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Biomedical subjects

R Ohno

Publications and source records attributed to R Ohno.

At least 199 records · Page 11Linked to original sources
PubMed1995

[A randomized double-blind controlled study of recombinant human granulocyte colony-stimulating factor in patients with neutropenia induced by consolidation chemotherapy for acute myeloid leukemia. (rG.CSF clinical study group)].

A multicenter, randomized, double-blind controlled study was performed to evaluate the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rG.CSF) in reducing infectious morbidity and neutropenia induced by consolidation chemotherapy for acute myeloid leukemia (AML). One hundred and twenty-four eligible patients were randomized to receive either rG.CSF (5 micrograms/kg/d d.i.v.; 59 patients) or placebo (65 patients) for 14 days from the day after chemotherapy. All of them were included in the safety analysis, while 57 patients receiving rG.CSF and 64 patients receiving placebo were included in the efficacy analysis. The duration of neutropenia as well as the incidence of fever and febrile neutropenia, and frequency of antibiotic therapy required, were all significantly reduced in the rG.CSF group. No serious adverse reactions were encountered; there was no significant difference between the two groups in terms of incidence of adverse events. These results demonstrate that rG.CSF is beneficial to alleviate neutropenic episodes induced by consolidation chemotherapy in patients with AML.

Adolescent↗
PubMed1995

Isoforms of PML-retinoic acid receptor alpha fused transcripts affect neither clinical features of acute promyelocytic leukemia nor prognosis after treatment with all-trans retinoic acid. The Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho).

All-trans retinoic acid (ATRA) has been used as a potent differentiation drug for acute promyelocytic leukemia (APL). Although the mechanism of its effectiveness upon APL remains unclear, the PML-retinoic acid receptor alpha (RARA) chimeric protein produced by t(15;17) is assumed to underlie the sensitivity of APL cells to ATRA. There are two major isoforms of PML-RARA transcripts; short (S) and long (L), according to the breakpoints in the PML gene. We therefore compared the clinical variables, the response to ATRA and the prognosis between 28 patients with type S and 68 patients with type L. Patients were treated in multi-institutional trials with ATRA, and chemotherapy was combined when peripheral blasts and leukocyte counts increased during the therapy. The clinical features at diagnosis were similar between the two molecular subtypes, and there was no significant difference in remission induction rates; 86% for the type S group and 90% for the type L group. There was no statistical difference in overall survival and CR duration as well as disease-free survival (DFS). In newly diagnosed patients, predicted 2-year DFS was 66% for the type S group and 67% for the type L group. In refractory or relapsed patients, it was 19 and 23%, respectively. These data indicated that isoforms of PML-RARA fused transcripts affect neither the clinical features of APL nor the prognosis after treatment with ATRA.

Adolescent↗
PubMed1995

[Characterization of the immunoglobulin heavy and light chain variable region sequences from human multiple myeloma cells].

Although multiple myeloma (MM) morphologically represents the terminal B cell differentiated stage as a plasma cell, it remains controversy that MM cells have arisen from a B cell at which stage of B cell development. The immunoglobulin heavy chain (IgH) variable region genes can serve as markers in clonal analysis because unique combinations of VH, D and JH gene elements and as a genealogical record of clonal selection and expansion, and molecular diversification during maturation of the immune response. We analyzed the IgH variable region sequences from human MM cells. Furthermore, to compare with normal bone marrow (BM) plasma cell repertoire, we determined the IgH variable region sequences of PCR amplified cDNA libraries consisting of C mu, C gamma, and C alpha transcripts from human normal BM cells. The VH segments in MM cells, except for Bence-Jones protein (BJP) type, were extensively mutated, and the characteristic structure of the IgH variable region essentially reflect those from normal BM C gamma and C alpha transcripts. Although the replacement/silent (R/S) mutation ration in MM cells was under the value which reflect antigen selected substitutions, such a lower value was also observed in normal BM C gamma and C alpha transcripts, suggesting that the transformation of MM dose not necessarily take place before the antigen-dependent selection, rather can after clonal expansion. However, BJP type MM might arise from an earlier stage of B cell development than the other types because of lower incidence of somatic mutation in their VH segments which was the same as normal BM C mu transcripts.

Humans↗
PubMed1995

Prognostic significance of the RT-PCR assay of PML-RARA transcripts in acute promyelocytic leukemia. The Leukemia Study Group of the Ministry of Health and Welfare (Kouseisho).

Minimal residual disease (MRD) was prospectively monitored at the 10(-5) level by the reverse transcriptase-polymerase chain reaction (RT-PCR) of PML-retinoic acid receptor alpha (RARA) transcripts from 27 acute promyelocytic leukemia (APL) patients who achieved complete remission (CR) with all-trans retinoic acid and chemotherapy (previously untreated patients, 15; refractory to chemotherapy or relapsed, 12). The RNA quality from bone marrow cells was firstly assessed by gel electrophoresis to avoid false negativity because of the fragility of the APL cells and the PML-RARA transcripts. In 12 of 15 untreated patients, RT-PCR became negative during consolidation and intensification therapy 4-16 months after the initiation of therapy, whereas it remained positive in nine of 12 refractory patients. At the end of therapy, RT-PCR was negative in 14 patients and positive in 13 patients. The former patients remained in CR at median follow-up of 9 months after the end of therapy. In the latter, however, 10 patients relapsed at a median of 5 months after the end of therapy. These results suggest that the RT-PCR assay can evaluate the quality of CR in APL and predict subsequent relapse.

Adult↗
PubMed1995

[Clinicopathological report of cisplatin encephalopathy].

A 61-year-old woman was treated with cisplatin and etoposide for ovarian carcinoma. After the second course of chemotherapy she developed acute encephalopathy which manifested itself as headache, fever, a partial seizure, confusion, and mild right hemiparesis, although no evidence of a central nervous system infection was found. Ten days after the onset of neurological symptoms, she experienced a sudden loss of vision in both eyes. Neurological findings were compatible with cortical blindness. Neurological symptoms subsided and visual acuity completely returned over the next months. The total cumulative dose of cisplatin was 325 mg/m2. She died of aspiration pneumonia on the 43rd day. Postmortem examination revealed severe nerve cell loss, gliosis and spongy changes in the bilateral occipital cortex including visual field, and slight to moderate demyelination in the subcortical white matter of the occipital cortex, Goll's tract, and dorsal root ganglia. As far as we know this encephalopathy is the second report in which the neuropathological changes associated with cisplatin therapy have been demonstrated by autopsy findings. The first was a case report of leukoencephalopathy, which differed significantly from our case in the primary lesions of the brain. We measured the platinum level in several parts of the cerebrum and cerebellum, optic nerve, spinal cord, and cauda equina by using an atomic absorption spectrophotometric technique. Platinum was detected in the bilateral occipital cortex, spinal cord, and cauda equina. These results were consistent with the distribution of pathological lesions. The mechanism of cisplatin-induced focal encephalopathy remains speculative.(ABSTRACT TRUNCATED AT 250 WORDS)

Blindness↗
PubMed1995

[Recent progress in the treatment of adult acute leukemia].

Due to the advance of chemotherapy and bone marrow transplantation, adult acute leukemia has become a curable disease. In acute myeloid leukemia, the JALSG AML89 study resulted in 77% complete remission (CR) rate in 326 adults and 38% 4.5-year disease-free survival (DFS) in CR cases. However, the result of acute lymphoblastic leukemia in the JALSG ALL87 study is not satisfactory; 84% CR in 116 adults and only 24% 6-year DFS. For acute promyelocytic leukemia (APL), all-trans retinoic acid works remarkably, and the JALSG AML92 study for newly diagnosed APL resulted in 89% CR in 109 adults and 81% 2.5-year DFS.

Adult↗
PubMed1995

Continuing immunoglobulin heavy chain gene rearrangements in chronic myeloid leukemia with recurrent B-lymphoid blast crises after bone marrow transplantation.

We sequentially analyzed the immunoglobulin heavy chain variable (IgH V) region gene of leukemia cells obtained from a chronic myeloid leukemia (CML) patient who had three episodes of B-lymphoid crisis after bone marrow transplantation. Southern blot analysis using the JH probe showed different rearranged bands at each crisis, although the same rearranged bands of the BCR gene were observed. We amplified and sequenced the IgH V region gene of the leukemia cells by reverse transcriptase polymerase chain reaction (RT-PCR) using the primers corresponding to the consensus 5'VH and mu constant regions. The dominant leukemia clone at each crisis had a unique VH-D-JH rearrangement; VH4A (V79)-DLR2-J5 (clone-1), VH4B (DP70)-DK4-J6 (clone-2) and VH4A (V79)-DN4-J6 (clone-3) at the first, second and third crises, respectively. Further analysis by PCR amplification using the consensus 5'VH and clone-specific primers revealed that clone-1 underwent VH4-->VH3 replacement at the second crisis, and that clone-3 was already in existence at the first crisis. Moreover, the DN4-J6 joining clone, in which the sequence was the same as that of clone-3, was identified at the first and third crises by PCR amplification using primers corresponding to the region upstream of the DN4 segment and DN4-J6 boundary of clone-3. These observations suggest that multiple clones were generated from the progenitor cells of blast crisis, which were transformed at a very early stage of B-lymphocyte ontogeny, by continuing rearrangement mechanisms of the IgH genes, and that the dominant clone at each crisis was undergoing change.

Adult↗
PubMed1995

[Progress of chemotherapy in adult acute leukemia].

Due to the advance of chemotherapy and bone marrow transplantation (BMT), adult acute leukemia has become a curable disease. Since in BMT a good prognosis is obtained in chemotherapy-induced remission cases, chemotherapy plays a major role for the cure of this disease. In acute myeloid leukemia, the JALSG AML 89 study resulted in a 77% complete remission (CR) rate in 326 adults, 38% of whom had a 4.5-year diseases-free survival (DFS) rate in CR cases. However, the results of acute lymphoblastic leukemia in the JALSG ALL 87 study were not satisfactory; 84% CR in 116 adults and only 24% 6-year DFS.

Adult↗
PubMed1995

Detection of minimal residual disease in patients with childhood common acute lymphoblastic leukemia after autologous bone marrow transplantation with ex vivo purging and systemic IL-2 infusion: unsuccessful prediction of subsequent relapse.

We sequentially analyzed minimal residual disease (MRD) in 7 children with common acute lymphoblastic leukemia (cALL) after autologous bone marrow transplantation (ABMT) with ex vivo purging followed by systemic interleukin-2 infusion. After ABMT, 3 of the 7 patients remained in complete remission (CR) for more than 1 year, and 4 subsequently relapsed. MRD was estimated by polymerase chain reaction amplification to detect the leukemia clone-specific immunoglobulin heavy chain third complementarity determining region (IgH CDR-III). The IgH CDR-III sequences from the relapsed patients were identical with those determined at each respective initial diagnosis. In 2 patients, the levels of MRD were 10(-2) and 10(-5) in the harvested bone marrow (BM) cells, and even after purging the levels were 10(-4) and 10(-5) cells, respectively. One of the 2 patients relapsed 3 months after ABMT, while the other remained in CR for 33 months after ABMT. Among the 4 patients who subsequently relapsed after ABMT, MRD was not detected in the BM samples even 1 month before relapse. Our results suggest that PCR-negativity does not necessarily indicate a lower risk of subsequent relapse. Detection of MRD tends to favor the assessment of the therapeutic effects rather than prediction of relapse.

Base Sequence↗
PubMed1995

[Efficacy of early administration of G-CSF after intensive chemotherapy in acute leukemia: a randomized controlled trial. Tokai Infection Study Group on Hematological Disorders].

The effect of granulocyte colony-stimulating factor (G-CSF) on neutropenia and infection was studied in a randomized trial in patients receiving intensive chemotherapy for acute leukemia. Fifty seven patients with acute leukemia (35 cases of refractory acute myeloid leukemia, 19 cases of acute lymphoblastic leukemia and 3 cases of blast crisis of chronic myeloid leukemia) were given G-CSF under either of the following two conditions; 1) Group A: starting G-CSF (200 micrograms/m2iv) administration 24 hrs after chemotherapy. 2) Group B: the same dose of G-CSF administration after a febrile episode of 38 degrees C with neutropenia (less than 1,000/microliters). Five patients were excluded from the study. Group A (27 patients) showed a shorter febrile period (2.15 +/- 2.98 days) than the 25 patients of Group B (3.40 +/- 4.78 days), but the difference was not statistically significant. Compared to Group B, Group A showed significantly early recovery of neutrophil counts as well as early recovery from documented infections. There was no evidence that early administration of G-CSF accelerates the growth of leukemic cells nor causes early relapse of acute leukemia.

Acute Disease↗
PubMed1994

Bernard-Soulier syndrome Kagoshima: Ser 444-->stop mutation of glycoprotein (GP) Ib alpha resulting in circulating truncated GPIb alpha and surface expression of GPIb beta and GPIX.

The platelet membrane glycoprotein (GP)Ib/IX complex is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX, and functions as a platelet receptor for von Willebrand factor. All three subunits are reported to be requisite for efficient surface expression of the complex. The absence of the GPIb/IX complex on platelet membrane is the hallmark of a congenital qualitative platelet disorder, termed the Bernard-Soulier syndrome (BSS). We describe here the molecular basis of a novel variant phenotype of BSS in a female patient, designated as BSS Kagoshima. Her platelets completely lacked the surface expression of GPIb alpha, but expressed a residual amount of GPIb beta and GPIX. Unexpectedly, her platelets and plasma contained a truncated GPIb alpha polypeptide with an apparent molecular weight of 116 kD (under nonreducing conditions). The amounts of truncated protein were 23% and 60% of the normal values in platelets and plasma, respectively. The abnormal protein contained a normal amount of sialic acid as demonstrated by digestion with neuraminidase. DNA sequencing analysis showed a homozygous single nucleotide substitution from the serine codon (TCA) to a nonsense codon (TAA) at residue 444 in the GPIb alpha gene. The mutant gene generated a truncated GPIb alpha molecule lacking the transmembrane region and cytoplasmic tail. Her parents were heterozygotes for the mutation. These findings suggest that this type of truncated GPIb alpha was produced, normally glycosylated, and subsequently secreted into the plasma. Furthermore, the truncated GPIb alpha might be associated with the process of the surface expression of incomplete GPIb/IX complex, GPIb beta and GPIX.

Adult↗
PubMed1994

A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group.

We conducted a prospective, double-blind controlled study to determine the efficacy of a recombinant granulocyte colony-stimulating factor (G-CSF, 200 microgram/m2) starting daily from 2 days before an induction therapy until neutrophils recovered to above 1,500/microL or until 35 days after the therapy in 58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty-eight patients in the G-CSF group showed significantly faster recovery of neutrophils (P < .001) than 30 patients in the placebo group. The incidence of febrile episodes and of documented infections was almost the same in both groups. However, among 39 patients who did not show any infectious episodes during the 2-week period after the start of chemotherapy, the incidence of documented infections after the third week tended to be lower in the G-CSF group, but not statistically significantly. There was no evidence that G-CSF stimulated the growth of AML cells in the bone marrow during the 2-day period before the chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5-week period after the therapy. Fifty percent of patients in the G-CSF group and 37% in the placebo group had complete remission (CR). Although the rate was higher in the G-CSF group, the difference was not statistically significant (P = .306). There was no difference between the two groups in event-free survival of all patients and in disease-free survival of patients who had achieved CR.

Adolescent↗
PubMed1994

Treatment of adult T-cell leukaemia-lymphoma with irinotecan hydrochloride (CPT-11). CPT-11 Study Group on Hematological Malignancy.

A late phase II study of a new camptothecin analogue, irinotecan hydrochloride (CPT-11), was conducted to evaluate the anti-tumour effect and toxicity in patients with refractory leukaemia and lymphoma including adult T-cell leukaemia (ATL)-lymphoma, in a multi-institutional cooperative study. All the patients with ATL had been previously treated with various conventional combination chemotherapies and were refractory to these therapies or had relapsed. CPT-11 was administered at a dose of 40 mg m-2 day-1 for three consecutive days repeated weekly until evidence of disease progression. One complete remission and four partial remissions were achieved in 13 assessable patients with ATL. The median total dose to achieve remission was 240 mg m-2 and the median duration of response was 31 days. The major toxicities were leucopenia (83%), diarrhoea (62%) and nausea/vomiting (69%). These were relatively severe, but they were generally tolerable and reversible. However, one patient died probably as a result of this therapy. No effective chemotherapy for adult T-cell leukaemia-lymphoma has yet been established, and the prognosis for patients with this disease is very poor. Our results suggest that CPT-11 may be a promising agent for this disease. Further combination therapy with CPT-11 is needed to improve the therapy for ATL.

Adult↗
PubMed1994

Activation and destruction of platelets in patients with rheumatic heart disease.

We evaluated the activation and destruction of platelets in 24 patients with rheumatic heart disease (RHD) involving the mitral valve. Ex vivo platelet aggregation induced by adenosine diphosphate (ADP) and collagen was significantly increased in RHD patients as compared with normal controls. Plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 were also elevated. Plasma concentrations of glycocalicin, a proteolytic fragment of platelet membrane glycoprotein Ib, were increased, while platelet counts were decreased in RHD patients as compared with normal controls. RHD patients with, versus those without, atrial fibrillation demonstrated significant differences in beta-TG levels and platelet counts. However, we observed no difference in glycocalicin levels between the two groups. The present study demonstrated that increased platelet activation, as well as platelet destruction, occur in patients with RHD.

Adult↗
PubMed1994

Characterization of immunoglobulin heavy chain gene rearrangements in chronic myeloid leukemia with recurrent B-lymphoid blast crisis following bone marrow transplantation.

We sequentially analyzed the immunoglobulin heavy chain (IgH) variable region gene of leukemia cells obtained from a chronic myeloid leukemia (CML) patient who had three episodes of B-lymphoid crisis after bone marrow transplantation. Southern blots using the JH probe showed a single rearranged band which differed at each crisis, although the rearranged bands of the BCR gene were the same at each crisis. The IgH variable region sequences of the leukemia cells at each crisis were different. These observations suggested that multiple clones were generated from the progenitor cells of the blast crisis, which were transformed at a very early stage of B-lymphocyte ontogeny.

Adult↗
PubMed1994

Differentiation therapy of myelodysplastic syndromes with retinoic acid.

Clinical trials of differentiation therapy on MDS with retinoic acid are reviewed, and it is discussed whether the differentiation therapy with this drug has scientific relevance for MDS. 13-Cis retinoic acid (13-CRA) may have moderate effect on 20-30% of patients with MDS. In general, the responses are short and toxicity is significant. Since the responses may take at least three weeks and sometimes several months to occur, only patients with a relatively indolent clinical course of MDS would be suitable candidates for this therapy. However, a placebo-controlled prospective randomized study could not confirm the effectiveness of this retinoic acid on MDS. There are only a few clinical trials of all-trans retinoic acid (ATRA) for treatment of MDS. ATRA may have a moderate effect on MDS, but no such a remarkable effect shown on acute promyelocytic leukemia. A placebo-controlled randomized study as having been conducted in 13-CRA is definitely needed to confirm the effectiveness of ATRA on MDS.

Clinical Trials as Topic↗