For debate. Does breast cancer screening depend on a wobbly hypothesis?
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Breast Neoplasms↗
Biomedical subjects
S Roy
Publications and source records attributed to S Roy.
Typhoid fever with severe pancytopenia.
A patient suffering from typhoid fever with severe pancytopenia is presented. Bone marrow examination revealed extensive haemophagocytosis which possibly contributed to the pancytopenia.
Adult↗
Protection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidants.
In many cell lines, glutamate cytotoxicity is known to be medicated by an inhibition of cystine transport. Because glutamate and cystine share the same transporter, elevated levels of extracellular glutamate competitively inhibit cystine transport leading to depletion of intracellular glutathione. A glutathione-depleted state impairs cellular antioxidant defenses resulting in oxidative stress. It was therefore of interest to investigate whether proglutathione agents, e.g., N-acetylcysteine and lipoic acid, are able to protect against glutamate cytotoxicity. Both lipoic acid (100 microM-1 mM) and N-acetylcysteine (100 microM-1 mM) completely protected C6 cells from the glutamate-induced cell death. Both agents facilitate extracellular supply of cysteine, the reduced form of cystine, that is transported into the cell by a glutamate-insensitive transport mechanism. Protection by lipoic acid and N-acetylcysteine corresponded with a sparing effect on cellular glutathione, which is usually depleted after glutamate treatment. In the presence of L-buthionine-(S,R)-sulfoximine, a gamma-glutamylcysteine synthetase inhibitor, low doses (< 100 microM) of lipoic acid and N-acetylcysteine did not protect cells against glutamate-induced cytotoxicity. At higher concentrations (> 500 microM), however, both lipoic acid and N-acetylcysteine provided partial protection against glutamate cytotoxicity even in glutathione synthesis-arrested cells. These results indicate that at low concentrations the primary mechanism of protection by the thiol antioxidants was mediated by their proglutathione property rather than direct scavenging of reactive oxygen. At higher concentrations (> 500 microM), a GSH-independent direct antioxidant effect of lipoic and N-acetylcysteine was observed. Dichlorofluorescin fluorescence, a measure of intracellular peroxides, increased sixfold after glutamate treatment of C6 cells. Lipoic acid and N-acetylcysteine treatment significantly lowered glutamate-induced dichlorofluorescin fluorescence compared with that of controls. Interestingly, alpha-tocopherol (50 microM) also suppressed glutamate-induced dichlorofluorescin fluorescence, indicating the peroxides detected by dichlorofluorescin were likely lipid hydroperoxides. Both thiol antioxidants, particularly lipoic acid, appear to have remarkable therapeutic potential in protecting against neurological injuries involving glutamate and oxidative stress.
Acetylcysteine↗
Fish oil and vitamin E supplementation in oxidative stress at rest and after physical exercise.
Fish oil supplementation and physical exercise may induce oxidative stress. We tested the effects of 8 wk of alpha-tocopherol (vitamin E) and fish oil (FO) supplementation on resting and exercise-induced oxidative stress. Rats (n = 80) were divided into groups supplemented with FO, FO and vitamin E (FOVE), soy oil (SO), and SO and vitamin E (SOVE), and for FOVE and SOVE they were divided into corresponding exercise groups (FOVE-Ex and SOVE-Ex). Lipid peroxidation [thiobarbituric acid-reacting substances (TBARS)] was 33% higher in FO compared with SO in the liver, but oxidative protein damage (carbonyl levels) remained similar in both liver and red gastrocnemius muscle (RG). Vitamin E supplementation, compared with FO and SO, markedly decreased liver and RG TBARS, but liver TBARS remained 32% higher in FOVE vs. SOVE. Vitamin E also markedly decreased liver and RG protein carbonyl levels, although levels in FOVE and SOVE were similar. Exercise increased liver and RG TBARS and RG protein carbonyl levels markedly, with similar levels in FOVE-Ex and SOVE-Ex. FO increased lipid peroxidation but not protein oxidation in a tissue-specific manner. Vitamin E markedly decreased lipid peroxidation and protein oxidation in both FOVE and SOVE, although liver lipid peroxidation remained higher in FOVE. Despite higher levels of hepatic lipid peroxidation at rest in FOVE compared with SOVE, liver appeared to be relatively less susceptible to exercise-induced oxidative stress in FOVE.
Animals↗
Homeotic genes and the regulation of myoblast migration, fusion, and fibre-specific gene expression during adult myogenesis in Drosophila.
We have investigated the roles of homeotic selector genes in the migration and fusion of myoblasts, and in the differentiation of adult muscle fibres of Drosophila. Altering intrinsic homeotic identities of myoblasts does not affect their segment-specific migration patterns. By transplanting meso - and metathoracic myoblasts into the abdomen, we demonstrate that the fusion abilities of myoblasts are independent of their segmental identities. However, transplanted thoracic myoblast nuclei are 'entrained' by those of the host abdominal muscles to which they fuse and are unable to 'switch on' a thoracic muscle-specific reporter gene. This process is likely to be mediated by homeotic repression because mis-expression of an abdominal muscle-specific homeotic gene, Ultrabithorax, in the thoracic muscles results in the repression of the thoracic muscle-specific reporter gene. Finally, we show that removal of Ultrabithorax function specifically from muscle cells of the first abdominal segment, results in the expression of thoracic muscle properties. Many of these functions of homeotic genes in muscle patterning in Drosophila could be conserved during myogenesis in other organisms.
Animals↗
Growth hormone normalizes renal 1,25-dihydroxyvitamin D3-24-hydroxylase gene expression but not Na+-phosphate cotransporter (Npt2) mRNA in phosphate-deprived Hyp mice.
The murine X-linked Hyp mutation is characterized by decreased renal expression of type II Na+-phosphate (Pi) cotransporter (Npt2) mRNA and an abnormal vitamin D response to Pi deprivation. The latter is manifest by an aberrant fall in serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D) levels that is associated with an increase in renal 1,25(OH)2D-24-hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway. Because growth hormone (GH) enhances renal Na+-Pi cotransport and permits the adaptive 1,25(OH)2D response in Pi-deprived hypophysectomized rats, we examined the effects of GH on vitamin D metabolism and renal Npt2 mRNA abundance in Hyp mice fed control and low Pi diets. GH significantly decreased renal 24-hydroxylase activity (0.202+/-0.020 to 0.098+/-0.008 pmol/mg of protein/minute, p < 0.05) and mRNA abundance, relative to beta-actin mRNA (299+/-13 to 78+/-14, p < 0.05), in Hyp mice fed the low Pi diet but had no effect on either parameter in mutants fed the control diet. Moreover, after GH treatment, renal 24-hydroxylase gene expression was no longer elevated in Pi-deprived Hyp mice relative to mutants fed control diet. In contrast, GH did not correct the serum concentration of 1,25(OH)2D in Pi-deprived Hyp mice. We also demonstrate that GH did not normalize renal Npt2 mRNA expression, relative to beta-actin mRNA, in Hyp mice fed either control or low Pi diets. The present data demonstrate that normalization of renal 24-hydroxylase gene expression in Pi-deprived Hyp mice by GH is not sufficient to correct the serum concentration of 1,25(OH)2D and is not associated with an alteration in renal Npt2 mRNA expression.
Animal Feed↗
Genetic stability among temporally and geographically diverse isolates of Barmah Forest virus.
An increase in the incidence of polyarthritis caused by Barmah Forest (BF) virus, and its recent emergence into Western Australia, prompted a study of the molecular epidemiology of this Australian mosquito-borne alphavirus. The nucleotide sequence of a 500-basepair region of the 3' end of the envelope (E2) gene of the prototype BF virus strain (BH2193) was compared with other members of the alphavirus genus, and to a panel of isolates of BF virus collected more for than 20 years from different geographic regions of Australia. The BF virus was shown to be genetically distinct from other members of the alphavirus genus. A high degree of sequence homology (98-100%) was found between the BF isolates, with no evidence of geographic or temporal divergence. This nucleotide homogeneity was similar to that observed with other Australian mosquito-borne viruses with avian vertebrate hosts, such as Sindbis, Murray Valley, and Kunjin viruses, but it contrasts to the heterogeneity reported for Ross River virus, an alphavirus with mammalian vertebrate hosts.
Alphavirus↗
Severe right ventricular contraction asynchronism revealing a large pericardial effusion.
A gated blood-pool equilibrium radionuclide angiography was performed in a patient to determine the ejection fraction for doxorubicin cardiotoxicity evaluation. The phase image of the first harmonic of the Fourier analysis revealed a severe delay of the right ventricular contraction compared with that of the left ventricle. This right ventricular contraction asynchronism was due to a large pericardial effusion, confirmed by the presence of the halo sign on the summed gated images and by echocardiography. The phase delay moves towards normalization after pericardiocentesis. Although radionuclide angiocardiography is not the best method for identification of pericardial effusion, this diagnosis should be evoked when a severe homogenous delay of the right ventricular contraction is observed.
Cardiac Tamponade↗
Benign pleomorphic adenoma of the larynx: report of a case and review and analysis of 20 additional cases in the literature.
Among the benign pleomorphic adenomas of the minor salivary glands, those that develop in the larynx are very rare. One such case of benign pleomorphic adenoma of the larynx in an adult female is described. The patient was treated with epiglottectomy with a lateral pharyngotomy approach. Review of the literature showed an additional 20 well-described cases of benign pleomorphic adenoma of the larynx. These patients usually present with hoarseness, dyspnea or dysphagia, or any combination of these depending on the site of origin and the size of the tumor. Occasionally the tumor may be discovered incidentally. The tumor can occur in any part of the larynx with the epiglottis being the most common site. Clinically they are indistinguishable from other benign laryngeal neoplasms, as surface mucosal lining remains intact. Histopathological examination is used to make the definitive diagnosis, but rarely, misinterpretation may occur. Conservative surgery provides a lasting cure.
Adenoma, Pleomorphic↗
Relevance of performing a 'sepsis screen' in a surgical neonate.
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Congenital Abnormalities↗
[Study of myocardial viability after myocardial infarction. Value and limits of magnetic resonance imaging compared with myocardial scintigraphy].
The aim of this study was to compare myocardial thickness measured by magnetic resonance imaging and quantified fixation of thallium. Twenty-one patients 61.2 +/- 11 years were investigated after myocardial infarction of the anterior wall in 8 cases, inferior in 10 cases, lateral in 2 cases and apical in one case. The mean angiographic ejection fraction was 46.5 +/- 19%. Myocardial scintigraphy was performed after an exercise or pharmacological stress test and followed by a study of redistribution. The data was analysed by a quantitative method. Magnetic resonance imaging was performed with vertical and horizontal long axis views in systole and diastole with division of the left ventricle into the same 12 regions. Three groups were defined according to fixation during redistribution. Group I: regions with fixation > 80% (n = 155); group II: 60 to 80% (n = 78); group III: fixation < 60% (n = 19). All measurement of myocardial thickness were correlated (p < 0.01) with the fixation of thallium during redistribution. Systolic thickening, was significantly greater in group I (3.80 +/- 3.1 mm) than in groups II (2.20 +/- 3.8 mm) and III (1.56 +/- 2.4 mm) in which it was comparable. Regions in group III had systolic (8.61 +/- 3.53) and diastolic (6.89 +/- 3.3 mm) thicknesses significantly inferior to those in groups I (13.79 +/- 4.4 mm: 9.95 +/- 2.8 mm) and II (11.59 +/- 5.5 mm: 9.38 +/- 2.9 mm). Ninety per cent of regions with a systolic thickness of over 10 mm had fixation during redistribution of more than 60%. This study shows that myocardial thickness is correlated to scintigraphic data. The systolic thickness over 10 mm would confirm the viability of a given region.
Adult↗
Imaging thin and thick sections of biological tissue with the secondary electron detector in a field-emission scanning electron microscope.
A field-emission scanning electron microscope (FESEM) equipped with the standard secondary electron (SE) detector was used to image thin (70-90 nm) and thick (1-3 microns) sections of biological materials that were chemically fixed, dehydrated, and embedded in resin. The preparation procedures, as well as subsequent staining of the sections, were identical to those commonly used to prepare thin sections of biological material for observation with the transmission electron microscope (TEM). The results suggested that the heavy metals, namely, osmium, uranium, and lead, that were used for postfixation and staining of the tissue provided an adequate SE signal that enabled imaging of the cells and organelles present in the sections. The FESEM was also used to image sections of tissues that were selectively stained using cytochemical and immunocytochemical techniques. Furthermore, thick sections could also be imaged in the SE mode. Stereo pairs of thick sections were easily recorded and provided images that approached those normally associated with high-voltage TEM.
Animals↗
Endothelium-dependent contractile effect of trypsin-activated receptor (PAR2) stimulation in rat vascular tissue.
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Animals↗
Evaluation of lymphocyte proliferation assay to purified protein derivative, enzyme linked immunosorbant assay, and tuberculin hypersensitivity in Eales' disease.
The purpose of this study was to evaluate the immunological responses against mycobacterial antigens in Eales' disease. Fifty six patients with Eales' disease and fifty age-and-sex-matched healthy volunteers with normal fundus findings taken as controls, were subjected to Mantoux test, using 2 TU/0.1 ml of purified protein derivative (PPD), lymphocyte proliferation assay to PPD, and ELISA to detect IgM and IgG antibodies against mycobacterial A-60 antigen. The results of Mantoux test and lymphocytes proliferation assay did not differ significantly in the two groups suggesting a similar cellular immune response. The number of individuals with recent exposure/reexposure to tuberculosis (IgM+) was significantly higher among patients. However the number of people with past exposure (IgM-IgG+) was significantly higher among controls. Our study indicates that there are no statistically significant differences in the humoral and cellular immune responses to mycobacterial antigens between the patients with Eales' disease and controls, except for a significantly higher IgM positivity among the patients.
Adolescent↗
The Trp64Arg mutation of the beta3 adrenergic receptor gene has no effect on obesity phenotypes in the Québec Family Study and Swedish Obese Subjects cohorts.
The beta adrenergic system plays a key role in regulating energy balance through the stimulation of both thermogenesis and lipid mobilization in brown and white adipose tissues in human and various animal models. Recent studies have suggested that a missense Trp64Arg mutation in the beta3 adrenergic receptor (ADRB3) gene was involved in obesity and insulin resistance. We have investigated the effect of this mutation on obesity-related phenotypes in two cohorts: the Québec Family Study (QFS) and the Swedish Obese Subjects (SOS). In QFS, no association was found between this mutation and body mass index (BMI), body fat including abdominal visceral fat, resting metabolic rate, various diabetes and cardiovascular risk factors, and changes in body weight and body fat over a 12-yr period. With the exception of RMR (P = 0.04), no evidence of linkage was detected between the mutation and phenotypes of QFS based on sib-pair data. In SOS, the frequency of the Trp64Arg allele was not significantly different between nonobese and obese female subjects and no association was found between the mutation and body weight gain over time. These findings do not support the view that there is an association between the Trp64Arg mutation in the ADRB3 gene and obesity.
Adult↗
Cancer services. Takes your breath away.
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Continuity of Patient Care↗
In vitro assembly of the component chains of fibrinogen requires endoplasmic reticulum factors.
Human fibrinogen (340 kDa) is a dimer, with each identical half-molecule composed of three different polypeptides (Aalpha, 66 kDa; Bbeta, 55 kDa; and gamma, 48 kDa). To understand the mechanisms of chain assembly, a coupled in vitro transcription translation system capable of assembling fibrinogen chains was developed. Fibrinogen chain assembly was assayed in an expression system coupled to rabbit reticulocyte lysate in the presence or absence of dog pancreas microsomal membranes. Fibrinogen chain assembly required microsomal membranes and oxidized glutathione. Co-expression of two of the chains, Bbeta and gamma or Aalpha and gamma, yielded free chains and two-chain complexes. Unlike combinations of Aalpha with gamma and Bbeta with gamma, co-expression of Aalpha and Bbeta did not form a single two-chain complex but produced a mixture of two-chain complexes. Co-expression of all three chains yielded free chains, two-chain complexes, and higher molecular weight complexes that corresponded to a half-molecule and to fully formed fibrinogen. Upon treatment of this mixture with thrombin and factor XIIIa, a gamma.gamma dimer, similar to that obtained from cross-linked human fibrin, was produced, indicating that properly folded fibrinogen was formed in vitro. Molecular chaperones may participate in fibrinogen assembly, since antibodies to resident proteins of the endoplasmic reticulum (BiP, Hsp90, protein disulfide isomerase, and calnexin) co-precipitated the chaperones together with nascent fibrinogen chains and complexes.
Animals↗
Murine splenocyte proliferation by porin of Shigella dysenteriae type 1 and inhibition of bacterial invasion of HeLa cell by anti-porin antibody.
The purified porin of Shigella dysenteriae type 1 showed strong mitogenic activity for murine splenocytes. Preincubation of S. dysenteriae type 1 with anti-porin antibody reduced the bacterial plaque formation in HeLa cell monolayers by 45%. The two immunobiological activities indicate that porin might be important in the induction of protective immunity against shigellosis.
Animals↗