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RS-22A, B and C are novel 36-membered macrolide antibiotics produced by Streptomyces violaceusniger. The structures of these antibiotics were unambiguously determined by 1D and 2D NMR and tandem-mass analysis of the oxidative derivative of RS-22C.

Three novel 36-membered macrolide antibiotics, RS-22A, B and C produced by Streptomyces violaceusniger have been isolated. These antibiotics were purified from an acetone extract of the mycelia followed by butanol extraction, centrifugal partition chromatography and HPLC. RS-22A, B, C showed antimicrobial activity against fungi and Gram-positive bacteria.

A 58-year-old female, who had complained of dryness of the conjunctiva and mouth for nine years, was admitted to our hospital because chest X-ray films revealed increases in both the size and the number of pulmonary nodules in comparison to four years earlier. Histological findings of the salivary gland biopsy confirmed a diagnosis of Sjögren's syndrome. An open lung biopsy was performed. Histologically, the pulmonary nodules consisted of homogeneous, acellular eosinophilic materials, which were identified as amyloid by Congo red staining. Immunohistochemical examination showed the amyloid to be composed of AA protein. There were no deposits in other organs. Peribronchial lymphocytic infiltration associated with Sjögren's syndrome was present. Nodular pulmonary amyloidosis with Sjögren's syndrome is very rare condition. To our knowledge, this case is only the ninth to be reported in the literature.

A 47-year-old female, who had undergone hysterectomy and unilateral oophorectomy in 1975, was admitted to our hospital in 1989 because chest X-ray films revealed an increase in size and number of pulmonary nodules for two years. On admission, a left inguinal tumor was found and histologically it consisted of smooth muscle cells with nuclear atypia arranged in interlacing fascicles. An open-lung biopsy was performed. Pulmonary tumors revealed similar histology to the inguinal tumor. They were diagnosed as metastatic low-grade leiomyosarcoma, so-called benign metastasizing leiomyoma (BML), on the basis of location and history, reinforced by mild histologic atypia. The tumor contained a high progesterone receptor level (400 fmol/mg). Therefore, medroxyprogesterone acetate, 600 mg daily, was administered orally. At two years the pulmonary lesions had regressed. BML is a rare condition, considered to be pulmonary metastasis from low-grade leiomyosarcoma of the uterus. Measuring estrogen and progesterone receptors in lung biopy material may help determine the most appropriate therapy.

Respinomycins are a novel group of anthracycline antibiotics produced by Streptomyces xanthocidicus. Respinomycins A1, A2, B, C and D were isolated by EtOAc extraction, silica gel column chromatography, centrifugal partition chromatography and preparative silica gel thin layer chromatography. Respinomycins A1 and A2 induced the terminal differentiation of human leukemia K-562 cells.

Respinomycins A1, A2, B, C and D were revealed to be novel anthracycline antibiotics with molecular formulae of C51H72N2O20, C43H58N2O15, C35H43NO14, C36H45NO14 and C51H70N2O22, respectively. Their structures were determined by means of 1H-1H COSY, 13C-1H COSY and HMBC spectra. The structure of the aglycone of respinomycins was unambiguously determined by LSPD experiments and NOESY. The common skeleton of respinomycins is a new type and is distinguished from that of the nogalamycin group.

Three cases of pulmonary actinomycosis are reported. Case 1 was a 33-year-old man complaining of hemosputum. A large mass lesion was noted in the right upper lobe and surgically resected. Actinomycosis was diagnosed pathologically. The second case was a 41-year-old man with lung abscess. An actinomyces species was cultured by percutaneous aspiration biopsy. He was effectively treated with clindamycin. The third case was a 46-year-old man with a chronic cough and cavitary lesion. Gram staining of sputum revealed sulfur granules. Piperacillin was administered with prompt response. All three cases had dental disease and two had diabetes mellitus. In patients with a mass lesion or those with lung abscess not effectively treated by cephem antibiotics, actinomycosis should be suspected especially when diabetes mellitus and/or dental disease coexists. Adequate treatment may not always require long-term antibiotics.

A 64-year-old man was admitted because of some infection of the airway. Chest roentgenography showed a bilateral reticulonodular shadow which was similar to the shadow of DPB. Pathological findings obtained by lung biopsy indicated bronchiolitis. This case was diagnosed as Sjögren's syndrome because of the increase of titers of anti-ssA and anti-ssB antibody, lachrymal dysfunction, pathological findings and sialography. The relationship between DPB and lung lesions of Sjögren's syndrome was investigated.

The chemical structure of tautomycetin (C33H50O10) was determined by chemical degradation and spectroscopic evidence. Tautomycetin exists in methanol-buffer solution (1% diethylamine-formic acid, pH 7.3) as an equilibrium mixture of a 2,3-dialkylmaleic anhydride and its dicarboxylic acid. The structure of tautomycetin is similar to tautomycin in many respects.

Carcinogenicities of mutagenic heterocyclic amines in cooked foods have been tested in CDF1 mice and F344 rats of both sexes. Eight heterocyclic amines--Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, MeA alpha C, A alpha C, IQ, and MeIQ--were given to mice and/or rats at 0.02 to 0.08% in the diet continuously. In mice, all heterocyclic amines tested were demonstrated to be carcinogenic. Hepatocellular carcinomas were induced in a high incidence in all groups treated with heterocyclic amines. Hemangioendothelial sarcomas were also induced by Glu-P-1, Glu-P-2, MeA alpha C, and A alpha C. Most hemangioendothelial sarcomas were located in the interscapular brown adipose tissue. In mice given IQ, forestomach and lung tumors were also observed in a high incidence. Carcinogenicity tests on MeIQ are ongoing, and interim data by week 83 show that MeIQ also induces forestomach tumors in addition to liver tumors. In rats, hepatocellular carcinomas were induced by Trp-P-1, Glu-P-1, Glu-P-2, and IQ. In rats given Glu-P-1, Glu-P-2, and IQ, adenocarcinomas in the small and large intestines, squamous cell carcinomas in the Zymbal gland and clitoral gland were also observed in a high incidence.

13C NMR analysis of 13C-labeled cytovaricin which was obtained by feeding sodium [1-13C]-, [2-13C]-, and [1,2-13C]acetates, [1-13C]- and [3-13C]propionates, [1-13C]isobutyrate and [methyl-13C]methionine to cultures of Streptomyces diastatochromogenes showed that the aglycone of cytovaricin is derived from nine acetate units, six propionate units and one isobutyrate unit and the methoxy group at C-3' of cymarose moiety is derived from the methionine-S-methyl group. The 13C NMR spectra of 13C-labeled cytovaricins which were obtained from feeding experiments allowed the complete assignment of the 13C NMR spectrum of cytovaricin.

Synthesis of an alanylsulfamoyl nucleoside antibiotic, ascamycin was achieved by the condensation of N6-t-butyloxycarbonyl-2-chloro-9-(2',3'-O-isopropylidene-5'-O-sulfamoyl- beta-D- ribofuranosyl)adenine(3) with t-butyloxycarbonyl-L-alanylimidazole in the presence of NaH in DMF. Deprotection with 90% trifluoroacetic acid gave ascamycin in 61% overall yield. This procedure may be applicable for preparation of a number of amino acid analogs of ascamycin.

A newly isolated strain of Streptomyces sp. produces a new nucleoside antibiotic, ascamycin and the corresponding dealanyl derivative. The structure of ascamycin was determined to be 2-chloro-9-beta-[5-O-(N-L-alanyl)sulfamoyl-D-ribofuranosyl]-adenine. Remarkable selective toxicity of ascamycin compared to the dealanyl derivative was accounted for on the basis of a dealanylating enzyme present in the envelope of sensitive bacteria. After dealanylation, it becomes permeable to cell membrane.