Hepatocellular adenoma of the placenta: report of a case associated with maternal bicornuate uterus and fetal renal dysplasia.
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Adenoma, Liver Cell↗
Biomedical subjects
D Thomas
Publications and source records attributed to D Thomas.
Inactivation of Bacillus subtilis spores on packaging surfaces by u. v. excimer laser irradiation.
Ultraviolet (u.v.) laser irradiation has been used to inactivate Bacillus subtilis spores deposited on to planar aluminium- and polyethylene-coated packaging surfaces. Kill kinetics were found to be diphasic, with an initial rapid inactivation phase followed by tailing. Although no definitive evidence was obtained, it is thought that spores located within packaging crevices/pores were primarily responsible for the observed tailing. Surviving spores were also found on the unexposed underside of cards and, to a lesser extent, within clumps. The log count reduction in B. subtilis was dependent on spore loading and total u.v. dose. In comparison, packaging surface composition, fluence (2-18 Jm-2) and frequency (40-150 Hz) had only a negligible effect. By irradiating boards carrying 106 spores, with a dose of 11.5 J cm-2, a log count reduction >5 was obtained. The mode of spore inactivation was primarily through DNA disruption. This was confirmed by the high sensitivity of spores lacking protective, small, acid-soluble proteins, in addition to the high frequency of auxotrophic and asporogenous mutations found amongst survivors.
Bacillus subtilis↗
Plasma adrenomedullin, a new independent predictor of prognosis in patients with chronic heart failure.
BACKGROUND: Adrenomedullin, a potent endogenous vasodilating and natriuretic peptide, may play an important role in the pathophysiology of chronic heart failure. Plasma levels of immunoreactive adrenomedullin were examined for prediction of prognosis in chronic heart failure. METHODS AND RESULTS: Plasma levels of immunoreactive-ADM (ir-ADM) were measured by radioimmunoassay in 117 chronic heart failure patients with idiopathic or ischaemic cardiomyopathy (mean ejection fraction: 28 +/- 10%, in the NYHA functional class I/II/III/IV:8/73/29/7, and treated with ACE inhibitors and diuretics. Plasma levels of immunoreactive adrenomedullin were significantly increased in chronic heart failure patients by comparison to controls (618 +/- 293 pg x ml(-1) vs 480 +/- 135 pg x ml(-1), P=0.01). During the follow-up period (237 +/- 137 days) 14 cardiovascular deaths and four urgent cardiac transplantations occurred. In the univariate Cox model, immunoreactive adrenomedullin plasma levels were related to prognosis (P=0.004). A multivariate analysis including heart rate, systolic blood pressure, NYHA class, left ventricular ejection fraction, left ventricular echocardiographic end-diastolic diameter, plasma levels of immunoreactive adrenomedullin, endothelin-1, norepinephrine and atrial natriuretic peptide was performed: plasma levels of immunoreactive adrenomedullin (P=0.03), of endothelin-1 (P=0.0001), and systolic blood pressure (P=0.003) were significantly associated with outcome. CONCLUSION: Our results suggest that elevated plasma levels of immunoreactive adrenomedullin are an independent predictor of prognosis in predominantly mild to moderate chronic heart failure treated by conventional therapy and provide additional prognostic information.
Adrenomedullin↗
Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence.
This report describes a cross-sectional survey of the prevalence of antibodies to hepatitis C virus (anti-HCV) in a rural Egyptian community in the Nile Delta. One half of the village households were systematically selected and examined by questionnaire and testing sera for anti-HCV and HCV RNA. Blood samples were obtained from 3, 888 (75.4%) of 5,156 residents >/=5 years of age; an additional 111 samples were obtained from children younger than 5 years. Overall, 973 (24.3%) of 3,999 residents were anti-HCV-positive, and the age- and gender-adjusted seroprevalence was 23.7%. Anti-HCV prevalence increased sharply with age, from 9.3% in those 20 years of age and younger to >50% in those older than 35 years. Currently or previously married individuals were more likely to be seropositive than those never married, controlling for age (Mantel-Haenszel risk ratio = 1.8; 95% CI: 1.3, 2.6). Of the 905 anti-HCV-positive samples tested, 65% were also positive for HCV RNA. Active schistosomal infection was not associated with anti-HCV status; however, history of antischistosomal injection therapy (reported by 19% of anti-HCV positives) was a risk for anti-HCV (age-adjusted risk ratio = 1.3; 95% CI: 1.2, 1.5). This study, the largest community-based survey to date, supports earlier reports of high levels of anti-HCV among adults in rural areas of Egypt, although many of those who are seropositive will not have active liver disease. The large reservoir of HCV infection in the community provides an opportunity to investigate risk factors for transmission, the natural history of infection and effectiveness of preventive methodologies, and raises concern about the prospect of an increasing incidence of chronic liver disease in the coming decades.
Adult↗
A comparison of fluorescent Ca2+ indicator properties and their use in measuring elementary and global Ca2+ signals.
Quantifying the magnitude of Ca2+ signals from changes in the emission of fluorescent indicators relies on assumptions about the indicator behaviour in situ. Factors such as osmolarity, pH, ionic strength and protein environment can affect indicator properties making it advantageous to calibrate indicators within the required cellular or subcellular environment. Selecting Ca2+ indicators appropriate for a particular application depends upon several considerations including Ca2+ binding affinity, dynamic range and ease of loading. These factors are usually best determined empirically. This study describes the in-situ calibration of a number of frequently used fluorescent Ca2+ indicators (Fluo-3, Fluo-4, Calcium Green-1, Calcium Orange, Oregon Green 488 BAPTA-1 and Fura-Red) and their use in reporting low- and high-amplitude Ca2+ signals in HeLa cells. All Ca2+ indicators exhibited lower in-situ Ca2+ binding affinities than suggested by previously published in-vitro determinations. Furthermore, for some of the indicators, there were significant differences in the apparent Ca2+ binding affinities between nuclear and cytoplasmic compartments. Variation between indicators was also found in their dynamic ranges, compartmentalization, leakage and photostability. Overall, Fluo-3 proved to be the generally most applicable Ca2+ indicator, since it displayed a large dynamic range, low compartmentalization and an appropriate apparent Ca2+ binding affinity. However, it was more susceptible to photobleaching than many of the other Ca2+ indicators.
Aniline Compounds↗
Is there a simpler method for predicting lower pole stone clearance after shockwave lithotripsy than measuring infundibulopelvic angle?
BACKGROUND AND PURPOSE: Several anatomic factors influence the clearance of lower pole stones treated with shockwave lithotripsy (SWL). One of these is the infundibulopelvic angle, but its measurement is complex. METHODS: We proposed a more simple measure of caliceal dependence, the caliceal pelvic height (CPH), which we defined as the distance between a horizontal line from the lowermost point of the calix containing the stone to the highest point of the lower lip of the renal pelvis. RESULTS: In 62 patients who had SWL for solitary lower pole stones, a CPH < 15 mm was associated with a stone clearance rate of 92%, whereas with a CPH > or = 15 mm, the clearance rate was only 52% (p < 0.05). A majority (74%) of the patients with an infundibular width of > or = 5 mm were rendered stone free compared with 40% of those with a width of < 5 mm (p < 0.05). CONCLUSION: Measurement of the CPH, in conjunction with other anatomic factors, may more accurately predict the outcome of SWL in patients with lower pole stones.
Adult↗
The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome.
BACKGROUND: Orthostatic hypotension during upright tilt is an important physical disorder in patients with chronic fatigue syndrome. We have tested its occurrence during prolonged standing, whether it is correctable, and whether reduced circulating erythrocyte volume is present. METHODS: Fifteen patients were randomly selected from a large population of patients with chronic fatigue syndrome, studied, and observed for several years (by DSB). Blood pressure (BP) and heart rate (HR) measured with Dinamap every minute for 30 minutes supine and 60 minutes standing were compared with these findings in 15 healthy age- and gender-matched control subjects and later during lower body compression with military antishock trousers (MAST). Plasma catecholamines and circulating erythrocyte and plasma volumes were also measured by isotopic dilution methods. RESULTS: Abnormal findings in the patients included excessive orthostatic reductions in systolic (P < 0.001) and diastolic BP (P < 0.001) and excessive orthostatic tachycardia (P < 0.01), together with presyncopal symptoms in 11 of the 15 patients and in none of the control subjects after standing for 60 min. Lower body compression with the MAST restored all orthostatic measurements to normal and overcame presyncopal symptoms within 10 min. Circulating erythrocyte but not plasma volumes were subnormal in the 12 women (P < 0.01) and plasma norepinephrine concentration rose excessively after standing for 10 min. CONCLUSION: Delayed orthostatic hypotension and/or tachycardia caused by excessive gravitational venous pooling, which is correctable with external lower-body compression, together with subnormal circulating erythrocyte volume, are very frequent, although not invariably demonstrable, findings in moderate to severe chronic fatigue syndrome. When present, they may be involved in its pathogenesis.
Adolescent↗
Acquired, but not innate, immune responses to Streptococcus pneumoniae are compromised by neutralization of CD40L.
Streptococcus pneumoniae is a significant pathogen of young children and the elderly. Systemic infection by pneumococci is a complex process involving several bacterial and host factors. We have investigated the role of CD40L in host defense against pneumococcal infection. Treatment of mice with MR-1 antibody (anti-CD154/CD40L) markedly reduced antibody responses to the pneumococcal protein PspA, elicited by immunization of purified protein or whole bacteria. In mice immunized with whole bacteria, MR-1 treatment reduced antibody responses to capsular polysaccharides but not cell wall polysaccharides. MR-1 did not suppress antibody responses to isolated capsular polysaccharides but did reduce the production of antibody to a capsular polysaccharide-protein conjugate, indicating that when presented in the context of whole bacteria, the humoral response to capsular polysaccharides is partially T-cell dependent. Despite the reduction of the protective humoral responses to pneumococcal infection, administration of MR-1 had no effect on sepsis, lung infection, or nasal carriage in nonimmune mice inoculated with virulent pneumococci. Thus, short-term neutralization of CD40L does not compromise innate host defenses against pneumococcal invasion.
Animals↗
Enrichment of immediate-early 1 (m123/pp89) peptide-specific CD8 T cells in a pulmonary CD62L(lo) memory-effector cell pool during latent murine cytomegalovirus infection of the lungs.
Interstitial cytomegalovirus (CMV) pneumonia is a clinically relevant complication in recipients of bone marrow transplantation (BMT). Recent data for a model of experimental syngeneic BMT and concomitant infection of BALB/c mice with murine CMV (mCMV) have documented the persistence of tissue-resident CD8 T cells after clearance of productive infection of the lungs (J. Podlech, R. Holtappels, M.-F. Pahl-Seibert, H.-P. Steffens, and M. J. Reddehase, J. Virol. 74:7496-7507, 2000). It was proposed that these cells represent antiviral "standby" memory cells whose functional role might be to help prevent reactivation of latent virus. The pool of pulmonary CD8 T cells was composed of two subsets defined by the T-cell activation marker L-selectin (CD62L): a CD62L(hi) subset of quiescent memory cells, and a CD62L(lo) subset of recently resensitized memory-effector cells. In this study, we have continued this line of investigation by quantitating CD8 T cells specific for the three currently published antigenic peptides of mCMV: peptide YPHFMPTNL processed from the immediate-early protein IE1 (pp89), and peptides YGPSLYRRF and AYAGLFTPL, derived from the early proteins m04 (gp34) and M84 (p65), respectively. IE1-specific CD8 T cells dominated in acute-phase pulmonary infiltrates and were selectively enriched in latently infected lungs. Notably, most IE1-specific CD8 T cells were found to belong to the CD62L(lo) subset representing memory-effector cells. This finding is in accordance with the interpretation that IE1-specific CD8 T cells are frequently resensitized during latent infection of the lungs and may thus be involved in the maintenance of mCMV latency.
Animals↗
The putative natural killer decoy early gene m04 (gp34) of murine cytomegalovirus encodes an antigenic peptide recognized by protective antiviral CD8 T cells.
Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, the m152 gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the "missing self." The retention, however, is counteracted by the m04 early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 might serve to silence NK cells and thereby complete the immune evasion of MCMV. In light of these current views, we provide here results demonstrating an in vivo role for gp34 in protective antiviral immunity. We have identified an antigenic nonapeptide derived from gp34 and presented by the MHC-I molecule D(d). Besides the immunodominant immediate-early nonapeptide consisting of IE1 amino acids 168-176 (IE1(168-176)), the early nonapeptide m04(243-251) is the second antigenic peptide described for MCMV. The primary immune response to MCMV generates significant m04-specific CD8 T-cell memory. Upon adoptive transfer into immunodeficient recipients, an m04-specific CTL line controls MCMV infection with an efficacy comparable to that of an IE1-specific CTL line. Thus, gp34 is the first noted early protein of MCMV that escapes viral immune evasion mechanisms. These data document that MCMV is held in check by a redundance of protective CD8 T cells recognizing antigenic peptides in different phases of viral gene expression.
Animals↗
Readministration of adenovirus vector in nonhuman primate lungs by blockade of CD40-CD40 ligand interactions.
The interaction between CD40 on B cells and CD40 ligand (CD40L) on activated T cells is important for B-cell differentiation in T-cell-dependent humoral responses. We have extended our previous murine studies of CD40-CD40L in adenoviral vector-mediated immune responses to rhesus monkeys. Primary immune responses to adenoviral vectors and the ability to readminister vector were studied in rhesus monkeys in the presence or absence of a transient treatment with a humanized anti-CD40 ligand antibody (hu5C8). Adult animals were treated with hu5C8 at the time vector was instilled into the lung. Immunological analyses demonstrated suppression of adenovirus-induced lymphoproliferation and cytokine responses (interleukin-2 [IL-2], gamma interferon, IL-4, and IL-10) in hu5C8-treated animals. Animals treated with hu5C8 secreted adenovirus-specific immunoglobulin M (IgM) levels comparable to control animals, but did not secrete IgA or develop neutralizing antibodies; consequently, the animals could be readministered with adenovirus vector expressing alkaline phosphatase. A second study was designed to examine the long-term effects on immune functions of a short course of hu5C8. Acute hu5C8 treatment resulted in significant and prolonged inhibition of the adenovirus-specific humoral response well beyond the time hu5C8 effects were no longer significant. These studies demonstrate the potential of hu5C8 as an immunomodulatory regimen to enable administration of adenoviral vectors, and they advocate testing this model in humans.
Adenoviridae↗
Repression of virus-induced interferon A promoters by homeodomain transcription factor Ptx1.
Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by substitutions in the proximal positive virus responsive element A (VRE-A) of their promoters and by the presence or absence of a distal negative regulatory element (DNRE). The functional feature of the DNRE is to specifically act by repression of VRE-A activity. With the use of the yeast one-hybrid system, we describe here the identification of a specific DNRE-binding protein, the pituitary homeobox 1 (Ptx1 or Pitx1). Ptx1 is detectable in different cell types that differentially express IFN-A genes, and the endogenous Ptx1 protein binds specifically to the DNRE. Upon virus induction, Ptx1 negatively regulates the transcription of DNRE-containing IFN-A promoters, and the C-terminal region, as well as the homeodomain of the Ptx1 protein, is required for this repression. After virus induction, the expression of the Ptx1 antisense RNA leads to a significant increase of endogenous IFN-A gene transcription and is able to modify the pattern of differential expression of individual IFN-A genes. These studies suggest that Ptx1 contributes to the differential transcriptional strength of the promoters of different IFN-A genes and that these genes may provide new targets for transcriptional regulation by a homeodomain transcription factor.
Animals↗
Recollection of children following intensive care.
BACKGROUND AND AIMS: The recollections of critically ill children following discharge from the paediatric intensive care unit (PICU) have not previously been described. We have interviewed such children to establish the nature of their recollections. METHODS: Children aged 4 years and above were interviewed following discharge from the PICU at the Queens Medical Centre, Nottingham, either in hospital or at home, using a semistructured interview. Their recollections were recorded and interpreted by content analysis. RESULTS: A total of 38 interviews were carried out; 44 specific recollections were reported, the majority being neutral (60%) or positive (25%). Only 15% of recollections were negative. Negative recollections related to aspects of medical care and environmental factors. No child treated with neuromuscular blocking agents remembered any period of therapeutic paralysis. CONCLUSIONS: Children's recollections of PICU are mainly neutral or positive. Mechanically ventilated children sedated with midazolam and morphine remember little of endotracheal intubation.
Adolescent↗
Novel characteristics of a misprocessed mutant HERG channel linked to hereditary long QT syndrome.
Hereditary long QT syndrome (hLQTS) is a heterogeneous genetic disease characterized by prolonged QT interval in the electrocardiogram, recurrent syncope, and sudden cardiac death. Mutations in the cardiac potassium channel HERG (KCNH2) are the second most common form of hLQTS and reduce the delayed rectifier K(+) currents, thereby prolonging repolarization. We studied a novel COOH-terminal missense mutation, HERG R752W, which segregated with the disease in a family of 101 genotyped individuals. When the mutant cRNA was expressed in Xenopus oocytes it produced enhanced rather than reduced currents. Simulations using the Luo-Rudy model predicted minimal shortening rather than prolongation of the cardiac action potential. Consequently, a normal or shortened QT interval would be expected in contrast to the long QT observed clinically. This anomaly was resolved by our observation that the mutant protein was not delivered to the plasma membrane of mammalian cells but was retained intracellularly. We found that this trafficking defect was corrected at lower incubation temperatures and that functional channels were now delivered to the plasma membrane. However, trafficking could not be restored by chemical chaperones or E-4031, a specific blocker of HERG channels. Therefore, HERG R752W represents a new class of trafficking mutants in hLQTS. The occurrence of different classes of misprocessed channels suggests that a unified therapeutic approach for altering HERG trafficking will not be possible and that different treatment modalities will have to be matched to the different classes of trafficking mutants.
Action Potentials↗
Catalysis by anti-idiotypic antibodies.
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Acetylcholinesterase↗
Association between air pollution and lung function growth in southern California children.
Average growth of lung function over a 4-yr period, in three cohorts of southern California children who were in the fourth, seventh, or tenth grade in 1993, was modeled as a function of average exposure to ambient air pollutants. In the fourth-grade cohort, significant deficits in growth of lung function (FEV(1), FVC, maximal midexpiratory flow [MMEF], and FEF(75)) were associated with exposure to particles with aerodynamic diameter less than 10 micrometer (PM(10)), PM(2.5), PM(10)-PM(2.5), NO(2), and inorganic acid vapor (p < 0.05). No significant associations were observed with ozone. The estimated growth rate for children in the most polluted of the communities as compared with the least polluted was predicted to result in a cumulative reduction of 3.4% in FEV(1) and 5.0% in MMEF over the 4-yr study period. The estimated deficits were generally larger for children spending more time outdoors. In the seventh- and tenth-grade cohorts, the estimated pollutant effects were also negative for most lung function measures, but sample sizes were lower in these groups and none achieved statistical significance. The results suggest that significant negative effects on lung function growth in children occur at current ambient concentrations of particles, NO(2), and inorganic acid vapor.
Adolescent↗
Exposure measurement error in time-series studies of air pollution: concepts and consequences.
Misclassification of exposure is a well-recognized inherent limitation of epidemiologic studies of disease and the environment. For many agents of interest, exposures take place over time and in multiple locations; accurately estimating the relevant exposures for an individual participant in epidemiologic studies is often daunting, particularly within the limits set by feasibility, participant burden, and cost. Researchers have taken steps to deal with the consequences of measurement error by limiting the degree of error through a study's design, estimating the degree of error using a nested validation study, and by adjusting for measurement error in statistical analyses. In this paper, we address measurement error in observational studies of air pollution and health. Because measurement error may have substantial implications for interpreting epidemiologic studies on air pollution, particularly the time-series analyses, we developed a systematic conceptual formulation of the problem of measurement error in epidemiologic studies of air pollution and then considered the consequences within this formulation. When possible, we used available relevant data to make simple estimates of measurement error effects. This paper provides an overview of measurement errors in linear regression, distinguishing two extremes of a continuum-Berkson from classical type errors, and the univariate from the multivariate predictor case. We then propose one conceptual framework for the evaluation of measurement errors in the log-linear regression used for time-series studies of particulate air pollution and mortality and identify three main components of error. We present new simple analyses of data on exposures of particulate matter < 10 microm in aerodynamic diameter from the Particle Total Exposure Assessment Methodology Study. Finally, we summarize open questions regarding measurement error and suggest the kind of additional data necessary to address them.
Air Pollution↗
alpha-Amylase production by free and immobilized Bacillus subtilis.
The effect of glucose on the alpha-amylase production by Bacillus subtilis ATCC-21556 was studied. Initial glucose concentrations up to 20 g/L were found to be directly proportional to the specific alpha-amylase production in an immobilized-cell batch system, whereas a free-cell batch system presented an inversely proportional relationship with the initial glucose concentration. This might be owing to the alpha-amylase repression by the glucose present in the culture medium. Three hundred eighty-five percent of the specific alpha-amylase production with the free-cell system was produced by the immobilized-cell batch culture.
Bacillus subtilis↗