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Biomedical subjects

A Tada

Publications and source records attributed to A Tada.

At least 19 recordsLinked to original sources

Adduct formation at C-8 of guanine on in vitro reaction of the ultimate form of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine with 2'-deoxyguanosine and its phosphate esters.

We examined the reactivity of the N-hydroxyamino derivative of a carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), after its O-acetylation with four 2'-deoxyribonucleoside 3'-monophosphates. 32P-Postlabeling analysis demonstrated that the levels of adducts with 2'-deoxyguanosine 3'-monophosphate were much higher than those with the other three nucleotides. 1H-NMR, mass spectral and UV absorption spectral analyses of the major adducts formed by N-acetyoxy-PhIP with 2'-deoxyguanosine and with its phosphate esters indicated that PhIP bound at the C-8 position of guanine, as previously demonstrated with other heterocyclic amines.

Acetic Anhydrides

[A case of pulmonary atypical mycobacteriosis complicated with aplastic anemia, treated with surgical resection and postoperative sparfloxacin].

A few weeks after treatment with INH, RFP and SM, severe aplastic anemia developed in a 49-year-old man with pulmonary atypical mycobacteriosis due to M. kansasii. All drugs were discontinued immediately after bone marrow examination revealed severely hypoplastic marrow, but pancytopenia continued for several months. Although M. kansasii was sensitive to other drugs including CS and TH, these two drugs were also discontinued because of their respective psychiatric and hepatic adverse effects. Ofloxacin (OFLX), to which M. kansasii was sensitive, was administered without clinical improvement and complete resistance to OFLX developed after several months treatment. Right upper and middle lobectomy and S6 partial lobectomy was performed, and postoperative sparfloxacin (SPFX) administration resulted in cure of the disease. Drug sensitivity testing revealed that the organism had acquired resistance to OFLX, but was still sensitive to SPFX. Thus, SPFX appears to be an useful drug for the treatment of atypical mycobacteriosis.

Anemia, Aplastic

[Secondary sideroblastic anemia caused by long term administration of anti-tuberculous agents including isoniazid].

A 54 year-old man, who had been treated for several years with isoniazid, was transferred to our hospital because of intractable pulmonary tuberculosis. He was given several anti-tuberculous agents including INH, CS and/or PZA for a long period of time without improvement of the pulmonary tuberculosis. After 7 years' treatment with INH, hypochromic microcytic anemia developed. Parenteral administration of iron preparation failed to improve the anemia. The bone marrow findings revealed erythroid hyperplasia and a few erythroblasts showed megaloblastic change. The bone marrow iron staining revealed increased sideroblasts of which 88% were ringed-form. INH was then discontinued and pyridoxal phosphate was administered with rapid complete improvement of the anemia. INH is well known as a causative agent for acquired secondary sideroblastic anemia, however only one case of INH-induced sideroblastic anemia has been reported in Japan. This is the second reported Japanese case of INH-induced secondary sideroblastic anemia, which appears to be a very rare condition because of genetically determined rapid acetylation of INH in Japanese.

Anemia, Sideroblastic

[Post-gastrectomized vitamin B12 deficient anemia with marked leukoerythroblastosis and ringed sideroblasts].

A 77 year-old man, who had received total gastrectomy and splenectomy 11 years ago for gastric cancer was transferred to our hospital because of severe macrocytic anemia. He had been treated with vitamin B1, B2, C and iron preparations for several weeks. Ten days before admission numbness developed in his legs. On physical examination he appeared severely anemic. Laboratory findings revealed severe macrocytic anemia with poikilocytosis, anisocytosis, polychromasia, red cell fragmentation, Howell-Jolly bodies, Cabot rings and marked erythroblastosis (421/100 WBC). Hypersegmented neutrophils and immature granulocytes were also seen in the blood. The bone marrow picture showed marked erythroid hyperplasia, but erythroblasts revealed only slight megaloblastic changes. On bone marrow iron staining all erythroblasts were classified as type III sideroblasts and 15% of them were ringed-form. Serum vitamin B12 was low (44 pg/ml). Methylcobalamin given intramuscularly led to the rapid improvement of all hematological abnormalities including leukoerythroblastosis. Two weeks after vitamin B12 administration, ringed sideroblasts could no longer be detected in the bone marrow. Post-gastrectomy vitamin B12 deficiency anemias combined with erythroblastosis and ringed sideroblasts is a rare condition. Splenectomy is thought to play an important role in the pathogenesis of these conditions.

Aged

[A case of rush dust (IGUSA-SENDO) pneumoconiosis with a large conglomerate mass shadow].

A 61-year-old woman, who had engaged in "tatami" mat production for 20 years, showed a gradually increasing large conglomerate mass shadow associated with small irregular opacities on chest X-ray film. Transbronchial lung biopsy revealed findings consistent with pneumoconiosis, with no suggestion of pulmonary tuberculosis or lung cancer. After 6 years' observation, right upper lobectomy was performed because the mass shadow was still increasing in size. Histological examination revealed a well-defined large mass composed of numerous macrophages containing abundant silicate minerals and fibroblasts proliferating in storiform fashion. No evidence of tuberculosis or malignancy has ever been detected. These findings are compatible with the previously reported pathological findings of "IGUSA-SENDO" pneumoconiosis; however, PR4 type "IGUSA-SENDO" pneumoconiosis has never been previously reported. This is the first reported case of PR4 type "IGUSA-SENDO" pneumoconiosis.

Female

[In vitro activities of newly developed quinolones, fleroxacin, lomefloxacin and sparfloxacin against Mycobacterium tuberculosis].

In vitro antituberculous activities of three newly developed quinolones, fleroxacin (FLRX, AM-833), lomefloxacin (LFLX) and sparfloxacin (SPFX, AT-4140) were evaluated in comparison to that of ofloxacin (OFLX) using M. tuberculosis strains isolated from patients and the Ogawa egg medium. SPFX was apparently more active than OFLX, but both FLRX and LFLX were less active. SPFX inhibited completely the growth of all 20 strains of M. tuberculosis isolated from patients who were not previously treated with OFLX in a concentration of 1.25 micrograms/ml. However, this agent inhibited the growth of only 4 strains (28.6%) of 14 OFLX-resistant M. tuberculosis in a concentration of 1.25 micrograms/ml, suggesting a partial cross-resistance between SPFX and OFLX.

Anti-Infective Agents

Characterization of bovine papillomavirus type 1-transformed clones which show distinct transformed phenotypes.

Seventeen independent cell clones were isolated from C127 cells transformed by bovine papillomavirus type 1 (BPV-1). Transformants showed differing degrees of expression of the transformed phenotype as monitored by saturation density, doubling time, growth in medium with a low serum concentration and colony-forming efficiency in soft agar. The degree of expression of the transformed phenotype did not correlate with either the BPV-1 copy number or levels of BPV-1-specific RNA in the transformed cell clones. A characteristic transformed cell clone, T1c, showed the lowest degree of expression of the transformed phenotype but contained the highest copy number of BPV-1 DNA and the highest level of BPV-1-specific mRNA. When we analysed different transformants by two-dimensional gel electrophoresis, we found that a set of six proteins changed quantitatively. Changes in the expression of these proteins were most consistent in clones expressing the greatest number of parameters of transformation, e.g. clone T4a. These data indicate that changes in the expression of cellular genes may correlate with the degree of expression of the transformed phenotype.

Animals

[A randomized trial comparing ACF (adriamycin, cyclophosphamide, ftorafur) and ACF/MVMF (mitomycin C, vincristine, methotrexate, ftorafur)--a non-cross-resistant alternating chemotherapy of recurrent and advanced breast cancer].

Of 47 consecutive patients with advanced breast cancer, we randomly assigned 24 to receive Arm A; ACF alone (Adriamycin, Cyclophosphamide, Ftorafur) and 23 to receive Arm B; 2 cycles of ACF alternating one cycle of MVMF (Mitomycin C, Vincristine, Methotrexate, Ftorafur--a combination of drugs not cross-resistant with ACF). The response rate was 66% in Arm A and 52% in Arm B. The median duration of response was significantly longer in Arm B (11 months in Arm A, 28.8 months in Arm B) due to prolongation of duration to administer adriamycin in Arm B. But the median survival time was 30.7 months in Arm A and 24.5 months in Arm B, and significantly longer in Arm A until 10 months. These results were due to the difference in response rate during induction therapy (58% in Arm A, 26% in Arm B) reflected in the dose intensity of Adriamycin (13 mg/m2/w in Arm A, 6.7 mg/m2/w in Arm B) and the higher CR rate in Arm A, because CR cases had a significantly longer survival than PR and NC cases in both arms. We suppose that achieving CR by an intensive regimen containing adriamycin and adopting a non-cross-resistant regimen can help prolong survival in advanced breast cancer.

Adult

[Chemotherapy of aggressive non-Hodgkin's lymphomas: a retrospective analysis of a single institution].

In order to assess the curability of diffuse non-Hodgkin's lymphoma, a total of 93 patients who had entered into protocol studies in our institution was analysed retrospectively. Between 1977 and 1988, 53 large cell lymphoma (DL), 16 mixed cell lymphoma (DMx), and 24 medium-sized cell lymphoma (DM) patients with advanced disease were treated with CHOP, CHOP-Bleo, or CHOP-Bleo alternating with POEM-Bleo (5-drug combination of mitoxantrone, etoposide, vincristine, bleomycin, and prednisolone). The complete response rate was 70% for DL, 69% for DMx, and 54% for DM. The response was most durable in DL, compared with DMx and DM: the relapse-free survival rate at 5-year was 71% for DL, both 38% for DMx and DM. Almost all the relapses had occurred within 2 years in DL, DMx and DM, as well, thus responding patients over 2 years after cessation of chemotherapy appeared to have been cured. Relapse-free survival rate was almost the same for T- and B-lymphoma, however, the 5-year survival rate of T-lymphoma was lower than that of B-lymphoma, reflecting the poor complete response rate of the former. Finally, the disease-free survival rate at 5-year was 39% for all the 93 patients, with a trend favoring for DL histology with a rate of 51%. The alternating CHOP-Bleo/POEM-Bleo regimen appears beneficial compared with conventional regimens such as CHOP and CHOP-Bleo on the basis of response rate and response durability, and these results warrant further clinical trials.

Adolescent

[Current status of chemotherapy in the treatment of malignant lymphomas].

Chemotherapy of malignant lymphomas has accomplished a significant progress during the two decades. Cure can be expected in a significant proportion of patients, even those with advanced disease. The major obstacle for cure is selection and overgrowth of a drug-resistant tumor cell population. For this reason, a number of investigators have tested the efficacy of intensive chemotherapy including non-cross-resistant alternating regimens and hybrid regimens. Today, with intensive combination chemotherapy, at least 60% of patients with advanced Hodgkin's disease and 50% of those with diffuse large cell lymphoma can be curable. The authors update the review of the chemotherapy for malignant lymphomas, and also report outcomes of chemotherapy in our own patients.

Adolescent

Expression of human papillomavirus type 6b E2 gene product with DNA-binding activity in insect (Bombyx mori) cells using a baculovirus expression vector.

Human papillomavirus type 6b (HPV6b) has been shown to be a major etiologic agent of genital condylomas. The E2 gene, one of the early genes, has been shown to activate the enhancer element in trans in cells transformed with bovine papillomavirus type 1a (BPV1a) but the E2 gene product of any HPV has not been identified. The E2 gene of HPV6b was inserted into the polyhedrin gene of a Baculovirus, Bombyx mori nuclear polyhedrosis virus (BmNPV), 156 bp downstream from the translational start codon, and transferred into BmNPV by allelic replacement in a cotransfected Bombyx mori cell line, Bm-N. The predicted 46-kDa protein was produced by a recombinant virus in the infected Bm-N cells at a high level under the control of the polyhedrin promoter. We obtained the antibody against the putative E2-polyhedrin fusion protein by immunizing a rabbit with this protein. This protein reacted with the antibodies against polyhedrin and the fusion protein. This protein did specifically bind to the upstream regulatory region of the HPV6b and BPV1a genomes. This DNA binding activity was blocked by the antibody against this protein.

Animals

Expression of the E2 open reading frame of papillomaviruses BPV1 and HPV6b in silkworm by a baculovirus vector.

To produce and characterize the nature of the E2 protein of papillomaviruses, we have developed a system to express the DNA sequence containing an open reading frame (ORF) as a fusion protein in cultured insect cells and silkworms. The DNA fragments of the E2 ORF predicted from the DNA sequence of bovine papillomavirus type 1 and human papillomavirus type 6b were linked to the N-terminal part of polyhedrin gene of the Baculovirus Bombyx mori nuclear polyhedrosis virus (BmNPV) vector. Hybrid proteins composed of polyhedrin protein (52 amino acids) and the E2 proteins of BPV1 (410 amino acids) or HPV6b (346 amino acids) were efficiently produced in B. mori cells and silkworm larvae infected with recombinant viruses. The amount of E2 fusion proteins produced by recombinant viruses was comparable to that of polyhedrin produced by wild type BmNPV. The hybrid proteins were immunologically reactive to antiserum against polyhedrin.

Animals

Vasoconstrictor effects of endogenous digitalis-like factors extracted from urine of hypertensive patients.

The vascular effects of endogenous digitalis-like factors (EDLFs) extracted from the urine of hypertensive patients were investigated in isolated and perfused intermediate auricular and mesenteric arterial preparations of dogs. EDLFs produced a transient vasoconstriction in a dose-related manner in intermediate auricular arteries but only a slight constriction in mesenteric arteries. Ouabain induced a long-lasting vasoconstriction with tachyphylaxis in intermediate auricular arteries, but it did not constrict mesenteric arteries. EDLF-induced vasoconstrictions were reproducible and were not modified by alpha-adrenoceptor blockade. They were slightly suppressed by a potent calcium entry blocker, verapamil, in doses which markedly suppressed KCl-induced vasoconstrictions. Noradrenaline- and KCl-induced vasoconstrictions were not significantly modified by either EDLF or ouabain. From these results, it is concluded that EDLF has clear vasoconstrictor properties which are not due to adrenergic or calcium entry mechanisms and that there are differences in the vasoconstrictor effects of EDLFs with respect to different vascular beds. This is similar to what was found with ouabain.

Animals

Time dependent impairment of vagally mediated inhibition of noradrenaline release in the dog heart.

The effects of right vagal nerve stimulation on changes in heart rate, mean coronary sinus blood flow, and noradrenaline overflow rate induced by right cardiac sympathetic nerve stimulation were investigated in anaesthetised decentralised, open chest dogs, when autonomic nerve fibres were stimulated tonically at a frequency of 4 or 5 Hz for 2.5 min. Sympathetic nerve stimulation produced a mean(SEM) increase in each of the variables (50(7.0)% in heart rate, 48(6.3)% in coronary sinus blood flow, and 87.0(12.3) ng.min-1 in noradrenaline overflow rate into coronary sinus blood at 30 s), and the increments remained almost constant during continued stimulation. Vagal nerve stimulation induced a decrease of 34(3.4)% in heart rate and of 22(4.5)% in coronary sinus blood flow and a slight reduction (-9(3.2) ng.min-1) in noradrenaline overflow rate at 30 s. Only the decrease in heart rate faded slightly with time. Combined stimulation of the sympathetic and parasympathetic nerves induced a decrease of 19(5.0)% in heart rate and 4(7.5)% in coronary sinus blood flow and an increase of 34.3(12.0) ng.min-1 in noradrenaline overflow rate at 30 s. The decrease in heart rate and coronary sinus blood flow faded, and noradrenaline overflow rate increased significantly to 86.4(17.3) ng.min-1 at 120 s. The temporal changes in heart rate, coronary sinus blood flow, and noradrenaline overflow rate caused by combined nerve stimulation were readily inhibited by treatment with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Combination chemotherapy of diffuse large-cell non-Hodgkin's lymphoma--superiority of the adriamycin combination].

In patients with diffuse large-cell non-Hodgkin's lymphoma, the results of combination chemotherapy containing adriamycin (ADM) were compared with those of combination chemotherapy without ADM. None of the patients had had any prior therapy and there was no difference in any other background factors for these two treatment groups. Of 32 patients treated without ADM, 19 (59%) achieved complete response (CR) and 12 (38%) achieved partial response (PR). Of 20 patients treated with ADM. 14 (70%) achieved CR and 6 (30%) achieved PR. For patients treated without ADM, median duration of CR was 9 months, projected 5-year relapse-free rate was 27%, median survival time was 1 year 6 months and projected 5-year survival rate was 27%. For patients treated with ADM, median duration of CR was not reached, projected 5-year relapse-free rate was 85%, median survival time was 2 years 2 months and projected 5-year survival rate was 49%. Combination of ADM was superior and therefore should be used for the initial treatment of this type of non-Hodgkin's lymphoma.

Adolescent