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Biomedical subjects

D Barnes

Publications and source records attributed to D Barnes.

At least 55 records · Page 3Linked to original sources
PubMed1999

IL-7 enhances Ag-specific human T cell response by increasing expression of IL-2R alpha and gamma chains.

Interleukin-7 has demonstrated potent enhancing effects on the growth and differentiation of several immature cell types, including thymocytes, and on survival of resting and antigen activated T cells. In this study, we evaluated the effects of IL-7 on post-thymic antigen-specific T cells from human blood. IL-7 was found to enhance proliferation responses and IFN-gamma secretion of myelin or recall Ag-specific Th1 cells through the selective up-regulation of the IL-2Ralpha and gamma but not beta chains in both an Ag-dependent and Ag-independent manner, but did not affect monocytes, B cells, or NK cells. These functions of IL-7 enhanced the detection of Th1 but not Th2 cell frequency by >2.5 fold, and promoted selection of Ag-specific Th1 cells by the limiting dilution method. Moreover, IL-7 pretreatment conferred increased resistance of CD4+ T cells to CD8+ cell lysis. These studies demonstrate that IL-7 promotes the growth and survival of circulating Ag-specific human Th1 cells through a mechanism that probably involves the gammac common receptor for IL-2 family members that includes IL-7.

Antigens, CD19↗
PubMed1999

Comparative genomic hybridization of breast tumors stratified by histological grade reveals new insights into the biological progression of breast cancer.

How does breast cancer progress? There is evidence both to support (S. W. Duffy et al., Br. J. Cancer, 64: 1133-1138, 1991; R. Rajakariar et al., Br. J. Cancer, 71: 150-154, 1995) and refute (M. Hakama et al., Lancet, 345: 221-224, 1995; R. R. Millis et al., Eur. J. Cancer, 34: 548-553, 1998) the hypothesis of dedifferentiation; the theory that as breast cancers grow they evolve from well differentiated (grade I) to poorly differentiated (grade III) tumors. We provide evidence to support the view that the majority of grade I tumors do not progress to grade III tumors. Comparative genomic hybridization was used to screen entire genomes of a large sample (40 grade I and 50 grade III) of invasive ductal breast carcinomas, stratified by grade. We found distinct genetic differences between grade I and grade III tumors. Significantly, we found that 65% of grade I tumors lost the long arm of chromosome 16 compared with only 16% of grade III tumors. This pattern of loss leads us to conclude that the majority of grade I tumors do not progress to grade III tumors. These findings have important implications because they suggest that different breast tumor grades may have distinct molecular origins, pathogenesis, and behavior and, therefore, potentially present distinct molecular targets for research and treatment.

Breast Neoplasms↗
PubMed1999

Imaging protein kinase Calpha activation in cells.

Spatially resolved fluorescence resonance energy transfer (FRET) measured by fluorescence lifetime imaging microscopy (FLIM), provides a method for tracing the catalytic activity of fluorescently tagged proteins inside live cell cultures and enables determination of the functional state of proteins in fixed cells and tissues. Here, a dynamic marker of protein kinase Calpha (PKCalpha) activation is identified and exploited. Activation of PKCalpha is detected through the binding of fluorescently tagged phosphorylation site-specific antibodies; the consequent FRET is measured through the donor fluorophore on PKCalpha by FLIM. This approach enabled the imaging of PKCalpha activation in live and fixed cultured cells and was also applied to pathological samples.

3T3 Cells↗
PubMed1999

Lead and copper contamination of soil from industrial activities and firing ranges.

Lead still remains one of the most thoroughly investigated heavy metals in the environment. Although the identification of lead in soil is a routine matter, its environmental consequence is still much debated because of its potential mobility. We have investigated lead- and copper-contaminated soil from two different areas. One was in an urban area, which formerly had a lead smelter within the city. The other a firing range, in which hundreds of thousands of rounds were fired into a very large mound known as a berm. Homogeneity tests, depth profiles, and Pb-Cu correlations are discussed.

Copper↗
PubMed1999

Macleod's syndrome presenting with spontaneous pneumothorax.

A 19-year-old woman with a recent history of recurrent bronchitis presented with a spontaneous left pneumothorax. Review of the chest radiographs revealed features of Macleod's syndrome on the same side, with unilateral lucency and hypoplastic hilar vessels. To our knowledge this is the first report of Macleod's syndrome presenting with spontaneous pneumothorax.

Adult↗
PubMed1999

Simian virus 40 large T antigen J domain and Rb-binding motif are sufficient to block apoptosis induced by growth factor withdrawal in a neural stem cell line.

Serum-free mouse embryo (SFME) cells are a neural stem cell line that is dependent upon epidermal growth factor (EGF) for survival. Removal of EGF results in the G1 arrest and apoptosis of SFME cells. We have shown that the expression of simian virus 40 large T antigen in SFME cells blocks apoptosis and allows cell survival and division in the absence of EGF. Therefore the presence of T antigen abrogates the EGF requirement. The steady-state levels of p53, p21, and mdm-2 do not increase as SFME cells undergo apoptosis upon EGF withdrawal. Furthermore, the amino-terminal 136 amino acids (N136) of T antigen are sufficient to block death and to promote proliferation in the absence of EGF, while the carboxy-terminal fragment (C251-708), which contains the p53 binding site, is unable to block death. Taken together, these data suggest that SFME cells deprived of EGF undergo p53-independent apoptosis. Mutations that disrupt either the J domain or Rb family binding abolish the ability of T antigen to block SFME cell apoptosis and to promote cell growth. We conclude that T antigen must act on one or more members of the Rb family to inhibit SFME cell apoptosis.

Animals↗
PubMed1999

Assessment of reliability of lung function screening programs or longitudinal studies.

The aim was to determine reliability of lung function measurements performed according to recommendations of the American Thoracic Society (ATS) at a screening program in a large South African gold mine and to determine the usefulness of the reliability coefficient G for monitoring the reliability of lung function measurements in a mass screening program. The reliability coefficient G estimates the amount of random error of measurement, relative to the total variation in a measurement. The coefficient G was calculated as a correlation coefficient between two consecutive lung function tests performed within 6 mo, over a period of 43 mo on 3,378 miners. There was significant temporal variability in the reliability. For FEV(1), the coefficient G showed increased variability over the first 5 mo and stabilized at a value of 0.93 for the next 23 mo, after which it systematically declined over the next 15 mo. We estimated that in a large screening program, an optimal sample size of around 900 miners, examined randomly throughout the year, on a yearly basis, would provide a sufficient sample to examine monthly or quarterly fluctuation in the reliability. The value of the reliability coefficient G did not change when the time between two consecutive tests increased up to 15 mo. In conclusion, monitoring of lung function reliability in a screening program by the reliability coefficient G should improve data quality, and provide a measure on which the confidence in a decision-making process could be based when examining temporal changes in lung function for individual subjects.

Adult↗
PubMed1999

Serum vitellogenin levels and reproductive impairment of male Japanese Medaka (Oryzias latipes) exposed to 4-tert-octylphenol.

The induction of synthesis of the "female" yolk precursor protein vitellogenin (VTG) in male fish by estrogenic chemicals in the environment has been demonstrated in many recent reports. However, little is known about the organismal and biological significance of this phenomenon. To examine the relationship between VTG production in male fish and reproductive impairment, adult male medaka were exposed to 4-tert-octylphenol (OP), a known environmental estrogen, in concentrations ranging from 20 to 230 ppb for 21 days, under flow-through conditions. Following exposure, male fish were mated, in the absence of OP, with unexposed females. Breeding groups composed of exposed males and control females produced about 50% fewer eggs than control groups. VTG levels in serum of male fish increased with increasing OP exposure concentration and decreased after OP exposure was discontinued. Nevertheless, significant correlations (p<0.01) were observed between VTG levels in exposed male fish and 1) OP exposure concentrations, 2) percent of fertilized eggs, and 3) survival of embryos. OP-induced VTG synthesis and reproductive impairment appear to be closely linked phenomena. Histological examination indicated spermatogenesis in OP-exposed fish was inhibited, and some exposed fish had oocytes in their testes. Finally, OP caused a significant increase in the number of abnormally developing embryos, suggesting that OP may be genotoxic as well as estrogenic.

Animals↗
PubMed1999

Migraine in a specialist menopause clinic.

OBJECTIVES: Epidemiological studies suggest that migraine and headache worsen during the climacteric. The authors noted that women attending a specialist hospital-based menopause clinic frequently reported vasomotor and other common climacteric symptoms but few spontaneously reported headache or migraine. The aim of this study was to assess the prevalence of migraine and headache in women attending this clinic. METHODS: Seventy-four women consecutively attending the menopause clinic at St. Bartholomew's Hospital were questioned about headache. Those with a positive response were further interviewed to obtain a headache diagnosis. RESULTS: Headache was found to be a common symptom affecting 57% of women in the 3 months before attending a specialist menopause clinic. Migraine affected 29% of patients in the preceding 3 months. This condition was associated with significant disability: 80% of women reported that attacks were more frequent than once a month; 75% reported that the attacks were severe; 50% reported that the duration of treated attacks was longer than 1 day. DISCUSSION: The high prevalence of headache and migraine in this group suggests that perimenopausal women should routinely be asked about headache and offered appropriate advice. This should include optimal attack therapy and strategies for preventing attacks, which may include hormone replacement therapy (HRT). Further studies are warranted to evaluate the relationship between climacteric symptoms, headaches, migraine and HRT.

Adolescent↗
PubMed1998

Use of a clinical model for safe management of patients with suspected pulmonary embolism.

BACKGROUND: The low specificity of ventilation-perfusion lung scanning complicates the management of patients with suspected pulmonary embolism. OBJECTIVE: To determine the safety of a clinical model for patients with suspected pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Five tertiary care hospitals. PATIENTS: 1239 inpatients and outpatients with suspected pulmonary embolism. INTERVENTIONS: A clinical model categorized pretest probability of pulmonary embolism as low, moderate, or high, and ventilation-perfusion scanning and bilateral deep venous ultrasonography were done. Testing by serial ultrasonography, venography, or angiography depended on pretest probability and lung scans. MEASUREMENTS: Patients were considered positive for pulmonary embolism if they had an abnormal pulmonary angiogram, abnormal ultrasonogram or venogram, high-probability ventilation-perfusion scan plus moderate or high pretest probability, or venous thromboembolic event during the 3-month follow-up. All other patients were considered negative for pulmonary embolism. Rates of pulmonary embolism during follow-up in patients who had a normal lung scan and those with a non-high-probability scan and normal serial ultrasonogram were compared. RESULTS: Pretest probability was low in 734 patients (3.4% with pulmonary embolism), moderate in 403 (27.8% with pulmonary embolism), and high in 102 (78.4% with pulmonary embolism). Three of the 665 patients (0.5% [95% CI, 0.1% to 1.3%]) with low or moderate pretest probability and a non-high-probability scan who were considered negative for pulmonary embolism had pulmonary embolism or deep venous thrombosis during 90-day follow-up; this rate did not differ from that in patients with a normal scan (0.6% [CI, 0.1% to 1.8%]; P > 0.2). CONCLUSION: Management of patients with suspected pulmonary embolism on the basis of pretest probability and results of ventilation-perfusion scanning is safe.

Algorithms↗
PubMed1998

Structural and kinetic evidence for strain in biological catalysis.

A classic hypothesis for enzyme catalysis is the induction of strain in the substrate. This notion was first expressed by Haldane with the lock and key analogy-"the key does not fit the lock perfectly but exercises a certain strain on it" (1). This mechanism has often been invoked to explain the catalytic efficiency of enzymes but has been difficult to establish conclusively (2-7). Here we describe X-ray crystallographic and mutational studies of an antibody metal chelatase which strongly support the notion that this antibody catalyzes metal ion insertion into the porphyrin ring by inducing strain. Analysis of the germline precursor suggests that this strain mechanism arose during the process of affinity maturation in response to a conformationally distorted N-alkylmesoporphyrin.

Amino Acid Sequence↗
PubMed1998

A microsatellite within the MUC1 locus at 1q21 is altered in the neoplastic cells of breast cancer patients.

Paired DNA samples from the neoplastic and nonneoplastic cells of 118 patients with the sporadic, nonfamilial form of breast cancer were analyzed for evidence of genetic alteration at a polymorphic microsatellite mapped to intron 6 within the MUC1 gene at 1q21. Two other microsatellite loci, D1S104 and APO-A2, which also map to 1q21, were analyzed as well. The frequency of alteration at the microsatellite within the MUC1 locus was significantly higher than D1S104 or APO-A2 (P < 0.001). Analysis by Southern blotting of the VNTR region of the MUC1 gene revealed an amplification of one allele in 34 of 54 informative cases (63%). There was no significant association between these alterations and alterations of the microsatellite within the same locus, suggesting independent mechanisms were responsible for the genetic changes. Microsatellite loci D17S579 at 17q21, the site of the BRCA1 gene, and D18S34 at 18q21-qter, the deleted in colorectal cancer locus, were also analyzed by PCR. Alterations at D17S579 and D18S34 were detected in 18.8% and 6.2% of patients, respectively (P < 0.001, and P < 0.1 relative to the frequency of alteration at D1S104 or APO-A2). A previously described polymorphism of hMSH2 was altered in 16.4% of cases.

Breast Neoplasms↗
PubMed1998

Schizosaccharomyces pombe isp4 encodes a transporter representing a novel family of oligopeptide transporters.

We have recently cloned an oligopeptide transport gene from Candida albicans denoted OPT1. This gene showed significant sequence similarity to three open reading frames (ORFs) with no previously established function: isp4 from Schizosaccharomyces pombe and Saccharomyces cerevisiae YJL212C and YPR194C, identified during the genome project. The S. pombe gene isp4 was originally identified by Sato et al. as a gene that was upregulated through nitrogen starvation induction of meiosis. However, an isp4delta strain exhibited a wild-type phenotype with respect to sexual differentiation. We have found that the same isp4delta strain is deficient in tetrapeptide transport activity as measured by its resistance to toxic tetrapeptides, by its inability to accumulate a radiolabelled tetrapeptide and by the inability to use tetrapeptides as a sole source of an amino acid to satisfy an auxotrophic requirement. Similarly, we found that the ORF YPR194C from S. cerevisiae encodes an oligopeptide transporter. Sequence analyses as well as physiological evidence has led us to propose that the proteins encoded by isp4 and the genes identified from S. cerevisiae and C. albicans comprise a new group of transporters specific for small oligopeptides, which we have named the OPT family.

Amino Acid Sequence↗