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Biomedical subjects

R A Phillips

Publications and source records attributed to R A Phillips.

At least 37 records · Page 2Linked to original sources
PubMed2000

The effects of various definitions of dipping and daytime and night-time on the characterization of 24 h profiles of blood pressure.

BACKGROUND: Ambulatory blood pressure monitoring allows characterization of the patient's average blood pressure load as well as various profiles of blood pressure. Results from clinical studies suggest that dippers (patients whose blood pressures decrease during night-time) have a lower risk of cardiovascular events than do nondippers with similar daytime blood pressures. However, the definitions of dipping as well as of daytime and night-time vary among clinical studies. OBJECTIVE: To determine whether various definitions lead to markedly different classifications of dipper status. DESIGN AND METHODS: We analyzed 894 24 h ambulatory blood pressure recordings that had been performed at our institution according to three previously published definitions of daytime and night-time and five definitions of dipping. RESULTS: There were small but statistically significant differences among the mean daytime and night-time blood pressures determined using the various definitions. Likewise, the proportions of dippers varied significantly with definitions of dipping and of daytime and night-time. CONCLUSIONS: Differences among definitions of dipping as well as of daytime and night-time lead to significant variations in the characterization of patients' 24 h blood blood pressure profiles. The results of this analysis can be used when comparing the results of clinical studies as well as in their design.

Adult↗
PubMed1999

Nuclear localization conferred by the pocket domain of the retinoblastoma gene product.

The tumor suppressor Rb is a nuclear phosphoprotein that controls cell growth and differentiation by modulating the activity of certain transcription factors. Transport of Rb to the nucleus is affected by both a bipartite nuclear localization signal (NLS) in the C-terminus of the protein and a central domain, termed A/B or pocket, through which Rb interacts with transcription factors and viral oncoproteins. Mutations in either the A or B subdomains of the pocket render a NLS-deficient Rb completely cytoplasmic. Fusing the A/B domain of Rb to the Escherichia coli beta-galactosidase, to create betagal-A/B, confers nuclear localization upon this bacterial protein. Moreover, co-expression with the adenovirus oncoprotein, E1A, further augments nuclear localization of betagal-A/B. These findings provide direct evidence that the pocket domain of Rb is not only required but also sufficient to induce nuclear transport by a 'piggyback' mechanism. Thus, nuclear localization of Rb is dictated by two independent and autonomous domains: (i) the bipartite NLS and (ii) the pocket domain. We suggest that via these domains, Rb chaperons and co-compartmentalizes with its associated factors and preempts their activity prior to nuclear transport.

3T3 Cells↗
PubMed1999

Cumulative effect of phosphorylation of pRB on regulation of E2F activity.

The product of the retinoblastoma susceptibility gene, pRB, is a nuclear phosphoprotein that controls cell growth by binding to and suppressing the activities of transcription factors such as the E2F family. Transactivation activity is inhibited when E2F is bound to hypophosphorylated pRB and released when pRB is phosphorylated by cyclin-dependent kinases (CDKs). To determine which of 16 potential CDK phosphorylation sites regulated the pRB-E2F interaction, mutant pRB proteins produced by site-directed mutagenesis were tested for the ability to suppress E2F-mediated transcription in a reporter chloramphenicol acetyltransferase assay. Surprisingly, no one CDK site regulated the interaction of pRB with E2F when E2F was bound to DNA. Instead, disruption of transcriptional repression resulted from accumulation of phosphate groups on the RB molecule.

Animals↗
PubMed1999

Effect of long-term eprosartan versus enalapril antihypertensive therapy on left ventricular mass and coronary flow reserve in stage I-II hypertension. Eprosartan Study Group.

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200-300 mg b.i.d.) or enalapril (5-20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 +/- 0.3 and a decrease in CFR in the enalapril group to 1.3 +/- 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.

Acrylates↗
PubMed1999

Hypertension: setting new goals for lower readings.

Mean systolic blood pressures increase and mean diastolic pressures decrease with aging, primarily in response to the stiffening of blood vessels. These trends are related to the interplay of genetic factors that control renal, vascular, and hormonal functions. The prevalence of hypertension and the rate of blood pressure control vary among population groups; only one-fourth (24%) of all Americans with hypertension are controlled. Some persistent myths about hypertension may interfere with its diagnosis and treatment. Other barriers to control appear to be the side effects and cost of medications. Control rates improve when physicians increase their emphasis on patient education.

Aged↗
PubMed1999

Hypertension: therapeutic approach to weight loss, exercise, and salt intake.

Ideal body weight is difficult to achieve, but losing 10 lbs may be beneficial in controlling high blood pressure. Patients are more likely to exercise if they enjoy the activity, establish a routine, and exercise with a friend. Older Americans consume a lot of processed foods, the source of 80% of dietary salt. Most older African-Americans, especially those with obesity and type 2 diabetes, are salt-sensitive. Four steps to successful patient education are: 1) tell patients their blood pressure readings; 2) tell them about their medications and potential side effects; 3) provide culturally-sensitive printed materials; 4) use video tapes to educate all new patients and those with compliance problems.

Aged↗
PubMed1999

Hypertension: how comorbid disease influences the choice of therapy. Part 4 of a roundtable discussion.

Two categories of comorbid conditions affect the choice of therapy for hypertension: compelling indications, where outcomes data show improved survival, and indications where therapies may be beneficial but do not affect survival. In patients with diabetes, low-dose diuretics effectively lower blood pressure, but metabolic derangements may occur. A diuretic may exacerbate urinary incontinence and therefore may not be a first-choice therapy for some older women. Monotherapy is not effective in controlling blood pressures in patients with renal insufficiency. In patients with a history of MI, even those age 85 and older benefit from beta blockade. Lowering blood pressure over a 3- to 5-year period is effective in preventing left ventricular hypertrophy and congestive heart failure.

Aged↗
PubMed1999

Sex difference in response of blood pressure to calcium antagonism in the treatment of moderate-to-severe hypertension.

BACKGROUND: The pressor response to examination in the clinic setting is called the 'white coat effect' (WCE). This response may be a confounder when investigators use clinic blood pressure as a measure of response to antihypertensive therapy. OBJECTIVE: ;To study the effect of the pressor response by evaluating the sex-specific effect of treatment with calcium antagonism on blood pressure measured in the clinic and by ambulatory blood pressure monitoring (ABPM). METHODS: Untreated hypertensive subjects (n=39) with seated clinic diastolic blood pressures (DBP) > or = 100 and < or = 130mmHg were studied. Same-day clinic systolic blood pressure (SBP) and ambulatory SBP were obtained after 1 week of placebo, and after 1 month of treatment with either nifedipine or verapamil in a randomized, blinded, parallel trial. RESULTS: With placebo, women s average SBP was 18+/-;4mmHg lower than clinic SBP. By contrast, men s average SBP with placebo was 4+/-15mmHg lower than clinic SBP. There was a significantly greater reduction in clinic SBP for women than there was for men after 1 month of treatment (by 33+/-13 versus 18+/-18mmHg, P<0.005). However, reduction in ambulatory SBP after 1 month was the same for both sexes (20+/-11 versus 19+/-12mmHg). CONCLUSIONS: In this study of moderate-to-severe hypertensives, the large WCE measured for women, which markedly diminished with treatment, accounts for the observed sex difference in response of clinic SBP to calcium antagonism. By contrast, with ABPM there was an equivalent response to treatment for both sexes. Use of ABPM could be a valuable means of eliminating the WCE as a confounder in clinical research.

Blood Pressure↗
PubMed1998

Midwall fractional shortening is an independent predictor of left ventricular diastolic dysfunction in asymptomatic patients with systemic hypertension.

Conventional measures of left ventricular (LV) systolic performance suggest that diastolic dysfunction precedes the development of systolic dysfunction in hypertension. Midwall fractional shortening is a new measure of systolic function that identifies hypertensive patients who have evidence of target-organ damage, impaired contractile reserve, and increased mortality. We therefore sought to determine whether depressed midwall fiber shortening is associated with abnormal diastolic function. Echocardiograms were obtained in 102 otherwise healthy hypertensive patients without treatment with normal conventional measures of systolic function. Of these, 15 had depressed midwall shortening based on previously described normative relations. Patients with depressed midwall shortening had slightly higher blood pressure. Abnormal diastolic function, defined as late (A) LV inflow velocity greater than early (E) velocity, was observed in 33% of those with normal midwall shortening but in 60% of those with depressed shortening (p <0.05). Patients with A/E >1 had lower absolute midwall fiber shortening (15 +/- 3% vs 18 +/- 3%, p <0.0001) but similar endocardial shortening. Patients with abnormal midwall shortening had higher A/E and longer isovolumic relaxation times (both p <0.05). In multivariate analysis, midwall fractional shortening, age, and heart rate were independent predictors (p <0.01) of A/E in a model including blood pressure, LV mass, and endocardial shortening. We conclude that subnormal midwall shortening predicts LV diastolic abnormalities in this population of hypertensive patients with otherwise normal measures of LV systolic function. Contrary to our previous understanding, depressed LV systolic performance, when identified with this newer method, occurs coincidentally with impaired diastolic function.

Adult↗
PubMed1998

Resting diastolic function and left ventricular mass are related to exercise capacity in hypertensive men but not in women.

We evaluated the impact of diastolic function and gender on exercise capacity in sedentary, untreated hypertensive subjects (34 men, 23 women) using echocardiography and a bicycle ergometry with measurement of oxygen consumption (VO2). In men, peak (A) mitral inflow velocity and left ventricular (LV) mass were inversely related to peak VO2 (r = -0.64) and maximal workload (r = -0.57) and were the sole independent determinants of exercise capacity. In women, there was no relationship between any echocardiographic measure and exercise capacity. Thus, LV mass and Doppler-determined diastolic function predict maximal VO2 in hypertensive men but not in women. This finding may be related to gender differences in the contribution of diastolic filling to exercise capacity or may reflect limitations of resting Doppler echocardiography to predict exercise diastolic filling in hypertensive women.

Adult↗
PubMed1998

Relation among left ventricular mass, insulin resistance, and blood pressure in nonobese subjects.

Because left ventricular (LV) mass (LVM) is a powerful predictor of future cardiovascular events, it is important to identify hemodynamic and nonhemodynamic factors that increase LVM. We studied the separate contribution to LVM of daily arterial blood pressure (BP) and insulin resistance in a consecutive series of 29 (mean+/-SD age, 43+/-13 yr) nonobese (body mass index, 24+/-1.8 kg/m2), nondiabetic, glucose-tolerant subjects with untreated borderline or mild hypertension. The insulin sensitivity index (SI) was quantitatively determined from the frequently sampled iv glucose tolerance test. BP was characterized by ambulatory 24-h BP monitoring, and LVM index (LVMI) was determined by two-dimensional directed M-mode echocardiography. LVMI was directly related to 24-h mean BP (r=0.47; P=0.01). LMVI was also significantly related to Si (r=-0.43; P=0.02). In this nonobese group, neither LVMI nor Si was related to body mass index or age. After adjustment for the influence of BP on LVMI, a significant relation remained between LVMI and Si (P < 0.05). We conclude that in nonobese subjects with high normal BP, insulin sensitivity is related to LVM independently of BP and may be an important modulator of LV growth. In addition to a reduction of arterial BP, optimal prevention of LV hypertrophy in hypertensives may require improved insulin sensitivity.

Adolescent↗
PubMed1997

The retinoblastoma gene family is differentially expressed during embryogenesis.

We report differential expression of the RB1 tumor suppressor gene and the homologous genes p107 and p130 during embryogenesis. Abundant RB1 transcripts were detected during neurogenesis, hematopoiesis, myogenesis, lens development and in the ganglion cell layer of the embryonic retina, prior to and during differentiation. The expression pattern of RB1 mirrored the defects in RB1 mutant mice (RB-/-). In the heart, lung, kidney and intestine, p107, but not RB1, was expressed. In the liver and the central nervous system p107 and RB1 were co-expressed, consistent with the accelerated cell death observed in RB-/-; p107-/- double knock-out mice. In the central nervous system, p107 expression was restricted to proliferating cells surrounding the ventricles, while RB1 was expressed in areas of both proliferating and differentiating cells. In contrast to RB1 and p107, expression of p130 was low throughout embryogenesis. In situ hybridization and Western blot analyses showed that the expression of p107 and p130 was not markedly altered in RB-/- embryos compared to control littermates. Our results suggest that members of RB1 gene family have distinct, but overlapping roles in embryogenesis, with p107 and RB1 possibly having redundant functions in the central nervous system and liver.

Animals↗
PubMed1997

Ambulatory blood pressure monitoring for detecting the relation between angiotensinogen gene polymorphism and hypertension.

Compared to office measurements, ambulatory monitoring is a more accurate method of blood pressure (BP) characterization and may therefore be useful in a genetics study of hypertension. We studied the relation between the M235T polymorphism of the angiotensinogen gene and hypertension using office and ambulatory (BP) measurements. We enrolled untreated subjects (33 men and 17 women) who were referred for evaluation of office BP >140/90 mm Hg on at least two separate occasions. The M235T genotypes of the angiotensinogen gene were determined by polymerase chain reaction (PCR) amplification of DNA extracted from peripheral blood leukocytes and digested with BSTU1. The distribution of the genotypes were MM = 0.22, MT = 0.44, TT = 0.34. Based on office measurements, a significant difference in diastolic blood pressure (BP) was detected only between the TT and the MT genotype subjects (office BP: MM = 150 +/- 25/97 +/- 13 mm Hg, MT = 147 +/- 23/ 95 +/- 13 mm Hg, TT = 161 +/- 25/104 +/- 15 mm Hg). By contrast, with ambulatory BP monitoring, both systolic and diastolic blood pressures were significant higher in TT versus MM and MT (ambulatory BP, MM = 138 +/- 10/88 +/- 9 mm Hg, MT = 141 +/- 15/89 +/- 11 mm Hg, TT = 152 +/- 18/97 +/- 12 mm Hg). Covariate analysis revealed an independent relationship between the M235T genotype and systolic, diastolic, and mean ambulatory BP. Ambulatory monitoring improved the analytic power of our study and allowed detection of a clear and consistent relationship between angiotensinogen polymorphism and hypertension with a relatively small sample size.

Adult↗
PubMed1997

Expression patterns of the E2F family of transcription factors during mouse nervous system development.

The E2F family of transcription factors consists of two subgroups termed E2F and DP. E2F is required for cell proliferation, and is necessary for fruit fly development. E2F activity is a target for regulation by the retinoblastoma gene family, which includes pRB, p107 and p130. Mutant RB-/-, RB-/-:p107-/- and p107-/-:p130-/- mice develop abnormally, probably as a result of dysregulation in the activity of E2F, indicating the importance of E2F in mammalian development. To investigate the role of E2F in murine development, we have examined the patterns of expression of E2F-1 through E2F-5, and DP-1 in the developing nervous system by in situ hybridization. E2F-1, E2F-2 and E2F-5 are first detected in the 9.5 days post-coitus (dpc) forebrain. Expression of these E2F forms extends caudally thereafter and includes the developing brain and the upper half of the 10.5 dpc spinal cord. By 11.5 dpc, these E2F factors are expressed throughout the central nervous system. In 12.5 dpc embryos, E2F-1, E2F-2 and E2F-5 are highly expressed in proliferating, undifferentiated neuronal precursors. As neurons differentiate and migrate to the outer marginal zones in the nervous system, expression of these E2F members is extinguished. In the developing retina, another neuronal tissue, E2F-1 expression is also confined to the proliferating, undifferentiated retinoblastic layer. In contrast, E2F-3 expression is up-regulated as retinoblasts differentiate into the ganglion cell layer. In non-neuronal tissues, high E2F-4 transcript levels are present in regions corresponding to proliferative chondrocytes, whereas E2F-2 and E2F-4 transcripts are very abundant in the thymic cortex, which contains immature thymocytes. We conclude that individual E2F forms are differentially regulated during the development of distinct tissues, and especially during neuronal development.

3T3 Cells↗