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Biomedical subjects

N DeLuca

Publications and source records attributed to N DeLuca.

At least 19 recordsLinked to original sources
PubMed2000

Herpes simplex virus type 1 ICP4 promotes transcription preinitiation complex formation by enhancing the binding of TFIID to DNA.

Infected-cell polypeptide 4 (ICP4) of herpes simplex virus type 1 (HSV-1) activates the expression of many HSV genes during infection. It functions along with the cellular general transcription factors to increase the transcription rates of genes. In this study, an HSV late promoter consisting of only a TATA box and an INR element was immobilized on a magnetic resin and incubated with nuclear extracts or purified TFIID in the presence and absence of ICP4. Analysis of the complexes formed on these promoters revealed that ICP4 increased the formation of transcription preinitiation complexes (PICs) in a TATA box-dependent manner, as determined by the presence of ICP4, TFIID, TFIIB, and polymerase II on the promoter. With both nuclear extract and purified TFIID, it was determined that ICP4 helped TFIID bind to the promoter and the TATA box. These observations differed from those for the activator Gal4-VP16. As previously observed by others, Gal4-VP16 also increased the formation of PICs without helping TFIID bind to the promoter, suggesting that ICP4 and VP16 differ in their mechanism of activation and that ICP4 functions to facilitate PIC formation at an earlier step in the formation of PICs. We also observed that the DNA binding activity of ICP4 was not sufficient to help TFIID bind to the promoter and that the region of ICP4 that was responsible for this activity is located between residues 30 and 274. Taken together these results demonstrate that a specific region of ICP4 helps TFIID bind to the TATA box and that this in turn facilitates the formation of transcription PICs.

DNA↗
PubMed1999

Seasonal enumeration of fecal coliform bacteria from the feces of ring-billed gulls (Larus delawarensis) and Canada geese (Branta canadensis).

Water suppliers have often implicated roosting birds for fecal contamination of their surface waters. Geese and gulls have been the primary targets of this blame although literature documenting the fecal coliform content of these birds is quite limited. To determine the actual fecal coliform concentrations of these birds, fecal samples from 249 ring-billed gulls and 236 Canada geese in Westchester County, N.Y., were analyzed over a 2-year period. Results indicate that gull feces contain a greater average concentration of fecal coliform bacteria per gram (3.68 x 10(8)) than do goose feces (1.53 x 10(4)); however, average fecal sample weights of the geese were more than 15 times higher than those of the gulls.

Animals↗
PubMed1998

The high mobility group protein 1 is a coactivator of herpes simplex virus ICP4 in vitro.

ICP4 is an activator of herpes simplex virus early and late gene transcription during infection and in vitro can efficiently activate the transcription of a core promoter template containing only a TATA box and an initiator element. In this study, we noted that the extent of activation by ICP4 in vitro was highly dependent on the purity of TFIID when recombinant TFIIB, TFIIE, and TFIIF were used as sources of these factors. ICP4 efficiently activated transcription with a crude TFIID fraction. However, when immunoaffinity-purified TFIID was used in place of the less pure TFIID, ICP4 activated transcription to a significantly lesser extent. This finding indicated that the crude TFIID fraction may contain additional factors that serve as coactivators of ICP4. To test this hypothesis, the crude TFIID preparation was further fractionated by gel filtration chromatography. The TFIID that eluted from the column lacked the hypothesized coactivator activity. A fraction well separated from TFIID contained an activity that when added with the TFIID fraction resulted in higher levels of transcription in the presence ICP4. Further purification of the coactivator-containing fraction resulted in the isolation of a single 30-kDa polypeptide (p30). p30 was also shown to serve as a coactivator of ICP4 with immunoaffinity-purified TFIID; however, p30 had no effect on basal transcription. Amino acid sequence analysis revealed that p30 was the high mobility group protein 1, which has been shown to facilitate the formation of higher-order DNA-protein complexes.

Amino Acid Sequence↗
PubMed1995

HSV as a gene transfer vector for the nervous system.

Gene therapy for diseases of the nervous system requires vectors capable of delivering the therapeutic gene into postmitotic cells in vivo. Herpes simplex virus type 1 is a neurotropic virus that naturally establishes latency in neurons of the peripheral nervous system. Replication defective HSV vectors have been developed; these are deleted for at least one essential immediate early regulatory gene, rendering the virus less cytotoxic, incapable of reactivation, but still capable of establishing latency. Foreign genes can be vigorously expressed from an HSV-based vector in a transient manner in brain and other tissues. Long-term but weak foreign gene expression may be achieved in the nervous system by exploiting the transcriptional control mechanisms of the natural viral latency active promoter. To meet the needs of specific applications, either highly active long-term or regulatable transgene expression will be needed, requiring further studies in order to design the appropriate latency-based promoter systems.

Gene Transfer Techniques↗
PubMed1994

Effects of one-year treatment with rilmenidine on systemic hypertension-induced left ventricular hypertrophy in hypertensive patients.

In patients with essential hypertension, left ventricular hypertrophy (LVH) increases the risk for cardiovascular morbidity and mortality. Thus its reversal represents one of the principal end-points of antihypertensive treatment. We assessed the cardiovascular effects of 1-year antihypertensive treatment with rilmenidine (1 or 2 mg/day orally), a new oxazoline with a potent antihypertensive action that acts selectively through imidazoline-preferring receptors. In 11 hypertensive patients (mean age, 49 +/- 2 years) with LVH, we measured systemic hemodynamics, large artery compliance, cardiac anatomy, and endocrine function. Patients underwent M-mode and 2-dimensional echocardiography as well as Doppler and peripheral pulsed Doppler flowmetry, determination of plasma atrial natriuretic factor (ANF) levels and renin activity (PRA), and of 24-hour urinary electrolyte and creatinine excretion in control conditions (systolic/diastolic blood pressure, 148 +/- 3/102 +/- 1 mm Hg), 4 weeks after blood pressure normalization (131 +/- 2/84 +/- 2 mm Hg; p < 0.01), after 1 year of satisfactory antihypertensive treatment (142 +/- 3/90 +/- 1 mm Hg; p < 0.01) and, finally, 1 month after therapy withdrawal (155 +/- 3/106 +/- 2 mm Hg; difference not significant [NS]). One-year of rilmenidine treatment induced an improvement in brachial artery compliance (from 0.92 +/- 0.06 to 1.16 +/- 0.08 cm4/dyne; p < 0.05), which persisted after withdrawal of treatment (1.17 +/- 0.06 cm4/dyne; p < 0.05). LVH was reversed after 1 year of rilmenidine treatment (from 152 +/- 5 to 131 +/- 4 g/m2 body surface area; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1994

Requirements for activation of the herpes simplex virus glycoprotein C promoter in vitro by the viral regulatory protein ICP4.

During infection with herpes simplex virus, infected-cell polypeptide 4 (ICP4) activates transcription of most herpes simplex virus genes. In the present study, the mechanism of activation of transcription by ICP4 was investigated by using a reconstituted in vitro system with fractionated and purified general transcription factors, coupled with DNA-binding assays. The templates used in the reactions included regions of the gC and thymidine kinase (tk) promoters in plasmids, and on isolated fragments, allowing for the evaluation of the potential function of naturally occurring and inserted ICP4-binding sites and elements of the core promoter. ICP4 efficiently activated transcription of the gC promoter by facilitating the formation of transcription initiation complexes. ICP4 could not substitute for any of the basal transcription factors. Moreover, TATA-binding protein (TBP) could not substitute for TFIID in activation, suggesting a requirement for TBP-associated factors. Interactions between ICP4 and DNA 3' to the start site was necessary for activation of the gC promoter. The requirement for DNA-protein contacts could be met either by the presence of an ICP4-binding site in the gC leader, by the presence of a site more than 150 nucleotides further downstream, by an inserted site that normally acts to repress transcription, or by the addition of sufficient non-site-containing DNA. The gC TATA box and start site, or initiator element (inr), were individually sufficient for activation by ICP4 and together contributed to optimal activation. In contrast to gC, the tk promoter was poorly activated in the reconstituted system. However, the tk TATA box was efficiently activated when the tk start site region was replaced with the gC inr, suggesting that activation was mediated through the inr and inr-binding proteins. In addition, mutation of the inr core resulted in a gC promoter that was very poorly activated by ICP4. The results of this and previous studies demonstrate that ICP4 activates transcription in a complex manner involving contacts with DNA 3' to the start site, TBP, TFIIB, TBP-associated factors, and possibly proteins functioning at the start site of transcription.

Base Sequence↗
PubMed1993

Abnormalities of sodium handling and of cardiovascular adaptations during high salt diet in patients with mild heart failure.

BACKGROUND: Sodium retention and hormonal activation are fundamental hallmarks in congestive heart failure. The present study was designed to assess the ability of patients with asymptomatic to mildly symptomatic heart failure and no signs or symptoms of congestion to excrete ingested sodium and to identify possible early abnormalities of hormonal and hemodynamic mechanisms related to sodium handling. METHODS AND RESULTS: The effects of a high salt diet (250 mEq/day for 6 days) on hemodynamics, salt-regulating hormones, and renal excretory response were investigated in a balanced study in 12 untreated patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (NYHA class I-II, ejection fraction < 50%) (HF) and in 12 normal subjects, who had been previously maintained a 100 mEq/day NaCl diet. In normal subjects, high salt diet was associated with significant increases of echocardiographically measured left ventricular end-diastolic volume, ejection fraction, and stroke volume (all P < .001) and with a reduction of total peripheral resistance (P < .001). In addition, plasma atrial natriuretic factor (ANF) levels increased (P < .05), and plasma renin activity and aldosterone concentrations fell (both P < .001) in normals in response to salt excess. In HF patients, both left ventricular end-diastolic and end-systolic volumes increased in response to high salt diet, whereas ejection fraction and stroke volume failed to increase, and total peripheral resistance did not change during high salt diet. In addition, plasma ANF levels did not rise in HF in response to salt loading, whereas plasma renin activity and aldosterone concentrations were as much suppressed as in normals. Although urinary sodium excretions were not significantly different in the two groups, there was a small but systematic reduction of daily sodium excretion in HF, which resulted in a significantly higher cumulative sodium balance in HF than in normals during the high salt diet period (P < .001). CONCLUSIONS: These results show a reduced ability to excrete a sodium load and early abnormalities of cardiac and hemodynamic adaptations to salt excess in patients with mild heart failure and no signs or symptoms of congestion.

Adaptation, Physiological↗
PubMed1992

Activation of human immunodeficiency virus by herpes simplex virus.

Heterologous viruses have been examined for their ability to accelerate the course of infection with the human immunodeficiency virus (HIV) type 1. In this study, ACH-2 cells persistently infected with HIV-1 exhibited augmented HIV-1 replication as a result of superinfection with herpes simplex virus (HSV) type 1. Using HSV-1 mutants with deletions in the genes encoding immediate-early proteins ICP0, ICP4, and ICP27, it was found that ICP0 and ICP27, but not ICP4, were essential for up-regulation of HIV replication. Northern blot analysis showed that this activation of HIV was characterized by an initial rise in the level of the small, subgenomic (2.0 and 4.3 kb) mRNA species, followed by an increase in the level of unspliced genomic (9.2 kb) mRNA. Such a shift in transcriptional phase recapitulates the early-to-late transition seen in single-step growth curves of acute HIV-1 infection. Thus, HSV can activate HIV-1 from latency in ACH-2 cells, this activation of HIV is independent of productive HSV replication since the delta ICP4 deletion mutant is replication-incompetent, and this activation is evident as an increase in the steady-state levels of HIV transcripts.

CD4-Positive T-Lymphocytes↗
PubMed1992

Angiotensin converting enzyme inhibition restores cardiac and hormonal responses to volume overload in patients with dilated cardiomyopathy and mild heart failure.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibition exerts a favorable effect on the response to exercise in heart failure. This study was planned to define the influence of ACE inhibition on the adaptation to volume overload. METHODS AND RESULTS: We studied the hemodynamic, hormonal, and renal responses to acute volume expansion (sodium chloride, 0.9%, 0.25 ml.kg-1.min-1 for 2 hours) in patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (New York Heart Association class I or II, ejection fraction < or = 50%). The patients were studied without any pretreatment (n = 14) or after 1 week of treatment with the oral ACE inhibitor quinapril at a dosage of 10 mg/day (n = 11). Seven patients were studied during constant intravenous infusion with nitroglycerin (0.1 micrograms.kg-1.min-1). The study groups had similar hemodynamic and clinical characteristics and hormonal profile at baseline evaluation. In the untreated patients, volume expansion did not increase left ventricular end-diastolic volume measured by echocardiography and was associated with a reduction in ejection fraction (p < 0.05) and with a paradoxical increase in forearm vascular resistance (p < 0.05) estimated by plethysmography. In addition, plasma atrial natriuretic factor did not change, and plasma norepinephrine was increased by saline loading. In contrast, in the patients treated with quinapril, volume expansion induced an increase of both left ventricular volumes (p < 0.001) without changing ejection fraction and reduced forearm vascular resistance (p < 0.05). In addition, in this group, plasma atrial natriuretic factor levels increased (p < 0.05) and plasma norepinephrine did not change during volume overload. During nitroglycerin infusion, volume expansion was associated with peripheral vasodilatation, increases of left ventricular volumes, and no change in ejection fraction. In this group, however, plasma atrial natriuretic factor levels did not change in response to volume overload. CONCLUSIONS: We conclude that pretreatment with the ACE inhibitor quinapril significantly improves compromised responses to acute isotonic volume overload in patients with dilated cardiomyopathy and mild heart failure. The favorable influence of ACE inhibition on cardiovascular and hormonal responses to volume expansion seems to be related to the cardiac unloading produced by this treatment.

Adult↗
PubMed1991

[The early hemodynamic and hormonal changes in patients with left ventricular dysfunction].

The aim of this study was to highlight a different hormonal and hemodynamic pattern in patients with mild cardiomyopathy. For this purpose, we studied subjects with mild heart failure (CHF; NYHA class I and II; post-ischemic and idiopathic) who underwent an isotonic saline load (SL) (0.22 ml/kg/min of 0.9% NaCl for 120 min). A second group of age- and sex-matched normal subjects (C) was studied as a control. Basal hormonal and hemodynamic values of the 2 groups differed only in atrial natriuretic factor (ANF), left ventricular end-diastolic diameter and ejection fraction (EF). There were, on the contrary, no differences in basal plasma renin activity (PRA) and plasma aldosterone (PA) values. After SL, in C, percent changes in EF, cardiac output and ANF values were significantly higher than in CHF while total peripheral resistances increased only in CHF but not in C. In both groups there were decrements of PRA and PA, but these responses were significantly higher in C than in CHF. In conclusion, our results show that hormonal, renal and hemodynamic responses to salt/volume load are compromised in the early asymptomatic phase of heart failure. These abnormalities may predict the progressive deterioration of cardiac function, and may indicate appropriate therapeutic interventions since the early phases of the disease.

Aldosterone↗
PubMed1989

Effects of long-term antihypertensive treatment with tertatolol on diastolic function in hypertensive patients with and without left ventricular hypertrophy.

UNLABELLED: We assessed the effects of long-term antihypertensive treatment with 5 mg tertatolol, a noncardioselective beta-blocker, on left ventricular hypertrophy (LVH) and diastolic function. Fifteen hypertensive patients were selected as good responders to previous treatment with tertatolol (supine blood pressure less than 140/90 mm Hg). They were divided into 2 groups: group 1 with LVH (n = 6) and group 2 without LVH (n = 9). After a one month wash-out period, all patients received 5 mg tertatolol once daily. In case of uncontrolled blood pressure (BP), the dose was doubled after 2 weeks in 10 patients. BP control was obtained in all patients. M-mode echocardiography and Doppler-echocardiography were performed under controlled conditions after BP normalization and after 6 months of treatment. Long-term BP normalization significantly reduced left ventricular mass index (LVMI) in group 1 (from 137 +/- 3 to 121 +/- 3 g/m2, P less than .01), but not in group 2 (from 120 +/- 3 to 114 +/- 4 g/m2, P = NS). After 2 weeks of effective therapy, the ratio between early and late diastolic peak flow velocity across the mitral valve (E/A ratio), significantly increased in both groups (from 0.72 +/- 0.04 to 0.87 +/- 0.06 in group 1, P less than .05; and from 1.13 +/- 0.06 to 1.26 +/- 0.07 in group 2, P less than .05). After 6 months, together with the reduction of LVMI, a further increase of E/A ratio was only observed in group 1 (to 1.30 +/- 0.12, P less than .05). IN CONCLUSION: (1) LVH contributes to left ventricular diastolic dysfunction in hypertensive patients since its reversal is able to improve diastolic filling, and (2) effective antihypertensive treatment with tertatolol improves diastolic function independently from its effect on LV mass.

Adrenergic beta-Antagonists↗
PubMed1988

Reduction of atrial natriuretic factor circulating levels by endogenous sympathetic activation in hypertensive patients.

The effects of endogenous activation of sympathetic nervous system on systemic and regional hemodynamics and on plasma levels of atrial natriuretic factor (ANF) were studied in subjects with essential hypertension. Stimulation of sympathetic nervous system was reflex-induced by a selective deactivation of carotid baroreceptors obtained by increasing external neck-tissue pressure (NTP) by means of a neck chamber. The effects of graded levels (+30, +45, and +60 mm Hg) and one single and sustained level (+45 mm Hg for 15 min) of NTP were studied. As expected, NTP caused reflex increases in blood pressure, heart rate, and forearm vascular resistance, whereas atrial pressures did not change significantly and cardiac output tended to increase. In the studies based on graded levels of NTP, immunoreactive ANF (irANF) progressively fell (from 31.7 +/- 10 to 13.3 +/- 4 fmol/ml; p less than .05) and the changes in irANF were significantly correlated with those observed in FVR (r = -.671, p less than .001). Both hemodynamic and irANF changes were prevented by adrenergic blockade (phentolamine + propranolol). During +45 mm Hg NTP for 15 min, the levels of irANF fell both in the pulmonary artery and in the inferior vena cava. The irANF arteriovenous difference also fell during this maneuver. These data show that, in hypertensive patients, factors other than atrial wall tension may influence ANF release. They also show that endogenous sympathetic activation may reduce ANF release.

Atrial Natriuretic Factor↗
PubMed1988

Long-term reduction of peripheral resistance with celiprolol and effects on left ventricular mass.

The antihypertensive efficacy of a new beta-blocker, celiprolol, was compared with that of a well established antihypertensive drug, metoprolol. Systemic and forearm haemodynamic effects were investigated using echocardiography and two-dimensional pulsed Doppler flowmetry, respectively. Twenty hypertensive patients completed the double-blind crossover randomized study. Each 6-week active treatment period was both preceded and followed by 2 weeks of placebo treatment such that the total duration of the study was 18 weeks. Despite comparable efficacy in reducing systolic and diastolic blood pressures by approximately 10% of the basal value, the two drugs differed in their systemic and haemodynamic effects. Celiprolol significantly decreased forearm peripheral resistance and total peripheral resistance. Cardiac output remained unchanged and forearm blood flow was increased. Metoprolol reduced cardiac output through a reduction in heart rate, but stroke volume was unaltered. Neither drug significantly modified cardiac performance, as evaluated by left ventricular circumferential fibre shortening and left ventricular ejection fraction. Differences in the systemic and regional haemodynamic effects of the two drugs could account for the different blood pressure response seen in some patients. There was no observable change in left ventricular wall thickness or left ventricular mass. These results confirm previous reports which demonstrate that antihypertensive treatment with beta-blockers does not reduce left ventricular mass in patients with a left ventricle of normal size. It is generally accepted, however, that the ability of beta-blockers to reverse left ventricular hypertrophy is unrelated to the individual pharmacological characteristics of each agent.

Adrenergic beta-Antagonists↗
PubMed1984

Genome locations of temperature-sensitive mutants in glycoprotein gB of herpes simplex virus type 1.

A plasmid containing a herpes simplex virus type 1 (HSV-1) insert from strain KOS, prototypic coordinates 0.345 to 0.368 (3.45 kilobases) was mutagenized in vitro, and potential mutations were introduced into intact viral DNA by cotransfection. Functions normally associated with the glycoprotein gB are in the 1-9 complementation group, and the above coordinates include those that specify the gB glycoprotein gene. Following cotransfection, individual plaques were screened for temperature sensitivity (ts) of viral growth. A total of seven ts mutants was obtained, of which four were spurious mutations due to alterations outside the cloned sequences, presumably mediated by some aspect of the Ca-precipitation-cotransfection method. The remaining three did not complement known mutants of the 1-9 complementation group. These three mutants, along with tsJ12 (P.A. Schaffer, G.M. Aron, N. Biswal, and M. Benyesh-Melnick, 1973, Virology 52, 57-71) and tsJ33 (C.-T. Chu, D.S. Parris, R.A.F. Dixon, F.E. Farber, and P.A. Schaffer, 1979, Virology 98, 168-181), were physically located by marker-rescue experiments to three different restriction fragments between 0.345 to 0.368 map units. Sodium dodecyl sulfate-gel electrophoresis was used to analyze the glycoproteins synthesized during continuous or pulse-chase labeling protocols. All five mutants were found to synthesize a precursor of gB but did not accumulate mature gB during a pulse, a chase, or continuous labeling at the nonpermissive temperature.

Animals↗
PubMed1983

The effect of ammonium chloride and tunicamycin on the glycoprotein content and infectivity of herpes simplex virus type 1.

Infectious virions of MP, a syncytial strain of herpes simplex virus type 1, are formed in the presence of 50 mM NH4Cl. Underglycosylated virion glycoproteins are synthesized in infected cells and are incorporated into virions in the presence of the same concentration of NH4Cl. We conclude that fully glycosylated glycoproteins are not required for viral infectivity. Virus particles, deficient in glycosylated glycoproteins, are assembled in the presence of tunicamycin but they are not infectious. The decrease in infectivity could be due to the decreased amount of the gB or possibly other peptides and/or to the lack of the high-mannose saccharides of precursor glycoproteins.

Ammonium Chloride↗