Solitary neurofibroma of the larynx.
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Adult↗
Biomedical subjects
S Berry
Publications and source records attributed to S Berry.
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↗
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↗
Caring for communities.
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Hospitals, Community↗
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↗
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↗
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↗
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↗
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↗
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↗
The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.
Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.
BRCA2 Protein↗
Low incidence of BRCA2 mutations in breast carcinoma and other cancers.
Inherited mutant alleles of familial tumour suppressor genes predispose individuals to particular types of cancer. In addition to an involvement in inherited susceptibility to cancer, these tumour suppressor genes are targets for somatic mutations in sporadic cancers of the same type found in the familial forms. An exception is BRCA1, which contributes to a significant fraction of familial breast and ovarian cancer, but undergoes mutation at very low rates in sporadic breast and ovarian cancers. This finding suggests that other genes may be the principal targets for somatic mutation in breast carcinoma. A second, recently identified familial breast cancer gene, BRCA2 (refs 5-8), accounts for a proportion of breast cancer roughly equal to BRCA1. Like BRCA1, BRCA2 behaves as a dominantly inherited tumour suppressor gene. Individuals who inherit one mutant allele are at increased risk for breast cancer, and the tumours they develop lose the wild-type allele by heterozygous deletion. The BRCA2 coding sequence is huge, composed of 26 exons that span 10,443 bp. Here we investigate the rate of BRCA2 mutation in sporadic breast cancers and in a set of cell lines that represent twelve other tumour types. Surprisingly, mutations in BRCA2 are infrequent in cancers including breast carcinoma. However, a probable germline mutation in a pancreatic tumour cell line suggests a role for BRCA2 in susceptibility to pancreatic cancer.
BRCA2 Protein↗
The impact of zidovudine compared with didanosine on health status and functioning in persons with advanced HIV infection and a varying duration of prior zidovudine therapy. AIDS Clinical Trials Group 116/117 Study Group.
The objective of this study was to compare the effects of zidovudine and didanosine on health-related quality of life in persons with advanced HIV infection and varying duration of prior zidovudine exposure. It was designed as a substudy nested in two similar placebo-controlled active-control-arm randomized trials, using sites of the AIDS Clinical Trials Group participating in the randomized trials of zidovudine versus didanosine (ACTG 116 and 117). The patients comprised 356 participants enrolled in ACTG 116 and 117. All had HIV infection and either a CD4 count of <200 cells/mm3, or a CD4 count of <300 cells/mm3 plus symptoms of HIV disease. Participants were randomized equally within strata defined by duration of prior zidovudine therapy, to receive didanosine sachets at a dose of 500 mg daily (334 mg in subjects weighing <60 kg) or 750 mg daily (500 mg in subjects weighting <60 kg) plus inactive capsules resembling zidovudine, or to receive zidovudine capsules at a dose of 600 mg daily plus inactive sachets resembling didanosine. The main outcome measures were self-reported health-related quality of life, healthcare utilization, disability, work and symptom impact. The results showed no differences in reported symptom impact or healthcare utilization, and most measures of disability were similar. In the group with more than 8 weeks of prior zidovudine therapy, several of the health status scale scores for ongoing participants were significantly better for didanosine recipients, but average differences were small. Use of several different approaches to combining health status and survival showed no differences in the overall quality-time experiences between the treatment groups. Individuals taking zidovudine, low-dose didanosine and high-dose didanosine experienced 33, 34 and 35 weeks, respectively, in at least the typical health state if they had fewer than 8 weeks of previous zidovudine therapy, and had 23, 23 and 26 weeks, respectively, if they had more than 8 weeks previous use of zidovudine. Results did not differ when data were analysed within strata ofpatients who had any versus no prior exposure to zidovudine, or AIDS versus non-AIDS status. In conclusion, functional status and health-related quality of life were substantially similar among persons receiving either zidovudine or didanosine, regardless of the duration of prior zidovudine treatment.
Adult↗
Electric-field-induced electronic instability in amorphous Mo3Si superconducting films.
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Journal Article↗
Entropy, irreversibility and evolution.
The Second Law of Thermodynamics is investigated with respect to its value as an indicator of the direction of the evolutionary process. Non-thermodynamic entropy concepts and possible errors in the use of thermodynamic entropy are discussed. The importance of genuine thermodynamic potentials and their correct application for understanding processes is emphasized. There is no direct connection between evolutionary events such as speciation and thermodynamic entropy changes; the irreversibility of evolution is not a consequence of thermodynamic irreversibility.
Animals↗
Health status and function with zidovudine or zalcitabine as initial therapy for AIDS. A randomized controlled trial. Roche 3300/ACTG 114 Study Group.
OBJECTIVE: To evaluate the functional and health status implications of prescribing zalcitabine or zidovudine for initial therapy of acquired immunodeficiency syndrome (AIDS). DESIGN: A substudy of a randomized controlled trial. SETTING: Private and public clinics and referral centers. PATIENTS: Had human immunodeficiency virus (HIV) infection, less than 0.20 x 10(9)/L (200 microliters) CD4+ cells, and either a history of Pneumocystis carinii pneumonia or symptoms of HIV infection. Fifty-eight percent (338/668) of main study enrollees representing 90% of enrollees at participating sites were included in this substudy. INTERVENTIONS: Either zalcitabine at 0.75 mg every 8 hours plus inactive capsules identical in appearance to zidovudine or zidovudine at 200 mg (later 100 mg) every 4 hours plus inactive tablets identical in appearance to zalcitabine. MAIN OUTCOME MEASURES: Results of a periodically completed self-report survey instrument containing specific questions about symptom impact, disability, work, functioning, and utilization as well as nine health and functioning scales adapted from the Medical Outcomes Study (MOS). RESULTS: Zalcitabine recipients were twice as likely to undergo an invasive procedure (P = .004) or be admitted to hospital (P = .01). Zalcitabine recipients reported greater than 40% more symptoms that interfered with activity (P = .001) and greater than 50% more disability days (P < .01). They also had a 7% lower employment rate and a 35% lower monthly income. Average observed health status scores were lower in zalcitabine recipients overall, but especially in the early portion of the study. New methods for combining survival and health status data showed that, over 76 weeks of study, a typical zidovudine recipient spent about 4 (10%) more weeks with at least the typical health state than did a typical zalcitabine recipient. CONCLUSIONS: Zidovudine has substantial advantages over zalcitabine in initial monotherapy of AIDS in terms of functional outcomes such as symptoms impact, disability, work, utilization, and health status. In this case, the differences in functional outcomes presaged differences in physiological and clinical measures. The inclusion of functional outcomes can greatly improve the information available from a clinical trial.
Acquired Immunodeficiency Syndrome↗
A comparison between detailed and simple histories in the diagnosis of genital herpes complicating pregnancy.
OBJECTIVE: All women seropositive for herpes simplex virus-2 are at risk for asymptomatic viral shedding at the onset of labor and neonatal transmission of the virus. Unfortunately, only 20% to 35% of seropositive adults give a history consistent with genital herpes. We evaluated whether more detailed questioning during pregnancy might elucidate symptoms predictive of seropositivity and therefore better identify women at risk for herpes simplex virus shedding at delivery. STUDY DESIGN: During pregnancy 201 randomly selected women were asked in-depth questions about recurrent genital symptoms and whether they "currently have or have ever had genital herpes." An assessment was made whether the patient had a history compatible with genital herpes. This assessment and the "yes/no" history of genital herpes obtained by physicians at the initial prenatal visit were both compared with herpes simplex virus serologic studies by Western blot. RESULTS: Of 201 patients interviewed, 177 gave no history of genital herpes. Of these, 30.4% were seropositive for herpes simplex virus-2. Detailed histories on these 177 patients indicated that among the 159 subjects without suggestive symptoms or with somewhat suggestive symptoms the corresponding rates of seropositivity were 28% and 30%. Among the 18 (10.2%) subjects with highly suggestive symptoms, only 50% were seropositive. The positive predictive values for recurrent genital symptoms to predict herpes simplex virus-2 seropositivity ranged from 30% to 57%. CONCLUSION: A detailed history of genital symptoms is no better at identifying an herpes simplex virus-2 seropositive patient than is simply asking if she has ever had genital herpes. Serologic screening is a more accurate method of identifying women with past genital herpes or those who are at risk for acquiring genital herpes during pregnancy.
Adolescent↗
5-Hydroxytryptamine2A (5-HT2A) receptor desensitization can occur without down-regulation.
The connection between agonist-induced desensitization and down-regulation of 5-hydroxytryptamine2A (5-HT2A) receptors was examined in a clonal cell line that stably expresses the 5-HT2A receptor. Brief (2-hr) and prolonged (24-hr) exposure to the agonist quipazine or the agonist 4-iodo-(2,5-dimethoxy)- phenylisopropylamine (DOI) diminished 5-HT2A receptor-mediated phosphoinositide hydrolysis; no change in 5-HT2A receptor number or affinity was measured after 24 hr of exposure to DOI or quipazine. Immunohistochemical studies demonstrated that a 24-hr exposure to DOI did not alter surface 5-HT2A receptor immunoreactivity. Western blot analysis with G alpha q- and G alpha 11-selective antibodies indicate that a 24-hr agonist exposure did not alter the levels of phospholipase C-dependent G proteins. These results suggest that desensitization after prolonged DOI exposure can occur via a process independent of the levels of phospholipase C-coupled G proteins. Studies with a mutant 5-HT2A receptor (F340L) indicated that binding per se is not sufficient for desensitization. Down-regulation of the protein kinase C isozymes alpha and epsilon by overnight exposure to phorbol-12,13-dibutyrate attenuated the intermediate phase (i.e., after 2-6 hr of agonist exposure) of DOI- and quipazine-induced desensitization. These results indicate that the intermediate phase of DOI-induced desensitization is mediated by the alpha- and/or epsilon-protein kinase C isozymes but that neither is involved in the later phase (i.e., after 24 hr of agonist exposure) of desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)
3T3 Cells↗