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Biomedical subjects

S Tagawa

Publications and source records attributed to S Tagawa.

At least 91 records · Page 5Linked to original sources

Brief induction chemotherapy followed by involved-field irradiation for the treatment of localized intermediate- and high-grade non-Hodgkin's lymphoma.

In an attempt to assess the effects and toxicity of brief induction chemotherapy plus involved-field irradiation for localized intermediate- and high-grade non-Hodgkin's lymphoma, we conducted a single-arm prospective trial between May 1987 and July 1991. Patients received four cycles of a five-drug chemotherapy regimen consisting of cyclophosphamide, doxorubicin, vincristine, prednisolone, and bleomycin (CHOP-Bleo) followed by involved-field irradiation of 30 Gy. Of 32 patients consecutively enrolled, 30 patients had measurable and/or evaluable disease, while two had no evaluable disease, as their major tumors had been surgically removed. All the patients were in complete remission at the conclusion of all treatment. Four patients have relapsed so far and one died of the disease at 17 months. With a median follow-up time of 33 months (range, 8 to 58), the actuarial disease-free survival rate was 82% and the overall survival rate was 96%. The toxicity was generally mild and all the patients received the planned treatment course. This treatment modality appeared to be safe and effective for localized intermediate- and high-grade non-Hodgkin's lymphoma.

Adult↗

Alternating chemotherapy of CHOP-Bleo and POEM-Bleo for diffuse large-cell lymphoma: a single-institutional study with a long-term follow-up.

Diffuse large-cell lymphoma (DLCL) is a neoplasm that is curable with chemotherapy in an appreciable percentage of patients. However, not all patients are cured and the best drug combination and optimal dose intensity have not yet been established. In an attempt to improve complete response rate and survival with minimal toxicity, we devised an alternating combination chemotherapy consisting of CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisolone, and bleomycin) and POEM-Bleo (prednisolone, vincristine, etoposide, mitoxantrone, and bleomycin). Between March 1986 and October 1990, 30 newly-diagnosed patients with advanced DLCL were treated with the regimen. Of these 30 patients, 14 (47%) were 61 years of age or more, 15 (50%) had stage IV disease, 14 (47%) presented with constitutional symptoms, and 7 (23%) had T-cell lymphoma. After the completion of therapy, 23 (77%) achieved a complete response and 6 (20%) had a partial response. The actuarial relapse-free survival at 5 years is 52% and the overall survival projected to 5 years is 47%. Toxicity was generally mild and well tolerated. Although this alternating regimen had substantial activity as front-line chemotherapy for advanced DLCL, we conclude that the observed response rate and survival do not essentially differ from those achieved with conventional regimens and further clinical trials are thus not warranted.

Adult↗

Primary pulmonary non-Hodgkin's lymphoma in a Japanese renal transplant recipient.

Pulmonary non-Hodgkin's lymphoma (NHL) developed in a 31-year-old renal transplant recipient 3 years after transplantation. Chest roentgenogram showed rapidly progressive multiple nodules in both lungs. The pleural fluid obtained by needle aspiration contained many atypical cells with surface B cell antigen and abnormal karyotype. The patient died of pulmonary edema shortly after combination chemotherapy was begun without regression of the tumors. Autopsy revealed diffuse large cell NHL confined to both lungs. Immunological examination and DNA analysis of the tumor showed monoclonal B cell NHL.

Adult↗

[Multiple myeloma and adhesion molecules].

The physiological role of fibronectin (FN) on the human plasma cells were examined using three PC cell lines, FR4ds, OPM1 and OPM1ds. FR4ds was reactive with anti-VLA-alpha 4 and anti-alpha 5. In contrast, OPM1 and OPM1ds were not reactive with anti-VLA-alpha 5. FN induced spreading in FR4ds and OPM1ds. Albumin blocked these spreadings. FR4ds with mature plasma cell phenotype of alpha 4+ and alpha 5+ was more sensitive for FN than OPM1 and OPM1ds with immature phenotype of alpha 4+ and alpha 5-. Spreading cells proliferated more than floating cells. All these cell lines showed chemotaxis toward FN. alpha 5+ FR4ds was more sensitive for FN than OPM1 and OPM1ds with alpha 5- phenotype. These new abilities of PC of spreading and chemotaxis we found are summarized to be an affinity to organs. It is likely that alpha 4+ and alpha 5- PC with low affinity to organs are stored in peripheral blood as a result. We examined the chemotaxtic activity of myeloma cells in bone marrow and these in pleural effusions in a patient with multiple myeloma. These cells in pleural effusions showed more chemotaxic activity than these in bone marrow. FN induced growth, production of Ig, and motility of PC, which resulted in the augmentation of humoral immunity.

Bone Marrow Cells↗

Genomic organization of human fetal specific P-450IIIA7 (cytochrome P-450HFLa)-related gene(s) and interaction of transcriptional regulatory factor with its DNA element in the 5' flanking region.

P-450IIIA7 is a form of cytochrome P-450 which was isolated from human fetal livers and termed P-450HFLa. This form has been clarified to be expressed during fetal life specifically (Komori, M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K. and Kamataki, T. (1990) Biochemistry 29, 4430-4433). In the present study, we isolated five independent clones which probably corresponded to the human P-450IIIA7 gene. These clones were completely sequenced, all exons, exon-intron junctions and the 5' flanking region from the cap site to-869. Although the sequences in the coding region were completely identical to P-450IIIA7, it is possible that genomic fragments sequenced in this study encode portions of other P-450IIIA7-related genes since we could not obtain a complete overlapping set of genomic clones. Within its 5' flanking sequence, the putative binding sites of several transcriptional regulatory factors existed. Among them, it was shown that a basic transcription element binding factor (BTEB) actually interacted with the 5' flanking region of this gene.

Adult↗

Monocytes appearing repeatedly after chemotherapies had an identical rearrangement pattern of immunoglobulin with leukemic blasts in a patient with CD13+ acute lymphoblastic leukemia.

We recently encountered a patient with acute lymphoblastic leukemia (ALL) who showed temporal monocytosis of an unusually high cell count (5,000-30,000 monocytoid cells/microliter) five times after treatment with different chemotherapies. The leukemic cells expressed B-cell-associated antigens, CD19 and CD10, E-rosette receptor, CD2 and monocyte/myeloid antigen, CD13 simultaneously. They were peroxidase-negative. One week after the initiation of conventional chemotherapy for ALL, the leukemic blasts had disappeared. Alternatively, monocytoid cells appeared along with the recovery from nadir status. They showed several features of monocytes; they were weakly dot-positive for nonspecific esterase, reactive with CD14 and CD13 and Fc gamma-receptor-positive. Furthermore, they migrated into a fungally infected joint space. Features incompatible with normal monocytes were the absence of peroxidase reactivity, the expression of B-cell-associated antigens, CD19 and CD10 and E-rosette receptor, CD2. Southern blot hybridization analysis revealed an unexpected result that HindIII digested DNA from both leukemic blasts and monocytoid cells had the same rearranged band of IgH. Thus, an identical clonality of monocytoid cells, temporally appearing after chemotherapies and leukemic lymphoblasts, was determined in this patient with CD13+ ALL.

Antigens, CD↗

Transformation of large granular lymphocytic leukemia during the course of a reactivated human herpesvirus-6 infection.

A patient with CD3+ large granular lymphocytic (LGL) leukemia developed transformation (TF). The phenotype of the leukemic cells was CD3+, CD4+ and CD8-. The leukemic cell count increased rapidly; the cells became large and the nuclear outline, which had been reniform, became lobulated. Anti-HTLV-1 and anti-HIV antibodies were negative in the serum of the patient and no HTLV-1 specific sequences were detected in the cDNA of the leukemic cells by polymerase chain reaction (PCR). Comparison of the karyotype abnormality of the leukemic cells before and after TF revealed an abnormality of the 21 trisomy in 90% of mitotic cells of the patient. Analysis of the cell cycle revealed that 13.7% of the leukemic cells were in DNA synthesis phase which was not previously found. The titer of anti-human herpesvirus-6 (HHV-6) immunoglobulin G which had been high at chronic phase (1:1640 compared to normal titer of less than 1:160), became 1:20,000 at TF. The titer of anti-HHV-6 immunoglobulin M also increased from less than 1:4 at the chronic phase to 1:120 at TF (normal value less than 1:4). A HHV-6-specific DNA sequence was detected by PCR in the peripheral mononuclear cells collected at TF but not at the chronic phase. These data suggests that TF occurs not only in CD3-negative but also in CD3-positive LGL leukemia. HHV-6 reactivation is therefore a possible cause in immunocompromised hosts whose general conditions are deteriorated.

Aged↗

[Clinical effects of cefodizime in severe infections complicated with hematological diseases. Hanshin Infection Study Group].

One hundred thirty-eight patients with severe infections accompanying hematological diseases were treated with cefodizime (CDZM). CDZM was administered by intravenous injection at daily doses ranging from 2 g to 8 g for about 3 to 18 days. Clinical efficacies of CDZM were excellent in 30 cases, good in 37 cases, fair in 1 case and poor in 53 cases. The efficacy rate was 55.4%. The efficacy rate was 56.4% in patients from whom causative organisms were not identified. The efficacy rate against Gram-negative bacteria (66.7%) was higher than that against Gram-positive bacteria (28.6%). No significant differences in the efficacy rates were found among groups of patients with different initial neutrophil counts (less than 100, 100-499, and over 500/microliters). Skin eruption caused by CDZM was observed in 2 patients (1.5%). Hepatic disorders, renal dysfunction and urinary test abnormality (protein and urobilinogen) were observed in 7 (5.0%), 1 (0.7%) and 1 (0.7%), respectively. Therefore, CDZM was considered to be a clinically useful antibiotic for severe infections complicated with hematological diseases.

Adolescent↗

[Therapeutic effects of meropenem against severe infections in patients with hematopoietic disorders. Hanshin Study Group of Hematopoietic Disorders and Infection].

The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.

Adolescent↗

[Large granular lymphocytic leukemia].

We investigated the surface markers, cell-function, clonality, and the association of IL-2 receptors and a second messenger of src family of tyrosine kinase p56lck in IL-2 signal transduction of the leukemic cells of 12 patients with large granular lymphocytic leukemia (LGL leukemia). The leukemic cells of 5 patients were CD3+ and 5 of them were CD3-. In three patients with CD3- leukemia examined, one showed karyotype abnormality of 46, XY, -10, +mar and the delta gene of TCR was rearranged in one patient. The TCR of the leukemic cells of a patient MH with CD3+, CD4 and CD8 (double positive marker: DP) recognised rabbit IgG presented by macrophages. The recognition was class II restricted. We examined the expression pattern of CD8 subunits and found that DP leukemic cells commonly expressed CD8 alpha+ beta-. These results suggested that DP leukemic cells were CD4+ T cells and expressed CD8 alpha secondarily. The p75 IL-2 receptors were detected, however, the modulation of p56lck in the process of IL-2 signal transduction were not found out. There was no association between p75 and p56lck when leukemic LGL cells proliferated on stimulation with IL-2.

Antigens, CD↗

Chromosomal abnormalities define clonal proliferation in CD3- large granular lymphocyte leukemia.

Six patients with lymphoproliferative disorder of large granular lymphocytes (LDGL) were studied for chromosomal abnormalities. When the patients were divided into two groups depending on the expression of a mature antigen of T cell lineage, CD3, two with CD3+ phenotype had a stable disease, whereas three of the four patients with CD3- phenotype had marked hepatosplenomegaly and a highly aggressive disease. Chromosomal abnormalities were detected in four of six patients, indicating a clonal proliferation of large granular lymphocytes in individual patients. In particular, chromosomal abnormalities were found in three of the four patients with CD3- LDGL, all of which had a germ-line configuration of the T cell receptor beta-chain gene. Thus, the chromosomal abnormalities provide definitive evidence for the clonal origin of the expanded cells in the CD3- LDGL.

Adult↗

[Actual conditions of bacterial infection associated with hematopoietic disorders--changes in 10 years. The Hanshin Study Group of Hematopoietic Disorders and Infections].

This study showed several accumulated data through ten years from our experience in hematopoietic disorders and associated infections, which has been analyzed by the Hanshin Study Group of Hematopoietic Disorders and Infections. Since 1979 to 1988, our group had evaluated the sorts of causative organisms and the efficacy of various antibiotics therapy in 2119 cases of infectious diseases associated with hematopoietic disorders. On behalf of evaluating the changes of disease profile for ten years, we divided the accumulated data into three phases; former phase the first three years, middle phase the second three years and late phase the last four years. There was no significant difference in the frequency of various hematopoietic disorders among the three phases. Each leukemia patients occupied 77% of all cases. Sepsis suspected is the most frequent infectious disease accounting for 68.8%. The other infectious diseases were 8.4% of the sepsis, 14.8% of the respiratory infections and 3.1% of the urinary tract infections. Comparing the frequency of infections among the three phases, the respiratory and urinary tract infections inclined to decrease. Of the 532 strains isolated from 2119 cases and identified as causative organisms, gram-negative bacilli occupied 62.8% and gram-positive bacteria 36.5%. In comparing the percentage of gram-negative bacilli among the three phases, it showed a decreasing tendency in order former phase 63.6%, middle phase 76.4% and late phase 43.8%. Pseudomonas, however, had been isolated at almost constant ratio through ten years. On the other hand, the ratio of gram-positive bacteria isolated were 34.5% in former phase, 23.6% in middle phase and 56.3% in late phase, showing increasing a tendency through the period. Twenty-three kinds of antibiotics were administered by intravenous drip infusion. The efficacy rate was 43.9% to 67.2%. In particular, effectiveness of antibiotic therapy often depends on the change of peripheral neutrophil counts from the onset and during the therapy. The efficacy rate, however, was 36% even neutrophil counts have not shown the tendency of increase from less than 100/microliters.

Adolescent↗

Amylase-producing plasmacytoma cell lines, AD3 and FR4, with der(14)t(8;14) and dic(8)t(1;8) established from ascites.

We established two human plasma cell lines, FR4 and AD3, from ascitic fluid in a patient with IgA k plasmacytoma (PC). Aberrant amylase production was found in this patient. Both AD3 and FR4 were free of Epstein-Barr virus, and both produced Ig A k in vitro. They produced amylase of the salivary type in vitro. This was confirmed by the demonstration of amylase mRNA comigrating with salivary gland mRNA. These cell lines commonly had unusual chromosomal abnormalities der(14)t(8;14) and dic(8)t(1;8). AD3 had additional chromosomal abnormalities compared with FR4. This suggests that AD3 is a subline of FR4. The oncogene c-myc is rearranged in most case of Burkitt's lymphoma with t(8;14). However, neither rearrangement nor amplification of the c-myc allele was detected in our PC lines. These lines expressed c-myc of 2.4 kb. There were no structural changes in the amylase genes of AD3 and FR4 detectable with Southern blotting analysis. As these lines were authentic PC lines, they would be useful for the future study of the relationship between the mechanism of oncogenesis and the rare tumor aberration, amylase production.

Aged↗

Molecular analysis of T cell receptor and CD3 genes in CD3- large granular lymphocytes (LGLs): evidence for the existence of CD3- LGLs committed to the T cell lineage.

Seven patients with CD3- lymphoproliferative disorder of granular lymphocytes (LDGL) were analyzed for rearrangement of the T cell receptor (TCR) delta and alpha as well as gamma and beta genes. Among those patients six showed the germline configuration of all known rearranging TCR genes. Two analyzed patients of them lacked CD3-gamma transcripts and expressed nonfunctional TCR-beta transcripts. Meanwhile, TCR-delta gene rearrangement accompanied by expression of full-length TCR-delta transcripts was observed in one patient with CD3- LDGL. In addition, the cells from this patient transcribed the CD3-gamma gene which is one of the earliest events restricted to cells committed to the T cell lineage. These findings indicate that CD3- LGLs include not only cells belonging to the NK cell lineage but also precursor cells committed to the T cell lineage.

Antigens, Differentiation, T-Lymphocyte↗

Association of protein tyrosine phosphorylation with B cell differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA).

We have assessed whether tyrosine protein kinase (TPK) is involved in B cell differentiation. In vitro phosphorylation of an endogenous substrate in B cell leukemias showed that leukemic B cells at different stages of differentiation had specific endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. To clarify the relationship between TPK and the process of B cell differentiation, we studied protein tyrosine phosphorylation in two kinds of leukemic B cells, which showed distinct responses to TPA (12-O-tetradecanoylphorbol-13-acetate) in B cell differentiation. TPA-treated leukemic B cells from patients with B cell chronic lymphocytic leukemia (B-CLL) differentiated into cytoplasmic immunoglobulin (clg)+ plasmacytoid cells, while TPA-treated leukemic B cells from patients with hairy cell leukemia (HCL) did not differentiate into clg+ cells, but showed a peculiar morphological change, spreading. Untreated B-CLL cells and HCL cells showed similar TPK activities and tyrosine protein phosphorylation. When treated with TPA, enhanced phosphorylation was seen in B-CLL cells, while a clear reduction in phosphorylation was found in HCL cells. However, using 4-hydroxycinnamide derivatives which reduce TPK activity, we found that only the reduction of TPK activity did not lead HCL cells to spreading. These data suggest that protein tyrosine phosphorylation and/or dephosphorylation might be involved in B cell differentiation, but only the change of TPK activity in HCL cells is not sufficient to induce effects.

B-Lymphocytes↗

[Clinical evaluation of combination therapy with aspoxicillin and ceftazidime for severe infections complicating hematological disorders].

Clinical effects of a combination therapy using aspoxicillin (ASPC) and ceftazidime (CAZ) were investigated in 88 patients with severe infections which were complicating hematological disorders. ASPC and CAZ were administered intravenously at daily doses of 8 g and 4 to 6 g, respectively, in 2 to 4 divided doses for at least 3 days. The treatment was markedly effective in 20 cases; effective in 31; fairly effective in 4; and ineffective in 33 cases. Seventy-seven patients with whom detailed data were obtained showed an efficacy rate of 63.6%. Bacteria were detected in 9 patients, from whom 10 strains were isolated. The results of bacteriological effects were: 3 strains disappeared, 1 decreased, 3 unchanged, and 3 unclear. The bacteriological eradication rate was 42.9%. Of the detected 10 strains, 3 were identified as Pseudomonas aeruginosa, with 2 of the 3 strains eradicated and 1 decreased. An evaluation of the relationship between clinical efficacies and neutrophil counts before and after the ASPC-CAZ combination therapy showed that the patients with 500/mm3 or higher neutrophil counts before the therapy or those with increased neutrophils after the therapy tended to be more responsive to the therapy. Side effects were observed in 4 patients, but all of them disappeared upon discontinuation of the therapy. The combination therapy with ASPC and CAZ appears to be useful for the treatment of severe infections complicating hematological disorders.

Adolescent↗