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Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 19 recordsLinked to original sources
PubMed2007

What are subcutaneous adipocytes really good for?

Our acute awareness of the cosmetic, psychosocial and sexual importance of subcutaneous adipose tissue contrasts dramatically with how poorly we have understood the biology of this massive, enigmatic, often ignored and much-abused skin compartment. Therefore, it is timely to recall the exciting, steadily growing, yet underappreciated body of evidence that subcutaneous adipocytes are so much more than just 'fat guys', hanging around passively to conspire, at most, against your desperate attempts to maintain ideal weight. Although the subcutis, quantitatively, tends to represent the dominant architectural component of human skin, conventional wisdom confines its biological key functions to those of energy storage, physical buffer, thermoregulation and thermoinsulation. However, already the distribution of human superficial adipose tissue, by itself, questions how justified the popular belief is that 'skin fat' (which actually may be more diverse than often assumed) serves primarily thermoinsulatory purposes. And although the metabolic complications of obesity are well appreciated, our understanding of how exactly subcutaneous adipocytes contribute to extracutaneous disease - and even influence important immune and brain functions! - is far from complete. The increasing insights recently won into subcutaneous adipose tissue as a cytokine depot that regulates innate immunity and cell growth exemplarily serve to illustrate the vast open research expanses that remain to be fully explored in the subcutis. The following public debate carries you from the evolutionary origins and the key functional purposes of adipose tissue, via adipose-derived stem cells and adipokines straight to the neuroendocrine, immunomodulatory and central nervous effects of signals that originate in the subcutis - perhaps, the most underestimated tissue of the human body. The editors are confident that, at the end, you shall agree: No basic scientist and no doctor with a serious interest in skin, and hardly anyone else in the life sciences, can afford to ignore the subcutaneous adipocyte - beyond its ample impact on beauty, benessence and body mass.

Adipocytes↗
PubMed2006

Bilobalide prevents ischemia-induced edema formation in vitro and in vivo.

EGb761, a standardized extract of Ginkgo biloba, has neuroprotective properties in animal models of ischemia, an activity that is partially attributed to its constituent, bilobalide. EGb761 has also been reported to inhibit edema formation induced by toxins such as triethyltin. The goal of this study was to test the activity of pure bilobalide to prevent edema formation in models of ischemia. Oxygen-glucose deprivation (OGD) in rat hippocampal slices served as a model of in vitro-ischemia. OGD caused cellular edema formation as indicated by an increase of slice water contents in 30 min. Bilobalide (1-10 microM) reduced slice water contents in ischemic slices in a concentration-dependent manner. As a model of in vivo-ischemia, we performed middle cerebral artery occlusion (MCAO) in mice. Permanent MCAO caused cell death and swelling of the ischemic hemisphere within 24 h. Pretreatment of the mice with bilobalide (10 mg/kg i.p.) reduced infarct area by 43% (as judged by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining) and edema formation by 70% (as judged by hemispheric enlargement). In parallel experiments, pretreatment with bilobalide also reduced forebrain water contents in the ischemic hemisphere by 57%. As an alternative model of brain edema formation, we used water intoxication to increase brain water content; bilobalide, was, however, inactive in this model. We conclude that bilobalide strongly and specifically attenuates edema formation in models of brain ischemia in vitro and in vivo. Bilobalide may be therapeutically effective in brain edema which occurs secondarily to large hemispheric stroke and traumatic brain injury in humans.

Animals↗
PubMed2006

Kinetics of lactose fermentation using a recombinant Saccharomyces cerevisiae strain.

This work presents a multi-route, non-structural kinetic model for interpretation of ethanol fermentation of lactose using a recombinant flocculent Saccharomyces cerevisiae strain expressing both the LAC4 (coding for beta-galactosidase) and LAC12 (coding for lactose permease) genes of Kluyveromyces lactis. In this model, the values of different metabolic pathways are calculated applying a modified Monod equation rate in which the growth rate is proportional to the concentration of a key enzyme controlling the single metabolic pathway. In this study, three main metabolic routes for S. cerevisiae are considered: oxidation of lactose, reduction of lactose (producing ethanol), and oxidation of ethanol. The main bioprocess variables determined experimentally were lactose, ethanol, biomass, and dissolved oxygen concentrations. Parameters of the proposed kinetic model were established by fitting the experimental data obtained in a small lab-scale fermentor with the initial lactose concentrations ranging from 5 g/dm3 to 50 g/dm3. A very good agreement between experimental data and simulated profiles of the main variables (lactose, ethanol, biomass, and dissolved oxygen concentrations) was achieved.

Bioreactors↗
PubMed2006

Effect of endothelin-1 on erythropoietin production in a rat model under normoxia and functional carbon monoxide-induced hypoxia.

It has been hypothesized that autacoids, such as endothelin-1 (ET), may modulate erythropoietin (Epo) secretion. Therefore, we studied the effect of ET-1 infusion and of a nonselective ET(A/B) receptor antagonist on Epo secretion under carbon monoxide (CO) exposure. Anesthetized rats were supplied with room temperature air containing increasing concentrations of CO by an aerating cap. A CO-Epo dose-response curve over the range of 0.02-0.14 vol% CO was conducted. Subpressor doses of ET-1 (3 pmol/min/kg BW) and the ET(A/B) receptor antagonist LU302872 (LU; 30 mg/kg) were applied to anaesthetized rats under normoxia (controls CON, ET, LU) and following hypoxia (CO exposure; H-CON, H-ET, H-LU). Mean arterial blood pressure (MAP), glomerular filtration rate (GFR, inulin clearance), Epo and ET-1 serum concentrations (ELISA) and renal Epo mRNA (Light Cycler) were determined. The EC50 value for CO was 0.1 vol% with a 70-fold increase in Epo serum concentrations. CO exposure increased Epo serum and Epo mRNA concentrations in the expected range in all groups. None of the treatments with ET or LU influenced the effect of hypoxia on Epo serum concentrations and renal Epo mRNA content. Under hypoxia, administration of ET-1 as well as LU prevented the hypoxia-induced decrease in MAP (p<0.05). Under hypoxia, GFR was reduced by 50% except for H-LU with values comparable to normoxia. Taken together, the influence of hypoxia exceeds by far the effect of ET-1 on Epo production, irrespective of the presence or absence of exogenous ET-1. Thus, ET-1 does not appear to be a major modulator of Epo production.

Animals↗
PubMed2006

Uncertainty in diffusion tensor based fibre tracking.

BACKGROUND: Diffusion tensor imaging and related fibre tracking techniques have the potential to identify major white matter tracts afflicted by an individual pathology or tracts at risk for a given surgical approach. However, the reliability of these techniques is known to be limited by image distortions, image noise, low spatial resolution, and the problem of identifying crossing fibres. This paper intends to bridge the gap between the requirements of neurosurgical applications and basic research on fibre tracking uncertainty. METHOD: We acquired echo planar diffusion tensor data from both 1.5 T and 3.0 T scanners. For fibre tracking, an extended deflection-based algorithm is employed with enhanced robustness to impaired fibre integrity such as caused by diffuse or infiltrating pathological processes. Moreover, we present a method to assess and visualize the uncertainty of fibre reconstructions based on variational complex Gaussian noise, which provides an alternative to the bootstrap method. We compare fibre tracking results with and without variational noise as well as with artificially decreased image resolution and signal-to-noise. FINDINGS: Using our fibre tracking technique, we found a high robustness to decreased image resolution and signal-to-noise. Still, the effects of image quality on the tracking result will depend on the employed fibre tracking algorithm and must be handled with care, especially when being used for neurosurgical planning or resection guidance. An advantage of the variational noise approach over the bootstrap technique is that it is applicable to any given set of diffusion tensor images. CONCLUSIONS: We conclude that the presented approach allows for investigating the uncertainty of diffusion tensor imaging based fibre tracking and might offer a perspective to overcome the problem of size underestimation observed by existing techniques.

Adult↗
PubMed2006

Community associated MRSA: an alert to paediatricians.

Community associated methicillin resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen typically associated with skin and soft tissue infection, with occasional reports of fatality in previously healthy children and young adults. We report a case of invasive CA-MRSA and highlight the potential impact of such infections on empirical treatment of staphylococcal infections.

Anti-Bacterial Agents↗
PubMed2006

Adsorption of protein GlnB of Herbaspirillum seropedicae on Si(111) investigated by AFM and XPS.

The protein GlnB-Hs (GlnB of Herbaspirillum seropedicae) in diazotroph micro-organisms signalizes levels of nitrogen, carbon, and energy for a series of proteins involved in the regulation of expression and control of the activity of nitrogenase complex that converts atmospheric nitrogen in ammonia, resulting in biological nitrogen fixation. Its structure has already been determined by X-ray diffraction, revealing a trimer of (36 kDa) with lateral cavities having hydrophilic boundaries. The interactions of GlnB-Hs with the well-known Si(111) surface were investigated for different incubation times, protein concentrations in initial solution, deposition conditions, and substrate initial state. The protein solution was deposited on Si(111) and dried under controlled conditions. An atomic force microscope operating in dynamic mode shows images of circular, linear, and more complex donut-shaped protein arrangement, and also filament types of organization, which vary from a few nanometers to micrometers. Apparently, the filament formation was favored because of protein surface polarity when in contact with the silicon surface, following some specific orientation. The spin-coating technique was successfully used to obtain more uniform surface covering.

Adsorption↗
PubMed2005

Beta-blockers improve in-hospital and long-term survival in patients with severe left ventricular dysfunction undergoing major vascular surgery.

OBJECTIVES: To study whether beta-blockers reduce in-hospital and long-term mortality in patients with severe left ventricular dysfunction (LVD) undergoing major vascular surgery. DESIGN: Observational cohort study. MATERIALS: Five hundred and eleven patients with severe LVD (ejection fraction<30%) undergoing major non-cardiac vascular surgery. METHODS: In all patients, cardiac risk factors, medication (including beta-blockers), and dobutamine stress echocardiography (DSE) results were noted prior to surgery. DSE was evaluated for rest and stress-induced new wall motion abnormalities. Endpoint was in-hospital and long-term mortality. Propensity scores for beta-blockers were calculated and regression models were used to analyse the relation between beta-blockers and mortality. RESULTS: Mean age was 64+/-11 years and 383 patients (75%) were male. 139 patients (27%) used beta-blockers. Stress-induced ischemia occurred in 82 patients (16%). Median follow-up was 7 years (interquartile range: 3-10). In-hospital and long-term mortality was observed in 64 (13%) and 171 (33%) patients, respectively. After adjusting for clinical variables, DSE results and propensity scores, beta-blockers were significantly associated with reduced in-hospital and long-term mortality (OR: 0.18, 95% CI: 0.04-0.74 and HR: 0.38, 95% CI: 0.22-0.65, respectively). CONCLUSION: In patients with severe LVD undergoing major vascular surgery, the use of beta-blockers is associated with a reduced incidence of in-hospital and long-term postoperative mortality.

Adrenergic beta-Antagonists↗
PubMed2005

Isolation and partial characterization of a parapoxvirus isolated from a skin lesion of a Weddell seal.

A solitary skin lesion was found on the neck of a Weddell seal (Leptonychotes weddellii), chemically immobilized in Queen Maud Land (70 degrees 09'S, 05 degrees 22'E) Antarctica 2001. The lesion was elevated and 3cm in diameter, consisting of partly fresh and partly necrotic tissue, and proliferative papilloma-like structures were seen. Electron microscopy on a biopsy from the lesion revealed typical parapoxvirus particles. Polymerase chain reaction (PCR; B2L gene) generated amplicons of approximately 594 base pairs, comparable to Orf-virus, the prototype parapoxvirus. A comparison of these B2L PCR amplicon DNA sequences with corresponding sequences from other parapoxviruses, showed that the Weddell seal virus resembled isolates from grey seal (Halichoerus grypus) and harbour seal (Phoca vitulina) more than parapoxvirus from red deer (Cervus elaphus), sheep, cattle and Japanese serows (Capricornis crispus). It is thus concluded that the Weddell seal parapoxvirus belong to the tentative seal parapoxvirus species. Since parapox and orthopoxviruses may cause similar clinical diseases, we suggest that the term sealpox should be restricted to the clinical disease, whereas seal parapoxvirus should be used when caused by a parapoxvirus, rather than the general term "sealpox virus". This is the first verified case of parapoxvirus infection in a Weddell seal, and also the first report of any such infections in the Antarctic.

Animals↗
PubMed2005

Safety of low-dose low-molecular-weight-heparins in thrombocytopenic stem cell transplantation patients: a case series and review of the literature.

Few attempts have been made to examine the feasibility of safely administering low-molecular-weight-heparins (LMWHs) in the presence of concurrent thrombocytopenia. We retrospectively investigated the safety of low-dose LMWH in BMT patients, a population at risk of bleeding. In total, 26 patients received at least one dose of low-dose enoxaparin (ie <1 mg/kg/day) during thrombocytopenia. s.c. enoxaparin 40 mg once daily was given in 85% of the cohort. The mean number of platelet days <55 x 10(9) and <20 x 10(9)/l were 16.5 days (95% CI=8.04-24.96) and 4.14 days (95% CI=2.35-5.93), respectively. The mean number of low-dose enoxaparin administration days when platelet <55 x 10(9) and 20 x 10(9)/l were 9.89 days (95% CI=3.26-16.53) and 2.25 days (95% CI=0.57-3.93), respectively. Minor bleeding occurred in four patients (15%) whereas major episodes developed in two patients (8%). The latter two events occurred during the transition between full therapeutic (ie 1.5-2 mg/kg/day) and low-dose enoxaparin close to the onset of thrombocytopenia. The present case series, along with the discussed literature, descriptively suggests that low-dose enoxaparin may be safely administered at a platelet count in the range of 20 and 55 x 10(9)/l in BMT patients who weigh >55 kg.

Adult↗
PubMed2005

The beta3-adrenergic agonist CL316,243 inhibits insulin signaling but not glucose uptake in primary human adipocytes.

Insulin resistance and obesity are central components of the metabolic syndrome which has become the leading cause of cardiovascular morbidity and mortality worldwide. Direct interactions of the beta (3)-adrenoceptor system with adipocyte signaling and function in humans remain poorly understood. However, this might have important consequences for the regulation of energy homeostasis and insulin resistance in states of hyperinsulinemia and sympatho-adrenergic overactivity. We therefore investigated beta (3)-adrenoceptor-mediated effects on insulin signaling and glucose uptake in mammary adipocytes of healthy women that underwent breast reduction surgery. Glucose uptake was strongly induced by insulin stimulation. This was paralleled by robust induction of insulin receptor kinase activity, insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity, and protein kinase B phosphorylation. Treatment with the beta (3)-adrenoceptor-selective agonist CL316,243 alone, neither induced alterations in the early insulin signaling cascade nor changed the basal level of glucose uptake. By contrast, pretreatment with the beta (3)-adrenoceptor agonist inhibited the insulin-induced insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity by 50 % and protein kinase B phosphorylation by 40 % without affecting insulin receptor kinase activity upstream. However, on the functional level insulin-induced glucose uptake remained unchanged by beta (3)-adrenoceptor stimulation. Our data demonstrate an insulin receptor-independent negative influence of beta (3)-adrenoceptor stimulation on proximal insulin signaling. This inhibition is apparently dissociated from glucose uptake in human adipocytes.

Acrylates↗
PubMed2005

Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes.

Aldosterone is a mineralocorticoid hormone that regulates blood pressure and salt/water balance. Increased aldosterone levels are found in states of disturbed energy balance such as the metabolic syndrome. Adipose tissue has been recognized to play a pivotal role in the regulation of energy homeostasis. We investigated direct aldosterone effects on brown adipocyte function. Aldosterone dose-dependently inhibited expression of uncoupling protein-1 (UCP-1) by 30% (p < 0.01). Furthermore, aldosterone dose-dependently impaired insulin-induced glucose uptake by about 25% (p < 0.01). On a transcriptional level, mRNA of the proinflammatory adipokines leptin and monocyte chemoattractant protein-1 (MCP-1) was increased by 5,000% and 40%, respectively, by aldosterone exposure (p < 0.05). This study demonstrates that aldosterone directly impacts on major adipose functions including stimulation of proinflammatory adipokines.

Adipocytes↗
PubMed2005

The rate of marrow recovery and extent of donor engraftment following transplantation of ex vivo-expanded bone marrow cells are independently influenced by the cytokines used for expansion.

Successful stem cell transplantation depends on cell dose, and this is particularly true for placental/cord blood transplantation in which it has been clearly shown that both the success of engraftment as well as the speed of white cell and platelet recovery are dependent on the nucleated cell dose in the graft. Thus, if stem cell numbers could be increased, the speed as well as the likelihood of engraftment might be improved. We studied the effect of two different cytokine combinations--kit ligand (KL), interleukin-3 (IL-3), and Flt-3 ligand supplemented with thrombopoietin and IL-11 (combination 1) or granulocyte/macrophage colony-stimulating factor (GM-CSF) and G-CSF (combination 2)--for their ability to affect speed and extent of engraftment using limited numbers (5 x 10(4)) of murine bone marrow (BM) light-density (LD) cells or their progeny expanded ex vivo in the presence one or the other cytokine combination for 6 days. With combination 1, we found that speed of platelet recovery was enhanced, but at the expense of white blood cell (WBC) recovery and percent donor engraftment. Furthermore, the cytokine combination that best maintained donor engraftment, combination 2, did so at the expense of platelet recovery. In no case was percent donor engraftment improved over 5 x 10(4) unmanipulated LD BM cells. These results are consistent with the interpretation that immediate recovery of blood cells of different lineages and longterm donor engraftment are separate functions that can be influenced by the choice of cytokines used during the ex vivo expansion process.

Animals↗
PubMed2005

A comparison of the vertical infraclavicular and axillary approaches for brachial plexus anaesthesia.

BACKGROUND: This prospective, randomized study compared the efficacy of the vertical infraclavicular and axillary approaches using a single injection blockade of the brachial plexus. The primary endpoint was complete blockade in dermatomes C5-Th1, while secondary endpoints included onset time, motor block, block performance time, surgical success rate, patient satisfaction, and side-effects/complications. METHODS: Sixty patients, American Society of Anesthesiologists physical status I or II, scheduled for surgery of the forearm or hand received either a vertical infraclavicular (n = 30) or an axillary block (n = 30). A single injection of 0.5 ml/kg ropivacaine 7.5 mg/ml was made after electrolocalization of nerve fibres corresponding to the median nerve at maximum 0.5 mA (2 Hz, 0.1 ms). Onset and distribution of analgesia and motor block were assessed at 5, 10, 15, 20, 30 and 60 min after the local anaesthetic injection. A complete block was defined as analgesia in all dermatomes (C5-Th1) at 60 min post-injection. RESULTS: The vertical infraclavicular approach provided complete blockade in 29 patients (97%) and the axillary approach in 23 patients (77%). Analgesia in C5-C6 dermatomes and corresponding motor block occurred significantly more frequently in the vertical infraclavicular approach, which also had the shortest onset time. Block procedure was quicker in the axillary approach. Side-effects were similar in both groups, and there were no permanent sequelae. Patient satisfaction was equally high in both groups. CONCLUSION: The vertical infraclavicular approach provides a more complete block than the axillary approach when using a single injection technique and equal volumes/doses of local anaesthetic.

Adult↗
PubMed2005

High fatality rate of Epstein-Barr virus-associated lymphoproliferative disorder occurring after bone marrow transplantation with rabbit antithymocyte globulin conditioning regimens.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (EBV-LPD) following bone marrow transplantation can be fatal. The major risk factors for the development of EBV-LPD are ex vivo T-cell depletion or in vivo T-cell depletion with either antithymocyte globulin (ATG) or monoclonal anti-T-cell antibodies. Between March 1999 and January 2001, a total of 23 transplants with ATG of equine source (20 transplants) and ATG of rabbit source (3 transplants) used as part of the preparatory regimen were performed at the Barbara Ann Karmanos Cancer Institute in Detroit, Mich. The three patients who received rabbit ATG developed EBV-LPD between 60 and 90 days following bone marrow transplantation. However, there were no cases of EBV-LPD in the equine group. Treatment given in these cases consisted of tapering immunosuppression, antiviral therapy, unprocessed donor lymphocyte infusion, mobilized peripheral blood progenitor cell rescue infusion (one patient), and chemotherapy (one patient). All three patients died of complications from EBV-LPD. The association of rabbit ATG with the development of EBV-LPD suggests that patients receiving rabbit ATG as part of their preparatory regimens require close monitoring of the EBV viral load and possible early intervention with antiviral therapy.

Adult↗
PubMed2005

Directly measured second hand smoke exposure and asthma health outcomes.

BACKGROUND: Because they have chronic airway inflammation, adults with asthma could have symptomatic exacerbation after exposure to second hand smoke (SHS). Surprisingly, data on the effects of SHS exposure in adults with asthma are quite limited. Most previous epidemiological studies used self-reported SHS exposure which could be biased by inaccurate reporting. In a prospective cohort study of adult non-smokers recently admitted to hospital for asthma, the impact of SHS exposure on asthma health outcomes was examined. METHODS: Recent SHS exposure during the previous 7 days was directly measured using a personal nicotine badge (n = 189) and exposure during the previous 3 months was estimated using hair nicotine and cotinine levels (n = 138). Asthma severity and health status were ascertained during telephone interviews, and subsequent admission to hospital for asthma was determined from computerised utilisation databases. RESULTS: Most of the adults with asthma were exposed to SHS, with estimates ranging from 60% to 83% depending on the time frame and methodology. The highest level of recent SHS exposure, as measured by the personal nicotine badge, was related to greater asthma severity (mean score increment for highest tertile of nicotine level 1.56 points; 95% CI 0.18 to 2.95), controlling for sociodemographic covariates and previous smoking history. Moreover, the second and third tertiles of hair nicotine exposure during the previous month were associated with a greater baseline prospective risk of hospital admission for asthma (HR 3.73; 95% CI 1.04 to 13.30 and HR 3.61; 95% CI 1.0 to 12.9, respectively). CONCLUSIONS: Directly measured SHS exposure appears to be associated with poorer asthma outcomes. In public health terms, these results support efforts to prohibit smoking in public places.

Adult↗