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R A Faust

Publications and source records attributed to R A Faust.

31 records · Page 2Linked to original sources
PubMed1996

Nuclear matrix as an anchor for protein kinase CK2 nuclear signalling.

Nuclear matrix (NM) is not only the structural basis for nuclear shape but also is intimately involved in nuclear functional activities. Among the modulatory factors that may affect these diverse activities are the signals that may influence the state or composition of the NM proteins. One such mechanism for altering the functional activity of at least some NM proteins may be the extent of their phosphorylation. Protein kinase CK2 appears to associate with NM and to phosphorylate a number of NM-associated proteins. Chromatin- and NM-associated CK2 is rapidly modulated by mitogenic signals. We propose that NM serves as a physiological anchor for nuclear signalling of protein kinase CK2 which may influence functions of NM such as transcription of active genes and growth.

Animals↗
PubMed1996

Outpatient biopsies of the palatine tonsil: access to lymphoid tissue for assessment of human immunodeficiency virus RNA titers.

OBJECTIVES: Our objective was to assess the feasibility of using tonsillar lymphoid biopsy specimens obtained on an outpatient basis to quantitate a patient's lymphoid human immunodeficiency virus (HIV) RNA titers. DESIGN: A pilot cohort study was performed. PATIENTS: We evaluated ten HIV-seropositive patients who ranged in age from 26 to 48 years and had CD4+ cell counts ranging from 110 to 833 at enrollment. MAIN OUTCOME MEASURES: The main outcome measures were tolerance and safety of outpatient tonsil biopsies and quantitation of HIV RNA titers in tonsillar lymphoid biopsy specimens, plasma, and peripheral blood mononuclear cells determined by a new method of HIV RNA signal amplification with branched DNA probes. RESULTS: Outpatient tonsil biopsies were well tolerated and were performed without complications. Nine of 10 tonsil biopsies from the HIV-seropositive patients examined were positive for significant concentrations of HIV RNA, ranging from 106 to 101 HIV RNA equivalents per gram of tissue. All of the HIV RNA-positive tonsillar lymphoid specimens had HIV RNA titers that were 101 to 104 times greater than those recovered from plasma (per milliliter) of the same patient obtained at the time of biopsy. CONCLUSIONS: Sufficient tonsillar tissue can be obtained in an outpatient clinic setting to quantitate lymphoid HIV titers by the new branched-DNA signal amplification method with relative ease and without complication. The biopsy method described here affords ready access to the lymphoreticular system, which may help to advance our understanding of the pathogenesis of myriad immune diseases without the need for excisional node biopsies.

Adult↗
PubMed1995

Association of elevated protein kinase CK2 activity with aggressive behavior of squamous cell carcinoma of the head and neck.

BACKGROUND: Protein kinase CK2 (also known as casein kinase 2) is a messenger-independent protein serine/threonine kinase ubiquitously distributed in eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein synthesis, and differentiation. We therefore addressed the hypothesis that malignant transformation of upper aerodigestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity. MATERIALS AND METHODS: To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We then quantitated CK2 activity in cytosol and nuclei of these specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu). RESULTS: We found that CK2 activity was significantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to normal oropharyngeal mucosa. Moreover, CK2 activity in the cellular cytosolic fraction of SCCHN tumors was associated with less differentiated histologic grade (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clinical outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023). CONCLUSIONS: These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.

Adult↗
PubMed1990

Regulation of LTP-I secretion from human monocyte-derived macrophages by differentiation and cholesterol accumulation in vitro.

Human macrophages in vitro synthesize and secrete the cholesteryl ester (CE) transfer protein, LTP-I. The effect of differentiation of monocyte-to-macrophage on the synthesis and secretion of LTP-I cholesteryl ester transfer activity was investigated. One marker of macrophage differentiation is expression of the 'scavenger' receptor, which mediates macrophage uptake and degradation of acetylated low-density lipoprotein. Monocytes secreted very little detectable CE transfer activity in the first 24 h following cell isolation. Both CE transfer activity and scavenger receptor activity increased with time in culture. Thus, although circulating monocytes probably do not secrete CE transfer activity, tissue macrophages such as hepatic Kupffer cells may contribute to plasma CE transfer activity. Resident macrophages of the arterial wall are derived from circulating monocytes which enter the vessel wall where they differentiate into macrophages. Such macrophages are the principal source of lipid-laden foam cells of the atherosclerotic plaque. Cholesterol accumulation results when uptake of lipoprotein cholesterol overwhelms the capacity of macrophages to excrete cholesterol. Since LTP-I is postulated to function in reverse cholesterol transport, the effect on LTP-I secretion of loading macrophages with cholesterol was determined after exposure of macrophages to acetylated-LDL or free cholesterol (FC). Cholesterol loading by both these maneuvers resulted in dose-dependent increases in macrophage secretion of CE transfer activity, and there was a significant positive correlation between CE transfer activity secreted and accumulation of CE. Thus, LTP-I may function at the cellular level in maintenance of lipid homeostasis: macrophage LTP-I secretion may be a protective mechanism in response to excess cholesterol accumulation in resident macrophages of the arterial wall.

Blotting, Western↗
PubMed1989

Secretion of cholesteryl ester transfer protein-lipoprotein complexes by human HepG2 hepatocytes.

We have employed immunoaffinity chromatography to characterize the distribution of cholesteryl ester transfer activity in particles secreted by HepG2 hepatocytes. HepG2-secreted cholesteryl ester transfer activity is associated with apoprotein (apo) A-I (58%) as well as apo A-II (55%), and is not associated with apo B or E. In contrast, our previous studies have shown that most (88%) cholesteryl ester transfer activity in human plasma is associated with apo A-I whereas very little (7%) is associated with apo A-II. Thus, the distribution of cholesteryl ester transfer activity in plasma particles likely reflects active remodeling of nascent particles in the plasma compartment. Further data suggested that HepG2 cells secrete a lipid transfer inhibitor activity which is associated with apo E-containing lipoprotein particles. This inhibitory activity is heat labile.

Apolipoprotein A-I↗
PubMed1988

Regulated vectorial secretion of cholesteryl ester transfer protein (LTP-I) by the CaCo-2 model of human enterocyte epithelium.

We have investigated the human CaCo-2 enterocyte model for secretion of the plasma cholesteryl ester transfer protein, LTP-I. CaCo-2 cells secrete a cholesteryl ester transfer protein which possesses molecular identity with plasma LTP-I, demonstrated by anti-LTP-I immunoblot analysis and immunoinhibition of all cell-secreted cholesteryl ester transfer activity. When CaCo-2 are cultured on permeable membranes, cholesteryl ester transfer activity is detected only in the lower culture compartment. Thus, CaCo-2 vectorially sort and secrete LTP-I, as well as the intestinal apolipoproteins, from the basolateral cellular domain. Over a 24-h period, CaCo-2 secrete cholesteryl ester transfer activity in a time-dependent manner, at approximately twice the rate of HepG2. Furthermore, CaCo-2 enterocytes, but not HepG2 hepatocytes, regulate LTP-I secretion in response to fatty acid concentration in the culture medium. Based on these observations, we speculate that the intestine may be the principal regulated source of human plasma LTP-I.

Apolipoproteins↗
PubMed1976

Tetanus: 2,449 cases in 68 years at Charity Hospital.

The 68-year Charity Hospital experience with tetanus has been reviewed with particular emphasis on the past 8 years. There were 2,449 cases treated at Charity Hospital from 1906 through 1974. The mortality rate has remained high. There were 24 cases in the past 8 years, with a 58% case fatality rate. Clues to our high mortality rate could be: 1) many cases with a short period of onset, 2) none of our 24 cases received treatment at time of injury, and 3) there were more severe cases, as judged by the high rate of need for tracheostomy. The method of management emphasizes: 1) wound care, 2) neutralization of the toxin, 3) antibiotic therapy, 4) supportive measures including good nursing care with control of convulsions and seizures, and 5) completion of active immunization. Prophylaxis is stressed, with particular emphasis on wound debridement and toxoid. The decreasing incidence of the disease is encouraging, probably related directly to proper immunization. However, the mortality rate remains high and the solution to the problem of tetanus is still prophylaxis. Epidemiologic considerations were discussed with particular emphasis on tetanus in the five Gulf States, the South in general, and the decreasing incidence in endemic areas.

Adolescent↗
PubMedDate not supplied

Synthesis and secretion of plasma cholesteryl ester transfer protein by human hepatocarcinoma cell line, HepG2.

We have examined the synthesis, secretion, and functional and physical characteristics of a lipid transfer protein synthesized by a human hepatocellular carcinoma line. We found that this protein shares immunochemical determinants and many other properties with the lipid transfer protein, LTP-I, which has been purified from human plasma. We conclude that the human liver cell line, HepG2, synthesizes and secretes LTP-I. Thus, hepatocytes may be the source of LTP-I in human plasma.

Animals↗
PubMedDate not supplied

Noncancer inhalation toxicology of crystalline silica: exposure-response assessment.

Silicosis from inhalation of silica has long been recognized as an occupational hazard. Concern has arisen regarding the potential risk of silicosis from ambient silica (primarily quartz dust). This presentation reviews available data regarding ambient silica levels and estimates of the risk of silicosis at low exposure levels as they relate to the current U.S. Environmental Protection Agency National Ambient Air Quality Standards (NAAQS) for particulate matter. Current data indicate that for individuals not compromised by other respiratory ailments and for ambient environments expected to sustain 10% or less silica fraction in particulate matter with a mean aerodynamic diameter of < or = 10 microns (PM10), maintenance of the 50 micrograms/m3 annual NAAQS for PM10 is adequate to protect against fibrotic effects from ambient silica exposures. Issues such as the large divergence of risk estimates within the occupational setting (particularly at high cumulative exposures) and factors to consider for extrapolating risk in an occupational setting to risk from ambient exposure are discussed.

Air Pollutants↗