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Biomedical subjects

M Kuhn

Publications and source records attributed to M Kuhn.

At least 55 records · Page 3Linked to original sources
PubMed2000

LaXp180, a mammalian ActA-binding protein, identified with the yeast two-hybrid system, co-localizes with intracellular Listeria monocytogenes.

The Listeria monocytogenes surface protein ActA is an important virulence factor required for listerial intracellular movement by inducing actin polymerization. The only host cell protein known that directly interacts with ActA is the phosphoprotein VASP, which binds to the central proline-rich repeat region of ActA. To identify additional ActA-binding proteins, we applied the yeast two-hybrid system to search for mouse proteins that interact with ActA. A mouse cDNA library was screened for ActA-interacting proteins (AIPs) using ActA from strain L. monocytogenes EGD as bait. Three different AIPs were identified, one of which was identical to the human protein LaXp180 (also called CC1). Binding of LaXp180 to ActA was also demonstrated in vitro using recombinant histidine-tagged LaXp180 and recombinant ActA. Using an anti-LaXp180 antibody and fluorescence microscopy, we showed that LaXp180 co-localizes with a subset of intracellular, ActA-expressing L. monocytogenes but was never detected on intracellularly growing but ActA-deficient mutants. Furthermore, LaXp180 binding to intracellular L. monocytogenes was asymmetrical and mutually exclusive with F-actin polymerization on the bacterial surface. LaXp180 is a putative binding partner of stathmin, a protein involved in signal transduction pathways and in the regulation of microtubule dynamics. Using immunofluorescence, we showed that stathmin co-localizes with intracellular ActA-expressing L. monocytogenes.

Actins↗
PubMed2000

Emergency department ultrasound scanning for abdominal aortic aneurysm: accessible, accurate, and advantageous.

STUDY OBJECTIVE: This study was conducted to determine whether emergency physicians with relatively limited training and experience can accurately identify the presence or absence of abdominal aortic aneurysms (AAAs) by performing bedside ultrasound scanning, and to assess the potential impact of ultrasound scanning on clinical management. METHODS: Patients in whom AAAs were suspected, including those patients older than 50 years presenting with abdominal/back pain of unclear origin or presumed renal colic, were eligible for study entry. Consenting adults had ultrasound scanning by an emergency physician who was not responsible for their primary care. Treating physicians remained blinded to the results unless an unexpected AAAs was discovered. Scan accuracy was ascertained by comparing our ultrasound results with preselected gold standards. The clinical impact of the ultrasound studies was determined by comparing the preultrasound and postultrasound assessment sheets that detailed the presumed diagnosis, proposed investigations and therapies, and patient disposition. RESULTS: Our convenience sample includes 68 scans for AAAs; findings of 26 scans were positive, 40 scans yielded negative findings, and 2 scans were indeterminate. Scan interpretations were 100% accurate. The ultrasound results would have improved the care of 46 patients without adverse sequelae. Ultrasound scanning served primarily to exclude AAA in patients who proved not to have aneurysms; however, scans also provided significant benefits for those with AAAs and improved patient management plans. CONCLUSION: Relative neophytes can perform aortic ultrasound scans accurately. These scans appear useful as a screening measure in high-risk emergency department patients; they may also aid in rapidly verifying the diagnosis in patients who require immediate surgical intervention.

Abdominal Pain↗
PubMed2000

Interaction of Listeria monocytogenes with human brain microvascular endothelial cells: an electron microscopic study.

Internalization of Listeria monocytogenes into human brain microvascular endothelial cells (HBMEC) has recently been demonstrated to be dependent upon the inlB gene. In the present scanning electron microscopic study we show that L. monocytogenes efficiently interacts with the surface of HBMEC in an inlB-independent manner which is also different from invasion. The inlB-dependent invasion of HBMEC by L. monocytogenes is accompanied by intracellular multiplication, movement, and production of bacterium-containing protrusions. These protrusions extend from the cell surface without perturbation of any adjacent cellular membrane.

Bacterial Adhesion↗
PubMed2000

Eosinophilic pneumonia and respiratory failure associated with venlafaxine treatment.

Drugs are well known causes of eosinophilic lung disease. In many patients, symptoms increase slowly, pulmonary infiltrates and eosinophilia progress over weeks, and resolve upon withdrawal of the offending agent. Rarely, the disease presents like acute eosinophilic pneumonia with acute onset of symptoms and rapidly progressing infiltrates which may be associated with respiratory failure. This report describe a case of venlafaxine-induced acute eosinophilic pneumonia causing respiratory insufficiency that rapidly resolved upon institution of corticosteroid treatment. This 5-hydroxytryptamine and noradrenaline reuptake inhibitor was previously not known to cause lung or peripheral blood eosinophilia. Considering the increasing use of this class of medication physicians have to be aware of this life-threatening and fully reversible complication.

Acute Disease↗
PubMed2000

Evaluation of local and systemic immune responses induced by intramuscular injection of a Mycoplasma hyopneumoniae bacterin to pigs.

OBJECTIVE: To evaluate immune responses induced by administration of Mycoplasma hyopneumoniae bacterin to pigs. Animals-60 healthy 7- to 10-day-old cross-bred boars. PROCEDURE: Pigs were assigned to 1 of 4 pig groups (15 pigs/group): vaccinated, challenged; vaccinated, nonchallenged; nonvaccinated, challenged; nonvaccinated, nonchallenged. Vaccinated pigs received IM injections of a mycoplasma bacterin on days 0 and 14, whereas nonvaccinated pigs received saline (0.9% NaCl) solution. Pigs in the challenged groups were inoculated intratracheally with M hyopneumoniae on day 42. Pigs were euthanatized and necropsied 41, 44, 48, and 70 days after the first vaccination, and proportion of lung surface with pneumonic lesions was determined. Percentage of lymphocyte subpopulations and number of interferon-gamma (IFN-gamma) secreting lymphocytes in blood and tissues, cytokine and antibody concentrations in bronchoalveolar lavage (BAL) fluid, and serum antibody concentrations were determined. RESULTS: Vaccination against and infection with M hyopneumoniae induced a local mucosal immune response in the respiratory tract of pigs. Proportion of lung surface with pneumonic lesions in vaccinated challenged pigs was reduced on day 70, compared with nonvaccinated challenged pigs. Vaccination stimulated the production of M hyopneumoniae-specific IFN-gamma secreting blood lymphocytes. Tumor necrosis factor-alpha concentration in BAL fluid on day 70 was increased in nonvaccinated challenged pigs, compared with vaccinated challenged pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Vaccination against M hyopneumoniae induced local, mucosal, humoral, and cellular immune responses. Moreover, vaccination reduced the severity of lung lesions in challenged pigs, suggesting that mucosal antibodies, mediation of the inflammatory response, and cell-mediated immune responses are important for control of mycoplasmal pneumonia in pigs.

Animals↗
PubMed1999

Host cell signal transduction during Listeria monocytogenes infection.

The facultative intracellular bacterial pathogen Listeria monocytogenes invades and multiplies in many mammalian cell types. During the interaction with its host cells it strongly interferes with and modulates host cell functions. In the present review we summarize the current knowledge on the modulation of signal transduction pathways by secreted listerial products prior to bacterium-cell contact, during uptake, or while L. monocytogenes resides in the different intracellular compartments.

Animals↗
PubMed1999

[Ticlopidine-induced cholestasis].

UNLABELLED: We report a case of ticlopidine-induced cholestatic hepatitis. CASE SUMMARY: An 82-year-old man suffered a myocardial infarction in February 1998. Because of persistent angina pectoris a coronary stent was implanted in May 1998. At this time medication with 1 x 250 mg ticlopidine was started in addition to the preexistent medication of aspirin 1 x 100 per day, metoprolol fumarate 1 x 95 mg per day and isosorbide dinitrate 1 x 100 mg per day. Three weeks after starting ticlopidine the patient complained of itching, and on day 28 painless jaundice developed. At this time, the serum activities of alkaline phosphatase (923 U/l), gamma-GT (823 U/l) and total bilirubin concentration (129 mumol/l) were markedly elevated, whereas the activities of the transaminases (AST 131 U/l, ALT 194 U/l) were slightly increased. An extra- or intrahepatic biliary obstruction was ruled out, and there were no signs of a toxic, infectious or immunological cause for the hepatic injury. Liver biopsy showed centro-acinar cholestasis. After drug discontinuation the itching stopped after 4 weeks and jaundice disappeared after 2 weeks. Eight months after the onset of symptoms, the activities of alkaline phosphatase (226 U/l) and gamma-GT (213 U/l) were still elevated but the patient was asymptomatic. CONCLUSIONS: Ticlopidine-induced mild serum liver enzyme elevations have been observed in some studies (incidence 1-2%). The incidence of severe hepatitis has been estimated at 0.0013%. Only a few cases (in approximately 20 patients receiving ticlopidine) of a severe cholestatic pattern of injury have been reported. In all cases the jaundice resolved and serum liver enzyme concentrations normalised over a period of months. Characteristically, liver biopsies demonstrated centro-acinar cholestasis. Monitoring of serum liver enzyme concentrations is not recommended. When itching or jaundice occur in a patient taking ticlopidine, the possibility of toxic liver damage should be taken into account.

Aged↗
PubMed1999

Listeria monocytogenes infection of Caco-2 human epithelial cells induces activation of transcription factor NF-kappa B/Rel-like DNA binding activities.

The effect of Listeria monocytogenes infection on the cellular level of transcription factor NF-kappa B in the human epithelia-like cell line Caco-2 was investigated. Infection with L. monocytogenes or treatment with lipoteichoic acid induced the formation of three NF-kappa B-like DNA-protein complexes C1, C2, and C3, which were identified as containing either, RelA and p50, RelB and p50, or p50, respectively. NF-kappa B activation in L. monocytogenes-infected Caco-2 cells was distinct from NF-kappa B activation in infected P388D1 macrophages concerning the NF-kappa B complexes formed and the kinetics of the induction.

Caco-2 Cells↗
PubMed1999

[Extensive eosinophilic pulmonary infiltrates in a depressive patient treated with maprotiline].

A 74 year old man developed progressive dyspnea under treatment with the tetracyclic antidepressant maprotiline for three months. A chest x-ray revealed extended pulmonary infiltrates. Marked eosinophilia of the periperal blood was found (up to 2300/microliter). Rapid clinical and radiological improvement was observed solely by withholding the drug. The eosinophil count retourned to normal within a few weeks. The possible pathogenesis is discussed and the literature reviewed.

Aged↗
PubMed1999

An alpha-actinin binding site of zyxin is essential for subcellular zyxin localization and alpha-actinin recruitment.

The LIM domain protein zyxin is a component of adherens type junctions, stress fibers, and highly dynamic membrane areas and appears to be involved in microfilament organization. Chicken zyxin and its human counterpart display less than 60% sequence identity, raising concern about their functional identity. Here, we demonstrate that human zyxin, like the avian protein, specifically interacts with alpha-actinin. Furthermore, we map the interaction site to a motif of approximately 22 amino acids, present in the N-terminal domain of human zyxin. This motif is both necessary and sufficient for alpha-actinin binding, whereas a downstream region, which is related in sequence, appears to be dispensable. A synthetic peptide comprising human zyxin residues 21-42 specifically binds to alpha-actinin in solid phase binding assays. In contrast to full-length zyxin, constructs lacking this motif do not interact with alpha-actinin in blot overlays and fail to recruit alpha-actinin in living cells. When zyxin lacking the alpha-actinin binding site is expressed as a fusion protein with green fluorescent protein, association of the recombinant protein with stress fibers is abolished, and targeting to focal adhesions is grossly impaired. Our results suggest a crucial role for the alpha-actinin-zyxin interaction in subcellular zyxin localization and microfilament organization.

Actinin↗
PubMed1999

[Rhabdomyolysis and cholestatic hepatitis under treatment with simvastatin and chlorzoxazone].

Acute rhabdomyolysis under treatment with HMG-CoA reductase inhibitors ("statins") is a group-specific if rare side effect. Muscle toxicity of statins can be potentiated by medication influencing their metabolism. Here drug interactions on the level of the microsomal cytochrome P450 enzymes play an important role. We report the first case of marked rhabdomyolysis with cholestatic hepatitis in a 73-year-old woman treated with simvastatin and chlorzoxazone. Withdrawal of the causal medication and conservative therapy with volume substitution and forced diuresis was followed by almost complete resolution of the symptoms with normalisation of the blood tests. Possible mechanisms involved in the drug interactions are discussed. Thorough knowledge of the enzyme systems involved in drug metabolism helps to predict possible adverse drug interactions and prevent toxic effects.

Aged↗
PubMed1999

[Angioedema induced by ACE inhibitors and angiotensin II-receptor antagonists: analysis of 98 cases].

Angiooedema has been reported as a rare but in most cases serious adverse effect of ACE inhibitors. Recent reports have indicated that angiotensin II-receptor antagonists may also induce angiooedema. As part of the spontaneous reporting scheme in Switzerland the Swiss Drug Monitoring Centre (SANZ) has received reports on 94 cases of ACE inhibitor-induced and 4 cases of angiotension II-receptor antagonist-induced angiooedema. These 98 spontaneously reported cases were analysed in detail. 28 cases were classified as serious and in three patients intubation was even required. In 35% of cases angiooedema was induced within the first week of therapy and in 64% within the first year. In one case the angio-oedema displayed latency of 8 years. Latency of this duration shows that this adverse drug reaction (ADR) may be hard to detect. In 45 of the 98 cases the oedema persisted for more than one day (maximum 2 months), although in some instances the patients continued ACE-inhibitor therapy. In 25 cases the oedema recurred, in one instance as many as 20 times. In rare cases angiooedema may also be induced by angiotensin II-receptor antagonists, although in such instances the course of the oedema was usually milder. In two of the four reported cases angiooedema recurred after switching from an ACE inhibitor to an angiotensin II-receptor antagonists. The four reported cases from Switzerland showed a similar profile when compared with 25 internationally documented cases. Our data indicate that angiooedema is a specific ACE inhibitor ADR. A protracted latency period may be observed and recurrence of oedema is frequent. Angiotensin II-receptor antagonist-induced angiooedema may also occur in rare instances.

Adult↗
PubMed1999

Postmarketing safety information: how useful are spontaneous reports?

UNLABELLED: From 1995 until June 1998 123 new chemical entities (NCEs) were launched in Switzerland. In this time period 250 reports of adverse reactions (ADRs) involving 56 different NCEs were reported to the Swiss Drug Monitoring Center SANZ directly by physicians within the voluntary spontaneous reporting scheme (SRS). No cases from observational or clinical postmarketing studies were included. Of the reports 88% were suspected to be drug-related and 20% of them were serious. In 64% the ADRs were unlabelled and not notified to the health professionals. Disorders of the central nervous system (CNS) were reported in 32% and cardiovascular disorders in 26% of the unlabelled and serious cases. The non-serious cases accounted for 80% of the reported NCE-ADRs and 60% of them were unlabelled. Skin reactions were reported most frequently (18%), followed by psychic (15%), gastrointestinal (10%), cardiovascular and CNS disorders (8% each). In the labelled non-serious cases gastrointestinal and skin reactions were reported in 25% and 24% respectively. The other system organ classes were involved to a much smaller extent (<8%). CONCLUSIONS: (1) Spontaneous reports are of great value in optimizing postmarketing safety information. (2) Early reports give rise to a different ADR profile than expected from premarketing safety information. (3) Spontaneous reports have a strong signalling function especially for drugs used by general practitioners. (4) Sensitive signal detection systems are of great value in detecting non-labelled and serious ADRs in an early phase.

Journal Article↗
PubMed1999

Dendritic cells need T cell help to prime cytotoxic T cell responses to strong antigens.

Peptide-pulsed mouse dendritic cells (DC) primed peptide-specific CD8+ cytotoxic T cell responses very effectively if they expressed minor histocompatibility antigens, which could stimulate a CD4+ T helper cell response. These DC could also prime most syngeneic mice, although there was no deliberate immunization for help (the DC were prepared in syngeneic mouse serum, to avoid any response to fetal calf serum antigens). In contrast, DC were unable to prime MHC class II-deficient mice for cytotoxic responses to the classical helper-dependent antigens Qa1a and HY. More strikingly, Balb.B DC failed to prime B6 MHC class II-deficient mice for cytotoxic responses to Balb minor antigens, even though these two strains differ at more than 40 minor histocompatibility loci. When peptide-pulsed DC were prepared without enzymes (used to release DC from lymphoid tissues), they failed to prime the majority of normal syngeneic mice, even though they expressed high levels of B7 and ICAM-1 co-stimulatory molecules, suggesting that help was provided by responses to antigens in the enzyme cocktail. The enzyme treatment itself did not provide signals that could substitute for help, since DC prepared with enzymes could not prime MHC class II-deficient mice. The observation that highly immunogenic minor-incompatible DC failed to prime MHC class II-deficient mice suggests that in the absence of inflammatory signals, even strong antigens cannot stimulate CD8+ T cell responses without help.

Animals↗
PubMed1999

[Lung diseases in pregnancy].

Pulmonary diseases play a particular role during pregnancy. First, the adaptive hyperventilation of the mother implies sufficient pulmonary reserves, and second, and increasing oxygen consumption of the fetus during pregnancy might be compromised by maternal hypoxemia and could be followed by fetal growth retardation and fetal hypoxemia. Asthma bronchiale is the leading pulmonary disease in pregnancy and is not associated with higher risk for pregnancy and fetus when sufficiently threatened. First line medicaments are beta-2-agonists and steroids. Pneumonia however is a serious menace to the pregnant women, especially when not early diagnosed and correctly treated. Respecting the leading germs, macrolids or wide-spectrum penicillins are used. Tuberculosis has no deleterious effect on pregnancy with early diagnosis and treatment, which follows the usual guidelines during pregnancy with isoniacid, rifampicin and ethambutol. Cystic Fibrosis is not a strict contraindication for a pregnancy, especially for mild clinical forms. However, preconceptional counseling and regular clinical controls before and during pregnancy are indispensible. Deep vein thrombosis and pulmonary embolism are more frequent during pregnancy; the search for risk factors, prophylaxis and treatment are essential to avoid these complications. Heparin is the ideal prophylaxis and treatment in pregnancy, while oral anticoagulants should be avoided because of their effect on the fetus.

Adult↗
PubMed1999

Intra-and inter-individual variations in transepidermal water loss on the face: facial locations for bioengineering studies.

The volar forearm is the favored location for bioengineering studies. However, transepidermal water loss (TEWL), which is an important indicator of the function of the epidermal barrier, shows regional variations, and for the evaluation of cosmetic formulations, facial skin would be more suitable. In this study, we have compared 10 facial locations with 1 test site on the volar forearm for absolute TEWL values, reproducibility, and correlation. Measurements were performed over 3 consecutive days. The TEWL values of the facial test sites were higher compared to forearm values and did not correlate with the forearm. On the face, there was a good correlation between the values of the right compared to the left side of the face. The sites superior to the nervus supraorbitalis, the medial borders of the musculus masseter, and the center of the chin proved to be locations with relatively stable TEWL values. There was a greater variability at the center of the forehead and at the center of the cheeks. It is recommended that TEWL measurements on facial locations with stable TEWL values are used for the evaluation of cosmetic formulations.

Adult↗