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Biomedical subjects

A Honda

Publications and source records attributed to A Honda.

At least 181 records · Page 10Linked to original sources

[Chemotherapeutic evaluation of pulmonary tuberculosis patients with a complication of hepatic dysfunction].

A retrospective study on the evaluation of antituberculous drugs for patients with hepatic dysfunction was undertaken to clarify treatment regimens. The values of GOT, GPT and T. Bil were used as indicators of liver function, and the "deterioration" in the liver function was defined as a level greater than 1.5 times the initial value. Of total 538 cases of active pulmonary tuberculosis, 103 cases (19.1%) had abnormalities in liver functions before chemotherapy, and 21 of 103 cases showed the deterioration in their liver functions during chemotherapy. There was little relationship between the initial status of liver functions and the incidence of their deteriorations after chemotherapy. Nine of 21 cases did not exceed the 3 times of normal ranges of liver functions. These nine cases could tolerate the same regimens of chemotherapy, and showed satisfactory clinical responses to chemotherapy with two exceptions: one died of tuberculosis and the other cerebrovascular disease. On the other hand, of 12 cases with elevated values of hepatic function greater than 3 times the normal limits, 6 cases discontinued chemotherapy. One case, however, died of hepatic failure related to chronic active hepatitis. Eight of 12 cases showed the rapid improvement of liver dysfunctions. These results suggest that antituberculous drugs are acceptable to patients with hepatic dysfunction as long as the elevations of GOT, GPT and T. Bil stay within 3 times of normal limits. Further chemotherapy could be continued under careful monitoring of liver functions even if the cases exhibit elevated levels of liver functions greater than 3 times the normal ranges.

Adult↗

Induction of cyclo-oxygenase synthesis in human promyelocytic leukaemia (HL-60) cells during monocytic or granulocytic differentiation.

Cyclo-oxygenase (COX) production in human promyelocytic leukaemia (HL-60) cells was studied during monocytic differentiation induced by 1 alpha, 25-dihydroxyvitamin D3 (24 nM; 3 days) or phorbol 12-myristate 13-acetate (100 nM; 1 day), or during granulocytic differentiation induced by retinoic acid (1 microns; 4 days). Undifferentiated or differentiated HL-60 cells were labelled with [35S]methionine, and membrane-bound COX was solubilized and quantified by SDS/PAGE. Immunoprecipitated 35S-labelled COX from cells induced to differentiate into monocytic or granulocytic lineage were clearly detected on the autoradiograms as a protein of approx. 70 kDa molecular size, whereas only a very faint COX band was detected in untreated HL-60 cells. During both monocytic and granulocytic differentiation, COX activity (measured by the conversion of exogenous arachidonic acid into prostaglandin E2) was dramatically increased. In addition, thromboxane synthesis was preferentially enhanced during monocytic differentiation. HL-60 cells, induced to differentiate into the monocytic or granulocytic lineage, provide a useful tool to investigate the cellular mechanisms involved in regulation of the synthesis of individual prostanoid-metabolizing enzymes.

Calcitriol↗

Purification and molecular structure of RNA polymerase from influenza virus A/PR8.

The RNA-dependent RNA polymerase of influenza virus A/PR/8 was isolated from virus particles by stepwise centrifugation in cesium salts. First, RNP (viral RNA-NP-P proteins) complexes were isolated by glycerol gradient centrifugation of detergent-treated viruses and subsequently NP was dissociated from RNP by cesium chloride gradient centrifugation. The P-RNA (P proteins-viral RNA) complexes were further dissociated into P proteins and viral RNA by cesium trifluoroacetate (CsTFA) gradient centrifugation. The nature of P proteins was further analyzed by glycerol gradient centrifugation and immunoblotting using monospecific antibodies against each P protein. The three P proteins, PB1, PB2, and PA, sedimented altogether as fast as the marker protein with the molecular weight of about 250,000 Da. Upon addition of the template vRNA, the RNA-free P protein complex exhibited the activities of capped RNA cleavage and limited RNA synthesis. When a cell line stably expressing cDNAs for three P proteins and NP protein was examined, the three P proteins were found to be co-precipitated by antibodies against the individual P proteins. These results indicate that the influenza virus RNA-dependent RNA polymerase is a heterocomplex composed of one each of the three P proteins and that the RNA-free RNA polymerase can be isolated in an active form from virus particles. Furthermore, the three P proteins form a complex in the absence of vRNA.

Animals↗

[Pulmonary tuberculosis with chemotherapy related liver dysfunction].

A retrospective study of the hepatotoxicity of antituberculous drugs was undertaken to establish preventive measures for elevated transaminases by analyzing its clinical courses. Four hundred and forty six patients with normal liver function on admission were enrolled in this study. More than 50% of total 113 cases who showed abnormalities of transaminases were aggravated up to 4th week after administration of drugs, and 80% up to 8th week. The initial values of elevated transaminases did not relate to recovery rate, and could tolerate the additional administration of drugs. However, cases with higher peak values and exacerbation in transaminases showed a tendency of delayed normalization. These results indicate that the chronological observation of transaminases is useful to determine whether or not the antituberculous drugs should be discontinued when hepatic dysfunction occurs. Moreover, they suggest that patients with severe pulmonary tuberculosis may continue chemotherapy with the same regimen under careful observation of liver function even when their transaminase values exceed 100.

Adolescent↗

Insulin-like growth factor I (IGF-I) enhances hyaluronic acid synthesis in rabbit pericardium.

We examined which substances stimulate hyaluronic acid synthesis in rabbit pericardium and pericardial cells. (1) The addition of 10% (v/v) pericardial fluid to the incubation medium of the pericardium enhanced hyaluronic acid synthesis to about 2.5-times over the control, suggesting that there were some stimulating factors of the hyaluronic acid synthesis in the pericardial fluid. (2) The addition of 100 ng/ml insulin-like growth factor-I (IGF-I) to the incubation medium caused an approx. 2-fold increase of hyaluronic acid synthesis over the control in the pericardium. (3) IGF-I stimulated the hyaluronic acid synthesis in pericardial cells in a dose-dependent manner, but did not significantly stimulate the sulfated glycosaminoglycan synthesis. (4) The increase in the hyaluronic acid synthesis induced by IGF-I (100 ng/ml) or pericardial fluid was blocked by the copresence of monoclonal anti-IGF-I antibody. (5) IGF-I caused possible induction of the hyaluronic acid synthase activity and general protein and RNA synthesis before the initiation of DNA synthesis in pericardial cells. These results suggest a new biological action of IGF-I that stimulates hyaluronic acid synthesis in pericardium or the pericardial cavity of heart.

Animals↗

Abnormal synthesis of cartilage-characteristic proteoglycan in azaserine-induced micromelial limbs.

Administration of azaserine (250 micrograms) to day-4 chick embryos in ovo was shown to induce micromelial limbs. In the present study, biosynthesis of cartilage-characteristic proteoglycan H (PG-H) as an index of limb chondrogenesis was examined in normal and micromelial hind limbs from day-7 chick embryos by biochemical and immunological methods. (1) Metabolic labelling of the micromelial limbs with [6-3H]-glucose and [35S]sulphate, followed by analysis of labelled proteoglycans by glycerol-density-gradient centrifugation under dissociative conditions, showed a marked reduction in PG-H synthesis. (2) PG-H synthesized by micromelial limbs differed from that synthesized by normal limbs in possessing a slower sedimenting velocity and much lower amounts of chondroitin sulphates. (3) The amount of PG-H core protein in micromelial limbs was significantly decreased to about 19% on a per limb basis and about 42% on a per DNA basis of that in normal limbs, as determined by e.l.i.s.a. (4) The transition from PG-M to PG-H during limb formation was retarded in micromelial limbs as judged by an indirect immunofluorescence technique using antibodies against PG-M and PG-H. (5) The deficiency of incorporation of labelled glucose into chondroitin sulphate chains of PG-H in micromelial limbs was partially restored by using [6-3H]-glucosamine as a precursor, suggesting that the synthesis of UDP-N-acetylhexosamine, required for chondroitin sulphate chain synthesis of PG-H in micromelial limbs, was decreased. These results suggest that the reduction in the synthesis of PG-H as well as the production of an abnormal form of PG-H during a critical period of limb morphogenesis may be important factors in explaining the micromelia induced by azaserine.

Abnormalities, Drug-Induced↗

Nonsurgical embryo collection from sows with surgically shortened uteri.

To allow for the nonsurgical collection of swine embryos, the uteri of sows (n=7) were surgically shortened. A section of each uterine horn was resected to facilitate a transcervical flushing procedure. All sows with a shortened uterus exhibited natural estrus at least once after the operation. Four to six days after insemination, embryos were collected with a two-way Foley catheter. Embryos were collected (n=55, 6.3+/-6.0: x +/-SD ) from every treated sow. Although treated sows often did not exhibit estrus beyond 1 to 9 natural estruses, those sows (n=27) with persistent corpora lutea (CL) over a 4 to 5 wk period were given prostaglandin F(2alpha) (PGF(2alpha)) and they returned to estrus in 5.2+/-1.1 d: x +/-SD .

Journal Article↗

Promoter analysis of influenza virus RNA polymerase.

Influenza virus polymerase, which was prepared depleted of viral RNA, was used to copy small RNA templates prepared from plasmid-encoded sequences. Template constructions containing only the 3' end of genomic RNA were shown to be efficiently copied, indicating that the promoter lay solely within the 15-nucleotide 3' terminus. Sequences not specific for the influenza virus termini were not copied, and, surprisingly, RNAs containing termini identical to those from plus-sense cRNA were copied at low levels. The specificity for recognition of the virus sense promoter was further defined by site-specific mutagenesis. It was also found that increased levels of viral protein were required in order to catalyze both the cap endonuclease-primed and primer-free RNA synthesis from these model templates, as well as from genomic-length RNAs. This finding indicates that the reconstituted system has catalytic properties very similar to those of native viral ribonucleoprotein complexes.

Base Sequence↗

[A case of primary pulmonary sporotrichosis].

We report the first case of primary pulmonary sporotrichosis in Japan. A 53-year-old man was admitted to our hospital for further examination of the abnormal shadows on chest X-ray film. Six months before admission, he was admitted to another hospital because of alcoholic liver disease and diabetes mellitus. Since the initial chest film showed cavities with infiltration in the left upper lung field, he was treated with antituberculous drugs despite negative sputum cultures for mycobacterium. In spite of the medication, his chest X-ray film revealed another cavitary lesion, so he was referred to our hospital. He had been asymptomatic during this period. Chest X-ray on admission disclosed multiple cavities in the left upper lobe and a cavity in the right lower lobe. Repeated sputum specimens, bronchial washings and brushings for cytology and cultures were all negative. In an attempt to clarify the pathogen, percutaneous lung aspiration (PLA) was performed. The PLA sample yielded a positive culture of Sporothrix shenckii. After the diagnosis, S. schenckii was also cultured from sputa. A sporothrix skin test and yeast agglutination test for S. schenckii were positive. In the absence of a history for skin lesion, the patient was diagnosed as a primary pulmonary sporotrichosis. As iodide therapy was ineffective, he was started on a regimen of intravenous amphotericin B. However his renal function progressively deteriorated, so amphotericin B was discontinued. Now he receives miconazole intravenously and is still under careful observation. As far as we know, this is the first report of primary pulmonary sporotrichosis in Japan. The possibility of sporotrichosis should be considered in any cases of undiagnosed cavitary lung diseases.

Hemagglutination Tests↗

Structure requirements for antiproliferative and cytotoxic activities of marine coral prostanoids from the Japanese stolonifer Clavularia viridis against human myeloid leukemia cells in culture.

The structural requirements for antiproliferative and cytotoxic activities of marine coral prostanoids from Japanese stolonifer Clavularia viridis and related compounds were examined in HL-60 cells in culture. From our data on the structure-activity relationship of these compounds, we elucidated that 1) the alkylidenecyclopentenone structure in these prostanoids was required for the antiproliferative and cytotoxic activities against HL-60 cells, but the epoxy prostanoids without cross-conjugated cyclopentenone system had the activities; 2) the presence of hydroxyl group at C-12 position in the prostanoids enhanced the activities, but the stereospecificity of the 12-hydroxyl group was not required for the activities; 3) the introduction of halogen atom at C-10 position of the prostanoids potentiated the activities (Cl greater than Br = I greater than H); 4) the introduction of blocking groups for blocking beta-oxidation to the alpha-side chain of the prostanoids did not cause the marked increase of the activities; 5) the presence of dienone (C5-6 and C7-8) in the structure potentiated the activities. These results provide the basis for drug-design of a new class of antitumor agent from marine coral prostanoids.

Animals↗

Mycoplasma pneumoniae and other pathogens in the aetiology of lower respiratory tract infections among Japanese children.

The causes of lower respiratory tract infections in 1544 children attending a Japanese hospital over a period of 7 years were investigated. Both cultivation and two serological techniques were used to detect Mycoplasma pneumoniae whereas viral involvement was investigated only by serology. Pathogens were identified in 52% of 1175 patients with pneumonia and 36% of 369 patients without pneumonia. Mycoplasma pneumoniae infection was specifically diagnosed in 414 (26.8%) of the 1544 patients. Respiratory syncytial virus (RSV) was dominant in children up to 2 years of age. By the age of 3 years, M. pneumoniae was equalling it in incidence and became the main pathogen in older groups. It is suggested that M. pneumoniae may be more important in the 3-6 years age group than hitherto suspected. These observations may influence the choice of antibiotics for treating lower respiratory tract infections in childhood.

Adenovirus Infections, Human↗

Isolation of Mycoplasma pneumoniae from children with lower-respiratory-tract infections.

The prevalence and clinical pictures of Mycoplasma pneumoniae infections among children were studied using culture and serological techniques. The isolation rate was 22% (195 of 885) in pneumonic patients and 11% (66 of 600) in non-pneumonic patients. In patients three years of age or less, M. pneumoniae was isolated at the same rate from febrile and afebrile cases and from wheezy and non-wheezy cases. In older patients, however, M. pneumoniae was frequently isolated from febrile but non-wheezy cases. A peak in the number of the positive isolates was found in patients who were four years old. The peak number of M. pneumoniae infections at age four was confirmed serologically. This peak was in patients who were younger than those previously reported.

Adolescent↗

RNA polymerase of influenza virus: role of NP in RNA chain elongation.

Ribonucleoprotein (RNP) cores of influenza virus A/PR/8/34 were dissociated into RNA polymerase (PB1-PB2-PA complex)-associated genome RNA and nuclear protein (NP) fractions by CsCl centrifugation. The RNA polymerase-RNA complexes were capable of catalyzing the endonucleolytic cleavage of capped RNA, the initiation of primer-dependent RNA synthesis, and the synthesis of small-sized RNA, but were unable to synthesize template-sized RNA. By adding the NP protein to the RNA polymerase-RNA complexes, RNP (RNA polymerase-RNA-NP) complexes were reconstituted; they synthesized template-sized transcripts as did native RNP cores. These observations are consistent with the model where viral RNA polymerase is composed of the three P proteins while NP is essential for the elongation of RNA chains. RNP was completely dissociated into RNA-free proteins (PB1, PB2, PA, and NP) and a protein-free genome RNA fraction by centrifugation in cesium trifluoroacetate (CsTFA) and glycerol. By mixing the protein and RNA fractions, primer-dependent RNA-synthesizing activity was regained. These complexes, however, produced only small-sized RNA, presumably due to incorrect assembly of NP on viral RNA.

DNA-Directed RNA Polymerases↗

Stimulatory effect of vanadate on hyaluronic acid synthesis in mesothelial cells from rabbit pericardium.

Vanadate dose-dependently stimulated the incorporation of [3H]glucosamine into glycosaminoglycan, especially hyaluronic acid, in mesothelial cells from rabbit pericardium. The activity of hyaluronic acid synthase in the mesothelial cells treated with 50 microM vanadate for 0.5-1 h was stimulated to a level about 2 times over that of the control. Neither DNA synthesis nor protein synthesis in the mesothelial cells under the same experimental conditions was affected. The enhancement of the activity of hyaluronic acid synthase in the mesothelial cells treated with vanadate (50 microM) was not inhibited by the addition of cycloheximide (1 microgram/ml). These results suggest that vanadate stimulates the hyaluronic acid synthesis by activation of hyaluronic acid synthase in mesothelial cells from rabbit pericardium.

Animals↗

Prolonged survival time of sarcoma 180-bearing mice treated with lipid microspheres-entrapped antitumor marine coral prostanoids.

Antitumor marine coral prostanoids (clavulone II and chlorovulone I) were entrapped into lipid microspheres of 0.2 micron diameter to make lipo-drugs. Daily treatment with lipo-chlorovulone I (1.6 mg/kg/day, i.p.) and lipo-clavulone II (12.5 mg/kg/day, i.p.) on days 1 through 5 markedly prolonged the survival time (135% ILS and 73% ILS, respectively) of mice inoculated with sarcoma 180 as compared with that of a corresponding dose of respective free chlorovulone I and clavulone II. These results suggest that lipid microspheres may be used as drug delivery carriers for antitumor coral prostanoids in vivo.

Animals↗

Altered proteoglycan synthesis by micromelial limbs induced by 6-aminonicotinamide. Appearance of abnormal forms of cartilage-characteristic proteoglycan (PG-H).

Since administration of 6-aminonicotinamide (10 micrograms) to day-4 chick embryos in ovo was shown to induce micromelial limbs, biosynthesis of cartilage-characteristic proteoglycan-H (PG-H) as an important index of limb chondrogenesis was examined in day-7 normal and micromelial hind limbs by biochemical and immunological methods. (1) Metabolic labelling of the micromelial limbs with [6-3H]glucosamine and either [35S]sulphate or [35S]methionine, followed by analyses of labelled PG-H by glycerol density-gradient centrifugation under dissociative conditions, showed a marked reduction in the PG-H synthesis. (2) PG-H synthesized by the micromelial limbs was much lower than that synthesized by the normal limbs in the biosynthetic ratio of chondroitin sulphate to keratan sulphate and glycoprotein-type oligosaccharide, although no significant difference was observed in the immunological properties of these proteoglycans. (3) The degree of sulphation of chondroitin sulphates of PG-H was lowered in the micromelial limbs as judged by the increase of unsulphated disaccharide (delta Di-OS) released by chrondroitinase ABC digestion, although there were no significant differences between the normal and the micromelial limbs in the average molecular size (Mr = 38,000) of labelled chondroitin sulphates of PG-H. (4) Addition of beta-D-xyloside, an artificial initiator for chondroitin sulphate synthesis, to the micromelial limbs in culture recovered the incorporation of labelled glucosamine into chondroitin sulphate to that comparable with the normal control with beta-D-xyloside, although the incorporation of [35S]sulphate was lower in the micromelia than in the control with beta-D-xyloside. These results suggest that the reduction in the biosynthesis of the PG-H as well as the production of altered forms of PG-H induced by 6-aminonicotinamide during a critical period of limb morphogenesis may be an important factor for the micromelia.

6-Aminonicotinamide↗

Multivalent regulation of the nusA operon of Escherichia coli.

The rate of synthesis and intracellular content of the NusA protein, a transcription termination factor, were determined for wild-type and nusA and/or nusB mutants of Escherichia coli. Both the rate and content of NusA in wild-type strains were similar to that of the RNA polymerase sigma subunit, a transcription initiation factor, on a molar basis, and about 30%-40% the levels of RNA polymerase beta beta' subunits. At the stationary phase of cell growth, the values increased in parallel for both transcription factors up to approximately the level of the beta beta' subunits. In nus mutants, the rate of synthesis and the content of the sigma subunit were significantly increased. These observations together suggest that the two transcription factors are coordinately regulated.

Bacterial Proteins↗