Biomedical subjects

J E Watson

Publications and source records attributed to J E Watson.

At least 37 records · Page 2Linked to original sources

PubMed1996

Cholesterol-lowering intervention program. Effect of the step I diet in community office practices.

BACKGROUND: A randomized study was conducted to test the feasibility of cholesterol lowering in physician office practices using the National Cholesterol Education Program Adult Treatment Panel 1 guidelines. METHODS: Twenty-two physician practices in phase 1 and 23 in phase 2 were recruited from communities in Western Pennsylvania and West Virginia. These physicians treated a total of 450 adults in phase 1 (190 men and 260 women) and 480 adults in phase 2 (184 men and 296 women) with hypercholesterolemia. Three models (Usual Care [phase 1], Office Assisted [phase 2], and Nutrition Center [phase 2]) for implementing the National Cholesterol Education Program Adult Treatment Panel 1 guidelines were tested over an 18-month period. The baseline serum cholesterol levels were as follows: 6.51 mmol/L (252 mg/dL) in the Usual Care Model; 6.80 mmol/L (262 mg/dL) in the Office Assisted Model; and 6.96 mmol/L (269 mg/dL) in the Nutrition Center Model. RESULTS: In the patients who were not taking lipid-lowering medication, the mean cholesterol response was significantly different between the 3 models (P < .01). Serum cholesterol levels declined by 0.14 mmol/L (5.4 mg/dL) in the Usual Care Model; by 0.31 mmol/L (12 mg/dL) in the Office Assisted Model; and by 0.54 mmol/L (20.9 mg/dL) in the Nutrition Center Model. Two factors-length of time to follow-up measurement and change in weight-were independently related to cholesterol response across all models. African Americans demonstrated a significantly smaller response than whites in the Usual Care Model, while men demonstrated greater declines in serum cholesterol levels than women in the Office Assisted Model. Patient satisfaction was very favorable in both enhanced conditions; however, those treated in the the Nutrition Center Model were more satisfied (P < .05) with program components. CONCLUSIONS: The impact of nutrition intervention delivered through physician practices on serum cholesterol levels is less than clinically desirable, and new approaches with more aggressive therapy should be tested and implemented.

Anticholesteremic Agents↗

PubMed1996

Definition and refinement of a region of loss of heterozygosity at 11q23.3-q24.3 in epithelial ovarian cancer associated with poor prognosis.

Previous cytogenetic and loss of heterozygosity (LOH) data suggest that disruption of chromosome 11q23-qter occurs frequently in epithelial ovarian cancer and is associated with an adverse clinicopathological phenotype. Ten polymorphic microsatellite repeat loci were analyzed by PCR from the 11q22-q25 region between D11S35 and D11S968 in 40 ovarian tumors (including 31 epithelial ovarian cancers). Two distinct regions of loss were detected, suggesting possible sites for genes involved in epithelial ovarian neoplasia: a large centromeric region between D11S35 and D11S933 (11q22-q23.3) and a telomeric 8.5-Mb region lying between D11S934 and D11S1320 (11q23.3-24.3) not previously defined. LOH of the latter region but not the former one was significantly associated with poor survival, despite all tumors in this study having LOH somewhere on chromosome 11. This analysis provides a starting point for positional cloning.

Carcinoma↗

PubMed1996

Effects of poverty on home environment: an analysis of three-year outcome data for low birth weight premature infants.

Investigated the relationship between poverty and parenting in a sample of low birth weight (< or = 2,500 grams) premature (LBWPT) infants (gestation < or = 37 weeks) who were control subjects in the Infant Health and Development Program. When classified using federal poverty levels, poor families scored lower on the HOME inventory (used to measure the caregiving environment) than nonpoor families. A regression model including poverty, race, site, and representative environmental, maternal, and child variables accounted for 60% of variance in total HOME scores. Poverty and maternal IQ had significant and independent effects on HOME scores, whereas maternal distress accounted for little of the variance. In a LBWPT sample, our results find a strong relationship between parenting and poverty, suggest a modest role for maternal psychological distress in this relationship, and indicate that the influence of poverty likely extends beyond commonly measured environmental, maternal, and child factors.

Child, Preschool↗

PubMed1996

Tc-99m sestamibi cardiac SPECT imaging during coronary artery occlusion in humans: comparison with dipyridamole stress studies.

PURPOSE: To compare the magnitude of change in regional myocardial perfusion during dipyridamole stress with that during coronary occlusion. MATERIALS AND METHODS: The authors prospectively studied 14 men with more than 50% diameter stenosis in at least one major coronary artery. Same-day rest and dipyridamole technetium-99m sestamibi single photon emission computed tomography (SPECT) was performed 24 hours before coronary angioplasty. During angioplasty, while the vessel was occluded, 15 mCi(555 MBq) of tracer was injected, and SPECT studies were obtained 60 minutes later. Extent of regional perfusion abnormalities was estimated. RESULTS: Regional perfusion defect was greater during stress and occlusion than during rest (20%, P = .001 and 14%, P = .009, respectively). SPECT defect during coronary occlusion was similar to that obtained during pharmacologic stress with dipyridamole (53% vs 47%, P = .02). CONCLUSION: Tc-99m sestamibi SPECT with dipyridamole stress is a good predictor of the extent of perfusion abnormalities that occur during coronary occlusion and may facilitate estimation of the total myocardium in jeopardy from a stenotic lesion.

Adult↗

PubMed1996

A carboxy-terminal deletion mutant of protein kinase C beta II inhibits insulin-stimulated 2-deoxyglucose uptake in L6 rat skeletal muscle cells.

Alternative splicing of pre-mRNA encoding the carboxy-terminal (C-terminal) exons of protein kinase C beta (PKC beta) leads to the expression of two protein isoforms, PKC beta 1 and PKC beta II, with the potential for different functions. PKC beta II expression is regulated by insulin via alternative mRNA splicing. A physiological consequence of its activation was investigated in L6 rat skeletal muscle cells expressing GLUT4 transporters, a cell line in which PKC is involved in glucose transport. We examined the contribution of PKC beta II for insulin-stimulated [3H]2-deoxyglucose uptake by constructing three PKC beta II C-terminal deletion mutants designated M216, M217, and M218. When transiently expressed in COS1 cells, M217, with nine amino acids deleted, demonstrated autophosphorylation activity 10-fold less than full-length PKC beta II. The mutants M218, with 13 amino acids deleted, and M216, with 52 amino acids deleted, demonstrated no autophosphorylation activity and are kinase negative. When transiently expressed in L6 myotubes, M217 inhibited insulin-stimulated 2-deoxyglucose uptake by 45% (with a 45% transfection efficiency) whereas M216 and M218, kinase-negative mutants, had no effect compared with cells transfected with control plasmid. Cotransfection of full-length PKC beta II with M217 was able to rescue the inhibition of insulin-stimulated 2-deoxyglucose uptake as compared with cotransfection of M217 with the control plasmid, suggesting that M217 acts as a dominant-negative. In contrast, cotransfection of full-length PKC beta I, the other alternatively spliced form, did not rescue inhibition of insulin-stimulated 2-deoxyglucose uptake by M217. To further demonstrate the involvement of PKC, specifically PKC beta II, in insulin-stimulated 2-deoxyglucose uptake, we used two inhibitors, CG41251 (a specific PKC inhibitor) and CG53353 (a PKC beta II-specific inhibitor at 1 microM). Both inhibited insulin-stimulated 2-deoxyglucose uptake 50-60% in L6 myotubes. We conclude that M217 may act as a specific PKC beta II dominant-negative and that PKC beta II is more specific for insulin-stimulated 2-deoxyglucose uptake in these cells than PKC beta I.

Amino Acid Sequence↗

PubMed1995

Regulation of alternative splicing of protein kinase C beta by insulin.

Insulin regulates a diverse array of cellular signaling processes involved in the control of growth, differentiation, and cellular metabolism. Insulin increases glucose transport via a protein kinase C (PKC)-dependent pathway in BC3H-1 myocytes, but the function of specific PKC isozymes in insulin action has not been elucidated. Two isoforms of PKC beta result via alternative splicing of precursor mRNA. As now shown, both isoforms are present in BC3H-1 myocytes, and insulin induces alternative splicing of the PKC beta mRNA thereby switching expression from PKC beta I to PKC beta II mRNA. This effect occurs rapidly (15 min after insulin treatment) and is dose-dependent. The switch in mRNA is reflected by increases in the protein levels of PKC beta II. High levels of 12-0-tetradecanoylphorbol-13-acetate, which are commonly used to deplete or down-regulate PKC in cells, also induce the switch to PKC beta II mRNA following overnight treatment, and protein levels of PKC beta II reflected mRNA increases. To investigate the functional importance of the shift in PKC beta isoform expression, stable transfectants of NIH-3T3 fibroblasts overexpressing PKC beta I and PKC beta II were established. The overexpression of PKC beta II but not PKC beta I in NIH-3T3 cells significantly enhanced insulin effects on glucose transport. This suggests that PKC beta II may be more selective than PKC beta I for enhancing the glucose transport effects of insulin in at least certain cells and, furthermore, that insulin can regulate the expression of PKC beta II by alternative mRNA splicing.

3T3 Cells↗

PubMed1995

Evaluating the efficacy of the National Cholesterol Education Program adult treatment guidelines: cholesterol lowering intervention program.

BACKGROUND: A cross-sectional analysis was conducted to test the feasibility of the National Cholesterol Education Program Adult Treatment Panel I Guidelines (ATPI) in physician office practices. METHODS: Twenty-two physician practices in communities from western Pennsylvania and West Virginia were recruited. Using a patient tracking system, 9,171 patients were assessed for cholesterol screening and treatment by their physicians according to the ATPI guidelines. RESULTS: Cholesterol screening was ordered for 1,698 patients or 19% of the population visiting the physician offices. The reasons for not screening included the patient was already under therapy (2,371), screened within the past 5 years (1,714), or acutely ill at the time of the visit (1,691). The frequency of patient refusal for screening was low (444). However, the majority of patient diagnoses were based on a single lipid measurement, and only 817 or 56% of patients evaluated had lipoprotein measures obtained prior to treatment. Follow-up measurement was not performed according to the ATPI schedule, and the magnitude of cholesterol response was inversely related to time to first follow-up measurement. CONCLUSIONS: Many patients in these physician practices had initial cholesterol screening. However, repeat measurements as recommended for initial evaluation were not performed routinely, nor were most patients followed within the recommended 3-month time period. This lack of follow-up is detrimental to effective, long-term patient management since the magnitude of the cholesterol response is related to time of the first follow-up measurement.

Adult↗

PubMed1995

222Rn in water: a study of two sample collection methods, effects of mailing samples, and temporal variation of concentrations in North Carolina groundwater.

The U.S. Environmental Protection Agency has proposed a drinking water standard for 222Rn in public water supplies. When promulgated, operators of public water supplies will be required to determine water 222Rn concentrations. Most likely, water samples will be collected and mailed to laboratories for analyses. Additionally, it is probable that homeowners will test private well water in a similar manner by collecting water samples and mailing them to a laboratory for 222Rn analyses. In anticipation of these actions, this study was conducted to evaluate two methods of water sample collection and to evaluate the potential losses of 222Rn from water samples mailed to a laboratory. Thirdly, temporal variations in 222Rn concentrations in several groundwater supplies in North Carolina were examined. Water supplies at four sites in eastern North Carolina and five sites in western North Carolina were sampled over a 7-mo period beginning in the fall of 1993 and continuing through the spring of 1994. Samples were analyzed using a liquid scintillation method. This study showed that a "slow-flow" method is not only suitable for sample collection, but may be the preferable method for water sample collection since slow-flow collection resulted in less 222Rn loss than was observed during syringe collection, i.e., the water 222Rn concentrations in samples collected by the slow-flow method were generally higher. Further, based on this study, mailing water samples to a laboratory for analysis should not have a substantial effect on the measured 222Rn concentrations. Consequently, water samples can be collected by the slow-flow method by water supply operators, as well as homeowners, and mailed to laboratories for 222Rn analyses with reasonable assurance that the samples have not suffered significant 222Rn loss. Temporal variations in water 222Rn concentrations were observed in this study. One factor complicating the study of temporal variations in 222Rn concentrations was the striking influence that inconstant water usage and inadequate well purging prior to sample collection had on 222Rn loss from the water.

Evaluation Studies as Topic↗

PubMed1995

Human repeat-mediated integration of selectable markers into somatic cell hybrids.

We describe a strategy to introduce preferentially the dominant selectable marker neoR into the human chromosome within a monochromosome hybrid cell line. Integration of a construct containing the marker is mediated by human-specific repeat elements that promote multilocus human-specific integration with a single targeting vector. We tested two classes of repeat elements: the Alu family of SINE repeats and the Line1 repeat family. We show that Alu sequences alone are insufficient to direct human-specific integration but when used in combination with a Line1 element, or when only Line1 elements are included, integration of the vector into the human component of a monochromosome somatic cell hybrid is favored. The vectors also carry sequences that facilitate mapping and selective cloning of the targeted region. This strategy provides a means to generate selectable human subchromosomal fragments that can be used for localization of genes through positional cloning and, more important, for the identification of functional units through DNA transfer.

Anti-Bacterial Agents↗

PubMed1995

Self-care behaviors of older women with urinary incontinence.

1. Despite the availability of effective treatments for urinary incontinence, many women self-manage incontinence and never have it evaluated or treated. 2. The vast majority of women in this study used one or more self-care behaviors to manage their incontinence; the most frequently used behaviors were locating or staying near bathrooms when out, voiding more frequently, and wearing some type of protective garment. 3. Most women reported that incontinence was not at all or only a little difficult to manage and were satisfied with the self-care behaviors they used to manage this problem despite the fact that most of these behaviors had little or no potential to reduce or eliminate their incontinence.

Aged↗

PubMed1995

Loss of heterozygosity at 11q22 correlates with low progesterone receptor content in epithelial ovarian cancer.

Forty-seven epithelial ovarian cancers were analyzed for loss of heterozygosity (LOH) at D11S35 (11q22), close to the progesterone receptor (PR) gene, and for tumoral estrogen receptor (ER) and PR content. Thirty-eight of 47 tumors were informative, and, of these, 14 exhibited LOH. There was a significant association (P = 0.014) between D11S35 LOH and low tumoral PR content. For all informative tumors, there was no correlation between ER and PR; however, exclusion of tumors with LOH from the informative series revealed a linear correlation between tumoral ER and PR (P = 0.013), and established ER (P = 0.025) and PR (P = 0.05) content as significant factors in relation to patient survival. Patients with ER-rich tumors with D11S35 LOH had particularly poor survival compared with ER-rich, D11S35 heterozygous, no loss patients (P = 0.014). Analysis of the same tumors using two other microsatellites, D11S935 (11p13) and NM23 (17q22), showed no statistically significant relationships, although there were nonsignificant trends for the correlation of ER and PR expression in informative tumors without allele loss at these loci. We propose that genomic structural alteration at or close to the PR gene locus has biological and clinical sequelae in ovarian cancer.

Chromosomes, Human, Pair 11↗

PubMed1994

Effects of chronic phenobarbital administration on forgetting functions in pigeons.

The present study examined the effect of chronic phenobarbital administration on forgetting functions based on delayed matching-to-sample performance in pigeons. The effects of IP injections of 10 and 20 mg/kg administered over five consecutive training sessions were compared to each other and a baseline (no drug) condition. Percent correct was reduced as a function of both increasing delay and dose of phenobarbital. A quantitative analysis using a negative-exponential function fitted to bias-free measures of discriminability demonstrated that impaired performance following administration of phenobarbital was reflected in both an increase in the rate of forgetting as well as a decrease in initial discriminability. Furthermore, the influence of proactive interference arising from stimuli on previous trials was attenuated at the highest dose level (20 mg/kg). Thus, chronic phenobarbital administration impairs memorial function and limits the influence of information gained from previous trials on subsequent performance. The current effects of chronic phenobarbital administration are consistent with the effects of acute administration on forgetting functions reported in prior studies.

Animals↗

PubMed1994

Heart rate changes following habituation testing of the motor response in normal human fetuses.

We examined the heart rate (HR) response immediately following habituation testing in 54 normal human fetuses between 34 and 40 weeks of gestation to determine if cardiac self-regulation was a function of the rate of motor habituation. All fetuses received eight trials of a 1-s vibroacoustic stimulus (VAS) with a 10-s interstimulus interval. A score of 0-10 was assigned for each trial based on subjective assessment of intensity and duration of the fetal motor response. Motor habituation was evaluated in terms of the rate of response decrement over trials. For each fetus the average post-VAS HR was calculated in 1-min blocks for the first 7 min following habituation testing. When subjects were divided into slow and fast motor habituators, we found that fetuses who were slow habituators displayed a significantly greater increase in HR above baseline at each of the first 7 min following habituation testing as compared to fetuses whose motor response habituated more rapidly, F(1,52) = 4.88, P = 0.03. However, there was no difference between slow and fast motor habituators in the rate at which the HR returned toward prestimulus levels. To further examine these results, we divided the 54 fetuses into four groups based on the medians of the slope of the post-VAS HR regression line and the variability in HR about this line. We found that fetuses whose HR decreased slowly after habituation testing displayed significantly greater variability in their cardiac response as compared to fetuses whose HR decreased more rapidly (chi 2 = 4.74, P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed1994

Estimation of radiation doses for workers without monitoring data for retrospective epidemiologic studies.

Dosimetry data are required for many epidemiologic studies of radiation workers. For several reasons, these data may not be available for some workers for some periods of time. An estimate of a worker's dose for such a time period can be made using data from nearby time periods for the worker or using data obtained for other workers during the same time period. This paper reports the results of an evaluation of a procedure for estimating external doses for workers included in retrospective epidemiologic studies. This evaluation was conducted using data for workers who had recorded doses for each year in a 5-y period. The dose for the middle year of the 5-y period was treated as unavailable and the dose was estimated several ways. These estimates were compared with the recorded dose. It was observed that averaging a worker's dose data for the years preceding and following a year for which data hypothetically were not available most often yielded the best estimate of the dose. At one facility studied, the use of nearby data for the same worker was a more reliable estimate for a dose than was the department or facility median or mean dose. However, at another facility, use of the department median or mean dose produced a more accurate estimate than did nearby data for the worker. These results indicate that a single procedure for estimating doses is not best for all facilities, and it is recommended that a test of the type reported in this paper be performed before a decision is made on how to estimate doses. The use of department medians or means to estimate doses consistently produced better estimates than were obtained using facility medians or means.

Humans↗

PubMed1994

Suicide attempt by means of aspirin enema.

OBJECTIVE: To report a suicide attempt with an aspirin enema. CASE SUMMARY: A patient presented to the emergency room after self-administering, in enema form, approximately 700 aspirin tablets dissolved in water. Over the next 12 hours the patient became progressively acidemic with eventual cardiac arrest and subsequent chronic hypoxic encephalopathy. DISCUSSION: This patient's poor outcome was the result of retained aspirin products in the rectal vault combined with the failure to recognize the delayed absorption properties of rectally administered aspirin. CONCLUSIONS: In rectal aspirin overdoses, aspirin absorption from the rectum may occur over a long period of time. It is important to remove as much aspirin from the rectum as possible and to closely monitor these patients so that appropriate therapy may be started quickly. Activated charcoal given both in enema and oral form may help decrease aspirin absorption. Hemodialysis should be available and performed without delay should the patient require it.

Administration, Rectal↗

PubMed1993

Low frequency of mutations in the WT1 coding region in Wilms' tumor.

A series of twenty unselected Wilms' tumors were analysed for alterations in the WT1 tumor suppressor gene. The entire coding region of WT1 was amplified by RNA-PCR, and then screened for mutations by single-strand conformational polymorphism analysis (SSCP). This method was shown to be capable of detecting point mutations in the WT1 gene, by using an experimentally produced mutation. A single mutation, a 226 bp intragenic deletion, was detected in a tumor from a patient with the WAGR syndrome. These results suggest that alterations in the WT1 gene may be involved in only a subset of Wilms' tumors, and that other loci need to be investigated as potential suppressor genes in sporadic Wilms' tumors.

Genes, Wilms Tumor↗

PubMed1993

Chronic effects of glucose on insulin signaling in A-10 vascular smooth muscle cells.

To examine the effects of hyperglycemia on insulin signaling in A-10 vascular smooth muscle cells, cells were treated with extracellular D-glucose and effects of insulin were studied on the diacylglycerol-protein kinase C signaling system. A-10 cells specifically bound 125I-insulin, and insulin-like growth factor-I did not displace the label. 125I-insulin binding was unaltered under hyperglycemic conditions. To determine if insulin receptors were coupled to other insulin-regulated processes, diacylglycerol, protein kinase C, and glucose transport were evaluated. Insulin increased cellular diacylglycerol (DAG) levels which were also increased following glucose treatment and not further stimulated by insulin. The uptake of 2-[3H]deoxy-D-glucose (2-DOG) was stimulated by insulin and 12-O-tetradecanoyl phorbol 13-acetate (TPA). Insulin- and TPA-stimulated 2-[3H]DOG uptake was inhibited by a protein kinase inhibitor, staurosporine. Preincubation of cells with 500 nM TPA overnight resulted in the inhibition of insulin- and TPA-stimulated 2-[3H]DOG uptake. Protein kinase C activity was translocated from cytosolic to membrane fractions following insulin treatment. Overnight glucose (25 mM) treatment resulted in a 50% decrease in protein kinase C enzyme activity and > 90% decrease in protein kinase C beta immunoreactive levels. Protein kinase C activity and levels were not affected by osmotic control media containing mannitol. A-10 cells express GLUT4-type glucose transporters. Neither insulin-regulatable glucose transporter (GLUT4) mRNA nor GLUT4 protein levels were diminished by glucose. Significant decreases in insulin- and TPA-stimulated 2-[3H]DOG uptake occurred, however, with glucose. The down-regulation of protein kinase C beta and resultant inhibition of 2-[3H]DOG uptake by chronic glucose suggests a biochemical link between hyperglycemia and DAG-protein kinase C signaling in vascular smooth muscle cells.

Alkaloids↗

PubMed1993

Long-term environmental trends: selection of sampling locations in a reactor-aquatic cooling system.

The study objective was to determine whether environmental radionuclide accumulations were occurring in an aquatic system with a 13-y history of supplying a power plant with reactor-cooling water as well as receiving plant discharge. The aquatic system consisted of the following: 1) a reactor-cooling lake; 2) a secondary lake approximately 8 km downstream; and 3) a small stream that interfaced with the two lakes. Gamma-emitting radionuclides were identified and quantified in samples of benthic sediments obtained from representative areas of the aquatic system. This study demonstrated that in a reactor-aquatic cooling system, the component of the aquatic system most likely to experience radionuclide accumulation will not necessarily be the reactor-cooling lake, but will be that component of the aquatic system whose benthic sediments contain the highest concentrations of organic matter. Further, it was shown that the quantity of oxidizable organic matter present in a sediment is a good predictor or marker for potential sites of radionuclide accumulation (i.e., 60Co and 137Cs).

Cesium Radioisotopes↗