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K Sakurada

Publications and source records attributed to K Sakurada.

At least 127 records · Page 7Linked to original sources
PubMed1988

Non-specific suppressor cells in murine bone marrow chimeras: their possible role in GVHD-associated immunodeficiency.

Suppressor cells against several mitogen-induced responses were detected in the spleen of murine bone marrow chimeras, regardless of intravenous (i.v.) or intrasplenic (i.s.) bone marrow transplantation (BMT). According to the time-course of the suppressor activity against Con A, PHA, and PWM, they were readily detected at 11-21 days after BMT and thereafter, either gradually decreased or remained at a plateau level. In contrast, the suppressor activity against the LPS-stimulated response increased at 39-52 days as compared to 24-34 days after BMT. Characterization studies of suppressor cells early (11-21 days) after BMT revealed that those in the i.v. and i.s. chimeras were composed of host-derived plastic dish adherent and/or anti-Thy 1.2 antibody-insensitive spleen cells in general. On the contrary, those in the i.v. and i.s. chimeras that possessed severer GVHD were mainly composed of host-derived plastic dish non-adherent spleen cells. Since the suppressor activity was higher in chimeras with severe graft-versus-host disease (GVHD) than in conventional chimeras, suppressor cells against the mitogen-induced responses may be related to the immunodeficiency associated with GVHD. Particularly, plastic dish non-adherent suppressor cells may closely relate to GVHD-associated immunodeficiency as compared with plastic dish adherent suppressor cells.

Animals↗
PubMed1988

Suppressor activity in the supernatant of T cell clones derived from chimeric mouse spleen cells.

The supernatant from cultures of T cell clones derived from (BALB/c----C3H/He) chimeras suppresses BALB/c anti-C3H/He or BALB/c anti-C57BL/6 MLRs. When we studied the alloantigen specificity of the suppressor activity in culture supernatant, we observed three types of the suppressor activity (i.e., the suppressor activity against BALB/c anti-C3H/He MLR, against BALB/c anti-C57BL/6 MLR, and against both MLRs) on day 3 after stimulation of the T cell clones with 20% crude IL2 and feeder cells. Since the alloantigen specificity fluctuated somewhat with time, we considered that a time-course study was needed to determine it correctly. We thought it unlikely that any IFN-gamma or PGE2 in the culture supernatant of the T cell clones would have mediated the suppression. Our results suggest that alloantigen specific and non-specific suppressor T cells exist in bone marrow chimeras. The former appears to play an important role in inducing and maintaining transplantation tolerance, while the latter seems to have a rather harmful effect upon chimeras.

Animals↗
PubMed1988

Pharmacokinetics of oral sulfa drugs and gastric emptying in the pig.

The plasma pharmacokinetics of sulfamonomethoxine (SMM) and sulfamethazine (SMZ) in the pig were examined after the oral and intravenous (i.v.) administration of the sodium salt solutions. Eight pigs from a commercial breed and 8 Goettingen minipigs were used. Both the Cmax and tmax of SMM and SMZ ranged widely. A flipflop phenomenon was found after the SMM solution but not after the oral SMZ. Duodenal cannulae were inserted in 5 pigs. The SMM solution and the SMM suspension were directly injected into the duodenum through the duodenal cannula. Both Cmax values were in a narrow range. Both tmax values were in a narrow range and were reached within 30 min. There was no flipflop phenomenon. Gastric emptying in the pig was examined using duodenal cannulated pigs. Phenol red solution and SMM suspension were administered orally. The time courses of gastric emptying of the two markers were nearly coincident and they approximated an exponential decrease. The times required for the 50% passage of the marker from the stomach ranged widely between 0.06-7.7 h, which may cause the variation in the Cmax and tmax of the sulfadrugs after oral administration. The kappa-GE (rate constant of the terminal phase of gastric emptying) also ranged widely. Nine kappa-GE values among 22 were smaller than the minimum value of the SMM kappa el values, which may cause the flipflop phenomenon of the oral SMM. In contrast, all of the kappa el values of SMZ were smaller than the minimum value of kappa-GE. And no flipflop phenomenon was found after the oral SMZ. Accordingly, the pharmacokinetics after the oral sulfonamides solution may be intimately influenced by the gastric emptying.

Administration, Oral↗
PubMed1988

[Therapy of the preleukemic state: effect of androgens on refractory anemia].

We have examined the efficacy of various drugs in 44 patients with MDS and found the different effectiveness which depends on the type of MDS. Namely, RA appears to respond to steroid hormone, androgen, and/or vitamin D3, regardless of single or combined use. In particular, it is obvious in androgen, and as our previous reports, high content of acidic ferritin in RBC with RA have changed to more basic ones by treatment with androgen. On the contrary, these drugs were not effective on RAEB, RAEB-T, and CMML. A long-term observation is needed to determine whether the prolonged or decreased occurrence of leukemia could be obtained in the effective cases with RA. Most of the cases who did not develop overt leukemia during this study died of bleeding or infections due to thrombocytopenia or leukocytopenia, thus indicating that supportive therapies are important in patients with MDS. Since it has recently been reported that recombinant G-CSF or GM-CSF is helpful to increase the number of leucocyte and to enhance their functional recovery in MDS, these factors may be powerful agents against infections when they are carefully used with regard to the activation of leukemic clones.

Adult↗
PubMed1988

[Experience of HLA-matched platelet transfusion in patients who are refractory to random donor platelets].

Platelets collected from random and multiple donors were as effective on transfusion as those obtained from single donor by platelet pheresis if patients were not alloimmunized. In alloimmunized patients, effects of platelet transfusion were correlated with the HLA-matching grade; 100% effective in A-match, 92% in B-match and 65% in C-match. This correlation was not observed if the patient had infection. The transfusion of A- or B-matched platelets resulted in a lowering or disappearance of HLA antibody activities in most patients. However, the transfusion of C-matched platelets caused increasing or appearance of HLA antibody activities in some patients. The ABO-incompatibility did not show a significant effect on platelet transfusion when anti-A or anti-B antibody activities in donors and antiglobulin tests on patients' red cells were negligible. Non HLA, platelet specific antibodies were produced in some patients and presumed to be participated in the destruction of transfused HLA-matched platelets.

Anemia, Aplastic↗
PubMed1987

Protein kinase C phosphorylation of protamine is Ca2+ independent, but the addition of DNA renders it Ca2+ dependent.

Protamine is a unique substrate of protein kinase C for its Ca2+-independent phosphorylation. The interaction between protein kinase C and protamine and the effect of DNA on the interaction was studied. Protein kinase C was retained in a protamine-immobilized Sepharose 4B column, even in the absence of Ca2+ and was eluted with ammonium sulfate or L-arginine. The eluted enzyme was fully activated by phosphatidylserine alone, when protamine was used as substrate. When DNA was included in the assay system, the activity elicited by phosphatidylserine alone was inhibited. The DNA effect on the activity in the presence of both Ca2+ and phosphatidylserine was much lower than on the activity elicited by phosphatidylserine alone, thereby demonstrating the Ca2+ sensitivity of protamine phosphorylation.

Animals↗
PubMed1987

Immunological functions and T-cell receptor gene rearrangement of proliferating lymphocytes in a case of T gamma lymphocytosis with neutropenia.

A case of T gamma lymphocytosis with neutropenia is presented. The patient showed mild lymphocytosis, splenomegaly, anemia, neutropenia and recurrent infections without progression for 15 years. The expanded lymphoid cells were morphologically large granular lymphocytes (LGL), had receptors for both sheep red blood cells and IgG-Fc portion and were positive for OKT3 and 8 antigens. They displayed ADCC activity, whereas they showed low responses to T-cell mitogens and deficient NK activity. They showed neither suppressor activity on antibody production by B-cells nor suppressor activity on CFU-C formation. The DNA isolated from the expanded cells of the patient showed T-cell beta-chain (T beta) gene rearrangement, indicating monoclonality of the proliferation. This finding supports that the proliferation of T8 lymphocytes in the present case is neoplastic rather than reactive, regardless of the benign clinical course.

Adult↗
PubMed1987

Non-T, non-B acute lymphocytic leukemias: cellular origin based on molecular analyses of immunoglobulin and T-cell alpha- and beta-chain receptor gene rearrangements.

Fifteen non-T, non-B acute lymphocytic leukemia (ALL) cases were investigated for determining cellular origin based on molecular (immunoglobulin and T-cell alpha-receptor (TcR alpha) and T-cell beta-receptor (TcR beta) genes) and immunophenotypical analyses. As defined by monoclonal antibodies, they were classified into 2 groups; 12 cases as common ALL antigen (CALLA)-positive ALL and 3 cases as CALLA-negative ALL. Southern blot analysis revealed that 11 CALLA-positive ALL cases contained rearranged JH gene and 2 of them contained rearranged Jx genes, similar to recent views that most CALLA-positive leukemic cells are neoplastic B-cell precursors. One CALLA-positive ALL case, whose leukemic cells were also Leu-1 positive, showed no rearrangement of JH and TcR beta genes. On the other hand, non-T, non-B CALLA-negative ALL, so called null ALL, consisted of heterogenous groups with regard to lymphocyte differentiation and lineage; one out of 3 null ALL cases may be truely undifferentiated as shown neither JH nor TcR beta gene rearrangement, but other 2 cases showed either JH or TcR beta gene rearrangement. Dual rearrangements of Ig and TcR beta genes occur frequently in 3 out of 15 non-T, non-B ALL cases, but all cases of bigenotype showed no doubly marked profile and retained a completely fidelous immunophenotypic pattern. We further investigated the possibility that analysis of TcR alpha gene may be useful for determining cellular origin of non-T, non-B ALL leukemic cells.

Genotype↗
PubMed1987

Characterization studies of suppressor cells in murine bone marrow chimaeras.

When BALB/c bone marrow cells were transferred to lethally X-irradiated C3H/He mice either intrasplenically (i.s.) or intravenously (i.v.), suppressor cells were detected by means of MLR coculture assays in the spleen of i.s. and i.v. chimaeras. Some but not all of the suppressor cells expressed a Thy 1.2 antigen, indicating that suppressor cells either sensitive or insensitive to anti-Thy 1.2 antibody plus complement treatment were generated in the spleen of i.s. and i.v. chimaeras. According to the examination of Lyt alloantigen expression on suppressor T cells, Lyt 1+2-, Lyt 1-2+, and Lyt 1+2+ suppressor T cells appeared to be present. The culture supernatants from several T-cell clones showed the suppressor activity against alloreactive MLR. Cell surface markers of these clones were composed of Lyt 1+2-, Lyt 1+2+ and Lyt 1-2+. In addition, since Carrageenan treatment abrogated the suppressor activity of plastic dish adherent cells, we conclude that some of them were composed mainly of macrophages.

Animals↗
PubMed1987

Establishment and characterization of a cell line, TOM-1, derived from a patient with Philadelphia chromosome-positive acute lymphocytic leukemia.

A new Philadelphia chromosome (Ph1)-positive cell line, designated TOM-1, was derived from bone marrow cells of a patient with Ph1-positive acute lymphocytic leukemia (ALL). The TOM-1 cells were positive for Ia and B1 antigens and terminal deoxynucleotidyl transferase (TdT) but negative for common ALL antigen. Although neither surface Ig nor cytoplasmic Ig was detected, the TOM-1 cells contained rearranged immunoglobulin-H chain genes but retained germ-line kappa chain and germ-line T cell receptor beta-chain genes. These results indicate that the TOM-1 cells reside as the progenitor of pre-B cells. We have investigated the chromosome 22 breakpoint and c-abl gene expression in the TOM-1 cells. We found that the breakpoint on chromosome 22 was within the breakpoint cluster region (bcr) in the TOM-1 cells. We also found the breakpoints within or near bcr in four of six Ph1-positive ALL cases, similar to the findings in Ph1-positive CML cases. Amplification of the c-abl gene was not detected in the TOM-1 cells. The leukemic cells isolated from a patient with CML in myeloid crisis contained a novel 8-kilobase (kb) abl-related messenger RNA (mRNA), but the TOM-1 cells contained c-abl transcripts of only normal sizes, despite the fact that they showed the bcr gene rearrangement.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1987

[An autopsy case of severe miliary tuberculosis in a patient with acute lymphatic leukemia (ALL)].

A 58-year-old Japanese man being diagnosed as having ALL suffered from continuous fever and dysfunction of the liver and kidneys despite being in a state of haematological remission. Further clinical investigations, however had not been able to find the causes of his condition before his death. The autopsy revealed severe miliary tuberculosis affecting many organs including the heart, lungs, liver, spleen, kidneys, thyroid gland, pancreas, bone marrow, and central nervous system, which is compatible with multiple organ failures. Recent pharmacological advances have increased the usage of many kinds of antineoplastic drugs, and this has resulted in increased chances of opportunistic infections by various microorganisms in the course of treatment. The present case implies the significance of the reactivation of tuberculosis in the secondary immunodeficient syndrome (SIDS).

Humans↗