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Biomedical subjects

W K Williams

Publications and source records attributed to W K Williams.

7 recordsLinked to original sources

Immunohistochemical study of childhood rhabdomyosarcomas and related neoplasms. Results of an Intergroup Rhabdomyosarcoma study project.

The authors assessed a panel of immunohistochemical stains against 109 pediatric solid tumors, primarily rhabdomyosarcomas, under the auspices of the Intergroup Rhabdomyosarcoma Study. Fresh tumor tissue received from participating organizations was divided into portions that were either frozen or fixed in formalin, alcohol, or B5. Immunostaining was performed by the avidin-biotin complex method using monoclonal antibodies to desmin, neurofilaments, vimentin, cytokeratin, and leukocyte common antigen on cryostat sections. Tissue was also embedded in paraffin and stained with antimuscle-specific actin (MSA) and polyclonal antibodies to desmin, creatine kinase M subunit (CKM), myoglobin, and neuron-specific enolase (NSE). Antidesmin staining of cryostat sections was the most sensitive indicator of rhabdomyosarcoma (58 of 62 specimens positive). Results with this reagent in alcohol-fixed and formalin-fixed tissue were similar (46 of 56 positive versus 43 of 56 positive, respectively) and comparable with results with anti-MSA in formalin-fixed tissue (43 of 55 positive). However, the proportion of cells stained by antidesmin was higher in alcohol-fixed tissue than in formalin-fixed tissue. Staining with antimyoglobin and anti-CKM was much less satisfactory, with positivity rates of 17 of 37 and 11 of 57, respectively, in formalin-fixed rhabdomyosarcomas. Immunostaining of muscle markers revealed evidence of myogenesis in six undifferentiated sarcomas and in two sarcomas with inadequate histologic study on hematoxylin-eosin-stained sections. However, positivity was also noticed in samples of fibromatosis, Wilms' tumor, ectomesenchyoma, peripheral primitive neuroectodermal tumor, renal rhabdoid tumor, myositis ossificans, malignant fibrous histiocytoma, and embryonal sarcoma of the liver. The authors conclude that combined use of antidesmin and anti-MSA enhances the diagnosis of childhood sarcomas, especially when employed with other techniques such as electron microscopic study.

Actins

Comparison of phospholipids in vaginal and amniocentesis specimens of patients with premature rupture of membranes.

Amniotic fluid was obtained from the vaginal pool and by transabdominal amniocentesis in 28 patients who were admitted to the hospital between 26 and 35 weeks' gestation with premature rupture of the membranes. Phospholipid profiles were obtained on all specimens with the use of high-performance liquid chromatography. The lecithin/sphingomyelin ratio, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, and lysolecithin were all analyzed to determine the effect of vaginal contamination. With the use of a paired t test, only lysolecithin was shown to be significantly affected by vaginal contamination (p less than 0.05). As determined by high-performance liquid chromatography, evaluation of phospholipids in vaginal fluid of patients with premature rupture of the membranes appears to be an accurate and reliable method for predicting fetal lung maturity.

Amniotic Fluid

Extraction of streptococcal type 12 M protein by cyanogen bromide.

Conditions for the release of streptococcal type 12 M protein from whole cells by cyanogen bromide are described; they demonstrated that methionine is not essential to the structural arrangements which account for some of its immunological and biological properties. The released M protein was separated from other proteins by column chromatography with hydroxylapatite. The type-specific molecules which reacted with precipitating antibodies were found only in the 0.3 M eluate, formed zones with mobilities less than 12% of that of the dye front on electrophoresis in the standard acrylamide disc gel system, formed at least four bands in sodium dodecyl sulfate-acrylamide disc gels with molecular weights ranging from 12,000 to 23,000, and stimulated the formation of opsonic antibodies in rabbits. Cyanogen bromide provides a highly specific method for the release of M proteins which should prove particularly useful in analyses of structural-functional relationships among different M proteins.

Amino Acids

Development of a chemically defined medium for the synthesis of actinomycin D by Streptomyces parvulus.

A chemically defined medium, consisting of d-fructose, l-glutamic acid, l-histidine, K(2)HPO(4), MgSO(4).7H(2)O, ZnSO(4).7H(2)O, CaCl(2).2H(2)O, FeSO(4).7H(2)O, CoCl(2).6H(2)O, and deionized water, was developed for synthesis of high yields (500 to 600 mug/ml) of actinomycin D by Streptomyces parvulus. Under these nutritional conditions, growth and actinomycin formation did not follow a typical trophophase-idiophase pattern. The amino acids appeared to have a sparing action on the utilization of d-fructose which was slowly and incompletely metabolized during mycelium development and antibiotic production. A significant repression of actinomycin synthesis by S. parvulus was observed when d-glucose (0.01 to 0.25%) was added to the culture medium. The repression was not due to a decline in the pH of the medium during glucose catabolism.

Amino Acids

Novel actinomycins formed by biosynthetic incorporation of cis- and trans-4-methylproline.

Streptomyces parvulus (Streptomyces parvullus) normally produces actinomycin D; in the presence of cis-4-methylproline, this species synthesizes two additional actinomycins, designated K(1c) and K(2c), in which one and two proline sites, respectively, are occupied by cis-4-methylproline. Analogously, actinomycins K(1t) and K(2t) are formed in the presence of trans-4-methylproline. Both mixtures were separated chromatographically, and the four novel actinomycins were obtained in crystalline form. Their biological activities were compared with that of actinomycin D in respect to inhibition of ribonucleic acid, deoxyribonucleic acid, and protein synthesis and antimicrobial potency. In all cases examined, the order of activity D > K(1t) > K(1c) > K(2t) > K(2c) was observed, and the same sequence prevailed in a spectroscopic measure of their binding to deoxyribonucleic acid. In addition, proton nuclear magnetic resonance studies revealed that the replacement of proline by cis-4-methylproline alters the conformation of the antibiotic molecule.

Bacillus subtilis