Lymphoma arising in an S-pouch after total proctocolectomy for ulcerative colitis: report of a case.

The gastrointestinal tract is the most common extranodal site of primary non-Hodgkin's lymphoma. We present a case of a 50-year-old male with primary B cell lymphoma arising in an S-pouch eight years after a total proctocolectomy for ulcerative colitis. After chemoradiotherapy the patient remained asymptomatic, with an intact S-pouch. Pouch conservation is feasible in patients with primary lymphoma of the pouch, using chemoradiotherapy and close follow-up examinations.

Intrathyroid cysts of thyroglossal duct origin.

Thyroglossal duct cysts develop from a persistent portion of the thyroglossal tract and have been described as occurring anywhere from the base of the tongue to the manubrium. We present two patients who presented with a cystic thyroid nodule due to an intrathyroid thyroglossal duct cyst. A fine-needle aspiration biopsy was performed, which revealed benign squamous cells. Upon exploration, the first patient was found to have a 2-cm cyst within the thyroid isthmus, and in the second patient, a 1-cm cyst was found in the right thyroid lobe. Pathologic analysis revealed the cyst to be lined by a squamous epithelium consistent with a thyroglossal duct cyst. The lesions were completely surrounded by normal thyroid tissue. There was no evidence of a remnant of the thyroglossal duct extending from the thyroid in the region of the cyst. Both patients were treated by thyroid lobectomy and isthmusectomy and have remained without evidence of recurrence. Intrathyroid thyroglossal duct cysts should be included in the differential of patients with cystic thyroid lesions. Fine-needle aspiration revealing benign squamous cells is usually diagnostic and may detect an occult carcinoma arising within the cyst. Surgical resection is curative and should include a Sistrunk procedure if a thyroglossal duct tract is present.

Pulmonary responses of the guinea pig to inhaled A23187: a brief review.

The pulmonary effects of inhaled A23187 are reviewed. Guinea pigs challenged with this divalent cationic ionophore rapidly develop airway obstruction, which is maintained for at least 4 h. Pulmonary inflammation and increased airway responsiveness are also observed. Pharmacologic manipulations suggest that these actions are due to the release of multiple mediators. We have found A23187 challenge to be valuable as an approach for testing potential asthma drugs.

Congenital atransferrinemia. A case report and review of the literature.

A four-year-old Polynesian girl with a two-year history of severe microcytic, hypochromic anemia (which was refractory to iron therapy) had a decreased beta-globulin fraction on serum protein electrophoresis, resulting from the absence of the transferrin (TRF) band. Subsequent assays for TRF showed a level below the detectable range. Liver biopsy revealed significant deposition of hemosiderin within hepatocytes and Kupffer cells, in addition to early fibrosis. Two bone marrow aspirates were hypercellular, with decreased myeloid-erythroid ratios. This case represents the eighth reported example of congenital atransferrinemia, a rare, apparently autosomal recessive disease.

A21978C, a complex of new acidic peptide antibiotics: isolation, chemistry, and mass spectral structure elucidation.

A21978C, produced by Streptomyces roseosporus, NRRL 11379, is a complex of new acidic lipopeptolide antibiotics which inhibits Gram-positive bacteria. HPLC separation of the various components from the purified complex resulted in the isolation of A21978C1, -C2 and -C3 (major components) and -C4, -C5, and -C0 (minor components). Each of these components was fermented with cultures of Actinoplanes utahensis (NRRL 12052) to give the identical inactive peptide ("A21978C nucleus") by removal of the fatty acid acyl groups from the N-terminus. This peptide was composed of 13 amino acids: L-kynurenine, L-threo-3-methylglutamic acid, L-asparagine, L-aspartic acid (3 residues), glycine (2 residues), L-tryptophan, L-ornithine, D-alanine, D-serine and L-threonine. The amino acid sequence was determined using a combination of the Edman degradation and gas chromatography mass spectrum (GC-MS) analysis of appropriately derivatized peptides obtained from partial hydrolysis. Each major component was shown to be acylated with a branched chain fatty acid at the N-terminus and the structure of this fatty acid was determined by 1H NMR and mass spectral methods. A structure for A21978C was assigned on the basis of this degradative and physico-chemical information.

Synthesis and biological activity of certain nucleoside and nucleotide derivatives of pyrazofurin.

A number of nucleoside and nucleotide derivatives of 4-hydroxy-3-beta-D-ribofuranosylpyrazole-5-carboxamide (pyrazofurin, 1) were prepared and tested for their antiviral and cytostatic activity in cell culture. Treatment of 1 with benzyl bromide gave 4-O-benzylpyrazofurin (4). Methylation of 4 with CH2N2 and subsequent removal of the benzyl group by catalytic hydrogenation provided 1-methylpyrazofurin (8). Direct methylation of 1 with CH3I furnished 4-O-methylpyrazofurin (6). Dehydration of the pentaacetylpyrazofurin (9) with phosgene furnished 4-acetoxy-3-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1-acetylpyrazol e-5-carbonitrile (10). A similar dehydration of the precursor tetraacetyl derivative of 4 gave the corresponding carbonitrile, which on deprotection and subsequent treatment with hydroxylamine furnished 4- (benzyloxy)-3-beta-D-ribofuranosylpyrazole-5-carboxamidoxime (13). Treatment of the tetraacetyl derivative of 4 with Lawesson's reagent and subsequent deacetylation furnished a mixture of 4- (benzyloxy)-3-beta-D-ribofuranosylpyrazole-5-thiocarboxamide (15) and the corresponding nitrile derivative (16). Phosphorylation of unprotected 4 with POCl3 and subsequent debenzylation of the intermediate 17 gave pyrazofurin 5'-phosphate (18), which provided the first chemical synthesis of 18. Similar phosphorylation of 4 with POCl3 and quenching the reaction mixture with either EtOH or MeOH, followed by debenzylation, furnished the 5'-O-(ethyl phosphate) (19b) and 5'-O-(dimethyl phosphate) (20b) derivatives of pyrazofurin. DCC-mediated cyclization of 17, followed by debenzylation, gave pyrazofurin 3',5'-(cyclic)phosphate (21b). The NAD analogue 23b was also prepared by the treatment of 17 with an activated form of AMP in the presence of AgNO3. The structural assignment of 7,8, and 20a were made by single-crystal X-ray analysis, and along with pyrazofurin, their intramolecular hydrogen bond characteristics have been studied. All of these compounds were tested in Vero cell cultures against a spectrum of viruses. Compounds 18 and 23b were active at concentrations very similar to pyrazofurin but are less toxic to the cells than pyrazofurin. Compounds 19b, 20b, and the 3',5'-(cyclic)phosphate 21b are less active than 1. Compounds 18, 19b, 20b, and 23b also exhibited significant inhibitory effects on the growth of L1210 and P388 leukemias and Lewis lung carcinoma cells in vitro, whereas B16 melanoma cells were less sensitive to growth inhibition by these compounds. Pyrazofurin derivatives modified at the 1-, 4-, or 5-position showed neither antiviral nor cytostatic activity in cell culture.

A37812: N-methylstreptothricin F.

A37812, a new member of the streptothricin class of antibiotics, has been isolated and characterized as N-methylstreptothricin F. The structure elucidation of A37812 is based on results from 13C and 1H NMR spectroscopies.

The structure of A201A, a novel nucleoside antibiotic.

The structure of the novel nucleoside antibiotic A201A has been determined by a combination of chemical and spectroscopic methods. It is composed of 6-dimethylaminopurine, 3-amino-3-deoxyribose, p-hydroxy-alpha-methylcinnamic acid, a novel unsaturated hexofuranose and 3,4-di-O-methylrhamnose. Structures have also been assigned to several related minor factors simultaneously isolated from the fermentation broth. These unique nucleosides have very interesting similarities and differences in structure with the known antibiotics puromycin and hygromycin A.

Actaplanin, new glycopeptide antibiotics produced by Actinoplanes missouriensis. The isolation and preliminary chemical characterization of actaplanin.

Actaplanin (A4696), a new complex of broad spectrum Gram-positive antibiotics is produced by Actinoplanes missouriensis. High performance liquid chromatography was used to show that this complex is composed of several actaplanins. Hydrolytic experiments with acetaplanins A, B1, B2, B3, C1 and G showed that these actaplanins were composed of the same peptide core, an amino sugar and varying amounts of glucose, mannose and rhamnose. The neutral sugar content was determined for each actaplanin. A bioautographic study of aglycone formation during hydrolysis of the actaplanin complex showed that within a short time a simple mixture of two antimicrobially active hydrolysis products was obtained. These substances retained the antimicrobial spectrum and a high percentage of the antibiotic activity of the parent actaplanin complex. Methanolysis of the acetaplanin complex as well as the individual actaplanins resulted in the selective loss of the neutral sugar moieties and the isolation of actaplanin psi (pseudo)-aglycone--the core peptide which still retained an amino sugar group. The 1H NMR spectrum of this substance indicated a similarity to many features of ristocetin psi-aglycone. Hydrolytic studies showed that the amino sugar present in actaplanin was identical with L-ristosamine. It is concluded that the aglycone of actaplanin is a complex peptide composed of aromatic amino acids, and that the actaplanins each possess this aglycone and L-ristosamine but are differentiated by their neutral sugar composition.

Structure-activity studies among 16-membered macrolide antibiotics related to tylosin.

Although a substantial number of 16-membered macrolides related to tylosin have now been isolated and evaluated as antibiotics, none appeared to be superior to tylosin in treating bacterial or mycoplasmal infections caused by sensitive organisms. Nevertheless, this comparison of the antibiotic activity of 16-membered macrolides clearly indicates that novel antibiotics with potentially useful activity can be obtained from mutant strains which have been blocked at various steps in their biosynthesis of antimicrobial agents. The novel compounds thus produced may also be used as starting materials for additional chemical and microbiological modification. Furthermore, the mutant strains which produced these novel compounds should be useful recipients for interspecific genetic recombination by protoplast fusion or gene cloning to yield hybrid antibiotics. Even greater exploitation of these methods will be required in the continuing search for new antibiotics and improved methods for producing them.

Novel fermentation products from Streptomyces fradiae: X-ray crystal structure of 5-O-mycarosyltylactone and proof of the absolute configuration of tylosin.

5-O-Mycarosyltylactone has been isolated as a predominant factor from fermentation broths of a Streptomyces fradiae mutant. The relative configurations of mycarose and tylactone (protylonolide) have been determined by X-ray crystal structure analysis. Hydrolysis of 5-O-mycarosyltylactone yielded (-)-tylactone and L-(-)-mycarose. Taken together, these two experiments establish the absolute configuration of (-)-tylactone. Bioconversion of (-)-tylactone to tylosin by tyl G mutants of S. fradiae proves the absolute configuration of tylosin. Physicochemical data for tylactone and a unique component piece of tylactone are also reported.

Biological activities of isolated tunicamycin and streptovirudin fractions.

The nucleoside antibiotics tunicamycin and streptovirudin were separated by high-performance liquid chromatography into a series of 256-nm-absorbing peaks. Most of the streptovirudin peaks eluted from a Biosil ODS column earlier than those of tunicamycin, indicating that they were less hydrophobic. With the exception of the first peak, 17 other tunicamycin peaks were potent inhibitors of the formation of dolichylpyrophosphoryl-N-acetylglucosamine with 50% inhibition of the solubilized GlcNAc-1-P transferase requiring about 10 ng of antibiotic per mL. These fractions also inhibited the synthesis of dolichylphosphorylglucose, but in these cases about 500 ng/mL was necessary to achieve 50% inhibition. In MDCK cells in culture, the four major tunicamycin peaks inhibited the incorporation of [2-(3)H]mannose into protein by 50% at about 0.2-0.5 microgram/mL, but [3H]leucine incorporation into protein was unaffected, except at high levels of antibiotic (5-10 microgram/mL). Essentially the same results were observed with the streptovirudin fractions except that they were somewhat less active and some inhibition of protein synthesis was observed with several of these peaks.

A35512, a complex of new antibacterial antibiotics produced by Streptomyces candidus. I. Isolation and characterization.

The new antibiotic complex A35512 produced by Streptomyces candidus was isolated from the filtered fermentation broth. The individual factors A, B, C, E, and H were separated and purified by column chromatography. A35512B, the major factor, was isolated as the dihydrochloride salt, a white crystalline compound with an approximate empirical formula of C90H101 N8O39Cl.2HCl. The A35512 antibiotics belong to the glycopeptide class of antibiotics and possess high in vitro and in vivo activity against Gram-positive bacteria.

Glycosylation of human leukocyte interferon: effects of tunicamycin.

Antiviral activity of interferon secreted by human leukocytes into the culture fluid in the presence of tunicamycin (1-2 microgram/ml) was significantly decreased, by 50-60 percent, in comparison to that produced in the absence of the antibiotic. No loss in antiviral activity occurred when tunicamycin was added to already harvested interferon preparations. Some physico-chemical and biological properties of human leukocyte interferon synthesized in the presence of tunicamycin (HL-IFT) were apparently altered by comparison with those of control preparations of human leukocyte interferon (HL-IF): HF-IFT had only one molecular weight component of 16,000 daltons in contrast to the two components of HL-IF of 16,000 and 21,000 daltons. HL-IFT also had a higher apparent hydrophobicity and was less efficiently neutralized by an antibody raised against HL-IF. However, some other properties remained unchanged: isoelectric point, pI about 6; affinity for immobilized polyriboinosinic acid and a spectrum of cross-species antiviral activity. These data support the notion that the major component of HL-IF (70%, 16,000 daltons) is apparently nonglycosylated whereas the minor component (30%, 21,000 daltons) is glycosylated via saccharide-lipid intermediates.

The isolation and characterization of narasin, a new polyether antibiotic.

Narasin is a new polyether antibiotic produced by a strain of Streptomyces aureofaciens. It is purified by organic solvent extraction and silica gel chromatography. Narasin is active in vitro against gram-positive bacteria, anaerobic bacteria, and fungi and is effective in protecting chickens from coccidial infections.