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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 325 records · Page 18Linked to original sources
PubMed1998

Maternal serum inhibin A can predict pre-eclampsia.

OBJECTIVE: To compare median levels of maternal serum inhibin A in the second trimester blood samples of women who subsequently develop pre-eclampsia and those who do not. DESIGN: Retrospective analysis of 13 18 week samples from a bank of serum stored at -40 degrees C, originally taken for Down's syndrome screening. SETTING: Antenatal clinics in a teaching hospital. SAMPLE: Twenty-eight pregnancies with pre-eclampsia and 701 controls. Samples were taken, on average, 22 weeks before the diagnosis. MAIN OUTCOME MEASURE: Median inhibin A level. RESULTS: The median inhibin A level in the cases was 2.01 multiples of the gestation-specific median in the controls, a statistically significant elevation (P < 0.001). Twenty-three (82%) had levels above the normal median; 19 (68%), 15 (54%), and 11 (39%) exceeded the normal 75th, 90th and 95th centiles, respectively. CONCLUSIONS: In pre-eclampsia the maternal serum inhibin A level can be increased months before the onset of symptoms. This provides an opportunity to study the early natural history of the disease and possibly to conduct treatment trials.

Biomarkers↗
PubMed1998

Standardizing the classification and description of follicular unit transplantation and mini-micrografting techniques. The American Society for Dermatologic Surgery, Inc.

Previous attempts at classifying small graft transplants have focused mainly upon graft size and have not taken into consideration other technical factors involved in graft production that may influence the outcome of the surgery. The proposed classification attempts to consider these factors by including various technical aspects of harvesting, dissection, and placement, all of which impact the quality and quantity of the small grafts used in the procedure. By standardizing the nomenclature, as well as the description of the other factors involved in the surgery, communication between physicians and patients may be facilitated. In addition, different procedures may be more accurately studied and compared.

Alopecia↗
PubMed1998

The role of level, spectral, and temporal cues in children's detection of masked signals.

Preschool-aged children and adults were asked to detect masked signals in four conditions that evaluated the role of level, spectral, and temporal cues on performance. Psychometric functions fitted to percent correct data at several signal-to-noise ratios showed higher thresholds and shallower slopes for the children in all conditions. Performance was similar in fixed and roving level conditions for both age groups suggesting use of level-invariant cues. When the signal was moved to the spectral edge of the masker the performance of the adults improved but that of the children did not. This suggested that children did not benefit from the additional cues provided by the off-center signal. Children's performance worsened when the signal was a narrow-band noise rather than a pure tone but the adults' did not, suggesting children's reliance on temporal changes in the masker with the introduction of the signal. Analyses of the stimuli suggested that the children's thresholds corresponded to signal-to-noise ratios at which multiple cues were present at magnitudes that were great enough to be discriminable.

Adult↗
PubMed1998

Functional differences between BHRF1, the Epstein-Barr virus-encoded Bcl-2 homologue, and Bcl-2 in human epithelial cells.

BHRF1, a component of the restricted early antigen complex of the Epstein-Barr virus lytic cycle, encodes a 17-kDa protein with both sequence and functional homology to the antiapoptotic Bcl-2 oncogene. Recent work has suggested that BHRF1 behaves like Bcl-2 in protecting cells from apoptosis induced by a range of stimuli. In this study, the effect of BHRF1 and Bcl-2 on the growth and differentiation of the SCC12F human epithelial cell line was examined. The levels of stable transfected BHRF1 expression achievable in SCC12F cells was consistently lower than that obtained with Bcl-2. While both BHRF1 and Bcl-2 inhibited epithelial differentiation, the effect of Bcl-2 was more pronounced, resulting in an almost complete blockade of differentiation in organotypic raft cultures. However, BHRF1-expressing SCC12F cells proliferated at a much higher rate than SCC12F cells expressing Bcl-2, and this effect was supported by cell cycle analysis which demonstrated that BHRF1, but not Bcl-2, promotes rapid transit through the cell cycle. These data highlight important differences between BHRF1 and Bcl-2 and suggest that BHRF1 may function to promote the survival and proliferation of lytically infected cells. The proliferative properties of BHRF1 described in this study, together with the demonstration that other oncogenic gamma herpesviruses encode Bcl-2 homologues, suggests that these proteins may serve to increase the susceptibility of virus-infected cells to oncogenic transformation, thereby contributing to the development of virus-associated tumors.

Apoptosis↗
PubMed1998

SWI-SNF complex participation in transcriptional activation at a step subsequent to activator binding.

The SWI-SNF complex in yeast and related complexes in higher eukaryotes have been implicated in assisting gene activation by overcoming the repressive effects of chromatin. We show that the ability of the transcriptional activator GAL4 to bind to a site in a positioned nucleosome is not appreciably impaired in swi mutant yeast cells. However, chromatin remodeling that depends on a transcriptional activation domain shows a considerable, although not complete, SWI-SNF dependence, suggesting that the SWI-SNF complex exerts its major effect at a step subsequent to activator binding. We tested this idea further by comparing the SWI-SNF dependence of a reporter gene based on the GAL10 promoter, which has an accessible upstream activating sequence and a nucleosomal TATA element, with that of a CYC1-lacZ reporter, which has a relatively accessible TATA element. We found that the GAL10-based reporter gene showed a much stronger SWI-SNF dependence than did the CYC1-lacZ reporter with several different activators. Remarkably, transcription of the GAL10-based reporter by a GAL4-GAL11 fusion protein showed a nearly complete requirement for the SWI-SNF complex, strongly suggesting that SWI-SNF is needed to allow access of TFIID or the RNA polymerase II holoenzyme. Taken together, our results demonstrate that chromatin remodeling in vivo can occur by both SWI-SNF-dependent and -independent avenues and suggest that the SWI-SNF complex exerts its major effect in transcriptional activation at a step subsequent to transcriptional activator-promoter recognition.

Chromatin↗
PubMed1998

Obstacles to timely neonatal screening in North Thames.

OBJECTIVE: To assess the timeliness of neonatal (Guthrie card) screening in North Thames, and to identify the most effective ways of improving it. DESIGN: Analysis of information routinely collected in the course of neonatal screening; reanalysis of published data on blood phenylalanine concentration in phenylketonuria (PKU) over the first two weeks; simulation studies on the impact of different interventions. SUBJECTS: 100,690 infants born over one year and screened at Great Ormond Street Hospital NHS Trust. OUTCOME MEASURE: Interval between birth and reading PKU screen results. RESULTS: Although 75% of samples (district range 55-91%) were collected by day 7, only 81% had arrived in the laboratory seven days later (range 57-96%). The average interval between birth and reading results was 14.5 days, with only 9.7% read by day 10. Samples could be collected from day 4 without significant impact on false negative rates for PKU. If samples were collected from day 4 and posted promptly (second class), the average interval between birth and reading results could be reduced to 9.3 days. If first class mail were used and the laboratory operated on Saturdays, and used assays that could be read the same day rather than bacterial inhibition assays, the average would be 7.8 days, with 96% read by day 10. CONCLUSION: Timeliness of neonatal screening shows unacceptable variation between districts, and delays in dispatch of specimens to the laboratory. Same day, first class posting should be introduced, and samples could be collected between days 4 and 8.

Blood Specimen Collection↗
PubMed1998

COPD guidelines.

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Adult↗
PubMed1998

Cardiac output and mixed venous O2 content measurements by a tracer bolus method: animal validation study.

A bolus method for noninvasive measurement of cardiac output (CO) and mixed venous oxygen content (O2) has been tested against absolute CO and O2 standards in dogs. No statistical differences in CO were found between bolus method and electromagnetic flowmeter measurement comparisons in an 18-dog study in which CO varied from 0. 5 to 3.0 l/min. The SD for all paired differences was 0.14 l/min; however, data averaging over 10-min intervals were found to reduce the CO measurement uncertainty to <0.08 l/min. The ability of the bolus method to follow rapid CO changes, experimentally produced by control of a pump (surgically placed between the superior and inferior vena cava and the right atrium), was documented and found to satisfy CO monitoring requirements of unstable subjects. O2 bolus values were found to be statistically equivalent to reference measurements.

Animals↗
PubMed1998

Differential expression of fibroblast growth factor receptors 1 to 4 and ligand genes in late fetal and early postnatal rat lung.

To characterize fibroblast growth factor (FGF) gene expression in the late fetal (days E18 to E22) and early postnatal lung (days P0 to P28), when the alveolar region undergoes extensive growth and reorganization, we analyzed the expression of four FGF receptors and six ligands. FGF receptor 1 (FGFR1) RNA levels were first low (E18) before rising late in the postnatal period (P28). FGFR2 RNA levels were detected early (at E18) and then increased (E20-P0) before falling (P2) to below later postnatal levels (P6 to P28). FGFR3 RNA levels were low at first (E18) and then increased, with peak levels in the days after birth (P2 to P10). FGFR4 RNA levels, barely detected in fetal lung (E18 to E22), increased at birth (P0) and remained high postnatally (P2 to P28). In fetal lung, FGF2 (basic FGF) RNA expression levels were low and FGF1 (acidic FGF) RNA levels were not detected: low RNA levels of each ligand were detected postnatally (P7 to P28). FGF3 to 5 and FGF7 RNA were not detected in fetal or postnatal lung. With in situ hybridization, predominantly the smooth muscle cells of large vessels expressed FGFR1 and 4 mRNA; the epithelial cells of large airways expressed FGFR1, 2, and 4; and alveolar cells expressed FGFR2, 3, and 4. Analysis of protein expression first identified FGF2 localized to the basement membrane of large airways and branching epithelial buds, to mesenchymal cells associated with buds, to the putative smooth muscle cells of large airways and vessels, and to pleural- and mesenchymal-associated cells (E18). Immediately before birth, this pattern of expression persisted (E20 to E22), with FGF2 also being expressed by putative smooth muscle cells of smaller airways and vessels (E22). After birth (P0 to P28), FGF2 expression remained relatively high in the smooth muscle cells of large and small vessels and in pleural cells; in airway smooth muscle cells and in most cells in the alveolar region, however, although FGF2 expression persisted in some cells, its intensity decreased with time.

3T3 Cells↗
PubMed1998

Doctor's dress.

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Adolescent↗
PubMed1998

Perception of risk, sexual behaviour and STD/HIV prevalence in western Kenya.

OBJECTIVE: To determine the feasibility and acceptability of collecting data on sexual practices, knowledge, attitudes and perception of risk with regard to HIV and STD infection in two clinic populations. DESIGN: A cross sectional survey carried out between June and July 1992. SETTING: An urban and a rural health centre in western Kenya. SUBJECTS: One hundred and sixty women attending Maternal Child Health (MCH) and Family Planning Clinics (FP). INTERVENTIONS: Screening STDs including N. gonorrhoea, C. trachomatis, T. vaginalis and syphilis. In addition subjects were interviewed about sexual practices, knowledge, attitudes and perception of risk with regard to HIV and STD infection. RESULTS: The presence of any STD including HIV was detected in 36.2% of women at the urban clinic and 21.2% of women at the rural clinic. The demographics of the two populations were similar with respect to age but were significantly different for several variables including marital status, ethnicity and education. Knowledge of STDs and HIV was nearly universal in both clinic populations with > 96% of patients being aware of the existence of such diseases. 76.3% of women at the urban clinic felt they could get an STD as compared to 48.8% at the rural clinic (p < 0.02). This awareness of vulnerability among the urban population was also seen for HIV. CONCLUSION: It appears to be feasible to conduct studies of sexual practices and perceptions of risk for STD/HIV acquisition in women attending health centres in Kenya.

Adult↗
PubMed1998

Plasma membrane structure and remodelling during sperm maturation in the epididymis.

All mammalian spermatozoa are surrounded by a limiting plasma membrane that mediates many of the early events during fertilization. The membrane is derived originally from spermatogonia/spermatocytes in the testis but is then modified considerably during spermiogenesis, epididymal maturation and capacitation. It is characterized by an unusually high proportion of polyunsaturated phospholipids that give it special physical characteristics and compartmentalization of many of its component proteins and lipids into discrete domains on the head and tail. During passage of spermatozoa through the epididymis remodelling of the plasma membrane is commensurate with acquisition of motility and fertilizing capacity. Remodelling processes include uptake of secreted epididymal glycoproteins, removal or utilization of specific phospholipids from the inner leaflet of the bilayer, processing of existing or acquired glycoproteins by endoproteolysis and re-positioning of both protein and lipid components to different membrane domains. These modifications are carefully coordinated at different zones of the epididymis and indirectly affect intracellular membranes, organelles and even nucleoprotein. Maturation changes are described and appraised within the context of current concepts of membrane structure and fertilization.

Animals↗
PubMed1998

Ranolazine Roche Bioscience.

Ranolazine is a metabolic modulator developed by Syntex (Roche) and is in phase III clinical trials as an anti-anginal agent and for the treatment of peripheral arterial disease, particularly intermittent claudication. It allows maintenance of energy output by muscle cells under hypoxic conditions. Ranolazine may be especially useful in angina patients in whom other therapies are ineffective. The licensee, CV Therapeutics (CVT), began a pivotal placebo-controlled, phase III clinical trial of ranolazine in October 1997 enrolling 150 angina patients [265551]. CVT plans to begin a second phase III trial in 350 to 400 angina patients receiving other anti-anginal medications during 1998 [279177]. Clinical studies suggest that ranolazine lowers the heart's demand for oxygen by increasing its ability to use carbohydrate, rather than fat, as a fuel. This is thought to be due to activation of pyruvate dehydrogenase and modulation of the activities of L-type calcium channels. This is achieved without reducing heart rate or blood pressure, or impairing pumping ability [253375,247228]. Ranolazine has been tested in more than 1300 US and European patients in phase I and phase II clinical trials, and is now being evaluated in a placebo-controlled, double-blind multicenter study to determine its effectiveness in treating stable angina. Phase II trials, in over 1200 patients with ischemic heart disease, were completed by Syntex. They demonstrated increased exercise times to onset of angina or electrocardiographic change associated with insufficient blood flow to the heart with three times daily dosing of ranolazine [224364]. Roche Bioscience claims that in the US and Western Europe approximately 1.4 million angina patients are not adequately treated with existing therapies and some 5 million patients suffer from intermittent claudication [166817]. In August 1998, CV Therapeutics signed an agreement with Catalytica Pharmaceuticals, which will manufacture specified quantities of ranolazine for use in clinical trials [293333].

Journal Article↗
PubMed1998

Comparison of efficacy and ease of handling of salmeterol and terbutaline powder inhalers.

A multicentre, randomised, open, parallel-group study was performed to compare the efficacy, tolerability and ease of handling of salmeterol xinafoate 50 micrograms twice daily via the Diskus inhaler with terbutaline sulphate 500 micrograms four times daily via the Turbuhaler inhaler. Two hundred and sixty-three patients (aged 18-79 years, baseline FEV1 50-90% predicted, mean PEFR 85% of response to salbutamol) were randomised to treatment with salmeterol (n = 136) or terbutaline (n = 127). A statistically significant difference in favour of salmeterol was seen between treatment groups for the primary efficacy variable, mean morning PEFR (difference in adjusted means 25.4 l/min, p < 0.001). Within the groups randomised to each device, ease of handling assessments favoured the Diskus inhaler over the Turbuhaler inhaler. More patients liked the Diskus inhaler than the Turbuhaler inhaler (98% vs 72%, p < 0.001). The Diskus inhaler received better scores than the Turbuhaler inhaler for all features assessed in the device questionnaire.

Adolescent↗
PubMed1998

Comparative effects of schizophrenia and temporal lobe epilepsy on memory.

The goal of this study was to further characterize episodic memory functioning in schizophrenia. This study compared verbal and visual learning and memory performance in (1) patients with schizophrenia (N = 35), (2) patients with temporal lobe epilepsy (TLE; N = 30), and (3) normal controls (N = 25). Results indicated significant memory impairments in patients with schizophrenia and TLE. "Savings" score measures of memory decay showed that the loss of information in schizophrenia and TLE was approximately equal, and quantitatively mild compared to that found in most neurologic groups with memory disorders. The severe difficulty shown by the schizophrenia group on a task of incidental recall suggested that the absence of instructional set added to a vulnerability to memory deficit. In contrast, relatively mildly impaired performance on paired associate learning suggested that patients with schizophrenia benefited from retrieval cues, multiple trials, and short (nonsupraspan) informational loads. Because patients with schizophrenia consisted of a relatively nonchronic sample with a mean IQ of 99.7, their memory disorder could not be attributed to schizophrenic dementia, nor was it accounted for by other potential confounds. Patients with schizophrenia, even those relatively early in the course of illness, have a mild episodic memory disorder.

Adolescent↗