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Biomedical subjects

T Koike

Publications and source records attributed to T Koike.

At least 487 records · Page 27Linked to original sources

T-cell receptor V beta repertoire of L3T4+ regulatory T cells in anti-L3T4 antibody-induced tolerant NOD mice.

In ongoing studies, we have found that short-term administration of anti-L3T4 monoclonal antibodies (mAb) prevents the development of overt diabetes in non-obese diabetic (NOD) mice. In the present work, we asked whether L3T4+ T cells or Lyt-2+ T cells can suppress the diabetes in these mice. L3T4+ T cells or Lyt-2+ T cells were sorted using a magnetic cell sorter, then were transferred into cyclophosphamide-induced male NOD mice. We obtained evidence that the L3T4+ but not Lyt-2+ T cells did inhibit the diabetes, thereby indicating that the former can regulate diabetes in anti-L3T4 mAb-induced tolerant NOD mice. Further analysis on T-cell receptor (TCR) V beta genes on splenic T cells from anti-L3T4 mAb-treated NOD mice revealed that V beta 4-positive T cells expanded predominantly, while L3T4+ T cells represented heterogeneity of the TCR V beta gene, hence, V beta 4-positive Lyt-2+ T cells generate predominantly. Our findings suggest that both L3T4+ and Lyt-2+ T cells renew and function as regulatory cells, through clonotypic interaction in tolerant NOD mice.

Animals↗

[Current topics in vascular disorders].

Much evidences have been accumulated that antiphospholipid antibodies (aPL), especially anticardiolipin antibodies (aCL) and lupus anticoagulant (LA), were associated with thromboembolism, recurrent fetal loss and thrombocytopenia. These patients with clinical manifestations and aPL are classified into antiphospholipid syndrome (APS). Patients with APS without known well-defined autoimmune diseases are assigned to primary APS. aCL found in sera from patients with the APS recognize epitope(s) on beta 2-glycoprotein I bound to cardiolipin. LA is bound to the complex of prothrombin and anionic phospholipids. Patients with APS can be treated by low dose aspirin, warfarin or heparin. A few patients with aPL develop an acute and multiple organ involvements of APS. These patients are designated as catastrophic APS and are treated intensively by corticosteroid, immunosuppression, plasmapheresis or streptokinase.

Antibodies, Anticardiolipin↗

V gene analysis of anti-cardiolipin antibodies from (NZW x BXSB) F1 mice.

In (NZW x BXSB) F1 (W/B F1) male mice, systemic lupus-like disease, thrombocytopenia and coronary vascular disease with myocardial infarction occur, due to the presence of platelet-associated antibodies, anti-platelet antibodies and anti-cardiolipin antibodies (aCL). We developed monoclonal aCL and analysed the specificity of aCL. In the W/B F1 mice, there are aCL with pathogenic properties, which have an IgG isotype and reveal a cofactor-dependent binding to CL, binding activity to platelets, and lupus anti-coagulant (LA) activity. Here, we analysed the usage of VH and V kappa genes of six aCL, including two pathogenic aCL, from W/B F1 mice, in an attempt to address the question of whether or not aCL with pathogenic properties use restricted Ig V genes. Sequence analysis of VH and V kappa genes of aCL showed that the pathogenic aCL had VHJ558 and V kappa 21 or V kappa 23 genes, whereas the other aCL without pathogenic features used mainly the 7183 VH family and the random V kappa gene group. However, two pathogenic aCL showed a 86.6% homology with the IgV region, each other, indicating that they were not closely related clones. Thus, these findings suggest the possibility that usage of Ig VH genes in pathogenic aCL is not random, but that there may exist a few epitopes of antigen recognized by the pathogenic aCL.

Amino Acid Sequence↗

Active lupus and preeclampsia: a life threatening combination.

A patient with active systemic lupus erythematosus presented with generalized convulsions and acute myocardial infarction during the first trimester. Serial determinations of biochemical variables and liver histology indicated that preeclampsia might be responsible for the life threatening episodes.

Abortion, Therapeutic↗

[A case of squamous cell carcinoma of negative tumor shadow arising from pulmonary cyst].

We report a case of 53-year-old man who performed resection of infected cystic lung lesion seen from his childhood. Chest X-ray showed no remarkable change in the wall of the cyst, and tumor shadow was negative. As the chest cavity was severely adhesive, operation was ended in partial resection including the cyst. Pathological study revealed moderately differentiated squamous cell carcinoma replacing the entire cystic wall. Right upper lobectomy and dissection of lymph nodes were performed as second operation. Microscopically, carcinoma was limited in the wall of the cyst.

Carcinoma, Squamous Cell↗

[Neuronal development and apoptosis].

There are several distinct mechanisms of neuronal cell death that occurs during development. Nuclear type of cell death involves cell shrinkage and chromatin condensation both typical of apoptosis. Here in this short review we summarize some recent advances concerning the mechanism of nuclear type of neuronal death in vitro. Particular focus is placed on superior cervical ganglion (SCG) cells and neuronal PC12 cells both undergoing apoptosis when they are deprived of NGF or serum/NGF. With regard to presynaptic regulation of neuronal death/survival in SCG both cholinergic and non-cholinergic innervations have a pivotal role. The former may involve the modulation of intracellular free Ca2+ concentration, while the latter may exert its effect through a cAMP-dependent mechanism. Finally, neuronal death/survival mechanism of cerebellar granule cells is discussed in terms of cerebellum development and synaptogenesis. Physiological implications are also described about fyn knockout mouse in which naturally-occurring neuronal death may be greatly impaired.

Animals↗

[A case with AML (M4EO) accompanied by recurrent reactive histiocytosis which showed spontaneous remission].

A 30-year-old female was admitted to our hospital complaining of high fever and fatigue. Laboratory findings showed as follows; WBC 41,500/microliter (40% of blasts), Hb 8.5g/dl, platelets 4.4 x 10(4)/microliter. Cytochemical staining of blasts was positive for peroxidase and non-specific esterase with NaF inhibition. Chromosome analysis showed 46, XX, inv (16p+,q-). AML with eosinophilia was diagnosed. During myelosuppression after remission induction therapy, she developed high fever, and did not respond to transfusions. Marrow smears showed the presence of phagocytic histiocytes consisting of 18% total nuclear cells. A diagnosis of reactive histiocytosis (RH) was made. She recovered spontaneously, but suffered two episode of recurrence during subsequent chemotherapy. Reactive histiocytosis is characterized by proliferation of histiocytes which phagocyte blood cells in immunodeficient cases, e.g. a myelosuppressive state after chemotherapy. RH causes high fever and prolonged myelosuppression. It is considered to be one of the poor prognostic factors in AML during chemotherapy, and spontaneous recovery is rare. In this report, the effect of hydrocortisone on histiocytes derived from patient marrow was also investigated in vitro.

Adult↗

Fatal thromboembolism in acute promyelocytic leukemia during all-trans retinoic acid therapy combined with antifibrinolytic therapy for prophylaxis of hemorrhage.

In contrast to patients with disseminated intravascular coagulation (DIC) due to other causes, patients with acute promyelocytic leukemia (APL) receiving standard cytotoxic chemotherapy can be treated safely with antifibrinolytic drugs for prophylaxis of hemorrhage, without the occurrence of thromboembolic complications. However, such drugs should be used cautiously in APL patients who are receiving all-trans retinoic acid (ATRA) differentiation therapy. We report here a patient with APL who had fatal thromboembolism after receiving ATRA and tranexamic acid therapy.

Acute Kidney Injury↗

The therapeutic significance of myeloperoxidase detectable only by electron microscopy in acute leukemia.

The lineage assignment is a prerequisite for successful therapy of acute leukemia because the optimal therapeutic agents and schedules are quite different between acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The most reliable marker for AML has been thought to be myeloperoxidase (MPO). We describe here two patients who were initially diagnosed with ALL owing to the negative light microscopic reaction for peroxidase and the positive reaction of T-lymphoid markers. While these patients were successfully treated by ALL-directed therapy and survived in remission for more than 5 years, ultrastructural study using preserved specimens retrospectively revealed that some blasts had MPO-positive granules. We suggest that some cases of acute leukemia with MPO-positive blasts detected only by electron microscopy, especially when accompanied by T-lymphoid markers, will benefit from ALL-directed therapy.

Acute Disease↗

Heparin administration and monitoring for neuroangiography.

PURPOSE: To establish the optimal protocol of heparin administration during interventional neuroradiology. METHODS: We assessed 100 cases of neuroangiography, including endovascular surgery, and measured activated coagulation time before and 5 minutes after heparin administration, and before and 5 minutes after protamine neutralization. In some cases actual heparin concentration was assayed using a chromogenic substrate technique. RESULTS: The actual plasma heparin concentration significantly correlated with the dose of heparin administered intravenously (r = .98; P < .0001) and changes in activated coagulation time (r = .85; P < .0001). The change in activated coagulation time significantly correlated with the dose of heparin injected intravenously (r = .54, P < .0001). The ratio of change in activated coagulation time significantly correlated with time elapsed after heparin administration (r = -.70, P < .0001). CONCLUSIONS: The activated coagulation time is useful in monitoring administration and neutralization of heparin during neuroangiography, and a bolus injection of 60 U/kg heparin should be adequate to carry out neuroangiography for 75 minutes safely, even for endovascular surgery.

Cerebral Angiography↗

Establishment of a new cell line with the characteristics of a multipotential progenitor from a patient with chronic myelogenous leukemia in early erythroblastic crisis.

A novel cell line (KH88) was established from a patient with chronic myelogenous leukemia in blastic crisis. The leukemic blasts had the features of undifferentiated blasts with basophilic agranular cytoplasm and they were focally positive for acid phosphatase and alpha-naphthyl acetate esterase. CD36, CD33, HLADR, and CD71 were expressed on the surfaces of the blast cells. Most blasts were positive for platelet peroxidase activity, and some of them had granules containing aggregates of ferritin molecules. These findings were compatible with those of 'early' erythroblastic leukemia, this established cell line (KH88) having similar characteristics, and actually producing hemoglobin A and hemoglobin F. Although the KH88 cells were negative for megakaryocytic markers, they were induced to express CD41 by phorbol ester. Further, a few KH88 cells were positive for myeloperoxidase. This cell line was thus revealed to have the capacity to differentiate into three lineages, providing a useful model for studying the differentiation of multipotential stem cells. Moreover, a subline of KH88 had a peculiar chromosome abnormality, del(3)(q21q25); it would be useful to study the significance of this chromosomal abnormality.

Aged↗

Alteration of cartilage specific proteoglycan with non-weight bearing articular cartilage.

The cartilage composed of chondrocytes and their surrounding extracellular matrix, and mechanical motion of joint may influence on the metabolism of cartilage. In order to determine whether non-weight bearing status alter the metabolism of cartilage, we made histological and biochemical analysis with incorporation of 35S and the distribution of the molecular size of proteoglycans produced in the case of disused cartilage. Histologically, there were seen no disorder in cell arrangement, but poorer in cellularity and thinner in cartilage width as compared with normal one. Biochemical analysis, however demonstrate that incorporation of 35S in newly synthesized glycosaminoglycan (GAG) was lower and the molecular size also smaller than that of control suggesting that mechanical stress is an important environmental factor in maintaining the differential function of the cartilage.

Cartilage, Articular↗

SCF/c-kit receptor-mediated arachidonic acid liberation in rat mast cells. Involvement of PLD activation associated tyrosine phosphorylation.

We have previously demonstrated PLD activation via c-kit receptor activation in rat peritoneal mast cells (Koike et al. 1993, J. Immunol. 151,359-366). In this study, the mechanism of arachidonic acid (AA) release in stem cell factor (SCF) stimulation was investigated. Genistein, a protein tyrosine kinase inhibitor, was found to inhibit the AA release in SCF-stimulated cells, whereas pretreatment with vanadate, a protein tyrosine phosphatase inhibitor, enhanced the AA release. Propranolol, an inhibitor of phosphatidate (PA) phosphohydrolase, repressed both AA liberation and 1,2-diacylglycerol (1,2-DG) formation. Short pretreatment with phorbol myristate acetate blunted the SCF-induced AA liberation. These results indicate that 1,2-DG generated via the phospholipase D pathway activated by tyrosine phosphorylation is a principle source for AA released in response to SCF in mast cells.

Animals↗

In vitro expansion of human peripheral blood CD34+ cells.

To elucidate the role of recombinant human colony-stimulating factors (CSFs) for expanding peripheral blood (PB) CD34+ cells, these cells were purified up to 94.5% +/- 1.3% and the effects of individual and combined CSFs on the proliferation and differentiation of these cells were studied in a 7-day suspension culture. The majority of CD34+ cells coexpressed CD38 (81.8% +/- 5.1%), but was negative for CD33 (88.5% +/- 3.4%). Among the individual CSFs examined, recombinant interleukin-3 (rIL-3) was identified as the most potent factor for expanding PB progenitor cells and increased nonerythroid progenitor cells 13- +/- 4-fold (P < .01). Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), recombinant granulocyte-CSF (rG-CSF), recombinant macrophage-CSF (rM-CSF), rIL-6, rIL-11, and recombinant stem cell factor (rSCF) did not alone expand nonerythroid progenitor cells. A combination of 5 CSFs, ie, rIL-3, rIL-6, rGM-CSF, rG-CSF, and rSCF, was identified as the most potent combination of those tested and increased nonerythroid progenitor cells 57- +/- 11-fold. After a 7-day suspension culture of CD34+ cells with these 5 CSFs, CD34+ cells expanded 14.5-fold, and CD34+/CD33- cells and CD34+/CD33+ cells were also expanded 2.9-fold and 307-fold, respectively. Most secondary colonies derived from expanded cells were small; however, the absolute number of large-sized colonies expanded 5.9- +/- 3.3-fold. Thus, the combination of CSFs can achieve a degree of amplification of PB CD34+ cells. The capability of in vitro expansion of PB CD34+ cells as an adjunct to PB stem cell transplantation is worthy of consideration.

Adult↗

The gamma subunit of the Escherichia coli F1-ATPase can be cross-linked near the glycine-rich loop region of a beta subunit when ADP + Mg2+ occupies catalytic sites but not when ATP + Mg2+ is bound.

A mutant of the Escherichia coli F1-ATPase, gamma S8C, has been reacted with a novel bifunctional reagent, N-maleimido-N'-(4-azido-2,3,5,6-tetrafluorobenzamido) cystamine (TFPAM-SS1). Modification of Cys-8 via the maleimide, followed by photolysis to convert the azido group to a reactive nitrene, led to cross-linking of the gamma subunit to a beta subunit. When this cross-linking was conducted with ADP + Mg2+ in catalytic sites, the predominant cross-linked product had a M(r) of 108,000. If cross-linking was done with uncleaved ATP + Mg2+ in catalytic sites, cross-linked products of 102,000 and 84,000 were formed. Cross-linking under both conditions led to inhibition of ATPase activity. TFPAM-SS1 could be cleaved by using reducing agents to break the disulfide bond that links the malemide and tetrafluorophenylazide moieties. Cleavage of this disulfide bond after formation of 102,000 and 84,000 species led to full recovery of ATPase activity. When the 108-kDa cross-linked product was cleaved, full activity was not restored, presumably because of insertion of the tetrafluorophenylazide into a functionally important site on the beta subunit. After cleavage of the disulfide bond, the free thiols could be reacted with [14C]N-ethylmaleimide, thereby radioactively tagging the sites of insertion of the tetrafluorophenylnitrene moiety. In this way, the site of cross-linking from Cys-8 of gamma to the beta subunit in the presence of ADP + Mg2+ was localized to within the sequence Val 145-Lys-155, which contains the glycine-rich loop. This loop region is a part of the catalytic site of the enzyme.

Adenosine Diphosphate↗

V gene analysis of anticardiolipin antibodies from MRL-lpr/lpr mice.

We analyzed the VH and V kappa genes of 14 hybridomas producing anticardiolipin antibodies (aCL) from MRL-lpr/lpr mice, in an attempt to address the question of whether aCL are generated by Ag-driven stimulation or by polyclonal B cell activation. Five of six aCL from one mouse and both aCL from the other mouse carried 98 to 100% homologous VH and V kappa genes, respectively, thereby indicating that aCL were derived from the oligoclonal B cell precursor in that individual mouse. Of nine clones, six (67%) used the VH gene of the J558 family, and three (43%) of seven clones used the V kappa gene of the V kappa 23 group. Three to five somatic mutations were detected in all VH and V kappa genes of the examined aCL. These results suggest the possibility that usage of VH/V kappa genes in aCL is not random and that aCL consist of somatically mutated Ig genes.

Amino Acid Sequence↗