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K Oshimi

Publications and source records attributed to K Oshimi.

At least 55 records · Page 3Linked to original sources

[Clinical effects of combination therapy with cefozopran and tobramycin for severe infections in patients with hematologic diseases].

We studied clinical effect of a combination therapy with cefozopran (CZOP) and tobramycin (TOB) for infections in 80 patients with hematologic diseases in 15 institutes. Combined doses with CZOP 2 g and TOB 60-90 mg twice a day had been given intravenously. Of the 80 patients, 61 patients (42 with acute leukemia, 10 with malignant lymphoma, 3 with aplastic anemia, 2 with chronic myeloid leukemia, 2 with multiple myeloma, and 2 with myelodysplastic syndrome) were evaluable. Those consisted of 6 patients with septicemia, 49 with suspected septicemia, 3 with pneumonia, and 3 with other infections. Clinical efficacy by the treatment was excellent in 24, good in 17, fair in 9, and poor in 11 patients, and the overall efficacy rate including excellent and good was 67.2%. Microbiologically, 5 of the 6 patients with septicemia (1 coagulase negative Staphylococcus, 2 S. pneumoniae, 1 S. oralis, and 1 E. coli) were responded. The efficacy rate in patients with severe granulocytopenia showing 100/microliter or lesser neutrophil counts during the drug administration was 57.1% (12/21). Side effects and abnormal changes of clinical laboratory findings were observed in 5 patients, and 16 patients, respectively, but most of them were mild. The findings above suggested that the combination therapy with CZOP and TOB is useful as an empiric therapy for severe infections in patients with hematologic diseases.

Adult↗

A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation.

We examined the effect of a hydroxamic acid-based matrix metalloproteinase inhibitor (KB-R7785), which we previously demonstrated to have a potent ameliorating effect on acute graft-versus-host disease (GVHD), and on the graft-versus-leukaemia (GVL) effect of allogeneic bone marrow transplantation (BMT). KB-R7785 was administered to (C57BL/6 x BALB/c) F1 (CBF1) mice that had been inoculated with IgE-producing B53 hybridoma cells of BALB/c origin as a model tumour, along with or without transplantation of C57BL/6 (B6) bone marrow cells and spleen cells (BMS). Administration of KB-R7785 without BMS significantly prolonged the survival of B53-inoculated CBF1 mice by inhibiting the infiltration of B53 cells into the liver and spleen. Transplantation of B6 BMS without KB-R7785 resulted in the death of most recipients due to acute GVHD while efficiently eliminating B53 cells. Administration of KB-R7785 along with B6 BMS resulted in a 50% survival of B53-inoculated CBF1 mice over 50 d without histological manifestations of acute GVHD or residual B53 cells. These results indicate the beneficial effects of KB-R7785 that inhibit tumour infiltration and prevent acute GVHD while preserving the GVL effect of allogeneic BMT.

Animals↗

True small lymphocytic T-cell chronic lymphocytic leukemia lacking the CD3 molecule and TCR-alpha beta on its cell surface.

We report a case of T-cell chronic lymphocytic leukemia (T-CLL) in which the lymphocytes were small and mature, did not have cytoplasmic granulation, and appeared to be similar to those of B-cell chronic lymphocytic leukemia (B-CLL). Immunophenotyping of the lymphocytes revealed CD2+, CD4+, CD5+, and CD25+ on the cell surface, but expression of the CD3 and TCR-alpha beta molecules was localized only in the cytoplasm. The clinical course was as indolent as that of B-CLL, and the patient was able to undergo open-heart surgery. Thus, we confirmed that true T-CLL is able to exist as a counterpart of B-CLL.

Aged↗

Differential effects of anti-Fas ligand and anti-tumor necrosis factor alpha antibodies on acute graft-versus-host disease pathologies.

Both tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD). In this study, we examined the ameliorating effects of neutralizing anti-FasL and/or anti-TNFalpha monoclonal antibody (MoAb) in a lethal acute GVHD model in mice. Whereas the treatment with either anti-FasL or anti-TNFalpha MoAb alone significantly delayed the mortality and improved the body weight, a complete protection was achieved by the administration of both MoAbs. Pathological examination indicated differential effects of anti-FasL or anti-TNFalpha MoAb on GVHD-associated pathologies. Hepatic lesion was improved by anti-FasL but not anti-TNFalpha MoAb. In contrast, intestinal lesion was improved by anti-TNFalpha but not anti-FasL MoAb. Cutaneous and splenic lesions were improved by either MoAb. The combination of both MoAbs improved all these lesions. These results indicate that FasL and TNFalpha differentially contribute to the GVHD pathologies and a complete protection from mortality can be achieved by neutralization of both FasL and TNFalpha.

Animals↗

Temporal and spatial distribution of DNA topoisomerase II alters during proliferation, differentiation, and apoptosis in HL-60 cells.

We related cellular content of DNA topoisomerase (topo) IIalpha and IIbeta with the cell cycle position in proliferating, differentiated, and apoptotic HL-60 cells using two-dimensional flow cytometry. In logarithmically growing HL-60 cells, topo IIalpha increased especially in late S to G2/M phases, although the topo IIbeta level was almost constant throughout the cell cycle. Induction of differentiation by all-trans retinoic acid dramatically reduced the topo IIalpha but not the topo IIbeta level. A new G2/M population containing virtually no topo IIalpha appeared during differentiation and was supposed to be alive and noncycling. Two-dimensional flow cytometry of topo IIalpha or IIbeta staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay showed that one topo IIbeta epitope situated at the C-terminal end decreased specifically in apoptotic HL-60 cells treated with Ara-C, etoposide, and vincristine. The amounts of a topo IIalpha epitope and another topo IIbeta epitope located at a more central portion were almost equal between apoptotic and nonapoptotic cells. Western blot analysis confirmed that topo IIbeta protein was completely degraded into smaller fragments and lost its C-terminal end during apoptosis. On the contrary, a large portion of topo IIalpha remained of its original size, although both topo IIalpha and IIbeta left from the nuclear fraction in apoptotic cells. Confocal laser microscopy showed nuclear localization of topo IIalpha and IIbeta in growing HL-60 cells. Although topo IIalpha and IIbeta were distributed throughout the cell during mitosis, only topo IIalpha was densely concentrated in the mitotic chromosomes. Both enzymes were dissociated from the genomic DNA even at an early phase of apoptosis and completely separated from the propidium iodide signal of DNA in the advanced stage. Chromatin condensation process in apoptosis is therefore completely topo II-independent and obviously differs from the mitotic one.

Apoptosis↗

Direct measurement of CD34+ blood stem cell absolute counts by flow cytometry.

For the collection of adequate numbers of peripheral blood stem cells (PBSC) for PBSC transplantation, an accurate quantification of circulating CD34+ stem cells is required for deciding the optimal time of the collection. To enumerate peripheral blood (PB) CD34+ stem cells, the percentage of CD34+ cells in the gated PB mononuclear cells should be multiplied by the percentage of the gated mononuclear cells among white blood cells (WBC) and by the total WBC count. Accordingly, a minor difference in the measured percentage of the CD34+ cells can lead to a major difference in the PB CD34+ cell concentration. In the present study, we measured the concentration of PB CD34+ stem cells with a flow cytometer designed to provide direct absolute counts of cell subsets from a single instrument. Whole blood was stained with a phycoerythrin-conjugated anti-CD34 monoclonal antibody, and, after the lysis of red blood cells, CD34+ cells were counted in a fraction of the lymphocyte and monocyte gate. The accuracy of our method was demonstrated in an experiment in which various dilutions of known numbers of CD34+ leukemic cells were mixed with normal blood; the predicted value of the CD34+ cell count was observed. The concentration of CD34+ cells in leukapheresis products was measured both by our direct assay and an indirect assay that calculates the number from the percentage of CD34+ cells in mononuclear cells, and our assay was shown to produce less variation. Further, our assay showed a significant correlation between the concentration of mobilized CD34+ cells in the PB and the number of harvested CD34+ cells in leukapheresis. These findings indicate that the monitoring of the concentration of PB CD34+ cells by the present method can be used to predict the number of stem cells collected in leukapheresis. This procedure is easy to perform and can be applied to daily monitoring to decide the appropriate timing for harvest of mobilized stem cells.

Antigens, CD34↗

Multicentric Castleman's disease associated with renal amyloidosis and pure red cell aplasia.

A 50-year-old man was admitted suffering from severe anemia and renal dysfunction. He had been admitted for the first time at the age of 49, and was diagnosed with multicentric Castleman's disease (MCD) and secondary amyloidosis. At that time, marked erythroid hypoplasia was demonstrated by both aspiration and biopsy of bone marrow. A diagnosis of pure red-cell aplasia (PRCA) was made. Immunosuppressive agents improved his symptoms and laboratory data. We report here a very rare case of PRCA following MCD and amyloidosis, and with reference to the literature, we discuss the relation between MCD and related diseases.

Amyloidosis↗

14q11 abnormality and trisomy 8q are not common in Japanese T-cell prolymphocytic leukemia.

We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.

Adult↗

Detection of chimaeric transcripts of the immunoglobulin heavy chain and BCL6 genes by reverse-transcriptase polymerase chain reaction in B-cell non-Hodgkin's lymphomas.

T(3;14)(q27;q32) is frequently detected in B-cell non-Hodgkin's lymphomas, especially the diffuse large cell type and the follicular type. The BCL6 gene encoding a putative transcriptional factor which resides on 3q27 rearranges to the immunoglobulin heavy chain (IgH) gene on 14q32 in this chromosomal translocation. The upstream regulatory region of the BCL6 gene is replaced by the IgH gene. Deregulation of the BCL6 gene may contribute to tumourigenesis of these diseases. The rearrangement between the IgH and BCL6 genes generates chimaeric transcripts in which the joining (J) region of the IgH gene fuses to exon 3 of the BCL6 gene. We established a method to detect these chimaeric transcripts by reverse transcriptase polymerase chain reaction (RT-PCR) using the consensus sequence of the J region and the sequence of exon 3 of the BCL6 gene as primers. Using the semi-nested RT-PCR method and a cell line carrying t(3;14)(q27;q32), we detected one lymphoma cell among 10,000 background cells. We detected these chimaeric transcripts in two out of 13 clinical samples by this method. This method can detect t(3;14)(q27;q32) easily, whereas this alteration is frequently overlooked by routine karyotype analysis. Since this technique is sensitive enough to detect a small number of lymphoma cells with this genetic abnormality, it could be employed to detect contaminating lymphoma cells in bone marrow and peripheral blood and minimal residual diseases.

Base Sequence↗

[Clinical efficacy of fosfomycin in combination with sulbactam/cefoperazone in the treatment of severe infections complicated to blood dyscrasia. Working Group of Kanto Combination Therapy for FOM + SBT/CPZ].

In the treatment of severe infections complicated to blood dyscrasia, the efficacy and usefulness of fosfomycin (FOM) in combination with sulbactam (SBT)/cefoperazone (CPZ) were compared between patients receiving FOM in the first followed by SBT/CPZ (Group A) and those receiving both drugs simultaneously (Group B). The following results were obtained. 1. The efficacy rate was 56.3% for Group A and 47.9% for Group B, with no significant difference. 2. The efficacy for patients suspected of the presence of septicemia, the efficacy rate was 57.9% for Group A and 54.3% for Group B, with no significant difference. 3. As for underlying disease, patients with acute myelogenous leukemia were most prevailing. In these patients, the efficacy rate was 57.1% for Group A and 27.3% for Group B, with no statistically significant difference. However, the efficacy rate tended to be higher in Group A. 4. The administration of antibiotics was effective to restore the neutrophil count to 501/microliters or higher in 77.8% and 45.5% of the cases for Groups A and B, respectively, with significantly higher efficacy for Group A. 5. In the safety evaluation a total of 115 cases were included. Side effects and laboratory abnormalities were seen in 3 cases each, but none of them were serious in degree. From these results, it was confirmed that the combination therapy consisting of administration of FOM followed by SBT/CPZ with some interval is effective for severe infections complicated to blood dyscrasia.

Anti-Bacterial Agents↗

[A 45-year-old man with peripheral monocytosis and right hemiparesis].

We report a 45-year-old man with monocytosis and right hemiparesis. The patient suffered from an acute myocardial infarction from which he recovered completely when he was 42 years old. One year prior to his death, he was found to have increase in monocyte count (35.5% of leukocytes) in peripheral blood and splenomegaly; he was admitted to the hematology service of our hospital. He was diagnosed as having chronic myelomonocytic leukemia after bone marrow examination. He was treated with radiation therapy with improvement in splenomegaly. In May of 1995, he had fever, anemia, and thrombocytopenia for which he needed daily blood transfusion. In November of 1995, he had an onset of weakness in his right hand, and neurologic consultation was asked for in November 27, 1995. Neurologic examination revealed a chronically ill japanese man in no acute distress. He was alert and not demented. Higher cerebral functions were intact. Cranial nerve examination revealed right facial paresis of the central type. Motor-wise, he was right hemiparetic. Generalized muscle wasting was noted apparently due to the chronic debilitating disease. Deep tendon reflexes were within normal range in the right upper extremity, but were diminished in other areas. Sensation was intact, and no meningeal signs were noted. Pertinent laboratory findings were as follows: Hb 8 g/dl, RBC 238 x 10(4)/microliter, WBC 2,900/microliter (band 1.0%, seg 18.5%, lym 28.0%, mono 44.0%, Baso 2.5%), Plt 13 x 10(4)/microliter, PT 16.6"/10.9", APTT 44.7"/35.0". CSF contained 87 mg/dl of protein, 155 mg/dl of glucose and 2 mononuclear cells/microliter. Bone marrow was slightly hypercellular with mild increase in blast forms. No chromosome abnormality was found. CT and MRI revealed a large mass in the left fronto-parietal region and the meninges showed marked thickening with enhancement after gadolinium-DTPA in MRI. The patient was treated with glycerol and steroid, but the subsequent course was complicated by a seizure, agitation, and pneumonia. He died from respiratory failure on January 13, 1996. The patient was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had chronic myelomonocytic leukemia with infiltration of leukemic cells into meninges and the parenchyme of the cerebrum. Thickening of the dura was thought to be in part a reaction to the subdural hematoma as well as to leukemic cells along the meninges. Postmortem examination revealed hypercellular bone marrow with increase in monocytic cells (more than 20%). The lungs showed pneumonia with scattered old tuberculous lesions. The heart showed an old myocardial infarction in the posterior wall of the left ventricle. The brain showed an old chronic subdural hematoma in the left fronto-temporal region and a cystic mass lesion in the left frontoparietal region. The mass was hypercellular and most of them were monocytes. The dura mater showed reactive thickening without leukemic cell infiltration. It was concluded that this patient had chronic myelomonocytic leukemia with a formation of leukemic mass in the brain. Pathologists thought that the mass was a hematogenous spread. It is rare for chronic myelomonocytic leukemia to form a mass lesion in the brain.

Brain↗

Systemic aspergillosis caused by an aflatoxin-producing strain of Aspergillus flavus.

The first case of human systemic infection by an Aspergillus flavus isolate demonstrated to produce aflatoxins in vitro and in vivo is described. The patient, a 41-year-old man with acute myelogenous leukaemia, developed a complication of suspected pulmonary Aspergillus infection during remission induction therapy. Antifungal chemotherapy brought about a considerable degree of improvement, but remission of the underlying disease was not attained. Bone marrow transplantation was also not effective. The patient showed recovery from neutropenia but died despite aggressive antifungal chemotherapy. The autopsy revealed lesions in the lungs, myocardium, kidneys, brain, thyroid gland and skin due to a suspected Aspergillus sp. A fungus isolated from the right lung and the skin lesions was identified as A. flavus. Aflatoxins B1, B2 and M1 were detected in culture filtrates of the isolated A. flavus, and in an extract of lung lesions. These aflatoxins are considered to have played an important role in damaging the immune system of the patient through their toxic effects.

Adult↗

[Mantle cell lymphoma with marked lymphocytosis at the presentation and with discordant morphology between the lymph node and peripheral blood].

A 72-year-old man was referred to our hospital because of lymphadenopathy, splenomegaly, and leukocytosis. His WBC count was 54,300/microliter, with 89.6% atypical lymphocytes two to three times the diameter of red blood cells, cleaved nuclei, and one or two nucleoli. A lymph node specimen revealed a vaguely nodular pattern, and the diagnosis of mantle cell lymphoma (MCL) was made. The lymphoma cells appeared smaller and more mature than the leukemic cells. The phenotype of the peripheral blood and the lymph node cells was CD5+ CD10- CD19+ CD20+ and the same rearranged JH bands were detected, suggesting that their lymphocytes were of the same origin. In addition, the phenotype of the leukemic cells was CD23+ CD38+ CD43- CD44+ FMC-7+ micro+ chi+. Cytogenetic analysis revealed complex anomalies but not t(11; 14). Cyclin D1 protein was not detected. Because the lymphocyte morphology of the peripheral blood and lymph nodes was discordant, we speculated that variant large cells had proliferated mainly in the peripheral blood. The patient achieved a partial response after 6 courses of CHOP regimen, and was then placed on a COP regimen. He seemed to have MCL, but the following findings were unusual: marked lymphocytosis at initial presentation, discordant morphology, CD5+ CD10- CD23+ CD43- phenotype with neither t(11; 14) or cyclin D1 over-expression.

Aged↗

[Mycosis fungoides].

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Administration, Topical↗

[Sézary syndrome].

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Antineoplastic Combined Chemotherapy Protocols↗

[Systemic aspergillosis caused by an aflatoxin-producing strain of Aspergillus in a post-bone marrow transplant patient with acute myeloid leukemia].

We report a case in which an aflatoxin-producing strain of Aspergillus flavus (A. flavus) caused systemic aspergillosis in a post-transplant 41-year-old man with acute myeloid leukemia. The leukemia was initially resistant to two courses of induction chemotherapy. The third course of chemotherapy, however, induced complete remission. Thereafter, the patient underwent bone marrow transplantation from his HLA identical brother. Pulmonary aspergillosis was suspected as a complication during induction chemotherapy. Twenty days after the transplant, the patient's absolute neutrophil count had increased to 500/microliter. However, the symptoms of pulmonary aspergillosis were aggravated following neutrophil and monocyte recovery. The patient died of sinus arrest due to complete atrioventricular block 31 days after his transplant. At autopsy, we found that the fungus had invaded the brain, lungs, spleen, kidneys, skin, and myocardium, including the sinoatrial conduction system. There was no sign of acute graft-versus-host disease. A strain of A. flavus was isolated from cultured tissue samples of fungal lesions and shown by thin-layer chromatography to produce aflatoxins. To our knowledge, this is the first case report describing an infection by an aflatoxin-producing A. flavus.

Acute Disease↗

A metalloproteinase inhibitor prevents lethal acute graft-versus-host disease in mice.

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We examined here the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a lethal acute GVHD model in mice. Administration of KB-R7785 into (BALB/c x C57BL/6) F1 that received C57BL/6 spleen cells markedly reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The ameliorating effect of KB-R7785 was superior to that of anti-TNF-alpha antibody. Our results suggest that KB-R7785 could be a potent therapeutic agent for GVHD.

Animals↗