Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 37 records · Page 2Linked to original sources

PubMed2003

The influence of gender and emotional valence of visual cues on FMRI activation in humans.

Emotional neuroscience maps neurocircuits associated with the processing of affective stimuli. To assess gender differences in brain activation elicited by affective stimuli, we used pictures from the International Affective Picture System in a functional magnetic resonance imaging (fMRI) study. Ten male and ten female age-matched healthy volunteers were included and viewed affectively negative versus positive pictures, which were presented in an event related design. There was a significant interaction between valence of emotional stimuli and gender in the sublenticular extended amygdala (SLEA) and the rostral anterior cingulate. fMRI activation in these regions was stronger for negative compared to positive cues in women. In men fMRI activation was independent of stimulus valence. These results suggest to take gender differences into account when emotional paradigms are tested in functional brain imaging.

Adult↗

PubMed2002

Development of alcohol-associated cues and cue-induced brain activation in alcoholics.

The objective of this study was to develop new standardized alcohol-associated cues and assess their effects on brain activation with functional magnetic resonance imaging (fMRI). Pictures of alcoholic and neutral beverages and affectively neutral pictures were presented to 44 abstinent alcoholics and 37 age-matched healthy control subjects. We assessed the skin conductance response, and the elicited arousal and valence. Alcoholics and control subjects did not differ in arousal, valence or skin conductance response evoked by alcohol-associated and affectively neutral stimuli, while nonalcoholic beverages were rated as more unpleasant and arousing by alcoholics compared with control subjects. In the fMRI pilot study, alcohol and abstract pictures were presented to six abstinent alcoholics and induced a significant activation of brain areas associated with visual emotional processes such as the fusiform gyrus, parts of the brain reward system (basal ganglia and orbitofrontal gyrus) and further brain regions in the frontal and parietal cortices associated with the attention network. These observations suggest that standardized pictures of alcoholic beverages can be used to assess brain circuits involved in the processing and evaluation of alcohol cues.

Adult↗

PubMed2002

The Aberdeen Trauma Screening Index: an instrument to predict post-accident psychopathology.

BACKGROUND: A key challenge in trauma care is the prevention of psychopathology. However, no definitive method of identifying individuals at risk of developing psychopathology exists. The Aberdeen Trauma Screening Index (ATSI) is a brief screening tool developed for use in a clinical setting by non-mental health professionals to facilitate the early identification of individuals most at risk of psychopathology 3-months post-accident. METHODS: The ATSI derived from a prospective study of a 150 out of an initial pool of 213 consecutive admissions to the Orthopaedic Trauma Unit and the Accident and Emergency Department of Aberdeen Royal Infirmary. Potential predictors were identified by a comprehensive assessment conducted within 1-week post-accident. Outcome at 3-months post-accident was measured using 'caseness' according to the General Health Questionnaire (GHQ-28). RESULTS: The ATSI is based on a final model comprising only seven variables with a sensitivity of 79% and specificity of 65%. A predictive index score (0-100) was produced to ensure the practical utility of the ATSI in a clinical setting. A ROC curve was constructed to illustrate the relationship between sensitivity and the specificity values with their corresponding threshold scores. On the basis of a prevalence rate of 55% 'caseness', as identified in the present study, a cut-off point of 45 provides the optimal outcome with a sensitivity value of 70% and a specificity value of 71%. CONCLUSIONS: The ATSI can accurately identify those most at risk of developing psychopathology 3-months post-accident in a sample of accidentally injured adult subjects recruited as consecutive admissions to an urban hospital in the North East of Scotland. However, to establish the generalizability of these findings, it is important that the ATSI be validated in both similar and diverse populations.

Accidents↗

PubMed2002

Chemical reactions and morphological stability at the Cu/Al2O3 interface.

The microstructures of diffusion-bonded Cu/(0001)Al2O3 bicrystals annealed at 1000 degrees C at oxygen partial pressures of 0.02 or 32 Pa have been studied with various microscopy techniques ranging from optical microscopy to high-resolution transmission electron microscopy. The studies revealed that for both oxygen partial pressures a 20-35 nm thick interfacial CuAlO2 layer formed, which crystallises in the rhombohedral structure. However, the CuAlO2 layer is not continuous, but interrupted by many pores. In the samples annealed in the higher oxygen partial pressure an additional reaction phase with a needle-like structure was observed. The needles are several millimetres long, approximately 10 microm wide and approximately 1 microm thick. They consist of CuAlO2 with alternating rhombohedral and hexagonal structures. Solid-state contact angle measurements were performed to derive values for the work of adhesion. The results show that the adhesion is twice as good for the annealed specimen compared to the as-bonded sample.

Journal Article↗

PubMed2002

Localization of the fertilized germinal disc in the chicken egg before incubation.

At the time of oviposition, the embryo in the fertilized chicken egg has developed the germinal disc on top of the yolk and contains thousands of blastodermal cells. The germinal disc escapes exact localization because it is surrounded by albumen and shell membranes under a calcified shell. This study investigated whether or not ultrasonography or nuclear magnetic resonance imaging (MRI) are suited to localize the germinal disc and, if so, to estimate the accuracy of localization. Hatchability of treated eggs was also recorded. The ultrasound waves were reflected by the shell. The germinal disc could be seen only after removal of the eggshell and the outer shell membrane. In all, 39 intact eggs, MRI localized the germinal disc within 2 mm thick image slices. The mean position of the germinal disc deviated 3.0+/-2.1 mm from the maximum vertical plane of the egg with a mean distance to the inner surface of the shell of 2.7+/-1.1 mm. Incubation resulted in 84.2 and 77.5% hatched chicks for imaged eggs and controls, respectively. The localization results of MRI were verified manually in 38 open shell cultures. Correlation coefficients for the position of the germinal disc were r = 0.86 to 0.99 for the x-axis, r = 0.75 to 0.89 for the y-axis, and r = 0.63 to 0.76 for the z-axis. The study thus shows that MRI is a reliable tool to localize the germinal disc within the intact freshly laid egg.

Animals↗

PubMed2002

[Synthesis of signaling N-acyl-homoserine-lactones participating in quorum sensing in rhizosphere and soil bacteria Pseudomonas and Xanthomonas].

Signaling molecules assigned to N-acyl-homoserine-lactones (AHL) serve as autoinducers for the genes controlling the quorum sensing regulatory system. In many gram-negative bacteria, AHL are the key factors responsible for density-dependent regulation of exoenzyme and secondary metabolite production; they also participate in interaction between bacteria and higher organisms. The soil and rhisosphere bacteria Pseudomonas and Xanthomonas from different geographical zones of Russia and the former USSR were analyzed for the presence of the AHL producers. Screening was conducted by using a test system based on the mutant strain Chromobacterium violaceum, which was unable to synthesize AHL but produced a pigment violacein in the presence of exogenous AHL. The AHL-like compounds proved to be formed by 9.7% of the studied bacteria. Various Pseudomonas species differed in the capacity to synthesize this compounds. In at least a half of the isolated P. aureofaciens and P. aeruginosa, an intense AHL production was observed, whereas the AHL-producers were far less frequent among the P. fluorescens, P. chlororaphis, P. lemonnieri, P. geniculata, and P. putida. None of the 41 Xanthomonas maltophilia strains examined synthesized AHL.

Homoserine↗

PubMed2001

Tyrosine phosphorylation of the beta 4 integrin cytoplasmic domain mediates Shc signaling to extracellular signal-regulated kinase and antagonizes formation of hemidesmosomes.

Ligation of the alpha(6)beta(4) integrin induces tyrosine phosphorylation of the beta(4) cytoplasmic domain, followed by recruitment of the adaptor protein Shc and activation of mitogen-activated protein kinase cascades. We have used Far Western analysis and phosphopeptide competition assays to map the sites in the cytoplasmic domain of beta(4) that are required for interaction with Shc. Our results indicate that, upon phosphorylation, Tyr(1440), or secondarily Tyr(1422), interacts with the SH2 domain of Shc, whereas Tyr(1526), or secondarily Tyr(1642), interacts with its phosphotyrosine binding (PTB) domain. An inactivating mutation in the PTB domain of Shc, but not one in its SH2 domain, suppresses the activation of Shc by alpha(6)beta(4). In addition, mutation of beta(4) Tyr(1526), which binds to the PTB domain of Shc, but not of Tyr(1422) and Tyr(1440), which interact with its SH2 domain, abolishes the activation of ERK by alpha(6)beta(4). Phenylalanine substitution of the beta(4) tyrosines able to interact with the SH2 or PTB domain of Shc does not affect incorporation of alpha(6)beta(4) in the hemidesmosomes of 804G cells. Exposure to the tyrosine phosphatase inhibitor orthovanadate increases tyrosine phosphorylation of beta4 and disrupts the hemidesmosomes of 804G cells expressing recombinant wild type beta(4). This treatment, however, exerts a decreasing degree of inhibition on the hemidesmosomes of cells expressing versions of beta(4) containing phenylalanine substitutions at Tyr(1422) and Tyr(1440), at Tyr(1526) and Tyr(1642), or at all four tyrosine phosphorylation sites. These results suggest that beta(4) Tyr(1526) interacts in a phosphorylation-dependent manner with the PTB domain of Shc. This event is required for subsequent tyrosine phosphorylation of Shc and signaling to ERK but not formation of hemidesmosomes.

Amino Acid Substitution↗

PubMed2001

[Medical ethics of heroin prescription by physicians].

Due to increasing public health and social issues as secondary problems of opiate dependence (e.g. mortality, risk of HIV- and hepatitis infection, high rate of criminal activities) heroin prescription to opiate addicts has been suggested. Scientific data do not yet allow a solid evaluation of this treatment. As generally accepted, the main criteria for an ethical evaluation of new treatments are a) beneficence (duty to help patients further their important and legitimate interests), b) respect for the patient's autonomy and c) social justice in the allocation of the limited resources of the health care system. Ethical problems of heroin prescription relate to the differentiation between medical concern for the individual patient's health and the public interests in reducing social problems, the problematic capability of addicts of a balanced evaluation of heroin prescription and economic considerations of the costs of heroin prescription in comparison with other forms of treatment of opiate addiction, especially methadone maintenance treatment.

Contraindications↗

PubMed2001

Classification of severe head injury based on magnetic resonance imaging.

OBJECT: In 1991 a new pioneering classification of severe head injuries had been proposed, based on CT findings. Unfortunately CT cannot visualise all lesions. Especially brain stem lesions may escape CT in spite of modern equipment, but may be demonstrated by MRI. The high incidence of CT negative but MRI positive posttraumatic brain stem lesions has already been demonstrated in a limited number of cases. A statistically significant evaluation is still missing. Therefore we have investigated a series of 102 comatose patients, in whom a statistical evaluation of MRI findings and their correlation with mortality and outcome of survivors was possible. PATIENTS AND METHODS: MRI was obtained within 8 days after servere head injury in 102 patients with a minimum of 24 hours of coma. The location of the lesions. identified by a neuroradiologist who was unaware of the clinical findings, was correlated with mortality, outcome of surviors and duration of coma. The correlation was analysed statistically. Follow-up ranged from 3 months to 3 years with a mean of 22 months. Four groups of lesions gave significant correlations: Grade I lesions were lesions of the hemispheres only; Grade II lesions were unilateral lesions of the brain stem at any level with or without supratentorial lesions; Grade III lesions were bilateral lesions of the mesencephalon with or without supratentorial lesions. Grade IV lesions were bilateral lesion of the pons with or without any of the foregoing lesions of lesser grades. RESULTS: Mortality increased from 14% in grade I lesions to 100% in grade IV lesions. The Glasgow outcome score differed significantly for each grade. The mean duration of coma increased from 3 days in grade I patients to 13 days in grade III. The correlations between the lesions grade I to IV with mortality, outcome of survivors and duration of coma were highly significant. CONCLUSION: The statistically significant correlations between the 4 groups of severe head injury patients, as identified by MRI, with mortality and outcome of survivors justify a new classification based on early MRI findings.

Adolescent↗

PubMed2001

Medical management of obesity.

Obesity has become a major health problem in many countries because of its high prevalence and causal relationship with serious medical complications. Many of the medical complications associated with obesity improve with intentional weight in a dose-dependent fashion, and even a modest weight loss of 50% of initial weight has beneficial effects. This article reviews the nonsurgical approaches for achieving weight loss in obese persons.

Adult↗

PubMed2001

A new 5-aminosalicylic acid multi-unit dosage form for the therapy of ulcerative colitis.

The aim of the present study was to develop a multi-unit dosage form containing 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis (UC), optimised on the basis of recent studies indicating that UC patients have higher intestinal pH than was previously thought to be the case. Pellets with a drug content of 77.4% were prepared by a granulation and spheronization process and then coated with a new pH sensitive poly(meth)acrylate copolymer (Eudragit((R)) FS 30D) to achieve site specific drug release close to the ileocecal valve. Dissolution tests were carried out in a paddle dissolution apparatus in media simulating pH conditions at various locations in the gastrointestinal tract. The pellets released rapidly at pH values above 7.5. Between 6.8 and 7.2 drug release was found to be zero order, while at pH 6.5 and below no release occurred. In a biorelevant medium which simulates the fasting proximal small intestine fluid it was shown that neither surfactants (sodium taurocholate and lecithin) nor changes in ionic strength trigger drug release. Compared to 5-ASA pellets coated with the well established Eudragit((R)) S, and to currently marketed products licensed for the treatment of UC, the multi-unit dosage form coated with the new polymer exhibited an in vitro dissolution profile more appropriate to the pH profile of the ileum and the colon observed in UC patients.

Acrylates↗

PubMed2001

Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle.

Adhesion to fibronectin through the alpha5beta1 integrin enables endothelial cells to proliferate in response to growth factors, whereas adhesion to laminin through alpha2beta1 results in growth arrest under the same conditions. On laminin, endothelial cells fail to translate Cyclin D1 mRNA and activate CDK4 and CDK6. Activated Rac, but not MEK1, PI-3K, or Akt, rescues biosynthesis of cyclin D1 and progression through the G(1) phase. Conversely, dominant negative Rac prevents these events on fibronectin. Mitogens promote activation of Rac on fibronectin but not laminin. This process is mediated by SOS and PI-3K and requires coordinate upstream signals through Shc and FAK. These results indicate that Rac is a crucial mediator of the integrin-specific control of cell cycle in endothelial cells.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Menstrual effects on asymmetrical olfactory acuity.

Gender specific discrepancies on psychometric examination are often interpreted to reflect static differences in cerebral hemisphere specialization, but dynamic alterations relating to circulating gonadal hormones may also be relevant after puberty. The often cited inference of a right hemisphere advantage in males and left hemisphere advantage in females derived from small but reliable differences on spatial tasks and verbal tasks, for example, may to some extent relate to gender-specific differences in circulating gonadal hormones. Performance fluctuations on other higher order cognitive tasks through the menstrual cycle tend to support a temporal association between alterations in cerebral laterality and hormone fluctuations. A potential left hemisphere advantage after menstruation when estrogen and progesterone levels are high in contrast to a right hemisphere advantage at menstruation when estrogen and progesterone levels are low has also received support from shifts in visual field perception. The present investigation continues this line of work by measurement of prospective changes in unirhinal olfactory acuity in the menstrual, ovulatory, and midluteal phases of the menstrual cycle in 11 healthy women who agreed to blood assays of estradiol and progesterone prior to completing a modified version of the Connecticut Chemosensory Perception Exam (CCPE). The CCPE detection of n-butanol showed a clear pattern of changes over the menstrual cycle marked by an asymmetry favoring the right nostril during menstruation when estradiol and progesterone levels were low, an asymmetry favoring the left nostril during ovulation when estradiol levels were high and progresterone levels were low, and an absence of asymmetry during the midluteal phase when estradiol levels decreased and progesterone levels increased. Preliminary correlation analyses revealed a potential competitive influence of estradiol and progesterone on this apparent shift in cerebral laterality. There is thus sufficient evidence to conclude that dynamic changes in relative cerebral hemisphere advantages have a temporal relation to fluctuations in circulating gonadal hormones and to suggest the value of additional investigation of more specific causal relations.

Adult↗

PubMed2001

Outcome success in obesity.

Intentional weight loss improves many of the medical complications associated with obesity. Moreover, many of these beneficial effects have a dose-dependent relationship with the amount of weight lost and begin after only modest weight losses of 5% to 10% of initial body weight. There is no conclusive evidence that weight loss decreases mortality in obese people. The therapeutic effect of weight loss on risk factors for cardiovascular disease (insulin resistance and diabetes, dyslipidemia, and hypertension) has received the most attention in clinical trials. The hazard of developing coronary heart disease is directly related to the concomitant burden of risk factors. Modest weight loss can affect the entire cluster of risk factors simultaneously. Both negative energy balance and weight loss improve insulin sensitivity and glycemic control in obese patients with type 2 diabetes. Most studies have found that weight loss decreases serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol concentrations and increases serum high-density lipoprotein cholesterol concentration. Regain of weight leads to relapse in triglyceride and cholesterol concentrations. Weight loss, independent of sodium restriction, decreases systolic and diastolic blood pressure. Dietary intervention is the cornerstone of weight-loss therapy. Most diets proposed for losing weight vary in two principal dimensions: energy content and macronutrient composition. Manipulation of food macronutrient content, energy density, and portion size can help decrease energy intake and facilitate weight loss.

Cardiovascular Diseases↗

PubMed2001

Orlistat inhibits dietary cholesterol absorption.

OBJECTIVE: Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low-density lipoprotein-cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration. RESEARCH METHODS AND PROCEDURES: Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by simultaneous administration of intravenous ([(2)H(6)] cholesterol) and oral ([(2)H(5)] cholesterol) cholesterol tracers. In protocol 1 (n = 9), cholesterol absorption was determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 (n = 9), cholesterol absorption was determined with and without orlistat therapy in a prospective, randomized, crossover design to assess the effect of orlistat on cholesterol absorption. RESULTS: In protocol 1, cholesterol absorption from the test meal was the same on both occasions (53 +/- 5% and 51 +/- 5%). In protocol 2, orlistat treatment caused a 25% reduction in cholesterol absorption, from 59 +/- 6% to 44 +/- 5% (p < 0.01). DISCUSSION: These data demonstrate that orlistat inhibits dietary cholesterol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself.

Adult↗

PubMed2001

Coaxial scanning near-field optical microscope tips: an alternative for conventional tips with high transmission efficiency?

Since the development of the first scanning near-field optical microscope, great effort has been put into the development of near-field optical probe tips with a good lateral resolution of the order of several tens of nanometres and a high power throughput. Several groups have proposed the use of scanning near-field optical tips with a coaxial structure. From electromagnetic theory, it is known that such structures have no cut-off frequency and a power transmission close to unity. In this paper we discuss some topics concerning the stimulation of optical coaxial waves and their propagation behaviour.

Electromagnetic Phenomena↗

PubMed2001

The KEX2 gene of Candida glabrata is required for cell surface integrity.

Candida glabrata has emerged as one of the most common causes of candidosis. In order to identify factors that are necessary for viability and pathogenicity of this fungal pathogen, we analysed the role of the KEX2 gene, which codes for a regulatory endoproteinase that is known to process certain virulence factors in Candida albicans. The KEX2 gene from C. glabrata was cloned and found to have 51% and 62% identity and high structural similarities to the homologous counterparts in C. albicans and Saccharomyces cerevisiae. KEX2 was expressed at all time points investigated during growth in complex medium. In order to investigate the role of this putative regulatory proteinase, Kex2-deficient mutants were produced. In addition to known kex2 phenotypes, such as pH and calcium hypersensitivity, the mutants grew in cellular aggregates and were found to be hypersensitive to several antifungal drugs that target the cell membrane, including azoles, amorolfine and amphotericin B. Ultrastructural investigation after exposure to low doses of itraconazole showed azole-specific alterations such as enlarged vacuoles and proliferation of the cytoplasmatic membrane in the kex2 mutants, but not in the control strains. In contrast, antifungals such as 5-flucytosine and hydroxypyridones inhibited growth of the kex2 mutants and the control strains to the same extent. In an in vitro model of oral candidosis, kex2 mutants showed reduced tissue damage in the presence of itraconazole compared with the control infections. These data suggest that Kex2 is involved in the processing of proteins that are essential for cell surface integrity of C. glabrata.

Amino Acid Sequence↗

PubMed2001

AGA technical review on parenteral nutrition.

This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Practice Economics Committee. The paper was approved by the Committee on September 13, 2001, and by the AGA Governing Board on May 18, 2001.

Gastroenterology↗