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Biomedical subjects

M Hanada

Publications and source records attributed to M Hanada.

At least 91 records · Page 5Linked to original sources

bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia.

The bcl-2 gene becomes transcriptionally deregulated in the majority of low-grade non-Hodgkin lymphomas as a result of t(14;18) translocations that place the bcl-2 gene at 18q21 into juxtaposition with the Ig heavy-chain locus at 14q32. This chromosomal translocation or similar bcl-2 gene rearrangements involving the Ig light-chain genes have been reported to occur in some cases of B-cell chronic lymphocytic leukemia (B-CLL). We analyzed the structure, methylation, and expression of the bcl-2 gene in 20 cases of B-CLL or closely related variants of this lymphoproliferative disorder, including at least 16 typical examples of CD5+ B-CLL. None of the 20 specimens had evidence of bcl-2 gene rearrangements, based on Southern blot analysis using three different bcl-2 probes. However, immunoblot analysis using antibodies specific for the Bcl-2 protein showed that 14 of 20 cases (70%) contained levels of p26-Bcl-2 that were equal to or greater than those found in a t(14;18)-bearing lymphoma cell line. Furthermore, in 19 of 20 cases (95%), the Bcl-2 protein was present at levels that were 1.7- to 25-fold higher than in normal peripheral blood lymphocytes. These differences in the relative levels of Bcl-2 protein among cases of B-CLL appeared to be functionally significant, in that a preliminary analysis of 3 representative cases showed that CLL cells with higher levels of Bcl-2 protein survived longer in culture and were delayed in their onset of DNA degradation relative to CLL cells with lower Bcl-2 protein levels. Evaluation of the methylation status of the bcl-2 gene using the isoschizomers Msp I and Hpa II, and a probe corresponding to the first major exon of the gene showed complete demethylation of both copies of the bcl-2 gene in a region corresponding to a 2.4-kb Msp I fragment in all 20 cases of B-CLL. In contrast, analysis of 6 of 6 B-cell lines that harbor a t(14;18) was consistent with hypomethylation of only one of the two bcl-2 alleles. Neither copy of the bcl-2 gene was demethylated in this region in 5 of 5 lymphoid cell lines that lack this translocation. However, hypomethylation of the bcl-2 gene did not necessarily correlate with the relative levels of Bcl-2 protein present in the B-CLL cells, suggesting that additional mechanisms for regulating bcl-2 expression are involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗

Peliosis of the spleen with intraperitoneal hemorrhage.

We encountered a patient with steroid-related peliosis of the spleen, a rare disease characterized by multiple blood-filled cavities in the splenic parenchyma, with spontaneous intraperitoneal hemorrhage. The ultrasonographic, computed tomographic, and angiographic images were compared with pathologic findings of the material obtained surgically.

Aged↗

Epocarbazolins A and B, novel 5-lipoxygenase inhibitors. Taxonomy, fermentation, isolation, structures and biological activities.

New 5-lipoxygenase inhibitors, designated epocarbazolins A and B, were isolated from the culture broth of Streptomyces anulatus T688-8. These compounds showed potent rat 5-lipoxygenase inhibitory activity with weak antibacterial activity. Structural studies revealed that epocarbazolins are new carbazole antibiotics having a novel substitution pattern and an epoxide in the side chain.

Animals↗

[Immunoblastic lymphadenopathy (IBL)-like T cell lymphoma associated with granulocytopenia and autoimmune hemolytic anemia].

A 65 year-old woman was admitted in May 1990, because of fever, generalized lymphadenopathy and eruption. Laboratory examination showed granulocytopenia, polyclonal hypergammaglobulinemia, positive Coombs' test, positive cold antibody and positive anti-E erythrocyte antibody. 7 days after admission autoimmune hemolytic anemia developed. The appearance of the anti neutrophil leukocyte antibody was suspected because of the absence of the segmented neutrophils in marrow specimen. Histological findings of the biopsied lymph node and the marker study of the tumor cell disclosed IBL-like T cell lymphoma. The patient was treated with G-CSF and VEPA chemotherapy. Granulocytes increased and she showed marked symptomatic improvement with complete remission. Our case showed various clinical pictures with hemolytic anemia and granulocytopenia, which could be based on the autoimmune mechanisms.

Aged↗

[Squamous papillomatosis of the left main bronchus and trachea: a case report].

A 49-year-old female complaining of dyspnea at exercise was admitted. Bronchoscopic examination revealed that the left main bronchus was almost obstructed by a tumor. A sleeve resection of the left main bronchus was performed. Histological examination confirmed that the tumor was squamous papilloma. After one year and eight months, bronchofiber examination disclosed papilloma in the trachea. Therefore, papilloma was treated with endoscopic methods, including Nd-YAG laser. The patient has survived for 11 years since first treatment.

Bronchial Neoplasms↗

Cellular immunosuppression in children with acute lymphoblastic leukemia: effect of consolidation chemotherapy.

The present study was designed to evaluate the chemotherapy-induced cellular immunosuppression in 20 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy. Peripheral blood was serially obtained from leukemic children during vincristine/cyclophosphamide/6-mercaptopurine/prednisone combined consolidation chemotherapy. The mean absolute number of peripheral blood lymphocytes as well as the mean absolute numbers of lymphocyte subsets (T cells, T cell subsets, B cells, and natural killer cells) from leukemic children before consolidation chemotherapy were all significantly lower than in control subjects; however, the percentages of lymphocyte subsets were similar in both groups. After consolidation chemotherapy, the percentages of CD4+ T lymphocytes and natural killer (NK) cells were significantly decreased and the percentages of monocytes and CD8+ T lymphocytes were significantly increased. Phytohemagglutinin- and 12-O-tetradecanoylphorbol-13-acetate-induced production of interleukin-2 (IL-2) and NK-cell-mediated cytotoxic activity by peripheral blood mononuclear cells (PBMC) were also substantially decreased in the post-therapy groups. NK activity correlated with the percentage of NK cells in PBMC. In contrast, OK432-induced production of tumor necrosis factor alpha (TNF alpha) and killer activity against NK-resistant target cells were significantly increased after therapy as compared with the pre-therapy and control groups. TNF alpha production correlated with the percentage of monocytes in PBMC. These results demonstrate that substantial quantitative and qualitative chemotherapy-induced abnormalities of the cellular immune system are present in the majority of patients treated with ALL. It is also suggested that the increased TNF alpha production by monocytes and the appearance of potent killing activity against NK-resistant targets might compensate for the defects of IL-2 production and NK activity during intensive consolidation chemotherapy.

Animals↗

Epoxomicin, a new antitumor agent of microbial origin.

An actinomycete strain No. Q996-17 produced a novel compound, epoxomicin, which exhibited in vivo antitumor activity against B16 melanoma. Structural studies indicated that it is a new member of the epoxy-beta-aminoketone group, and is closely related to eponemycin.

Actinomycetales↗

Protactin, a new antibiotic metabolite and a possible precursor of the actinomycins.

Streptomyces cucumerosporus strain L703-4 (ATCC 53784) produces a new 4-methyl-3-hydroxyanthraniloylpentapeptide lactone for which we have proposed the name protactin, in addition to several actinomycin components. Protactin is rather resistant to air oxidation but it can be converted to a new actinomycin, actinomycin Zp by ferricyanide oxidation. Actinomycin Zp possesses in vitro antibacterial activity and in vivo antitumor activity against P-388 leukemia in mice.

Amino Acid Sequence↗

Effects of orally administered beta-adrenergic blockers and calcium-channel blockers on the intraocular pressure of patients with treated hypertension.

Little attention has been paid to the influence of orally administered antihypertensive drugs on intraocular pressure (IOP). Therefore, we evaluated the effects of oral medications on the IOPs and visual fields of 70 patients with systemic hypertension who had no ocular symptoms and had not visited any eye hospital. In patients with systemic hypertension treated with medication, the IOP value (mean, 18.3 +/- 4.2 mmHg; age range, 63.3 +/- 11.6 years) was significantly higher than in a control group with a similar age range who were not receiving oral medication (mean, 13.7 +/- 2.0 mmHg; age range, 62.5 +/- 7.8 years). In the group in which hypertension was controlled by medication, the IOPs were lower when orally administered beta-adrenergic blockers were given than in those patients with uncontrolled hypertension. In the group to whom calcium-channel blockers were administered orally, the IOPs were not lower. Angiotensin-converting enzyme inhibitors made the visual fields worse. This study suggests a modulating influence of orally administered drugs on the IOP and visual fields, which may be affected by whether or not the patient's blood pressure is controlled.

Administration, Oral↗

Complete but transient visual loss after yttrium aluminum garnet laser transscleral cyclocoagulation.

We report the case of a patient who had no light perception after neodymium:yttrium aluminum garnet (Nd:YAG) laser transscleral cyclocoagulation. To the best of our knowledge, no similar cases have been reported previously. A 56-year-old man with intractable open-angle glaucoma had intraocular pressures of 42 mmHg OD and 35mmHg OS. The patient rejected a recommended filtering operation, although argon laser trabeculoplasty and maximal medication had been ineffective OU. We used the free-running mode of an Nd:YAG laser to treat this patient. After the tenth application, the patient suddenly noticed acute visual loss OD. He was admitted to the hospital immediately. His retinal vessels and papilla OD could not be seen during fluorescein angiography. We administered pulsed corticosteroids and a stellate ganglion block. Gradually, his symptoms improved. The indications for using Nd:YAG laser cyclocoagulation have been expanded. However, as a result of our experience in this patient, we concluded that such therapy should be limited to cases not amenable to other forms of medical and surgical treatment.

Autonomic Nerve Block↗

Hyperimmunoglobulinemia D following cancer chemotherapy.

Five classes of serum immunoglobulin levels were investigated in 107 children with malignant or benign tumors. Hyperimmunoglobulinemia D (hyper-IgD) was observed in 31 of 82 children who were in complete remission off chemotherapy with a median follow-up of 4.5 years after cessation of chemotherapy. On the other hand, hyper-IgD was not found among 12 children with malignant or benign tumors treated with chemotherapy and a low incidence of hyper-IgD was observed during chemotherapy (1 of 13 cases). The result indicates that hyper-IgD is not uncommon in children off chemotherapy, suggesting that dysregulation of IgD synthesis persists long after cessation of antineoplastic drugs.

Adolescent↗

Maduropeptin, a complex of new macromolecular antitumor antibiotics.

Maduropeptin, a complex of new macromolecular antitumor antibiotics, is a metabolite of Actinomadura madurae H710-49. The active components maduropeptins A1, A2 and B are acidic chromopeptides with MW of around 22,500 and composed of 14 types of amino acids and an unstable chromophore. The antibiotics are active in vitro against Gram-positive bacteria and highly cytotoxic to tumor cells. They produced significant prolongation of survival time of mice implanted with P388 leukemia and B16 melanoma.

Actinomyces↗

Hydramycin, a new antitumor antibiotic. Taxonomy, isolation, physico-chemical properties, structure and biological activity.

A new antitumor antibiotic hydramycin was isolated from the fermentation broth of Streptomyces violaceus P950-4 (ATCC 53807). It showed potent antibacterial and cytotoxic activity and increased the survival time of mice inoculated with P388 leukemia. A new structure related to the pluramycin group antibiotics was assigned by its spectroscopic experiments.

Animals↗