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Biomedical subjects

Y Morishima

Publications and source records attributed to Y Morishima.

At least 253 records · Page 14Linked to original sources

Serological study for in vitro use of monoclonal antibody for autologous bone marrow transplantation in null cell-type acute lymphocytic leukemia.

In connection with autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) patients, the optimal conditions for in vitro elimination of leukemia cells from transplanted bone marrow cells with monoclonal antibodies (MoAb) plus rabbit complement (C) were investigated. Three monoclonal antibodies, NL-1, NL-22 and HL-47, which were produced in our laboratories and shown to react predominantly to Null-ALL cells, were used. In most cases, 10 micrograms/ml of MoAb and 50% of C were required for optimal killing of leukemia cells. Combined use of MoAbs and multiple treatments were studied, but generally no significant increase in the cytotoxicity to the target leukemia cells was observed as compared with a single treatment with the most effective single MoAb. Selection of C was very important, because some lots had lower C activity from the beginning or after incubation with normal bone marrow mononuclear cells. Nonspecific cytotoxicity to human hematopoietic cells was also observed in some lots of C. Under the optimal conditions thus defined, the three MoAbs did not inhibit the growth of granulocyte-macrophage colony-forming units (CFU-GM) or three other types of hematopoietic stem cells. Modulation of the antigens was also examined, and NL-1 antigen showed mild modulation, whereas NL-22 and HL-47 antigen did not. The results obtained indicated that these three MoAbs may be useful for eliminating Null-ALL cells in vitro from bone marrow in autologous BMT.

Antibodies, Monoclonal↗

Preliminary clinical trial of autologous bone marrow transplantation after in vitro monoclonal antibody and complement treatments in null cell-type acute lymphocytic leukemia.

Autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) was carried out after depletion of leukemia cells from transplanted bone marrow. Patients' autologous bone marrow cells were harvested during remission and treated in vitro with complement and three monoclonal antibodies (NL-1, NL-22 and HL-47) reactive to Null-ALL cells, and then cryopreserved. Three patients were transplanted with the antibody-treated bone marrow cells during the first remission period after preconditioning with intensive chemotherapy and total body irradiation, while transplantations in two other patients, who were in poor clinical condition, were done during the fourth remission period and the third relapse, respectively. Good preservation of hematopoietic stem cells after antibody treatment and cryopreservation of bone marrow cells was demonstrated in all five cases studied. Clinically, prompt recovery of white blood cells and platelets was observed in the three patients who received BMT during the first remission period; two of them have continued remission (2 and 15 months), while the other relapsed after 7 months of remission. these results suggested that autologous BMT with these three antibodies may be an effective mode of therapy for Null-ALL patients.

Antibodies, Monoclonal↗

Prevalence of possible adult T-cell leukemia virus-carriers among volunteer blood donors in Japan: a nation-wide study.

A nation-wide survey of carriers of adult T-cell leukemia virus (ATLV) detected as anti-ATLA (ATLV-associated antigens) in volunteer blood donors was made in Japan. A total of 200 sera from donors between 40 and 64 years of age, collected in each of 64 blood centers located in eight districts, were tested for anti-ATLA by an indirect immunofluorescence test. The highest rate (8%) of seropositive donors was found in Kyushu and lower rates of 0.3 to 1.2% in other districts. However, the positive rate varied considerably in different localities even within districts with a high or low seropositive incidence. Further studies of all the donors (16 to 64 years old) in eight centers in Kyushu demonstrated two facts: (1) that the frequency of seropositive donors increased with age, and (2) that four centers in this district showed distinctly high incidences of seropositive donors, while the other four centers showed low incidences. The seropositive rate among all donors was estimated to be about 3% in Kyushu and 0.08 to 0.3% in all other districts.

Adolescent↗

Comparison of one-dimensional IEF patterns for serologically detectable HLA-A and B allotypes.

A new mouse monoclonal antibody (MoAb) 4E, which detects an epitope shared by HLA-B locus antigens, together with the MoAb W6/32, detecting a common HLA, B, C, determinant, and the MoAb4B, detecting HLA-A2 and A28, were used to isolate HLA-A and -B antigens in sequential immunoprecipitation. The HLA antigens obtained from metabolically labeled cell extracts of B-lymphoblastoid cell lines or from phytohemagglutinin (PHA)-activated peripheral blood lymphocytes were compared by one-dimensional isoelectric focusing (1D-IEF). The IEF banding patterns obtained with native HLA antigens segregated in a family with HLA. Neuraminidase treatment of isolated antigens reduced the number of bands to one or two, simplifying the analysis of characteristic patterns. Thus, we have cataloged IEF banding patterns for the majority of the serologically recognized HLA-A and -B allotypes obtained from 57 unrelated American Caucasians. While no HLA-A locus or HLA-B locus specific banding patterns were observed, the HLA-A antigens had, in general, slightly higher pI values than the HLA-B antigens. HLA-C antigens could not be detected in this assay system. The polymorphism detected by IEF banding patterns was as extensive as the serologically detected polymorphism identified by classical HLA serology. Moreover, variants for some HLA allotypes could be detected by this method. In addition to previously recognized A2 variants, new variants were identified for HLA-A1, A26, and Bw44. Each A1 and Bw44 variant was associated with particular haplotypes. The HLA-A2 antigens occurred on 43 HLA haplotypes in the unrelated Caucasian population. Only one of each A2 variants was identified in this population.

Alleles↗

Determination of low affinity platelet factor 4 in frozen and thawed human platelets by the newly developed enzyme immunoassay system.

By the use of a newly developed sandwich enzyme immunoassay method for low affinity platelet factor 4 (LA-PF4), the effects of repeated freeze-thawing on the contents of this protein in platelets were determined and compared with those of Triton-X 100 lysed platelets. The assay system consisted of polystyrene balls covered with immobilized antibody fragments F(ab')2 and the same antibody Fab' labeled with beta-D-galactosidase from E. coli. The assay was specific to LA-PF4 with no significant cross-reactivity with platelet factor 4. Coefficients of variation within-run and between-run for the assay of LA-PF4 were less than 12%. The results obtained with this enzyme immunoassay correlated well with those of a radioimmunoassay of beta-thromboglobulin which is immunologically identical with LA-PF4 (r = 0.961, slope = 1.056, y-intercept = -3.739 ng/ml; n = 22). The contents of LA-PF4 per 10(9) Triton-X 100 lysed platelets in platelet-rich plasma were 23.65 +/- 3.14 micrograms (mean +/- S.D.). The contents of LA-PF4 in platelets were increased from 46% to 95% of Triton-X 100 values by repeated freezing and thawing 1 to 7 times. The present data indicate that the freeze-thawing technique should be done carefully to obtain the reliable determination of LA-PF4 in platelets.

Blood Coagulation Factors↗

Sixteen adult patients with acute leukemia treated by chemotherapy, total body irradiation and allogeneic marrow transplantation.

Since 1976, 16 adult patients with acute leukemia have been treated by chemotherapy, total body irradiation (TBI) and allogeneic bone marrow transplantation (BMT) in the medical school hospital and the satellite hospitals of Nagoya University. The first group of 10 patients were given marrow grafts at the time of leukemic relapse and the second group of six patients were given the grafts in the period of remission of their disease. For the first group (ALL/ANLL 2:8, age (median) 33, M/F 8:2), HLA-identical donor cells (25 x 10(7)/kg [median]) were infused after the patients were conditioned with NSC D 245382 (ACNU) or daunorubicin, cyclophosphamide (CY) and a single shot of 1000 rad of TBI. For the second group (ALL/ANLL 4:2, age (median) 20, M/F 5:1), HLA-identical donor cells (22 x 10(7)/kg [median]) were infused after the patients were conditioned with CY and fractionated (250 rad x 4) TBI. All the patients were isolated in a laminar air flow room (LAF) after gut and skin decontamination. Engraftment of donor cells was confirmed in 15 out of the 16 patients. Febrile periods in LAF and the days required for platelet transfusion were prolonged in the first group. All the patients in the first group died within 12-214 days after BMT because of interstitial pneumonitis (7 patients) or bacterial infection (3 patients). On the other hand, five out of six patients in the second group are alive 84-540 days after BMT. For the surviving patients, the complications of chronic graft versus host disease, viral infections, tuberculosis, hepatitis, hemorrhagic cystitis and recurrence of leukemia are now the problems. It can be stated that the patient's clinical condition at the time of BMT is one of the most essential factors for the success of BMT although the effects of other variables, such a change in the conditioning regimens of the supportive care, must also be carefully analyzed.

Acute Disease↗

[Treatment of hematological malignancies with recombinant leukocyte A interferon (rIFN-alpha A)].

Twenty-three cases of hematological malignancies (18 plasma cell neoplasm, 2 leukemia and 2 malignant lymphoma) were treated with recombinant human leukocyte interferon (rIFN-alpha A). Among plasma cell neoplasms, excellent and good responses were obtained in 1 case of IgG myeloma and 1 case of Bence-Jones myeloma respectively and fair response was obtained in 5 other cases. Response rats was 11.4%, or 38.9% if fair response was included. Partial remission was obtained in 1 case of chronic lymphocytic leukemia. In one of 2 cases of acute lymphoblastic leukemia, marked reduction of peripheral leukemia cells was noted. Side effects included fever (65%), malaise (20%), nausea-anorexia (43%), leukopenia (52%) and thrombocytopenia (52%). However, all were not serious and disappeared quickly after discontinuation of rIFN-alpha A.

Adult↗

Local T cell subsets in mumps meningitis.

In the acute phase of mumps meningitis, more than 85% of the cells in cerebrospinal fluid (CSF) were OKT 3 positive, while 76% of the peripheral mononuclear cells (PMN) were OKT 3 positive. The ratio of OKT 4:8 positive cells in CSF was significantly lower than that in PMN, showing that suppressor/cytotoxic T cells had selectively accumulated in CSF. In addition, 58% of CSF cells were immune associated (Ia) positive, probably activated T cells.

Cerebrospinal Fluid↗

An in vitro evaluation of leukocyte-poor red blood cell concentrates prepared by reconstitution with phosphate buffer solution.

An effective method for removing leukocytes and platelets from red blood cell concentrates (RBC) reconstituted with phosphate buffer solution was investigated in vitro. Reconstituted RBC were warmed at 37 degrees C for 1 hr. Neither leukocyte count nor platelet count was decreased by the treatment. When compared with whole blood, leukocytes present in the fractions below the buffy coat layer were significantly less than those of whole blood, while the distribution of platelets in reconstituted RBC was unchanged. It is suggested that the reduction of leukocytes in red blood cells below the buffy coat layer may contribute to the preparation of RBC with a poor leukocyte.

Buffers↗

Analysis of two new leukemia-associated antigens detected on human T-cell acute lymphoblastic leukemia using monoclonal antibodies.

Two monoclonal antibodies (anti-3-3 and anti-3-40) were produced, which identify two new leukemia-associated antigens. Both antibodies reacted with most cell lines derived from patients with T lymphoblastic leukemia (T-ALL), but were not detected on suspensions of normal hematopoietic cells (including thymocytes) by cytotoxicity, absorption, or indirect immunofluorescence assays. Analysis of fresh leukemic cells indicated that anti-3-3 only reacted with T-ALL cells, while anti-3-40 also reacted with some non-T, non-B ALL cells and a few acute myelocytic leukemia (AML) cells. The 3-40 antigen was also found histopathologically in frozen sections of several normal tissues, including the epithelial cells and a few lymphoid cells of the thymus, and some malignant tissues. The 3-3 antigen was not found in any tissue studied. A "double absorption"assay provided additional serologic evidence that the two antibodies identify different antigenic determinants. Biochemical analysis indicated that the molecules immunoprecipitated by anti-3-3 and anti-3-40 have molecular weights of 35,000-40,000 daltons. This study demonstrated that the 3-3 and 3-40 antigens are markers for human T-ALL and can be used along with the normal T-lymphocyte antigen, 3A1, to discriminate T-ALL from cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia (ATL), and T-cell chronic lymphocytic leukemia (T-CLL).

Adult↗

Functionally different T lymphocyte subpopulations determined by their sensitivity to complement-dependent cell lysis with the monoclonal antibody 4A.

A human T lymphocyte antigen 4A (40,000 daltons) is defined by a monoclonal, complement- (C) fixing, hybridoma-produced antibody (moAb 4A). This antigen, which is identical to the previously reported antigen 3A 1, is expressed at quantitatively different levels on functional subsets of peripheral T lymphocytes as determined by the cell sensitivity to antibody and C. Peripheral T lymphocytes can be divided into two populations: 4A high-density T cells (4A increases), which are killed in vitro by moAb 4A + C, and 4A low-density T cells (4A decreases), which are not affected in vitro by moAb 4A + C treatment. The helper/inducer T cell lineage, defined by moAb Leu 3a, and the cytotoxic/suppressor T cell lineage, defined by moAb Leu 2A, contain both 4A increases and 4A decreases T cell populations. Functional studies by moAb 4A + C treatment show that 1) the 4A increases T cell population contains T helper cells, which are necessary for in vitro antibody production against red cell-bound determinant; 2) the 4A decreases T cell population contains the precursor T cells, which proliferate in vitro in MLC, and the precursor T cells, which are necessary for the in vitro generation of the alloreactive cytotoxic T cells; and 3) the cytotoxic activity of alloreactive T cells generated in CML assay is abrogated by moAb 4A + C treatment; 4) the activation of T cells by PHA and Con A increases the quantitative expression of 4A antigen.

Antibodies, Monoclonal↗