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Biomedical subjects

M Kuhn

Publications and source records attributed to M Kuhn.

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

Comparative genomics of Listeria species.

Listeria monocytogenes is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. We present and compare the genome sequences of L. monocytogenes (2,944,528 base pairs) and a nonpathogenic species, L. innocua (3,011,209 base pairs). We found a large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators, consistent with the ability of both species to adapt to diverse environments. The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events.

Adaptation, Physiological↗
PubMed2001

[Pseudotumor cerebri in minocyline treatment].

Pseudotumor cerebri or benign intracranial hypertension is a syndrome of raised intracranial pressure without obvious explanation. Most patients are obese women at childbearing age. Symptoms and signs usually include headache, nausea, vomiting, edema of the papilla, visual obscurations and rarely palsy of the nervus abducens. The prognosis is generally good, but progressive visual loss and eventual blindness are major risks. We report the case of a 21-year-old non-obese young woman who developed pseudotumor cerebri while taking minocycline for acne therapy. Identical symptoms occurred upon inadvert rechallenge with minocycline for the second time.

Acne Vulgaris↗
PubMed2001

Immunoisolation of TCR signaling complexes from Jurkat T leukemic cells.

The formation of multimolecular assemblies of signaling molecules at the plasma membrane is key to triggering signaling cascades following activation of transmembrane receptors at the plasma membrane. We have developed a method to immunoisolate activated T cell receptors (TCRs) and associated signaling molecules in plasma membrane subdomains from Jurkat T leukemic cells. The immunoisolation procedure for the signaling complexes uses magnetic beads, which are coupled to TCR-activating antibodies. Following mechanical cellular disruption using nitrogen cavitation, conjugates of these beads with Jurkat cells are formed and isolated. TCR-signaling complexes within plasma membrane fragments associate with the antibody-coupled beads and are retrieved along with the beads using a magnet. We found that the immunoisolated plasma membrane fragments are highly enriched for activated TCRs and associated signaling proteins. This isolation procedure allows a detailed and precise biochemical analysis of the assembly of signaling proteins in plasma membrane subdomains.

Antibodies, Monoclonal↗
PubMed2001

The anatomy of a shark attack: a case report and review of the literature.

Shark attacks are rare but are associated with a high morbidity and significant mortality. We report the case of a patient's survival from a shark attack and their subsequent emergency medical and surgical management. Using data from the International Shark Attack File, we review the worldwide distribution and incidence of shark attack. A review of the world literature examines the features which make shark attacks unique pathological processes. We offer suggestions for strategies of management of shark attack, and techniques for avoiding adverse outcomes in human encounters with these endangered creatures.

Adult↗
PubMed2001

Accuracy of emergency department bedside ultrasonography.

OBJECTIVES: To determine which focused ultrasound examinations can be interpreted accurately by emergency physicians who have limited training and experience. To determine whether image quality and/or the operator's level of confidence in the findings correlates with accurate scan interpretation. METHODS: A prospective sample of consenting adult emergency department patients with the conditions was selected for study. Scans were performed by emergency physicians who had attended a 3-day focused ultrasound examinations instruction course. All scans were videotaped and subsequently reviewed by a radiologist. Accuracy was determined by comparing the emergency physicians scan interpretation with preselected gold standards. Chi-squared tests were employed to determine if the individual performing the scan, the type of scan, patient's body habitus, image quality and/or operator confidence were reliable predictors of accuracy. RESULTS: Between September 1997 and January 1999, 221 scans were studied. Accuracy varied widely depending on the type of scan performed: aortic scans were 100% accurate whereas renal scans had 68% accuracy. On bivariate analyses, there was little variation in the various operators' levels of proficiency and accuracy of interpretation was not associated with patient body habitus, image quality or operator confidence. CONCLUSIONS: Neophytes can accurately perform and interpret aortic scans; additional training and/or experience appear to be necessary to achieve proficiency in conducting most of the other scans studied. Inexperienced operators are unable to discern whether their scan interpretations will prove accurate.

Adult↗
PubMed2001

[Clinical value of native and contrast enhanced MRI in staging prostatic carcinoma before planned radical prostatectomy].

PURPOSE: To assess the clinical value of MRI with and without contrast agent in the staging of prostatic carcinoma. Relevance for surgical management. METHODS: 60 patients with carcinoma proven by biopsy or suspected prostatic carcinoma were evaluated with MRI. The examinations were performed in a 1.5 T (Philips ACS-NT Gyroscan) imager with multiplanar orientations before and after intravenous application of 0.1 mmol/kg/bw Gadodiamide (Omniscan-Nycomed/Amersham). The gold standard was histology after radical prostatectomy and in case of non-operability the consensual final staging. RESULTS: Compared to histology MRI revealed a sensitivity of 75% and a specificity of 82% in the differentiation of locally advanced carcinoma (T 3/4). Including the non-surgical cases MRI showed a sensitivity of 82.5% and a specificity of 86%. Interindividual analysis showed no difference in diagnostic accuracy between the non-enhanced and the contrast-enhanced techniques. In 23% of cases (n = 14) MRI induced changes in patient management. CONCLUSIONS: MRI is an accurate procedure in the local staging of prostatic carcinoma. In combination with clinical findings, PSA, and grading scores MRI has a significant influence on treatment selection. Contrast agent administration does not seem to increase the diagnostic accuracy significantly.

Aged↗
PubMed2001

Gamma-hydroxybutyrate overdose and physostigmine: teaching new tricks to an old drug?

Gamma-hydroxybutyrate was introduced as an anesthetic agent in the 1960s and is still used in some countries, despite recognized disadvantages. More recently, it has emerged as a popular recreational drug. We report 3 cases of gamma-hydroxybutyrate overdose, the effects of which were reversed by the administration of low-dose intravenous physostigmine. The origins of this regimen and the case for physostigmine as a potential antidote are described.

Adult↗
PubMed2001

Listeria pathogenesis and molecular virulence determinants.

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal individuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research.

Animals↗
PubMed2001

Drug-induced bronchospasm: analysis of 187 spontaneously reported cases.

BACKGROUND: The Swiss Drug Monitoring Center (SANZ) uses a systematic approach to the collection of spontaneously reported individual cases on suspected adverse drug reactions (ADRs). Spontaneous reporting schemes are designed to detect new, rare and unexpected ADRs and to act as an early warning system but there is a tendency to overreport severe reactions. OBJECTIVES: The aim of the study was to determine drug-induced episodes of bronchospasm, their seriousness and predisposing risk factors. An ADR is classified as serious if the reaction results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity. RESULTS: From 1986 to 1995 SANZ received 8,191 case reports of suspected ADRs. In 187 cases (2%) bronchospasm was reported. In 55% of these cases the reaction was regarded as serious. Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) were reported most frequently and were involved in 24% of the cases of which 64.5% were classified as serious. In three cases a lethal outcome was reported after intravenous administration of metamizol. Anti-infectious agents were implicated in 18% (52% serious), cardiovascular drugs in 11% (50% serious), drug formulation agents in 9% (41% serious), vaccines and immunoglobulins in 5.5% (50% serious), and plasma volume expanders in 5.5% (80% serious). Other drug groups were involved in 27% of the cases. About 50% of patients experiencing bronchospasm after NSAIDs, pharmaceutical formulation agents, vaccines and immunoglobulins had predisposing risk factors such as asthma, atopy or drug allergy. In other drug groups a predisposing factor was identified in 27% or less. CONCLUSION: Drug-induced bronchospasm is frequently reported with NSAIDs, anti-infective agents, cardiovascular drugs and excipients with a high proportion of serious reactions.

Anti-Infective Agents↗
PubMed2001

High salt intake increases uroguanylin expression in mouse kidney.

The intestinal peptides, guanylin and uroguanylin, may have an important role in the endocrine control of renal function. Both peptides and their receptor, guanylyl cyclase C (GC-C), are also expressed within the kidney, suggesting that they may act locally in an autocrine/paracrine fashion. However, their physiological regulation within the kidney has not been studied. To begin to address this issue, we evaluated the distribution of uroguanylin and guanylin messenger RNA (mRNA) in the mouse nephron and the regulation of renal expression by changes in dietary salt/water intake. Expression was determined in 1) wild-type mice, 2) two strains of receptor-guanylyl cyclase-deficient mice (ANP-receptor-deficient, GC-A-/-, and GC-C-deficient mice); and 3) cultured renal epithelial (M-1) cells, by RT-PCR, Northern blotting and immunocytochemistry. Renal uroguanylin messenger RNA expression was higher than guanylin and had a different distribution pattern, with highest levels in the proximal tubules, whereas guanylin was mainly expressed in the collecting ducts. Uroguanylin expression was significantly lower in GC-C-/- mice than in GC-A-/- and wild-types, suggesting that absence of a receptor was able to down-regulate ligand expression. Salt-loading (1% NaCl in drinking water) increased uroguanylin-mRNA expression by >1.8-fold but had no effect on guanylin expression. Uroguanylin but not guanylin transcripts were detected in M-1 cells and increased in response to hypertonic media (+NaCl or mannitol). Our results indicate that high-salt intake increases uroguanylin but not guanylin expression in the mouse kidney. The synthesis of these peptides by tubular epithelium may contribute to the local control of renal function and its adaptation to dietary salt.

Animals↗
PubMed2000

[Reactivation of herpes virus infections by vaccination: evidence or coincidence?].

Varicella zoster and herpes simplex viruses cause latent infections by persisting in human cells. Reactivation has been associated with increasing age, immunosuppression, cancer, stress, fever, exposure to ultraviolet light, and tissue damage. Based on three cases reported to the Swiss Drug Monitoring Centre SANZ, we postulated previously that vaccinations may trigger reactivation of herpes virus infections due to vaccine-induced immunomodulation. In the meantime, 10 new cases of reactivated herpes virus infections soon after vaccinations have been reported. They involved 5 women and 5 men with an age range between 16 and 60. In only one case had a trauma preceded, otherwise healthy subjects with no known relevant comorbidity were vaccinated. The clustering of reports after publication points to a previous underreporting of similar cases. This may be explained by the fact that both vaccinations and reactivations of herpes virus infections are frequent, and a causal link is not suspected. However, these new cases do not prove causality, and extensive epidemiological or experimental studies are needed to elucidate the possible link between vaccination and reactivation of herpes virus infections.

Adult↗
PubMed2000

Selective accumulation of raft-associated membrane protein LAT in T cell receptor signaling assemblies.

Activation of T cell antigen receptor (TCR) induces tyrosine phosphorylations that mediate the assembly of signaling protein complexes. Moreover, cholesterol-sphingolipid raft membrane domains have been implicated to play a role in TCR signal transduction. Here, we studied the assembly of TCR with signal transduction proteins and raft markers in plasma membrane subdomains of Jurkat T leukemic cells. We employed a novel method to immunoisolate plasma membrane subfragments that were highly concentrated in activated TCR-CD3 complexes and associated signaling proteins. We found that the raft transmembrane protein linker for activation of T cells (LAT), but not a palmitoylation-deficient non-raft LAT mutant, strongly accumulated in TCR-enriched immunoisolates in a tyrosine phosphorylation-dependent manner. In contrast, other raft-associated molecules, including protein tyrosine kinases Lck and Fyn, GM1, and cholesterol, were not highly concentrated in TCR-enriched plasma membrane immunoisolates. Many downstream signaling proteins coisolated with the TCR/LAT-enriched plasma membrane fragments, suggesting that LAT/TCR assemblies form a structural scaffold for TCR signal transduction proteins. Our results indicate that TCR signaling assemblies in plasma membrane subdomains, rather than generally concentrating raft-associated membrane proteins and lipids, form by a selective protein-mediated anchoring of the raft membrane protein LAT in vicinity of TCR.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Immediate hypersensitivity reactions to parenteral glucocorticoids? Analysis of 14 cases].

Immediate hypersensitivity reactions to parenteral glucocorticoids are rare but often serious and life-threatening. In the medical literature some hundred case reports of corticoid hypersensitivity after parenteral administration have been published. The pathomechanism may be immunological or non-immunological in nature and the reaction can be due to the steroid itself or to the excipients. We report on 14 suspected hypersensitivity reactions occurring in 13 patients immediately after parenteral glucocorticoid administration. These cases were reported to the Swiss Drug Monitoring Centre SANZ between 1981 and 1999. 5 out of 26 preparations available in Switzerland and 4 out of the 6 glucocorticoids used for parenteral administration were involved (beta-methasone, methylprednisolone, prednisolone, triamcinolone). 9 reactions were life-threatening: 3 patients experienced an acute asthma attack and 6 a serious anaphylactic reaction including shock. Risk factors were known in 10 patients: allergy was mentioned in 6 patients, and asthma and aspirin-sensitivity in 2 patients each. In 2 patients a clinically relevant cross-reaction with another glucocorticoid was known, while 6 patients tolerated another steroid without problems. Only in 6 cases were skin tests performed: 3 were positive for the preparation, and in one of these cases the skin test was positive for the steroid itself. In 2 cases the hypersensitivity reaction could be traced back to the additive carboxymethylcellulose. Practitioners should be aware of hypersensitivity reactions to glucocorticoids whenever there is a worsening of the clinical status in spite of maximal steroid therapy.

Adult↗
PubMed2000

[Potential drug interactions and number of prescription drugs with special instructions at hospital discharge].

OBJECTIVE: Up to 6% of all hospitalizations are due to adverse drug reactions and 20% of these are caused by drug-drug interactions. There is only little information on the prescription frequency of drug-combinations with the potential to induce dangerous drug-drug interactions and drugs with the need for special patient instruction (e.g. inhalers). The aim of our study was to investigate the frequency of such drug prescriptions at hospital discharge. PATIENTS AND METHODS: In a retrospective, descriptive study drug prescriptions of 100 patients discharged consecutively from the department of internal medicine of a 300 bed-hospital were analysed. Possible drug-drug interactions were detected using a special computer program. Furthermore, the number of prescriptions warranting patient instruction such as anticoagulants, antidiabetics, hormones, immunosuppressive drugs, chemotherapeutics, antituberculotic and antiepileptic drugs as well as inhalatives and injections was recorded. RESULTS: The mean age of the 100 patients (61 men, 39 women) was 61.7 years, the mean duration of the hospital stay was 9.2 days. At discharge, patients took an average of 3.5 different drugs. Half of the patients were given drug-combinations with the potential for drug-drug interactions, whereby 5% were at risk for the development of interactions of severe and 42% of intermediate degree. All drug-combinations with potentially severe interactions were prescribed deliberately. 31% of all patients took medications with the need for special education, with inhalatives being the most frequent. The prescription of drugs with potential interactions and the necessity for special patient instruction was more frequent in the elderly. CONCLUSIONS: Drug-combinations with the potential of harmful interactions and drugs with the requirement for special patient instruction are frequently prescribed at hospital discharge. The frequency of prescribing these drugs increases with age. Detection of potentially dangerous drug-drug interactions is simplified by special computer programs. Careful patient instruction about the use of certain drugs is a key issue to improve patient compliance and to guarantee an optimal treatment effect.

Aged↗
PubMed2000

Bacterial replication in the host cell cytosol.

Intracellular bacteria in mammalian host cells can either live in a membrane-bound vacuole modified to support bacterial growth, or escape from the primary phagosome into the host cell cytoplasm. Phagosomal escape is best studied in Listeria monocytogenes in which a pore-forming cytolysin and two phospholipases are involved in the lysis of the phagosomal membrane. The mechanisms of and requirements for cytoplasmic growth are less clear but there is growing evidence that proficient replication of bacteria in the cytoplasmic compartment requires specific bacterial and cellular preconditions.

Animals↗