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R N Re

Publications and source records attributed to R N Re.

At least 19 recordsLinked to original sources
PubMed2001

In vitro evidence for an intracellular site of angiotensin action.

To differentiate the relative effects of nuclear and cell surface angiotensin II (Ang II) receptors, we mutated the angiotensinogen cDNA by removing the signal sequence-encoding region to produce a nonsecreted form of angiotensinogen [Ang(-S)Exp]. Rat hepatoma cells (which produce renin and angiotensin-converting enzyme mRNAs) were stably transfected with Ang(-S)Exp/pSVL (or a corresponding control) expression plasmid, and mitotic indices were measured for stably transfected cell lines. Experimental clonal cell lines demonstrate an average of 33+/-4.4% (P<0.001) increase in percentage-labeled nuclei compared with control cell lines. The mitogenic effect is blocked by 10(-6) mol/L losartan and by 1 micromol/L renin antisense phosphorothioate oligomers but not by 10(-6) mol/L candesartan. In addition, phenylarsine oxide, which blocks angiotensin receptor internalization, abolishes the losartan inhibitory effect, suggesting that after cell-surface receptor-mediated endocytosis, losartan blocks Ang II nuclear receptors. PDGF mRNA levels are elevated 2.2-fold in Ang(-S)Exp transfected cell lines; addition of anti-PDGF antibodies to the culture medium partially blocks the mitogenic effect of Ang(-S)Exp, while anti-Ang II antibodies have no effect. These results suggest that the Ang(-S)Exp growth effect is due, in part, to autocrine/paracrine stimulation by secreted PDGF after Ang II/Ang II receptor intracellular interactions. We further demonstrate that these cells produce the alternative renin transcript, renin 1A, which apparently lacks a signal sequence and is maintained intracellularly. Collectively, these studies of cultured cells suggest that some cell types may possess components of the renin-angiotensin system that permit intracellular processing of angiotensinogen to Ang II and that Ang II generated intracellularly may be mitogenic.

Alternative Splicing↗
PubMed2001

Testing efficacy with detection controlled estimation: an application to telemedicine.

Detection controlled estimation (DCE) is a powerful new econometric estimator in the family of missing data estimators. By collecting measures from a variety of inspectors or inspection technologies, DCE is able to make inferences about the entire population, even when that population is not directly observed. Using this innovative method, we were able to assess whether telemedicine technology could be substituted for in-person visits when providing maintenance care for patients with hypertension. Our findings indicate that there is no support for the proposition that telemedicine is less effective than in-person visits for determining whether patients have high blood pressure. Indeed, our results imply that telemedicine misses 7% fewer cases of high blood pressure than in-person visits do. The results of this study indicate that DCE may be an effective tool for use in cost-effectiveness or cost-benefit analysis in health care.

Aged↗
PubMed2001

The clinical implication of tissue renin angiotensin systems.

The presence, and in many cases the regulated synthesis, of components of the renin-angiotensin system have been demonstrated in multiple tissues, indicating the existence of tissue angiotensin-generating systems. These vary with respect to which renin-angiotensin system components are synthesized locally and which are taken up from plasma. Enzymes unrelated to the classical renin-angiotensin system may also contribute to tissue angiotensin synthesis. However, based on the available data, the prevailing opinion that kidney-derived renin is in all cases the only physiologically relevant renin in tissues must be revised. Also there is evidence indicating a role for tissue angiotensin systems in the pathogenesis of cardiovascular disease and in cardiovascular structural remodeling. The angiotensin-regulated synthesis of aldosterone in cardiac tissue has been described, suggesting the possibility that a renin-angiotensin-aldosterone system exists in the heart. In addition, intracellular (intracrine) sites of angiotensin action have been reported. Some of these findings have implications for therapeutics and, in particular, for the use of angiotensin converting-enzyme inhibitors and angiotensin receptor blockers. Finally, tissue angiotensin systems outside the cardiovascular system also appear to be physiologically relevant.

Blood Vessels↗
PubMed2001

Patient and physician satisfaction in a clinical study of telemedicine in a hypertensive patient population.

We studied patient and physician satisfaction with telemedicine for the care of a hypertensive population. Once recruited, participants were seen both in person and via telemedicine (in random order) on the same day. After each meeting, patient and physician satisfaction surveys were completed. In the 12-month study, there were 107 pairs of visits. The physicians reported a small but significant increase in workload, mental effort, technical skills and visit duration for telemedicine when compared with face-to-face consultations. They noted that the telemedicine system worked well in the majority of cases and could reduce the need for future treatment. Patients reported slightly but significantly higher satisfaction scores for the following for in-person than for telemedicine meetings: technical quality, interpersonal care and time spent. Patients reported high satisfaction scores for both telemedicine and in-person visits.

Aged↗
PubMed2001

The effect of education on patients' willingness to participate in a telemedicine study.

We assessed the effect of previous education on patients' willingness to participate in a clinical study of telemedicine for hypertensive patients. The design was a cross-sectional study of adult patients arriving for appointments in a hypertension clinic. Of the 259 patients approached, 86% completed a baseline survey and were subsequently asked if they would be willing to participate in a one-year telemedicine study. One hundred and fifty patients (58%) agreed to participate. A stepwise logistic regression analysis was performed to assess the effect of level of education on willingness to participate, while controlling for potentially confounding variables. In the final model, only education remained significant. The odds ratio for non-participation of patients with high-school education or less was 3.6 (95% confidence interval 1.9-7.0). Educational status should be carefully considered when designing, implementing and interpreting telemedicine studies.

Aged↗
PubMed1999

Effects of chromosomal integration site upon p53 interactions with DNA consensus sequence homologies.

In the present study, we report that, despite the presence of one perfect p53 consensus sequence homology (designated SCL CS) and four half-sites within the 3'-untranslated region of the stem cell leukemia (SCL) gene, the native endogenous gene is not regulated by p53. We employ a tet-repressible system to show that, under conditions in which the WAF1 mRNA steady-state level is upregulated fourfold by p53, the SCL mRNA level is not altered. In a previous report, we demonstrated that p53 interactions with the SCL CS can upregulate downstream reporter gene activity 43-fold in transient reporter assays. This disparity prompted us to explore the differences between p53 regulation of SCL CS activity in organized (chromosomally integrated) and disorganized (non-replicating episomal plasmid) chromatin. We show that p53 can increase (between 3-80-fold), decrease (between 5-33-fold) or have no effect upon transactivation of an SCL CS/reporter fusion gene depending upon chromosomal integration site. Most studies used to characterize p53 binding sites employ transient transfection assays. Our results suggest that characterization of consensus sequence homologies by assay of transiently transfected cells may be inaccurate.

3' Untranslated Regions↗
PubMed1997

Renin-angiotensin system: genes to bedside.

Atherosclerosis and its vascular sequela are responsible for considerable morbidity and mortality rates. Several risk factors have been implicated in the pathogenesis of atherosclerosis, and the search for other risk factors continues on the medical horizon. Renin-angiotensin system (RAS), a multienzyme, multilocale axis, has been extensively studied as an important mediator of atherosclerosis. Recently, the tissue-based angiotensin system has been suggested as the most significant pathway of RAS. A genetic polymorphism in the human gene for the angiotensin-converting enzyme (ACE), one of the two enzymes of RAS, has been found to have a strong association with higher risk for acute coronary events, sudden cardiac death, vascular restenosis after angioplasty, and idiopathic and hypertrophic cardiomyopathy. Clinical and animal data support angiotensin II to be the final common pathway in the enzyme cascade of RAS and ACE as the key enzyme in the generation of Angiotensin II. ACE gene polymorphism appears to modify expression of cellular and free ACE levels and could represent a genetic marker for cardiovascular disease.

Angioplasty, Balloon, Coronary↗
PubMed1997

The application of molecular genetic techniques to the study of hypertensive diseases.

The techniques of modern molecular genetics are shedding new light on hypertension and its sequelae. This article discusses techniques which have identified genes associated with hypertension and have pointed the way toward identifying the full cohort of genes operative in all forms of human hypertension. These techniques have expanded understanding of the pathophysiology of hypertension as well as its prevention.

Humans↗
PubMed1996

Adenovirus-mediated in vivo gene transfer in a rabbit model of allograft vasculopathy.

BACKGROUND: The long-term success of heart transplantation continues to be in jeopardy because of the development of accelerated vascular myointimal proliferation. Transfer of genes encoding products that can modulate the adverse consequences of phenomena that cause myointimal proliferation, into the allograft vessel wall, may modify these pathologic processes. The purpose of this study was to assess the feasibility of gene transfer and to evaluate the duration of gene expression in a rabbit heterotopic aortic transplant model of allograft vasculopathy. METHODS: The abdominal aortas of 32 outbred New Zealand rabbits were harvested and cross-sectionally bisected (n = 64). Six donor and recipient animals were used in a preliminary study to examine neointimal proliferation without accompanying gene transfer. Of the remaining 26 rabbits (52 allografts), one half of each allograft aorta was administered a control solution, while the other half was incubated with a replication-defective, recombinant, adenoviral vector-encoding, cytomegalovirus promoter-regulated beta-galactosidase. After a 20-minute incubation period, bilateral aorto-carotid transplantations were performed in 26 recipient rabbits. All animals received cyclosporine immunosuppression (10 mg/kg/day subcutaneously). The allografts were harvested at 3, 7, 10, 21, and 28 days after transplantation and assayed for beta-galactosidase activity. RESULTS: Neointimal areas showed an initially slow increase for the first 10 days, followed by a rapid increase up to 21 days, and tended to plateau thereafter. Significant beta-galactosidase was apparent in aortic sections dissected from host rabbits for all time points, except at 28 days. At the 21-day time point, the aortic section from one rabbit was positive, whereas the other two remained negative. However, the one positive section showed intense beta-galactosidase activity, suggesting variability in the experimental model. At 28 days, all aortic sections were negative. CONCLUSIONS: Our findings confirm that genes delivered by this method are expressed for the duration of early rapid intimal proliferation in this heterotopic rabbit model of aortic allograft vasculopathy. These findings suggest that this animal model can be used to assess the therapeutic potential of gene transfer at the time of vascular transplantation and may provide a novel therapeutic approach to prevent or ameliorate the genesis of allograft vasculopathy.

Adenoviruses, Human↗
PubMed1994

Predicting work status for patients in an occupational medicine setting who report back pain.

OBJECTIVE: To determine the ability of patient-reported health status information to predict physician-determined fit-for-work status for patients reporting complaints of low back pain. DESIGN: Cross-sectional study using survey methods. SETTING: Occupational medicine section of a large multispecialty private clinic. PATIENTS: Four hundred sixty-two questionnaire packets were distributed to patients who were seen for work-related conditions or disorders over a 13-week period; 235 questionnaires were returned (51% response rate). One hundred seven responders reported low back pain and completed the Low Back Pain TyPE (Technology of Patient Experience) Tool. The mean (+/- SD) age of respondents was 39 (+/- 12) years; 67% of respondents were male, 70% were white, 87% were receiving worker's compensation, 58% were married, and 55% had a high school education or less. INTERVENTIONS: Questionnaire packets for self-administration containing health/functional status questions (short form [SF]-36, COOP Charts) and the Low Back Pain TyPE Tool were distributed to the patients. Other variables were abstracted from the medical records and administrative databases. MAIN OUTCOME MEASURES: The primary study outcome measured was fitness for work; patients were examined and categorized as fit or not fit for work by physicians who were unaware of the questionnaire results. RESULTS: Logistic regression analysis consisted of variables from 107 patients who reported low back pain. The final model contained the physical functioning scale (SF-36), employment status, smoking status, and physical functioning (SF-36) by gender interaction. Seventy-seven percent of the fit-for-work cases and 90% of the not-fit-for-work cases were correctly classified. CONCLUSION: Patient-reported physical function (as modified by gender), smoking status, and employment status predicted physician-determined work status for patients reporting low back pain in this study. Larger studies will be required to confirm this finding.

Adult↗
PubMed1994

ACE inhibitor-mediated attenuation of mesangial cell growth. A role for endothelin.

Endothelin modulates human mesangial cell (HMC) proliferation in response to angiotensin II (Ang II). Angiotensin converting enzyme inhibitors (ACEIs) have variable effects on HMC growth depending on culture conditions. No studies, however, have investigated the effects of ACEIs on HMC production of endothelin-1 in either actively proliferating or quiescent HMCs. The present study was designed to evaluate the effects of ACEIs on HMC-associated mitogenesis, cell counts, and endothelin-1 production in the presence and absence of insulin in both quiescent and proliferating HMCs. It tests the hypothesis that ACEIs attenuate HMC growth through a reduction in HMC-associated endothelin-1 generation. The effects of four different ACEIs, an Ang II receptor antagonist, losartan, and a monoclonal antibody to endothelin-1 were evaluated. ACEIs inhibited HMC mitogenesis and cell counts in proliferative but not quiescent cells. This was due to the absence of ACE activity in HMCs and its presence in 10% fetal calf serum. Both ACEIs and losartan reduced endothelin-1 production per cell. Compared to vehicle, losartan reduced the amount of endothelin-1 in conditioned media to a greater extent than any ACEI (2.2 +/- 0.3, captopril v 1.9 +/- 0.5, quinaprilat v 3.8 +/- 0.3 delta pg/cell x 10(-3) endothelin-1, losartan; P < .05). Moreover, insulin potentiated the antimitogenic effects of both ACEIs and losartan on HMCs. Lastly, the attenuated increase of endothelin-1 in conditioned media and associated antimitogenic effect on HMCs with losartan alone was not potentiated by the addition of any ACEI to losartan. These data provide indirect evidence that Ang II production may occur in culture media when both its precursors and a sufficient amount of converting enzyme activity are present. This is predicated on the observation that HMCs lack ACE activity and that ACEIs blunt mitogenesis of proliferating HMCs. The kinetics of this reaction, as well as the mechanism of how insulin potentiates the antimitogenic effects of ACEIs, were not studied.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Health status assessment in a hypertension section of an internal medicine clinic.

The authors obtained health status instrument information with the SF-36 and COOP charts distributed in random order (along with selected items from the Hypertension Technology of Patient Experience [TyPE] tool) to patients attending the hypertension section of an internal medicine clinic. The goal was to examine and compare potential associations of clinical, demographic, and/or treatment variables with SF-36/COOP health status scale variables in a nonuniversity urban clinic. One hundred fifty-eight pairs of health status instruments were returned (62% response rate). One hundred (64%) had a diagnosis of hypertension, 81 (51%) were males, 94 (60%) were older than 65 years, and 122 (78%) were white. Clinical, demographic, and treatment measurements were studied using regression analysis; the estimated regressions accounted for 4-32% of the variation in the COOP scales and 8-19% in the SF-36 scales. The number of coexisting diseases, gender, and diagnosis of hypertension were the most frequent significant variables associated with health status scale outcomes for each health status instrument. For most COOP and some SF-36 scales, there was a significant hypertension by gender interaction indicating that women with a hypertension diagnosis report better health status than women seen for other conditions; hypertension diagnosis had little effect on men's reported health status for most scales. Further study is necessary to confirm these results, yet the regression models developed in this study suggest that health status as assessed by these instruments is affected by multiple and not always obvious factors.

Aged↗
PubMed1993

Expression of viral T-antigen in pathological tissues from transgenic mice carrying JC-SV40 chimeric DNAs.

Immunostaining methods were used to detect viral T-antigen and the cellular protein p53 in pathological tissues obtained from transgenic mice carrying JC-SV40 hybrid viral DNAs. A transgenic mouse carrying the SV40 regulatory region and JC virus (JCV) T-antigen-coding sequences exhibited an SV40-characteristic choroid plexus papilloma that expressed JCV T-antigen and p53. JCV-associated pathology was observed in two other mice in which the JCV regulatory signals directed SV40 T-antigen-induced adrenal neuroblastomas and brain neoplastic cells. However, these mice also exhibited an SV40-characteristic osteosarcoma and abdominal lymphoma that contained SV40 T-antigen and p53-positive cells. Contrasting thymic pathology was observed in the two types of mice where the SV40 regulatory region directed a JCV T-antigen-induced thymoma in one mouse, and the JCV regulatory region directed SV40 T-antigen-induced thymic hypoplasia in two other mice.

Adrenal Gland Neoplasms↗