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Biomedical subjects

L J Williams

Publications and source records attributed to L J Williams.

17 recordsLinked to original sources
PubMed1992

Complete inhibition of growth followed by death of human malignant melanoma cells in vitro and regression of human melanoma xenografts in immunodeficient mice induced by camptothecins.

The plant alkaloid camptothecin and three camptothecin derivatives were used to study responses of human malignant melanoma (BRO) cells xenografted in immunodeficient (nude) mice. Camptothecin and its derivatives 9-nitro-20(S)-camptothecin and 9-amino-20(S)-camptothecin inhibited growth of tumors and caused regression in all tumor-bearing mice. Tumor regression was accompanied by degenerative changes in the tumor cells, as assessed by microscopic observations of histological sections prepared from the tumors. No toxic effects were observed in the drug-treated mice, with or without xenografts. In parallel experiments, camptothecin, 9-nitro-20(S)-camptothecin, and 9-amino-20(S)-camptothecin inhibited proliferation of BRO cells in vitro and resulted in dramatic morphological cellular changes comparable to those observed in the sections of solid tumors. The derivative 12-nitro-20(S)-camptothecin had no effect on BRO tumors or cell cultures. The difference between 9-nitro-20(S)-camptothecin and 12-nitro-20(S)-camptothecin is the position at which the NO2 group is attached to the camptothecin molecule. In contrast to BRO melanoma cells, none of the camptothecin derivatives had any effect on cultured human melanocytes, the normal counterparts of melanoma cells. Taken together, the findings indicate that camptothecin and derivatives exert different effects on the growth and morphology of normal and malignant (BRO) melanocytes.

Animals↗
PubMed1992

Attachment of mitochondria to intermediate filaments in adrenal cells: relevance to the regulation of steroid synthesis.

The rate of steroid synthesis is regulated by the rate of transport of cholesterol from lipid droplets to mitochondria. We have previously demonstrated that lipid droplets in adrenal cells are tightly attached to intermediate filaments. Here we now show that mitochondria colocalize with intermediate filaments in modified double indirect immunofluorescence and by electron microscopy of extracted adrenal cells. Direct contact between mitochondria and intermediate filaments was established by examination of stereo pairs of electron micrographs from extracted cells. The attachment of both droplets and mitochondria to intermediate filaments suggests possible mechanisms for this form of intracellular transport of cholesterol to mitochondria and hence for the regulation of steroid synthesis.

Adrenal Glands↗
PubMed1992

Ornithine decarboxylase gene of Neurospora crassa: isolation, sequence, and polyamine-mediated regulation of its mRNA.

Ornithine decarboxylase (ODC), which initiates the biosynthesis of the polyamines putrescine, spermidine, and spermine, is encoded by the spe-1 gene of the fungus Neurospora crassa. This gene and its cDNA have been cloned and sequenced. The gene has a single 70-nucleotide intron in the coding sequence. The cDNA, comprising the entire coding region, recognizes a single 2.4-kb mRNA in Northern (RNA) blots. The mRNA transcript, defined by S1 mapping, has an extremely long, 535-base leader without strong secondary-structure features or an upstream reading frame. The translational start of the protein is ambiguous: a Met-Val-Met sequence precedes the Pro known to be the N terminus of the ODC polypeptide. The polypeptide encoded by the N. crassa spe-1 gene (484 amino acids) has 46% amino acid identity with that of Saccharomyces cerevisiae (466 amino acids) and 42% with that of mouse (461 amino acids). Alignment of the longer N. crassa sequence with S. cerevisiae and mouse sequences creates gaps in different sites in the S. cerevisiae and mouse sequences, suggesting that N. crassa ODC is closer to an ancestral form of the enzyme than that of either yeast or mouse ODC. N. crassa ODC, which turns over rapidly in vivo in the presence of polyamines, has two PEST sequences, found in most ODCs and other proteins with rapid turnover. In striking contrast to other eucaryotic organisms, the variation in the rate of ODC synthesis in response to polyamines in N. crassa is largely correlated with proportional changes in the abundance of ODC mRNA. Spermidine is the main effector of repression, while putrescine has a weaker effect. However, putrescine accumulation appears to increase the amount of active ODC that is made from a given amount of ODC mRNA, possibly by improving its translatability. Conversely, prolonged starvation for both putrescine and spermidine leads to the differentially impaired translation of ODC mRNA.

Amino Acid Sequence↗
PubMed1992

Attachment of steroidogenic lipid droplets to intermediate filaments in adrenal cells.

Light microscopy of living and extracted adrenal cells (Y-1 mouse adrenal tumour cells and cultured bovine fasciculata cells), using Nomarski optics and fluorescence with nile red to stain lipid, revealed in both cell types that lipid droplets remain attached to intermediate filaments when the cells are extracted to prepare these structures. Electron microscopy of thin sections shows the presence of lipid droplets in both cell types. The droplets differ in appearance but are, in both cases, surrounded by a complete capsule 5 nm wide. The droplets in Y-1 cells include those associated with lysosomes and crystalline structures in addition to typical rounded forms. Only the latter type is seen in bovine fasciculata. Intermediate filaments apparently ending in droplets can also be seen. Immunoelectron microscopy with anti-vimentin and Protein A conjugated to gold particles together with measurement of the diameter of these structures identifies them as intermediate filaments. When adrenal cells are permeabilised and extracted under mild or severe conditions using Triton X-100, thin sections showed that lipid droplets remain associated with the cytoskeleton and in particular intermediate filaments. Extraction under mild and severe conditions cleared the cell contents, revealing attachment of intermediate filaments to lipid droplets with greater clarity than in unextracted cells, i.e. homogenised cells or cells subjected to lysis. Such attachment was unequivocally demonstrated in stereo pairs. These observations support our earlier studies showing attachment of droplets to intermediate filaments, which suggests a role for these filaments in intracellular transport of cholesterol.

Adrenal Glands↗
PubMed1991

Heterotransplantation of human breast carcinomas in nude mice. Correlation between successful heterotransplants, poor prognosis and amplification of the HER-2/neu oncogene.

Four hundred and thirty-three human breast carcinomas and 23 cell lines derived from human breast carcinomas were heterotransplanted in nude mice. Twenty-eight tumors and 13 cell lines took and could be serially transplanted. Their human origin was established by isozyme analysis performed on successive passages. Sixteen primary infiltrating duct-cell carcinomas (PIDC) took, from a total of 262 transplanted (6.1%). This is in striking contrast to the greater than 50% rate of takes of most major cancers of epithelial origin. All 16 PIDC growing in nude mice were highly cellular and lacked desmoplastic hyperplasia. The clinical prognosis of the PIDC patients whose tumors were successfully transplanted was poor. Ten of 16 (63%) died of their disease within 3 years, compared to only 49 (20%) of the 246 PIDC patients whose tumors did not take in nude mice. This could not be attributed to later stage disease of the tumors that took, because only 15% of these patients had 4 or more positive axillary lymph nodes as opposed to 28% of the patients whose tumors did not take. Sixty-four percent of the breast carcinomas growing in nude mice exhibited amplification of the HER-2/neu oncogene which is also correlated with poor prognosis in human breast cancer. It is possible that the nude mouse is more susceptible to a population of highly invasive and lethal breast carcinomas.

Adult↗
PubMed1991

Comparative analysis of nucleotide sequences of the partial envelope gene (5' domain) among human T lymphotropic virus type I (HTLV-I) isolates.

Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The nucleotide sequences of 640 bp of the proviral genome (positions 5158-5797) derived from 11 HTLV-I-infected persons were analyzed using the polymerase chain reaction and M13-based sequencing techniques. Patterns of single nucleotide substitutions were characterized from the extracellular domain of the envelope gene (gp46). Compared with other retroviruses, the nucleotide sequences of the HTLV-I external envelope gene are highly conserved among the genotypes studied. We found no evidence of dual infections with HTLV-II among the seropositive asymptomatic persons or in patients with either ATL or HAM/TSP. No unique sequence differences were observed in the envelope gene of the HTLV-I isolates derived from patients coinfected with human immunodeficiency virus type 1 (HIV-1). However, comparative analysis of these data and other published HTLV-I envelope sequences indicated the presence of four subtypes of HTLV-I in relation to their geographic origin.

Base Sequence↗
PubMed1979

Covert modeling vs. Behavior rehearsal in the training and generalization of assertive behaviors: a crossover design.

Twenty-four underassertive individuals from the community were assigned randomly to two treatment orders that included covert modeling and behavior rehearsal in a crossover design. Dependent measures included two self-report inventories and a behavioral assertiveness test. This test included a self-rating scale, two nonverbal measures, and eight measures of speech content. No measurable differences between treatments were found, and both significantly improved assertive skills on 10 of the 13 measures. However, Ss had greater expectations of improvement from behavior rehearsal both during and after treatment. Generalization of assertive skills from trained to untrained situations occurred on 8 of the 11 behavioral measures. Suggestions were made for exploring the use of covert modeling as a personal coping procedure capable of enhancing generalization and maintenance.

Adolescent↗
PubMed1979

Infant nutrition.

Explore the source record for details and available documents.

Blood Glucose↗
PubMed1979

Hyperthermic treatment of human tumors heterotransplanted in nude mice.

A new model is presented for the study of the effects of supranormal temperatures on human tumors in vivo. Human tumors heterotransplanted serially in nude mice were heated in vivo by means of local radio-frequency heating. A lung carcinoma, a breast carcinoma, a colon carcinoma, and a malignant melanoma were studied. The tumors were transplanted s.c. in the inguinal area or under the kidney capsule of adult nude mice. The s.c. tumors were heated for 30 min. Temperatures of 43--44 degrees C were reached in the surrounding normal tissues, whereas in the center of the tumor temperatures of 46--49 degrees C were recorded. In 11 of 16 randomized pairs of mice, the growth of the tumor treated by hyperthermia was inhibited by 75% or more as compared with the growth of the untreated tumor control. No mortality and only temporary damage to skin and muscle were observed. The kidney tumors were also treated for 30 min, but it was possible to reach only 40 degrees C in the abdomen. Seventy-five % mortality was observed. Of seven randomized pairs evaluated, five exhibited a reduction of growth varying from 37 to 63%9 The model proposed appears to be a workable and promising one, especially for s.c. growing tumors.

Animals↗
PubMed1979

Eugenic sterilization: medico-legal and sociological aspects.

The court-ordered sterilization of a normal 18-year-old black female in North Carolina focused attention on the unfortunate impact of eugenic statutes that allow sterilization as a method of social control. The existence of these laws in many states allows misapplication and abuse of authority which, not infrequently, is directed liberally to blacks and other minority groups.Eugenic sterilization is, at this time, a legally accepted form of "medical treatment." The justification of such sterilization is the vague concept that the presumed "mentally deficient" individual is probably a potential parent of socially inadequate offspring who would likewise be socially inadequate.Since there never has been factual substantiation of whether the sterilization of these individuals will diminish the incidence of mental retardation, it is necessary to focus attention on the concept of eugenic sterilization and point out its many fallacies.

Adolescent↗
PubMed1978

Heterotransplantation of human cancers into nude mice: a model system for human cancer chemotherapy.

More than 200 human cancers have been successfully transplanted into nude athymic mice in our laboratory. Strict sterile techniques must be applied in caring for these animals and meticulous attention given to the preparation of the surgical specimens. That the tumors remain human in the mice has been documented by isozyme and karyotype analyses. Also, histopathologic comparisons between the original human tumors and their transplanted counterparts in the mice are strikingly similar or identical. Preliminary results of chemotherapy of human cancers in the nude mice are extremely encouraging. At this point, we believe that the greatest potential for the nude mice lies in their use in testing anticancer therapies for human neoplasms without placing the patients at risk.

Animals↗
PubMed1977

Calibration methods for automated hematology instruments.

Recent CAP survey data have documented marked improvement in the reproducibility of hematologic tests. The favorable outcome is attributable largely to the widespread use of automated whole-blood analyzers. Calibration variability, however, detracts from this enhanced precision, and there are clear indications that improvement is necessary. Primary calibration methods for hemoglobin, hematocrit and cell counting procedures are presented. The methods of applying these primary calibration methods to automated whole-blood analyzers are delineated. The use of both preserved reference blood and statistical control technics for the identification of calibration loss is described.

Automation↗
PubMed1976

Human neoplastic and normal cells in tissue culture. I. Cell lines derived from malignant melanomas and normal melanocytes.

Forty-six cell lines derived from 31 human melanomas obtained from 28 patients were cultured. Fourteen of 16 lines have produced malignant tumors when injected into nude (thymus-deficient) mice. Tumors in 5 of the nude mice metastasized to distant lymph nodes and/or to the lungs of the mouse host. Extreme variability from line to line was observed for doubling time (34 to 106 hr), plating efficiency (0-86%), and melanin production. All tested lines had type B glucose-6-phosphate dehydrogenase, thereby excluding HeLa cell contamination. HeLa cells have been grown for some time in our laboratory. Our results clearly demonstrated that HeLa cell contamination does not occur invariably in heteroploid lines growing in a laboratory simultaneously with Hela cells, provided that proper care is taken to avoid such occurrence. Multiple cell lines derived from the same tumor had identical phosphoglucomutase enzyme phenotype, which suggested a lack of significant cross-contamination between the lines. Four long-term cultures of normal human uveal embryo melanocytes have also been established and characterized. Although all produced melanin after reaching saturation density, they differed from the melanoma cells morphologically; they were flat, not refringent, and lacked piling up and plating ability. When melanoma cells were exposed to bromodeoxyuridine (BUDR) for long periods, a phenotypic change toward non-neoplastic characteristics was observed. Cells became flat and not refringent and, when injected into nude mice, tumors appeared after a long latent period. These changes were completely reversible in vitro and in vivo. The BUDR-treated cultures were undistinguishable from the untreated mother cultures after 2 to 3 passages. Lines derived from tumors in nude mice (obtained by injection of BUDR-treated cells) were again indistinguishable from the untreated mother line. Normal melanocytes were mostly euploid; all the melanoma cells were aneuploid. All 29 cell lines derived from 14 patients had an average chromosome number higher than 46. Detailed group-by-group chromosome analysis always showed an excess of C chromosomes, which suggested that hyperreduplication of one or more C chromosomes is a specific characteristic of human melanomas.

Adult↗
PubMed1975

Ultrastructure of the lung in Loeffler's pneumonia.

A case is presented fulfilling the diagnostic criteria of "Loeffler's eosinophilic pneumonia". No etiologic factors could be determined, and the chest roentgenogram returned to normal. Lung biopsy at the peak of the disease demonstrated an interstitial eosinophilic pneumonia without tissue necrosia or vasculitis. By electron microscopy, the alveolar capillary basement membranes were intact and exhibited no immune deposits. Normal appearing eosinophils were abundant in the alveolar capillaries, interstitium and alveolar spaces. Occasional eosinophils released their granules within the alveolar wall. Macrophages were increased in number in both the alveolar wall and alveolar spaces.

Biopsy↗