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Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 37 records · Page 2Linked to original sources
PubMed2001

Video-based computer-assisted learning.

As a relevant exemplar of MPEG-1 and MPEG-2 digital video use, a multimedia computer-assisted learning (CAL) application dealing with Critical Communication Issues in medicine was developed. The application allowed the student to navigate through a series of high-quality digital video and audio clips that were delivered in near real-time from an Intranet server. This paper gives a brief background to the MPEG-2 video compression system and discusses the use of digital video in a CAL environment.

Communication↗
PubMed2001

Whole-body and adipose tissue glucose metabolism in response to short-term fasting in lean and obese women.

BACKGROUND: Alterations in glucose metabolism during early fasting may be an important trigger of the hormonal and metabolic responses to fasting. OBJECTIVE: The purpose of this study was to determine whether glucose metabolism in response to brief starvation differs in lean and abdominally obese women. DESIGN: We evaluated whole-body glucose metabolism by use of stable-isotope tracer methods and glucose uptake in subcutaneous abdominal adipose tissue by use of arteriovenous balance in 7 lean [58 +/- 2 kg; body mass index (BMI; in kg/m(2)): 21 +/- 5] and 6 abdominally obese (96 +/- 2 kg; BMI: 36 +/- 1) women after 14 and 22 h of fasting. RESULTS: Between 14 and 22 h of fasting, whole-body glucose production and disposal declined in both groups (P < 0.05), but the reduction was 50% greater in lean than in obese women (P < 0.05). The decline in glucose uptake at 22 h of fasting was also lower in obese (0.11 +/- 0.04 micromol*100 g(-1) x min(-1)) than in lean (0.26 +/- 0.03 micromol x 100 g(-1) x min(-1)) women (P < 0.05). Decreases in plasma insulin and leptin concentrations between 14 and 22 h of fasting were also lower in obese than in lean women (insulin: 20 +/- 3% and 32 +/- 5%; leptin: 18 +/- 3% and 37 +/- 6%; both P < 0.05). CONCLUSIONS: The normal decline in glucose production and uptake that occurs during early fasting is blunted in women with abdominal obesity. These alterations in glucose metabolism are associated with a blunted decline in circulating concentrations of both insulin and leptin, which may explain some of the differences in the metabolic response to fasting observed between lean and abdominally obese persons.

Abdomen↗
PubMed2001

Comorbidities and quality of life in patients with interferon-refractory chronic hepatitis C.

OBJECTIVES: Patients with chronic hepatitis C (HCV) consistently report a reduction in multiple domains of health-related quality of life (HRQOL) that does not correlate with liver disease severity. This may in part be due to the use of insensitive HRQOL instruments or extrahepatic factors that independently influence HRQOL. We hypothesized that a past history of substance abuse or active medical and psychiatric comorbidities would correlate with HRQOL scores. METHODS: In 107 patients who had failed previous interferon therapy, HRQOL was measured by using the modified SF-36, a disease-specific instrument, and the Health Utilities Index (HUI) Mark III, a generic instrument. RESULTS: Multiple SF-36 subscale and summary scores as well as the HUI Mark III attributes of emotion and pain were significantly reduced in the study population compared with healthy controls (p < 0.001). Serum alanine aminotransferase and HCV RNA levels, HCV genotype, liver histology, and HCV risk factors as well as demographic variables did not correlate with modified SF-36 and HUI scores. In addition, a history of alcohol abuse or dependency and intravenous drug use or dependency, identified in 52 and 51% of participants, respectively, did not correlate with HRQOL scores. However, the presence of one or more active medical comorbidities, defined as a chronic medical condition requiring treatment and monitoring, was significantly associated with both the modified SF-36 scores and HUI attribute deficits (p < 0.001). In particular, painful medical comorbidities or depressed mood requiring treatment were significantly associated with modified SF-36 scores and with HUI attribute deficits and utility scores (p < 0.001). CONCLUSIONS: Active medical and psychiatric comorbidities may account for some of the reduction and variability in HRQOL scores in patients with chronic HCV who have failed previous interferon therapy. Future studies that control for the presence of active comorbidities in large groups of treatment naive patients with varying severity of chronic HCV are needed to confirm these findings.

Adult↗
PubMed2001

Effect of aging on glucose and lipid metabolism during endurance exercise.

Endurance exercise increases the use of endogenous fuels to provide energy for working muscles. Elderly subjects oxidize more glucose and less fat during moderate intensity exercise. This shift in substrate use is presumably caused by age-related changes in skeletal muscle, including decreased skeletal muscle respiratory capacity, because adipose tissue lipolysis and plasma fatty acid availability are not rate limiting. Endurance training in elderly subjects increases muscle respiratory capacity, decreases glucose production and oxidation, and increases fat oxidation thereby correcting or compensating for the alterations in substrate oxidation associated with aging.

Adipose Tissue↗
PubMed2001

Psychiatric sequelae and psychosocial adjustment following ocular trauma: a retrospective pilot study.

AIMS: To identify the prevalence of psychiatric and adjustment problems after ocular trauma and those factors related to a poor outcome. METHODS: 47 patients were assessed by structured interview, of whom 45 satisfactorily completed three standardised self report measures of psychological functioning, subjective distress, and social adjustment. RESULTS: 33% of patients displayed psychiatric "caseness". A number of features of the victim consistently resulted in poor outcome including a psychiatric history and peritraumatic dissociation. CONCLUSION: These preliminary findings suggest ocular trauma is associated with psychomorbidity and problems of adjustment. The improved management of such patients would benefit from a more detailed analysis by means of a longitudinal study involving larger samples.

Adaptation, Psychological↗
PubMed2001

Gender differences in lipid and glucose kinetics during short-term fasting.

Data obtained from studies conducted in animal models and humans suggest that gender affects the metabolic response to fasting. However, differences in body composition between males and females confound the interpretation of these studies, because increased adiposity itself alters the metabolic response to short-term fasting. We evaluated whole body lipid and glucose kinetics during basal (14-h fast) and short-term fasting (22-h fast) conditions in six women and six men who were matched for adiposity (24 +/- 2 and 23 +/- 2% body wt as fat, respectively). Substrate kinetics were measured by infusing stable isotope labeled tracers of glucose ([(2)H(2)]glucose) and glycerol ([(2)H(5)]glycerol). Basal glycerol rate of appearance (R(a)) in plasma, an indicator of whole body lipolytic rate, was greater in women than in men (2.1 +/- 0.2 vs. 1.5 +/- 0.1 micromol x kg body wt(-1) x min(-1); P < 0.05). However, the relative increase in glycerol R(a) with continued fasting was blunted in women compared with men (40 +/- 7 vs. 80 +/- 4% increase; P < 0.05), resulting in similar lipolytic rates in both genders at 22 h (2.8 +/- 0.2 and 2.6 +/- 0.1 micromol x kg body wt(-1) x min(-1) for women and men, respectively). In contrast, glucose R(a) was similar in men and women at 14 h (11 +/- 0.6 vs. 12 +/- 0.7 micromol x kg body wt(-1) x min(-1) and 22 h of fasting (9 +/- 0.6 vs 10 +/- 0.6 micromol x kg body wt(-1) x min(-1). These data demonstrate the presence of sexual dimorphism in lipid, but not glucose, metabolism during both basal and short-term fasting conditions.

Adipose Tissue↗
PubMed2001

Ambulance personnel and critical incidents: impact of accident and emergency work on mental health and emotional well-being.

BACKGROUND: The association between mental health and occupational factors among ambulance personnel has not been thoroughly investigated in the UK. AIMS: To identify the prevalence of psychopathology among ambulance personnel and its relationship to personality and exposure to critical incidents. METHOD: Data were gathered from ambulance personnel by means of an anonymous questionnaire and standardised measures. RESULTS: Approximately a third of the sample reported high levels of general psychopathology, burnout and posttraumatic symptoms. Burnout was associated with less job satisfaction, longer time in service, less recovery time between incidents, and more frequent exposure to incidents. Burnout and GHQ-28 caseness were more likely in those who had experienced a particularly disturbing incident in the previous 6 months. Concerns about confidentiality and career prospects deter staff from seeking personal help. CONCLUSIONS: The mental health and emotional well-being of ambulance personnel appear to be compromised by accident and emergency work.

Adaptation, Psychological↗
PubMed2001

Effect of short-term fasting on free and bound leptin concentrations in lean and obese women.

Plasma leptin exists in protein-bound and free forms, which may affect its hormonal bioactivity. Therefore, the relationship between bound and free leptin may be particularly important during physiological conditions that cause rapid alterations in total plasma leptin concentration, such as fasting. The purpose of this study was to evaluate the effect of short-term fasting on bound and free plasma leptin concentrations and leptin binding capacity (a measure of plasma leptin-binding protein content) in lean and obese women. Six lean (body mass index, 21 +/- 1 kg/m2) and 6 abdominally obese (BMI, 36 +/- 1 kg/m2) women were studied after 14 h and 22 h of fasting. Although total plasma leptin concentration was more than 6-fold greater in obese (45.4 +/- 7.6 microg/liter) compared with lean (7.4 +/- 1.0 microg/liter) women at 14 h of fasting (P < 0.05), the percentage of leptin in the bound form was greater in lean than obese subjects (29 +/- 2% vs. 12 +/- 3%; P < 0.05). Arterial total, free, and bound plasma leptin concentrations all declined between 14 h and 22 h of fasting in both lean and obese groups, but the relative decline of these fractions was greater in lean (36 +/- 4%, 60 +/- 9%, and 51 +/- 13%, respectively) than in obese (19 +/- 5%, 21 +/- 8%, and 12 +/- 7%, respectively) subjects (all P < 0.05). In contrast, leptin binding capacity was unchanged. The percentage of total plasma leptin present in bound form was constant between 14 h and 22 h of fasting in lean subjects and increased slightly but significantly in obese subjects. These data demonstrate that both free and bound fractions of leptin in plasma decrease quickly in response to energy restriction, but the decline is blunted in abdominally obese compared with lean women. In addition, the equilibrium between bound and free leptin fractions is maintained during brief fasting and is not regulated by leptin binding capacity.

Absorptiometry, Photon↗
PubMed2001

Caring for others can seriously damage your health.

To care for others is a privilege and a source of personal and job satisfaction. However, caregivers must also consider the implications of their work for their own health and welfare.

Adaptation, Psychological↗
PubMed2001

The effect of electrothermal cautery-assisted resection of diminutive colonic polyps on histopathologic diagnosis.

We examined diminutive colonic polyps to identify relationships between thermal electrocoagulation or resection trauma cytologic artifacts, type of thermal electrocoagulation, polyp size, and the interobserver variation among 3 pathologists. The 3 pathologists independently evaluated 119 colonic polyps 5 mm or less in maximum dimension for diagnosis and degree of thermal electrocoagulation or resection trauma cytologic artifacts. The maximum dimension of the polyps and type of thermal electrocoagulation were recorded. The average percentage of polyps in which a definitive diagnosis could not be made because of cytologic artifacts was 16.5% (range, 11.8%-19.3%). Decreasing polyp size was associated linearly with the inability to make a definitive diagnosis owing to cytologic artifacts. Polyps smaller than 2 mm significantly more often could not be definitively diagnosed by at least 1 pathologist owing to cytologic artifacts, including some polyps that were excised without thermal electrocautery. Interobserver variation increased with decreasing polyp dimension. Two millimeters seems to represent a cut point, below which the likelihood that a definitive diagnosis can be made can be increased if thermal electrocoagulation is used. This small size seems to make them especially susceptible to cytologically injurious forces.

Adenoma↗
PubMed2001

Photodynamic effects induced by aminolevulinic acid esters on human cervical carcinoma cells in culture.

Fluorescence diagnosis and photodynamic therapy using 5-aminolevulinic acid (ALA) provide new methods for the detection and treatment of cervical cancer and especially its precursors. However, these techniques are restricted by the rate of uptake of the hydrophilic ALA, its poor diffusion through the bilayer of biological membranes or both. In this study we evaluated the effect of some esterified ALA derivatives on the induction of the endogenous photosensitizer, protoporphyrin IX (PpIX), and the photodamage in cultured human cervical cells (C33-A and CaSki). The kinetics of PpIX accumulation showed that ALA esters, especially the ALA-hexylester (h-ALA), induced significantly faster PpIX formation than ALA at the same concentration (0.5 mM). The PpIX induction showed a dose-dependent characteristic. The highest PpIX values could be achieved by an up to 1.3-13-fold lower concentration of ALA esters than with ALA. Using the Annexin V assay, apoptosis was found to be induced rapidly after irradiation in both ALA- and ALA esters-treated cells. On measuring mitochondrial activity, the incubation with h-ALA induced a more pronounced photodamage. The results indicate that improved or at least comparable photodynamic effects can be achieved by using remarkably lower doses of ALA esters.

Aminolevulinic Acid↗
PubMed2001

Phosphatidylethanolamine participates in the stimulation of the contact system of coagulation by very-low-density lipoproteins.

We have analyzed the influence of plasma lipoproteins on the activation of the contact pathway of blood coagulation in platelet-rich plasma (PRP). The formation of thrombin in PRP incubated in vitro was abolished by the factor XIIa antagonist corn trypsin inhibitor and by severe factor XII deficiency, indicating mediation by the contact system. Addition of VLDL to the PRP shortened the lag period and increased the generation of thrombin. There was no effect of HDL and LDL. In whole blood, VLDL accelerated the rate of fibrin formation, the procoagulant effect being prevented by factor XII deficiency and by corn trypsin inhibitor. The thrombin formation in the PRP was strongly increased by microemulsions of the VLDL lipids while it was reduced by the aqueous phase of the particles. Separation of the VLDL lipids indicated the phospholipid component as the major activating principle. Vesicles supplemented with all VLDL phospholipids but lacking specifically the fraction containing phosphatidylethanolamine (PE) prolonged the lag time. The PE containing fraction alone as well as vesicles enriched with egg PE shortened the lag period. In summary, VLDL stimulates the contact pathway of blood coagulation, ethanolamine phospholipids being the most active components of the particles.

Adult↗
PubMed2000

Mice vaccination with interleukin 12-transduced colon cancer cells potentiates rejection of syngeneic non-organ-related tumor cells.

Cell-based gene therapy after cytokine gene transfer is being investigated for autologous and allogeneic vaccination in cancer therapy. Here we show that mice vaccinated with 3-5 x 10(6) interleukin 12 (IL-12) gene-transduced CT26 colon cancer cells developed a long-lasting antitumor immune memory able to reject not only parental cells but also syngeneic, LM3 mammary, and MCE fibrosarcoma tumorigenic cells. In contrast, mice vaccinated with 0.5-1 x 10(6) CT26 cells transduced with pBabe neo IL-12 retrovirus cells (CT26-IL12) were only able to reject parental cells. An increase in the total circulating levels of IgG2a and a clear shift toward a systemic Th1 response developed, regardless of the amount of injected CT26-IL12 cells. On the contrary, a strong increase in anti-CT26-specific IgG2a levels was observed only when 3-5 x 10(6) CT26-IL12 cells were injected. Immunocompetent mice vaccinated with 3-5 x 10(6) CT26-IL12 cells developed local nodules for a few days, which then ceased growing. These nodules comprised mainly blood vessels, suggesting that an angiogenic process was taking place. CD8+ T cells were responsible for the anti-LM3 tumor cell memory, whereas CD4+ T cells were not involved. Splenocytes and lymphocytes obtained from mice immunized against CT26 cells were able to kill LM3 cells in vitro. Adoptive transfer of lymphocytes obtained from animals immunized against CT26 colon cancer cells suppressed LM3 mammary tumor growth in tumor-bearing mice. The present studies raised the possibility of isolating CTL clones and identifying CTL epitopes shared by different tumor cell types, which can be a target for cancer therapy.

Animals↗
PubMed2000

The heterotrimeric Thermus thermophilus Asp-tRNA(Asn) amidotransferase can also generate Gln-tRNA(Gln).

Thermus thermophilus strain HB8 is known to have a heterodimeric aspartyl-tRNA(Asn) amidotransferase (Asp-AdT) capable of forming Asn-tRNA(Asn) [Becker, H.D. and Kern, D. (1998) Proc. Natl. Acad. Sci. USA 95, 12832-12837]. Here we show that, like other bacteria, T. thermophilus possesses the canonical set of amidotransferase (AdT) genes (gatA, gatB and gatC). We cloned and sequenced these genes, and constructed an artificial operon for overexpression in Escherichia coli of the thermophilic holoenzyme. The overproduced T. thermophilus AdT can generate Gln-tRNA(Gln) as well as Asn-tRNA(Asn). Thus, the T. thermophilus tRNA-dependent AdT is a dual-specific Asp/Glu-AdT resembling other bacterial AdTs. In addition, we observed that removal of the 44 carboxy-terminal amino acids of the GatA subunit only inhibits the Asp-AdT activity, leaving the Glu-AdT activity of the mutant AdT unaltered; this shows that Asp-AdT and Glu-AdT activities can be mechanistically separated.

Amino Acid Sequence↗
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↗