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Biomedical subjects

K Tsubaki

Publications and source records attributed to K Tsubaki.

At least 37 records · Page 2Linked to original sources

[Usefulness of hypoallergenic rice (AFT-R 1) and analysis of the salt insoluble rice allergen molecule].

An involvement of rice allergy in development and exacerbation of recalcitrant atopic dermatitis (AD) has been suggested in some cases, and it has been also known that elimination diet of rice results in improvement of AD and reduction of the doses of steroid ointment and anti-allergic drugs used for the treatment. We prepared the hypoallergenic rice grain, AFT-R 1 (Allergen-free Technology Lab. Inc.-Rice 1), with alkali treatment from the rice material, Koshihikari, which is popular in Japan. Its usefulness was evaluated clinically and serologically. The serological study with IgE-ELISA showed that the major allergic protein were remarkably reduced to less than 1/6400 of them in the AFT-R 1. Then it was applied to the clinical trial, and evaluated as useful by the clinical effect in 14 (93%) out of 15 patients, who were diagnosed to have rice allergy by the elimination (in 15 case) and ingestion (in 12 cases) of the regular rice. The serum taken from the patient, whom the AFT-R 1 was evaluated as unuseful in the clinical trial, was shown to have IgE antibodies reactive to the remaining protein in AFT-R 1 by IgE-ELISA, and the 60 kd protein band was detected as an IgE-binding component of AFT-R 1 by IgE-immunoblotting with the same serum. This 60 kd rice protein was identified as ADP (UDP)-glucose-starch glycosyl transferase (EC: 2.4.1.21) by N-terminal amino acid analysis. These results indicated that AFT-R 1 is very useful as a substitute of rice in many AD patients with rice allergy, although IgE-binding component such as the 60 kd protein is remaining in one.

Adolescent↗

No beneficial effect from addition of etoposide to daunorubicin, cytarabine, and 6-mercaptopurine in individualized induction therapy of adult acute myeloid leukemia: the JALSG-AML92 study. Japan Adult Leukemia Study Group.

To assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML), newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more), and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BHAC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BHAC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 patients were excluded because all-trans retinoic acid was used. Of 667 patients registered, 655 were evaluable. The median age was 49 (range 15 to 85). CR rates were 77% in the BHAC-DM group and 75% in the BHAC-EDM group. In 173 M4 patients, CR rates were 86% and 69% (P = 0.009), and in 32 M5 patients, 80% and 77% (P = 0.810) in the BHAC-DM and the BHAC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% (P = 0.925) for the BHAC-DM and BHAC-EDM groups, and the disease-free survival rates of CR patients were 25% and 35% (P = 0.352), respectively. Nonhematological toxicities after the first course of induction therapy were almost equal among the two groups, with the exception of a greater loss of hair (P = 0.024) and more frequent diarrhea (P = 0.013) in the BHAC-EDM group. We concluded that in the present study, the addition of etoposide to the standard individualized induction therapy showed no advantage in adult AML, even among M4 and M5 patients.

Acute Disease↗

[A study of aggravation of atopic dermatitis during Japanese cedar pollen season--correlation with grades of dermatitis on face and Cry j 1 specific IgE].

We studied influence of Japanese cedar pollen (Jcp) on aggravation of atopic dermatitis (AD) during the pollination season. 48.5% of 97 patients with atopic dermatitis showed aggravation of dermatitis during the pollination season and 85% of them had Japanese cedar pollinosis, whereas only 44% of AD patients without the aggravation had the pollinosis. There was no difference of grades of dermatitis on face between the groups with or without the aggravation. Furthermore, we measured specific IgE to Jcp and Cry j 1, a major allergen of Jcp, by ELISA in the sera from the 54 patients with AD. The levels of specific IgE antibodies to both allergens in the group with the pollinosis were significantly higher than in the group without the pollinosis. However, significant difference of those was not recognized between the groups with or without the aggravation of AD. Therefore, our study has suggested that Japanese cedar pollen is likely to be one of causes of seasonal aggravation of AD in individuals sensitized to the pollen, and some other factors, e.g. Jcp-specific T cells, might play an important roll in addition to the Jcp-specific IgE.

Adolescent↗

Infectious complications during remission induction therapy in 577 patients with acute myeloid leukemia in the Japan Adult Leukemia Study Group studies between 1987 and 1991.

The Japan Adult Leukemia Study Group analyzed infectious episodes in 577 patients with acute myeloid leukemia during remission induction therapy between 1987 and 1991. 542 patients (93.9%) experienced at least one infectious episode, 121 (21.0%) had microbiologically documented infection; there was clinically documented infection in 184 (31.9%) and unexplained fever in 237 (41.1%). Among 121 microbiologically documented infections, bacteremia/fungemia was observed in 68, pneumonia in 33, and other types of infections in 20. Among the bacteremia/fungemia, gram-negative bacteria accounted for 41.2% (Pseudomonas aeruginosa was the most common), gram-positive bacteria for 39.7%, fungi for 16.2% (Candida spp. being most frequent), and polymicrobial for 2.9%. The most frequent isolates among pneumonia were Pseudomonas aeruginosa and Aspergillus. A total of 70 patients (12.1%) died during remission induction. Mortality of 68 patients with bacteremia/fungemia was 26.5%; in these patients, mortality with concomitant pneumonia increased to 41.4%; without pneumonia, mortality was 15.4% (P < 0.05). Mortality according to the isolated microbes was 17.2% for gram-negative bacteria, 25% for gram-positive bacteria, and 54.5% for fungi. Mortality of 113 patients with pneumonia (33 microbiologically documented and 80 clinically documented), 20 with other microbiologically documented infections, 104 with other clinically documented infections, and 237 with unexplained fever was 25.7%, 5.0%, 5.8%, and 5.1%, respectively.

Acute Disease↗

A long term follow-up of a randomized trial comparing interferon-alpha with busulfan for chronic myelogenous leukemia. The Kouseisho Leukemia Study Group.

To evaluate the long-term effectiveness of interferon-alpha (IFN-alpha) therapy in patients with chronic myelogenous leukemia (CML) in chronic phase, we examined the updated outcomes of 159 patients who had been enrolled between 1988 and 1991 into a randomized trial comparing IFN-alpha with busulfan. At a median follow-up of 73 months, the median survival was 71 months in the IFN-alpha group and 55 months in the busulfan group (P=0.0563), and the median time of remaining in chronic phase was 58 months in the IFN-alpha group and 39 months in the busulfan group (P=0.4676). Landmark analysis showed a significant advantage in survival (P=0.009) and duration of chronic phase (P=0.0001) in patients with any cytogenetic response among the IFN-alpha group. About half patients were discontinued IFN-alpha administration in spite of cytogenetic response in this study. It appears that continuation of IFN-alpha might possibly confer a survival advantage. Pretreatment factors associated with cytogenetic response included high hemoglobin level, low percentage of peripheral basophils and low leukocyte counts. Multivariate analysis identified lower percentage of bone marrow basophilia (P=0.007) for survival advantage. If a group with a very good prognosis is predicted by a new prognostic model, it might be an option to wait for bone marrow transplantation.

Adult↗

Pregnancy among long-term survivors of acute leukemia. A second nationwide survey.

A second nationwide survey was conducted to determine the outcome of pregnancy in long-term survivors of acute leukemia and to clarify the influence of treatment on the offspring of long-term survivors. In July 1996, 336 survey responses were received from the 498 Japanese institutions surveyed. A total of 89 cases (39 spouses of male patients and 50 female patients) who had babies during their first remission were analyzed, including 43 patients from the first survey in 1991. Median age at the birth of first baby was 30.7 years for male patients and 28.6 years for female patients. A total of 109 of the 117 pregnancies resulted in live births and eight resulted in abortions. A total of 58 cases had single children and 23 cases had two or more, generally from separate pregnancies, but including two pairs of twins. The infant was male in 59 cases, female in 37 and gender was not reported in 13 cases. Ages of children ranged from 2 months to 20 years at the time of this study and all children were in good health. There were two minor anomalies, both of which were surgically corrected. Of the 81 parents bearing live infants, 75 remained in complete remission. Five fathers died (four of relapse and one of another disease). In conclusion, there was no apparent increase in pregnancy complications or congenital anomalies in the children of long-term survivors with acute leukemia.

Acute Disease↗

Response-oriented individualized induction therapy followed by intensive consolidation and maintenance for adult patients with acute lymphoblastic leukemia: the ALL-87 study of the Japan Adult Leukemia Study Group (JALSG).

The Japan Adult Leukemia Study Group conducted the ALL-87 study to determine whether response-oriented induction therapy and intensive consolidation and maintenance/intensification therapies could increase complete remission (CR) rate and survival in adult acute lymphoblastic leukemia (ALL). Of 121 patients registered, 116 were evaluated. Patients' ages ranged from 15 to 72 years (median, 38 years). Induction therapy, which consisted of doxorubicin, vincristine, cyclophosphamide, L-asparaginase and prednisolone, was given in a response-oriented individualized fashion. Patients were randomly allocated either to receive or not, intrathecal chemotherapy on day 8 of the induction therapy. Complete remission (CR) was obtained in 97 (83.6%) patients (90.2%) in patients of less than 50 years of age and 67.6% in patients 50 years of age or older). At a median follow-up period of 65 months, the predicted 6-year overall survival and event free survival (EFS) rates of 116 patients were 23.4 and 20.0%, respectively. Predicted 6-year survival and disease-free survival (DFS) rates of 97 CR patients were 28.2 and 24.5%, respectively. By multivariate analysis, patients under 40 years of age (P = 0.002) or those with a platelet count of more than 100,000/microliters (P = 0.004) were significant favorable prognostic factors for obtaining CR, and days to CR less than 50 (P = 0.003), patients under 50 years of age (P = 0.005) were significant favorable factors for longer DFS. There was no significant difference in CR rates and DFS between the two randomized groups according to the intrathecal chemotherapy on day 8. Response-oriented induction therapy produced a high CR rate, but fairly intensive consolidation and maintenance/intensification chemotherapies resulted in only a marginal effect on DFS in adult ALL. Although age is one of the most important prognostic factors in ALL, the outcome was unsatisfactory even in younger adult patients using chemotherapeutic regimen employed in this study.

Adolescent↗

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia.

Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4+CD8+ double-positive (DP) phenotype is seen in a few cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a matter of controversy. To address this issue, we studied phenotypical features in eight cases of DP T cell leukemia. Thymic DP T cells and peripheral CD8+ T cells have CD8 of alphabeta subunit, while CD8alphaalpha is induced in CD4+ T cells on activation with IL-4. We found that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim expression of CD8alphaalpha, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high levels of IL-4. These findings suggest that they may be derived from peripheral CD4+ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed CD8alphaalpha, suggestive of an activated peripheral T cell origin. One case expressed CD8alphaalpha dim and IL-4 mRNA, while the other two cases expressed no IL-4 mRNA and showed CD8alphaalpha bright phenotype, features not found in normal T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL) expressed CD8alphabeta. The DP phenotype is relatively common in T-PLL, and CD4+CD8alphabeta+ is characteristic of thymic T cells. The DP T-PLL cells did not express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down-regulated at the late stage of thymic T cell development. On the basis of these findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.

Adult↗

Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group.

PURPOSE: We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS). PATIENTS AND METHODS: All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. RESULTS: Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001). CONCLUSION: Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.

Adolescent↗

All-trans retinoic acid therapy for newly diagnosed acute promyelocytic leukemia: comparison with intensive chemotherapy. The Japan Adult Leukemia Study Group (JALSG).

We analyzed the results of treating patients with newly diagnosed acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) in the JALSG AML-92 study and compared them with those of the AML-87 and AML-89 studies, which consisted of standard chemotherapy. In the AML-92 study, patients were scheduled to receive 45 mg/ m2 oral ATRA daily until achievement of a complete remission (CR). If patients had initial leukocyte counts of > 3.0 x 10(9)/l, they received 40 mg/m2 daunorubicin (DNR) for 3 days and 200 mg/m2 behenoyl cytarabine (BHAC) for 5 days in addition to ATRA. During remission induction therapy, if the patients showed peripheral blood myeloblast and promyelocyte counts of > 1.0 x 10(9)/l, they received additional DNR and BHAC on the same schedule. After achievement of a CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. Of 196 evaluable patients, 173 (88%) achieved a CR: 59 of 62 (95%) treated with ATRA alone, 41 of 49 (84%) treated with ATRA plus later chemotherapy, 63 of 73 (86%) treated with ATRA plus initial chemotherapy, and 10 of 12 (83%) treated with ATRA plus both initial and later chemotherapy. The CR rate in AML-92 was significantly higher than that in AML-89, but not than that achieved in AML-87. In addition, the early mortality and relapse rates in AML-92 were significantly lower than those in AML-89, but were not than those in AML-87. At a median follow-up of 36 months the predicted 4-year event-free survival (EFS) rate for 196 evaluable patients and the 4-year disease-free survival (DFS) rate for the CR cases were 54% and 62%, respectively. There was a significant difference in DFS between AML-92 and AML-87 (P = 0.0418) but not between AML-92 and AML-89 (P = 0.0687). In contrast, significant differences in EFS between AML-92 and both AML-87 (P = 0.0129) and AML-89 (P = 0.005) were observed. These results suggest that non-cross-resistant therapy combined with ATRA and intensive chemotherapy for APL contributes synergistically to the significant improvement in EFS.

Adolescent↗

Case-control study of leukemia and diagnostic radiation exposure.

A case-control study of leukemia and diagnostic X-ray exposure was conducted by a multi-institution co-operative study group. The subjects were 134 patients with acute myelogenous leukemia, 57 with chronic myelogenous leukemia, 56 with acute lymphocytic leukemia and 50 with myelodysplasia syndrome, who were between 15 and 79 years old, and diagnosed at one of 27 hospitals between September 1993 and August 1995. The controls were 479 first-visit patients seen at eight of these 27 hospitals. History of diagnostic X-ray tests between 1982 and 1991 was determined by an anonymous self-administered questionnaire. The total relative dose of radiation exposure was calculated by summing the products of given weights and frequencies of each test. The relative risk was 0.83 (95% confidence interval (C.I.), 0.58-1.19) for relative dose of 10-30 (equivalent to 4-11 times of UGI series), 0.76 (0.48-1.20) for relative dose of 30 or more (more than 12 times of UGI series), when compared with relative dose of 0-10 (0-3 times of UGI series). Analysis according to type of leukemia revealed that only acute myelogenous leukemia had an estimated relative risk above unity (1.08, 95% C.I. 0.69-1.69, for relative dose 10-30). This study did not support the hypothesis that diagnostic X-ray tests increases leukemia risk.

Adolescent↗

Danazol induced thrombocytopenia.

A 34-year-old woman with a left ovarian cyst (clinically diagnosed as endometrial cyst) was treated with 400 mg of danazol per day. On the next day, after a total dose of only 600 mg of danazol, gingival bleeding and purpura occurred. Her laboratory findings were as follows: platelet count 1000/ mm3 hematocrit 39%, WBC 7300/mm3 and RBC 466 x 10(4)/mm3. Immune thrombocytopenic purpura (ITP) was diagnosed, and she was treated with 40 mg of methylprednisolone per day for 19 days. Her platelet count increased to 130,000/ mm3. Her left ovarian cyst was extirpated surgically, and the histological diagnosis was endometrial cyst. Danazol at 400 mg per day was therefore again administered. On the next day, she complained of gingival bleeding and purpura again, and her platelet count was 5000/mm3. We diagnosed this case as danazol induced thrombocytopenia.

Adult↗

Delivery after bone marrow transplantation with total lymphoid irradiation for severe aplastic anemia.

A 28-year old woman delivered a normal child at 85 months after bone marrow transplantation (BMT) for severe aplastic anemia (SAA). BMT was done after conditioning with cyclophosphamide (CY: 50 mg/kg/day for 4 days), anti-lymphocyte globulin (ALG: 50 mg/kg/day for 3 days) and total lymphoid irradiation (TLI: 5 Gy in a single fraction). Ovarian shielding was not done during irradiation. Six months after BMT, she gained normal menstruation spontaneously. Serum gonadotrophin levels were within the normal range, with an LH level of 34.6 mIU/ml (normal: 1-36 mIU/ml) and an FSH level of 13.4 mIU/ml (normal: 1-30 mIU/ml), at 38 months after BMT. She became pregnant 8 years after BMT and delivered a female child, who is now 3 years old and shows normal development.

Adult↗