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Biomedical subjects

C Prescott

Publications and source records attributed to C Prescott.

At least 19 recordsLinked to original sources

hnRNP C and polypyrimidine tract-binding protein specifically interact with the pyrimidine-rich region within the 3'NTR of the HCV RNA genome.

Like other members of the Flaviviridae family, the 3' non-translated region (NTR) of the hepatitis C virus (HCV) is believed to function in the initiation and regulation of viral RNA replication by interacting with components of the viral replicase complex. To inves-tigate the possibility that host components may also participate in this process, we used UV cross-linking assays to determine if any cellular proteins could bind specifically to the 3'NTR RNA. We demonstrate the specific interaction of two host proteins with the extensive pyrimidine-rich region within the HCV 3'NTR. One host protein migrates as a doublet with a molecular weight of 57 kDa and is immunoreactive with antisera specific for polypyrimidine tract-binding protein (PTB), and the other protein (35 kDa) is recognized by a monoclonal antibody specific for heterogeneous nuclear ribonucleoprotein C (hnRNP C). These results suggest that recognition of the large pyrimidine-rich region by PTB and hnRNP C may play a role in the initiation and/or regulation of HCV RNA replication.

3' Untranslated Regions↗

Ribosomes containing the C1054-deletion mutation in E. coli 16S rRNA act as suppressors at all three nonsense codons.

It was established some time ago that the deletion of base C1054 in E. coli 16S rRNA specifically affects UGA-dependent termination of translation. Based on this observation, a model for the termination event was proposed in which the UGA nonsense codon on the mRNA base-pairs with a complementary motif in 'helix 34' of the 16S rRNA, thus potentially providing a recognition signal for the binding of the release factor. This model has been re-examined here and evidence is presented which demonstrates that ribosomes containing the C1054 delta mutation enhance the activity of suppressors of both UAG and UAA termination codons introduced into the host. The results do not support the nonsense codon-16S rRNA base pairing model, and rather imply a more general involvement of 'helix 34' in the translation termination reactions.

Codon↗

The use of mental health measures in nursing home research.

To examine the quality of mental health research in nursing homes, 130 articles published in six geriatric specialty and health care delivery journals were reviewed. Thirty-nine (30%) articles used a mental health measure. Measures of cognitive function were most common, being used in 32 (25%) of the articles reviewed. Twenty-three (18%) studies measured abnormal mental experiences and 17 (13%) articles measured behavioral disorder. Many articles used measures or determinations with no established reliability. Twenty-six of the articles which used a mental health measure also used a measure of activities of daily living or physical function. Retrospective and prospective studies were similar in number. A minority of articles used control groups, random samples, or prepost measures while a majority (64%) identified an outcome measure. We conclude that nursing home research can be improved by the increased use of reliable measures of cognition and abnormal mental experiences and by the development of reliable measures of behavioral disorder. Study design can be improved by identifying a priori hypotheses and by the increased use of random sampling and control/comparison groups.

Aged↗

Influence of sequential pneumatic compression on postoperative venous function.

Sequential external pneumatic compression (SEPC) has been reported to decrease the incidence of acute deep venous thrombosis in postoperative patients by a direct mechanical action on the lower extremity veins and/or by inducing alterations in systemic fibrinolysis. To evaluate the effect of SEPC on venous function in the postoperative patient, pre- and postoperative venous capacitance (VC) and outflow (VO) were measured in a series of general surgical patients. In phase I, 17 limbs were evaluated in patients who had been fully ambulatory preoperatively and at complete bed rest postoperatively. VC decreased from 3.19 +/- 0.43 cc/100 cc of tissue (mean +/- standard error of the mean) preoperatively to 2.08 +/- 0.34 cc/100 cc of tissue postoperatively (p less than 0.05) and VO decreased from 87.2 +/- 10.6 cc/100 cc of tissue/min preoperatively to 58.1 +/- 8.7 cc/100 cc of tissue/min postoperatively (p less than 0.025). In phase II SEPC was begun preoperatively and continued for 24 hours postoperatively on one limb of 20 patients. SEPC prevented the decrease in VC and VO both in the pumped leg (VC-2.65 +/- 0.26 cc/100 cc of tissue preop, 2.40 +/- 0.18 cc/100 cc of tissue postop, p greater than 0.2; VO-72.3 +/- 5.9 cc/100 cc of tissue/min preop, 66.2 +/- 5.3 cc/100 cc of tissue/min postop, p greater than 0.2) and in the unpumped limb (VC-2.85 +/- 0.18 cc/100 cc of tissue preop, 2.41 +/- 0.24 cc/100 cc of tissue postop, p greater than 0.05; VO-66.1 +/- 5.2 cc/100 cc of tissue/min preop, 66.7 +/- 6.7 cc/100 cc of tissue/min postop, p greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Inducible expression of a gene specific to the RecF pathway for recombination in Escherichia coli K12.

The Mud(Aplac) operon fusion technique of Casadaban and Cohen (1979) was used to search for inducible functions specific to the RecF pathway of conjugal recombination. A fusion mutant of a recBC sbcB mutant which showed less than 1% of the normal level of recombination in Hfr crosses has been isolated and designated as rec-259. The mutation is shown to be closely linked to tyrA at approximately 57.5 min in relation to the standard genetic map, and is quite distinct from recA. Two point mutations within this gene have also been obtained. Mutation of this gene interferes specifically with the RecF pathway of recombination, and also causes increased sensitivity to mitomycin C and UV light. Expression of the lac genes in the rec-259 fusion strain is increased following damage to DNA, but not in lexA and recA derivatives. These observations demonstrate the existence of an inducible gene which is regulated by lexA and whose expression is required for RecF recombination and DNA repair.

DNA Repair↗

The effect of S-adenosylhomocysteine on DNA methylation in isolated rat liver nuclei.

DNA methylation was studied in vitro using whole nuclei from regenerating rat liver. Methyl incorporation from S-adenosyl-[Me-3H]methionine in nuclei from regenerating liver was four times higher than that of normal liver. The effect of S-adenosylhomocysteine on DNA methylation was examined, and it was found at equal molar concentrations of S-adenosylhomocysteine to to S-adenosylmethionine that DNA methylation was competitively inhibited 50%.

Animals↗

Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose.

Plasma concentrations and urinary excretion of DTZ and its metabolites were determined in 20 healthy volunteers (10 males and 10 females) after they had each been given a single oral 90 mg dose of DTZ. DTZ and six of its metabolites which included N-monodesmethyl DTZ (MA), deacetyl DTZ (M1), deacetyl N-monodesmethyl DTZ (M2), deacetyl O-desmethyl DTZ (M4) and deacetyl DTZ N-oxide (M1NO) and deacetyl N,O-didesmethyl DTZ (M6), were determined by a sensitive and specific HPLC assay. The major metabolites measurable in the plasma of all the volunteers were MA, M1, and M2. The terminal half-lives (t1/2) of M1 and M2 were considerably longer than those of DTZ and MA. Less than 5% of the dose was excreted as unchanged DTZ in the urine over the 24 h period. The major urinary metabolite was MA, followed by M6, M2, and then M1. Except for the urinary excretion of M4 there were no statistically significant differences in any of the pharmacokinetic parameters between the males and the females. The mean 24 h urinary recovery of M4 was higher in the males than in the females (P < 0.05). However there were large inter-individual variations in the plasma concentrations and urinary excretion of DTZ and its metabolites with some parameters differing by more than 20-fold. In addition, O-desmethyl DTZ (Mx) and N,O-didesmethyl DTZ (MB) were identified as two other major urinary metabolites.

Administration, Oral↗

Screening for dialysis access graft malfunction: comparison of physical examination with US.

PURPOSE: To test the reliability and performance of two physical diagnosis algorithms for use in physical examination of vascular access grafts. MATERIALS AND METHODS: Grafts were assessed in 39 patients by means of physical examination performed by four observers. Grafts were characterized as having a thrill, pulse, or indeterminate examination at three locations (arterial, midpoint, venous). Findings with this algorithm were compared with those from ultrasound (US) with volume flow measurements. RESULTS: Patients with a thrill at all three locations of the graft all had volume flows greater than 450 mL/min (negative predictive value = 100%). Of patients with a pulse at any of three locations, only 28% (positive predictive value) had a volume flow of 450 mL/min or less. CONCLUSION: Physical examination is a good screening test for ruling out the low flows associated with impending access graft failure, thereby eliminating the need for routine US for many patients.

Adult↗

Guide wire directed manipulation of malfunctioning peritoneal dialysis catheters: a critical analysis.

PURPOSE: To evaluate patency rates after guide wire directed manipulation of malfunctioning continuous ambulatory peritoneal dialysis (CAPD) catheters. MATERIALS AND METHODS: During a 58-month period, 23 patients underwent 34 outpatient guide wire directed manipulations of their CAPD catheter to improve function (n = 30) or reduce pain and improve function (n = 4) during dialysis. Catheter patency rates were subsequently determined by review of departmental, hospital, and dialysis center charts; procedural reports; and patient telephone interviews. RESULTS: Among 12 patients who underwent a single guide wire directed manipulation, long-term (> 30 days) catheter patency was achieved in seven (58%). With use of the Kaplan-Meier survival method, the 3-, 6-, and 12-month probability of patency after a single guide wire manipulation was 0.61, 0.54, and 0.11, respectively. The mean duration of patency achieved in this group was 131 days (range, 2-421 days). In those patients (n = 8) who underwent multiple catheter manipulations (n = 19), 11 (58%) procedures resulted in long-term patency, with each patient (100%) achieving at least one such period. The Kaplan-Meier survival method determined the probability of patency in this group at 3, 6, and 12 months to be 0.75, 0.69, and 0.54, respectively. The mean secondary catheter patency was 235 days (range, 2-646 days). Overall, 75% of patients followed up achieved at least one period of long-term catheter patency during the time of this study. One (3%) episode of postprocedure peritonitis occurred. CONCLUSION: Guide wire directed CAPD catheter manipulation is a relatively simple outpatient procedure that restores long-term catheter function for most patients with minimal risk for a major complication. Patients with nonfunctioning CAPD catheters who do not have peritonitis or sepsis will most likely benefit from at least one attempt at radiologic manipulation of their catheter.

Adolescent↗

Fragmentation of the ribosome to investigate RNA-ligand interactions.

RNA molecules perform a variety of important and diverse functions and, therefore, an understanding of their structure and interaction with proteins and ligands is essential. Large RNA molecules (for example, the ribosomal RNAs) are complex and hence reports describing their fragmentation into functional subdomains has provided a means for their detailed analysis. We present here an in vivo approach to study RNA-ligand interactions. This is based on the concept that an RNA fragment could mimic a drug-binding site present on the intact molecule. Overexpression of the fragment would sequester the drug thereby permitting the continued functioning of the ribosome and, thus, ensuring cell viability. Accordingly, a fragment of 16S rRNA encompassing the spectinomycin-binding domain in helix 34 (nucleotides 1046-1065 and 1191-1211) was cloned and in vivo expression resulted in drug resistance. Furthermore, an RNA fragment lacking flanking sequences to helix 34 was also selected from among a pool of random rRNA fragments and shown to confer spectinomycin resistance. A similar in vitro approach is also described for the analysis of rRNA molecules that interact with the yeast elongation factor 3 (EF-3).

Anti-Bacterial Agents↗