 mRNA levels were not expressed in ten samples from seven patients (I: 4, R: 6). By indirect immunofluorescent assay with MRK16 antibody P-glycoprotein was not detected in 30 samples from 18 patients (I: 13, R: 17). Thus, P-glycoprotein expression and mdr1 gene amplification occurred infrequently not only in leukemia cells at the initial presentation but also in those at the relapsed cases and may not be a major cause of refractoriness to antileukemia drugs in adult acute leukemia.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
A new polyvinylchloride blood bag plasticized with less-leachable phthalate ester analogue, di-n-decyl phthalate, for storage of platelets.
To compare changes in platelets stored in the new di-n-decyl phthalate (DnDP)-plasticized polyvinyl chloride (PVC) bag with those in a di-(2-ethylhexyl) phthalate (DEHP)-plasticized PVC bag, single-donor apheresis platelet concentrates (PCs), 133 +/- 11 x 10(7) platelets per ml (n = 7), were stored with 94 +/- 3 ml of plasma in a new 1-liter bag with a surface area of 44 +/- 7.1 cm2 per 10(10) platelets. Oxygen and carbon dioxide gas diffusion properties of PVC-DnDP films were respectively, 1.6 and 2 times those of standard PVC-DEHP films. The amounts of DnDP leaked into the plasma of PCs were low at 0.58 +/- 0.06 mg per bag after 5-day storage, which is about one-eightieth the amount of DEHP leaked. The pH of PCs in PVC-DnDP bags amounted to 6.99 +/- 0.03 after 5-day storage, with glycolysis accelerated somewhat in the new bags. However, the platelet oxygen consumption was no different from that in the PVC-DEHP bags. Platelet aggregation and responses to hypotonic shock were significantly better in the new bags at the end of storage. Shape changes of platelets into spherical forms with dendrites were more frequently observed in PVC-DnDP bags than in PVC-DEHP bags. The study indicated that platelets stored in the new DnDP-plasticized PVC bags have retained aggregation and responses to hypotonic shock more than platelets in the PVC-DEHP bags, but spherical forms and anaerobic metabolism increased in the new bags.
Adenosine Triphosphate↗
Comparison of the effects of ions and GTP on substance P binding to membrane-bound and solubilized specific sites.
Mg2+ increased but Na+ and GTP decrease [3H]substance P (SP) binding to rat cerebral cortical membranes and to 10 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS)-solubilized membrane fraction. To determine the binding parameters that are modified by the cations and GTP, inhibition experiments of [3H]SP binding by unlabeled SP were performed in both of the preparations. Nonlinear least-squares regression analysis of data in the membrane fraction indicated that optimal fitting of the inhibition curves in the presence of 10 mM MgCl2 was attained with a two-site model, corresponding to a "high-affinity (H)" and a "low-affinity (L)" state. By omitting MgCl2, or by addition of NaCl and GTP, the [3H]SP specific binding was decreased, the H state disappeared, and the L state and a new "super-low affinity (SL)" state observed. The SP/[3H]SP inhibition curves in the cerebral cortical membranes by in vivo treatment with pertussis toxin (islet-activating protein) were similar to that in the presence of GTP in control membranes. The effects of MgCl2, NaCl, and GTP were greater in the CHAPS-solubilized fraction than in the membrane fraction. In contrast to the membrane fraction, the inhibition curves of [3H]SP binding by unlabeled SP in the presence of MgCl2 in the CHAPS-solubilized fraction were best fitted to a one-site model. The KD value was relatively close to that of the low-affinity state in the membrane fraction. Even with the addition of NaCl or GTP, or by reducing MgCl2 concentration to 1 mM, although the inhibition curves consistently fit the one-site model, the KD values changed only slightly.
Animals↗
Association of HLA antigen and restriction fragment length polymorphism of T cell receptor beta-chain gene with Graves' disease and Hashimoto's thyroiditis.
HLA antigen phenotypes and BglII restriction fragment length polymorphism of T cell receptor beta-chain (TCR beta) gene were analyzed in 61 patients with Graves' disease and 50 patients with Hashimoto's thyroiditis. The antigen frequency of HLA-Bw46 in both Graves' disease (23.0%) and Hashimoto's thyroiditis (24.0%) was significantly higher than that in normal population (8.0%), with relative risks (RR) of 3.45 [corrected P (Pc) less than 0.009] and 3.66 (Pc less than 0.02), respectively. Significantly increased frequency of HLA-B51 antigen was also found in Hashimoto's thyroiditis (40.0% vs. 16.3% in controls; RR, 3.42; Pc less than 0.002). Hybridization of BglII-digested DNA with TCR beta probe revealed two alleles of 9.3 and 8.6 kilobases. The allele frequency of 8.6 kilobases in Graves' disease (79%) and Hashimoto's thyroiditis (76%) was significantly higher (P less than 0.01 and P less than 0.05, respectively) than that in controls (64%). The frequency of homozygous state 8.6/8.6 was significantly increased in both Graves' disease (62%) and Hashimoto's thyroiditis (60%) over that in controls (39%); the RR of 8.6/8.6 in Graves' disease and Hashimoto's thyroiditis were 2.55 (P less than 0.01) and 2.31 (P less than 0.05), respectively. These results indicate that in Japanese subjects at least two loci are involved in the susceptibility to Graves' disease and Hashimoto's thyroiditis, one related to HLA and another to TCR beta.
Alleles↗
Hemorrhagic cystitis associated with urinary excretion of adenovirus type 11 following allogeneic bone marrow transplantation.
We studied a total of 50 recipients who had received allogeneic bone marrow transplantation (BMT) and evaluated both the presence of hemorrhagic cystitis (HC) and the urinary excretion of adenovirus. Twelve recipients developed HC and eight of these 12 patients excreted adenovirus type 11 at the onset of cystitis. Urine for virus isolation was attempted 30, 60 and 100 days after BMT. Among 137 specimens examined, eight were positive for adenovirus type 11. Of these eight samples, six were collected during HC; while in the 129 samples which were negative for adenovirus, only three specimens was collected during HC. Female patients, seropositivity for the antibody to adenovirus prior to BMT and acute graft-versus-host disease (grade 2-4) showed a significant impact on the risk of adenovirus HC. It may be said that adenovirus type 11 is one of the causative agents of HC in BMT recipients.
Adenoviridae Infections↗
[Interstitial pneumonia (IP) in bone marrow transplantation in leukemia--120 cases analysis in Nagoya Bone Marrow Transplantation Group].
Results of the bone marrow transplantation (BMT) for 120 cases of leukemia, which were done in nine institutes in Nagoya (Nagoya Bone Marrow Transplantation Group) last ten years, were analyzed to determine the factors associated with an increased risk of developing interstitial pneumonia (IP). IP developed 49 out of 120 patients (49.8%) and case fatality rate was 63.3%. The median time from transplantation to onset of IP was 81 days (range 13-575 days), in 30 out of 49 cases (61.2%), this complication developed within 100 days after transplantation. Of the 49 patients who developed IP, cytomegalovirus (CMV) infection was associated in 18 cases (36.7%), no cases of P. carinii infection was detected. Five factors were associated with an increased risk for developing IP, (1) older age (greater than or equal to 47.0%: less than 10 y. 10.0%) (p less than 0.01) (2) disease stage at BMT (non-remission 76.2%: remission 32.5%) (p less than 0.01) (3) presence of acute GVHD ((+) 52.5% (-) 28.8%) (p less than 0.05) (4) onset day after BMT (less than or equal to 100 days 61.2%: greater than 100 d. 38.8%) (p less than 0.01) (5) sex matching between donor and patient (sex match 28.8%: sex mismatch 57.1%) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Monoclonal antibody and purging].
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Adolescent↗
[Cancer curable by chemotherapy: acute myelogenous leukemia].
Acute myelogenous leukemia (ALM) can be cured by chemotherapy. We have treated 121 adult AML cases for the past 9 years. With BHAC-DMP therapy starting in 1979, CR was obtained in 82% of 51 consecutive AML and the predicted 8-year continuing CR (CCR). Survival of CR cases was, 15 and 21%, respectively. Multivariate analysis of the prognostic factors revealed that % of blasts in the bone marrow at 2 weeks after the start of induction therapy was the most significant factor for CCR. Thus, we started BHAC-DMP (II) therapy with highly intensive induction therapy in 1983, but were forced to cancel this because of an intolerably high incidence of severe infections during the induction therapy. The CR rate was 76% in 29 consecutive patients, and the predicted 5-year CCR and survival of CR cases are 27 and 47%, respectively. Then we started M-85 protocol with intermediately intensive induction followed by 3 courses of highly intensive consolidation therapy using non-cross resistant drugs in 1985. The CR rate was 71% in 41 consecutive patients. Although 4 patients died of infections or myocardial infarction during the consolidation therapies, the predicted 2.5-year CCR and survival of CR cases are 76 and 74%, respectively, with a median follow-up of 28 months.
Adult↗
Generation and characterization of lymphokine-activated killer cells against fresh human leukemia cells.
Lymphokine-activated killer (LAK) cells generated from 15 acute leukemia patients in remission showed significant levels of cytotoxicity against Daudi 1A4, a natural killer-resistant cell line. This indicates that lymphocytes of leukemia patients in remission could respond to interleukin-2 to generate conventional LAK cells. However, LAK cells caused lysis of autologous leukemia cells at considerably lower levels in seven out of the 15 patients, with the exception of one case (48.6% cytolysis). None of the remaining eight patients exhibited LAK activity against autologous leukemia cells. On the other hand, patients' LAK could lyse allogeneic leukemia cells including those resistant to autologous LAK. Thus, patients' LAK seem not to be defective in lysis of leukemia cells. In the cold target competition analysis, the binding of patients' LAK to leukemia cells could be inhibited by autologous and allogeneic leukemia cell competitors, implying that almost all leukemia cells could be recognized by patients' LAK. Most LAK cells from normal donors showed significant lysis of allogeneic leukemia cells, but some leukemia cells were found to be resistant to lysis. LAK cells against both leukemia cells and Daudi 1A4 were phenotypically heterogenous, and were predominantly observed in the T3- fraction in the precursor phase. In the effector phase, whereas LAK activity against leukemia cells was also predominantly shown in the T cell-depleted fraction, similar levels of LAK activity against Daudi 1A4 were found in both the T cell-depleted and -enriched fractions.
Acute Disease↗
Screening of blood donors for antibody to human immunodeficiency virus type I by sensitive particle agglutination assay.
A particle agglutination (PA) assay for antibody to human immunodeficiency virus type I (anti-HIV) was used to screen blood donors and to test leukemia and hemophilia patients. Results by PA showed complete agreement with the results of two kinds of enzyme immunoassay (EIA), and the false-positive rate was the same as or lower than with the EIAs. The sensitivity of PA was 10- to 100-fold higher than that of the EIAs. This simple sensitive assay takes less time and fewer personnel than the EIAs, and has been used for massive screening of blood donors in our blood center.
Adolescent↗
Solubilization and characterization of substance P binding protein from bovine brainstem.
The specific binding protein for substance P (SP) was solubilized in an active form from the crude mitochondrial (P2) fraction of bovine brainstem. After incubation with 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) and 0.1 M NaCl at 0 degrees C for 30 min, the SP binding to the supernatant fraction (100,000 g, 60 min) was determined by the glass fiber filtration method reported by Bruns et al. (1983). The specific [3H]SP binding to the solubilized fraction was highly specific for SP and was displaced by nanomolar concentrations of SP and physalaemin, but only by micromolar concentrations of eledoisin. In addition, the binding was inhibited by GTP (approximately 40% of the specific binding decreased by 10 microM GTP) in both preparations. These results were virtually identical to those of P2 membrane preparations and suggested that this high-affinity SP binding site belongs to the SP-P type. Scatchard analyses of SP binding to the solubilized fraction revealed a single saturable component with a Bmax of 22.0 +/- 5.10 fmol/mg protein and a KD of 0.79 nM, and these values are almost the same as those obtained in the P2 fraction (Bmax = 31.3 +/- 3.56 fmol/mg protein, KD = 0.82 nM). Gel filtration analysis showed that the detergent-SP binding protein complex has two calculated molecular weights of greater than 1,000,000 and 55,000-60,000 (a corresponding Stokes radius of 35.5 nm).
Animals↗
New closed system using a sterile connection device and preconnected PRP pack for extended storage of apheresis platelet products.
In order to prevent bacterial contamination during the procedure of plateletapheresis, preconnected platelet-rich plasma (PRP) packs were prepared which include the apheresis bowl of a plasma collecting system (Haemonetics) with a 16G needle and a 0.6- and 1-liter double-bag system. The anticoagulant line of the PRP pack and that from the bag containing acid-citrate-dextrose formula A solution were welded by a sterile connection device (SCD model 312, DuPont). No additional care was needed to perform plateletapheresis with the present closed system. Platelet concentrates (PCs) stored in 1-liter bags made of polyvinyl chloride plastics with a plasticizer of either di (2-ethylhexyl) phthalate or tri (2-ethylhexyl) trimellitate were demonstrated to be sterile. The pH of PCs was maintained over 6.8 after 5-day storage. Preliminary studies suggest that the present closed system using the preconnected PRP pack and sterile connection device will be useful for reducing the risk of bacterial contamination in platelet products during single-donor plateletapheresis.
Blood Component Removal↗
Association of HLA-DR phenotypes and T-lymphocyte-receptor beta-chain-region RFLP with IDDM in Japanese.
Fifty Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 94 normal subjects were genotyped for BglII restriction-fragment-length polymorphism (RFLP) of the T-lymphocyte-receptor beta-chain (TLR beta)-region gene and analyzed in relation to HLA-DR phenotypes. The antigen frequencies of DR4 and DR9 in the IDDM population were significantly higher than those in the normal population, with relative risks of 1.87 (P less than .02) and 2.42 (P less than .01), respectively. Hybridization of digested DNA with the TLR beta probe revealed two alleles of 9.3 and 8.6 kilobases (kb). The allele frequency of 8.6 kb in patients with IDDM (79%) was significantly (P less than .05) higher than that in normal subjects (64%). When TLR beta-region RFLP in IDDM was further analyzed with respect to the HLA-DR phenotypes, the frequency of 8.6 kb was significantly increased in patients with DR4 but not DR9 (DR4/X) and those with DR9 but not DR4 (DR9/X) compared with the frequency found in normal subjects (P less than .05); the relative risks of 8.6 kb in DR4/X and DR9/X were 2.77 and 4.98, respectively. Although the frequencies of HLA-DR phenotypes and of TLR beta-region RFLP in IDDM and normal subjects were apparently different from those reported for Caucasians, this population-association study indicates that in the Japanese, genes conferring susceptibility to IDDM exist near or at the HLA-DR and the TLR beta loci, as has been demonstrated in Caucasians.
Adolescent↗
Functional and morphological differentiation induction of a human megakaryoblastic leukemia cell line (MEG-01s) by phorbol diesters.
The effect of differentiation induction by a tumor-promoting phorbol diester, 12-O-tetradecanoylphorbol-13-acetate (TPA) on a clonal human megakaryoblastic cell line, MEG-O1s, was investigated, and a prominent response was demonstrated. The cells became weakly adherent, developed conspicuous cytoplasmic blebs, and displayed mature megakaryocytic characteristics by light microscopy such as the development of azurophilic cytoplasmic granules and a mosaic pattern of oxyphilic patches, multiplication of nuclei, and enhancement of the PAS reaction and alpha-naphthyl acetate esterase staining. Ultrastructural studies demonstrated the development of prominent cytoplasmic blebs, budding of blebs, and multiplication of nuclei. Numerous granules with central nucleoids that are similar to alpha granules had developed as well as granules with high electron density and clearly demarcated zones. Surface marker analysis revealed a moderate increase in IgG Fc receptor levels and a profound decrease in C3 receptor sites. By an immunofluorescent technique using monoclonal and polyclonal antibodies, a dramatic change in the expression of several megakaryocyte-platelet-specific proteins was demonstrated. All the proteins that had been expressed before induction such as platelet glycoprotein (GP) IIb/IIIa, fibrinogen, von Willebrand factor, factor XIIIA, beta-thromboglobulin (beta-TG), and HLA class 1 antigen were profoundly enhanced after induction by TPA. Induction by TPA led to the expression of fibronectin and factor V, which were not detected on nontreated cells. An ultrastructural immunoperoxidase study demonstrated platelet GPIb and GPIIb/IIIa in both plasma membranes and protein synthesis areas such as perinuclear cisternae and endoplasmic reticulum after TPA induction. beta-TG was also observed in some cytoplasmic granules of TPA-treated cells. TPA remarkably increased the secretion of beta-TG into the culture medium of MEG-01s. Ploidy was also increased from 2C to 4C to 4C to 8C. Similar maturation of MEG-01s was induced by other phorbol diester analogues such as phorbol-12,13-dibutyrate, but not by phorbol itself. These results indicate that phorbol diester, TPA, can bring about differentiation and maturation of a human megakaryoblastic cell line (MEG-01s) and that MEG-01s cells will provide a useful model for studying megakaryocytic differentiation and numerous megakaryocyte-platelet-specific proteins.
Antibodies, Monoclonal↗