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Biomedical subjects

S Berry

Publications and source records attributed to S Berry.

At least 19 recordsLinked to original sources
PubMed1999

Proton to electron stoichiometry in electron transport of spinach thylakoids

According to the concept of the Q-cycle, the H+/e- ratio of the electron transport chain of thylakoids can be raised from 2 to 3 by means of the rereduction of plastoquinone across the cytochrome b6f complex. In order to investigate the H+/e- ratio we compared stationary rates of electron transport and proton translocation in spinach thylakoids both in the presence of the artificial electron acceptor ferricyanide and in the presence of the natural acceptor system ferredoxin+NADP. The results may be summarised as follows: (1) a variability of the H+/e- ratio occurs with either acceptor. H+/e- ratios of 3 (or even higher in the case of the natural acceptor system, see below) are decreased towards 2 if strong light intensity and low membrane permeability are employed. Mechanistically this could be explained by proton channels connecting the plastoquinol binding site alternatively to the lumenal or stromal side of the cytochrome b6f complex, giving rise to a proton slip reaction at high transmembrane DeltapH. In this slip reaction protons are deposited on the stromal instead of the lumenal side. In addition to the pH effect there seems to be a contribution of the redox state of the plastoquinone pool to the control of proton translocation; switching over to stromal proton deposition is favoured when the reduced state of plastoquinone becomes dominant. (2) In the presence of NADP a competition of both NADP and oxygen for the electrons supplied by photosystem I takes place, inducing a general increase of the H+/e- ratios above the values obtained with ferricyanide. The implications with respect to the adjustment of a proper ATP/NADPH ratio for CO2 reduction are discussed.

Journal Article↗
PubMed1998

Characterization of a carboxy-terminal BRCA1 interacting protein.

There are several lines of evidence indicating that the carboxy-terminal region of the tumor suppressor protein BRCA1 is a functionally significant domain. Using the yeast two-hybrid and in vitro biochemical assays, we show that a protein, CtIP, interacts specifically with the carboxy-terminal segment of human BRCA1 from residues 1602-1863. A germ line truncation mutation, Y1853ter, that removes the last 11 amino acids from the carboxy-terminus of BRCA1, abolishes not only its transcriptional activation function, but also binding to CtIP. The function of CtIP is unknown, but its reported association with a transcriptional repressor CtBP lends further support that it may have a role in transcription. A sequence based screen of a panel of 89 tumor cell line cDNAs for mutations in the CtIP coding region identified five missense variants. In the pancreatic carcinoma cell line, BxPC3, the non-conservative lysine to glutamic acid change at codon 337 is accompanied with apparent loss of heterozygosity or non-expression of the wild type allele. Thus it is plausible that CtIP may itself be a tumor suppressor acting in the same pathway as BRCA1.

Amino Acid Sequence↗
PubMed1998

Can the urea breath test for H.pylori replace endoscopy for the assessment of dyspepsia in primary care?

AIMS: The urea breath test may have value in the initial assessment of dyspepsia in primary care. This pilot study tracks patient and general practitioner behaviour which cannot be predicted with modelling studies. METHODS: The urea breath test was made available over a period of 18 months. The test was requested when general practitioners would normally have used a trial of medication or referred for endoscopy. Patients with a positive urea breath test had early endoscopy before treatment. Patients with a negative urea breath test were treated according to symptom response. A follow-up questionnaire was given 6-24 months after the urea breath test. RESULTS: Urea breath tests were requested on 249 patients; clinical notes and follow-up interview data were available for 207 patients (83%). The urea breath test was positive for 89 patients (43%); 70 were referred for endoscopy and peptic ulcer disease was found in 33 (47%). The urea breath test was negative for 118 patients; 14 were follow-up tests after previous H.pylori treatment. For the 104 patients with dyspepsia, a negative test and no previous treatment, 42% had 1 or more previous investigations for dyspepsia and 66% had dyspepsia symptoms for more than one year. During follow-up, 21 patients had endoscopy. Dyspepsia symptom scores were significantly lower at follow-up (p < 0.01). Using a global assessment, 66% had fewer symptoms, 22% same and 12% had more symptoms. The symptom improvement was greater if the duration of symptoms was less than one year (p < 0.05). Medication use did not change significantly. Twelve patients were dissatisfied with management; most of these would have preferred endoscopy. CONCLUSIONS: A negative urea breath test appears to have some reassurance value. The use of the urea breath test as initial assessment for dyspespia may prevent the need for some endoscopy. Further controlled studies of breath testing compared with early endoscopy are required.

Adult↗
PubMed1998

Psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI-VFQ). NEI-VFQ Field Test Investigators.

OBJECTIVE: To test the reliability and validity of the 51-item Field Test Version of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) across 5 common chronic eye conditions. DESIGN: Prospective observational cohort study of persons with 1 of 5 chronic eye diseases who were scheduled for nonurgent visits in ophthalmology practices or had low vision from any cause, and a reference sample of persons without eye disease. SETTING: Six university-based ophthalmology practices and the National Eye Institute Clinical Center, Bethesda, Md. PATIENTS: Eligible participants had to have 1 of the following eye conditions: age-related cataracts, age-related macular degeneration, diabetic retinopathy, primary open-angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. Each of the 7 sites also enrolled persons in a reference sample. Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error. All eligible persons had to be aged 21 years or older, English speaking, and cognitively able to give informed consent and participate in a health status interview. MEASUREMENTS AND MAIN RESULTS: To provide the data needed to assess the reliability and validity of the 51-item NEI-VFQ, all subjects completed an interview that consisted of the 51-item NEI-VFQ, the Medical Outcomes Study 36-Item Short-Form Health Survey, and at least 1 measure of vision-targeted functional status. Estimates of internal consistency and test-retest reproducibility indicate that the 51-item NEI-VFQ is reliable. Tests of association with other scales and clinical variables support the construct validity of the survey. CONCLUSIONS: In this cross-sectional study, the 51-item NEI-VFQ seems to be reliable and valid and should be a useful tool for group-level comparisons of vision-targeted, health-related quality of life in clinical research. Additionally, the psychometric properties of the NEI-VFQ were not influenced by the type or severity of the underlying eye disease, suggesting that the measure will provide reproducible and valid data when used across multiple eye conditions.

Activities of Daily Living↗
PubMed1998

Identifying the content area for the 51-item National Eye Institute Visual Function Questionnaire: results from focus groups with visually impaired persons.

OBJECTIVE: To identify the content area for a questionnaire designed to measure vision-targeted health-related quality of life and to determine whether problems with vision-related functioning are qualitatively similar across different common eye diseases. DESIGN: Twenty-six condition-specific focus groups were conducted with 246 patients from 5 geographic regions to identify the content area for a questionnaire for use among persons with diabetic retinopathy, glaucoma, macular degeneration, cytomegalovirus retinitis, and cataract. A standard protocol was used to structure each focus group discussion. Sessions were audiotaped, transcribed, and coded in preparation for a content analysis. SETTINGS: Five university-based ophthalmology practices and 1 nonprofit eye care foundation. PARTICIPANTS: Eligible participants had to have 1 of the following eye conditions: age-related cataracts, age-related macular degeneration, diabetic retinopathy, primary open angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. All eligible persons were older than 21 years, spoke English, and had sufficient cognitive function to provide informed consent. RESULTS: Among the 246 participants, 2623 problems with vision-related functioning were mentioned. The mean number of problems per person ranged from 13.5 for those with diabetic retinopathy to 7.9 for persons with glaucoma. For the sample overall, reading problems were mentioned most frequently, followed by driving, general problems with seeing clearly, and mental health complaints caused by vision. Although the proportion of persons who reported each problem varied by condition, at least some persons with each eye disease reported each problem. The 3 most common descriptors associated with each problem were difficulty or ease of performance (13%), psychological distress associated with performance of the activity (11%), and complete inability to participate in a visual activity (11%). CONCLUSION: An item-generation strategy for a new questionnaire using a standardized focus group method identified content areas and aspects of visual disability that are not included in currently available vision-specific instruments that assess the impact of common eye diseases on visual functioning in every-day life. Although participants mentioned problems that were unique to their disease, across conditions the problems mentioned were similar. These findings provide empirical evidence of content validity for a vision-targeted, health-related quality-of-life survey designed for use across conditions.

Adult↗
PubMed1997

Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor.

Mitogen-activated protein kinases function in signal transduction pathways that are involved in controlling key cellular processes in many organisms. A mammalian member of this kinase family, MKK4/JNKK1/SEK1, has been reported to link upstream MEKK1 to downstream stress-activated protein kinase/JNK1 and p38 mitogen-activated protein kinase. This mitogen-activated protein kinase pathway has been implicated in the signal transduction of cytokine- and stress-induced apoptosis in a variety of cell types. Here, we report that two human tumor cell lines, derived from pancreatic carcinoma and lung carcinoma, harbor homozygous deletions that eliminate coding portions of the MKK4 locus at 17p, located approximately 10 cM centromeric of p53. In addition, in a set of 88 human cancer cell lines prescreened for loss of heterozygosity, we detected two nonsense and three missense sequence variants of MKK4 in cancer cell lines derived from human pancreatic, breast, colon, and testis cells. In vitro biochemical assays revealed that, when stimulated by MEKK1, four of the five altered MKK4 proteins lacked the ability to phosphorylate stress-activated protein kinase. Thus, the incidence of coding mutations of MKK4 in the set of cell lines is 6 of 213 (approximately 3%). These findings suggest that MKK4 may function as a suppressor of tumorigenesis or metastasis in certain types of cells.

DNA, Neoplasm↗
PubMed1997

The acquisition of herpes simplex virus during pregnancy.

BACKGROUND: The acquisition of genital herpes during pregnancy has been associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. The frequency of seroconversion, maternal symptoms of the disease, and the timing of its greatest effect on the outcome of pregnancy have not been systematically studied. METHODS: We studied 7046 pregnant women whom serologic tests showed to be at risk for herpes simplex virus (HSV) infection. Serum samples obtained at the first prenatal visit, at approximately 16 and 24 weeks, and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV-2) by the Western blot assay, and the results were correlated with the occurrence of antenatal genital infections. RESULTS: Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes infection. Women who were initially seronegative for both HSV-1 and HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent; those who were initially seropositive only for HSV-1 had an estimated chance of HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2-seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among the 60 of the 94 pregnancies for which the time of acquisition of HSV infection was known, 30 percent of the infections occurred in the first trimester, 30 percent in the second, and 40 percent in the third. HSV seroconversion completed by the time of labor was not associated with an increase in neonatal morbidity or with any cases of congenital herpes infection. However, among the infants born to nine women who acquired genital HSV infection shortly before labor, neonatal HSV infection occurred in four infants, of whom one died. CONCLUSIONS: Two percent or more of susceptible women acquire HSV infection during pregnancy. Acquisition of infection with seroconversion completed before labor does not appear to affect the outcome of pregnancy, but infection acquired near the time of labor is associated with neonatal herpes and perinatal morbidity.

Adult↗
PubMed1997

Constitutive expression c-fos, c-jun, and NF kappa B mRNA is in nucleated fetal blood cells and up-regulation of c-fos and c-jun with anti-CD3 stimulation.

Fetal and neonatal lymphocytes are relatively resistant to activation and cytokine production when stimulated either via their T-cell antigen receptors or lectins. The molecular mechanism(s) responsible for this phenomenon have not been clearly elucidated. We have hypothesized that such defects in fetal/neonatal T-cell activation may be due to lack of expression of the transcriptional regulatory elements required for T-cell activation. We used reverse transcriptase-polymerase chain reaction to examine both fetal and term neonatal cord bloods for mRNA expression of three transcription factors implicated in T-cell activation: c-jun, c-fos, and NF kappa B (p50 subunit). We demonstrate that mRNAs for all three of these regulatory factors are expressed in fetal blood cells by the 27th week of gestation and in term cord bloods. Activation of term infant cord blood mononuclear cells with anti-CD3 monoclonal antibodies resulted in up-regulation of both c-jun and c-fos mRNAs within 15 min of stimulation. However, secretion of IL-2 by anti-CD3-stimulated cord blood mononuclear cells was still blunted compared with control cells from adults. We conclude that fetal nucleated blood cells constitutively express important genes for cytokine regulation and are able to increase intracellular accumulation of the mRNAs for these factors in response to anti-CD3 stimulation. Thus, qualitative differences in the capacity to regulate these factors could not be shown in fetal blood cells. Quantitative experiments comparing binding of these transcription factors to the IL-2 promoter are currently under investigation.

Adult↗
PubMed1997

The ethics of scientific research: an analysis of focus groups of scientists and institutional representatives.

BACKGROUND: Little is known about scientists' views on normative research ethics and how these compare with the views of the institutional representatives (IRs) involved in matters of scientific conduct. We qualitatively evaluated scientist and IR perceptions of the norms of science, ethical violations and their harms, factors contributing to violations, and approaches to improve scientific conduct. METHODS: Focus groups were conducted with National Science Foundation investigators and with IRs. Themes were extracted from observation, notes, and transcripts. Consensus and contrasts within and between groups were described. RESULTS: Scientists described a rich set of norms including honesty, integrity, service, sharing, openness, mentoring, and meticulous work habits. Institutional representatives focused on good citizenship and abiding by administrative rules. Both groups listed similar ethical violations, though scientists felt that severe violations were rare, that science was self-correcting, and that the greatest harm from misconduct disclosure was the loss of public trust and funding. Institutional representatives called for increased and less confidential misconduct investigations. Reporting misconduct was strongly supported by IRs but rejected by scientists. Both scientists and IRs believed that formal research ethics education was needed for trainees. CONCLUSIONS: Scientists in these focus groups upheld a complex set of norms that mirror prior codes of science and exceed national misconduct rules. The sharply contrasting views of scientists and IRs concerning responsibility to report misconduct, the utility of misconduct investigation, and penalties for misconduct highlight areas where open discussion and constructive resolution are needed to formulate a functional mechanism to enhance the ethical conduct of science.

Biomedical Research↗
PubMed1996

Screening for colorectal cancer: a survey of New Zealand general practitioners.

AIM: To determine the attitudes and reported behaviours of New Zealand general practitioners concerning colorectal cancer screening and diagnosis with special consideration of the use of faecal occult blood tests. METHOD: A postal survey of a random sample of 400 New Zealand general practitioners. RESULTS: The response rate to the survey was 63%. Most of the respondents did not support a screening programme for average risk patients but did support screening in high risk groups. General practitioners favoured a screening programme offered by themselves rather than a centrally organised screening programme. A majority of respondents agreed that there was a lack of clear guidelines and a need for education regarding screening for bowel cancer. CONCLUSION: Guidelines for colorectal cancer screening are required for New Zealand general practitioners. There appears to be a need for medical education concerning screening for colorectal cancer in particular and screening and prevention in general.

Adult↗
PubMed1996

Environmental change and hedonic cost functions for automobiles.

This paper focuses on how changes in the economic and regulatory environment have affected production costs and product characteristics in the automobile industry. We estimate "hedonic cost functions" that relate product-level costs to their characteristics. Then we examine how this cost surface has changed over time and how these changes relate to changes in gas prices and in emission standard regulations. We also briefly consider the related questions of how changes in automobile characteristics, and in the rate of patenting, are related to regulations and gas prices.

Automobiles↗
PubMed1996

Eradication treatment for Helicobacter pylori in general practice.

AIMS: To identify patients with a past history of peptic ulcer and to treat Helicobacter pylori infection if confirmed. METHODS: Patient records from 6.5 full-time equivalent general practitioners were reviewed to record prescribing of H2-receptor antagonists in the last year and to review previous upper gastrointestinal investigations. RESULTS: Two hundred and sixty-seven patients had used H2-receptor antagonists in the previous year. The indications for use were peptic ulcer 25%, reflux 21%, empiric treatment for dyspepsia 39% and dyspepsia with a normal investigation 15%. Short-term prescribing was common (52% of patients treated for 1-2 months only) and of these patients 50% had undiagnosed dyspepsia. The most common indication for long-term prescribing (6 months or more) was peptic ulcer (46%). The records of 96 patients with peptic ulcer were identified; 50 were traced and considered for recall and a 13C urea breath test for Helicobacter pylori. Thirty-eight patients agreed to a breath test; 23 were positive (60.5%). Follow up breath test was negative following eradication treatment in 16 of 22 treated patients (73%). CONCLUSION: Patients with peptic ulcer disease can be recalled using general practice case notes and treated with antibiotic treatment. The majority of H2-receptor antagonist use is for indications other than peptic ulcer disease.

Aged↗
PubMed1996

Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13.

An integrated approach involving physical mapping, identification of transcribed sequences, and computational analysis of genomic sequence was used to generate a detailed transcription map of the 1. 0-Mb region containing the breast cancer susceptibility locus BRCA2 on chromosome 13q12-q13. This region is included in the genetic interval bounded by D13S1444 and D13S310. Retrieved sequences from exon amplification or hybrid selection procedures were grouped into physical intervals and subsequently grouped into transcription units by clone overlap. Overlap was established by direct hybridization, cDNA library screening, PCR cDNA linking (island hopping), and/or sequence alignment. Extensive genomic sequencing was performed in an effort to understand transcription unit organization. In total, approximately 500 kb of genomic sequence was completed. The transcription units were further characterized by hybridization to RNA from a series of human tissues. Evidence for seven genes, two putative pseudogenes, and nine additional putative transcription units was obtained. One of the transcription units was recently identified as BRCA2 but all others are novel genes of unknown function as only limited alignment to sequences in public databases was observed. One large gene with a transcript size of 10.7 kb showed significant similarity to a gene predicted by the Caenorhabditis elegans genome and the Saccharomyces cerevisiae genome sequencing efforts, while another contained a motif sequence similar to the human 2',3' cyclic nucleotide 3' phosphodiesterase gene. Several retrieved transcribed sequences were not aligned into transcription units because no corresponding cDNAs were obtained when screening libraries or because of a lack of definitive evidence for splicing signals or putative coding sequence based on computational analysis. However, the presence of additional genes in the BRCA2 interval is suggested as groups of putative exons and hybrid selected clones that were transcribed in consistent orientations could be localized to common physical intervals.

BRCA2 Protein↗
PubMed1996

Blood-flow augmentation of intermittent pneumatic compression systems used for prevention of deep vein thrombosis prior to surgery.

PURPOSE: To compare, using Duplex ultrasonography, different intermittent pneumatic compression (IPC) systems to augment venous blood flow for deep venous thrombosis (DVT) prevention during and after surgery and during periods of immobility. METHODS: This cross-over study randomly assigned 26 young, healthy, adult subjects, without history of DVT, hypertension, diabetes, stroke. vascular or cardiac pathologies, to an order of knee-high, foam, single-pulse IPC device and thigh-high, vinyl, sequential-pulse pneumatic compression systems. Prior to making the flow measurement, the girth of the calf and thigh and length of the leg of each subject were determined. The right leg was used in this evaluation. RESULTS: The average flow augmentation, which is a direct measure of the amount of femoral vein blood flow velocity increase over the base, was 107%+/-49% with the knee-high system, and 77%+/-35% with the thigh-high IPC system (P<0.002). Augmentation was higher for 62% of the subjects with knee-high IPC, and for 23% of the subjects with the thigh-high system. Overall, the blood was actively moving through the vein during the decompression phase. On occasion, the velocity during the decompression phase would fall to zero for short intervals with both systems, indicating complete emptying of the vessel. Variation in limb anatomy did not significantly affect blood-flow augmentation with the knee-high IPC, but augmentation decreased with increase in girth with the thigh-high IPC. CONCLUSIONS: The study indicates that the knee-high, foam, single-pulse IPC device produces a significantly higher venous blood-flow augmentation than the thigh-high, vinyl, sequential-pulse system.

Adult↗
PubMed1996

Improved method to create the common ostium variant of the distal arteriovenous fistula for enhancing crural prosthetic graft patency.

PURPOSE: Successful use of the distal adjunctive arteriovenous fistula (dAVF) for the enhancement of prosthetic graft patency rates in the crural position is critically dependent on the qualitative and quantitative aspects of the arterial and venous runoff. Precise technical performance of the fistula is equally vital to secure optimal results. The purpose of this study was to determine current prosthetic graft patency and limb salvage rates using a modified version of the common ostium dAVF. METHODS: The standard method to create the common ostium variant of dAVF has been modified to improve apposition of the "otomy" sites of the artery and vein, avoid twisting and stenosis by terminating the fistula suture line at the artery-vein junctures, reshaping the ovoid ostium to a rectangular shape, and finally, use of multiple interrupted heel-toe sutures. RESULTS: Since 1979 we have created 290 fistulas in 281 patients who required leg revascularization procedures. In different time periods we have documented improving graft patency and limb salvage rates. Fistula patency, reflected by annual attrition rates of 13% to 26% per year, continues as a challenge for long-term results. Current 3-year secondary cumulative graft patency and limb salvage rates by life table analysis are 61% and 74%, respectively. The conduit material may play a role with regard to steal phenomena and the need for banding techniques. CONCLUSION: Configuration of the adjunctive dAVF may impact on prosthetic graft patency in the crural position. In addition, the type of graft material used for bypass may be instrumental in preventing or precipitating the steal phenomenon. These issues require further study to better understand flow dynamics, patterns of intimal hyperplasia, and blood distribution as a function of conduit material and impedance of the arterial and venous runoff.

Adult↗