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Biomedical subjects

K Horibe

Publications and source records attributed to K Horibe.

At least 73 records · Page 4Linked to original sources
PubMed1995

Detection of neuroblastoma cells in bone marrow and peripheral blood at diagnosis by the reverse transcriptase-polymerase chain reaction for tyrosine hydroxylase mRNA.

BACKGROUND: Bone marrow metastasis often occurs in patients with neuroblastoma; therefore, a sensitive assay to detect occult neuroblastoma cells in bone marrow (BM) and peripheral blood (PB) is needed. The feasibility and clinical value of using the reverse transcriptase-(RT) polymerase chain reaction (PCR) to amplify mRNA for tyrosine hydroxylase (TH), the first enzyme of catecholamine synthesis, was evaluated to detect neuroblastoma cells in patient samples. METHODS: Thirty-eight patients with Stages I to IV neuroblastoma and eight healthy donors were included in this study. Bone marrow and PB samples obtained at diagnosis were examined for TH mRNA. After preparation of complementary DNA, the PCR was performed to amplify the TH gene. RESULTS: Tyrosine hydroxylase mRNA was detected in neuroblastoma samples including a cell line and tumor tissues, but was not detected in normal BM or PB mononuclear cells. Neuroblastoma cells were detected at a level of 1 per 10(5-6) normal PB mononuclear cells by this method. Tyrosine hydroxylase mRNA was detected in 18 of 38 BM samples, and all 12 BM samples with cytologic evidence of tumor cells were positive for TH mRNA by the RT-PCR. Six of 26 patients without cytologic evidence of tumor cells in the BM were also positive for TH mRNA. TH mRNA was detected in BM samples from 1 of 14 patients with Stage I disease, 2 of 7 patients with Stage II disease, 1 of 3 patients with Stage III disease and all patients with Stage IV (11 patients) and IVS (3 patients) diseases. Tyrosine hydroxylase mRNA also was detected in 8 of 14 PB samples (one of five patients in Stages I, II or III, and 7 of 9 in Stage IV or IVS). CONCLUSIONS: Reverse transcriptase-polymerase chain reaction amplification of TH mRNA was a sensitive and specific method of detecting occult neuroblastoma cells in BM and PB samples. Neuroblastoma cells could be detected by this method in some BM samples that had no cytologic evidence of tumor cells and in some PB samples at the time of diagnosis. The clinical significance of these very low levels of neuroblastoma cells detected by RT-PCR requires further investigation.

Base Sequence↗
PubMed1995

Mutations of the p53 and ras genes in childhood t(1;19)-acute lymphoblastic leukemia.

We have investigated the alterations of p53 and ras genes including H-, K-, and N-ras genes in 22 acute lymphoblastic leukemia (ALL) cases and five cell lines carrying t(1;19) by use of polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis and direct sequencing. The mutations of the p53 gene were found in 2 of 20 t(1;19)-ALL cases at diagnosis (10%), all of 4 cases at relapse (100%), and 4 of the 5 cell lines (80%). Four of the five patients who died had missense mutations at codons 49, 177, 179, and 248. In cases examined sequentially, one had the same point mutation at codon 179 at both diagnosis and relapse, and another had the same p53 gene mutation at codon 240 both in leukemic cells at relapse and in a cell line derived at that time. The other case had no mutation at diagnosis but had the mutation at codon 177 at relapse and cell lines derived from blast cells at diagnosis, suggesting that a small number of leukemic cells with the p53 gene mutation at diagnosis might have escaped PCR-SSCP analysis. In cell lines, SCMC-L9 had three point mutations in the p53 gene at codons 175, 248, and 358, whereas SCMC-L10 had frame shift at codons 209-211. One case had a rare polymorphism at codon 11. We found only one mutation of the N-ras gene that was a 2-bp substitution of GGT(Gly) to GTC(Val) at codon 13 among 22 t(1;19)-ALL cases and five cell lines. This case showed no mutation of the p53 gene and has had a good course. These results suggest that in t(1;19)-ALL, mutations of the p53 and ras genes are infrequent at diagnosis and that p53 gene alterations may be associated with relapse phase or progression of t(1;19)-ALL.

Adolescent↗
PubMed1995

Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese.

To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan.

Adolescent↗
PubMed1994

Advanced primary non-Hodgkin's lymphoma of the small intestine in childhood: report of four cases.

Primary non-Hodgkin's lymphoma of the small intestine (PLI) is an uncommon malignancy in childhood which carries a poor prognosis. Consideration of the possible diagnosis of PLI is important when children have vague abdominal symptoms, since thoughtful multidisciplinary treatment can result in a better prognosis. This paper reports the cases of four children who have presented to our hospital since 1985 with advanced stage III or IV PLI. All the children had a huge abdominal mass but none of them had complete intestinal obstruction. Regarding the diagnosis, ultrasonography frequently reveals a hypoechoic thickening of the intestinal wall with dilated intestinal loops. A delayed primary or second-look operation may be the treatment of choice following adequate chemotherapy, while total parenteral nutritional support may prevent gastrointestinal complications. Three of the four patients have been in complete remission for 2 to 4 1/2 years since their initial treatment.

Child↗
PubMed1994

Prevention of chemotherapy-induced emesis with granisetron in children with malignant diseases.

PURPOSE: In a prospective crossover study, we evaluated the safety and antiemetic activity of granisetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, compared with conventional antiemetics regimen, including metoclopramide, in pediatric cancer patients. PATIENTS AND METHODS: Twenty-two children with malignant diseases were enrolled. The chemotherapy included cytarabine 3 g/m2 (regimen A), cisplatin 90 mg/m2 (regimen B), and actinomycin D 900 micrograms/m2 plus ifosfamide 3 g/m2 (regimen C). Granisetron 40 micrograms/kg was infused over 30 min just before each chemotherapy treatment. RESULTS: A complete response was obtained more often with granisetron than with conventional antiemetics (59.1% vs. 0%, p < 0.001). In terms of efficacy by chemotherapy type, complete response with granisetron was obtained in eight of 10 patients with regimen A, three of eight with regimen B, and two of four with regimen C. Major efficacy (vomiting fewer than two times) was also obtained more with granisetron than with conventional antiemetics (81.8% vs. 4.6%, p < 0.001). The number of vomiting episodes in the first 24 h was less with granisetron than with conventional antiemetics (1.1 +/- 1.46 vs. 9.0 +/- 4.97, p < 0.001). Normal appetite and activity were retained in more patients with granisetron than with conventional antiemetics. Extrapyramidal reactions, akathisia, and sedation were not seen in any case with granisetron. CONCLUSIONS: Granisetron 40 micrograms/kg is well tolerated and more effective than are conventional antiemetic regimens containing metoclopramide for children receiving cancer chemotherapy.

Adolescent↗
PubMed1994

Strain relatedness of Candida albicans strains isolated from children with leukemia and their bedside parents.

Candida yeasts are occasionally recovered from patients with leukemia in spite of antifungal therapy used during chemotherapy. It is not yet known whether yeasts in these patients are of endogenous or exogenous origin. We examined the strain relatedness of Candida albicans isolated from three patients with leukemia (A, B, and C) and their bedside parents using pulsed-field gel electrophoresis (PFGE), restriction fragment length polymorphism (RFLP) by SmaI digestion, and the Southern hybridization patterns of the RFLPs by the C. albicans-specific probe RPS1. SmaI digestion and Southern hybridization by RPS1 showed identical or similar patterns among Candida isolates in patients A and his mother, although their karyotypes were different. Isolates from patients B and both parents showed identical electrophoretic karyotypes, SmaI digestion patterns, and hybridization patterns. Since electrophoretic karyotypes are more variable than RFLPs and their hybridization patterns, the identity of the last two suggests a close relatedness between strains. Our results also suggest that transmission of yeast strains may have occurred between patient A and his mother and between patient B and her parents. Isolates from patient C and her mother are thought to have originated from different strains, since different patterns were obtained in electrophoretic karyotypes, SmaI digestion patterns, and Southern hybridization patterns.

Adult↗
PubMed1994

[Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank].

One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.

Adolescent↗
PubMed1994

[Coordination of unrelated bone marrow donors in the Tokai Bone Marrow Bank--psychological reactions of donors to donation].

The Tokai Bone Marrow Bank was established in 1989 and coordinated 1,415 patients with 3,000 HLA-A, B-typed donors. Of the 1,415 patients, 757 patients had HLA-A, B-identical donors, 206 patients had HLA-DR-identical donors, and 80 patients had MLC-compatible donors. Finally, 55 unrelated donor bone marrow transplantations were done. The most frequent reason of interruption in coordination was disagreement of donor's family. We sent several questions by mail around 1 month after the donation to 55 donors to analyze the psychological reactions of unrelated bone marrow donors to donation. Donors were generally quite positive about the donation. 92% of the donors felt it was worthwhile and no one felt it was not at all worthwhile. 73% of the donors would be willing to donate again in the future. 79% of donors would like to know the clinical course of the patient after the bone marrow transplantation. We hope that these results may be helpful in the development of the Japan Marrow Donor Program.

Bone Marrow↗
PubMed1994

[Outcome of treatment protocol 8704T for childhood T cell leukemia and lymphoma].

We reported the treatment outcome of Protocol 8704T, which included repeated L-asparaginase, for childhood T cell malignancies. Fifteen cases of acute lymphoblastic leukemia (T-ALL) and 11 cases of non-Hodgkin's lymphoma (T-NHL), aged 3 to 14 yrs (median 6 yrs), were enrolled. Twelve T-ALL had mediastinal mass. Murphy's stages of T-NHL were 6 with III and 5 with IV. Types of histology consisted of 8 lymphoblastic and 3 large cell. Treatment was performed for 2 years. Observation periods were from 14 months to 78 months (median 42 months). Twenty-three achieved remission and 6 of them were transplanted with bone marrow or peripheral stem cells in the first remission. The protocol was continued in 17 cases. Fourteen of them remain in first remission, but one died of measles and 2 died of relapse. The 5-year event-free survival was 76.1% for ALL and 65.5% for NHL. In terms of histology, it was 87.5% for lymphoblastic NHL and 33.3% for large cell NHL (p = 0.19). In terms of phenotypes in ALL, it was 88.7% for ALL positive to CD2, 5 and 7, while 2 ALL positive to CD7 alone both failed. Therefore, it was shown that this treatment protocol is very effective for T-lymphoblastic leukemia and lymphoma.

Adolescent↗
PubMed1994

[Chronic myelomonocytic leukemia developed 9 years after the diagnosis of idiopathic thrombocytopenic purpura in a child].

A 5-year-old girl was diagnosed as having idiopathic thrombocytopenic purpura (ITP) based on symptoms of nasal bleeding and purpura. The platelet count was 35,000/microliters without anemia or leukopenia. Micromegakaryocytes were observed in normocellular bone marrow without dyserythropoiesis or dysgranulopoiesis. She had periosteal fibroma of the rib and atopic dermatitis with elevated serum IgE. Prednisolone and azathioprine were administered but with no response. The cumulative dose of azathioprine was 20 g for 28 months. Nine years after the diagnosis of ITP, she was admitted because of dyspnea and anemia. The white cell count was 26,900/microliters with 17% monocytes. The hemoglobin was 3.9 g/dl and the platelet count was 9,000/microliters. Dyserythropoiesis, dysgranulopoiesis and micromegakaryocytes were observed in hypercellular bone marrow. The chromosome analysis demonstrated 47, XX, +21. She was diagnosed as having chronic myelomonocytic leukemia (CMMoL) and received bone marrow transplantation (BMT) from an HLA-identical sibling conditioned with high-dose busulfan and melphalan. After 17 months of remission, the disease recurred with an abnormal karyotype of 47, XX, +21, 7q+. Despite a second BMT conditioned with high-dose etoposide, cyclophosphamide and total body irradiation, she died of the disease. Refractory thrombocytopenia as a subgroup of myelodysplastic syndrome, rather than ITP, might have preceded the development of CMMoL, with the possibility of azathioprine-induced leukemia.

Adolescent↗
PubMed1993

Acute promyelocytic leukemia with t(15;17) abnormality after chemotherapy containing etoposide for Langerhans cell histiocytosis.

BACKGROUND: Epipodophyllotoxins, etoposide and teniposide, have been shown to be implicated in the development, of acute myelogenous leukemia in patients treated for solid tumors or acute lymphoblastic leukemia. Etoposide has been shown to be an effective agent against Langerhans cell histiocytosis (LCH) and has gained wider use recently for first-line and salvage chemotherapy in cases of systemic LCH. METHODS: The authors report two patients with secondary acute promyelocytic leukemia (APL) with a t(15;17) abnormality after chemotherapy that included etoposide for the treatment of LCH. RESULTS: Patient 1, a 6-year-old girl, had APL develop 11 months after cessation of therapy that included vinblastine, prednisolone, and etoposide (9600 mg/m2 in total dose) for LCH. Patient 2, a 3-year-old girl, had APL develop 9 months after cessation of therapy that included vincristine, methotrexate, prednisolone, cyclophosphamide (10,800 mg/m2), and etoposide (4800 mg/m2) for LCH. CONCLUSIONS: The authors have experience with four patients treated with etoposide for LCH and suggest that there is a predisposition to secondary APL with t(15;17) for patients with LCH treated with etoposide. The authors warn against the imprudent use of etoposide as a first-line therapy for LCH.

Child, Preschool↗
PubMed1993

New E2A/PBX1 fusion transcript in a patient with t(1;19)(q23;p13) acute lymphoblastic leukemia.

About 25% of the children with pre-B cell acute lymphoblastic leukemia (ALL) have a chromosomal translocation of t(1;19)(q23;p13). This translocation juxtaposes the E2A gene on chromosome 19 to the PBX1 gene on chromosome 1, leading to production of a fusion transcript. The fusion sites of the E2A and PBX1 coding sequence have been identical among all cases of t(1;19) ALL studied so far. Here we described a new fusion site of the E2A and PBX1 genes, which was detected in the leukemic blasts of a child with t(1;19) pre-B ALL using the reverse transcriptase polymerase chain reaction and direct sequencing. The fusion site was located just upstream of the DNA binding domain of the E2A gene, and was close to a homeodomain of the PBX1 gene.

Amino Acid Sequence↗
PubMed1993

[Treatment of aplastic anemia with antithymocyte globulin, Lymphoser Berna].

Twenty-four patients with aplastic anemia (19 severe: 5 moderate) were treated with combined immunosuppression consisting of antithymocyte globulin (ATG: Lymphoser Berna, Swiss Serum and Vaccine Institute Berne) and high-dose methylprednisolone. Danazol or meptiostane was administered concurrently for at least 3 months. Three batches of ATG were used, two were not absorbed with thrombocytes and one was absorbed with thrombocytes for the prevention of thrombocytopenia. Nine of 20 evaluable patient (45%) had sustained improvement in hematopoiesis within 3 months of treatment. Nine of 14 patients (64%) showed a response to ATG without thrombocyte absorption, on the other hand, none of 6 patients responded to ATG with thrombocyte absorption. By life table analysis, the 3 year probability of survival was 81 +/- 27% after the combined immunosuppressive therapy. These results indicated that ATG therapy was very effective in Japanese patients with aplastic anemia.

Adolescent↗
PubMed1992

Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation.

Minimal residual disease (MRD) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients received BMT at the time of hematologic and cytogenetic remission. However, MRD was detected in 8 of 10 patients evaluated. Seven patients, including three who had MRD before BMT, continue to have a disease-free survival 5 to 64 months after BMT. Twenty-one specimens obtained from these patients at various times after BMT did not show MRD. In three patients, MRD detected just before BMT seems to be eradicated by BMT protocol. The other eight patients developed cytogenetic or hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus, this technique for the detection of MRD appears to be useful for the more precise assessment of various antileukemia therapies and for early detection of leukemia recurrence.

Adolescent↗