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Biomedical subjects

R Ohno

Publications and source records attributed to R Ohno.

At least 253 records · Page 14Linked to original sources
PubMed1992

Effective treatment of adult T cell leukemia/lymphoma with a novel oral antitumor agent, MST-16.

Adult T cell leukemia/lymphoma (ATLL) induced by human T cell leukemia virus I is resistant to conventional therapy. Six patients with ATLL were treated with a new antitumor agent, MST-16, which is a derivative of bis(2,6-dioxopiperazine). Two patients achieved complete remission, lasting 12 months and more than 8 months, and 2 others partial remission, lasting 2 months and 6 weeks, respectively. The major toxicity was myelosuppression. Other toxicities were not severe and were well tolerable. Orally administered MST-16 is a promising agent for the treatment of ATLL.

Administration, Oral↗
PubMed1992

Characterization of the immunoglobulin heavy chain complementarity determining region (CDR)-III sequences from human B cell precursor acute lymphoblastic leukemia cells.

Sequence analysis of the immunoglobulin heavy chain complementarity determining region (CDR)-III of B-lineage cells at various stages has provided important insights concerning B cell maturation and selection. Knowledge of human CDR-III sequences has been relatively limited compared with that of the murine system. We analyzed the CDR-III sequences of B cell precursor acute lymphoblastic leukemia (pre-B ALL) cells in 23 newly diagnosed and 10 relapsed patients, in order to elucidate the organization of CDR-III in B cell precursors. We found a very low frequency of somatic mutations in D and JH regions, preferential use of DLR, DXP, DHQ52, and DN elements, and of 3' side JH segments, and no predominant usage of D coding frames. Unusual joinings such as VH-D-D-JH and VH-JH were observed in three, and one sequences, respectively. We compared the CDR-III sequences derived from 10 patients between diagnosis and relapse. Two of them had three spots of mutated nucleotides at relapse, all of which were found in the N region near the D segments. Our data showed the possibility of somatic mutation at relapse, in addition to developmentally regulated rearrangement of the immunoglobulin gene at the stage of B cell precursors.

Adolescent↗
PubMed1992

Remission induction of acute promyelocytic leukemia by all-trans-retinoic acid: molecular evidence of restoration of normal hematopoiesis after differentiation and subsequent extinction of leukemic clone.

Sequential molecular and cellular changes during remission induction were investigated in a case of acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA). By means of clonality analysis, the assessment of the retinoic acid receptor alpha gene alterations, as well as conventional cytologic studies, it was demonstrated that remission induction of APL by ATRA proceeds in two steps: first, the differentiation of the leukemic clone to mature granulocytes and its subsequent extinction; second, proliferation/differentiation of the residual normal clones to restore polyclonal hematopoiesis.

Adult↗
PubMed1992

[Supportive therapy in cancer treatment with colony stimulating factors and evaluation of their effect].

Several tumors are now curable. However, intensive chemotherapy or bone marrow transplantation is required for the cure, and thus myelosuppression and resultant serious infections are major obstacles for the cure of cancer. G-CSF and M-CSF are commercially available in Japan. By strict comparative studies, G-CSF has been shown to be a useful drug, shortening the recovery of neutrophils and reducing the incidence of documented infections. There have been no convincing data that G-CSF stimulates the regrowth of myeloid leukemia in vivo, and thus G-CSF is safe even in myeloid leukemia, if used with precaution.

Cell Division↗
PubMed1992

Randomized study of individualized induction therapy with or without VCR, and of maintenance of 4 or 12 courses in adult AML: JALSG-AML87. Japan Adult Leukemia Study Group (JALSG).

We asked 2 questions in this study. First was the additional effect of VCR in induction therapy, and the second was the duration of maintenance therapy. Adult AML were treated by an individualized response-oriented induction therapy with behenoyl Ara-C 200 mg/m2 daily + 6MP 70 mg/m2 daily + prednisolone 40 mg/m2 on days 1-4 + DNA 40 mg/m2 on days 1-3 and additionally on days 7, 8, 11, 12 (for M3, DNR 50 mg/m2 daily) (BHAC-DMP) until bone marrow became severely hypoplastic with less than 5% of blasts. Patients were randomized to BHAC-DMP or BHAC-DMP + VCR 0.35 mg/m2 on days 1-4. After obtaining CR, 3 courses of intensive consolidation therapy were given together with I.T. MTX+Ara-C+PSL. Maintenance intensification therapy was randomized to either 4 or 12 courses given every 2 months. Patients of age greater than or equal to 60 received about 2/3 reduced doses. From June 1987 to Sept. 1989, 265 consecutive adult AML were registered from 19 institutions and 258 were evaluable. Age ranged from 15 to 79 (med., 48). Out of 258, 200 (77.5%) achieved CR (80% in 209 of age less than 60 and 65% in 49 of age greater than or equal to 60). Unexpectedly, addition of VCR reduced the high CR rate of BHAC-DMP significantly (84% to 70%, p = 0.007). At the median follow-up of 37 mo., overall survival is 37%, and event-free survival (EVS) 27%. Survival, continuing CR and disease-free survival (DFS) rates of 200 CR cases are 45%, 40% and 35%, respectively. Patients received 12 courses of maintenance therapy showed better DFS (P = 0.0555). The VCR group had significantly worse EFS. By multivariate analysis, significant prognostic factors for the achievement of CR were age less than 60, PS 0-2 and no addition of VCR. Significant factors for longer DFS were induction of CR by one course, FAB M3 or M5 and age less than 50. The present multi-institutional study confirmed the high CR rates of the response-oriented individualized therapy reported from several centers in Japan, but failed to support an additional effect of VCR reported from one center.

Acute Disease↗
PubMed1992

All-trans-retinoic acid induced enrichment of functionally normal neutrophils in vivo in a patient with acute promyelocytic leukemia.

A patient with resistant acute promyelocytic leukemia was treated with all-trans-retinoic acid (45 mg/m2 per day for 42 days) and obtained complete remission at day 14. Analysis of the neutrophils from the patient at day 7 demonstrated that they were indistinguishable from neutrophils from normal individuals as far as this is assessed by presently available functional tests. Furthermore, the degree of peroxidase positivity of neutrophils obtained from the patient was similar to control values. Thus, taken together with the hematologic features, all-trans-retinoic acid induces leukemic promyelocytes to become functionally normal neutrophils. This therapy is particularly suitable in obtaining complete remission in patients with acute promyelocytic leukemia with neutropenia with or without previous chemotherapy.

Female↗
PubMed1991

A combination trial of human lymphoblastoid interferon and bestrabucil (KM2210) for adult T-cell leukemia-lymphoma.

Both human lymphoblastoid interferon (HLBI) and bestrabucil, the conjugate of chlorambucil and beta-estradiol, have antitumor activity against adult T-cell leukemia-lymphoma (ATLL). Because an in vitro study showed that these two agents combined had a synergistic antiproliferative effect on MOLT-4 and WI-38VA13 cell lines, the authors evaluated the clinical efficacy of this combination in a pilot study with a poor-risk group of ATLL patients. The patients were treated daily with 6 x 10(6) IU of HLBI subcutaneously and 100 mg of bestrabucil orally. In patients with lymphoma-type ATLL or hypercalcemia, prednisolone also was given daily. Of 12 patients suitable for evaluation, nine had partial responses, one had a minor response, and two had no response. All five patients with skin infiltration and both patients with hypercalcemia responded. A history of prior chemotherapy did not affect the response rate. The time to clinical response was 3 to 16 days (median, 11 days) after initiation of treatment. The response duration was 4 to 108+ weeks (median, 9 weeks), but all patients except one relapsed, even during continuing treatment. No serious side effects were observed. Although the response rate with this combination treatment was high, the response duration was short, and other treatments would have to be added to achieve control of this aggressive disease.

Adult↗
PubMed1991

Activated T lymphocyte subsets in experimental allergic neuritis.

Changes in activated T cell subsets in peripheral blood were examined during the course of experimental allergic neuritis (EAN), using two-color immunofluorescence flow cytometry. Both CD4+ and CD8+ activated T cells decreased transiently before the onset of clinical signs, and increased just around the time of onset of the disease. In contrast, during the recovery phase, the numbers of CD4+ activated T cells returned to the normal range, whereas CD8+ activated T cells continued to increase. These findings imply that activation of CD4+ helper/inducer cells contributes mainly to the evolution of EAN, and that of CD8+ suppressor cells are necessary for recovery.

Animals↗
PubMed1991

Treatment of myelodysplastic syndromes with orally administered 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate.

1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (fosteabine) was administered orally to patients with myelodysplastic syndromes (MDS); refractory anemia with excess of blasts (RAEB), RAEB in transformation, acute leukemia derived from RAEB and chronic myelomonocytic leukemia, in an early phase II study in a multi-institutional study. Among 62 evaluable patients, 2 patients achieved a complete remission, 6 a good response and 8 partial response by daily oral administration of 100-200 mg of fosteabine. The overall response rate was 25.8%. The response rates were almost the same among the four subtypes of MDS. Responses were reached 2-23 weeks (median, 8 weeks) after the start of therapy and continued for 3-50 weeks (median, 10 weeks). Major side effects were myelosuppression and gastrointestinal toxicities. In spite of the disadvantages, such as unpredictable absorption, this newly developed orally administrable cytarabine analogue will be a useful drug in the treatment of MDS.

Adult↗
PubMed1991

[Recent progress in the treatment of acute leukemia].

Acute leukemia has become a curable disease. In 3 studies for adult AML (BHAC-DMP, BHAC-DMP (II) and M-85) at Nagoya University Hospitals from 1979 to 1987, intensive induction resulted in higher cure rate, and the reduction of the blasts in bone marrow at 2 weeks after the initiation of therapy to less than 20% was the most important prognostic factor to predict the long CR. However, it seemed impractical to give very intensive chemotherapy during the induction because of high frequency of complications due to prolonged myelosuppression. Thus, consolidation should be as intensive as possible. In M-85 protocol, the predicted 5-years survival and disease-free survival (DFS) of CR cases are 70 and 53% respectively. The result of JALSG-AML 87 study seems to confirm the above result. As for the indication of bone marrow transplantation (BMT) at the first CR for adult AML, only a prospective randomized study will answer this important question. In case that DFS of chemotherapy will exceed 40 to 45%, it seems be wise to give chemotherapy first, and then BMT when the leukemia relapse. Differentiation induction therapy seems to be indicated in acute promyelocytic leukemia, although a confirmative study is awaited.

Acute Disease↗
PubMed1991

Establishment and characterization of a new human Bence Jones-type myeloma cell line, NOP-2.

A new human myeloma cell line NOP-2, producing immunoglobulin (Ig)-lambda-light chain was established from a patient with Bence Jones-type multiple myeloma. Morphologically, the cell line had plasmacytoid characteristics by light- and electron-microscopic examination. Phenotypic studies of NOP-2 cells revealed no surface Ig, but they were positive for cytoplasmic Ig-lambda, OKT10 (CD 38), and PCA-1. Epstein-Barr nuclear antigen was not detected. Chromosomal abnormalities of t(11;14) and t(8;22) were found in both NOP-2 cells and the original myeloma cells obtained from the patient. NOP-2 cells produced and secreted Ig-lambda light chain, but lacked immunoglobulins of any heavy chains. Rearrangements of both immunoglobulin heavy- and light-chain genes were observed in NOP-2 cells, though the cells expressed detectable mRNA only for Ig-lambda light chain. This cell line may serve as a useful model for understanding the hierarchy of human immunoglobulins and the pathophysiology of Bence Jones-type multiple myeloma.

Antigens, Neoplasm↗
PubMed1991

Expression of H-related antigen on human megakaryocytes and megakaryocytic leukemia cells.

A mouse monoclonal antibody (MoAb), MG-2, was produced by immunizing a characterized human megakaryoblastic cell line, MEG-01. Since MG-2 reacted with erythrocytes of all ABH blood groups except Oh (O Bombay), and since anti-H MoAb inhibited MG-2 binding to MEG-01 cells, MG-2 is considered to recognize a molecule closely related to blood group antigen H. MG-2 reacted more strongly with normal smaller sized megakaryocytes than with larger sized ones, and not with platelets. The expression of the intrinsic H-related antigen on MEG-01 cells decreased concomitant to megakaryocytic differentiation induced by phorbol esters. This H-related antigen was expressed on leukemia cells with the megakaryocytic features from blast crisis of chronic myelogenous leukemia and acute megakaryoblastic leukemia.

ABO Blood-Group System↗
PubMed1991

[Roentgenological and pathological studies on the development of discitis in canine models].

Discitis was experimentally induced in 42 dogs by intradiscal injections of bacterial suspensions and sequentially studied by X-rays and histopathology up to 24 weeks. 1. A narrowing of the serpentine intervertebral disc space was seen roentgenologically in the Pseudomonas and E. coli groups. 2. Histologically, the acute inflammation began to subside in eight weeks, at which time new bone formation started to appear, and fusion of the adjacent vertebrae became apparent in eight weeks. The degree of the disease process was more advanced in the Staph. aureus group and less severe in the Pseudomonas group. The E. coli group lay in between. 3. The inflammatory process seemed to be confined in the disc for a week after the injection, during which time the cartilagenous cells in the nucleus pulposus underwent atrophy and degeneration. This resulted in direct exposure of the cartilagenous plate to the infection, causing invasion of the inflammatory process into the vertebral body. 4. The presence of the epiphyseal line, however, seemed to act as a barrier to hinder the inflammatory process invading the vertebral body.

Animals↗
PubMed1991

[An autopsy case of Gerstmann-Sträusser-Scheinker's disease with spastic paraplegia as its principal feature].

A 38-year-old woman developed slowly progressive gait disturbance. At age 39 years she was admitted to our department because she could not walk without assistance. On neurological examination she was alert with normal mental functions. Horizontal nystagmus on both sides, minimal clumsiness in the left upper extremity on the finger-to-nose test and moderate degree of spasticity in bilateral lower extremities without evident motor weakness were present. The gait was spastic with small steps on a wide base. There was no sensory abnormalities. The deep tendon reflexes were hyperactive on both sides, on the lower extremities, with positive Babinski's sign. The sphincter functions were intact. During the following 5 years she gradually deteriorated and pseudobulbar palsy, emotional incontinence and the progressive dementia appeared in addition to severe spastic paraplegia. At age 45 years she was admitted to our nursing home and she died 3 months later, of pneumonia, on 6 years after the onset of her illness. Two elder sisters of her 7 siblings had the similar neurologic illness. The brain weighed 1,060 g. There was mild atrophy of cerebrum, cerebellum and brainstem. There were neuronal loss and gliosis in layers IV-VI of cerebral cortex with no evidence of the spongy state. Cerebellar cortex, cerebellar peduncles and spinocerebellar tracts were preserved. There was marked degeneration of corticospinal tract from cerebral peduncle to lateral funiculus of lumbar spinal cord. The most prominent feature was appearance of numerous multicentric amyloid plaques, which were marked in layers I-III of cerebral cortex and to a lesser extent in corpus striatum, hippocampus and the white matters of cerebrum and cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1991

Intensive individualized induction therapy with behenoyl cytarabine, daunorubicin and 6-mercaptopurine followed by intensive consolidation including intermediate-dose continuous cytarabine, mitoxantron, etoposide and vinca alkaloids in acute myeloid leukemia in adults.

Forty-one consecutive adult patients with acute myeloid leukemia (AML) were treated with an intensive individualized induction therapy of behenoyl cytarabine, daunorubicin, and 6-mercaptopurine, 29 patients (71%) achieved complete remission (CR). Patients then received three courses of intensive consolidation therapy, including intermediate-dose continuous cytarabine (400 mg/m2, for 5 days) and non-cross resistant drugs such as mitoxantron, etoposide and vincristine. During the course of the consolidation therapy, three patients died of infections and one died of myocardial infarction. Four patients underwent allogeneic bone marrow transplantation. The patients then received six courses of moderately intensive maintenance therapy for 1 year. The predicted 5-year continuing CR and disease-free survival rates of the CR patients were 62% (95% confidence limit, 41% to 83%) and 53% (33% to 73%), respectively. Although the number of patients in this study is small, the present study indicated that it may be possible to cure a fairly large proportion of AML patients by chemotherapy alone, if intensive induction therapy is followed by intensive consolidation therapy.

Acute Disease↗
PubMed1991

Disappearance of minimal residual lymphoblastic leukemia cells 6 months after allogeneic bone marrow transplantation without GVHD.

The recent development of the polymerase chain reaction (PCR) has enabled us to determine the hypervariable sequence of immunoglobulin heavy chain known as complementarity determining region (CDR)-III. We amplified the leukemia-specific CDR-III from common acute lymphoblastic leukemia (cALL) cells using the PCR and determined its sequence. To detect minimal residual leukemia (MRL) cells, a second round PCR was performed with clone-specific primers corresponding to 5' and 3' ends of CDR-III to detect MRL cells. A million-fold diluted leukemia cells were clearly detected. Using stepwise diluted materials, the number of residual cells was semiquantitatively estimated. In one patient with cALL, induction chemotherapy resulted in a hematologically complete remission with only a 2-log reduction of the leukemia cells. MRL cells at a level of 10(-6) were also detected within 1 month after bone marrow transplantation (BMT), but leukemia cells were not detectable 6 months after BMT.

Adult↗
PubMed1991

Treatment of myelodysplastic syndromes with orally administered N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex).

N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex) was administered orally, to patients with myelodysplastic syndromes (MDS) and acute leukemia derived from MDS, in a multi-institute study. Out of 77 patients evaluated, one achieved a complete remission, three a good response and two a partial response while 71 failed to respond to a daily oral administration of 30 mg ubenimex. The overall response rate was 7.8% (95% confidence limits; 3.6-16.0%); 7.0% (3.0-15.4%) in 71 MDS and 16.6% (3.0-56.3%) in acute six leukemias derived from MDS. Responses continued for six to 24 (median 10.5) weeks. No serious hematologic, biochemical or clinical toxicity was encountered, except for gastro-intestinal (GI) toxicity in one patient. The present study demonstrated ubenimex not to be generally beneficial for patients with MDS, and not to be recommended as a standard treatment for the disease.

Acute Disease↗