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J Figge

Publications and source records attributed to J Figge.

At least 19 recordsLinked to original sources
PubMed1992

Endothelin-1 stimulates DNA synthesis and proliferation of pulmonary artery smooth muscle cells.

Endothelin-1 (ET-1), a 21-amino acid peptide released from the endothelium, elicits a variety of biological effects that include vascular smooth muscle cell (VSMC) contraction, release of secondary mediators, and cell proliferation. The present study was undertaken to examine the proliferative potential of ET-1 toward pulmonary artery VSMC in culture. In the presence of low serum and epidermal growth factor (EGF), ET-1 stimulated marked DNA synthesis and proliferation of VSMC. The contributing factor from serum appeared to be platelet-derived growth factor (PDGF) because the antibody to PDGF eliminated the stimulatory activity. The antibody to EGF also prevented the stimulation, suggesting that both PDGF and EGF are required for the full expression of the VSMC growth-promoting activity of ET-1. A paradoxical aspect of ET-1 effect on VSMC was the ability of ET-1 to inhibit the EGF-stimulated DNA synthesis when the two factors were added together to a high baseline DNA synthetic activity. The inhibition was prevented if ET-1 was added 12-18 h after the addition of EGF or if ET-1 and EGF were added to a protein kinase C-depleted VSMC. The inhibition by ET-1 may be mediated by protein kinase C activation followed by inhibition of EGF binding to its receptor. The results indicate that ET-1 under appropriate conditions can modulate the growth of pulmonary artery VSMC in both positive and negative directions.

Animals↗
PubMed1992

Serum proteins and acid-base equilibria: a follow-up.

A mathematic model that described the acid-base behavior of blood plasma has been revised to incorporate pK values of individual histidine residues on human serum albumin determined by nuclear magnetic resonance spectroscopy. With the insights derived from the model a method for evaluation of the strong ion difference has been developed. Thus if pH, PCO2, and the concentrations of serum albumin and phosphate are measured, all independent variables, which physically determine "acid-base balance" in plasma, can be quantified. New ways to evaluate "unidentified anions" in metabolic acidosis can be explored with this approach.

Acid-Base Equilibrium↗
PubMed1991

Image analysis quantitation of immunoreactive retinoblastoma protein in human thyroid neoplasms with a streptavidin-biotin-peroxidase staining technique.

Studies investigating the molecular pathogenesis of common thyroid neoplasms have shown altered expression and/or structure of proto-oncogenes, G-proteins, and growth factors. Growth suppressor genes, genomic DNA segments that code for proteins believed to function as growth suppressors, have not been evaluated for a potential role in the pathogenesis of thyroid neoplasms. The retinoblastoma gene (RB1) maps to chromosome 13q14 and encodes a 110 kilodalton variably phosphorylated nuclear protein (Rb) that functions as a growth suppressor in a wide variety of human tissues. The frequent association of Rb protein loss with multiple neoplasms has prompted the authors to apply a specific and rapid immunohistochemical technique using streptavidin-biotin-peroxidase technology evaluated by image analysis that can be used to quantitate the level of immunoreactive Rb protein (iRb) in thyroid neoplasms. In utilizing streptavidin-biotin technology for nuclear iRb detection, artifacts that can be associated with the use of avidin such as nonspecific binding at physiologic pH and nonspecific complex formation with cellular components including chromatin are avoided. By this method, positive nuclear staining for iRb in the follicular cells of three follicular adenomas and in CV-1 control cells known to express Rb was demonstrated. Two papillary carcinomas, two medullary carcinomas and a SAOS-2 cell line known to produce a defective form of Rb stained at significantly lower levels (P less than .001). The authors conclude that the streptavidin-biotin-peroxidase staining technique evaluated by image analysis is a sensitive and specific detection system for nuclear iRb studies; has significant advantages over previously used techniques; and that thyroid neoplasms may variably express iRb which may, in part, reflect their variable pathogenesis.

Adenoma↗
PubMed1991

The role of serum proteins in acid-base equilibria.

Serum proteins act as weak acids and participate in acid-base balance. Their effects are imprecisely quantified; in particular, the roles of albumin and globulins need reevaluation. We approached the problem in three steps. First, in artificial solutions resembling serum but with human serum albumin as the only protein moiety, we varied the strong ion difference (SID), partial pressure of carbon dioxide (Pco2) and the concentration of albumin [( Alb]) and fixed the concentration of inorganic phosphate [( Pi]). We measured pH and derived the charges on albumin. Second, extending the work of Stewart (Stewart PA. How to understand acid-base. A quantitative acid-base primer for biology and medicine. New York: Elsevier, 1981:1-286), we developed a mathematical model that solves for pH and for the charges on albumin as functions of SID, Pco2, [Pi], and [Alb]. The calculated values fit the observed values well; that is, the model describes well the behavior of these solutions over a wide range of simulated complex acid-base disturbances. Finally, in human serum samples containing both albumin and globulins, we varied SID, Pco2, and total protein concentration [( TP]); we fixed [Pi] and then measured pH and derived the charges on proteins as above. When we applied to these data the computer model developed for albumin alone, the calculated pH and derived charges on albumin values agreed well with the observed pH and derived charges on proteins. We conclude first that human serum globulins play a negligible role in acid-base equilibria, and second, that in normal human serum at pH 7.40 with [TP] = 7 and [Alb] = 4.3 gm/dl, the charges attributed to proteins are approximately 12 mEq/L; this is substantially less than the value of approximately 17 mEq/L given by many contemporary texts, based on work of van Slyke et al. (van Slyke DD, Hastings AB, Hiller A, Sendroy J Jr. Studies of gas and electrolyte equilibria in blood. XIV. Amounts of alkali bound by serum albumin and globulin. J Biol Chem 1928;79:769-80). These findings should be considered when evaluating acid-base balance in patients with abnormal serum albumin concentration, for example, when interpreting values of the anion gap.

Acid-Base Equilibrium↗
PubMed1990

Drosophila Krüppel protein is a transcriptional repressor.

Krüppel (Kr), one of the zygotically active Drosophila segmentation genes, is expressed in a restricted domain during the blastoderm stage of embryogenesis and is involved in the control of development of the thoracic and abdominal segments of the fly. Kr encodes a polypeptide containing DNA-binding zinc-finger motifs, disruptions of which yield Kr mutants. We have assayed the transcriptional activities of wild-type Kr protein as well as Lac repressor/Kr fusion proteins in HeLa and CV-1 cells. Wild-type Kr and a Lac-Kr chimaeric protein repressed transcription from reporter promoters in which a consensus Kr binding site derived from sequences within the even-skipped promoter had been inserted in an upstream position. We mapped the repression function of Kr to an alanine-rich amino-terminal region of the protein, as a Lac/Kr fusion protein containing only amino acids 26-110 of Kr repressed transcription from a reporter promoter containing upstream lac operators. This demonstrates that the DNA-binding and repression activities of the Kr protein are distinct. These data are consistent with genetic evidence that Kr represses even-skipped and hunchback expression, and suggest that Kr is a negative regulator of transcription in Drosophila.

Animals↗
PubMed1990

The effects of amiodarone on thyroid hormone function: a review of the physiology and clinical manifestations.

Amiodarone, an iodinated benzofuran derivative, is used for treatment of refractory cardiac arrhythmias. Certain features of the drug's structure resemble those of the biologically active thyroid hormone, triiodothyronine (T3). In addition, the drug has a variety of complex effects on thyroid hormone physiology, including a number of possible antagonistic effects on thyroid hormone function at the cellular level. The drug occasionally causes clinically overt hyperthyroidism and hypothyroidism. We review these effects and discuss their clinical implications.

Amiodarone↗
PubMed1990

Acid helix-turn activator motif.

A common sequence/structural motif pattern has been identified within the steroid/thyroid hormone receptors and other transcriptional activators using a new massively parallel symbolic learning assistant computer system. The pattern appears nearly diagnostic of transcription activation, including relative activation strength, among nuclear and DNA-binding prokaryotic proteins. In cases where mutation/deletion/chimeric studies have identified the activation domain, the pattern matches within that domain. These facts and the nature of the pattern itself strongly support the idea that the patterned domain is directly involved in a protein-protein transcription activation interaction.

Amino Acid Sequence↗
PubMed1988

SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene.

Monkey cells synthesizing SV40 large T antigen were lysed and the extracts immunoprecipitated with either monoclonal anti-T antibody or monoclonal antibody to p110-114, the product of the retinoblastoma susceptibility gene (Rb). T and p110-114 coprecipitated in each case, implying that the proteins are complexed with each other. Substitution and internal deletion mutants of T that contain structural alterations in a ten residue, transformation-controlling domain failed to complex with p110-114. In contrast, T mutants bearing structural changes outside of this domain bound to p110-114. These results are consistent with a model for transformation by SV40 which, at least in part, involves T/p110-114 complex formation and the perturbation of Rb protein and/or T function.

Animals↗
PubMed1988

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.

Acetyltransferases↗
PubMed1988

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.

Adult↗
PubMed1988

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.

Humans↗
PubMed1988

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.

Adenovirus Early Proteins↗
PubMed1987

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.

Acetyltransferases↗
PubMed1986

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.

Adaptation, Psychological↗
PubMed1979

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.

Animals↗