Neospora threatens livestock, dogs.
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Abortion, Veterinary↗
Biomedical subjects
C Smith
Publications and source records attributed to C Smith.
Retrieval of p53 protein in paraffin-embedded head and neck tumor tissues.
OBJECTIVES: To improve the detection of p53 protein in formalin-fixed, paraffin-embedded head and neck tumor tissues. DESIGN: Cohort. SETTING: University and Veterans Administration medical centers. PATIENTS OR OTHER PARTICIPANTS: Retrospective samples. INTERVENTION: Surgery for head and neck carcinoma. MAIN OUTCOME MEASURES: Retrieval of p53 antigen. Hypothesis formulated after data collection. RESULTS: An antigen retrieval method facilitated the unmasking of previously inaccessible p53 antigenic determinants in formalin-fixed, paraffin-embedded tissues. This approach has made possible a much more reliable and sensitive immunohistochemical detection of p53 antigen. The procedure is simple, requiring only microwave heating of tissue sections to 100 degrees C in the presence of a zinc sulfate solution. CONCLUSIONS: Antigen retrieval method in formalin-fixed, paraffin-embedded tissue demonstrated a significant increase in p53 immunostaining.
Genes, p53↗
Distinct effects of bFGF and PDGF on oligodendrocyte progenitor cells.
We have compared the effects of platelet-derived (PDGF) and basic fibroblast (bFGF) growth factors on the shape, migration, and differentiation of oligodendrocyte progenitor cells, the precursors of myelin-forming cells in the CNS. In the presence of bFGF, oligodendrocyte progenitors purified from rat neonatal brain cultures were stellate, non-motile, and had a morphological complexity of 1.26 +/- 0.03 as measured by fractal dimension (D). These cells expressed transcripts encoding the POU-homeodomain transcription factor Oct-6, but not myelin genes. Upon addition of PDGF, bFGF-treated cells became motile and twofold less complex in shape (D = 1.19 +/- 0.03). These changes occurred within 6 +/- 4 h and were dependent on de novo transcription and translation, but not DNA synthesis. Upon removal of PDGF the cells reverted to their stellate shape (D = 1.26). Removal of both bFGF and PDGF resulted in oligodendrocyte differentiation after 3 days, with a fourfold increase in complexity of shape (D = 1.55 +/- 0.08), loss of Oct-6 transcripts, and gain of myelin transcripts. Thus PDGF is both necessary and sufficient to induce a motile state in progenitor cells growing in the presence of bFGF. Together with our previous data (McKinnon et al.: Neuron 5:603, 1990), our results suggest that bFGF and PDGF may control distinct phases of proliferation and migration of oligodendrocyte progenitor cells in vivo.
Animals↗
Identification and partial characterization of a candidate gene for X-linked retinopathies using a lateral approach.
Using library to library cross-screening we have identified a number of genomic clones that harbor X-linked sequences expressed in the human choroid/retina. We describe the characterization of one of these, designated XEH.8 (DXS542), which is localized to Xp11.3-q12. Isolation, partial sequencing, and Northern analysis of the cognate cDNA (XEH.8c), has shown that the cDNA has some homology to the dystrophin gene and hybridizes to a 10-kb mRNA present in the choroid and retina but not in fibroblasts. This expressed sequence maps to the same region of the X chromosome as several known X-linked ophthalmic diseases, including Norrie disease, retinitis pigmentosa 2, congenital night blindness and Aland Island eye disease.
Amino Acid Sequence↗
Structure and polymorphisms of the human annexin III (ANX3) gene.
A 75-kb region encompassing the human annexin III (ANX3) gene on chromosome 4q21 was characterized from directly amplified genomic DNA and from six genomic clones in phage lambda (lambda ANX3-1 to lambda ANX3-6). The gene was mapped with restriction enzymes BamHI, EcoRI, HindIII, SacI, and XbaI, and primers were developed for nine sequence-tagged sites throughout the gene. The transcribed region spans 58 kb and contains 12 introns ranging from 0.3 to 19.1 kb and 13 exons ranging from 53 to 374 bases. Northern blots showed a single mRNA species of approximately 1.7 kb in all tissues examined. Three intragenic polymorphisms were identified: a tandem repeat of the sequence TAAA with at least six alleles, a two-allele SalI polymorphism detectable by polymerase chain reaction, and a two-allele BglII polymorphism.
Amino Acid Sequence↗
Nucleotide sequence and genomic organization of rice tungro spherical virus.
Rice tungro disease is caused by a combination of two viruses: rice tungro spherical virus (RTSV) and rice tungro bacilliform virus (Jones et al. (1991) J. Gen. Virol. 72, 757-761.). The genome of RTSV is a single-stranded polyadenylated RNA. We present here the 12,433-nucleotide complete sequence of RTSV genomic RNA and its deduced coding regions. This sequence contains a large open reading frame (ORF) which initiates following a 514-nucleotide 5' leader sequence and is capable of encoding a viral polyprotein of 390.3 kDa. Two viral subgenomic RNAs of ca. 1.2 and 1.4 kb, respectively, were detected in RTSV-infected leaf tissues and mapped by S1 nuclease protection assay. These RNAs were determined to be congruent with the genomic RNA sequence proximal to the 3' terminus and could contain up to two small ORFs in their 5' to 3' orientation. There are at least three capsid protein subunit cistrons near the N-terminus of the large ORF. A computer-aided search of the C-terminal half of the large ORF revealed conserved protein sequence motifs for a viral RNA polymerase, proteinase, and a putative NTP-binding protein. These sequence motifs are arranged in a manner that resembles those of picorna-like viruses. Taken together, these data indicate that RTSV is a distinct type of positive-strand RNA virus. The evolutionary relationships between RTSV and other picorna-like plant viruses are discussed.
Amino Acid Sequence↗
Selective serotonin re-uptake inhibitors decrease schedule-induced polydipsia in rats: a potential model for obsessive compulsive disorder.
Schedule-induced polydipsia was used to determine the effects of selective serotonin re-uptake inhibitors on adjunctive water consumption. Polydipsia was induced in food deprived rats by exposure to a fixed time feeding schedule (FT = 60 s) for 150 min per day for 22 days. Selected polydipsic rats consumed 3-4 times greater volume of water compared to food deprived control rats. Chronic administration of the selective serotonin re-uptake inhibitors fluoxetine and clomipramine (CMI) at 5 mg/kg per day and fluvoxamine at 10 mg/kg twice a day significantly decreased schedule-induced polydipsia (SIP) on day 15 and throughout the remainder of the study compared to control rats. The noradrenergic re-uptake inhibitor, desipramine (DMI), only decreased SIP behavior on day 1. The neuroleptic, haloperidol (0.03 and 0.1 mg/kg), and the benzodiazepine, diazepam (2.5 mg/kg), failed to alter SIP behavior. Since obsessive-compulsive disorder (OCD) and polydipsic behavior both involve excessive expression of a normal behavior, the polydipsia model may be relevant for the prediction of compounds useful in the treatment of OCD.
Animals↗
Graded balloon dilation atrial septostomy as a bridge to lung transplantation in pulmonary hypertension.
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Catheterization↗
Determinants of near fatality in acute severe asthma.
PURPOSE: The data extrapolated from cases of acute severe asthma that narrowly miss being fatal may prove valuable in the identification of the factors implicated in mortality. The purpose of this study was, therefore, to identify determinants of near fatality in patients with acute severe asthma. PATIENTS AND METHODS: We studied 81 patients with acute severe asthma in whom mechanical ventilation was required. Near fatality was defined as the occurrence of respiratory arrest and/or coma necessitating emergency tracheal intubation and resuscitation. In the cases that were not regarded as near fatal, tracheal intubation was performed electively because of deteriorating arterial blood gas values and/or the anticipation of exhaustion. Various continuous and categorical variables were compared in these two groups of patients. Patients with a hyperacute attack (period from onset of attack to mechanical ventilation less than 3 hours) were specifically sought and studied to determine the impact of such a course on near fatality. RESULTS: The "attack duration" (period from onset of attack to mechanical ventilation) was an important determinant of near fatality and of the subsequent clinical course. It was shorter in the group with a near-fatal episode (p < 0.03), and hyperacute attacks were uniformly near fatal. The attack duration correlated positively with the duration of the requirement for mechanical ventilation (p < 0.01). A longer attack duration was associated with an increased likelihood of the occurrence of major atelectasis (p < 0.01). There was no evidence of a relationship between near fatality and the side effects of bronchodilators as regards hypokalemia, arrhythmias, or cardiotoxicity. There was evidence of considerable under-treatment in the patient population as a whole, particularly in regard to the use of corticosteroids. CONCLUSIONS: A short attack duration is associated with an increased risk of near fatality in acute severe asthma. This is particularly evident in hyperacute attacks. Hyperacute attacks resolve rapidly once bronchodilator therapy has been instituted, suggesting that smooth muscle spasm is the predominant pathogenetic mechanism. The importance of routine anti-inflammatory therapy in mild to moderate asthma requires re-emphasis but, in addition, all patients should be provided with, and educated in the use of, bronchodilator rescue therapy, which should be available at all times. Despite current trends, the use of regular, prophylactic bronchodilator therapy in strict conjunction with anti-inflammatory agents may still be indicated. There is little evidence in the present data obtained from near-fatal cases to support the concept that cardiotoxicity related to bronchodilators contributes significantly to mortality from asthma.
Acute Disease↗
Right atrial angiosarcoma causing a coronary artery fistula: diagnosis by transesophageal echocardiography.
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Adult↗
Memory for visuospatial patterns in Alzheimer's disease.
Immediate memory for visuospatial information was assessed in patients affected by Alzheimer-type dementia but with unimpaired visuo-perceptual functions. Patients were given two tasks: one was a traditional visuospatial memory task (Corsi's block tapping test), the second explored specifically immediate memory for visuospatial patterns. The experiment was conducted in two parallel groups of patients in Italy and the United States, each with its own appropriate sample of normal control subjects. Results showed a specific deficit of visual working memory in demented patients, even in a task in which control subjects achieved error-free performance. These data are interpreted in the light of the Working Memory Model, and suggest that in dementia the functions of the Visuospatial Scratchpad, unlike the functions of the verbal subsystems, may be impaired.
Aged↗
Regulation of collagen synthesis and messenger RNA levels in normal and hypertrophic scar fibroblasts in vitro by interferon alfa-2b.
Hypertrophic scars, which commonly occur after thermal and traumatic injury of the skin, are a fibroproliferative disorder of the dermal matrix wherein components of the inflammatory process, including the fibrotic growth factor, transforming growth factor-beta, appear to activate dormant fibroblasts leading to cellular proliferation and excessive matrix synthesis. To investigate the potential beneficial role and mechanism of interferon alfa-2b in controlling excessive collagen production in hypertrophic scar, we measured dose response, time of onset, and duration of action in hypertrophic scar fibroblasts in vitro and compared them with those of site-matched normal fibroblasts obtained from four patients after thermal injury. Interferon alfa-2b reduced collagen protein synthesis and type I messenger RNA levels in both hypertrophic scar and normal fibroblasts after treatment, but these changes were apparent only after approximately 72 hours. Significant reductions in collagen synthesis occurred in four pairs of normal and hypertrophic scar fibroblasts (p < 0.05), accompanied by significant reductions in type I (p < 0.05) but not type III procollagen messenger RNA. Hypertrophic scar fibroblasts recovered completely from the effects of interferon alfa-2b on procollagen type I messenger RNA within 48 hours of cessation of treatment in contrast to normal skin fibroblasts, in which the reduction in type I procollagen messenger RNA by interferon alfa-2b persisted beyond 72 hours after treatment. These data suggest that interferon alfa-2b reduces collagen synthesis in both normal and hypertrophic fibroblasts but the hypertrophic fibroblast may remain less sensitive to its effects.
Journal Article↗
Microalbuminuria in a normotensive insulin-treated diabetic population.
Thirty-five insulin-treated diabetics without overt proteinuria or hypertension, and taking no antihypertensive medications were screened at three clinical centers for the presence of microalbuminuria. In addition to the presence of albuminuria, patients were evaluated for duration and type of diabetes, retinopathy, blood pressure, and degree of diabetic control. In these patients, it was possible to examine the degree of microalbuminuria as a function of systolic and diastolic blood pressures, age and sex of the patient, site of recruitment, duration of diabetes, and glycemic control. On multivariate statistical analysis, systolic blood pressure was the only factor that contributed to microalbuminuria. An additional 37 patients had urinary albumin excretion measured, although biochemical and clinical characteristics were incompletely determined. Blood pressures were documented to be normal in 23 of these individuals, while the other fourteen were normal by history. The range of urinary albumin excretion was comparable in the patients with complete data bases and those without. Overall, 22.2% of the normotensive insulin-treated patients screened had microalbuminuria, 5.5% had gross albuminuria, while 72.2% had normal urinary albumin excretion. We agree with previous reports that microalbuminuria is relatively uncommon in the normotensive diabetic population, but further conclude that even in the context of "normal" blood pressure, systolic blood pressure should be carefully observed in diabetic patients. It is possible that these individuals should be considered for more aggressive monitoring programs, e.g., ambulatory blood pressure recording.
Adult↗
A method of screening for genes of major effect.
This paper describes a method for screening animal populations on an index of calculated probabilities of genotype status at an unknown single locus. Animals selected by such a method might then be candidates in test matings and genetic marker analyses for major gene detection. The method relies on phenotypic measures for a continuous trait plus identification of sire and dam. Some missing phenotypes and missing pedigree information are permitted. The method is an iterative two-step procedure, the first step estimates genotype probabilities and the second step estimates genotypic effects by regressing phenotypes on genotype probabilities, modeled as true genotype status plus error. Prior knowledge or choice of major locus-free heritability for the trait of interest is required, plus initial starting estimates of the effect on phenotype of carrying one and two copies of the unknown gene. Gene frequency can be estimated by this method, but it is demonstrated that the consequences of using an incorrect fixed prior for gene frequency are not particularly adverse where true frequency of the allele with major effect is low. Simulations involving deterministic sampling from the normal distribution lead to convergence for estimates of genotype effects at the true values, for a reasonable range of starting values, illustrating that estimation of major gene effects has a rational basis. In the absence of polygenic effects, stochastic simulations of 600 animals in five generations resulted in estimates of genotypic effects close to the true values. However, stochastic simulations involving generation and fitting of both major genotype and animal polygenic effects showed upward bias in estimates of major genotype effects. This can be partially overcome by not using information from relatives when calculating genotype probabilities-a result which suggests a route to a modified method which is unbiased and yet does use this information.
Alleles↗
Crutches, confetti or useful tools? Professionals' views on and use of health education leaflets.
This paper examines the views on and use of health education leaflets by a number of professional groups: health visitors, midwives, occupational health workers, pharmacists and school health education co-ordinators. Eighty nine percent currently obtain leaflets from health promotion units, with the exception of health visitors, professionals are largely satisfied with the units' service. Seventy six percent use commercial or sponsored leaflets primarily because of the large numbers and topics that are available. The numbers and type of leaflets used were found to vary across the professions. All professionals see an increasingly important role for leaflets in their work. A number of them, pharmacists and occupational health workers in particular, saw the numbers they use rising. These views were accompanied by lower levels of belief in a leaflets ability to increase knowledge and behaviour as well as lower levels of satisfaction with current leaflet use and a concern over the public's reception of leaflets. Methods of leaflet distribution to the public largely reflect the professionals' work contexts. Most popular were handing out leaflets with advice, leaving them in a public place and using them as a back-up to a meeting. A number of contradictions emerge between distribution practices and perceived effectiveness. Few professionals thought leaving leaflets in a public place was effective, and few health visitors and midwives believed giving leaflets to the family of a client was effective despite large numbers doing so. The implications of these findings for health promotion policy and practice are discussed.
Attitude of Health Personnel↗
Effect of morphine or phenobarbital on teicoplanin elimination pharmacokinetics.
Elimination kinetics following a single dose of teicoplanin in rats pre-treated with morphine sulphate (MS), phenobarbital sodium (Pb), and normal saline (NS) were determined. A microbioassay was used to measure teicoplanin levels. A significant increase in the total clearance of teicoplanin was found in rats pre-treated with MS as compared to controls (P < 0.048). Wide variability was observed in the renal and non-renal clearances of teicoplanin. The mean renal clearance for rats pre-treated with MS, Pb and NS was 0.61 +/- 0.07.mL/min/kg, 0.60 +/- 0.13 mL/min/kg, and 0.46 +/- 0.02 mL/min/kg, respectively; the mean non-renal clearance was 0.33 +/- 0.18 mL/min/kg, 0.17 +/- 0.15 mL/min/kg, and 0.08 +/- 0.03 mL/min/kg, respectively. The differences among the groups for renal and non-renal clearance were not statistically significant. The mean apparent volume of distribution of teicoplanin at steady state was significantly lower in the Pb-pre-treated rats as compared to controls (P < 0.043). The mean half-life for MS-, Pb-, and NS pre-treated groups was 8.1 +/- 3.1 h, 5.9 +/- 3.3 h, and 34.6 +/- 20.7 h, respectively. The differences in mean half-life among the groups achieved statistical significance (P < 0.016). The increase in the total clearance of teicoplanin can best be explained by an increase in both renal elimination and hepatic metabolic pathways.
Animals↗
A study of acute community-acquired pneumonia, including details of cardiac changes.
We prospectively studied 102 patients, aged 15-50 years, with acute community-acquired lobar pneumonia without underlying cardiorespiratory illness, admitted to Baragwanath Hospital May 1990-April 1991. Demographic, clinical, microbiological and laboratory data and negative prognostic features of these patients are described. In particular, we documented electrocardiographic changes and studied their possible relevance in patients with pneumonia. Electrocardiographic changes occurred in 32 patients (31%). The commonest changes were clockwise rotation (16%), followed by P. pulmonale (9.8%) and S1 Q3 T3 pattern (7.8%) Other changes included right axis deviation (n = 6), right bundle branch block (n = 3), ventricular extrasystoles (n = 2), atrial fibrillation (n = 1) and nodal rhythm (n = 1). These changes returned to normal in survivors after a mean of 2 days. The S1 Q3 T3 pattern was associated with cardiac enzyme leak (CK-MB fraction), hypoxia and a high Simplified Acute Physiology Score (SAPS). In addition, P. pulmonale, right axis deviation and clockwise rotation correlated with hypoxia and a high SAPS score. Clockwise rotation also correlated with serum (including cardiac fraction) enzymes leak (LDH and CK-MB fraction), and pulmonary artery pressure. The overall mortality rate was 10.8%, with no association between electrocardiographic changes and mortality. The negative prognostic factors documented were hypoxia (p < 0.0001), multilobar pulmonary consolidation (p < 0.0001), tachycardia (p = 0.0001), tachypnoea (p = 0.0002), renal dysfunction function (p = 0.0009), hypotension (systolic p < 0.02, diastolic p < 0.003), bacteraemia (p = 0.003), and serum (including cardiac fraction) enzymes leak: LDH (p < 0.02), CK (p < 0.002) and CK-MB fraction (p = 0.0002). These factors, with the exception of renal dysfunction, also correlated with the need for intensive care unit admission. Acute and reversible electrocardiographic changes are common in acute community-acquired lobar pneumonia. Electrocardiographic changes, especially those compatible with acute cor pulmonale and accompanied by cardiac enzyme (CK-MB fraction) leak, correlated with severity of illness but not with mortality.
Adolescent↗
Isoflurane minimum alveolar concentration reduction by fentanyl.
BACKGROUND: Isoflurane is commonly combined with fentanyl during anesthesia. Because of hysteresis between plasma and effect site, bolus administration of fentanyl does not accurately describe the interaction between these drugs. The purpose of this study was to determine the MAC reduction of isoflurane by fentanyl when both drugs had reached steady biophase concentrations. METHODS: Seventy-seven patients were randomly allocated to receive either no fentanyl or fentanyl at several predetermined plasma concentrations. Fentanyl was administered using a computer-assisted continuous infusion device. Patients were also randomly allocated to receive a predetermined steady state end-tidal concentration of isoflurane. Blood samples for fentanyl concentration were taken at 10 min after initiation of the infusion and before and immediately after skin incision. A minimum of 20 min was allowed between the start of the fentanyl infusion and skin incision. The reduction in the MAC of isoflurane by the measured fentanyl concentration was calculated using a maximum likelihood solution to a logistic regression model. RESULTS: There was an initial steep reduction in the MAC of isoflurane by fentanyl, with 3 ng/ml resulting in a 63% MAC reduction. A ceiling effect was observed with 10 ng/ml providing only a further 19% reduction in MAC. A 50% decrease in MAC was produced by a fentanyl concentration of 1.67 ng/ml. CONCLUSIONS: Defining the MAC reduction of isoflurane by all the opioids allows their more rational administration with inhalational anesthetics and provides a comparison of their relative anesthetic potencies.
Adult↗