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PubMed1995

Clinical acceptability of ACE inhibitor therapy in mild to moderate hypertension, a comparison between perindopril and enalapril.

The aim of this 3-month double-blind study was to assess the antihypertensive effect and acceptability of perindopril in comparison with enalapril in patients with mild to moderate essential hypertension. After a 4-week placebo run-in period, 161 patients with supine diastolic blood pressure (DBP) between 95 and 115 mmHg were randomized to receive perindopril 4 mg or enalapril 10 mg once daily. If supine DBP was higher than 90 mmHg, treatment was adjusted monthly, first by doubling the dose and then by addition of hydrochlorothiazide 12.5 mg. After 3 months of active treatment the decrease in supine and standing blood pressures was statistically significant within both groups but was not statistically different between groups. The percentage of patients (65%) who achieved supine DBP of < or = 90 mmHg in the perindopril group was not significantly different from the enalapril group (73%). Monotherapy resulted in control of supine DBP in 56% of the perindopril group and 58% of the enalapril group; the addition of hydrochlorothiazide resulted in control of supine DBP in 6% and 15% respectively. The number of withdrawals for adverse events was statistically significant between groups (0 in the perindopril group and 7 in the enalapril group, p = 0.01). During active treatment the most frequently reported complaints were headaches and cough; there was not statistically difference between groups. Changes in laboratory parameters were minor and not significantly different between the two groups except for serum glucose, potassium, and triglyceride levels. In conclusion, there was no significance between perindopril and enalapril in terms of efficacy. Clinical acceptability seems to be better in the perindopril group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Simultaneous pharmacodynamic modeling of the non-steady-state effects of three oral doses of 1,3-glyceryl dinitrate upon blood pressure in healthy volunteers.

The organic nitrate 1,3-glyceryl dinitrate (1,3-GDN) is one of the primary dinitrate metabolites of the antianginal agent nitroglycerin (GTN). Investigational New Drug Approval was sought to administer oral solution doses of 1,3-GDN to a small number (n = 3) of healthy volunteers; each subject receiving three doses at 1.2, 2.4, and 3.6 mg. With volunteers confined to a semirecumbent posture for the duration of each treatment (4-hr period postdose), diastolic blood pressure (DBP) was recorded and plasma samples collected for 1,3-GDN concentration analysis. Appreciable concentration-related decreases in DBP were observed, with maximal decreases from predose baseline values approximating 11 to 25 mm Hg. For each subject parametric pharmacodynamic modeling was performed with simultaneous analysis utilizing the DBP vs. time data from all three doses; an inhibitory Emax pharmacodynamic model was adopted. The temporal relationship between plasma 1,3-GDN concentrations and DBP displayed rapid equilibration. For subjects 1, 2 and 3, respectively, Emax was predicted as 12.9, 23.4, and 29.7 mm Hg, representing 21.5, 31.6, and 39.5% decreases in DBP from predose baseline values; plasma concentrations at half Emax (C50) were 2.75, 2.43, and 5.93 micrograms/L. Utilizing pharmacokinetic-pharmacodynamic modeling, 1,3-GDN plasma concentrations appear to relate to a systemic "effect measure" that is mechanistically representative of the therapeutic actions of organic nitrates as peripheral vasodilators. The establishment of a GDN plasma concentration-effect relationship together with the relatively high plasma levels of GDN achieved following GTN dosing supports the hypothesis that the GDNs contribute significantly to the hemodynamic effect observed with GTN.

Administration, Oral↗
PubMed1988

A double-blind comparison of felodipine and hydrochlorothiazide added to metoprolol to control hypertension.

Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained greater than or equal to 95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective 'calcium antagonist' felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metoprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if 'control' of BP (dBP less than 90 mmHg) was not achieved on the initial doses. Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose. Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.

Adult↗
PubMed1990

Safety and efficacy of once-daily carvedilol vs twice-daily labetalol in mild to moderate hypertension.

A multicenter, randomized, double-blind, parallel-group trial of 8 weeks' duration was designed to compare the efficacy and safety of once-daily carvedilol with that of twice-daily labetalol in patients with essential hypertension. A total of 61 patients (13 women and 48 men) aged 26-64 years (mean +/- SEM = 49.6 +/- 1.3 years) were enrolled. All patients had mild to moderate hypertension, defined as diastolic blood pressure (DBP) of 95-114 mm Hg at the end of a 1- to 2-week single-blind placebo period. In all, 30 patients received carvedilol (25 mg once daily) and 31 received labetalol (200 mg twice daily). The initial dose could be doubled for both treatment groups at day 29 if the DBP was greater than 90 mmHg on days 28 and 29. Hemodynamic parameters, including supine and standing DBP, systolic blood pressure (SBP), and heart rate (HR), were measured and safety was evaluated at baseline and at days 14, 28, and 56 at the end of the dosing interval. In all, 3 patients on carvedilol and 4 patients on labetalol required upward dose titration after 1 month. At the end of the trial, 26 of 30 carvedilol-treated patients and 27 of 31 labetalol-treated patients (87% of each group) had a supine DBP of less than or equal to 90 mm Hg. On day 56, mean decreases in supine DBP, SBP, and HR in the carvedilol group were 18.5 and 23.4 mm Hg and 11 beats/min, respectively, from baseline values of 101.6 and 163.8 mm Hg and 80 beats/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1995

Vitamin D metabolites in childhood nephrotic syndrome.

We measured serum levels of total and ionised calcium, phosphate, intact parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and the vitamin D binding protein (DBP) in 14 children with idiopathic nephrotic syndrome and 10 healthy, age-matched controls. In all nephrotics serum DBP levels were below the normal range. Serum 25(OH)D was below 7 ng/ml in 10 of 14 nephrotic children and in the low normal range in the remaining 4 patients. The average serum 1,25(OH)2D levels were lower in the nephrotic patients than in the controls. However, free 1,25(OH)2D levels were normal in the nephrotic patients. Both serum 25(OH)D and 1,25(OH)2D correlated positively with the concentration of DBP. There was a significant negative correlation between serum DBP levels and the urinary protein excretion and a significant positive correlation between the urinary excretions of DBP and albumin. From this study it can be concluded that the nephrotic child is capable of maintaining appropriate serum concentrations of free calcitriol despite important urinary losses of both substrate and bound calcitriol.

Adolescent↗
PubMed1995

Comparison of a lifestyle modification program with propranolol use in the management of diastolic hypertension.

OBJECTIVE: To compare the management of mild diastolic hypertension (90 to 104 mm Hg) using a nonpharmacologic intervention with that using propranolol or placebo. DESIGN: Randomized, placebo-controlled trial with a 2 x 2 factorial design. SETTING: University-based ambulatory care center. PARTICIPANTS: Two hundred seven men and 105 women, 22 to 59 years of age, 73% white, who had mild diastolic hypertension untreated for at least eight weeks. INTERVENTIONS: 1) a multicomponent lifestyle modification intervention (lifestyle focus group, or LFG) administered in eight weekly meetings + placebo, 2) LFG + propranolol, 3) propranolol alone, and 4) placebo alone, followed for 12 months. MEASUREMENTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and self-reported adverse effects at each of nine follow-up visits; fasting total cholesterol, triglycerides, and glucose at baseline and 12 months; 24-hour urine sodium (Na+) and potassium (K+), three-day food records and physical activity questionnaire at three and 12 months; and a quality of life questionnaire at 12 months. MAIN RESULTS: The mean decreases in DBP at 12 months were: 8.5 mm Hg in the LFG + propranolol group; 7.7 mm Hg in the propranolol-only group; 5.9 mm Hg in the placebo-only group; and 5.4 mm Hg in the LFG + placebo group. Repeated-measures analysis of covariance showed that level of baseline DBP (p < 0.0001), time of follow-up (p < 0.0001), and propranolol use (p < 0.0001) were significantly associated with a decrease in DBP at 12 months. Despite reductions in urinary Na+ (-35 mEq; 95% CI = -50, -19), dietary Na+ (-521 mg; 95% CI = -710, -332), total calories ingested (-238; 95% CI = -335, -140), and weight (-1.4 lb; 95% CI = -3.7, +0.8), and significant increases in dietary K+ (+294 mg; 95% CI = +107, +480) and in mets-minutes of exercise (+43; 95% CI = +20, +67) at three months, assignment to the LFG intervention had no effect on DBP at three or 12 months. The subjects assigned to take propranolol more frequently reported fatigue during ordinary activities, sleep disturbance, decrease in sexual activity, and depressed feelings, when compared with the subjects taking placebo, but the numbers of study withdrawals did not differ by drug assignment. No significant difference in total cholesterol and glucose levels was observed by group assignment. Triglycerides increased significantly in the subjects assigned to propranolol (mean difference = +20 mg/dL; 95% CI of difference +1.5, +39). There was no difference in the responses to 21 quality of life items between the subjects assigned to propranolol and those assigned to placebo. CONCLUSIONS: This multicomponent lifestyle modification intervention was unable to promote persistent behavior changes and thus was inferior to propranolol therapy for the treatment for mild diastolic hypertension. Future research should focus on single modifiable factors to lower blood pressure.

Adult↗
PubMedDate not supplied

Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension.

This 12-week randomized, parallel-group, multicenter study compared fixed combinations of delapril (D) 30 mg plus indapamide (I) 2.5 mg and fosinopril (F) 20 mg plus hydrochlorothiazide (H) 12.5 mg in 171 adult patients with mild to moderate essential hypertension. After a 2-week placebo run-in, sitting and standing systolic (SBP) and diastolic blood pressure (DBP) was measured by conventional sphygmomanometry. The primary efficacy endpoint was the percentage of normalized (sitting DBP < or =90 mm Hg) and responder (sitting DBP reduction of 10 mm Hg or DBP < or =90 mm Hg) patients. Treatment effects were analyzed in the intention-to-treat (ITT; n = 171) and the per-protocol (PP; n = 167) populations. The percentage of normalized and responder patients did not differ significantly between the D + I (87.4% and 92%) and the F + H (81% and 86.9%) ITT groups. Similar results were seen in the PP population. In ITT and PP patients, sitting and standing SBP and DBP values were comparable at baseline in the two groups and were significantly (P<.01) and similarly reduced at weeks 4, 8, and 12. Neither treatment induced reflex tachycardia, and both regimens were well tolerated. Four patients in the F + H group dropped out because of adverse events. In this study, the efficacy and safety of D + I were comparable to those of F + H in patients with mild to moderate essential hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations.

BACKGROUND: Preclinical results in rats have demonstrated anxiolytic-like effects of a tryptic bovine alphaS1-casein hydrolysate. AIM OF THE STUDY: We investigated the putative effects of this tryptic hydrolysate on systolic (SBP), diastolic (DBP) blood pressures, heart rate (HR) values and plasma cortisol concentrations (CC) in human healthy volunteers facing successive stress situations. METHODS: The subjects were (double blind) randomly allocated to ingest three times, 12 hours apart, two capsules containing either 200 mg of alphaS1-casein hydrolysate (TS) or bovine skimmed milk powder as a placebo (CS). On the morning of the test day, a first blood sample for baseline measurement of CC was taken before the subjects were submitted to the Stroop test (ST) and, after a 30-min rest, to a Cold Pressor test (CPT). SBP, DBP, and HR were continuously recorded for 5 min before the ST and during each stress situation. A second blood sample was taken 15 min after the end of the CPT condition. RESULTS: ST and ST + CPT combined test situations increased SBP, DBP and HR. The significant "Treatment x SBP" and "Treatment x DBP" interactions indicated the lower percentage changes in SBP and DBP of the TS. In addition, the results showed a significant decrease of the CC in the TS but not in the CS throughout the ST + CPT combined stress tests. HR remained stable in TS between the initial rest period and the CPT unlike what happened in CS. CONCLUSION: On the basis of blood pressure and cortisol changes, these results suggest an antistress profile of this alphaS1-casein hydrolysate in human subjects.

Analysis of Variance↗
PubMed2000

Face temperature and cardiorespiratory responses to wind in thermoneutral and cool subjects exposed to -10 degrees C.

The effects of the thermal state of the body (slightly cool and neutral) and moderate wind speeds on face temperature, blood pressure, respiratory function and pain sensation during cold exposure were studied on eight healthy male subjects. They were dressed in cold-protective clothing and preconditioned at + 20 degrees C (TN) and -5 degrees C (CO) for 60 min, then exposed to -10 degrees C and 0 m x s(-1) (NoW), 1 (W1) and 5 (W5) m x s(-1) wind for 30 min. Thus, each individual was exposed six times. The exposure to wind entailed a combination of strong cooling of the bare face and mild body cooling. The forehead, cheek and nose temperatures decreased during cold exposure, and the decrease was greater at higher air velocities (P < 0.0001). All subjects reported pain sensations at 5 m x s(-1). At the end of exposure only the nose temperature was significantly lower in CO than in TN subjects; it was about 2 degrees C and reached 0 degrees C in two experiments. The systolic and diastolic blood pressure (SBP and DBP, respectively) increased significantly by 7.7 and 5.9 mmHg, respectively, during preconditioning at -5 degrees C, but did not change at + 20 degrees C. SBP and DBP increased during exposure to -10 degrees C in TN by approximately 9 mmHg. However, the total average increase of blood pressure (1-90 min) was similar in TN and CO (SBP 15 mmHg and DBP 13 mmHg). SBP and DBP increased more during exposure to 5 m x s(-1) at -10 degrees C than NoW. Blood pressure responses as observed in this study (SBP and DBP up to 51 and 45 mmHg, respectively) are potential health risks for hypertensive individuals and angina patients. Respiratory functions (FVC, FEV1) were reduced by about 3% by the cold (-5 and -10 degrees C) compared to pre-experiment values. Furthermore, the Wind Chill Index seems to underestimate the cooling power of 5 m x s(-1) at -10 degrees C of bare skin (e.g. face). Therefore it needs to be revised and we suggest that it is expanded to include risk levels for pain sensation.

Adult↗
PubMed2004

Hypopnea in pediatric patients with obesity hypertension.

Obesity is associated with the development of hypertension but it is still not clear why hypertension is not observed in all obese patients. Obesity is a risk factor for the development of obstructive sleep apnea syndrome (OSAS) in children. OSAS has been linked to the development of hypertension in adults and children. The purpose of this study was to test the hypothesis that OSAS is one of the reasons that some obese children are hypertensive and some are not. The overnight polysomnography records of 90 patients (aged 4.2-18.8 years) were reviewed. BMI(score) [body mass index (BMI)/95th percentile BMI for age, sex, and race] was used to express the degree of obesity. The severity of systolic hypertension and diastolic hypertension were expressed as SBP(score) (systolic BP/the 95th percentile systolic BP for age, sex, and height) and DBP(score) (diastolic BP/the 95th percentile diastolic BP for age, sex, and height), respectively. OSAS was defined as more than one episodes of apnea per hour (AI) or an O(2) saturation associated with obstructive apnea of less than 90%. There were 56 obese patients; 42 were hypertensive and 40 patients were diagnosed with OSAS. The incidence of hypertension (68% vs. 30%) and obesity (75% vs. 52%) was higher in OSAS patients than those without OSAS. Compared with the non-obese patients, obese patients had a higher incidence of hypertension or OSAS, a higher BMI(score), SBP(score), DBP(score), AI, hypopnea index (HI), and apnea-hypopnea index (AHI). In obese patients, both SBP(score) and DBP(score) correlated positively with BMI(score), arousal index, and HI. DBP(score) also correlated positively with AHI. Multiple regression analysis showed that HI and BMI(score) were significant independent predictors of SBP(score) or DBP(score). Obese and hypertensive patients had a higher HI, AHI, and incidence of OSAS (64% vs. 29%) than the obese and normotensive patients. In conclusion, HI had a significant correlation with the degree of hypertension in obese patients, which could not be attributed to the degree of obesity. These findings are consistent with the hypothesis that OSAS is one of the reasons why some obese children are hypertensive and some are not.

Adolescent↗
PubMed1994

Efficacy and safety of atenolol, enalapril, and isradipine in elderly hypertensive women.

PURPOSE: This trial was designed to evaluate the efficacy and safety of three different classes of antihypertensive agents in elderly women. PATIENTS AND METHODS: The trial had three phases: 4 to 8 weeks of placebo, 6 weeks of titration, and 16 weeks of maintenance. White women between 60 and 80 years old with sitting diastolic blood pressures (DBPs) from 95 through 114 mm Hg treated with placebo were evaluated by history, physical examination, laboratory studies, and quality-of-life interview. After double-blind randomization with low-dose atenolol, enalapril, or isradipine, the dose was increased stepwise and hydrochlorothiazide added as needed to achieve goal DBP (less than 90 mm Hg and greater than 10 mm Hg below baseline). During maintenance, patients not at goal were "stepped up," and patients with uncontrolled DBP at maximum dosage were removed from the study. The pretreatment (baseline) blood pressure of the 315 randomized participants averaged 161/100 mm Hg; 92% had been treated previously for hypertension, 15% had diabetes mellitus, 11% smoked, and 38% consumed alcohol. RESULTS: For 245 patients completing the trial, the average decrease in blood pressure during treatment was 18.2/15.6 mm Hg. Antihypertensive efficacy was similar for the monotherapy drug regimens, with 84%, 71%, and 80% of patients receiving atenolol, enalapril, and isradipine, respectively, achieving DBP goal. Of the 70 patients who did not complete the trial, 42 left because of symptoms and 19 because of uncontrolled DBP. No important, unexpected drug-induced changes in symptoms or blood chemistries were noted. Symptom frequency differed little among the three dosage levels, becoming maximal by the second visit at the same dosage level. CONCLUSION: All three drugs lowered DBP comparably, and none produced alarming effects. Thirteen percent of patients left the study because of symptoms.

Aged↗
PubMed1986

Sequential binding of actin monomers to plasma gelsolin and its inhibition by vitamin D-binding protein.

Functional studies that distinguish free from actin-bound gelsolin based on the ability of the former to sever actin filaments reveal that the binding of actin monomers to gelsolin is highly cooperative and can be prevented by prior incubation of actin with vitamin D-binding protein (DBP), even though the apparent affinity of gelsolin for actin is 50-fold greater than that of DBP. Measurements of actin binding by immunoprecipitation and pyrene-actin fluorescence establish that DBP-actin complexes do not bind to gelsolin and that DBP removes one of the actin monomers in a 2:1 actin-gelsolin complex. These studies may explain why DBP-actin complexes exist in blood plasma in vivo in the presence of free gelsolin and suggest that the interaction of gelsolin with actin in cells and plasma may be regulated in part by actin monomer binding proteins.

Actins↗
PubMed1985

Determination of vitamin D binding protein by Scatchard analysis and estimation of a free 25-hydroxy-vitamin D index.

A simple method for the quantification of the vitamin D binding capacity (concentration of vitamin D binding protein, DBP) in serum is described. 25-Hydroxy-vitamin D can conveniently be measured by a binding protein assay utilizing dilute human serum as a source of DBP. The same methodology was used to determine the concentration of DBP by Scatchard analysis. In comparison to radial immunodiffusion, a correlation coefficient of 0.863 (p less than 0.001) was found with a regression line y = 0.963x + 0.08 (n = 52). Normal values were between 3 and 8 mumol/l, the coefficient of variation was less than 7% (median 4.9%). A simple routine version of this test requiring only 5 tubes per sample at a sample dilution of 1:15 000 had an interassay variation of less than 8%. The apparent affinity constants of DBP obtained by the Scatchard analysis had a very poor interassay reproducibility. Thus, the molar ratio of 25-hydroxy-vitamin D and DBP was used as a 'free 25-hydroxy-vitamin D index'. The normal range for a control group was 0.005-0.015, with samples taken in winter.

Binding, Competitive↗
PubMed1995

Micronucleus formation induced by three polycyclic aromatic hydrocarbons in rat bone marrow and spleen erythrocytes following intratracheal instillation.

Benz[a]anthracene (BA), dibenz[a,h]anthracene (DBA) and dibenzo[a,i]pyrene (DBP) are polycyclic aromatic hydrocarbons (PAHs) found in incomplete combustion products of fossil fuels, coal tar, and other organic materials. Workers in related industries may be exposed to these chemicals by inhalation. The information related to the potential health hazards of these chemicals to the exposed workers, however, is very limited. In the present study, micronucleus (MN) formation in rat bone marrow and spleen polychromatic erythrocytes (PCEs) was determined following three intratracheal instillations within a 24-h period with either BA, DBA or DBP. Three doses with five rats per dose were used for each chemical. Bone marrow and spleen cells were harvested 24 h after the first dosing. Results showed that the order of toxicity for the three PAHs was DBP > DBA > BA. BA induced MN in a dose-related manner in both bone marrow and spleen PCEs at doses above 25 mg/kg. DBA caused significant increases in the frequencies of MN in both spleen and bone marrow PCEs at the dose of 8.5 mg/kg or higher. At 10 mg/kg, DBP significantly increased MN frequency in spleen PCEs, but the increase in bone marrow PCEs was not significantly different from the control. These results indicate that: (1) all three PAHs studied are absorbed through the respiratory tract and their genotoxic metabolites reach the bone marrow and/or spleen; (2) except for DBP which does not induce MN in the bone marrow, all three PAHs induced MN in both bone marrow and spleen PCEs; and (3) the sensitivity of the spleen to the three PAHs is comparable to or higher than that of the bone marrow.

Air Pollutants, Occupational↗
PubMed1987

Functional interactions of the domains of the adenovirus DNA binding protein.

The 34-kDa fragment of the carboxyl end of the adenovirus (Ad) DNA binding protein (DBP) binds to single-stranded (ss) DNA and is able to replace the intact 72-kDa DBP needed for Ad DNA replication in vitro. A similar fragment prepared from the temperature-sensitive (ts) mutant, H5ts107, which has a single amino acid change in the carboxyl end of the DBP, is temperature sensitive for DNA replication and defective in binding to ssDNA. However, in 20 mM NaCl which is the salt concentration during Ad DNA replication in vitro, the intact 72-kDa H5ts107 DBP is defective only in replication but not binding to DNA at nonpermissive temperatures. These observations indicate that the amino domain of the H5ts107 DBP can stabilize the binding of its carboxyl end to DNA.

Adenoviridae↗
PubMed1988

Common epitopes of glycoprotein B map within the major DNA-binding proteins of bovine herpesvirus type 2 (BHV-2) and herpes simplex virus type 1 (HSV-1).

Bovine herpesvirus 2 (BHV-2) specifies a glycoprotein of 130 kDa (gB BHV-2) which shows extensive homology to glycoprotein B (gB-1) of herpes simplex virus 1 (HSV-1). The BHV-2-specific 130-kDa glycoprotein is able to induce cross-reacting antibodies, some of which even cross-neutralize HSV-1. In order to determine the genome localization of gB BHV-2 and in order to identify conserved antigenic domains in both glycoproteins, we established libraries of subgenic fragments of BHV-2 and HSV-1 DNA in the prokaryotic expression vector lambda gt11 and screened them with cross-reacting monoclonal antibodies which allowed us to identify recombinant lambda gt11 clones expressing gB fusion protein. Nucleotide sequencing of inserted DNA fragments within these recombinant lambda gt11 clones revealed that they originated from the carboxy-terminal part of the major DNA-binding proteins (dbp) of BHV-2 (dbp BHV-2) and its counterpart ICP8 in HSV-1. Antisera raised against the beta-galactosidase fusion protein of recombinant phage lambda-113/2 coding for an 84 amino acid (aa) polypeptide originating from dbp BHV-2 neutralized infectivity of BHV-2 and HSV-1 in the presence of complement and precipitated [3H] glucosamine-labeled gB BHV-2 and gB-1. This antiserum also reacts with ICP8 and presumably with dbp BHV-2. Two hypotheses are discussed to explain this unexpected result: (i) epitopes in the carboxy-terminal part of gB BHV-2 and gB-1 are similar to antigenic determinants in the amino-terminal region of the gBs, thus providing cross-reacting antibody-binding sites; (iii) during gene expression a carboxy-terminal part of dbp BHV-2 and ICP8 genes might be spliced to the amino-terminal region of the glycoproteins gB BHV-2 and gB-1.

Amino Acid Sequence↗
PubMed1988

A subclass of the adenovirus 72K DNA binding protein specifically associating with the cytoskeletal framework of the plasma membrane.

We have analyzed by immunofluorescence microscopy and by biochemical cell fractionation the subcellular distribution of the adenovirus type 2 72K DNA binding protein (DBP) during the course of infection in HeLa cells. Early in infection, the 72K DBP was strictly localized in the cell nucleus. However, as infection progressed, the 72K DBP was additionally found in other subcellular fractions, notably in association with the cytoskeletal framework of the plasma membrane, the plasma membrane lamina. Pulse-chase experiments demonstrated that this association was specific. Control experiments excluded the possibility of an artificial redistribution of the 72K DBP during cell fractionation. Our data, therefore, demonstrate that a significant portion of the 72K DBP during late times of infection associates specifically with the cytoskeletal framework of plasma membranes of infected cells.

Adenoviridae Infections↗
PubMed1985

Need to prevent and control high-normal and high blood pressure, particularly so-called "mild" hypertension: epidemiological and clinical data.

The need to prevent and control high blood pressure (HBP), including so-called "mild" hypertension [diastolic blood pressure (DBP) 90-104 mm Hg in adults age 30+] stems from the extensive data on the increased risks due to these common blood pressure (BP) levels, including risk of catastrophic cardiovascular events (coronary, cerebrovascular, etc.), both nonfatal and fatal. Prospective population data from the national cooperative Pooling Project and the Chicago Heart Association Detection Project in Industry illustrate the extensively documented facts. They also show that only a small minority of middle-aged and older Americans have optimal low-normal BP levels, i.e., DBP less than 80 mm Hg (SBP less than 120). Thus, the problem of BP above optimal level for health over a long life span is a population-wide problem. The data also show that the great majority of excess catastrophic events attributable to elevated BP occur among people with DBP 90-104 and 80-89 mm Hg, levels very common in the population. Most people with such BP levels also have one or more other major risk factors (e.g., hypercholesterolemia, cigarette use, ECG abnormalities) and thus are at markedly increased risk, both relative and absolute. In addition to these excess risks for major illness, disability, and death, people with BP above optimal levels are more highly prone to other events, clinical and subclinical, that have adverse effects on long-term prognosis, including development of target organ damage and severe hypertension. These data lead to the following inferences about medical care and public health strategy: (a) A key task is, by safe nutritional-hygienic means, to shift the entire population distribution of BP downward, for both primary and secondary prevention of HBP. Such means include prevention and control of obesity, high sodium and alcohol intake, and sedentary habit, from early childhood on. (b) People with DBP 80-89 mm Hg need to be identified promptly, with institution of nutritional-hygienic measures to prevent development of frank hypertension and to correct other risk factors. (c) People with DBP 90-104 and higher need to be identified promptly, with institution of measures to normalize BP and control other major risk factors, by nutritional-hygienic means alone whenever possible or in combination with drug treatment for HBP when necessary to prevent organ system damage, serious illness, disability, and premature death.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗