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Biomedical subjects

M Arndt

Publications and source records attributed to M Arndt.

At least 37 records · Page 2Linked to original sources
PubMed2000

Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans.

BACKGROUND: Previous studies have suggested that atrial fibrillation (AF) is associated with the activation of the atrial angiotensin system. However, it is not known whether the expression of angiotensin II receptors changes during AF. The purpose of this study was to determine the atrial expression of angiotensin II type 1 and type 2 receptors (AT(1)-R and AT(2)-R) in patients with AF. METHODS AND RESULTS: Atrial tissue samples from 30 patients undergoing open heart surgery were examined. Eleven patients had chronic persistent AF (> or =6 months; cAF), 8 patients had paroxysmal AF (pAF), and 11 patients were in sinus rhythm. AT(1)-R and AT(2)-R were localized in the atrial tissue by immunohistochemistry and quantified at the protein and mRNA level by Western blotting and quantitative polymerase chain reaction. Both types of AT-R were predominantly expressed in atrial myocytes in all groups. The amount of AT(1)-R was reduced to 34.9% during cAF (P<0.01) and to 51.7% during pAF (P<0.05) compared with patients in sinus rhythm. In contrast, AT(2)-R was increased during cAF (246%; P=NS) and pAF (505%; P<0.01). AT(1)-R/AT(2)-R mRNA content was similar in all groups. CONCLUSIONS: AF is associated with the down-regulation of atrial AT(1)-R and the up-regulation of AT(2)-R proteins. These findings may help define the pathophysiological role of the angiotensin system in the structural remodeling of the fibrillating atria.

Adult↗
PubMed2000

Specific inhibitors of dipeptidyl peptidase IV suppress mRNA expression of DP IV/CD26 and cytokines.

The dipeptidyl peptidase IV is an activation marker on T, B and NK cells. Specific inhibitors of DP IV suppress DNA synthesis, as well as cytokine protein production. Here, we describe for the first time the quantitative changes of mRNA expression of IFN-gamma, IL-2, IL-12 and DP IV after inhibition of DP IV. Due to the stimulation of human peripheral blood mononuclear cells (PBMC) with pokeweed mitogen (PWM) both cytokine as well as DP IV mRNA expression is increased significantly. Treatment with DP IV inhibitor suppresses dose-dependently these changes. Importantly, mRNA expression of DP IV itself was inhibited. The presented data are fully compatible with our hypothesis that inhibition of DP IV leads to cell cycle arrest in late G1 due to enhanced TGF-beta 1 expression.

Autocrine Communication↗
PubMed2000

Modulation of WNT-5A expression by actinonin: linkage of APN to the WNT-pathway?

Inhibition of alanyl-aminopeptidase gene expression or enzymatic activity compromises T cell proliferation and function. Molecular mechanisms mediating these effects are not known as yet. Applying the cDNA array technique we identified the proto-oncogen Wnt-5a strongly affected by APN-inhibition. Wnt-5a and other members of the Wnt family of secreted factors are implicated in cell growth and differentiation. Wnt-5a was moderately expressed in resting T cells, but strongly down-regulated in response to activation by OKT3/IL-4/IL-9. Actinonin increased Wnt-5a-mRNA contents as confirmed by RT-PCR. In addition, expression of GSK-3 beta, an inherent component of the Wnt-pathway, was found to be increased in response to activation, but suppressed by actinonin at both the mRNA and protein level. These findings may provide a rationale for the strong growth inhibitory effects resulting from an inhibition of alanyl aminopeptidase expression or activity.

CD13 Antigens↗
PubMed2000

Matrix metalloproteinases and TACE play a role in the pathogenesis of endometriosis.

Endometriosis, a benign gynecologic disorder, occurs in about 10% of women in reproductive age and in up to 50% of women with infertility. The basic etiologic factors causing this disease are unknown as yet. Matrix metalloproteinases (MMP) are involved in degradation of the extracellular matrix (ECM). Their proteolytic activity is regulated by tissue inhibitors of metalloproteinases (TIMPs). Tumor necrosis factor-alpha converting enzyme (TACE) is a membrane-bound disintegrin metalloproteinase that processes the membrane-associated cytokine proTNF-alpha to its mature soluble form. TNF-alpha induces the secretion of several MMPs. In order to study the expression of MMP-1, -2, -3 and -9, TIMP-1 and -2, TACE and TNF-alpha in endometrium and endometriotic tissue, we investigated formalin-fixed paraffin sections of endometriotic tissues and normal endometrium with immunohistochemical techniques and in situ hybridisation. Furthermore, quantitative PCR was used for quantification of TACE-mRNA in fresh tissue. We found in this study significant higher protein expression of MMP-1 and TACE and significant lower protein expression of TMP-1 and -2 in endometriotic tissue compared to endometrium. This data may suggest that high TACE expression causes the increased conversion of membrane-bound proTNF-alpha into its soluble form, which stimulates the increased secretion of MMP-1. The simultaneous deficiency of TIMP-1 and -2 in endometriotic tissue suppose an additional proteinase inhibitor imbalance in endometriosis.

ADAM Proteins↗
PubMed2000

Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.

OBJECTIVES: The purpose of this study was to determine whether atrial expression of the extracellular signal-regulated kinases Erk1/Erk2 and of the angiotensin-converting enzyme (ACE) is altered in patients with atrial fibrillation (AF). BACKGROUND: Recent studies have demonstrated that atrial fibrosis can provide a pathophysiologic substrate for AF. However, the molecular mechanisms responsible for the development of atrial fibrosis are unclear. METHODS: Atrial tissue samples of 43 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or =6 months; CAF), 8 patients had paroxysmal AF (PAF) and 18 patients had no history of AF. Erk expression was analyzed at the mRNA (quantitative reverse transcription polymerase chain reaction), the protein (immunoblot techniques) and atrial tissue (immunohistochemistry) levels. Erk-activating kinases (MEK1/2) and ACE were analyzed by immunoblot techniques. RESULTS: Increased amounts of Erk2-mRNA were found in patients with CAF (75 +/- 20 U vs. sinus rhythm: 31 +/- 25 U; p < 0.05). Activated Erk1/Erk2 and MEK1/2 were increased to more than 150% in patients with AF compared to patients with sinus rhythm. No differences between CAF and PAF were found. The expression of ACE was three-fold increased during CAF. Amounts of activated Erk1/Erk2 were reduced in patients treated with ACE inhibitors. Patients with AF showed an increased expression of Erk1/Erk2 in interstitial cells and marked atrial fibrosis. CONCLUSIONS: An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF. These findings may have important impact on the treatment of AF.

Aged↗
PubMed2000

The more things change, the more they stay the same.

For decades, the hospital environment has been described as turbulent and hostile. At the same time, the transfer of business practices into hospitals has been advocated, accompanied by the largely untested assumption that these practices are crucial to performance and even survival. As this pattern became entrenched, the accumulated knowledge gained within the industry of managing in a hostile and turbulent environment has been overlooked. We argue that it is time to question the pattern.

Commerce↗
PubMed1999

R-esp1, a rat homologue of drosophila groucho, is differentially expressed after optic nerve crush and mediates NGF-induced survival of PC12 cells.

The differential display reverse transcription polymerase chain reaction method was used to detect alterations in gene expression in the superior colliculus after optic nerve crush in adult rats. One of the most prominent changes observed was the selective induction of R-esp1, a homologue of the Drosophila enhancer of split locus (Groucho). Therefore, we studied the influence of R-esp1 on nerve growth factor (NGF)-induced cell survival of PC12 cells. Overexpression of R-esp1 promotes cell survival even in the absence of NGF and, conversely, it is reduced by antisense-mediated inhibition of R-esp1 expression. In conclusion, we propose a novel model in which R-esp1 protein mediates the NGF-signaling pathway.

Animals↗
PubMed1999

Role of alanyl aminopeptidase in growth and function of human T cells (review).

Alanyl aminopeptidase (APN, CD13) is highly expressed in human monocytes, and anti-CD13 monoclonal antibodies are well established routine markers in leukaemia typing. Due to activation or malignant transformation other leukocyte subpopulations including human T cells exhibit significant APN-gene and surface expression. The function of leukocyte APN is poorly understood, especially the knowledge of physiological ligands/substrates of the enzyme is limited. Abnormal expression of APN on malignant lymphocytes, the activation-dependent induction of APN expression in peripheral T cells and the strong anti-proliferative effects of aminopeptidase inhibitors lead to the interesting hypothesis of a linkage of APN expression and/or function to leukocyte growth. In support of this hypothesis we detected mutations in the APN-gene of patients suffering from leukaemia or lymphoma. This review outlines evidence for APN contributing to the regulation and realisation of lymphocyte growth and function by modulating the mRNA expression of IL-2, IL-1 receptor antagonist, and TGF-beta1 and increasing the activity of MAP kinase p42/Erk2.

Base Sequence↗
PubMed1998

Inhibition of alanyl aminopeptidase induces MAP-kinase p42/ERK2 in the human T cell line KARPAS-299.

Inhibition of alanyl aminopeptidase (EC 3.4.11.2, aminopeptidase N, CD13) expression, or activity compromise cell proliferation in a number of cell systems [1, 2, 3, 4, 5, 6]. The underlying mechanisms and the molecular components involved have not been identified as yet. In this study we show that inhibition of alanyl aminopeptidase enzymatic activity decreases the proliferation rate of the CD13-positive T cell line Karpas-299. By using the ATLAS cDNA expression array (Clontech) we identified the p42/ERK2 MAP kinase as one downstream target of probestin, a potent inhibitor of alanyl aminopeptidase. Probestin and another specific aminopeptidase inhibitor, actinonin, in addition to their capability of inducing erk-2 mRNA levels, significantly increase p42 phosphorylation state. This is the first report on signal transduction components possibly mediating the growth-modulatory effects of alanyl aminopeptidase inhibitors.

CD13 Antigens↗
PubMed1998

Reengineering: deja vu all over again.

There is growing interest among hospitals in reengineering. It promises dramatic improvements in performance: Costs will be reduced while work processes, productivity, and patient care will all improve. A review of the health care literature on reengineering shows that little evidence exists to support its claims. This article critiques the existing literature on reengineering and addresses the conundrum hospital executives encounter when faced with the decision to adopt a new management technique--such as reengineering--in the absence of proof of its efficacy.

Cost-Benefit Analysis↗
PubMed1998

[Sore throat after use of the laryngeal mask and intubation].

The laryngeal mask was developed by Brain in 1981 and described for the first time in 1983. It has been applied a few million times worldwide since 1988. One of the main complication is soreness of the throat. Two hundred unselected patients who had gynaecological procedures under general anaesthesia--100 under laryngeal mask airway and 100 under intubation--were surveyed to ascertain the incidence of sore throats under laryngeal mask airway. Each patient was asked about soreness of the throat during the next two days. The incidence and duration of sore throats were recorded using a pain scale (0-100). After narcoses with the laryngeal mask, 63 patients had no complaints. Thirty-seven had sore throats with an average pain score of 8.1 +/- 13.8 on the day of operation. The average pain scores showed a decreasing tendency (4.2 +/- 9.5 and 0.4 +/- 2.6) for the first and second postoperative day. After intubation narcoses, we recorded sore throats significantly more frequently (p < 0.05) and the average pain score on the day of operation was significantly higher (13.2 +/- 17.5; p < 0.05) than after narcoses with the laryngeal mask. Also after narcoses with the laryngeal mask, the average pain scores decreased quickly on the first and second postoperative days (5.1 +/- 9.0 and 0.2 +/- 1.4). There were no differences regarding sore throats between narcoses with the laryngeal mask or intubation on these two postoperative days. Using both anaesthesiological methods, sore throat was not related to duration of anaesthesia or the experience of the anaesthetist.

Adolescent↗