The shrewd grasp of RNA polymerase.
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Base Composition↗
Biomedical subjects
J W Roberts
Publications and source records attributed to J W Roberts.
Open versus stereotactic breast biopsy.
BACKGROUND: Stereotactic breast biopsy has been developed as a less invasive means of performing biopsy for mammographic abnormalities. METHODS: From July 1994 through June 1995, 103 women with mammographic abnormalities requiring biopsy were prospectively evaluated. RESULTS: Fifty-one women had open biopsy, and 52 women had stereotactic biopsy. The average age in both groups was 60 years. Pathology revealed malignancy in 12% of stereotactic biopsies and 13% of open biopsies. Complications occurred in 6% of the open biopsies and 4% of the stereotactic biopsies and were limited to hematomas or seromas. The average cost was $2400 for open biopsy and $650 for stereotactic biopsy (P < 0.01). One hundred and one patients returned for a follow-up mammogram within 6 months, and 1 patient in each group required a second biopsy, which revealed benign pathology. A Patient Satisfaction Survey revealed no significant differences in patient satisfaction between the two types of procedures. CONCLUSION: There were no differences between open and stereotactic biopsies in regards to diagnostic accuracy, complications, or patient satisfaction. A significant difference was noted in charges during the time frame of our study.
Biopsy, Needle↗
Experiences in C.D.T. testing.
The value of carbohydrate deficient transferrin (CDT) as the most direct and most accurate indicator of alcohol abuse has been amply demonstrated in the scientific literature. The CDT assay used by GIB Laboratories to assess serum samples for significant levels of alcohol abuse was validated using 184 clinically defined positive and 203 clinically defined negative specimens. Using a defined cutoff of significance and a special testing algorithm, GIB Laboratories has determined, in this study, that the sensitivity of the commercial CDT enzyme immunoassay (CDT EIA) is 88 percent, the specificity is greater than 99 percent, and the intra- and inter-run reproducibility is less than seven percent, about three times more precise than most confirmatory tests for CDT. Given the very low expected frequency of true physiological causes of non-specificity (less than one percent), the excellent specificity of the assay (in GIB Laboratories' experience), and the technical problems, time delays, and costs associated with all "confirmatory" technologies, it cannot be recommended that CDT confirmatory testing be performed, unless an individual laboratory experiences unacceptable specificity in its screening tests. It would appear that, performing CDT "confirmatory" testing when the specificity of the screening test is as high as this study has found it to be, can result in three probabilities: 1) an increase in the number of false negative results; 2) few corrections in the very small number of false positive results; and 3) in greater cost and delay for the laboratory's clients.
Adult↗
Kinetics of RNA polymerase initiation and pausing at the lambda late gene promoter in vivo.
We have measured the kinetics of transcription initiation and pausing by Escherichia coli RNA polymerase (RNAP) at the bacteriophage lambda late promoter, pR's, in growing cells. RNAP initiating transcription from pR' pauses after transcribing 16 or 17 nucleotides, and escape from this pause could in theory be the rate-limiting step in promoter function. We tested this hypothesis by analyzing pausing and non-pausing variants of both the pR' promoter segment and a more active mutant version of pR'; we measured reporter gene expression and used KMnO4 footprinting to measure directly occupancy of the promoter and pause sites in growing cells. We find that RNAP paused at +16/+17 does not limit expression of pR'. However, RNAP paused at +16/+17 does limit expression from the more active promoter by impeding formation of open complex. Therefore, the activity of the late gene regulatory protein Q to suppress the early pause, in addition to its antitermination activity, is unlikely to be important in phage gene expression.
Bacteriophage lambda↗
Putting prevention into practice. Impact of a multifaceted physician education program on preventive services in the inner city.
BACKGROUND: Physicians' prevention practices often differ from guidelines published by national authorities. Effective preventive services are most needed in inner city settings that suffer disproportionately from preventable diseases. This study examined the impact of a multifaceted physician prevention education program on the provision of preventive services in an inner city municipal hospital. METHODS: The study used a controlled intervention comparative design at two inner city municipal hospitals--Harlem Hospital Center, New York, NY (intervention site) and Kings County Hospital, Brooklyn, NY (comparison site)--serving predominantly African-American patient populations. The intervention site received prototype materials for physicians, patients, and the office setting from the US Public Health Service's Put Prevention Into Practice campaign and a series of prevention lectures from November 1991 through April 1992. Change in physician prevention practices and knowledge was assessed by self-administered questionnaires and change in patients' reports of preventive services received was assessed by structured interviews. RESULTS: Physicians at Harlem Hospital Center reported a greater postintervention increase in prevention practices and demonstrated a greater increase in prevention knowledge in comparison with physicians at Kings County Hospital. Patients at Harlem Hospital Center reported receiving increased preventive services from physicians after the intervention, while patients at Kings County Hospital did not report any significant change in preventive services received. CONCLUSIONS: A multifaceted physician education program using prototype materials from the Put Prevention Into Practice campaign with prevention lectures significantly increased the prevention knowledge and practices reported by physicians and the preventive services reported received by patients at an inner city municipal hospital.
Adult↗
Transluminal extraction catheter atherectomy in long saphenous vein grafts.
Lesions in distal coronary vasculature present unique problems for catheter-based interventions. We report two cases of attempted transluminal extraction catheter (TEC) atherectomy for very distal lesions in long circular saphenous vein grafts. One case succeeded with a simple modification of the TEC device; another failed because of excessive tortuosity in the proximal graft. This experience helps define the potential and limitations of TEC.
Aged↗
Exposure of children to pollutants in house dust and indoor air.
This review summarizes occurrence and exposure studies for pollutants in house dust and related indoor air exposures. A standard sampling method and control methods to reduce these exposures are discussed, including recommendations for future research. Infants and toddlers receive a broad and significant range of exposures to lead, pesticides, PAHs, allergens, and VOCs in house dust and indoor air. Carpet dust in eight Columbus and nine Seattle homes contained concentrations of potentially carcinogenic PAHs ranging from 3 to 290 micrograms/g, of lead from 250 to 2250 micrograms/g, and of PCBs from 210 to 1900 ng/g. Dust collected from ten used sofas in Seattle averaged 16.3, 37.2, and 229 micrograms/g for dust mite allergen, cat allergen, and lead, respectively; dust samples showed mutagenic activity. Biological and chemical pollutants in indoor dust and air have been associated with lead poisoning, cancer, allergy, asthma, damage to the nervous system, and sick building symptoms. The 11% of toddlers who have pica tend to have the highest exposures and risks. Further, the exposure of toddlers to lead via the dust pathway can be greater than by other routes. Standard method ASTM 5438.94 for sampling house dust has been used to characterize current and chronic exposure of toddlers in epidemiological studies. The accumulation of dust, dust mites, and tracked-in soil in old carpets, sofas, and mattresses appears to be a major source of exposure to lead, pesticides, allergens, PAHs, and VOCs. Remodeling and energy conservation can reduce ventilation and increase relative humidity, dust, dust mites, molds, VOCs, and other indoor air pollutants. The U.S. faces large and increasing costs from asthma and allergy. Asthma incidence in the U.S. has increased from 0.5% in 1930 to 8%-12% in 1991. Asthma hospitalization rates for children are increasing at the rate of 4%/yr in the U.S. and 14%/yr in Seattle. Such hospital visits would be rare with effective diagnosis, patient education, and control of home exposures. Asthma was estimated to cost $6.2 billion in 1990; hospital visits of children in Seattle cost $2,526,000 in 1993. Forty percent of the U.S. population has been sensitized to allergens; one in three homes has high relative humidity, which favors dust mites, molds, allergies, asthma, and other respiratory diseases. Reducing indoor allergens can reduce costs, severity, and the risk of being sensitized and developing allergic disease. Use of volunteer Master Home Environmentalists to do free in-home surveys and education in Seattle may reduce immediate health costs from allergens as well as long-term risks from lead, carcinogens, and home chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)
Air Pollutants↗
Measuring and reducing exposure to the pollutants in house dust.
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Child, Preschool↗
Transanal excision of rectal carcinoma.
Twenty-two men and 16 women with a mean age of 67 years were treated for rectal carcinoma by transanal excision. Patients presented with rectal bleeding (63%), change in bowel habits (11%), rectal pain (4%), or were asymptomatic and discovered on screening proctosigmoidoscopy (22%). The tumors were located from the anal verge to 8 cm proximally and ranged in size from 1 to 4 cm. Pathologic findings included adenocarcinoma (92%), squamous cell carcinoma (4%), and cloacogenic carcinoma (4%). Postoperative hospitalization averaged two days (0 to 29 days). One patient died of a perioperative myocardial infarction for an operative mortality of 3 per cent. Morbidity was 7 per cent and included urinary retention and pneumonia. Postoperative radiation therapy was administered to 11 patients with either undifferentiated tumors or invasion into the muscularis propria. Follow-up in these 38 patients averaged 30 months. One patient died of metastatic carcinoma, and two patients developed local recurrence that was treated successfully by a low anterior resection or abdominoperineal resection. Transanal excision of rectal carcinoma can be performed in properly selected patients with good overall survival and local control.
Adenocarcinoma↗
Determination of intrinsic transcription termination efficiency by RNA polymerase elongation rate.
Transcription terminators recognized by several RNA polymerases include a DNA segment encoding uridine-rich RNA and, for bacterial RNA polymerase, a hairpin loop located immediately upstream. Here, mutationally altered Escherichia coli RNA polymerase enzymes that have different termination efficiencies were used to show that the extent of transcription through the uridine-rich encoding segment is controlled by the substrate concentration of nucleoside triphosphate. This result implies that the rate of elongation determines the probability of transcript release. Moreover, the position of release sites suggests an important spatial relation between the RNA hairpin and the boundary of the terminator.
Base Sequence↗
Function of a nontranscribed DNA strand site in transcription elongation.
A prolonged pause in transcription elongation at positions +16 and +17 of the phage lambda late gene operon has an important role in the modification of RNA polymerase by the lambda gene Q transcription antiterminator. Mutations included in the transcription bubble of the paused transcription complex, particularly at +2 and +6, abolish pausing and the ability of Q protein to modify RNA polymerase. By transcribing heteroduplex templates made in vitro, we show that the sites identified by these mutations act through the nontranscribed strand of DNA. This result suggests unexpected regulatory functions of the nontranscribed DNA strand in transcription.
Bacteriophage lambda↗
Deletion analysis of the lambda tR1 termination region. Effect of sequences near the transcript release sites, and the minimum length of rho-dependent transcripts.
In order to determine how much of the natural sequence is required for function of the lambda tR1 rho-dependent terminator, and to determine the minimum length required, we made two deletion series of a tR1 derivative that contains mostly foreign DNA, encoding C-rich RNA, substituted for the natural upstream sequences of tR1. We find the minimum transcript length to be 85 to 90 nucleotides, although an additional 10 to 25 nucleotides provide more efficient termination. Sequences as close as ten nucleotides to the release sites could be replaced without destroying termination, although termination efficiency was reduced by substitution of these proximal regions with DNA encoding the cytidine-rich RNA that is active at upstream sites. These results suggest that sequences proximal and distal to release sites have different functions and optimal structures for rho activation. We also show that two potential stem-loop structures in the tR1 region are not essential for terminator function, or for pausing at the release region. The results are consistent with the model that any pause site downstream of DNA encoding unstructured C-rich RNA is a potential rho-dependent terminator.
Bacteriophage lambda↗
Wearing-off fluctuations in Parkinson's disease: contribution of postsynaptic mechanisms.
Wearing-off phenomenon that complicates levodopa therapy of Parkinson's disease has been attributed to a reduction in striatal dopamine storage due to the progressive degeneration of presynaptic dopaminergic terminals. To determine whether postsynaptic mechanisms also contribute to these response fluctuations, the duration of the antiparkinsonian response in parkinsonian patients grouped by disease severity was compared following discontinuation of a steady-state optimal-dose infusion of apomorphine. Although the plasma half-life of this dopamine receptor agonist remained constant, its mean efficacy half-time declined from 66 minutes in early, levodopa-naive patients to 33 minutes in advanced, complicated parkinsonians (p < 0.005). Since the motor effects of apomorphine do not depend on the presence of dopaminergic terminals, changes at the postsynaptic level undoubtedly contribute to the diminished response duration. The only slightly greater attenuation of levodopa's motor effects observed previously under similar conditions suggests these postjunctional alterations, possibly involving relatively plastic striatal dopaminoceptive systems, account for most of the shortening in the duration of levodopa action that underlie wearing-off fluctuations.
Apomorphine↗
A prospective randomized trial comparing open versus laparoscopic appendectomy.
OBJECTIVE: The authors determined whether there was an advantage to laparoscopic appendectomy when compared with open appendectomy. SUMMARY/BACKGROUND DATA: The advantages of laparoscopic appendectomy versus open appendectomy were questioned because the recovery from open appendectomy is brief. METHODS: From January 15, 1992 through January 15, 1993, 75 patients older than 9 years were entered into a study randomizing the choice of operation to either the open or the laparoscopic technique. Statistical comparisons were performed using the Wilcoxon test. RESULTS: Thirty-seven patients were assigned to the open appendectomy group and 38 patients were assigned to the laparoscopic appendectomy group. Two patients were converted intraoperatively from laparoscopic appendectomies to open procedures. Thirty-one patients (81%) in the open group had acute appendicitis, as did 32 patients (84%) in the laparoscopic group. Mean duration of surgery was 65 minutes for open appendectomy and 87 minutes for laparoscopic appendectomy (p < 0.001). There were no statistically significant differences in length of hospitalization, interval until resumption of a regular diet, or morbidity. Duration of both parenteral and oral analgesic use favored laparoscopic appendectomy (2.0 days versus 1.2 days, and 8.0 days versus 5.4 days, p < 0.05). All patients were instructed to return to full activities by 2 weeks postoperatively. This occurred at an average of 25 days for the open appendectomy group versus 14 days for the laparoscopic appendectomy group (p < 0.001). CONCLUSIONS: Patients who underwent laparoscopic appendectomies have a shorter duration of analgesic use and return to full activities sooner postoperatively when compared with patients who underwent open appendectomies. The authors consider laparoscopic appendectomy to be the procedure of choice in patients with acute appendicitis.
Acute Disease↗
D-cycloserine treatment of Alzheimer disease.
Degeneration of cortical glutamatergic projections may contribute to the cognitive decline in Alzheimer disease (AD). To evaluate whether 1glutamate system stimulation might confer symptomatic benefit, we administered D-cycloserine, a putative partial indirect agonist at certain N-methyl-D-aspartate (NMDA) glutamate receptors, to 12 patients with probable AD. The patients (seven men, five women) had a mean age of 65 +/- 8.4 years; Mini Mental State Examination scores ranged from 15 to 25. A dose escalation phase, in which cycloserine was given in daily oral doses from 25 to 500 mg (total of six dose levels, 1 week per dose), was followed by a "best dose" crossover comparison with placebo under double-blind conditions. The crossover phase consisted of 2 weeks of cycloserine and 2 weeks of placebo, separated by a 1-week washout period. We observed no significant or consistent effect on neuropsychological outcome measures. The results suggest that short-term potentiation of NMDA-mediated glutamatergic transmission may not prove useful in the symptomatic treatment of Alzheimer dementia.
Aged↗
Role of echocardiography in mitral commissurotomy with the Inoue balloon.
There are well-defined roles for echocardiography in the evaluation of patients with mitral stenosis who undergo percutaneous transvenous mitral commissurotomy. Transthoracic echocardiography is used to assess mitral valve morphology with particular attention to commissural fusion and valve leaflet calcification, the two most important determinants of the severity of mitral stenosis. This assessment has proven to be useful in patient selection, as immediate and long-term outcome can be predicted from echocardiographic grading scores. The degree of mitral regurgitation can also be assessed and has an influence on outcome. The newer technique of transesophageal echocardiography aids in the detection of left atrial thrombi and may be useful in guiding transseptal puncture and in predicting clinical outcomes. Future applications in this ever-expanding field may ultimately include the use of dobutamine stress echocardiography and intravascular ultrasound catheters. It would appear that balloon valvuloplasty and echocardiography are inexorably linked.
Catheterization↗
Iatrogenic hyperlipidaemia with GM1 ganglioside.
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Dose-Response Relationship, Drug↗
RNA and protein elements of E. coli and lambda transcription antitermination complexes.
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Bacteriophage lambda↗