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Biomedical subjects

R Ohno

Publications and source records attributed to R Ohno.

At least 307 records · Page 17Linked to original sources
PubMed1988

The occurrence of acute lymphoblastic leukemia shortly after the cessation of human growth hormone therapy.

We encountered a case of a 21-year-old man who had developed acute lymphoblastic leukemia (ALL) shortly after the cessation of approximately six years' human growth hormone treatment for pituitary dwarfism. The patient had also been treated with thyroid preparations and methylandrostanolone, a kind of anabolic steroid. Factors relating to the onset of ALL in this case are discussed.

Child↗
PubMed1988

False-negative lumbar discograms. Correlation of discographic and histological findings in postmortem and surgical specimens.

To investigate the causes of false-negative discograms, 181 lower thoracic and lumbar intervertebral discs that had been removed as part of en bloc specimens during thirty autopsies were studied first by discography and then histologically. Comparison of the results of the two methods showed that if fissures and cysts were present in a degenerated anulus fibrosus, but did not establish continuity between the nuclear cavity and the site of a herniation, the discogram was false-negative. Under these circumstances, the inner fiber bundles of the anulus fibrosus were intact and their orientation was often reversed, so that they bulged inward. This finding suggested that a protrusion or a prolapse of tissue from just the anulus fibrosus might have been developing. Ten of the fifty-seven discs that had such changes in the orientation of the fibers had a histologically proved protrusion or prolapse of the anulus fibrosus. However, the discograms showed protrusion in only six of the ten discs and demonstrated a false-negative result in the other four. The cases of seventy-seven patients in whom discography had been performed and a herniation had been subsequently confirmed at operation were also studied. Fifty-nine of the patients had a protrusion and eighteen had a prolapse of the disc. The discograms were falsely interpreted as negative in 32 per cent (nineteen) of the fifty-nine patients who had a protrusion and in 56 per cent (ten) of the eighteen who had a prolapse. Histologically, the prolapses were interpreted as protrusions of a portion of the anulus fibrosus. It was concluded that false-negative discograms are more frequent when a protrusion or a prolapse involves the anulus fibrosus rather than the nucleus pulposus, and that a negative discogram does not exclude the possibility of extensive degeneration of the anulus fibrosus.

Adult↗
PubMed1988

[Phase II study of carboplatin in malignant lymphoma].

A phase II study of carboplatin for malignant lymphoma was conducted. Thirty-nine patients with malignant lymphoma were entered into this study, and 6 of them were excluded from evaluation due to violation of selection criteria. The remaining 33 cases were studied to assess the effectiveness and safety of this drug. Two CR and 11 PR were obtained with this medication (effective rate 39%). The significant affecting factors were previous treatment, disease stage and P.S. score. Many cases suffered from gastrointestinal symptoms and reduced hematopoiesis. The former complication was self-limited without any fatal episodes. However, the latter included severe cases, especially thrombocytopenia, which is suggested to be a dose limiting factor (DLF) of this drug.

Adolescent↗
PubMed1988

[Treatment of myelodysplastic syndromes (MDS) with oral administration of N4-palmitoyl-1-beta-D-arabinofuranosyl cytosine (PLAC)].

A phase II clinical trial on MDS was conducted in a cooperative study with orally administrable ara-C analogue, PLAC, which is resistant to cytidine deaminase and had shown an anti-tumor activity on various experimental tumors by oral route. Fifty MDS (3 RA, 18 RAEB, 11 RAEB-T, 18 RAEB-blast crisis (BC) were treated orally with 100 to 400mg/body of daily PLAC. One good response (GR) and 3 partial responses (PR) were obtained in 18 RAEB, and 2 complete remissions, 1 GR and 1 PR were noted in 11 RAEB-T, while 3 PR were seen in 18 RAEB-BC. Overall CR rates were 4%, GR rates 4% and PR rates 14%. Thus, 22% of MDS responded to oral PLAC. No clear daily dose-response was noted. Response, however, was dependent on the treatment period and was obtained in cases which had been treated for more than 20 days. Besides myelosuppression, side effects were mainly gastrointestinal, and anorexia (32%), nausea/vomiting (30%) and diarrhea (8%) were observed. Oral PLAC seems to be active on MDS which does not necessarily require admission to hospital.

Administration, Oral↗
PubMed1988

Analysis of immunophenotype, genotype, and lineage fidelity in blastic transformation of chronic myelogenous leukemia: a study of 20 cases.

We have examined the immunophenotype and genotype of leukemic cells from 20 patients with the blastic phase of chronic myelogenous leukemia (CML), which is known to arise from a pluripotential hematopoietic stem cell. The phenotypic analysis of surface antigens with a panel of lineage-specific monoclonal antibodies revealed that six of 20 cases expressed phenotypes of lymphoid blastic transformation with pre-B cell markers. One of these cases was shown to coexpress cluster designation 2 of T cell marker on the same cells by two-color immunofluorescence analysis. Eight cases, including two cases that also had a megakaryocytic component, showed phenotypes expressing differentiation antigens of myeloid series. Three expressed a phenotype of megakaryoblastic transformation. The remaining three cases had no surface marker characteristic of any cellular lineage. The genotypic analysis by Southern blot hybridization showed that immunoglobulin heavy chain genes were rearranged in all of six lymphoid blastic transformations and that rearrangement of a T cell receptor beta chain gene was present in only one lymphoid blastic transformation that had no T cell surface marker. DNA samples in all cases of nonlymphoid blastic transformation were retained in the germ line configuration for both immunoglobulin and T cell receptor genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1987

Interferons in the treatment of multiple myeloma.

A review of the clinical studies in which interferons have been involved has shown that they may have a role in the treatment of multiple myeloma. Twelve studies, each of which involved at least 10 evaluable cases (352 in total) with various dose schedules involving leukocyte, lymphoblastoid and recombinant alpha-IFNs, reported 8-33% objective responses. The response duration was rather short but, in a few cases, it lasted for more than a year. In addition to a decrease in the levels of M-protein and/or urine Bence-Jones protein, a decrease in the number of plasma cells in the bone marrow, disappearance of bone pain, healing of bone lesions, increase of hemoglobin and/or restoration of normal immunoglobulins were observed. Higher doses of recombinant alpha-interferons seemed to exert a stronger effect. No clear difference in response rate was observed between myeloma which had been previously treated and that which was not treated. At least clinically, therefore, there seems to be no cross-resistance between alpha-interferons and conventional anti-tumor drugs. A randomized study comparing low-dose leukocyte interferon with intermittent high-dose melphalan-prednisone has given a lower response rate for interferon. Beta- and gamma-interferons have not yet been extensively studied. They have been used at low doses producing an objective response in 7% of 68 and 2% of 45 evaluable cases, respectively. Since the myelosuppression of interferons is transient and, after discontinuation of interferon therapy, peripheral blood cells usually recover within a week, it may be possible to use interferon in combination with agents that have strong myelosuppressive effects provided there is no synergism.

Bence Jones Protein↗
PubMed1987

A phase II study of (2"R)-4'-0-tetrahydropyranyladriamycin (THP) in hematological malignancies.

A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13-34 mg/m2 for 3-5 consecutive days or 35-50 mg/m2 at 3-4 week intervals. Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6. The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for acute leukemia and malignant lymphoma.

Acute Disease↗
PubMed1987

Phase I study of recombinant human tumor necrosis factor.

A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1 x 10(5) units/m2. The dose was escalated up to 16 x 10(5) units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16 x 10(5) units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12 x 10(5) units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5 x 10(5) units/m2.

Adult↗
PubMed1987

Treatment of acute leukemia and malignant lymphoma with (2"R)-4'-O-tetrahydropyranyladriamycin.

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3-4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m2 THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR + PR) was noted in 10 (40%) of 25 patients treated every 3-4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.

Adult↗
PubMed1987

Cell-mediated immunity to bovine P2 protein and neuritogenic synthetic peptide in experimental allergic neuritis.

Cellular reactivity to bovine P2 protein (P2) and its two synthetic peptides, SP66-78 and SP70-78, was serially examined by the lymphocyte proliferation test in animals with experimental allergic neuritis (EAN). SP66-78 and SP70-78 correspond to residues 66-78 and 70-78 of bovine P2. Proliferative response to SP66-78 as well as P2 appeared at day 7 before the onset of EAN and was clearly manifested at day 14 in the active stage, thereafter disappearing in the stable stage, whereas no response to SP70-78 was detected during the course of the disease. These results suggest that cell-mediated immune response to P2 and the specific part residues 66-78 of P2 play an important role in the pathogenesis of EAN.

Animals↗
PubMed1987

Detection of cross-reactive antibody to BLV p24 in sera of human patients infected with HTLV.

For detection of antibody to bovine leukemia virus (BLV) major core protein of p24 and cross-reactive antibody in human patients infected with human T cell leukemia virus type I (HTLV-I), monoclonal antibody, D432 against BLV p24 was used by competitive binding enzyme-linked immunoadsorbed assay (ELISA). In sera from cattle with enzootic bovine leukosis (EBL) which were positive for BLV antibodies by immunodiffusion test, 109 out of 112 (97.3%) were positive for BLV p24 antibody by competitive binding ELISA. By using the same procedures, 21 samples from adult T cell leukemia (ATL) patients and healthy carriers with HTLV-I were tested for cross-reactive antibody to BLV p24. All 21 samples were positive for HTLV-I antibodies by immunofluorescence test and/or ELISA. By competitive binding ELISA using non-treated BLV antigens, none of these 21 samples inhibited the binding of the D432. When the BLV antigen was treated by several different denaturation procedures, several HTLV-I positive samples showed the inhibition of the D432 binding and the most effective treatment was by 2-mercaptoethanol (2-ME). Sixteen out of 21 samples showed the presence of cross-reactive antibody against 2-ME-treated BLV antigens. The cross-reactivity of human sample to BLV p24 antigen was further confirmed by Western blotting of the 2-ME-treated BLV antigens. None of the 28 samples from leukemia patients other than ATL which were negative for HTLV-I antibodies showed inhibition of the D432 by the competitive binding ELISA.

Antibodies, Viral↗
PubMed1987

High-dose intravenous corticosteroids in the treatment of multiple sclerosis.

The effectiveness of high-dose intravenous corticosteroid therapy for acute bouts of multiple sclerosis (MS) was evaluated in comparison with the conventional oral prednisolone therapy. Group I comprised 11 cases of MS treated with oral prednisolone, 30-60 mg daily, and group II comprised 16 cases treated with intravenous corticosteroids; 11 cases given 1000 mg of methylprednisolone for the initial 3 days followed by 100 mg of prednisolone, while the remaining 5 were given 100 mg of prednisolone alone. The initial dosage was maintained for 1 or 2 weeks in each group, tailing off with a period of several weeks of oral prednisolone. The clinical status was evaluated using Kurtzke's expanded disability status scale (EDSS) and functional system scale before and 1, 2 and 4 weeks after the initiation of therapy. EDSS score significantly declined from week 0 (before) to weeks 1, 2 and 4 in group II, respectively, whereas no significant decline of EDSS score was observed in group I. The frequency of improvement (0.5 of an increment in EDSS score) in group II was significantly higher than that in group I at weeks 1, 2 and 4. It was thus suggested that high-dose intravenous corticosteroid therapy might be more useful in acute bouts of MS, especially for obtaining an early improvement, than conventional oral prednisolone therapy.

Administration, Oral↗
PubMed1987

Predominant suppression of neutrophil colony growth by recombinant human tumor necrosis factor.

To investigate the suppressive effect of recombinant human tumor necrosis factor (rH-TNF) on colony growth of human granulocyte-macrophage progenitor cells (CFU-GM), cytochemical examinations of CFU-GM colonies were performed by a triple staining method. Each colony was classified into five subtypes, and the effects of rH-TNF on each subtype were analyzed. Neutrophil colony growth was inhibited by rH-TNF in a dose-dependent manner, and it was almost completely suppressed at 100 U/ml. In contrast, no significant suppressive effect of rH-TNF was found on the growth of monocyte-macrophage and eosinophil colonies at 100 U/ml or less. When recombinant human granulocyte colony-stimulating factor which almost exclusively stimulates neutrophil colony formation was used as a source of colony-stimulating activity, the total colony growth was almost completely suppressed by 100 U/ml of rH-TNF. These results indicate predominant inhibition of neutrophil colony growth by rH-TNF.

Adolescent↗
PubMed1987

[Clinical studies on interferon in cancer therapy in Japan].

Since the late 1970s, 18 clinical studies have been conducted in Japan with various types of human interferon (IFN) for their possible anti-tumor efficacy under the control of the Special Committee for Clinical Application of IFN of the Ministry of Health and Welfare. Objective antitumor effects have been observed in renal cell carcinoma, brain tumor, multiple myeloma, malignant lymphoma, adult T cell leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and by local injections in skin cancer such as malignant melanoma and cutaneous lymphoma. In this paper, updated results of clinical studies of the 3 types of IFNson various malignant tumors in Japan was reviewed, and the potential usefulness of IFNs as the first cytokine introduced into a clinical trial of the treatment of cancer was discussed.

Brain Neoplasms↗
PubMed1987

Phorbol ester induces interleukin-2 receptor on the cell surface of precursor thymocyte leukemia with no rearrangement of T cell receptor beta and gamma genes.

The early event of thymocyte maturation has been analyzed using acute lymphoblastic leukemia (ALL) cells. A group of ALL cells whose cell surface phenotype was CD2 (SRBC receptor) negative and CD7 (T cell antigen) positive has been considered as precursor thymocyte ALL (pre-T-ALL). No rearrangements of the T cell receptor beta-gene (TCR beta) and gamma-gene (TCR gamma) were found in three of four pre-T-ALL patients. Stimulation of these pre-T-ALL cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) induced only CD25 (Tac) antigen but no other T cell antigens. These findings suggest that the activation pathway of interleukin 2 (IL-2) receptor already exists in the most immature precursor thymocytes. Pre-T-ALL cells from the fourth patients showed the expression of CD3 antigen, and both TCR beta and TCR gamma rearrangement. TPA induced the differentiation of the more mature pre-T-ALL cells of this case in vitro, and not only CD25 (Tac) antigen but also CD4 and CD8 antigens appeared on the cell surface. The low affinity binding of 125I-IL-2 to TPA-stimulated leukemia cells was observed in the three cases of pre-T-ALL tested, and the addition of recombinant IL-2 to TPA-stimulated cells showed no effect on cell proliferation.

Antibodies, Monoclonal↗
PubMed1987

Possible absence of common polymorphisms in coagulation factor IX gene in Japanese subjects.

Four distinct intragenic polymorphisms in the coagulation factor IX gene which have been reported to be important for family diagnosis of Caucasian hemophilia B were studied in 51 normal Japanese subjects (21 males and 30 females). High-molecular-weight DNA prepared from peripheral blood lymphocytes were digested with endonuclease, Ddel, Mspl, Taql or Xmnl, and were studied by Southern blot analysis with factor IX complementary DNA as a probe. None of the minor fragments produced by these enzymes was found in the normal Japanese DNA samples tested, although the probe detects minor allelic forms in control Caucasian DNA samples. Our data suggest that the frequent polymorphic sites found in Caucasians are possibly absent in the Japanese population.

Asian People↗
PubMed1987

Detection of multidrug resistance markers, P-glycoprotein and mdr1 mRNA, in human leukemia cells.

We have examined the expression of P-glycoprotein in clinical leukemic cell samples by using a monoclonal antibody (MRK16) against P-glycoprotein. We found that leukemia cells isolated from 3 out of 6 patients with blast crisis of chronic myelogenous leukemia were reactive to MRK16. These 3 cell lines expressed high levels of mdr1 mRNA, which codes for P-glycoprotein. The present result indicates that the clinically refractory state of the tumor may be predicted in part by determining P-glycoprotein expression using the monoclonal antibody against P-glycoprotein, and the mdr1 probe.

ATP Binding Cassette Transporter, Subfamily B, Mem↗