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Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 73 records · Page 4Linked to original sources
PubMed2000

Suicide by patients: questionnaire study of its effect on consultant psychiatrists.

OBJECTIVE: To identify the effect of patients' suicide on consultant psychiatrists in Scotland. DESIGN: Confidential coded postal questionnaire survey. PARTICIPANTS: Of 315 eligible consultant psychiatrists, 247 (78%) contributed. SETTING: Scotland. MAIN OUTCOME MEASURES: Experience of patient suicide; the features and impact of "most distressing" suicide and what helped them to deal with it. RESULTS: 167 (68%) consultants had had a patient commit suicide under their care. Fifty four (33%) reported being affected personally in terms of low mood, poor sleep, or irritability. Changes in professional practice were described by 69 (42%) of the psychiatrists-for example, a more structured approach to the management of patients at risk and increased use of mental health legislation. Twenty four (15%) doctors considered taking early retirement because of a patient's suicide. Colleagues and family or friends were the best sources of help, and team and critical incident reviews were also useful. CONCLUSIONS: Suicide by patients has a substantial emotional and professional effect on consultant psychiatrists. Support from colleagues is helpful, and professional reviews provide opportunities for learning and improved management of suicide and its aftermath.

Emotions↗
PubMed2000

Signal transduction by a nondissociable heterotrimeric yeast G protein.

Many signal transduction pathways involve heterotrimeric G proteins. The accepted model for activation of heterotrimeric G proteins states that the protein dissociates to the free G(alpha) (GTP)-bound subunit and free G(betagamma) dimer. On GTP hydrolysis, G(alpha) (GDP) then reassociates with G(betagamma) [Gilman, A. G. (1987) Annu. Rev. Biochem. 56, 615-649]. We reexamined this hypothesis, by using the mating G protein of the yeast Saccharomyces cerevisiae encoded by the genes GPA1, STE4, and STE18. In the absence of mating pheromone, the G(alpha) (Gpa1) subunit represses the mating pathway. On activation by binding of pheromone to a serpentine receptor, the G(betagamma) (Ste4, Ste18) dimer transmits the signal to a mitogen-activated protein kinase cascade, leading to gene activation, arrest in the G(1) stage of the cell cycle, production of shmoos (mating projections), and cell fusion. We found that a Ste4-Gpa1 fusion protein transmitted the pheromone signal and activated the mating pathway as effectively as when Ste4 (G(beta)) and Gpa1 (G(alpha)) were coexpressed as separate proteins. Hence, dissociation of this G protein is not required for its activation. Rather, a conformational change in the heterotrimeric complex is likely to be involved in signal transduction.

Blotting, Western↗
PubMed2000

Antithrombotic efficacy of RPR208566, a novel factor Xa inhibitor, in a rat model of carotid artery thrombosis.

Coagulation factor Xa is the sole enzyme responsible for activating the zymogen prothrombin to thrombin, resulting in fibrin generation, platelet activation, and subsequent thrombus formation. Our objective was to evaluate the antithrombotic efficacy of the novel factor Xa inhibitor, 2-(3-carbamimidoyl-benzyl)-3-[(3', 4'dimethoxy-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester-trifluoroacetate (RPR208566), in a well-established rat model of arterial thrombosis, and to compare the results with those obtained with argatroban and heparin, direct and indirect inhibitors of thrombin, respectively. Thrombus formation was initiated by placing a filter paper saturated with FeCl(2) on the adventia of the carotid artery for 10 min. Time-to-occlusion was measured from initiation of injury until blood flow reached zero. Formed thrombi were removed and weighed 60 min after the placement of the filter paper. RPR208566, heparin, and argatroban dose-dependently increased time-to-occlusion and reduced thrombus mass. When administered at 500 microgram/kg+50 microgram/kg/min, RPR208566 prolonged time-to-occlusion to 56+/-4 min (vs. 18+/-2 min for vehicle) and reduced thrombus mass to 3.0+/-0.7 mg (vs. 7.3+/-0.6 mg for vehicle). The highest doses of argatroban (500 microgram/kg+50 microgram/kg/min) and heparin (300 U/kg+10 U/kg/min) increased time-to-occlusion to the maximum of 60 min and decreased thrombus mass to 5.5+/-0.8 and 2.6+/-0.3, respectively. The antithrombotic effects of heparin and argatroban at these doses were associated with increases in activated partial thromboplastin time of 5.6+/-0.9- and 2.9+/-0.3-fold over baseline, respectively. However, the highest dose of RPR208566 produced a modest 1.3+/-0.1-fold increase in activated partial thromboplastin time. These results indicate that factor Xa inhibition with compounds such as RPR208566 may be an attractive mechanism for novel antithrombotic drug therapy.

Amidines↗
PubMed2000

Biochemical analysis of the arginine methylation of high molecular weight fibroblast growth factor-2.

The post-translational methylation of the N-terminally extended or high molecular weight (HMW) forms of fibroblast growth factor-2 (FGF-2) has been shown to affect the nuclear accumulation of the growth factor. In this study, we determined the extent and position of methyl groups in HMW FGF-2. Using mass spectrometry and amino acid sequence analysis, we have shown that the 22- and 22.5-kDa forms of HMW FGF-2 contain five dimethylated arginines located at positions -22, -24, -26, -36, and -38 using the methionine residue normally used to initiate the 18-kDa form as position 0. The 24-kDa form of HMW FGF-2 contains seven to eight dimethylated arginines located at positions -48, -50, and -52, in addition to positions -22, -24, -26, -36, and -38. In vitro methylation reactions demonstrate that the N-terminal extension of HMW FGF-2 acts as a specific substrate for yeast Hmt1p and human HRMT1L2 arginine methyltransferases. These findings indicate that HMW FGF-2, with the presence of five or more dimethylated Gly-Arg-Gly repeats, contains an RGG box-like domain, which may be important for protein-protein and/or protein-RNA interactions.

3T3 Cells↗
PubMed2000

Chronic fatigue syndrome: an examination of the phases.

The present study examined the Fennell Phase Inventory, an instrument designed to measure the phases typically experienced by individuals with chronic fatigue syndrome (CFS). This inventory yields three factor scores of Crisis, Stabilization, and Integration. These factor scores have been employed in a cluster analysis, yielding four clusters that matched the four phases predicted by Fennell: Crisis, Stabilization, Resolution, and Integration. The present study represents a partial replication study of a prior investigation of the Fennell Phase Inventory by Jason et al. (in press), but that earlier study did not have an independent physician examination to diagnose patients with CFS. In the present study, 65 patients diagnosed with chronic fatigue syndrome by a physician were recruited and administered the Fennell Phase Inventory and other measures assessing CFS-related symptoms, disability, and coping. Each of the 65 patients was classified into one of four predefined clusters measuring a Crisis phase, a Stabilization phase, a Resolution phase, and an Integration phase. Relationships were explored between three of these cluster groupings and measures of symptoms, disability, and coping. Results confirmed Fennell's model, revealing significant differences between the three clusters in terms of levels of disability and modes of coping. Results suggest that the Fennell Phase Inventory accurately differentiates phases of adaptation to illness experienced by individuals with CFS.

Adaptation, Psychological↗
PubMed2000

The dimensional complexity of the EEG during cognitive tasks reflects the impaired information processing in schizophrenic patients.

The aim of the present study was to investigate whether schizophrenic patients show a different change of the dimensional complexity of the EEG, as represented by the Grassberger-Procaccia correlation dimension D(2,) under cognitive challenge compared to normal control subjects. With respect to results reported in the literature, it was expected that the complexity of the signal under cognitive challenge is higher in schizophrenic patients than in normal control subjects reflecting the impaired information processing abilities of the patients. Eighty-seven schizophrenic and 30 matched control subjects performed two different types of the continuous performance task. The results revealed differences between schizophrenic patients and control subjects for the performance as well as the complexity measures. Schizophrenic patients produced more omission errors than normal subjects did. For the EEG complexity measure no differences occurred under the baseline condition. In contrast, during the first minute under task conditions the control subjects showed a decrease of the dimension while no changes were found for the schizophrenic group. These results occurred for both types of the cognitive task but they reached clear significance only in one of them. The results are interpreted as reflecting the ability of normal subjects to adapt their information processing system to the cognitive challenge and to focus their attention on the task while schizophrenic subjects do not show this adaptation to the task.

Adult↗
PubMed2000

The effects of the participation of patients with cancer in teaching communication skills to medical undergraduates: a randomised study with follow-up after 2 years.

The importance of good doctor-patient communication is widely recognised. The aims of this study were to evaluate the immediate effects of the participation of patients with cancer on the attitudes and skills of undergraduate medical students receiving an interview skills training programme, and to assess the effects of the participation of patients with cancer on the attitudes and interview performance of students 2 years later. It was hypothesised that the participation of cancer patients would have specific beneficial effects on attitudes and interview performance. Before participating in a 6-session interview methods course in third year, students were randomised to be taught with patients who had cancer (experimental group) or with patients with other diagnoses (control group). Before and after participating in the course, 233 students (94% response rate) completed an Attitudes Questionnaire. When they reached their fifth year, 54 students again completed the Attitudes Questionnaire and, in addition, made a video recording of an interview with a patient who had gynaecological cancer. These recordings were rated independently by two researchers using the Interview Rating Instrument. Immediately after the course, a number of differences were found between the two groups. For example, students in the experimental group were more likely to consider the ability to listen an extremely important characteristic of hospital doctors and to consider more strongly that trust is an essential part of the doctor-patient relationship. 2 years after the course, the ability of hospital doctors to communicate with patients, and the need for clinical decisions to reflect patients' wishes, were considered to be more important by students in the experimental group, although even 96% of controls felt both these issues were very or extremely important. As hypothesised, the experimental group had better ratings in terms of responding empathically, showing regard and concern for the patient, and assessing the impact of the symptoms on the patient's life. The participation of patients with cancer has beneficial and enduring effects on the attitudes and interview performance of medical undergraduates. Medical schools should consider how best patients with cancer can make an important contribution to communication skills training.

Clinical Competence↗
PubMed2000

Localization of Xho1 repetitive sequences on autosomes in addition to the W chromosome in chickens and its relevance for sex diagnosis.

Repetitive sequences of the Xho1 family comprise about 70% of the W chromosome in chickens, are considered to be restricted to this sex chromosome and are used in sex diagnosis. This study investigated the reliability of sex diagnosis on small cell numbers. Fluorescent in situ hybridizations (FISH) with the Xho1 repeat sequence were performed on metaphases and signals were detected on the W chromosome and on some autosomes. Differences in signal intensity suggested that the number of repeats ranged from several thousand on the W chromosome to only a few on the autosomes. These results confirm the report from Clinton (1994) of minor male products in sex specific PCR of the Xho1 repeat. We adopted his PCR protocol to analyze small numbers of cells. FISH on blastomeres and on blood cells from E3 to E11 embryos were compared to PCR results. The FISH procedure as well as the PCR protocol are suitable for sexing. For single cells FISH was slightly more consistent.

Animals↗
PubMed2000

[Magnetic resonance imaging diagnosis of craniobasal cerebrospinal fluid fistulas by 3D-CISS sequence].

Recently, a Magnetic Resonance Imaging (MRI)-technique has been developed to diagnose the exact anatomical location of fistulas of the cerebrospinal fluid (CSF). This method is called 3D-constructive interference steady state-sequence (CISS) but it is not well known in clinical practice. Aim of the study was the evaluation of specificity and sensitivity of CISS-MRI. 12 patients with rhinoliquorrhea after head injury (n = 7) or skull base tumours (n = 5) were examined by CISS-MRI. The examinations were performed with a 1.5 T whole body MRI scanner in prone position and coronal plane sections. In cases of CSF leckage the sensitivity for detection of a CSF fistula was 100%. In comparison with intraoperative findings, specificity was 100%: in all cases, a dural lesion in anatomical correlation to MRI was detected. Further advantages of this method are its non-invasive character, no need for contrast application, no radiation exposure, and exact localisation of additional anatomical findings (brain herniation, brain contusions).

Adolescent↗
PubMed2000

Facial nerve repair: a retrospective review.

UNLABELLED: The purpose of this article is to review a large series of patients evaluated for disorders of the facial nerve in order to assess the indications for surgery, the timing of surgery, the techniques of nerve repair, and to better define those factors associated with a favorable outcome. STUDY DESIGN: A retrospective review of patients undergoing facial nerve repair from 1963-1997. METHODS: One hundred and three patients underwent surgical intervention designed to repair a disrupted facial nerve. All procedures were performed by one of the senior surgeons (M.M.) Seventy-two patients had a complete data set and at least one year of follow-up. RESULTS: Eighty percent of patients attained an outcome considered superb to fair. Twenty percent of patients had a poor outcome. There was a slight worsening of outcome with increased time to repair. Patients with a neoplastic etiology of nerve paralysis tended to have a worse outcome. CONCLUSIONS: Facial nerve grafting is most successful if intervention is undertaken at or near the time of initial injury. However, prolonged time (up to two years) to repair does not preclude the potential for some recovery. The limitations of the current systems for grading facial recovery after nerve repair are well known, and the adoption of a new grading scale for assessing recovery after reanimation procedure is recommended.

Adolescent↗
PubMed2000

Student Research Award 1999: comparative contrast of voice measurements.

Currently, a variety of objective and subjective measures are available to describe voice and voice function. Despite these various tools, there is no standard measure of voice function that incorporates both objective and subjective measures. The goal of this research was to study the relationship between objective, subjective, and patient-based measures of voice function. Objective voice function was measured with 4 laboratory-based parameters (subglottic pressure, airflow at the lips, maximum phonation time, and vocal efficiency), subjective function with the GRBAS (grade, rough, breathy, asthenic, strained) scale, and patient-based function according to an overall global rating of quality. The objective and subjective measures were significantly related to each other (P < 0.05); the objective and patient-based measures were also related (P = 0.019), but the subjective and patient-based measures were not related. We demonstrate a significant relationship between some but not all measures of voice function. We believe that subjective measures provide additional valuable information not obtained from objective measures alone.

Adult↗
PubMed2000

Growth on indium-tin oxide-coated glass enhances 32P-phosphate uptake and protein labelling of adherent cells.

A method to improve the efficiency of labelling of adherent cells with radioactive 32p is described. Cells are grown on a glass surface which is coated with indium-tin oxide, a commercially available, transparent material which permits excellent cell adhesion and growth. The results show that a 2 to 3-fold increase in 32p uptake by the cells can be achieved by growing cells on this material, compared to conventional tissue culture plastic.

Animals↗
PubMed2000

Molecular analysis of the Saccharomyces cerevisiae YHR076w gene.

Our results demonstrate that open reading frame (ORF) YHR076w on chromosome VIII of Saccharomyces cerevisiae that was previously described as a hypothetical gene is expressed. This ORF is transcribed as an mRNA of approximately 1,100 nucleotides. A 41.2-kDa polypeptide and three others predicted to be modified forms of Yhr076wp are detected by Western blot with a Yhr076wp-specific antibody. Promoter activity assays indicate that YHR076w transcription is regulated by carbon source and primarily by ethanol. Consistent with this observation, we have identified two potential ADR1 regulatory elements in the YHR076w upstream DNA region. Potential YAP1 and HSP elements are also identified in this region, suggesting other forms of regulation. YHR076w knockout strains do not exhibit any measurable growth or morphological phenotype under any conditions tested. However, increased YHR076w gene dosage confers a growth advantage to both wild-type and YHR076w knockout strains on 2% ethanol or 2% galactose medium in a low O2 growth environment. The fluorescence emitted by a Yhr076wp protein fusion to A. aquorin GFP colocalizes with the mitochondria in vivo.

Calmodulin-Binding Proteins↗
PubMed2000

Lipid metabolism during endurance exercise.

Endogenous triacylglycerols represent an important source of fuel for endurance exercise. Triacylglycerol oxidation increases progressively during exercise; the specific rate is determined by energy requirements of working muscles, fatty acid delivery to muscle mitochondria, and the oxidation of other substrates. The catecholamine response to exercise increases lipolysis of adipose tissue triacylglycerols and, presumably, intramuscular triacylglycerols. In addition, increases in adipose tissue and muscle blood flow decrease fatty acid reesterification and facilitate the delivery of released fatty acids to skeletal muscle. Alterations in fatty acid mobilization and the relative use of adipose and intramuscular triacylglycerols during exercise depend, in large part, on degree of fitness and exercise intensity. Compared with untrained persons exercising at the same absolute intensity, persons who have undergone endurance training have greater fat oxidation during exercise without increased lipolysis. Available evidence suggests that the training-induced increase in fat oxidation is due primarily to increased oxidation of non-plasma-derived fatty acids, perhaps from intramuscular triacylglycerol stores. Fat oxidation is lower in high-intensity exercise than in moderate-intensity exercise, in part because of decreased fatty acid delivery to exercising muscles. Parenteral lipid supplementation during high-intensity exercise increases fat oxidation, but the effect of ingesting long-chain or medium-chain triacylglycerols on substrate metabolism during exercise is less clear. This review discusses the relation between fatty acid mobilization and oxidation during exercise and the effect of endurance training, exercise intensity, and lipid supplementation on these responses.

Adipose Tissue↗
PubMed2000

DNA motif associated with meiotic double-strand break regions in Saccharomyces cerevisiae.

Meiotic recombination in yeast is initiated by DNA double-strand breaks (DSBs) that occur at preferred sites, distributed along the chromosomes. These DSB sites undergo changes in chromatin structure early in meiosis, but their common features at the level of DNA sequence have not been defined until now. Alignment of 1 kb sequences flanking six well-mapped DSBs has allowed us to define a flexible sequence motif, the CoHR profile, which predicts the great majority of meiotic DSB locations. The 50 bp profile contains a poly(A) tract in its centre and may have several gaps of unrelated sequences over a total length of up to 250 bp. The major exceptions to the correlation between CoHRs and preferred DSB sites are at telomeric regions, where DSBs do not occur. The CoHR sequence may provide the basis for understanding meiosis-induced chromatin changes that enable DSBs to occur at defined chromosomal sites.

Argininosuccinate Lyase↗
PubMed2000

Leptin production during early starvation in lean and obese women.

We evaluated abdominal adipose tissue leptin production during short-term fasting in nine lean [body mass index (BMI) 21 +/- 1 kg/m(2)] and nine upper body obese (BMI 36 +/- 1 kg/m(2)) women. Leptin kinetics were determined by arteriovenous balance across abdominal subcutaneous adipose tissue at 14 and 22 h of fasting. At 14 h of fasting, net leptin release from abdominal adipose tissue in obese subjects (10.9 +/- 1.9 ng x 100 g tissue x (-1) x min(-1)) was not significantly greater than the values observed in the lean group (7.6 +/- 2.1 ng x 100 g(-1) x min(-1)). Estimated whole body leptin production was approximately fivefold greater in obese (6.97 +/- 1.18 microg/min) than lean subjects (1.25 +/- 0.28 microg/min) (P < 0.005). At 22 h of fasting, leptin production rates decreased in both lean and obese groups (to 3.10 +/- 1.31 and 10.5 +/- 2.3 ng x 100 g adipose tissue(-1) x min(-1), respectively). However, the relative declines in both arterial leptin concentration and local leptin production in obese women (arterial concentration 13.8 +/- 4.4%, local production 10.0 +/- 12.3%) were less (P < 0.05 for both) than the relative decline in lean women (arterial concentration 39.0 +/- 5.5%, local production 56.9 +/- 13.0%). This study demonstrates that decreased leptin production accounts for the decline in plasma leptin concentration observed after fasting. However, compared with lean women, the fasting-induced decline in leptin production is blunted in women with upper body obesity. Differences in leptin production during fasting may be responsible for differences in the neuroendocrine response to fasting previously observed in lean and obese women.

Abdomen↗
PubMed2000

Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women.

We measured whole body and regional lipolytic and adipose tissue blood flow (ATBF) sensitivity to epinephrine in 8 lean [body mass index (BMI): 21 +/- 1 kg/m(2)] and 10 upper body obese (UBO) women (BMI: 38 +/- 1 kg/m(2); waist circumference >100 cm). All subjects underwent a four-stage epinephrine infusion (0.00125, 0.005, 0.0125, and 0.025 microgram. kg fat-free mass(-1). min(-1)) plus pancreatic hormonal clamp. Whole body free fatty acid (FFA) and glycerol rates of appearance (R(a)) in plasma were determined by stable isotope tracer methodology. Abdominal and femoral subcutaneous adipose tissue lipolytic activity was determined by microdialysis and (133)Xe clearance methods. Basal whole body FFA R(a) and glycerol R(a) were both greater (P < 0.05) in obese (449 +/- 31 and 220 +/- 12 micromol/min, respectively) compared with lean subjects (323 +/- 44 and 167 +/- 21 micromol/min, respectively). Epinephrine infusion significantly increased FFA R(a) and glycerol R(a) in lean (71 +/- 21 and 122 +/- 52%, respectively; P < 0.05) but not obese subjects (7 +/- 6 and 39 +/- 10%, respectively; P = not significant). In addition, lipolytic and ATBF sensitivity to epinephrine was blunted in abdominal but not femoral subcutaneous adipose tissue of obese compared with lean subjects. We conclude that whole body lipolytic sensitivity to epinephrine is blunted in women with UBO because of decreased sensitivity in upper body but not lower body subcutaneous adipose tissue.

Abdomen↗