Biomedical subjects
J Figge
Publications and source records attributed to J Figge.
Stringent regulation of stably integrated chloramphenicol acetyl transferase genes by E. coli lac repressor in monkey cells.
Monkey cell lines that constitutively synthesize 38.6 kd lac repressor protein and bear stably integrated chloramphenicol acetyl transferase (CAT) genes linked to a lac operator-containing SV40 early promoter-enhancer were generated. When grown in medium containing isopropyl beta-D-thiogalactoside (IPTG), these cells acquired a CAT+ phenotype. In contrast, when grown in parallel in medium lacking IPTG, the cells remained CAT-. Maximum induction of CAT activity occurred after 4 days of IPTG exposure. Three days after removal of IPTG, induced cells had reverted to CAT-. Specific CAT activity increased up to 60-fold after induction, while background activity in uninduced cells was similar to or only slightly above that of parental, CAT- cells. CAT activity increased stepwise over a wide range of IPTG concentrations. Thus lac repressor-operator complexes can form on primate chromosomes and stringently block transcription from an adjoining promoter.
Comparison of excretion of nicotinuric acid after ingestion of two controlled release nicotinic acid preparations in man.
We tested an inexpensive controlled-release nicotinic acid product (Bronson Pharmaceuticals, LaCanada, CA) and compared it with the standard, more expensive, controlled release product, Nicobid (Rorer Pharmaceuticals), by measuring the 24 hour urinary recovery of nicotinic and nicotinuric acids from ten subjects following 500 mg oral ingestion of each product. Nicotinuric acid is the major detoxification product of nicotinic acid and may serve as a simple quantitative index of hepatic biotransformation of nicotinic acid. Although both products demonstrated controlled release profiles, the rate of appearance of nicotinic and nicotinuric acid in the urine as well as the rate of in vitro drug dissolution of the Bronson product were more rapid compared with Nicobid. Moreover, the total amounts of nicotinic acid and nicotinuric acid recovered in the urine after 24 hours were greater for the Bronson product (P less than .05). Since sustained presentation of nicotinic acid to the liver may correlate with clinical antihyperlipidemic effects, our results suggest that the Bronson product may prove to be a clinically useful preparation.
Nicotinic acid: a review of its clinical use in the treatment of lipid disorders.
Nicotinic acid (niacin) is a water-soluble vitamin widely used for the treatment of lipid disorders. In pharmacologic doses (1 g or more/day), alone or in combination with other lipid-lowering drugs, nicotinic acid lowers very low-density (VLDL) and low-density lipoprotein (LDL) levels, while concurrently increasing high-density lipoprotein (HDL) levels. It may reduce long-term mortality in patients with known coronary artery disease and may slow or reverse the progression of atherosclerosis. A major consideration against using nicotinic acid is the occurrence of frequent, bothersome, adverse reactions such as cutaneous flushing, skin rash, and gastric upset. Careful dosing titration may, however, minimize these effects. The beneficial effects, taken together with the low cost of nicotinic acid therapy and the relative freedom from serious side effects, have made nicotinic acid the agent of choice for the treatment of many patients with hyperlipidemia.
Prediction of similar transforming regions in simian virus 40 large T, adenovirus E1A, and myc oncoproteins.
Regions containing similar elements of primary and predicted secondary structure were identified in simian virus 40 large T, adenovirus E1A, c-myc and v-myc proteins by a computer program with a set of highly specific, complex pattern descriptors. In all cases these regions were localized in domains of the respective proteins known to be required for transforming activity. We suggest that these apparently structurally similar regions may mediate a common biological function.
lac repressor can regulate expression from a hybrid SV40 early promoter containing a lac operator in animal cells.
The E. coli lac operator and repressor were adapted for function in mammalian cells. Plasmids containing an SV40 early region (pSVlacO) or a chloramphenicol acetyl transferase gene (pSVlacOCAT) linked to a hybrid SV40 early promoter bearing a lac operator were tested for function. Identical plasmids lacking an operator (pX-8 and pX-8CAT) were controls. In vitro, early transcription from pSVlacO, but not from pX-8, was inhibited by lac repressor, and repression was overcome by IPTG. Repression of large T synthesis or CAT activity occurred in vivo only when the respective operator-containing plasmid was cotransfected with a plasmid encoding lac repressor, or when the recipient cells stably synthesized lac repressor. IPTG substantially relieved repression in both cases. CAT enzyme repression was paralleled by a decrease in CAT mRNA abundance. Thus regulatory elements of the lac operon function physiologically in mammalian cells.
The elderly coping at home: a study of continuity of nursing care.
Thirty-three elderly clients who had been hospitalized and required continued care at home were studied for 3 months, with 836 visits made. Coping at home was studied in relationship to their certainty/uncertainty scores, perceived level of health, and perceived satisfaction with nursing care services. The relationship between coping and certainty/uncertainty was significant at P less than 0.001 and P less than 0.005 (first and second visits); the relationship between coping and perceived level of health was significant at P less than 0.001 and P less than 0.05 (first and second visits); and the relationship between coping and perception of care was not significant. This study presents significant data to contribute to nursing knowledge in the care of elderly people at home.
[The elderly coping at home: a study of continuity of nursing care].
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Localization of the simian virus 40 small t antigen in the nucleus and cytoplasm of monkey and mouse cells.
Monkey and mouse cells producing simian virus 40 small t antigen in the absence of clearly detectable intact or truncated large T antigens were subjected to indirect immunofluorescence and biochemical cell compartment analyses. Results revealed specific immunofluorescence and small t polypeptide in both the nucleus and cytoplasm of these cells.
Role of small t antigen in the acute transforming activity of SV40.
A plasmid, pHR402, containing SV40 sequences that include a truncated early region bearing an intact t-coding sequence and a functionally intact late region, was introduced into thymidine kinase deficient (tk-) mouse L cells by cotransformation with a cloned tk gene. tk+ cotransformants synthesized SV40 t but not T antigen, and no truncated T-coding sequence products were detected. The viral sequences of pHR402 were reconstituted as a virus in COS1 cells, and acute infection of untransformed mouse cells with this viral stock (SV402) also led to the appearance of t but not T or a truncated T. Abortive transformation assays of such infected cells were negative, as were those performed on the same cells infected with either of two viral mutants (dl883 and dl884), each of which leads to T but not t synthesis. However, mixed infection with SV402 and either dl883 or dl884 led to a clear abortive and permanent transformation response. Thus, at least in part, t and T appear to function in a complementary fashion in eliciting transformation expression by SV40-infected cells.
Tricyclic antidepressants: potent blockade of histamine H1 receptors of guinea pig ileum.
Six tricyclic antidepressants were tested for their ability to antagonize histamine actions at histamine H1 receptors in a bioassay for these receptors (histamine-induced contractions of guinea pig ileum). All compounds were competitive antagonists with equilibrium dissociation constants in the range of 5.6 x 10(-11) M to 1.5 x 10(-7) M. Doxepin hydrochloride and amitriptyline hydrochloride were the most potent compounds of the series and may be the most potent antihistamines known. Antagonism at histamine H1 receptors by these compounds may explain their sedative effects.
[CD44 gene expression in cancerous thyroid cells].
The peculiarities of alternative CD44 mRNA splicing in thyroid cancer tissue of children from radiocontaminated areas was investigated. CD44 gene expression in thyroid cancer tissues of children exposed to radiation resembled that in spontaneously emerged cancers. It was concluded that CD44 gene expression is not the primary target of radioactive irradiation. Probably, the CD44 mRNA splicing deregulation is the consequence of cancer.
[Study of HRas1 minisatellite frequencies in children with thyroid papillary cancer].
The "rare" alleles of HRas1 gene minisatellite are well-known factor of predisposition to many kinds of cancer. We have studied HRas1 minisatellite frequencies among patients with papillary thyroid cancer which is related to consequences of Chernobyl accident. The HRas1 minisatellite was analysed in 32 patients who suffered from papillary carcinoma and underwent operation in 1996-2001 and in 75 Belorussian residents. Of 64 HRas1 alleles revealed in patients 14 were defined as "rare" (21.9%); in the control group we have detected 17 "rare" alleles (11.3%) of the examined 150 alleles. The higher frequency of "rare" HRas1 minisatellite alleles in patient group was statistically significant (p < 0.01). We can suppose that the "rare" alleles of HRas1 minisatellite are associated with increased risk of papillary thyroid cancer formation in children and adolescents after Chernobyl accident.
Structural characterization of a 14-residue peptide ligand of the retinoblastoma protein: comparison with a nonbinding analog.
The retinoblastoma protein, a 110-kDa nuclear anti-oncoprotein, complexes specifically with transforming proteins of several oncogenic DNA viruses. A peptide [NLFCSEEMPSSDDE] derived from one of the viral proteins (simian virus 40 large T antigen) is known to competitively bind retinoblastoma protein, but a mutant analog [NLFCSKEMPSSDDE] does not. We studied the T peptide with HPLC to determine whether it can dimerize, and we employed circular dichroism spectroscopy to determine whether both peptides can exist in stable secondary structural conformations. HPLC analyses revealed that the T peptide is subject to oxidation and readily dimerizes. Circular dichroism analyses showed that both peptides can be induced to form stable secondary structural conformations under conditions that stabilize intramolecular hydrogen bonding in short peptides (90% 2,2,2-trifluoroethanol; 4 degrees C). The circular dichroism spectra of both peptide species were similar except for a statistically significant difference in the contour near 210 nm. Spectral analysis of the T-derived peptide species predicted elements of alpha-helix (18%), antiparallel beta-sheet (21%), beta-turn (22%) and unordered conformations (41%). An analysis of the mutant peptide species also predicted elements of alpha-helix (8%), antiparallel beta-sheet (28%), beta-turn (22%) and unordered conformations (40%). Thus, a small difference in the stabilized secondary structural conformations of the two sets of peptide species might partly explain their differential binding affinities for retinoblastoma protein, but it is likely that electrostatic charge differences resulting from the glutamic acid to lysine substitution play a dominant role.
[Differential diagnosis of hyperthyroidism syndrome using a highly sensitive method of determining TSH level in blood: clinical review and recommendations on use in Russia and the USA].
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Environmental effects on the folding of functional peptide segments from steroid hormone receptors.
Recent improvements in circular dichroism (CD) instrumentation now allow investigators to obtain highly reliable and reproducible CD spectra in the far-UV range to near 180 nm. These advances, coupled with new computer software for spectral interpretation, allow accurate calculations of secondary structural content in proteins and polypeptides. CD is particularly reliable for the calculation of alpha-helical content. We have utilized these features to determine the propensity of alpha-helix formation in highly purified synthetic peptides corresponding to segments from proteins. We obtain CD spectra of the peptides in 90% 2,2,2-trifluoroethanol (90% TFE; an alpha-helix promoting solvent) and in 2 mM sodium dodecyl sulfate (2 mM SDS; a beta-sheet promoting solvent) to assess helix stability in these different chemical environments. Using this methodology, we demonstrate that a peptide corresponding to a biologically active segment of the human estrogen receptor forms a stable alpha-helix in both environments. In contrast, peptide segments of equal length from other steroid receptors are alpha-helical in TFE but not in 2 mM SDS. These results show that the conformation of a peptide is a function of both its amino acid sequence and the local chemical environment.