Decay D0--> phiK-bar0.
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Biomedical subjects
Publications and source records attributed to N Katayama.
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We have isolated a DNA fragment containing exon I of rat cellular proto-oncogene of K-ras and sequenced the exon I. The obtained sequence was compared with that of the corresponding region in viral oncogene of Kirsten strain of murine sarcoma virus (Ki-MSV). The results showed that the exon I sequences of cellular K-ras genes in rat and human cells could encode the same amino acid sequence, while the viral K-ras gene could code for two different amino acids corresponding to the 12th and 37th positions from the N-terminus of K-ras gene product. The amino acid substitutions found between viral and cellular K-ras genes are discussed in relation to the transforming ability of Ki-MSV.
Twenty-one patients were entered for a clinical study of KM 2210, the benzoate of an estradiol-chlorambucil conjugate, in the treatment of hematopoietic malignancies. These included 4 cases of chronic lymphocytic leukemia (CLL), 5 cases of chronic myelogenous leukemia (CML), 5 cases of malignant lymphoma (ML) and 7 cases of multiple myeloma (MM). Twelve cases had prior chemotherapy. KM 2210 was given orally at a dose of 50-300 mg daily. Of 19 evaluable cases, two cases with CLL achieved complete response and 6 cases including 2 with CLL, 2 with CML and 3 with ML achieved partial response. There were no responders among the cases of MM. The partial and complete response rate was 47%. Toxicity included mild breast or nipple pain (28.6%), genital bleeding (9.5%), appetite loss (9.5%) and gynecomastia (4.8%). These side effects may have been due to increased levels of estrogen. Hematopoietic toxicity was mild and well tolerated. No cardiac, hepatic or renal toxicity was observed in this study. These results suggest that KM 2210 might be an effective candidate for the treatment of hematopoietic malignancies, especially CLL.
Synovial osteochondromatosis is an uncommon lesion in the metatarsophalangeal joint of the great toe. The condition is usually monoarticular, involving a large joint. Common locations include the knee, elbow, shoulder, hip and ankle. The histopathology is one of apparent cartilaginous bodies. Since these cartilage cells often display nuclear atypism, an accurate diagnosis is essential to avoid the erroneous diagnosis of chondrosarcoma. A case of synovial osteochondromatosis as it occurs in the metatarsophalangeal joint is presented, and this condition is discussed with a review of the literature.
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A Gram-negative bacterium produces new monocyclic beta-lactam antibiotics with a formylamino substituent, named formadicins A, B, C and D. The producing bacterium was taxonomically characterized and designated as Flexibacter alginoliquefaciens sp. nov. YK-49. Formadicins have narrow antibacterial spectra. They are highly active against some species of Pseudomonas, Proteus and Alcaligenes. Of the four, formadicin C shows the most potent antibacterial activity. Several amino acids such as glycine, D-alanine and D-leucine were antagonistic against formadicins. Formadicins, especially formadicins A and C having the formylamino substituent bound to the 3-position of a beta-lactam nucleus, were highly resistant to hydrolysis by various types of beta-lactamases. Formadicins A and C showed affinity for penicillin-binding proteins (PBPs) 1A and 1B in Pseudomonas aeruginosa IFO 3080, but formadicin B and nocardicin A showed affinity only for PBP 1B. Formadicins A and C did not lyse Escherichia coli LD-2 solely at their MICs, but when combined with mecillinam each induced a rapid lysis of this organism.
New monocyclic beta-lactam antibiotics, formadicins A, B, C and D, were isolated from the culture filtrate of Flexibacter alginoliquefaciens sp. nov. YK-49 by various types of column chromatography and preparative reverse-phase HPLC. Their structures were determined by spectroscopic analyses and degradation studies. They have a nocardicin-type skeleton and a formylamino group at the 3- or 12-position. Formadicins A and B each have a D-glucuronide moiety and give formadicins C and D, respectively, upon hydrolysis using beta-D-glucuronidase.
New 7-methoxycephem antibiotics were found in culture filtrates of a bacterium isolated from a plant and named cephabacin M1-6. They are the first members of 7-methoxycephem antibiotics of bacterial origin. The producing organism was taxonomically characterized and identified as Xanthomonas lactamgena YK-431; other strains of this species have recently been reported to produce cephabacin F and H group antibiotics. Cephabacin M1-6 exhibited moderate antibacterial activity against Gram-negative and Gram-positive bacteria. Cephabacin M1-6 were as stable as cephamycin C to cephalosporinases. They showed inhibitory activity against a cephalosporinase of Proteus vulgaris GN 4413. The mode of action of cephabacin M1 was examined using Escherichia coli and Bacillus subtilis as test organisms; primary lethal targets of cephabacin M1 are penicillin-binding protein (PBP) 1 in E. coli and PBP 4 in B. subtilis.
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Three Gram-negative bacteria produce new cephem antibiotics, named cephabacins, with unique 3-side chains. Cephabacins include F group antibiotics with a 7-formylamino substituent and H group antibiotics without the substituent. The producing bacteria were taxonomically characterized and designated as Lysobacter lactamgenus sp. nov. YK-90 and Xanthomonas lactamgena sp. nov. YK-278 and YK-280.
Cephabacin F group antibiotics with a 7-formylamino substituent showed antibacterial activity against a wide variety of bacteria including beta-lactamase-producing clinical isolates and anaerobic bacteria. Cephabacin H group antibiotics without the substituent showed more potent activity against Gram-positive bacteria than cephabacin F group antibiotics, but were not active against Gram-negative bacteria producing beta-lactamases. Cephabacin F group antibiotics were highly resistant to hydrolysis by various types of beta-lactamases and showed strong inhibitory activity against a cephalosporinase of Proteus vulgalis GN 4413 due to the 7-formylamino substituent. Mode of action of cephabacin F1 and H1 was examined using Escherichia coli and Bacillus subtilis as the test organisms. They showed strong lytic activity against these organisms and inhibited their peptidoglycan synthesis. Cephabacin F1 had the highest affinity for penicillin-binding protein (PBP) 1 in E. coli and PBP 4 in B. subtilis. Cephabacins showed a protective effect in experimentally infected mice.
Clinical investigation of combination use of cefotiam (CTM), aminoglycoside, or (and) penicillin against complicated infections with hematopoietic disorders was performed, and the results were as follows. Fifty-one patients were administered CTM in combination with aminoglycoside or (and) penicillin. The clinical response was excellent 19.6%, good 27.4%, fair 21.6%, and poor 31.4% showing efficacy rate of 47.1%. The combined therapy of CTM and aminoglycoside was clinical effective in 70% of 10 patients with complicated sepsis. Therefore, combination use of CTM and aminoglycoside is considered to be the first choice for the treatment of complicated sepsis with hematopoietic disorders. The clinical effectiveness of CTM was not influenced by the number of mature neutrophil at the first phase of CTM treatment, but was influenced at the end phase of CTM treatment. Gram-negative bacilli were dominantly isolated from the patients. Pseudomonas sp. was isolated from 70% of the patients with sepsis. No remarkable side effects were observed in this investigation.
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