[29-year-old patient with gynecomastia and small testis].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
S Brand
Publications and source records attributed to S Brand.
Detection of colonic dysplasia by light-induced fluorescence endoscopy: a pilot study.
Light-induced fluorescence endoscopy (LIFE) has been shown to differentiate between normal mucosa and dysplastic lesions, and dysplastic lesions of the colon occult to routine white-light colonoscopy may thus be visualized by LIFE. We compared the sensitivity and specificity of LIFE to routine white-light colonoscopy in patients with colonic dysplasia. In a pilot study 20 patients with colonic adenoma, inflammatory bowel disease, or with a history of colon cancer were screened for colonic dysplasia during routine colonoscopy. Forty-two sites of mucosal abnormalities regarded as suspicious for dysplasia during white-light colonoscopy were additionally examined with a prototype LIFE system. Biopsies were taken from all 42 colonic sites. The LIFE images were classified as positive or negative for dysplasia. Sensitivity and specificity were calculated by correlating positive and negative findings to the histopathological results. Histopathology detected 21 adenomas with low-grade dysplasia and one with high-grade dysplasia. All dysplastic lesions were found by routine white-light endoscopy. The specificity of conventional white-light endoscopy was 80%. Of the 22 dysplastic lesions 20 were detected by LIFE (sensitivity 91%). The specificity of LIFE was 90% (two false-positive results). LIFE combined with conventional endoscopy may thus improve the detection of colonic dysplasia.
Adult↗
Inhibition of NF-kappa B activation in vitro and in vivo: role of 26S proteasome.
It is becoming increasingly apparent that NF-kappa B plays a critical role in regulating the inflammatory response. Data obtained from studies in our laboratories demonstrate that the proteasome plays an important role in the inflammatory cascade by regulating the activation of NF-kappa B. Indeed, the availability of selective and orally active proteasome inhibitors should prove useful in delineating the roles of the proteasome and NF-kappa B in other pathophysiological conditions such as cancer and heart disease.
Acetylcysteine↗
Profiles of self-esteem in early adolescence: identification and investigation of adaptive correlates.
Investigated profiles of self-esteem during early adolescence and their adaptive correlates in two separate longitudinal studies. Using multidimensional ratings of self-esteem within a developmental-ecological framework, cluster analysis revealed five distinct profiles for each sample. The profiles found were characterized by differing patterns of self-evaluation across major contexts of development, including consistently positive or negative ratings for all domains as well as more variable patterns in which ratings for one or more domains (e.g., school) were elevated or diminished relative to those for other areas. Profiles, in turn, were found to be related to measures of youth adjustment both concurrently and longitudinally, independent of their associations with ratings of global self-esteem. Prospective analyses in each study further revealed that profile type predicted differential change in measures of youth adjustment over time, whereas this type of relationship was not found for global ratings of self-esteem. Implications for esteem-enhancement interventions with youth are discussed.
Adaptation, Psychological↗
Molecular cloning and tissue-specific expression of the mutator2 gene (mu2) in Drosophila melanogaster.
We present here the molecular cloning and characterization of the mutator2 (mu2) gene of Drosophila melanogaster together with further genetic analyses of its mutant phenotype. mu2 functions in oogenesis during meiotic recombination, during repair of radiation damage in mature oocytes, and in proliferating somatic cells, where mu2 mutations cause an increase in somatic recombination. Our data show that mu2 represents a novel component in the processing of double strand breaks (DSBs) in female meiosis. mu2 does not code for a DNA repair enzyme because mu2 mutants are not hypersensitive to DSB-inducing agents. We have mapped and cloned the mu2 gene and rescued the mu2 phenotype by germ-line transformation with genomic DNA fragments containing the mu2 gene. Sequencing its cDNA demonstrates that mu2 encodes a novel 139-kD protein, which is highly basic in the carboxy half and carries three nuclear localization signals and a helix-loop-helix domain. Consistent with the sex-specific mutant phenotype, the gene is expressed in ovaries but not in testes. During oogenesis its RNA is rapidly transported from the nurse cells into the oocyte where it accumulates specifically at the anterior margin. Expression is also prominent in diploid proliferating cells of larval somatic tissues. Our genetic and molecular data are consistent with the model that mu2 encodes a structural component of the oocyte nucleus. The MU2 protein may be involved in controlling chromatin structure and thus may influence the processing of DNA DSBs.
Amino Acid Sequence↗
Selective proteasome inhibitors as anti-inflammatory agents.
Nuclear factor kappaB (NF-kappaB) is an ubiquitous transcription factor and pleiotropic regulator of numerous inflammatory and immune responses. Once activated, NF-kappaB translocates from the cytosol to the nucleus of the cell, where it binds to its consensus sequence on the promoter-enhancer region of different genes. By so doing, this activates the transcription of a variety of different pro-inflammatory cytokines, adhesion molecules and specific enzymes, such as the inducible forms of nitric oxide synthase and cyclooxygenase. A number of different cytokines, bacterial products and oxidants activate NF-kappaB via selective phosphorlyation, polyubiquitination and degradation of the inhibitor protein, IkappaB. Since the 26S proteasome complex degrades the post-translationally modified IkappaB, thereby liberating the transcriptionally active p50/p65 heterodimeric NF-kappaB, this proteolytic complex represents a critical step in the activation of NF-kappaB. This review discusses the basic biology of the ubiquitin-proteasome pathway as it relates to the inflammatory response, and highlights those studies demonstrating that selective proteasome inhibitors are effective anti-inflammatory agents in vivo.
Journal Article↗
Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis.
The transcription factor NF-kappaB activates a number of genes whose protein products are proinflammatory. In quiescent cells, NF-kappaB exists in a latent form and is activated via a signal-dependent proteolytic mechanism in which the inhibitory protein IkappaB is degraded by the ubiquitin-proteasome pathway. Consequently, inhibition of the proteasome suppresses activation of NF-kappaB. This suppression should therefore decrease transcription of many genes encoding proinflammatory proteins and should ultimately have an anti-inflammatory effect. To this end, a series of peptide boronic acid inhibitors of the proteasome, exemplified herein by PS-341, were developed. The proteasome is the large multimeric protease that catalyzes the final proteolytic step of the ubiquitin-proteasome pathway. PS-341, a potent, competitive inhibitor of the proteasome, readily entered cells and inhibited the activation of NF-kappaB and the subsequent transcription of genes that are regulated by NF-kappaB. Significantly, PS-341 displayed similar effects in vivo. Oral administration of PS-341 had anti-inflammatory effects in a model of Streptococcal cell wall-induced polyarthritis and liver inflammation in rats. The attenuation of inflammation in this model was associated with an inhibition of IkappaBalpha degradation and NF-kappaB-dependent gene expression. These experiments clearly demonstrate that the ubiquitin-proteasome pathway and NF-kappaB play important roles in regulating chronic inflammation and that, as predicted, proteasome inhibition has an anti-inflammatory effect.
Animals↗
Pharmacological modulation of the refractory period of retinal spreading depression.
Spreading depression (SD) is a propagating wave of neuronal activity in the central nervous system and may play a role in triggering classical migraine. The retina serves as a model system for examining the phenomenon of SD and the influence of various drugs on it. After a SD wave passes a new wave can not be elicited in the absolute refractory period of the tissue (about 2 min), this is followed by a relative refractory phase of about 20 min before complete recovery. The aim of the present study was to describe the effects of Ba2+, a blocker of glial cell K+ channels, octanol, a gap junction blocker and diethylbarbiturate, a GABA(A) chloride channel-activating drug on the modulation of the refractory period of the retinal SD and to examine the possible mechanisms underlying this modulation. Two properties of SD, which are highly sensitive to any changes in the experimental conditions, are the propagation velocity of the wave and the accompanying slow negative potential shift. We measured the propagation velocity and the field potential amplitude in the chicken retina as a function of the recovery state of the tissue under control conditions and compared them with measurements in the presence of Ba2+, octanol or diethylbarbiturate. Under these conditions the manner of the recovery of the tissue changed significantly. Although after blocking the glial (Müller) cell K+ channels with Ba2+ (200 microM), the curve of recovery of the propagation velocity to its maximum value has the same shape as under control conditions, the propagation velocity is reduced in the whole recovery period and in the recovered retina to 84% of the control velocity. The importance of electrical coupling in the refractory phase and in the recovered tissue was examined by adding octanol (1 mM) to the perfusion solution. In this case the relative recovery phase was shortened and the field potential amplitude (110% of control) and propagation velocity (112% of control) are increased in the completely recovered retina. With the GABA(A)-chloride channel-activating drug diethylbarbiturate (800 microM) the propagation velocity (112% of control) and the amplitude of the field potential (111% of control) in the complete recovered retina are increased, but this seems to have no influence on the refractory state.
1-Octanol↗
Incomplete holism in pre-registration nurse education: the position of the biological sciences.
There is an ongoing debate in nurse education concerning the role and delivery of the biological sciences in the nursing curriculum. One of the fundamental questions raised by this debate asks how best can teachers impart biological knowledge in a manner that can be readily applied by students and qualified nurses to inform their clinical practice. This paper will include a discussion of some of the features of pre-registration education that may have influenced the manner in which biological sciences are perceived, taught and used by nurses. It will be argued that nursing may have developed a form of incomplete holism and that this may be in part responsible for the challenges that remain to be met within this area of the nursing curriculum. As a response to incomplete holism an innovative approach within pre-registration education will be introduced. This development involves the use of linked teaching sessions which aim to develop the analytical skills necessary to apply physiological knowledge to nursing practice.
Biological Science Disciplines↗
Proteasome inhibition attenuates nitric oxide synthase expression, VCAM-1 transcription and the development of chronic colitis.
The objectives of this study were to (1) assess the role of the 26S proteasome complex in regulating the expression of the inducible isoform of nitric oxide synthase (iNOS) and vascular cell adhesion molecule-1 (VCAM-1) in a model of chronic granulomatous colitis in vivo and (2) determine the role of the proteasome in regulating the inflammatory response observed in this model of chronic gut inflammation. The selective proteasome inhibitor MG-341 (0.3 mg/kg) was administered by gavage beginning immediately before the induction of colitis and continuing daily thereafter for the entire 14-day experimental period. We found that chronic proteasome inhibition using MG-341 significantly attenuated the peptidoglycan/polysaccharide (PG/PS)-induced up-regulation of iNOS in the colon and spleen and the consequent increase in plasma levels of nitrate and nitrite. Furthermore, we found that the proteasome inhibitor suppressed the up-regulation of the adhesion molecule VCAM-1 in the colon. We also found that MG-341 attenuated PG/PS-induced increases in macroscopic colonic inflammation, bowel wall thickness, colonic dry weight and colonic MPO activity. Treatment with MG-341 also significantly reduced PG/PS-induced increases in macroscopic spleen inflammation, spleen weight and spleen MPO activity. We conclude that the 26S proteasome complex plays an important role in regulating the PG/PS-induced up-regulation of iNOS and VCAM-1 in vivo and appears to be important in regulating colonic and splenic inflammation.
Animals↗
Properties of retinal glial cell potassium channels.
The patch-clamp technique was used to investigate the nature of potassium channels localised in the end-feet-membrane of Müller (glial) cells of the chicken retina. Two different preparations were used to examine ion channels in this membrane area. The ion channels were investigated either in eye-cup preparation, leaving the retina intact, or in isolated endfeet. In both preparations the ion channels showed identical characteristics. We found three K+ channels that could be distinguished by their electrical properties. In the inside-out configuration, in a standard bathing solution (6 mM potassium) with the pipette solution containing 100 mM potassium, these channels showed conductances of 15 pS, 29 pS and 68 pS. Whereas the 29 pS-channel was not voltage-dependent, the 15 pS- and 68 pS-channel showed significant voltage-dependence of the open-state probability. By membrane depolarisation the open-state probability of both channels types increased. The resting membrane potential of the glial cells was estimated to be about -80 mV, which is, as result of the high selectivity of the glial membranes for K+, more negative than that of retinal neurons.
Animals↗
Socioeconomic disadvantage, proximal environmental experiences, and socioemotional and academic adjustment in early adolescence: investigation of a mediated effects model.
This study investigated interrelations among conditions of household socioeconomic disadvantage, proximal environmental experiences, and adaptational outcomes in a sample of 398 middle grade, early adolescents from a predominantly poor, rural area. Findings indicated that levels of disadvantage were related to both socioemotional and academic adjustment, with those from relatively disadvantaged backgrounds faring most poorly. Specifically, youth from homes in which adults were employed in low-income, unskilled occupations were found to have lower levels of school performance and achievement compared to those from homes in which adults were employed in higher paying semi-skilled or skilled/professional occupations. Further, youth from families in which neither parent had graduated from high school exhibited significantly worse socioemotional and academic adjustment than did those whose parents had higher educational levels. Youth who lived in relatively disadvantaged homes also reported more negative experiences of proximal environmental conditions relating to family and school contexts and greater exposure to stressful life events. Most notably, findings provided support for employing an ecological-mediational perspective to understand patterns of linkage between socioeconomic disadvantage and levels of adjustment. Support for this viewpoint included the finding that proximal environmental experiences were significant predictors of adolescent adjustment, independent of shared variance with conditions of household disadvantage, whereas conditions of disadvantage in several instances were no longer related significantly to indices of adjustment once their association with proximal environmental conditions was taken into account. The discussion considers implications for the targeting and scope of ecologically oriented approaches to preventive intervention.
Achievement↗
Apolipoprotein AI, AII, and AIV isoforms in plasma determined by automated isoelectric focusing with PhastSystem and immunofixation.
Distinct genetic variants of apolipoprotein (apo) AI have been shown to influence concentrations of high-density lipoprotein (HDL) cholesterol. The genetic polymorphism of apo AIV may modulate HDL-cholesterol, plasma triglycerides, and lipoprotein(a) concentrations. There is evidence for an antagonizing role of apo AII in reverse cholesterol transport. Since genetic polymorphisms and variants of these apolipoproteins are detectable by isoelectric focusing (IEF), we developed a rapid and easy automated method for IEF analysis of apos AI, AII, and AIV on self-made or commercially available gels, using the PhastSystem. Diluted plasma or serum samples (1 microL) are applied automatically onto the gel and IEF is carried out for 35-45 min. Afterwards, the apo A bands are precipitated by specific polyclonal antibodies and visualized by automated silver staining. This rapid procedure is suitable as a routine or screening method for IEF analysis of these major HDL apolipoproteins.
Apolipoprotein A-I↗
Rapid determination of apolipoprotein E phenotypes from whole plasma by automated isoelectric focusing using PhastSystem and immunofixation.
The influence of the genetic apolipoprotein (apo) E isoforms on human plasma lipoproteins is well established. There is, however, still a need for a phenotyping procedure applicable in laboratories not specialized in lipid research. To this end, we developed a rapid, automated electrophoresis method for apoE phenotyping. Either self-made or commercially available precasted gels can be used. Fresh or frozen samples corresponding to 0.1 microliter of plasma are applied automatically after lipid extraction in a urea-containing buffer onto the gel and isoelectric focusing is carried out for 45 min. Thereafter, apoE bands are precipitated by specific polyclonal antibodies and visualized by automated silver staining. The method is reliable, easily and quickly performed, and not restricted to specialized laboratories.
Apolipoproteins E↗
The developmentally-regulated Drosophila gene rox8 encodes an RRM-type RNA binding protein structurally related to human TIA-1-type nucleolysins.
We report the molecular analysis of a novel Drosophila melanogaster gene, rox8, isolated in a PCR-based screen for sequences encoding RRM-type RNA-binding polypeptides. The rox8 gene is predicted to encode a 50-kilodalton protein displaying extensive amino acid sequence similarities (46% overall identity; 57 to 60% similarity) to the two recently described human TIA-1-type nucleolysins. These cytolytic granule associated proteins, which bind polyadenylated sequences in vitro and trigger DNA fragmentation in permeabilized target cells, are suspected to participate in the apoptotic cell death pathway induced by T-lymphocytes and natural killer cells. The structural relatedness of the three proteins includes three tandemly-repeated consensus RNA-recognition motifs at the N-terminal end and a putative membrane targeting signal at the C-terminal end. rox8 cytologically maps to 95D5-9 on the right arm of the third chromosome. Two rox8 transcripts of 3 and 3.3 kb in length, respectively, result from a developmentally-modulated alternative usage of different polyadenylation sites and are differentially accumulated throughout the fly life cycle. Molecular characterization of rox8 represents the first step in a genetic analysis of the potential roles of a TIA-1-related protein in RNA metabolism and/or programmed cell death in Drosophila.
Amino Acid Sequence↗
A prospective study of life stress, social support, and adaptation in early adolescence.
This study employed a 2-year longitudinal design to examine the relation of stressful life events and social supports to psychological distress and school performance among 166 early adolescents (mean age = 13.5 years). A prospective approach was utilized to control for initial levels of adjustment when examining the relation of Time 1 stress and support variables to Time 2 psychological distress and school performance. Both stress and support variables made significant contributions to the prediction of subsequent psychological distress. Stresses, but not supports, made a significant contribution to the prediction of subsequent school performance. Evidence for reciprocal and interactive linkages was also found, including effects of psychological distress and school performance on subsequent stresses and supports, and greater adaptive impact of school-based supportive resources under conditions of heightened risk outside of school. Implications for ecological and transactional models of development relating to the targeting and efficacy of preventive efforts are discussed.
Adaptation, Psychological↗
Reduction in vitro of red cell glutathione reproduces defects of cellular sodium transport seen in oedematous malnutrition.
Red cells in oedematous malnutrition (kwashiorkor) have an increased sodium content, 'leakiness' to sodium and enhanced sodium pumping. In non-oedematous malnutrition (marasmus) there is a reduction in the sodium pump activity. The explanation has hitherto been unknown but the glutathione content of red cells is low in kwashiorkor and normal in marasmus. We artificially lowered the glutathione content of normal red cells to values characteristic of mild oedematous malnutrition, using the enzyme inhibitors bischloronitrosourea (BCNU) and buthionine sulfoximine (BSOX). After preincubation, the cells were washed to remove the inhibitors and oxidized glutathione. Cellular content of sodium and potassium, and 86Rb influx were then measured. The reduction in glutathione reproduced the abnormalities of sodium content and flux observed in kwashiorkor. We suggest that oxidant stress in kwashiorkor, by reducing cellular glutathione, may affect cell membrane electrolyte transport. This may act through alterations in membrane sulfhydryl groups. Glutathione depletion may therefore play an important role in the clinical picture and natural history of oedematous malnutrition and may have relevance to other conditions where oxidant stress occurs.
Adult↗
[Obturator neuralgia (Howship-Romberg phenomenon)].
A 73-year-old patient with obturator neuropathy presenting as disabling thigh pain is described. The clinical diagnosis was verified by electromyography. No indication for surgery could be found. The patient's discomfort was not influenced by common pain-killers, but was relieved by the antipsychotic drug Melleril.
Aged↗