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Biomedical subjects

S Roberts

Publications and source records attributed to S Roberts.

At least 217 records · Page 12Linked to original sources

Treating periodontal diseases by blocking tissue-destructive enzymes.

A new therapeutic approach involves the discovery by the "Stony Brook group," that tetracyclines, but not other antibiotics, can inhibit host-derived collagen-destructive enzymes. This newly discovered property of tetracyclines is unrelated to the antimicrobial activity of these drugs. Examples support the hypothesis that this unexpected property of tetracyclines provides a new approach to treating periodontal diseases as well as a variety of medical disorders.

Gingival Crevicular Fluid↗

The detection of acquired immunodeficiency syndrome-associated Kaposi sarcoma cells in pleural effusion by CD34 immunostain.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS) cells have not been reported in pleural effusions. This study identifies the effusional form of AIDS-KS cells with the CD34 antibody, a newly recognized marker for vascular neoplasia. METHODS: In the pleural effusion of a patient with AIDS and biopsy proven pulmonary KS, the authors found bizarre amoeboid cells. Parallel sections from the cell blocks of the pleural effusions from the index patient and six other patients with AIDS were immunostained for cytokeratin, CD68, leukocyte common antigen (LCA), Factor VII:R, and CD34. RESULTS: The atypical cells were not observed in the pleural effusions of the other six patients with AIDS. The atypical cells were positive for CD34 (4+) and Factor VIII:R (1+) but were negative for cytokeratin, CD68, or LCA, which were expressed by mesothelial cells, macrophages, and lymphocytes, respectively. The expression for CD34 and Factor VIII:R was limited to a sharply delineated perinuclear region in the cytoplasm, corresponding to the erythrocyte-containing intracytoplasmic space of the atypical cells on the filter. CONCLUSION: In conclusion, the erythrocyte-containing intracytoplasmic space within the atypical cells most likely represents the intracytoplasmic lumina of the AIDS-KS endothelial cells and the CD-34-positive atypical cells represent the effusional form of the AIDS-KS cells.

AIDS-Related Complex↗

The cartilage end-plate and intervertebral disc in scoliosis: calcification and other sequelae.

The morphology and composition of the intervertebral disc and also of the cartilage end-plate were studied in patients with idiopathic or congenital scoliosis. The cartilage end-plate was investigated because of its function as an epiphyseal plate in humans and the association between growth and progression of the scoliotic curve. The proteoglycan and water contents were reduced in both structures in specimens from scoliotic patients, particularly toward the concavity of the curve, compared with autopsy material. The distribution of some collagen types differed in tissue from scoliotic patients and autopsy tissue. Calcification of the cartilage end-plate, and sometimes of the adjacent disc, occurred in all but three scoliotic patients, whereas there was minimal calcification in the autopsy specimens. We suggest that, although these changes are probably a secondary response to altered loading in the scoliotic patients, they may be highly significant to the progression of the scoliotic curve.

Adolescent↗

Overexpression of wild-type p53 and c-Myc in human fetal cells transformed with adenovirus early region 1.

The expression of p53 in a large panel of adenovirus (Ad) 2/5- and 12-transformed human, rat, and mouse cells has been examined. In all cases, in the absence of the larger Ad E1B protein, the level of p53 is very low. In human and rat cells when the Ad 12 E1B 54K polypeptide is expressed, p53 is much more abundant, although this is not the case in Ad 12 E1-transformed mouse cells. We conclude that expression of p53 is determined by virus serotype, host cell type, and viral proteins expressed. p53 in Ad 12 E1-transformed human cells is wild type but has an extended half-life. Stabilization is not through protein-protein interaction with the Ad E1B protein. The level of expression of c-Myc is also elevated in Ad-transformed human cells but this does not correlate with the presence of the E1B protein or with p53. However, Northern blot analysis indicates a direct correlation between mRNA and protein levels. We conclude that c-Myc is regulated at the transcriptional level, whereas p53 is regulated at the post-translational level in adenovirus transformants.

Adenovirus E1B Proteins↗

Specificity of bipartite geminivirus movement proteins.

Pseudorecombinants produced by exchanging genome components (DNAs A and B) of the geminiviruses African cassava mosaic virus (ACMV) and Indian cassava mosaic virus (ICMV), ACMV, and tomato golden mosaic virus (TGMV), and TGMV and abutilon mosaic virus (AbMV) are not infectious in their common host Nicotiana benthamiana. In each case, DNA A was unable to trans-replicate the heterogenomic DNA B component in a N. benthamiana leaf disc assay. The non-viability of the pseudorecombinants has been exploited to investigate the specificity of geminivirus movement proteins, encoded by DNA B, by co-inoculating N. benthamiana with both genome components of one virus and DNA A of a second virus. We demonstrate that ACMV can mediate the systemic movement of ICMV, TGMV and AbMV DNA A components. In reciprocal experiments, neither TGMV nor AbMV can mediate the systemic movement of ACMV DNA A although they can support the movement of each other's DNA A. The variation in movement protein specificity suggests evolutionary divergence of New and Old World geminiviruses. Co-inoculation of combinations of ACMV and ICMV genome components into discriminating hosts and comparison of their behavior in N. benthamiana and N. tabacum leaf disc assays suggests that the host range of ICMV, a subset of that of ACMV, is restricted by impaired viral DNA replication rather than the inability of the virus to spread in non-host backgrounds.

DNA Replication↗

Cutaneous and mucosal human papillomavirus E4 proteins form intermediate filament-like structures in epithelial cells.

Human papillomavirus (HPV) type 1 (HPV 1) is associated with benign cutaneous warts and HPV type 16 (HPV 16) with mucosal epithelial lesions that can progress to invasive carcinoma. The primary structure of the HPV E4 proteins is not highly conserved between types and their role in the viral life cycle is still unknown. A large panel of Simian virus 40 (SV40)-transformed human and monkey epithelial and fibroblast cell lines were infected with recombinant SV40/HPV1 E4 or SV40/HPV 16 E4 viruses and the expression of the viral proteins was analyzed by indirect immunofluorescence. Both HPV 1 and HPV 16 E4 proteins formed extensive and organized filamentous cytoplasmic networks that co-localized with the cytokeratin intermediate filaments. However, only HPV 16 E4 induced the collapse of the cytokeratin filaments. Furthermore, when both virus type E4 proteins were expressed within the same cell the collapse of the HPV 16 E4 filaments did not induced the collapse of the HPV 1 E4 network. Similar E4 filamentous structures were also observed in the cytoplasm of cells of the parabasal layer of an HPV 1-induced experimental wart. The HPV 16 E4 protein formed cytoplasmic networks in all SV40-transformed cell lines examined, but HPV 1 E4 only formed filamentous networks in human keratinocytes and in a monkey stomach epithelial cell line. In keratinocyte cells HPV 1 E4 species of 16, 17, 32, and 34 kDa were expressed, while in Cos-1 cells (in which no E4 networks are formed) only the 17 and 34 kDa polypeptides were found. The specific behavior of E4 proteins of cutaneous and mucosal HPVs expressed in cultured cells may suggest that these viral proteins have evolved to perform a similar function at different epithelial sites.

Animals↗

The New York High-Risk Project: anhedonia, attentional deviance, and psychopathology.

In the New York High-Risk Project (NYHRP) we followed subjects at risk for schizophrenic or affective disorders and low-risk controls from childhood to adulthood, with the goal of identifying early predictors of later schizophrenia-related psychopathology. In this article, we focus on two potential predictors: the Physical Anhedonia Scale administered in adolescence and the Attention Deviance Index obtained in childhood. Subjects of this report are 161 members of the NYHRP's first sample (sample A), who had scores on both attention and anhedonia and had followup clinical assessments in adulthood. We used a path analysis model and several separate regression analyses to examine the relationships of the parent diagnostic groups, attentional dysfunction, and anhedonia to each other and to each of three psychopathological outcomes: schizophrenia and schizophrenia-related psychoses, major affective disorder, and social isolation in nonpsychotic subjects. Subject groups did not differ in anhedonia scores but did differ in childhood attentional dysfunction, psychosis, and social isolation, all of which are more common in subjects at risk for schizophrenia. In these subjects at risk for schizophrenia, but not in the other two groups of subjects, childhood attentional dysfunction is related to anhedonia, social isolation, and possibly nonparanoid psychosis. Anhedonia is associated with social isolation and with psychosis in females. Several other gender effects are also noted.

Adolescent↗

Multiple functional domains of human transcription factor IIB: distinct interactions with two general transcription factors and RNA polymerase II.

Transcription factor IIB (TFIIB) plays a pivotal role in the formation of transcription-competent initiation complexes. TFIIB was found to interact with the TATA-binding protein, the small subunit of TFIIF, and RNA polymerase II. These interactions require distinct domains in TFIIB. Using the gel mobility-shift assay, it was found that the amino terminus of TFIIB was necessary for the formation of complexes containing RNA polymerase II and TFIIF, whereas the carboxy-terminal domain, which is composed of two imperfect direct repeats and includes a putative amphipathic alpha-helix, was sufficient for the formation of complexes containing the TATA-binding protein and TFIIB (DB complex). Protein-protein interaction analyses demonstrate that the amphipathic alpha-helix in TFIIB is important for the interaction with the TATA-binding protein. Specific residues mapping to the carboxyl terminus of the second direct repeat were found to be crucial for the interaction of TFIIB and RNA polymerase II. The interaction with the small subunit of TFIIF was mapped to the amino terminus of TFIIB, which includes a zinc finger.

Base Sequence↗

Surfactant replacement therapy in neonates less than 32 weeks gestation: effect on neonatal intensive care resource utilization.

The effect of synthetic surfactant (Exosurf) replacement on complications from hyaline membrane disease (HMD) in infants < 32 weeks gestation and their resource utilization within a neonatal intensive care unit was studied in 1991-92. A control group was selected from infants admitted to the same unit during the preceding 3 years when Exosurf was not available. The infants were controlled for gestation, weight and severity of HMD. Infants given Exosurf had a significant reduction in the incidence of pulmonary interstitial emphysema (PIE), and a marginal decrease in the incidence of pneumothorax. They required fewer days on the ventilator and consumed less of the scarce financial resources. There was no difference in the mortality rate among the two groups. The changes seen were more evident among those infants between 30 and 31 weeks gestation, compared to those < 28 weeks.

Case-Control Studies↗

Cardiff puerperal mood and hormone study. 1. Saliva steroid hormone profiles in late pregnancy and the puerperium: endocrine factors and parturition.

Participants were 120 primiparous women who had vaginal delivery of a non-handicapped child. Saliva was collected twice daily through parturition to day 35 post-partum. In the prepartum, a highly significant circadian rhythm was seen in cortisol, with a lower-amplitude rhythm in progesterone (AM/PM = 1.12). Evening samples showed a rise in cortisol, with a highly significant rise on day -1. The rise was small. The fall in progesterone in the 3 days before parturition was also small (approximately 6%). Neither change provides an obvious trigger for parturition.

Adolescent↗