Biomedical subjects
Publications and source records attributed to S Gomi.
In vitro activities of benanomicins and their analogues against human immunodeficiency virus and fungi including Candida, Cryptococcus and Aspergillus, were examined. The free carboxyl group and at least one sugar moiety in the benanomicins were essential for their activities. Benanomicin A was most active and had low toxicity, and was selected as the best candidate for chemotherapy.
Four minor benanomicins, dexylosylbenanomicins A and B, 2'-demethylbenanomicin A and 7-methoxybenanomicinone have been isolated from the culture filtrate of Actinomadura sp. MH193-16F4. Their structures were confirmed by spectral analyses. Dexylosylbenanomicins A and B were derived chemically from benanomicins A and B, respectively.
The number and proliferative state of megakaryocyte progenitor cells (CFU-Meg) were compared between 13 patients with idiopathic thrombocytopenic purpura (ITP) and hematologically normal controls. The mean frequency of CFU-Meg assayed by the plasma clot method was 27.8 +/- 12.2 (+/- SD)/2 x 10(5) bone marrow light-density cells for the ITP patients, which did not differ significantly from the control value of 31.9 +/- 16.1. The percentage of CFU-Meg in DNA synthesis estimated by the 3H-thymidine suicide technique was 41.3% +/- 9.2% in ITP, which was significantly greater than the control value of 27.1% +/- 7.4% (P less than 0.01). The megakaryocyte counts for histological sections prepared from bone marrow aspirates from the ITP patients and controls were 34.5 +/- 8.5/mm2 and 11.2 +/- 5.8/mm2, respectively, with the difference being highly significant (P less than 0.001). These results suggest that increased cycling activity in a quantitatively unchanged CFU-Meg pool may lead to increased megakaryocytes in the bone marrow of ITP patients.
A new antibiotic, MK4588, structurally related to xanthocillin, was isolated from the culture broth of Leptosphaeria sp. L-179. Antibiotic MK4588 exhibited inhibitory activity against a limited range of Gram-positive and Gram-negative bacteria. The antibiotic was degraded by alkali to a more active product. The structures of MK4588 and the degradation product were determined to be (1R*,6S*,7S*)-7-(Z)-(1-isocyano-2-(4-methoxyphenyl]ethenyl-1-hydro xy-7- isocyanobicyclo[4,2,0]oct-2-en-4-one and (Z)-2,3-diisocyano-1-(4-methoxyphenyl)buta-1,3-diene, respectively, by NMR spectral analyses coupled with X-ray crystallographic analysis of MK4588.
A 59 years old woman, born in Fukuoka Prefecture, was admitted to our hospital in Aug, 1988 because of diarrhea, fever and skin eruption. Physical examination revealed systemic lymphadenopathy and hepatosplenomegaly. The white blood cell count was 11,200/microliters with 28% atypical lymphocytes with convoluted nuclei. Mild anemia, thrombocytopenia and hypercalcemia were also observed. Antibody against the adult T-cell leukemia (ATL) associated antigen in serum was positive. OKT 4/8 ratio was high. A diagnosis of ATL was made. Because of the complications of pneumonia and herpes simplex, systemic chemotherapy was not given, and interferon (IFN)-alpha-2b was intramuscularly injected daily from Oct, 1988, resulting in the disappearance of atypical lymphocytes and improvement of skin lesions. The effect of IFN therapy lasted for three months, followed by increase of atypical lymphocytes. Although the patient became refractory to systemic IFN therapy, local injection of IFN into a buccal tumor infiltrated with atypical lymphocytes resulted in its regression of size. In spite of continued administration of IFN, the patient died of pneumonia in Jan, 1989.
Mouse megakaryocyte colonies developed in a fibrin clot culture system were morphologically classified into three types: immature homogeneous (IH), heterogeneous (H), and mature homogeneous (MH) colonies. The colony size (number of megakaryocytes per colony), the ploidy distribution of megakaryocytes in colonies, and the ratios of their progenitors (megakaryocyte colony-forming units, CFU-Meg) in the S-phase of the cell cycle were compared among the three types. Also, morphological changes in colonies were examined in time sequence. The mode of the number of megakaryocytes per colony on day 6 of culture was greater than 64, between 17 and 32, and between 4 and 8, in IH, H, and MH colonies, respectively. The mean DNA content of megakaryocytes was 3.1N, 4.2N, and 7.2N on day 6 of incubation, in IH, H, and MH colonies, respectively, these values being significantly different from each other (p less than 0.001). The mean proportion of CFU-Meg synthesizing DNA was 21.9%, 26.0%, and 48.6% for CFU-Meg forming IH, H, and MH colonies, respectively (p less than 0.01; IH- versus MH-CFU-Meg and H- versus MH-CFU-Meg). Successive observation of the colony morphology from days 5 to 11 of culture suggested a transformation of the colony types from IH colony to MH colony through H colony. These observations indicate that the three types of megakaryocyte colonies classified on the basis of their morphological features reflect various stages of differentiation of mouse CFU-Meg.
Sweating function and retinal arterial reactivity in patients with migraine were examined during headache-free intervals. The sweat glands were stimulated by intradermal injection of pilocarpine hydrochloride, and molds of sweat droplets were obtained using Silastic. The number of droplets in classic migraine was significantly lower than that in the controls. The retinal arterial response to changes in perfusion pressure was measured by means of a fundus camera. The retinal vasomotor index (-change in retinal arterial diameter (%)/change in effective MABP (mmHg)) was significantly lower in classic and in common migraine than in controls. The above results suggest that sweating function and retinal arterial reactivity are impaired in patients with migraine and that the impairment may play an important role in the pathophysiology of migraine attacks.
The biosynthesis of benanomicins A and B, produced by actinomycete strain MH193-16F4, was investigated by feeding experiments with 14C- and 13C-labeled compounds followed by measurement of radioactivity and 13C NMR analysis. A 2D double quantum coherence NMR spectrum of benanomicin A derived from sodium [1,2-13C2]acetate provided the location of intact acetate units, and confirmed the 13C assignments of benanomicins. The results indicate that the aglycone of benanomicins is derived from a dodecaketide, methionine and alanine.
A case of extensive bone marrow necrosis due to cancer metastasis is reported. A 55-year-old female, who had a history of subtotal gastrectomy for signet ring cell carcinoma of the stomach 7 years ago, was admitted to our hospital with a complaint of lumbago on October 25, 1987. Red blood cell count was 92 X 10(4)/microliters, hemoglobin 2.7 g/dl, hematocrit 8.0%, platelet 6.4 X 10(4)/microliters, and white blood cell count 13,400/microliters with leukoerythroblastosis. Bone marrow aspiration of the sternum, left iliac crest, and bilateral posterior superior iliac supine showed extensive bone marrow necrosis. Serum ALP was increased to 7410IU/l, dominated isozyme of bone type. Hemostatic findings suggested a complication of consumption coagulopathy. Skull, vertebrae, iliac and pelvic bone X-ray showed multiple osteolytic lesions, and irregular isotope uptake was recognized on the bone scintigraphy using 99mTc. Sixth bone marrow examination at the right iliac crest revealed signet ring cell carcinoma metastasis. In spite of detailed examinations, there was no evidence of primary carcinoma, including the remnant of stomach. We speculated that the signet ring cells were originated from the respected gastric cancer. The patient has received anti-cancer chemotherapy with UFT and OK432, and is still alive 9 months after diagnosis.
A case of secondary erythroleukemia treated with apparent success with androgen is reported. The patient is 63-year-old Japanese female. She had a history of multiple myeloma and had been treated with melphalan, vincristine and prednisolone. She developed erythroleukemia 88 months after the initiation of chemotherapy, while her myeloma was a complete remission. She was treated first with vitamin D3 with no beneficial effect and subsequently with 0.5 mg/kg of mepitiostane. A hematologic improvement began two months from the initiation of androgen therapy, and a complete remission of erythroleukemia was attained thereafter. A chromosomal abnormality of bone marrow cells, which was observed at the time of developing erythroleukemia, also disappeared after the treatment. She remained in good condition and hematologic remission under the androgen therapy at the latest follow-up, 1-year after the development of erythroleukemia. Androgen therapy may be considered as a useful treatment for secondary erythroleukemia.
Quantitative in-vitro autoradiographic study was performed to localize two prominent second-messenger systems (the adenylate cyclase and phosphoinositide systems) in the normal gerbil brain. [3H] Forskolin and [3H] phorbol 12, 13-dibutyrate (PDBu) were used to identify the regional distribution of adenylate cyclase and protein kinase C, respectively. The localization of the forskolin binding was not uniform, being particularly concentrated in the striatum, the accumbens nucleus, the olfactory tubercle, the substantia nigra, the CA3 region of the hippocampus and the molecular layer of the cerebellum. On the other hand, the PDBu binding was rather uniform, although the superficial layer of the cerebral neocortices, the strata oriens of the CA1 region of the hippocampus and the molecular layer of the cerebellum showed relatively dense binding. Quantitative autoradiography of the second-messenger systems in the brain is expected to provide important information concerning the role of neurotransmitters in the pathophysiology of various conditions.
Edema formation following severe permanent or temporary cerebral ischemia in gerbils with an artificially reduced platelet count was investigated. Acute focal cerebral ischemia was produced by extracranial carotid ligation, and the local cerebral blood flow was estimated using the hydrogen clearance method. Brain tissue water and sodium and potassium contents were taken as indexes of brain edema. The platelet count was reduced in some gerbils by intravenous injection of neuraminidase. After 60 minutes of ischemia, a marked increase in tissue water and sodium contents accompanied by a decrease in potassium content was observed in untreated gerbils. However, gerbils with a reduced platelet count revealed similar but significantly smaller changes in all the measured parameters. Restoration of blood flow after 60 minutes of ischemia resulted in further accumulation of water and sodium and in depletion of potassium in both groups. These changes were significantly smaller in the gerbils with a reduced platelet count. It is concluded that platelets, activated by cerebral ischemia, may be involved in the development of ischemic brain edema in gerbils.
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Structures of new antifungal antibiotics, benanomicins A and B were determined to be N-[[5-[6-deoxy-3-O-(beta-D-xylopyranosyl)-beta-D-galactopyranosyloxy+ ++ ]-5, 6-dihydro-1,6,9,14-tetrahydroxy-11-methoxy-3-methyl-8,13-dioxobenzo++ + [a]naphthacen-2-yl]carbonyl]-D-alanine and N-[[5-[4-amino-4,6-dideoxy-3-O-(beta-D-xylopyranosyl)-beta-D- galactopyranosyloxy]-5,6-dihydro-1,6,9,14-tetrahydroxy-11-methoxy- 3-methyl-8,13-dioxobenzo[a]naphthacen-2-yl]carbonyl]-D-al ani ne, respectively, by spectral analyses and chemical degradation studies.
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New antibiotics SF2446A1, A2, A3, B1 and B2 have been isolated from the culture of Streptomyces sp. SF2446 and antibiotic SF2446B3 has been obtained by methanolysis of SF2446B1 or B2. SF2446A1, A2 and B1 showed strong inhibitory activities against mycoplasmas and Gram-positive bacteria. Empirical molecular formulae of antibiotics SF2446-A1, A2, A3, B1, B2 and B3 were determined to be C34H35NO15, C26H21NO11, C34H35NO14, C34H35NO14 and C26H21NO10, respectively.
Structures of new antibiotics SF2446A1, A2, A3, B1, B2 and B3 have been deduced by means of spectral analyses and chemical studies. The structure of SF2446A1 which is a main product of fermentation and has the strongest antimicrobial activity, has been proposed to be 11-(2,4-di-O-methyl-beta-L-rhamnopyranosyl)amino-5,6,6a,14a-tetrah ydro- 1,6,8,14a-tetrahydroxy-6a-methoxy-2-methoxycarbonyl-3-methyl- benzo[a]naphthacene-7,9,12,14-tetra-one. All of antibiotics have a novel benzo[a]naphthacene quinone skeleton and SF2446A1, A2, B1 and B2 have an N-glycosidic linkage with 2,4-di-O-methyl-L-rhamnose.
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