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Biomedical subjects

K Kawa

Publications and source records attributed to K Kawa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Long-term survivors of advanced neuroblastoma with MYCN amplification: A report of 19 patients surviving disease-free for more than 66 months.

PURPOSE: According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN proto-oncogene developed progressive disease within 8 months. The prognosis for such patients, however, should now be reevaluated in light of recent results achieved with up-to-date combination chemotherapy. PATIENTS AND METHODS: Patients with stage 3, 4, and 4S neuroblastoma and more than 10 copies of MYCN received induction chemotherapy, which from January 1985 to February 1991 consisted of regimen A(1 )(cyclophosphamide 1,200 mg/m(2) on day 1, vincristine 1.5 mg/m(2) on day 1, pirarubicin 40 mg/m(2) on day 3, and cisplatin 90 mg/m(2) on day 5) and from March 1991 to September 1993 consisted of regimen A(3 )(cyclophosphamide 1,200 mg/m(2) on days 1 and 2, pirarubicin 40 mg/m(2) on day 3, etoposide 100 mg/m(2) on days 1 through 5, and continuous infusion cisplatin 25 mg/m(2) on days 1 through 5). Most of these patients underwent radical surgery to remove the original tumor and local metastases, irradiation, and supralethal preconditioning regimens, followed by blood stem-cell transplantation (SCT). Data on the patients were collected in December 1998, and the factors contributing to disease-free survival were analyzed. RESULTS: During the study period, 66 patients with more than 10 copies of MYCN were treated. Five of nine patients with stage 3 disease, 13 of 55 with stage 4, and one of two with stage 4S survived for at least 66 months. It is interesting that all but one patient who survived for more than 66 months underwent SCT, in contrast with only five of 45 patients who died. CONCLUSION: Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Evidence that CD31, CD49b, and CD62L are immunodominant minor histocompatibility antigens in HLA identical sibling bone marrow transplants.

Despite complete matching of siblings for the HLA loci, after bone marrow transplantation (BMT), approximately 20% develop graft-versus-host disease (GVHD). This is presumably due to incompatibility of minor histocompatibility antigens (mHa). We investigated the polymorphisms of 14 adhesion molecules (CD2, CD28, CD31, CD34, CD36, CD42, CD44, CD48, CD49b, CD54, CD62L, CD86, CD102, and CD106) in Japanese subjects and their association with the occurrence of GVHD after allogeneic HLA identical BMT. Six molecules (CD2, CD31, CD42, CD49b, CD54, and CD62L), which were found to be polymorphic, were then examined in 118 HLA identical sibling donors and recipients who had undergone BMT. Association of the incompatibility of the polymorphic molecules with the presence or absence of GVHD was examined. In these six, we observed a significant correlation between acute GVHD and the compatibility of CD31 (codons 563/670) (Pcorrected = .018), and CD31 (codons 563/670) + CD62L (Pcorrected = .018) in patients with the HLA-B44-like superfamily. In patients with the HLA-A3-like superfamily, the compatibility of CD62L (Pcorrected = .03) and CD62L + CD49b (P = . 004, Pcorrected = .078) was associated with acute GVHD. Therefore, CD31, CD49b, and CD62L might be candidates for immunodominant mHa.

Adolescent↗
PubMed1998

Stratification of treatment of stage 4 neuroblastoma patients based on N-myc amplification status. Study Group of Japan for Treatment of Advanced Neuroblastoma, Tokyo, Japan.

BACKGROUND: It has been shown that children aged more than 12 months with stage 3 and 4 neuroblastoma with N-myc amplification do worse than those without amplification. Development of an innovative chemotherapeutic protocol for patients in such an extremely poor-risk group was the purpose of this study. PROCEDURE: Since March 1991 a new protocol for the treatment of advanced neuroblastoma was started. When N-myc was amplified more than 10-fold, patients received regimen A3, in which cyclophosphamide 1,200 mg/m2 was given on days 1 and 2; hence the dose of cytotoxic drugs was doubled. Patients with fewer than 10 copies of N-myc received regimen new A1, which is very similar to regimen A1 that had been used until March 1991 for all patients with advanced neuroblastoma with/without N-myc amplification. The efficacy of regimen A3 was evaluated. RESULTS: The relapse-free survival rate at 1 and 2 years for stage 4 patients older than 12 months of age with N-myc amplification of more than 10-fold was 43% and 29%, respectively, with regimen A1 and that for the same subgroup of patients treated with regimen A3 since March 1991 was 79% and 49%, respectively; the difference is statistically significant. On the other hand, there were no differences in the relapse-free survival rate at 1 year and 2 years for stage 4 patients with fewer than 10 copies of N-myc between those treated with regimen A1 and those treated with new A1 since March 1991. CONCLUSIONS: Stratification based on N-myc amplification into new A1 and A3 treatment protocols is of significant clinical importance. Regimen A3 was well tolerated and showed an improvement in clinical results in stage 4 patients with N-myc amplified more than 10-fold.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

CD34+ progenitor cell transplantation from two HLA-mismatched healthy fathers to two infants with severe aplastic anemia.

Pluripotent stem cells of hematopoiesis are included among CD34+ cells in the blood and bone marrow. After granulocyte-colony stimulating factor (G-CSF) mobilization, 1-2% of the mononuclear cells in the blood are CD34+ cells, which can be obtained by leukapheresis. We performed CD34+ progenitor cell transplantation in two children with severe aplastic anemia (SAA) who lacked HLA-matched donors. The donors were treated with G-CSF, 600 micrograms/body/day subcutaneously, for 4-5 days. CD34+ cell selection was performed from the apheresis concentrate with mouse anti-CD34 antibody 9C5 and magnet beads coated with sheep anti-mouse IgG1. After the transplantation, the patients received tacrolimus to prevent graft-versus-host disease (GVHD). G-CSF was given to both patients. A mean number of 4.96 x 10(6) CD34+ cells per kilogram of body weight were transplanted. The hematopoietic recovery after the CD34+ cell transplantation was rapid, except for platelets, and acute GVHD was less than or equal to grade I. Case 1, who demonstrated mixed chimerism, anemia and thrombocytopenia after the graft, received a second transplant with intensified preconditioning, and now sustains complete and stable hematopoiesis after a follow-up of 314 days posttransplant. Although Case 2 showed early rejection and received a second transplant, sustained engraftment was never achieved. However, the patient's own hematopoiesis appeared. For SAA patients who do not have HLA-matched donors, this type of approach seems to be a feasible and useful method. However, an intensified preconditioning regimen to overcome the high likelihood of rejection should be employed.

Adult↗
PubMed1998

Cord blood transplantation from sibling donors in Japan. Report of the national survey.

A joint national survey on cord blood transplantation (CBT) was conducted in Japan and 18 sibling CBTs were reported. Diseases of the patients were leukemia (ten), neuroblastoma (one), bone marrow failure (four) and inborn errors of metabolism (three). A volume of 50-141 ml of cord blood containing 27-197 x 10(7) nucleated cells was collected from sibling infants soon after delivery. HLA antigens were identical in 14 and one to three antigens mismatched in four. Engraftment of donor cord blood was achieved in 17 cases. Autologous hematopoiesis was recovered in one case. Days of engraftment were 13-29 days (median 19 days) for neutrophils (500/microliter), 18-67 days (median 30 days) for reticulocytes (2%) and 21-96 days (median 46 days) for platelets (50 x 10(3)/microliter). Acute GVHD was grade 0 in seven cases, grade I in five cases and grade II in one case in HLA-identical pairs, but became grade II in two cases and grade III in two cases in HLA-mismatched pairs. Chronic GVHD of limited type developed in two out of 17 evaluable cases, however both responded to immunosuppressive therapy. Altogether, 14 out of 18 patients are currently surviving 4-27 months following transplantation. Probabilities of overall survival and disease free survival were estimated to be 77.0 and 71.8% using Kaplan-Meier tests. These findings suggest the feasibility of cord blood transplantation from sibling donors and the possibility of unrelated cord blood transplantation. A cord blood banking system is necessary for the universal use of cord blood stem cells from unrelated donors.

Anemia, Aplastic↗
PubMed1998

Effects of mass screening for neuroblastoma on incidence, mortality, and survival rates in Osaka, Japan.

OBJECTIVES: To evaluate the effects of mass screening for neuroblastoma, time trends of incidence, mortality, and survival of neuroblastoma in Osaka Prefecture were analyzed. METHODS: Data for this analysis was obtained from the population-based Osaka Cancer Registry. Time trends of incidence and mortality rates were analyzed by calendar year and by birth cohort. Survival was compared between before and after the introduction of systematic screening. RESULTS: From 1970-94, 457 cases of neuroblastoma and 182 deaths from neuroblastoma were observed in Osaka. The annual age-standardized incidence rate per million children increased from 7.5 in 1970-84 to 20.5 in 1985-94, while the mortality rates did not differ between these two periods. Analysis by birth cohort showed that the incidence rate at 0 year of age per 100,000 live births increased from 2.30 in 1970-79 (unscreened) to 19.80 in 1988-89 (screening by high-performance liquid chromatography, HPLC). The incidence rate in children 1 and 2-4 years of age also increased according to the introduction of HPLC. The mortality rate in children 1-4 years of age per 100,000 live births slightly decreased from 3.87 in 1970-79 to 3.30 in 1988-89, which was presumed to be derived from the improvement in survival due to the progress in treatment. CONCLUSIONS: It is strongly suggested that mass screening for neuroblastoma causes harm because of overdiagnosis, and it has little effect on decreasing the incidence and the mortality of neuroblastoma at 1-4 years of age.

Adolescent↗
PubMed1997

Ophthalmic findings in a case of hemophagocytic syndrome.

PURPOSE: To report a case of hemophagocytic syndrome, which is characterized by hemophagocytosis of histiocytes; optic nerve involvement, and unusual retinal white patches. METHOD: Case report. A 10-year-old boy had repeated relapses of hemophagocytic syndrome. He complained of swelling of the right upper eyelid and bilateral visual disturbance. RESULTS: Ophthalmoscopic examination disclosed bilateral optic disk edema, retinal hemorrhages, and multiple perivenous white patches in the retina. Magnetic resonance imaging demonstrated enlargement of both optic nerves. After chemotherapy and bone marrow transplantation, his visual acuity improved in both eyes, and retinal patches changed to inactive-appearing scars. CONCLUSION: Hemophagocytic syndrome may manifest with ophthalmic findings such as optic nerve involvement, retinal hemorrhages, and multiple white perivenous retinal patches.

Child↗
PubMed1997

[Clinical characteristics of Epstein-Barr virus-associated natural killer cell lymphoma/leukemia].

Granular lymphocytes proliferative disease(GLPD) is a heterogeneous disorder and the pathogenesis is likely to be complex. More recently, however, it has become obvious that about one third of GLPD belongs to NK-lineage and nearly one half of the NK-GLPD contains EBV-DNA. In addition, lethal midline granuloma(a subtype of nasal lymphoma) is also classified as NK/T-lineage and exclusively contains EBV-DNA. These NK-GLPD likely represent fever, splenomegaly and extranodal involvement, such as skin, lung and G-I tract. Although some elderly patients show a chronic clinical course, most of the patients present with an aggressive course and sometimes hemophagocytic syndrome is observed in the clinical course.

Adolescent↗
PubMed1997

[Current diagnosis and prognostic importance of EBV-associated neoplasms].

In addition to endemic Burkitt's lymphoma and nasopharyngeal carcinoma a variety of other epithelial-and lymphoid-derived proliferative diseases has been shown to closely link with Epstein-Barr virus (EBV) infection. The former include thymic lymphoepithelial carcinoma, oral hairy leukoplakia and gastric carcinoma. The latter include B-cell lymphoproliferative disorders arising in individuals with primary or secondary immunodeficiency, Hodgkin's disease and T/NK lymphoma. The significance of serological, immunohistochemical and molecular biological methods such as PCR, in situ hybridization and Southern blotting is described. And also the possible prognostic impact of EBV in T/NK-lymphoma is discussed.

Herpesviridae Infections↗
PubMed1997

[Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy].

Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy is reported. The conditioning regimen consisted of thiotepa (150 mg/m2 x 4), melphalan (70 mg/m2 x 2) and 12 Gy total body irradiation. She received peripheral blood CD34 positive cells (4.17 x 10(6)/kg) from her HLA-mismatched father and tacrolimus hydrate was used for GVHD prophylaxis. Engraftment was rapid and grade 1 acute GVHD of the skin responded well to pulse therapy. From day 27 she became irritable and sleepless, and right facial convulsions developed on day 37. No abnormality was found in the cerebrospinal fluid. Cranial CT findings showed no abnormalities except for low density lesions around the bilateral ventricle. Leukoencephalopathy was suspected and tacrolimus hydrate was discontinued. Thereafter psychosomatic symptoms improved, temporarily however, similar symptoms again developed following cyclosporine administration. Therefore we had to halt the administration of both tacrolimus and cyclosporine. She died on day 104 because of GVHD and fungal infection without recovering from leukoencephalopathy.

Brain Diseases↗
PubMed1997

[Epstein-Barr virus-infected T-cell malignancy in an adult patient with Behçet's disease-like symptoms].

A 20-year-old woman was hospitalized on November 11, 1994 with Behçet's disease-like symptoms (fever, genital ulcer and aphtha in the oral cavity). Bilateral cervical lymph node swelling was also noted and diagnosed as lymphadenitis on biopsy. Chronic active Epstein-Barr virus infection (CAEBV) was diagnosed based on the high titer of antibodies to the EBV capsid antigen, early antigen, and nuclear antigen. She was treated with prednisolone and acyclovir and all symptoms improved. However, ten months after onset of symptoms, T-cell malignancy was diagnosed on bone marrow aspiration, which revealed 34.9% blast cells that had rearrangement of TCR-beta. She died on May 8, 1995, despite anticancer therapy. In analyzing the blast cells, the monoclonal junctional DNA structure of the EBV terminal repeat was analyzed by Southern blotting and provided definitive evidence for the monoclonality of EBV-infected T cells. These findings strongly suggest that EBV plays a pathogenic role in T-cell malignancy. EBV-infected T-cell malignancy, such as this case, is very rare in Japan, especially in adult.

Adult↗
PubMed1996

ADP-induced rapid inward currents through Ca(2+)-permeable cation channels in mouse, rat and guinea-pig megakaryocytes: a patch-clamp study.

1. The rapid inward currents in mouse megakaryocytes evoked by adenosine diphosphate (ADP), a ubiquitous platelet-activating substance, were studied. Time and current resolution were improved by using patch-clamp recording and an extracellular fast perfusion ("Y tube') technique. 2. Application of ADP (40 microM) to megakaryocytes immersed in physiological saline evoked rapid inward currents (80-340 pA at -42 mV). The cellular responses to a second ADP application were markedly reduced, but in the absence of external Ca2+, responses to repeated ADP application were maintained and did not deteriorate. 3. The ADP-induced current recorded in Ca(2+)-free external media showed short latency (less than 20 ms) and approximately exponential decay (time constant, 300-500 ms), which was independent of the holding potential and seemed to be caused mainly by receptor desensitization; it took over 5.5 min for complete recovery. 4. The ADP concentration response relationship of the megakaryocytes revealed that the half-maximal concentration and the Hill coefficient were 12.6 microM and 1.4, respectively. 5. An ion replacement experiment showed that the ADP-induced currents could be carried by Na+, Cs+ and K+, but not Cl-, and the cation channels were permeable to Ca2+, Ba2+ and Mg2+. 6. Neither Ca2+ chelators (10 mM EGTA and 10 mM BAPTA) nor hydrolysis-resistant guanine nucleotides (2 mM GDP-beta-S and 0.4 mM 5'-guanylylimidodiphosphate) in the internal saline affected the rapid responses to ADP, and ADP-induced currents were recorded in excised membrane patches, suggesting that the ADP receptor site and the molecular structure forming the cation channel are tightly coupled and/or parts of the same molecule. 7. In rat and guinea-pig megakaryocytes, ADP-induced rapid inward currents showed the same properties as in mouse megakaryocytes.

Adenosine Diphosphate↗
PubMed1996

[Natural killer cell lymphoma having a nodular shadow in the lung as an initial finding, developed to leukemia complicated with hemophagocytic syndrome at the time of relapse].

A 57-year-old female was admitted to Uji hospital for the further evaluation of nodular shadow on her right lung. During the period of admission, she developed cervical lymph node swelling. She was diagnosed as having malignant lymphoma (diffuse, small cleaved cell) by lymph node biopsy. She received combined chemotherapy and obtained partial remission for seven months until she developed fever and pancytopenia. Laboratory data showed increased number of large granular lymphocytes (LGLs) in blood. Bone marrow revealed increased number of LGLs with hemophagocytosis by macrophage. Surface marker analysis revealed LGLs were positive for CD2 CD16, and CD56 and negative for CD3, CD4, CD8, and CD20. T-cell receptor genes beta and gamma were in germ line configuration. Analysis of Epstein-Barr virus genome using termini probe indicated a monoclonal proliferation of LGLs. Reexamination of the biopsy specimen of lymph node revealed LGLs which was negative for CD3 and CD20. The patient was diagnosed as a leukemic phase of natural killer (NK) cell lymphoma complicated with hemophagocytic syndrome (HPS). Serum levels of interferon-gamma, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-6 increased, which might be related to HPS.

Antigens, CD↗