PubMed Health⌕ Search

Biomedical subjects

R Friis

Publications and source records attributed to R Friis.

At least 19 recordsLinked to original sources
PubMed2003

Role of DDC-4/sFRP-4, a secreted frizzled-related protein, at the onset of apoptosis in mammary involution.

Using differential display, we isolated DDC-4, a secreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the DDC-4/sFRP-4 cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3beta (GSK-3beta), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.

Animals↗
PubMed1998

Apoptosis-associated gene expression in the corpus luteum of the rat.

The involution of the corpus luteum (CL) at parturition is an example of physiological apoptosis, a complex process involving massive vascular regression while luteal cells undergo apoptosis. In the present study, changes in gene expression associated with physiological apoptosis were examined. Three genes isolated in our laboratory because of their association with apoptotic processes in the ovary, mammary gland, and prostate served as the focus of our investigation: Y81, Gas-1, and the gene IAP encoding integrin-associated protein. Y81 is a novel gene for which three transcripts are apparent. A Y81 cDNA clone representing the longest transcript has been isolated; it shows an open reading frame exhibiting a region of very high homology with members of the frizzled family, the prototypes of which are cell autonomous polarity genes encoding seven-pass transmembrane receptor proteins, for example the receptor for Wingless. Gas-1 is known as a growth-arrest gene that inhibits DNA synthesis when microinjected into cells. Integrin-associated protein is a beta 3-integrin-binding protein for which, recently, a thrombo-spondin-binding activity has been recognized. These three genes, all sharply up-regulated in the course of physiological involution processes in the ovarian CL, in mammary gland, and in prostate, seem promising candidates-by virtue of their specific expression in distinct tissues undergoing programmed cell death-as mediators of stimuli leading to apoptosis and subsequent phagocytosis. In this study, sulfated glycoprotein-2, previously observed in many instances of physiological apoptosis, was further employed as an indicator for incipient apoptosis, and stromelysin was followed as a marker for the tissue remodeling activity that is intimately associated with apoptosis during involution.

Amino Acid Sequence↗
PubMed1998

Review of social epidemiologic research on migrants' health: findings, methodological cautions, and theoretical perspectives.

The phenomenon of world-wide immigration and migration has major implications for the health of the migrants in addition to its impact upon social and other service providers. Studies of migrants that utilize social epidemiologic methods fall within the traditional boundaries of descriptive and analytic approaches; this article reviews some of the studies that exemplify these approaches. It then suggests specific methodological issues and cautions pertaining to research on migrants and provides a theoretical model for organizing the diverse research studies that have been conducted. By stimulating discussion regarding social epidemiologic research on migrants' health, this model is intended to serve as a compass point for future research and needed interventions.

Causality↗
PubMed1998

The role of home care in integrated delivery systems.

The health care field is moving rapidly toward integrated delivery systems (IDS). The role of home care in such system is unclear. This study seeks to describe the current status of home care in IDS and to examine health care administrators' perceptions about the importance of IDS components. A random sample of 1600 administrators was surveyed, 400 each from home care agencies, hospitals, nursing homes, and medical groups. Results reveal that hospitals lead integration, nursing homes are least involved, and home care agencies and medical groups fall in between. Administrator's opinions vary considerably about the importance of select services and integrating mechanisms.

Administrative Personnel↗
PubMed1997

DDC-4, an apoptosis-associated gene, is a secreted frizzled relative.

The differential display method has been used in our laboratory as a coincidence analysis to isolate genes expressed in common in each of three different rat tissues undergoing physiological apoptosis: mammary gland, ovarian corpus luteum and ventral prostate. The most interesting of these isolates, DDC-4, shows a clear association with apoptosis, its expression being confined to these three organs, and only during their involution. Using DDC-4 as probe, we screened a rat ovarian cDNA library to obtain full-length isolates. One isolate, Y81 clone 40, gives rise to a protein of approximately 40 kDa with coupled in vitro transcription/translation. Sequencing of this clone indicates an open reading frame of 1044 nucleotides encoding a protein of 39.7 kDa with a putative signal sequence. This clone exhibits a high homology with the cysteine-rich domain, i.e. the ligand-binding domain, of the fizzled gene family originally defined as tissue polarity genes in Drosophila. The homology of Y81 clone 40 is most extensive with the newly described secreted frizzled relatives, the frzb subfamily.

Amino Acid Sequence↗
PubMed1996

The health insurance status of US Latino women: A profile from the 1982-1984 HHANES.

OBJECTIVES: This research studied the correlates of health insurance status among three major subpopulations (Mexican, Puerto Rican, and Cuban) of adult (ages of 20 to 64) Latino women. METHODS: Data from the Hispanic Health and Nutrition Examination Survey (HHANES), 1982-1984, were examined to determine the percentages of health insurance coverage among the sample populations and to assess the relationship between access to coverage and selected sociodemographic employment/income, ancestry, and acculturation variables. RESULTS: Variations in health insurance coverage existed by Latina subpopulation. While Puerto Rican women had the highest percentage of any health insurance coverage, Mexican-origin women (particularly those 50 to 64 years old) had the lowest. For all three Latina groups, health insurance coverage was greater among those who reported a family income above the poverty level than among those whose income fell below the poverty level; employment location, acculturation variables, and ancestry were also related to coverage. CONCLUSIONS: Eligibility requirements, particularly for Mexican-and Cuban-origin women, need to be streamlined, and innovative health insurance programs need to be developed to increase access of Latinas to health insurance.

Acculturation↗
PubMed1993

c-myc gene activation as a permanent trait of RSV-infected quail cells.

A high level of c-myc gene expression was found to be a constant feature of v-src transformation. The c-myc gene product was analyzed in quail embryo cells transformed by different mutants of Rous sarcoma virus (RSV) that were temperature-sensitive with respect to various parameters of v-src function. The high-level expression of c-myc proved not to be temperature-sensitive: at both permissive (35 degrees C) and non-permissive (41 degrees C) temperatures, the same high levels of c-myc gene product were found for all RSV mutants tested. This result, in agreement with earlier evidence for a v-src-induced proliferative stimulus which was unaffected by ts mutants at the non-permissive temperature, shows that certain v-src functions have not yet been fully characterized.

Animals↗
PubMed1993

Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene.

Loss of histotypic organization of epithelial cells is a common feature in normal development as well as in the invasion of carcinomas. Here we show that the v-src oncogene is a potent effector of epithelial differentiation and invasiveness. MDCK epithelial cells transformed with a temperature-sensitive mutant of v-src exhibit a strictly epithelial phenotype at the nonpermissive temperature for pp60v-src activity (40.5 degrees C) but rapidly loose cell-to-cell contacts and acquire a fibroblast-like morphology after culture at the permissive temperature (35 degrees C). Furthermore, the invasiveness of the cells into collagen gels or into chick heart fragments was increased at the permissive temperature. The profound effects of v-src on intercellular adhesion were not linked to changes in the levels of expression of the epithelial cell adhesion molecule E-cadherin. Rather, we observed an increase in tyrosine phosphorylation of E-cadherin and, in particular, of the associated protein beta-catenin. These results suggest a mechanism by which v-src counteracts junctional assembly and thereby promotes invasiveness and dedifferentiation of epithelial cells through phosphorylation of the E-cadherin/catenin complex.

Animals↗
PubMed1992

Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells.

As a common characteristic of tumor cells, as well as of normal proliferating cells in the G1-phase of cell cycle, one finds constitutive high levels of all the glycolytic metabolites arising between glucose 6-phosphate and phosphoenolpyruvate. Thus, it is that the phosphometabolites fructose 1,6-bisphosphate, ribose 5-P, P-ribose-PP, NAD, GTP, CTO, UTP, UDP-glucose, glycerol 3-P, glycerol phosphocholine and glycerol phosphoethanolamine are useful in the 31P-nuclear magnetic resonance (NMR) detection of solid tumors in animals and man. This expansion of phosphometabolites is achieved during tumor formation as a result of reductions in levels of enzymes degrading phosphometabolites, owing to the decline in the glycerol 3-P hydrogen shuttle, and as a consequence of alterations in the glycolytic isoenzyme equipment. Tumor cells typically express a particular isoenzyme of pyruvate kinase called type M2 (K) at high levels. This isoenzyme is subject to a complex regulation by amino acids, by fructose 1,6-bisphosphate, and by hormonal- and oncogene-dependent phosphorylation. Pyruvate kinase type M2 is a substrate for the oncogene encoded PP60v-src-tyrosine kinase. A drastic decrease in the affinity for its substrate phosphoenolpyruvate found after transformation by the src-oncogene can be explained as a consequence of the phosphorylation of pyruvate kinase in serine and tyrosine. These phosphorylations induce the breakdown of tetrameric pyruvate kinase to the trimeric and dimeric forms. Unlike the tetrameric form, the dimeric form as a low affinity for phosphoenolpyruvate. Partial inactivation of pyruvate kinase and enolase on the one hand, and a hyperactivation of hexokinase and phosphofructokinase on the other hand, lead to an expansion of all metabolites. Only when these metabolites attain high levels, thereby assuring a sufficient supply of metabolites for RNA, DNA, lipid, and complex carbohydrate synthesis, can cell proliferation proceed. This accumulation of metabolites in the G1-phase cells has been termed a "metabolic budget system" because it senses not only the actual nutrient levels, but also the supply over a period of time. Monoclonal antibodies specific for the dimeric form of pyruvate kinase type M2 can be used for the immunohistological detection of tumor cells. The amount of the dimeric form in tumor cells closely correlates with the degree of malignancy and can be used for a nonspecific detection of tumors based on assays performed with patient's plasma.

Adenosine Triphosphate↗
PubMed1991

Establishment and characterization of two immortalized cell lines of the osteoblastic lineage.

Osteoblastic cells were cloned by culturing rat calvariae cells in agarose in the presence of TGF-beta and EGF. Two bone cell lines were established by immortalizing such an osteoblastic clonal cell population by the introduction of the avian v-mycOK10 gene in the form of a mouse ecotropic retrovirus. Although originating from the same clonal cell population, the two lines exhibited somewhat differing properties. IRC10/30-myc1 expressed alkaline phosphatase (AP), showed PTH- and PGE2-induced cAMP production, synthesized mainly collagen type I and a minor fraction of type III, and produced mRNA for the bone-specific protein osteocalcin. IRC10/30-myc3 did not express AP, showed no PTH responsiveness, and synthesized only about one-third as much collagen as IRC10/30-myc1 (4 versus 12% of total protein synthesis). However, the cell line IRC10/30-myc3 was induced to synthesize cAMP by PGE2 and produced osteocalcin mRNA. When cultured in vivo in diffusion chambers, both lines proved to be osteogenic. Besides bone, both lines also formed cartilage and fibrous tissue. Thus, by immortalizing a clonal cell population of the osteoblastic phenotype, cell lines expressing varying properties can emerge. Furthermore, the expression of alkaline phosphatase and PTH-inducible adenylate cyclase are not prerequisites for a cell to form bone in vivo. Finally, cells expressing the phenotype of differentiated osteoblasts, including osteocalcin synthesis, still have a multipotential differentiation capacity and form bone and cartilage in vivo.

Adenylyl Cyclases↗
PubMed1989

Exercise-induced silent ischemia: age, diabetes mellitus, previous myocardial infarction and prognosis.

The purposes of this study were 1) to determine the prognosis of silent ischemia in an unselected group of patients referred for exercise testing, and 2) to assess whether age or the presence of myocardial infarction or diabetes mellitus influences the prevalence of silent myocardial ischemia during exercise testing. The design was retrospective, with a 2 year mean follow-up period. The study group consisted of 1,747 predominantly male in-patients and outpatients referred for exercise testing at a 1,200 bed Veterans Administration hospital. The main result was that the mortality rate was significantly greater (p = 0.02) among patients with abnormal ST segment depression than in patients without ST depression. The presence or absence of angina pectoris during exercise testing was not significantly related to death. The prevalence of silent ischemia was not significantly different among patients categorized according to myocardial infarction or diabetes mellitus status, but was directly related to age. It is concluded that, in patients with an ischemic ST response to exercise testing, the presence or absence of angina pectoris during the test does not alter the risk of death. The prevalence of silent ischemia during exercise testing is not statistically different among patients with recent, past or no myocardial infarction or with insulin-dependent or noninsulin-dependent diabetes mellitus.

Age Factors↗
PubMed1989

Oncogene mediated repression of glucocorticoid hormone response elements and glucocorticoid receptor levels.

We have previously described the inhibition of glucocorticoid-dependent transcription from the mouse mammary tumor virus long terminal repeat promoter by products of the H-ras and v-mos oncogenes. We have studied the effects of conditional oncogenes on expression of glucocorticoid-dependent indicator genes. Expression of the glucocorticoid-dependent transcription of the tyrosine aminotransferase gene was monitored in FTO-2B rat hepatoma cells during Mr 21,000 protein (p21) H-ras induction. A strong transcriptional repression of the tyrosine aminotransferase gene followed p21 H-ras expression. The sequences in a glucocorticoid-dependent promoter which are responsible for the oncogene-mediated repression could be localized to the glucocorticoid response element; a construct in which a 15-base pair glucocorticoid response element was inserted 5' of the thymidine kinase promoter exhibited the oncogene-mediated repression of transcription. We observed a strong repression of glucocorticoid-dependent promoters and promoter constructs not only in the presence of p21 H-ras and p37 v-mos but also with p60 v-src. p57 v-myc, however, had no effect. Oncogene expression is not a sufficient prerequisite for an initial repression of glucocorticoid hormone-dependent gene transcription, since even in the presence of constitutively high levels of oncogene product a transient stimulation of glucocorticoid-dependent gene expression was found. Protein synthesis inhibition experiments revealed that no hormonally induced cellular protein is needed for the oncogene-mediated repression. It seemed reasonable that this phenomenon might reflect oncogene effects on the glucocorticoid receptor. We, therefore, made measurements of the glucocorticoid receptor protein. In the presence of glucocorticoid hormone the receptor translocated rapidly from the cytoplasm to the nucleus. In normal NIH 3T3 cells, after 24-h treatments the nuclear receptor levels had declined to about 50% of those determined at 2 h and in the presence of p21 H-ras they declined to 15%. The levels of cytoplasmic receptor were not affected by p21 H-ras expression.

Animals↗
PubMed1989

Optimal sampling interval to estimate heart rate at rest and during exercise in atrial fibrillation.

To investigate the ideal sampling interval for the estimation of heart rate (HR) at rest and during exercise in atrial fibrillation (AF), maximal exercise testing with continuous electrocardiographic acquisition was performed in 10 patients with chronic AF (mean age 66 +/- 4 years) and 10 subjects in normal sinus rhythm (mean age 31 +/- 6 years). Measurements of HR were obtained at 9 different sampling intervals (1, 2, 3, 6, 10, 15, 20, 30 and 60 seconds) at rest and 7 different sampling intervals (1, 2, 3, 6, 10, 15 and 20 seconds) during the last 30 seconds of each minute during exercise. The HR obtained from each interval was compared with true HR (determined by a 4-minute sample at rest and by the last 30 seconds of each minute during exercise). Among patients with AF, large differences were observed between the HR obtained and true HR, both at rest and during exercise, using small sampling intervals. The mean of these differences ranged between 16 +/- 11 beats/min (range 14 to 22) using 1-second sampling intervals and 2.2 +/- 2.0 beats/min (range 1.6 to 4.4) using 20-second sampling intervals during progressive exercise. Variability of the HR obtained from a given random sample was also high when short sampling intervals were used among patients with AF. These observations were contrasted by subjects in normal sinus rhythm, among whom neither variability nor measurement error were influenced remarkably by changing the sampling interval or increasing HR.

Adult↗
PubMed1989

Correlation between macrovascular disease as assessed by bioimpedance plethysmography and various parameters used to assess diabetic "control".

Blood flow in a segment of the leg was determined by bioimpedance plethysmography in 47 diabetic patients and in 19 normal volunteers. The blood flow through the limb, expressed as stroke volume/m2 (SV/m2), was not significantly different in the two populations. SV/m2 showed significant negative correlation with the presence of peripheral vascular disease, fasting serum cholesterol concentration, glycosylated hemoglobin (HbA1c) concentration, and the duration of diabetes. The presence or absence of retinopathy (27.7% of cases) or nephropathy (4.3% of cases) did not show strong association with the SV/m2. Neither the duration of the hypertension nor the systolic or diastolic blood pressure correlated significantly with blood flow in the extremity. These data suggest that only some of the parameters used to assess "control" of diabetic patients can be useful predictors of macrovascular as well as microvascular disease in diabetic patients.

Adult↗
PubMed1988

High-frequency electrocardiography: an evaluation of lead placement and measurements.

Before there is widespread clinical application of the high-frequency ECG, differences resulting from the leads used and the measurement criteria for late potentials must be resolved. Therefore 113 consecutive patients without resting QRS conduction abnormalities referred for Holter monitoring were studied. Four different lead systems were used: a standard bipolar orthogonal lead system and three bipolar lead systems mapping the left ventricle. Measurements made of late potentials included normal and high-frequency QRS duration, their difference, the duration of low-amplitude signals (less than 40 uV) in the terminal QRS, and the root mean square of the last 40 msec of the high-frequency QRS duration. We found that the left ventricular leads tended to give more abnormal measurements than the orthogonal system and that the various measurements failed to agree with each other. In addition, even in this population in which abnormalities of QRS conduction were excluded, the late potential measurements tended to be more abnormal as QRS duration lengthened. These differences in lead systems and measurement criteria must be considered when clinically applying information regarding late potentials measured from the high-frequency ECG.

Adult↗