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Biomedical subjects

K Horibe

Publications and source records attributed to K Horibe.

At least 109 records · Page 6Linked to original sources
PubMed1988

Use of cyclophosphamide and total lymphoid irradiation combined with cyclosporine in bone marrow transplantation for transfused severe aplastic anemia.

Between February 1984 and August 1987, 10 patients with severe aplastic anemia were treated with bone marrow transplantation from HLA-identical sibling donors after preparation with cyclophosphamide (CY) 200 mg/kg and total lymphoid irradiation (TLI) 750 cGy. Ages ranged from 5 to 28 years (median 14 years). All patients were previously transfused. Median number of transfusions was 16 (range, 3-886). For post-transplant immunosuppression all patients were given cyclosporine and the last three patients received additional immunosuppression with short-term methotrexate. All patients had initial engraftment and survived for more than 3-46 months after transplantation. One patient developed significant acute graft-versus-host disease (GVHD) and three of nine recipients who survived more than 100 days developed chronic GVHD. One male patient who had received 21 transfusions from his marrow donor before transplantation suffered from persistent granulocytopenia. Otherwise all have Karnofsky performance scores of 90-100%. Although the number of patients is small, it appears that allogeneic bone marrow transplantation with the regimen of CY + TLI for preparation combined with cyclosporine (+ short-term methotrexate) for post-transplant immunosuppression is a promising modality for treatment of previously transfused patients with severe aplastic anemia.

Adolescent↗
PubMed1987

Differential prognosis detected by immunophenotyping in acute lymphoblastic leukemia of childhood with poor prognostic factors.

Immunological phenotypes of leukemic blasts from 50 children with acute lymphoblastic leukemia (ALL) have been examined with a panel of monoclonal antibodies to evaluate their prognostic significance. Thirty-seven of them were common-ALL positive for CD10 "common-ALL antigen (CALLA)" (NL-1), CD19(B4) and HLA-DR. One was pre-B ALL negative for CALLA and another null-ALL which expressed HLA-DR alone. Six of the remaining 11 cases were traditional T-ALL positive for CD2(9.6), and the other five tentative pre-T ALL positive for CD7(Tp40) but negative for CD2. Twenty-one out of 39 patients with non-T ALL were treated with the standard regimen. The 18 children with non-T ALL having poor prognostic factors, five with pre-T ALL and six with T-ALL were treated with the more intensive regimen. The median follow-up period was 36 (range 4 to 74) months. Their disease-free survival probabilities were compared. It was found that the disease-free survival of non-T ALL patients with poor prognostic factors was comparable to that of the patients without such factors as a result of the more intensive chemotherapy. Among the patients with poor prognostic factors, those with pre-T ALL as well as those with T-ALL, which were positive for CD7 antigen, were found to have significantly short disease-free survival times (P less than 0.03). CD7 antibody is most useful for detecting ALL patients with poor prognoses.

Antibodies, Monoclonal↗
PubMed1987

[Studies on the absorption of elemental diets containing "small peptides" as a nitrogen source].

Previous studies have shown that small peptides (di-or tri-peptide) are more rapidly and more evenly absorbed through the small intestine than free amino acid mixture of the same amino acid composition. Since a method to produce protein hydrolysate rich in di-or tri-peptide (SP) was developed, absorption studies were performed to ascertain if the SP shows superior efficiency in absorption to the free amino acid mixture (AA) and large peptide (LP) of the same amino acid composition. A practical elemental diet which contained SP as a nitrogen source, was made (SP-ED) and the absorption rates of nitrogen, carbohydrate and water were studied using dog Thiry-Vella loop in comparison with ED prepared with AA (AA-ED) or LP (LP-ED) with the same amino acid composition. The results are as follows: 1) Absorption rates of nitrogen and water in SP were higher than in AA and LP, when the osmolarities of these solutions were not adjusted to the same level. 2) When the osmolarities of the solutions were adjusted to the same level using mannitol, the absorption rate of nitrogen was still the highest in SP. 3) Nitrogen absorption rate was significantly higher in SP-ED than in AA-ED and LP-ED and carbohydrates were absorbed to a significantly greater extent from the SP-ED than from the AA-ED. These results indicate that small peptides are suitable for use as the nitrogen source for ED.

Animals↗
PubMed1986

Complexity of the supertypic HLA-DRw53 specificity: two distinct epitopes differentially expressed on one or all of the DR beta-chains depending on the HLA-DR allotype.

The supertypic HLA-DRw53 specificity is associated with three allelic class II specificities defined by alloantisera: HLA-DR4, -DR7, and DRw9. The present study demonstrates the complexity of this supertypic DR specificity by comparing two DRw53-related determinants defined by the monoclonal antibodies PL3 and 109d6. For every HLA-DR4 cell line tested, both monoclonal antibodies were found to bind to the same subpopulation of DR molecules. This PL3+, 109d6+ DR subpopulation is also found on most, but not all, DR7+ cell lines with a beta-chain pattern that is identical to the beta-chain pattern of the PL3+, 109d6+ subpopulation on DR4 cell lines. However, some DR7+ cells which carry the HLA haplotype Bw57, DR7, DRw53, DQw3 were also found which completely lack the expression of the 109d6 determinant, but continue to express the PL3 determinant and some of the DRw53 determinants recognized by alloantisera. This results from the fact that the PL3 determinant is expressed on all of the DR molecules found on DR7 cells, including the distinct subpopulation of molecules that carry the HLA-DR7 determinant recognized by the monoclonal antibody SFR16-DR7. This PL3+, SFR16-DR7+ subpopulation does not carry the 109d6 determinant, demonstrating that the PL3 and 109d6 DRw53-related determinants are distinct and can be expressed on a different number of DR molecules, depending on the allotype of the cells. Blocking studies were also performed by using these monoclonal antibodies with alloreactive HLA-DR7-specific cytotoxic T cell clones. In these studies, the T cell-defined HLA-DR7 determinants were found to be carried by the same subpopulation of DR molecules recognized by the HLA-DR7-specific monoclonal antibody and not carried by the DR molecules recognized by 109d6. The DR7+ cell lines which do not express the 109d6 determinant also fail to express another supertypic determinant recognized by the monoclonal antibody IIIE3 carried on this molecule. Furthermore, no additional allelic forms of this unique DR beta-chain were found associated with the nonpolymorphic DR alpha-chain on these cells, suggesting that this DR beta-chain gene is not expressed. These cells also behave as homozygous typing cells for the Dw11 subtype of DR7 in HLA-D typing in the mixed lymphocyte culture assay. This suggests that the lack of expression of a specific class II gene may contribute additional genetic polymorphism within the known HLA-DR allotypes.

Alleles↗
PubMed1986

Cell surface antigens of murine leukemias induced by radiation leukemia virus. Recognition of individually distinct cell surface antigens by cytotoxic T cells on leukemias expressing crossreactive transplantation antigens.

The specificity of transplantation immunity and T cell cytotoxicity against leukemias induced by RadLV was examined. Subcutaneous inoculation of two RadLV leukemias induced in BALB/c mice, BALBRVB and BALBRVD, resulted in initial tumor growth in CB6F1 mice, followed by complete tumor regression. Mice that had rejected leukemias BALBRVB or BALBRVD were subsequently challenged with various tumors of BALB/c origin. The growth of all five RadLV leukemias tested, and of one radiation-induced leukemia, was significantly inhibited. Another radiation-induced leukemia, a methylcholanthrene-induced sarcoma, and a leukemia induced by the Moloney leukemia virus, were not inhibited. The results indicate that RadLV leukemias share cell surface antigens that induce transplantation immunity in vivo. Cytotoxic lymphocytes were generated by coculturing spleen cells from mice that had rejected leukemia BALBRVB or BALBRVD with the corresponding leukemia cells. Direct tests and inhibition tests showed that such cytotoxic cells recognized individually specific antigens on leukemias BALBRVB and BALBRVD, distinct from the shared antigens detected in transplantation experiments. The effector cells in cytotoxicity assays were Thy-1+, Lyt-1+,-, Lyt-2+, and Lyt-3+ T cells.

Animals↗
PubMed1986

A new supertypic HLA class II determinant (PL2) differentially expressed with DR7, DRw11(5), DRw13(w6), DRw14(w6), DR3, and DR2 and biochemically localized to DR7 molecules.

A monoclonal antibody, PL2, has been produced that reacts with a new supertypic determinant expressed on the peripheral blood B lymphocytes and B-leukemic cells (B-CLL) from all individuals who are HLA-DR7 and some individuals who are HLA-DR5 positive. The genetic linkage of the PL2 determinant to the HLA region was demonstrated by family segregation studies. When cultured Epstein-Barr virus (EBV) transformed B cell lines were examined, PL2 was again found to be expressed on all cell lines homozygous for HLA-DR7 and the DRw11(5) subtype of HLA-DR5 positive cells, while one DRw12(5) cell line was negative, suggesting PL2 may distinguish between these DR5 subtypes. In addition, using the panel of EBV-transformed B-cell lines, PL2 was also found to be weakly expressed on HLA-DRw14(w6), -DRw13(w6), -DR3, and -DR2 positive cells but was completely absent from HLA-DR1 and -DR4 positive cells, and is probably absent also from DRw8- and DRw10-positive cells. From titration analysis and quantitative absorption studies the PL2 determinant was found to be expressed at quantitatively different levels in the following order: DR7 greater than DRw11, DRw14 greater than DRw13 greater than DR3 greater than DR2. The molecules carrying the PL2 determinant on DR7 cells have been characterized biochemically to be a subpopulation of HLA class II molecules recognized by the DR specific monoclonal antibody, L243. Furthermore, by two-dimensional gel analysis, PL2 immunoprecipitated only two of three beta chains associated with the DR-apha chain, which are the same two chains that carry the DR7 allodeterminants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Whole body protein turnover, synthesis and breakdown in patients receiving total parenteral nutrition (TPN) before and after recovery from surgical stress].

This study was conducted to clarify the mechanisms underlying the loss of body nitrogen after trauma. Six patients who underwent abdominal surgery and six for control were studied. The measurement of whole body protein turnover was made on the third and tenth postoperative day during TPN with constant infusion of [15N] glycine according to Picou and Taylor-Roberts. The measurement was also made on six control patients during TPN in non-stressed state. The rates of whole body protein turnover (Q), synthesis (S) and breakdown (B) were calculated from the plateau 15N enrichment of urinary total N, which was analyzed with a mass spectrometer. The values were compared with control and the changes in the individual patients were examined by a paired t-test. Immediately after operation, Q and B were significantly elevated (p less than 0.05 and p less than 0.02, respectively), and reduced with the improvement of N-balance after recovery from stress by 0.95 +/- 0.21 and 0.61 +/- 0.13 g X protein/kg X day, respectively. The changes in Q and B were statistically significant (p less than 0.005 and p less than 0.005, respectively). Whereas, no tendency of alteration in S was found throughout the study. It is concluded that protein turnover rate increases in surgical stress, and that the increased protein catabolism rather than the alteration in synthesis could account for the postoperative nitrogen losses.

Adult↗
PubMed1984

Biochemical and functional evidence that an MT3 supertypic determinant defined by a monoclonal antibody is carried on the DR molecule on HLA-DR7 cell lines.

A cytotoxic monoclonal antibody, PL3, was produced by immunizing mice with a cell line homozygous for the HLA class II antigenic specificity DR7. The serologic specificity of PL3 was completely concordant with the MT3 supertypic specificity, which is tightly associated with HLA-DR4, -DR7, and -DRw9. This was confirmed by the finding that F(ab')2 fragments of PL3 blocked the cytotoxicity of anti-MT3 alloantisera. Although PL3 bound to each of the MT3-positive cell lines, it showed significantly weaker binding to HLA-DR4 and -DRw9 cells relative to -DR7 cells, both in titration and in quantitative absorption assays. This differential pattern of binding was not found for the polyclonal MT3 alloantisera, suggesting that the PL3 determinant may be one of several closely related determinants that comprise the MT3 allospecificity. To identify which of the subpopulations of class II molecules carry the PL3 determinant, several approaches have been used. F(ab')2 fragments of PL3 which block the anti-MT3 alloantisera were also tested with anti-MB2 and anti-DR7 sera. Binding of the PL3 F(ab')2 fragments to DR7 homozygous target cells had no effect on the anti-MB2 sera, but significantly enhanced the cytotoxic reactivity of some anti-DR7 sera. This finding suggested that the PL3 determinant is distinct from the DR7 determinant, but is carried on the same molecule. PL3 was also used in blocking studies with allocytotoxic T cell clones which only recognize DR7-positive cell lines. Binding of PL3 to the DR7-positive target cells was found to completely inhibit these T cell clones. Complete blocking was also found with a monoclonal antibody, PL8, which recognizes a monomorphic determinant found on the DR subpopulation of class II molecules. This finding suggested that the PL3 determinant is carried on the same molecule that carries these T cell-defined DR7 allodeterminants. In biochemical studies with DR7-positive cell lines, PL3 and PL8 were found to immunoprecipitate the same subpopulation of class II molecules recognized by other DR-specific antibodies, SG157 and TAL-1B5. Two-dimensional gel analysis demonstrated that the pattern of alpha- and beta-chains immunoprecipitated by PL3, PL8, and TAL-1B5 were identical. In sequential immunoprecipitation studies, both PL3 and TAL-1B5 were capable of removing the same DR subpopulation of molecules recognized by PL3, PL8, TAL-1B5, or SG157 while leaving the additional class II molecules (DS) recognized by SG171 on DR7 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Autologous and allogeneic typing of human leukemia cells: definition of surface antigens restricted to lymphocytic leukemia cells.

Serum from a patient (CO) with acute lymphoblastic leukemia was reactive in immunoadherence assays with autologous leukemia cells but not with autologous blood lymphocytes or bone marrow cells during complete remission. Extensive absorption tests with an array of leukemia cells and normal cells were performed in order to define the specificity of the reaction. The autologous leukemia reactivity was either completely or partially absorbed with acute lymphoblastic leukemia cells obtained from 10 of 14 patients but not with acute nonlymphoblastic leukemia cells or normal hematopoietic cells. Some cultured lymphocytic leukemia lines also showed expression of the antigen. The absence of alloantibodies in CO's serum detectable in our assay allowed direct testing of CO's serum on allogeneic target cells. The results of these tests correlated with the results of absorption tests, indicating that small populations of antigen-positive cells were not missed with absorption tests. In addition, absorption tests with CO-positive allogeneic leukemia target cells showed the same pattern of antigen distribution as tests with autologous targets. CO reactivity was not removed by absorption with cell lines expressing human T-cell leukemia virus, nor did CO's serum react with adult T-cell leukemia cells from three patients.

Antigens, Neoplasm↗