Functional organization of secondary lymphoid organs by the chemokine system.
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Animals↗
Biomedical subjects
G Müller
Publications and source records attributed to G Müller.
[Reduction of colonization of new mattresses with bacteria, moulds and house dust mites by complete mattress covers].
BACKGROUND AND OBJECTIVE: We investigated if the colonisation of new mattresses with house dust mites, bacteria, and fungi could be reduced by using synthetic mattress covers as compared to common cotton covers. PATIENTS/METHODS: 84 healthy volunteers were assigned to two groups. Group A (n = 43) received the cotton covers, group B (n = 41) the synthetic covers which were made of a polyester microfaser with a polyurethane surface layer (Pro-Tex, Germed, Schwarzenbek, Germany). RESULTS: The mite antigen concentration after six months was significantly lower in group B. Three months after the start of the study counts of bacteria and moulds were significantly higher in group A compared to group B. CONCLUSIONS: It can be recommended that patients suffering from an allergy to mites or moulds may reduce their domestic allergen exposure by using the synthetic mattress covers tested in this study. Since cotton covers are very likely to become colonised by bacteria and moulds, they must be cleaned periodically (at least every 2nd-3d month).
Animals↗
Prevalence of GB virus C/hepatitis G virus RNA and anti-E2 glycoprotein antibodies in homosexual men with HIV coinfection.
BACKGROUND: The objective of this cross-sectional, nonrandomized, prospective study was to generate data on the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) in a cohort of HIV-infected homosexuals from Munich. PATIENTS: A total of 71 HIV-infected homosexual men were analyzed for prevalence of GBV-C RNA and antibodies to the E2 envelope glycoprotein (E2Ab). 475 healthy volunteer blood donors in southern Bavaria served as a control group. RESULTS: The prevalence of GBV-C RNA was 27% (control group: 2.3%) and the prevalence of E2Ab was 35% (control group: 6%). The total prevalence for present and past infection was 62%. The differences between the HIV-infected patients and the control group were significant (p < 0.0001). GBV-C RNA and E2Ab were not detected simultaneously in any serum sample. The E2Ab positive patients were older than the GBV-C RNA positives (mean 46 years versus 39 years, p = 0.0350). The GBV-C RNA and E2Ab negative patients were older than the GBV-C RNA positives (mean 47 years versus 39 years, p = 0.0236). The E2Ab positive patients had suffered sexually transmitted diseases more frequently than the patients negative for markers of GBV-C infection (p = 0.0308). E2Ab positive patients also had higher mean levels of alanine aminotransferase compared to patients without evidence of GBV-C infection (p = 0.0164). 59.4% of all individuals were anti-HBc IgG positive. CONCLUSION: The data can be interpreted as indirect evidence for sexual transmission of GBV-C.
Adult↗
Determination of the in vivo loading of the lumbar spine with a new approach directly at the workplace--first results for nurses.
OBJECTIVE: To determine the magnitude of workplace loading for nurses with and without a history of low back pain. DESIGN: A measurement system for the assessment of workplace loading as well as a model for the calculation of lumbo-sacral junction loading was designed and applied to a group of 12 nurses with and without a history of low back pain. BACKGROUND: Disagreement exists regarding the key factors in the aetiology of low back pain. Traditionally workplace loading is viewed as the dominant influence. Data for workplace loading in jobs with non-uniform tasks, however, do rarely exist. METHODS: A three-dimensional inverse-dynamic and force distribution model as well as the respective data acquisition system was used to assess the workplace loading of 12 nurses from surgical departments of two hospitals. The nurses were assigned to two groups based on their history of low back pain (with/without). Workplace loading was measured continuously for 4 h. RESULTS: No differences in workplace loading between nurses with/without a history of low back pain were found. Maximum values of the compressive force at the lumbo-sacral junction were high and well above suggested workplace load limits. High values occurred only during short-time periods (about 0.4% of total shift duration). CONCLUSIONS: A system for the assessment of overall workplace loading has been developed. First results for nurses suggest that critical loadings do exist at the workplace, even so they might not be the decisive factor for the development of low back pain. RELEVANCE: Preventative measures for low back pain in nursing have to include prevention of critical workplace loading. This approach by itself, however, is probably not sufficient.
Adult↗
Influence of pulsed laser irradiation on the morphology and function of the guinea pig cochlea.
Recent experimental and clinical studies have demonstrated that several pulsed laser systems are also suitable for stapedotomy. The aim of the study was to investigate morphological and functional inner ear changes after irradiating the basal turn of the guinea pig cochlea with two pulsed laser systems of different wavelengths. The Er:YSGG (lambda=2.78 mcm) and Ho:YAG (lambda=2.1 mcm) lasers were used applying the laser energies necessary for perforating a human stapes footplate. The cochleas were removed 90 min, 1 day, 2 weeks, or 4 weeks after laser application. Acoustic evoked potentials (compound action potentials) were measured before and after laser application and at the above times immediately before removal of the cochleas. The organ of Corti was examined by scanning electron microscopy. Application of Er:YSGG laser parameters effective for stapedotomy had no adverse effects on Corti's organ in the guinea pig cochlea. On the other hand, effective Ho:YAG laser parameters cause damage to the outer hair cells with fusion of stereocilia and formation of giant cilia leading to partial or total cell loss. The inner hair cells and supporting cells were usually normal. These morphological data show a good correlation with the electrophysiological measurements. Our results clearly demonstrate that, besides achieving efficient bone management, the Er:YSGG laser has high application safety. On the other hand, the Ho:YAG laser is not well tolerated in our animal study. Its use in stapedotomy would be unreliable and dangerous for the inner ear.
Action Potentials↗
Steady-state movement-related potentials evoked by fast repetitive movements.
We investigated steady-state movement-related cortical potentials elicited by fast repetitive movements (1/sec) with 50-channel EEG. The experimental design comprised a comparison (a) between unilateral movements of the digits and the toes and (b) between metronome-paced and self-paced initiation of the movements. A distinct biphasic pattern of electrical activity following movement onset was observed, namely a frontal negative peak at a latency of 90 ms (post-MP100) anda frontal positive peak at a latency of 310ms (post-MP300). Pacing exerted its effects mainly on the amplitude and on the latency of the post-MP300. Source analysis revealed that both peaks could be modelled by a single source. The source locations were highly reproducible across the metronome-paced and self-paced conditions, and, they followed the expected somatotopic organisation.
Adult↗
TNF down-regulation of receptor tyrosine kinase-dependent mitogenic signal pathways as an important step in cytostasis induction and commitment to apoptosis of Kym-1 rhabdomyosarcoma cells.
Growth of Kym-1 rhabdomyosarcoma cells depends on endogenous receptor tyrosine kinase signals activated by insulin and insulin-like growth factors (IGF), as revealed from enhancement of proliferation by insulin and IGF-1 and cytostatic action of inhibitors of IR/IGFR kinases. Depending on the presence or absence of the caspase inhibitor z-VAD-fmk, TNF induced full growth arrest or apoptosis, respectively, indicating dominance of TNF over mitogenic signal pathways in Kym-1 cells. In accordance with a caspase-independent cytostatic action, TNF downregulated IR kinase activity and caused a profound inhibition of downstream mitogenic signals including the MAPK cascade and STAT5, key pathways of proliferation and cell survival. Removal of z-VAD-fmk after 24 h induced rapid cell death in the absence of TNF. The inhibition of survival signals concomitant with persisting proapoptotic signals may tip the balance towards an irreversible commitment of the cell to apoptosis that becomes apparent upon relief of suppression of effector caspases.
Amino Acid Chloromethyl Ketones↗
Therapeutic application of T cell receptor mimic peptides or cDNA in the treatment of T cell-mediated skin diseases.
An 8-amino acid peptide encoding a sequence of the transmembrane region of the T cell receptor alpha chain (TCR-alpha) was shown to inhibit T cell function by preventing functional assembly of the T cell receptor (mimic peptide). To avoid systemic immunosuppression by peptide application in vivo, we used a topical application of the peptide. In the system of murine contact sensitivity, topical application of the peptide inhibited the elicitation of contact sensitivity following application of a contact allergen in sensitized animals. Alternatively, when naked DNA encoding the peptide sequence was injected into skin before application of a contact allergen to sensitized animals, local immunosuppression was also observed. To investigate the effects of this peptide in humans, patients with psoriasis, atopic eczema, lichen planus, or contact dermatitis were treated topically with mimic peptide or control peptide. All patients except for one reported a marked improvement or cure of their skin disease following application of the TCR-alpha peptide, but not controls. These data indicate that TCR-alpha peptide or cDNA treatment might be a proper treatment for human T cell-mediated dermatoses substituting for corticosteroids.
Allergens↗
Fetal calf serum-free generation of functionally active murine dendritic cells suitable for in vivo therapeutic approaches.
UNLABELLED: Standard protocols to generate mouse dendritic cells (DC) generally use culture medium supplemented with fetal calf serum; however, reinjection in vivo of DC cultured in fetal calf serum results in priming to xenogeneic proteins that clearly limits the use of such DC. We therefore established a fetal calf serum-free culture system for the generation of murine DC from bone marrow precursors. DC can be generated fetal calf serum-free using RPMI supplemented with 1.5% syngeneic mouse serum. Although the yield of DC grown under fetal calf serum-free conditions was somewhat lower than that of the standard culture, large numbers of DC could be generated without the exposure to xenogeneic proteins. The yield of fetal calf serum-free cultured DC was further enhanced by addition of the proinflammatory cytokines TNF-alpha and IL-1beta with the combination resulting in up to 10% more DC. Phenotypically, CD11c + DC cultured fetal calf serum-free homogenously coexpressed the DC-specific molecule DEC-205 as well as the costimulatory molecules CD40, CD80, and CD86. In contrast, only a subpopulation of the CD11c + DC cultured in fetal calf serum-containing medium coexpressed these molecules. Functionally, fetal calf serum-free DC showed strong stimulatory capacity for naïve allogeneic CD4 + and CD8 + T cells. Importantly, fetal calf serum-free DC showed spontaneous in vivo migratory activity. Moreover, 5 x 105 subcutaneously injected TNBS-conjugated fetal calf serum-free DC were able to mediate contact sensitivity. Furthermore, the intravenous or subcutaneous injection of a single dose of 5 x 105 OVA-pulsed fetal calf serum-free DC resulted in the induction of an OVA-specific immune response in naïve TCR transgenic animals. Thus DC cultured under fetal calf serum-free conditions are suitable instruments for in vivo therapeutic approaches, especially in autoimmune models. KEYWORDS: DC vaccines/dendritic cell development/fetal calf serum-free culture conditions for DC/in vivo therapeutic DC approaches.
Animals↗
Rosai-Dorfman disease and generalized AA amyloidosis: a case report.
We report on a patient who, at 31 years of age, was found to suffer from sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) with nodal and extranodal involvement as described previously. Five years later the patient presented with nephrotic syndrome caused by a generalized AA amyloidosis, and he subsequently died from pulmonary thromboembolism owing to renal vein thrombosis. Retrospective analysis of serum levels of C-reactive protein (CRP) showed that during the last 3 years before his death, he had a persistently elevated CRP level ranging from 73 to 161 mg/L, despite antiinflammatory treatment with prednisolone, methotrexate, or 6-mercaptopurine. These figures indicate that the patient was probably suffering from a permanent acute phase response which, in the absence of any other evidence of a chronic inflammatory disease which commonly causes AA amyloidosis, was most likely owing to SHML.
Adult↗
Intraosseous blood gases during hypothermia: correlation with arterial, mixed venous, and sagittal sinus blood.
OBJECTIVE: Especially in pediatric patients with severe hypothermia, intraosseous access may be more readily available than intravascular access during an early phase of treatment and therefore, may be helpful to optimize management. The purpose of this study was to determine whether intraosseous blood gases are comparable with arterial, mixed venous, and sagittal sinus blood gases during different degrees of hypothermia. DESIGN: Prospective, descriptive laboratory investigation using a porcine model. SETTING: University hospital laboratory. SUBJECTS: Twelve anesthetized, 12- to 16-wk-old domestic pigs weighing 30-35 kg. INTERVENTIONS: Volume-controlled ventilated animals were instrumented with arterial, pulmonary artery, sagittal sinus, and 16-gauge intraosseous catheters. Blood samples were obtained from each site every 15 mins during surface cooling with crushed ice until mean +/- SEM core temperature decreased from 38.5+/-0.1 degrees C [101.3+/-0.2 degrees F] to 27+/-0.5 degrees C [80.5+/-0.9 degrees F] over 2 hrs. MEASUREMENTS AND MAIN RESULTS: Intraindividual correlation of Pco2 and pH values were determined as the difference (delta) between intraosseous and reference blood samples. With hypothermia, absolute values of Pco2 decreased and pH increased in samples from all sites. At 27 degrees C, intraosseous--arterial delta P(CO2) and delta pH (mean +/- 95% confidence intervals) were 2.6+/-10.6 torr [0.35+/-1.4 kPa] and -0.11+/-0.07 units; intraosseous - mixed venous were 0.4+/-12.2 torr [0.05+/-1.6 kPa] and -0.06+/-0.08 units; and intraosseous - sagittal sinus were -7.3+/-16 torr [-0.97+/-2.1 kPa] and 0.001+/-0.14 units, respectively. Intraosseous Pco2 was not comparable to end-tidal values (deltaP(CO2) 17.4+/-14.6 torr [2.3+/-1.9 kPa]), and intraosseous lactate did not correlate with arterial, mixed venous, or sagittal sinus values. CONCLUSIONS: During hypothermia, intraosseous P(CO2) values were predictable for mixed venous Pco2 and arterial P(CO2). Intraosseous pH values also correlated with mixed venous and sagittal sinus blood samples. Accordingly, interpretation of blood gas values obtained from bone marrow aspirates may be helpful to adjust ventilation and optimize fluid and drug therapy during the early treatment of patients with severe hypothermia.
Animals↗
Permanent pacemaker therapy before and after the reunification of Germany: 16 years of experience at an East German regional pacing center.
The reunification of Germany had a significant influence on the management of patients with bradyarrhythmias. The current study was performed in a regional pacing center located in the former German Democratic Republic. It compares the situation of patients with critical bradyarrhythmias before and after the reunification of Germany in 1990 focusing on (1) indication for pacemaker implantation, (2) pacemaker modalities and function, (3) type of leads, (4) frequency of reintervention, and (5) early and late complications. The study covers 9 years before and 7 years after the reunification. A total of 1,125 patients were included, and the database was formed by the patients' files and the protocols of implantation. The situation before reunification was characterized by a nonavailability of modern physiological pacing devices and insufficient diagnostic equipment. Between 1981 and 1990, 384 patients underwent pacemaker implantation solely receiving single chamber devices with no or only minimal feasibility of programming. Between 1990 and 1996, 741 patients were treated, and they all received modern pacemakers having the capability of multiprogramming and telemetry. Regarding complications of pacemaker therapy, lead related problems significantly decreased after the reunification (dislocation, 5.3% vs 1.7%, P < 0.05; exit block, 6.7% vs 1.4%, P < 0.05) opposite to pacemaker infections, which significantly increasing after dual chamber pacemakers were implanted (2.2% vs 6.0%, P < 0.05). The reunification of Germany dramatically improved the situation of patients with critical bradyarrhythmias leading to free access to high-tech pacing equipment within a few months. However, the abrupt change from antiquated to modern pacemaker therapy created some new problems, especially regarding application and handling of modern physiological pacing devices.
Equipment Design↗
Detection of tumor genetic alterations of bladder carcinomas in body fluids depends on sample treatment before DNA isolation.
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Body Fluids↗
Cross talk of pp125(FAK) and pp59(Lyn) non-receptor tyrosine kinases to insulin-mimetic signaling in adipocytes.
Signaling molecules downstream from the insulin receptor, such as the insulin receptor substrate protein 1 (IRS-1), are also activated by other receptor tyrosine kinases. Here we demonstrate that the non-receptor tyrosine kinases, focal adhesion kinase pp125(FAK) and Src-class kinase pp59(Lyn), after insulin-independent activation by phosphoinositolglycans (PIG), can cross talk to metabolic insulin signaling in rat and 3T3-L1 adipocytes. Introduction by electroporation of neutralizing antibodies against pp59(Lyn) and pp125(FAK) into isolated rat adipocytes blocked IRS-1 tyrosine phosphorylation in response to PIG but not insulin. Introduction of peptides encompassing either the major autophosphorylation site of pp125(FAK), tyrosine 397, or its regulatory loop with the twin tyrosines 576 and 577 inhibited PIG-induced IRS-1 tyrosine phosphorylation and glucose transport. PIG-induced pp59(Lyn) kinase activation and pp125(FAK) tyrosine phosphorylation were impaired by the former and latter peptide, respectively. Up-regulation of pp125(FAK) by integrin clustering diminished PIG-induced IRS-1 tyrosine phosphorylation and glucose transport in nonadherent but not adherent adipocytes. In conclusion, PIG induced IRS-1 tyrosine phosphorylation by causing (integrin antagonized) recruitment of IRS-1 and pp59(Lyn) to the common signaling platform molecule pp125(FAK), where cross talk of PIG-like structures and extracellular matrix proteins to metabolic insulin signaling may converge, possibly for the integration of the demands of glucose metabolism and cell architecture.
Adipocytes↗
Cortisol and 17-hydroxyprogesterone levels in saliva of healthy neonates: normative data and relation to body mass index, arterial cord blood ph and time of sampling after birth.
The measurement of cortisol and 17-hydroxyprogesterone (17-OHP) in saliva has become a reliable tool for both the scientist and the clinician for studying adrenal cortical function in the adult and the older child. We have now established in parallel normative data for salivary cortisol and 17-OHP levels in healthy neonates. We have asked whether or not there is a circadian rhythm of cortisol and 17-OHP saliva levels in neonates. Furthermore, we have asked whether salivary hormone levels correlated with auxologic and clinical data and time of sampling. Cortisol and 17-OHP levels in saliva samples from 119 healthy neonates (55 girls, 64 boys) were measured using in-house time-resolved fluorescent immunoassays. Saliva samples were obtained using a saliva collecting tube three times a day on the first or second day of life. Gender and gestational age did not influence salivary cortisol and 17-OHP levels. No significant circadian rhythm of salivary hormone levels was detected in this group of newborns. However, body mass index, arterial cord blood pH and time of saliva sampling significantly influenced salivary hormone levels. In conclusion, measurement of cortisol and 17-OHP in saliva is feasible in healthy neonates. The existence of normative data forms the basis for future studies on pathophysiologic states in the newborn period.
17-alpha-Hydroxyprogesterone↗
Body fat mass, leptin and puberty.
Leptin, the ob gene product, provides a molecular basis for the lipostatic theory of the regulation of energy balance. Leptin circulates as a monomeric 16 kDa protein in rodent and human plasma and is also bound to leptin binding proteins that may form large high molecular weight complexes. Initial models of leptin action included leptin-deficient ob/ob mice and leptin-insensitive db/db mice. Peripheral or central administration of leptin reduced body weight, adiposity, and food intake in ob/ob mice but not in db/db mice. In ob/ob mice leptin treatment restored fertility. Leptin interacts with many messenger molecules in the brain. For example, leptin suppresses neuropeptide Y (NPY) expression in the arcuate nucleus. Increased NPY activity has an inhibitory effect on the gonadotropin axis and represents a direct mechanism for inhibiting sexual maturation and reproductive function in conditions of food restriction and/or energy expenditure. By modulating the hypothalamo-pituitary-gonadal axis both directly and indirectly, leptin may thus serve as the signal from fat to the brain about the adequacy of fat stores for pubertal development and reproduction. Normal leptin secretion is necessary for normal reproductive function to proceed and leptin may be a signal allowing for the point of initiation of and progression toward puberty.
Adipose Tissue↗
Towards 3D structures of G protein-coupled receptors: a multidisciplinary approach.
Current strategies in pharmaceutical research comprise two methodologically different but complementary approaches for lead finding purposes, namely the random screening of compound libraries and the structure-based effort, commonly termed rational drug design. The structure-based approach is aimed to exploit 3D structure data of the molecular components involved in the molecular recognition event that underlies the attempt to therapeutically modulate the biological function of a macromolecular target with proven pathophysiological relevance for a disease state. In this context, G protein-coupled receptors (GPCRs) constitute the most prominent family of validated drug targets within biomedical research, since approximately 60 % of approved drugs elicit their therapeutic effects by selectively addressing members of that target family. From a 3D structure point of view, these transmembrane signal transduction systems represent the most challenging task for structure determination, which is due to the heterogeneous and fine-balanced environment conditions that are necessary for structural and functional integrity of the receptor protein. This contribution will address the different concepts to derive structurally relevant information on the transmemebrane seven-helix protein (7TM) domain of GPCRs with special emphasis laid on the multidisciplinarity of the applied methodologies. The current status of electron-cryo-microscopy on 2D crystals and even high-resolution x-ray crystallography on 7TM proteins will be introduced highlighting the transferability of the emerging structural principles onto the GPCR superfamily. Special techniques from bioinformatics and homology-related molecular modeling in combination with tailor-made protein simulation methodologies complement the experimentally derived data, in that they facilitate the 3D structure generation and structure validation process. This contribution summarises the most recent results of GPCR structure studies with the aim to underline the impact of structure data not only for the purpose of rationalising structure-activity data on low-molecular weight antagonists within the context of a protein binding pocket, but also for a better understanding of e.g. mutagenesis experiments, thus qualifying GPCR structure models as valid communication platforms establishing a functional link between molecular biology, biophysics, bioinformatics and organic chemistry in a highly efficient manner.
Amino Acid Sequence↗
Epidermal overexpression of granulocyte-macrophage colony-stimulating factor induces both keratinocyte proliferation and apoptosis.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is released by keratinocytes in sizeable amounts only under pathological conditions, e.g., after topical application of a tumor promoter, in atopic dermatitis (AD), and after wounding. To study the biological function of this cytokine release, we generated transgenic mice that constitutively overexpress GM-CSF in the epidermis. An increase in the numbers of mast cells and Langerhans cells (LCs) in transgenics versus nontransgenic controls was observed but no severe inflammation. This is consistent with a central role of this cytokine in the development and maturation of LCs. Mitotic activity in the epidemnis of transgenic mice was elevated, but epidermal thickness and differentiation were normal. Homeostasis is maintained by an increase of apoptosis in the epidermis. We describe the differential expression of regulators of apoptosis and discuss a potential mechanism for this novel proapoptotic activity of GM-CSF on keratinocytes. Both stimulation of proliferation and promotion of apoptosis are of great relevance to tumorigenesis. The latter may be a means of removing damaged cells after genotoxic stress or injury.
Animals↗