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Biomedical subjects

D Kraus

Publications and source records attributed to D Kraus.

At least 19 recordsLinked to original sources
PubMed2006

Molecular mechanisms of bacterial resistance to antimicrobial peptides.

Cationic antimicrobial peptides (CAMPs) are integral compounds of the antimicrobial arsenals in virtually all kinds of organisms, with important roles in microbial ecology and higher organisms' host defense. Many bacteria have developed countermeasures to limit the efficacy of CAMPs such as defensins, cathelicidins, kinocidins, or bacteriocins. The best-studied bacterial CAMP resistance mechanisms involve electrostatic repulsion of CAMPs by modification of cell envelope molecules, proteolytic cleavage of CAMPs, production of CAMP-trapping proteins, or extrusion of CAMPs by energy-dependent efflux pumps. The repertoire of CAMPs produced by a given host organism and the efficiency of microbial CAMP resistance mechanisms appear to be crucial in host-pathogen interactions, governing the composition of commensal microbial communities and the virulence of bacterial pathogens. However, all CAMP resistance mechanisms have limitations and bacteria have never succeeded in becoming fully insensitive to a broad range of CAMPs. CAMPs or conserved CAMP resistance factors are discussed as new mediators and targets, respectively, of novel and sustainable anti-infective strategies.

Animals↗
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↗
PubMed2003

[Parents as partners in school-based health promotion and addiction prevention: an empirical study for the example of Class2000].

Starting from the premise of the incomparable importance of the parent-child relationship for development, Class2000, a wide-reaching programme for the promotion of health and prevention of addiction in primary schools, focuses especially on the integration of parents. A questionnaire survey among 1430 parents in Hesse with children in the second primary class shows that the overriding majority of pupils (90 %) speak about Class2000 at home and initiate discussions with their parents on health-related topics. The various Class2000 information materials are acknowledged by up to 77 % of parents (comparatively more rarely in the case of the fathers) and are read, as a rule, with interest. Specific information on the contents of the programme is for the parents rather more important than general stimuli. Invitations to special informative events are accepted by well 80 % of the parents. Class2000 convinces more than 82 % of the participants. 71 % of the parents are prepared to contribute to the costs of Class2000. 12 % are undecided in this regard. Participation in parent evenings increases the readiness for financial involvement.

Adult↗
PubMed2002

Do we alter ultraviolet sensitivity in vivo with stratum corneum rehydration? A pilot study and review of the literature.

BACKGROUND: Numerous therapeutic schemes recommend topical administration of emollients immediately prior to ultraviolet (UV) B therapy. The rationale behind the clinical improvement is a presumed enhancement of UV transmission through the epidermis. Originating from this clinical observation, there has been some concern as to whether a well-hydrated skin in general might be more susceptible to actinic damage. OBJECTIVES: To investigate whether rehydration of healthy skin causes an altered UVB sensitivity in vivo. METHODS: We determined minimal erythema doses (MEDs) and erythema sum scores (ESSs) after differential rehydration of the skin in 10 healthy volunteers. In each subject six UVB phototests were performed after pretreatment with five different emulsifying ointments (unguentum emulsificans and dilutions with 30, 50, 70 and 90% aqua purificans) plus a negative control. In vivo evaluation of stratum corneum hydration was performed by measurement of electrical capacitance. RESULTS: The results of this randomized, double-blind in vivo study indicated that rehydration of normal stratum corneum with the emulsifying ointments tested did not result in a significantly altered sensitivity to the erythematous effects of UVB irradiation (no significant differences in MED and ESS). Furthermore, there was no correlation between measured stratum corneum hydration and the erythema response of healthy skin. CONCLUSIONS: Although many schemes recommend the administration of emollients prior to UV therapy, there have also been calls for caution, as an uncritical application may interfere with such treatment. We showed that the emulsifying ointments tested exhibited no photoprotective potential and thus are suitable for the pretreatment of psoriasis prior to phototherapy. It has long been discussed whether the effects of emollient pretreatment on response to UV occur only in psoriatic skin or also in healthy skin. Our results indicated that stratum corneum rehydration did not result in a significantly increased erythema response of healthy skin to UVB exposure. With regard to the use of rehydrating cosmetics in everyday life, the outcome of our pilot study is reassuring, as we could not confirm with our experimental design that well-hydrated healthy skin is more prone to actinic damage.

Adult↗
PubMed2002

Leptin secretion and negative autocrine crosstalk with insulin in brown adipocytes.

Leptin is an important adipocytokine whose main regulative effects on energy metabolism are exerted via activation of signalling pathways in the central nervous system. Another important regulator of energy homeostasis is insulin. The role of direct autocrine leptin effects on adipose tissue and crosstalk with insulin, in particular in the thermogenically active brown adipose tissue, remains unclear. In the present study, we have investigated leptin secretion and interaction with insulin in highly insulin-responsive immortalised mouse brown adipocytes. Leptin was secreted in a differentiation-dependent manner, and acute leptin treatment of mature adipocytes dose- and time-dependently stimulated phosphorylation of STAT3 and MAP kinase. Interestingly, acute pretreatment of fully differentiated brown adipocytes with leptin (100 nM) significantly diminished insulin-induced glucose uptake by approximately 25%. This inhibitory effect was time-dependent and maximal after 60 min of leptin prestimulation. Furthermore, it correlated with a 35% reduction in insulin-stimulated insulin receptor kinase activity after acute leptin pretreatment. Insulin-induced insulin receptor substrate-1 tyrosine phosphorylation and binding to the regulatory subunit p85 of phosphatidylinositol 3-kinase (PI 3-kinase) were diminished by approximately 60% and 40%, respectively. Taken together, this study has demonstrated strong differentiation-dependent leptin secretion in brown adipocytes and PI 3-kinase-mediated negative autocrine effects of this hormone on insulin action. Direct peripheral leptin-insulin crosstalk may play an important role in the regulation of energy homeostasis.

Adipose Tissue, Brown↗
PubMed2002

Congenital choledochal cysts in adults--comparative study.

Congenital choledochal cysts are rare anomalies of the biliary tree and their presentation in adults is infrequent. They are more common in Asia. Females are more commonly affected. Surgery remains the treatment of choice. Nine patients were operated for congenital choledochal cysts in the last fifteen years, i.e. from 1988 to 2002. The diagnosis was established by case history, clinical features and laboratory tests. The imaging methods proved to be the most informative among them. Classification of the choledochal cysts was based on modified Todani classification. All patients have undergone cyst excision with Roux-en-Y hepaticojejunostomy. The complications, like recurrent cholangitis or pancreatitis, were avoided.

Adult↗
PubMed2001

A common regulatory locus affects both HNF4/HNF1alpha pathway activation and sensitivity to LPS-mediated apoptosis in rat hepatoma cells.

Lipopolysaccharide (LPS) has been shown to protect certain cultured mammalian cells from undergoing programmed cell death (apoptosis) when exposed to tumor necrosis factor (TNF). However, LPS has also been reported to induce apoptosis in cultured endothelial cells, suggesting that apoptotic response mechanisms may be dependent upon cell type. In order to understand the influence of tissue-specific gene expression on apoptosis, we compared LPS-induced apoptosis in hepatoma cells with dedifferentiated hepatoma variant cells that have been selected for the loss of the liver-enriched HNF4/HNF1alpha transcriptional activation pathway. We report here that while human, rat and mouse hepatoma cell lines are resistant to LPS-mediated cell death, the HNF4-/HNF1alpha- rat hepatoma variant cells undergo rapid apoptosis (as determined by morphological analysis, DNA laddering and the TUNEL assay) upon exposure to LPS. Genetic rescue experiments show that restoration of the HNF4/HNF1alpha pathway via chromosome transfer render the hepatoma variant cells resistant to LPS-mediated apoptosis. However, the introduction of HNF1alpha alone failed to alter the apoptotic phenotype, suggesting that the defect(s) in the hepatoma variant cells that influence apoptotic responses lies upstream of HNF4/HNF1alpha expression. This study provides for the first time direct evidence of a common regulatory locus involved in activation of hepatic gene expression and sensitivity to LPS-mediated apoptosis.

Animals↗
PubMed2000

Intracellular calcium dynamics--sparks of insight.

Calcium ions are of key importance in a large number of cellular functions. In the past decade a large variety of cells have been found to show localized increases in the intracellular calcium concentration named calcium sparks. In this brief review, the methodology of detecting calcium sparks by confocal microscopy is summarized. Some of the properties of calcium sparks in muscle (cardiac, skeletal and smooth muscles), neurons, nerve terminals and oocytes aredescribed. Speculations are put forward regarding their possible role in microcontrol of cell function.

Animals↗
PubMed1999

Critical care for the severely ill head and neck patient.

OBJECTIVE: To delineate the frequency and causes of admission to a critical care environment for patients undergoing head and neck surgery at Memorial Sloan-Kettering Cancer Center. DESIGN: Retrospective clinical investigation. SETTING: Adult intensive care unit of a tertiary referral cancer center. PATIENTS: All head and neck surgery patients admitted to the special care unit (SCU) of Memorial Sloan-Kettering Cancer Center between January 1, 1994 and December 31, 1995 were included in this study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The data collected included demographic, operative procedures, clinical, laboratory, and physiologic variables at time of SCU admission, at 24 hrs, as well as vital status at the time of discharge from the SCU and hospital. Other data collected were the need for mechanical ventilation and inotropic agents. During the period of January 1, 1994 through December 31, 1995, 37 (1.5%) of 2,346 patients undergoing head and neck surgical procedures required admission to the SCU. During the same period, six patients receiving medical treatment only for head and neck malignant disease were transferred to the SCU. These 43 admissions served as the basis for the study. The causes of admission to the SCU were pulmonary (15/43), cardiac (14/43), wound related (8/43), and other (15/43). The median length of stay in the SCU was 2 days, and the median hospitalization for patients requiring critical care services was 22 days. Seventy-four percent of patients requiring critical care services were eventually discharged to home. CONCLUSIONS: Current preoperative evaluation, operative and anesthetic techniques, and perioperative care result in a low frequency of utilization of critical care services by patients undergoing head and neck surgery. There is no single identifiable cause of complications for patients after head and neck surgery leading to utilization of critical care services.

Adolescent↗
PubMed1999

Children's fractures: a population based study.

OBJECTIVE: To measure the incidence of childhood fractures in a defined population. SETTING: Accident and emergency (A&E) departments covering the Swansea and Neath Port Talbot areas of South Wales in 1996. METHODS: Linkage of data from A&E departments with population data to produce fracture incidence rates by anatomical site and cause in children aged 0-14 years. RESULTS: During 1996, 2463 new fractures occurred in 2399 residents yielding a fracture rate of 36.1/1000 children. Fractures were more common in boys than girls and increased with age in both groups. Sports and leisure activities accounted for 36% of fractures, assaults for 3.5%, and road traffic accidents 1.4%. Fractures of the radius/ulna were most frequent (36%). CONCLUSIONS: The fracture rate in South Wales children is twice the rate reported in previous studies. Further research is required to elucidate the reasons behind this high rate. Many fractures could be prevented by the use of safer surfaces in school playgrounds, and wrist protection in in-line skaters and possibly in soccer players.

Adolescent↗
PubMed1999

[Destructive cults: part curse, part blessing].

Psychiatrists and Psychologists often reject new religious movements as dangerous to their members' mental health or they defend such groups against criticism. These position lack a thorough understanding of the psychodynamic function of new religious commitments. In order to show such functions the author will present and discuss a current member's report about his life and experience. He suggests that commitments to new religious movements strengthen individual defense structures and thus relieve of stress, yet also hamper psychological development.

Aged↗
PubMed1998

Transgenic mice overexpressing the complement inhibitor crry as a soluble protein are protected from antibody-induced glomerular injury.

Complement receptor 1-related gene/protein y (Crry) is a potent murine membrane complement regulator that inhibits classical and alternative pathway C3 convertases. In nephrotoxic serum (NTS) nephritis, injected antibodies (Abs) bind to glomeruli, leading to complement activation and subsequent glomerular injury and albuminuria. To study the phenotypic effects of continuous complement pathway blockade, transgenic mice were created that express recombinant soluble (rs) Crry directed by the broadly active and heavy metal-inducible metallothionein-I promoter. One transgenic line expressing high levels of rsCrry was propagated. Serum rsCrry levels were 18.7 +/- 2.7 microg/ml (n = 5) at basal level and increased to 118.1 +/- 20.6 microg/ml 4 d after addition of zinc to the drinking water. By reverse transcription polymerase chain reaction (RT-PCR), transgene messenger (m)RNA was present in liver, kidney, brain, lung, and spleen, but not in heart. By in situ RT-PCR analysis of kidneys, transgene mRNA was widely expressed both in renal glomeruli and tubules. Urinary excretion of rsCrry was 113.4 +/- 22.4 microg/ml with a fractional excretion relative to creatinine of 13.2 +/- 2.7%, consistent with local renal production of rsCrry and secretion into urine. The founder and all transgene positive adult animals have remained healthy with no mortality or apparent phenotypic abnormalities, including infection or immune complex disease. To determine whether rsCrry blocked complement-mediated injury, NTS nephritis was induced by injection of NTS immunoglobulin (Ig)G, followed by an 18-h urine collection to quantitate the excretion of albumin as a measure of glomerular injury. In transgene-negative littermates (n = 15), transgene-positive animals (n = 10), and transgene-positive animals fed zinc (n = 10), albuminuria was 4,393 +/- 948, 1,783 +/- 454, and 1,057 +/- 277 microg/mg creatinine, respectively (P < 0.01 by ANOVA). Glomerular C3 was evident by immunofluorescence staining in 12/15 transgene-negative animals, but in none of the transgene-positive animals fed zinc. Thus, we have produced the first transgenic animals that overexpress a soluble C3 convertase inhibitor. rsCrry expression markedly ameliorates an Ab-induced disease model in vivo. These results support the hypothesis that continuous complement inhibition at the C3 convertase step is feasible and effective in complement-mediated injury states.

Animals↗
PubMed1998

Complementary recognition of alternative pathway activators by decay-accelerating factor and factor H.

The alternative complement pathway (ACP) functions as a surveillance mechanism by which microorganisms are opsonized with C3b in the absence of specific antibodies. The effectiveness of the ACP relies on its ability to distinguish self from non-self. This recognition function is mediated by C3 regulatory proteins including serum factor H, membrane cofactor protein (MCP), and membrane decay-accelerating factor (DAF). H activity against bound C3b can be increased by host components such as sialic acid and decreased by microbial polysaccharides. DAF and MCP may also recognize cell surface changes such as the presence of viral glycoproteins, since some virus-infected and tumor cells activate the ACP. In the present study, liposomes containing wild-type and mutant Salmonella minnesota lipopolysaccharide (LPS) were tested for ACP activation in serum. LPS-containing liposomes with bound C3b were then tested for their susceptibility to C3 convertase regulation by H and membrane DAF and for the sensitivity of their bound C3b to the cofactor activity of H. The results indicate that while the shortest mutant, Re595 LPS, did not induce ACP activation, R7 LPS containing an additional disaccharide did. This activation was poorly regulated by DAF but was inhibited by H. The regulatory activity of H for liposome-bound C3b, however, decreased when LPS of greater polysaccharide size was present in the membrane. In contrast the ACP activation induced by the phospholipid phosphatidylethanolamine was effectively inhibited by DAF but only poorly inhibited by H.

CD55 Antigens↗
PubMed1997

NHS acute sector expenditure for diabetes: the present, future, and excess in-patient cost of care.

We set out to determine the present proportion of in-patient revenue used for the care of diabetes and its related complications and to use these data to determine (1) the trend in future hospital costs for the condition and (2) the excess cost of admissions for diabetic patients over and above that expected had these patients not had diabetes, using a cross-sectional descriptive study in conjunction with a population modelling exercise in a District Health Authority with a resident population of 408 000 people. The crude proportion of admissions for people with diabetes was 7.0% of activity in financial year 1994/5 (of 115929 total in-patient and day case admissions). Patients with diabetes occupied 10.7 % of bed days and had a crude mean length of stay of 10.7 days vs 6.7 days for the non-diabetic group. The proportion of revenue used for their treatment was 8.7 %. This translated locally to 11.9 M. In year 2011 overall cost of in-patient care is predicted to increase by 9.4 %, however, the proportion of revenue used for the care of people with diabetes will increase by 15% because of age-related effects. The excess cost associated with treating diabetes is estimated to be 82% of admissions for the diabetic population, 88% of their bed days, and 86% of expenditure associated with their care. Most of this excess cost is associated with the recognised vascular complications of diabetes. We conclude that the cost of in-patient care for patients with diabetes is notably disproportionate to the population prevalence of diabetes-9 % compared to 1.36% in South Glamorgan-and will increase disproportionately with time. As much of the long-term morbidity is known to be preventable by earlier intervention, strategies should reflect the imperative to reduce the burden of diabetes.

Adolescent↗
PubMed1997

[MDMA ("Ecstasy") use--an overview of psychiatric and medical sequelae].

Epidemiological research and Substance Abuse Warning Systems point to a sharp increase in the use of "Ecstasy" (MDMA), as well as to structural changes in the drug scene in and outside Europe. For some consumers, "Ecstasy" opens the door to the abuse of other illegal substances. Since the mid-eighties psychiatric complications and consequences of the abuse of MDMA have been reported in at least 48 cases. It is necessary to differentiate between acute psychiatric complications, which subside completely when the level of intoxication comes down, toxic psychoses and long-term psychiatric diseases as a consequence of substance abuse. The latter involve atypical and paranoid psychoses, depressions, panic disorders, depersonalisation and behavioural disorders. Convulsive seizures are among the most common problems involving the central nervous system. Furthermore, there have been reports on cerebrovascular accidents and intracranial haemorrhages. Literature reports on at least 53 cases of medical complications in abusers of MDMA, 14 of which came to a lethal end. Research still blatantly lacks prospective epidemiological and clinical studies on a sufficiently large scale to identify different developments of dependency and predictors of harmful and unhealthy consumption.

Brain↗