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Biomedical subjects

K Wassermann

Publications and source records attributed to K Wassermann.

At least 19 recordsLinked to original sources
PubMed2006

Modification of surface antigens in blood CD8+ T-lymphocytes in COPD: effects of smoking.

In contrast to the effects of cigarette smoke on T-lymphocyte subsets in the airways, it has not yet been determined whether smoking has immunomodulatory effects on surface antigens of peripheral blood T-lymphocytes and, if that is the case, whether these effects differ in smokers with and without chronic obstructive pulmonary disease (COPD). The present authors have, therefore, examined the expression of the surface activation marker CD28, the levels of cytotoxic effector lymphocytes (CD27-/CD45RA+) and the expression of the lung type (Tc)1-specific chemokine receptor CXCR(3)+ on peripheral blood CD8+ T-lymphocytes. The present authors have also studied the chemotactic activity of CD8+ T-lymphocytes on monocyte chemotactic protein (MCP)-1 and compared 13 nonsmoking controls, 12 smokers with COPD and 14 smokers without airflow limitation. There was a decrease in the total count of CD8+ T-cells and an increase in the CD4+/CD8+ ratio in smokers with COPD compared with smokers without COPD and controls. Expression of the Tc1-specific chemokine receptor CXCR(3)+ by CD8+ T-cells was increased in smokers with COPD compared with smokers without COPD and controls. The expression of activated and of cytotoxic effector CD8+ T-cells in smokers with and without COPD showed an increase compared with controls. CD8+ T-cells from smokers with and without COPD showed a decrease in chemotactic activity to MCP-1 compared with controls. In conclusion, chronic obstructive pulmonary disease may be a systemic immunomodulatory disease associated with the modification of surface antigens in blood CD8+ T-lymphocytes.

Antigens, CD↗
PubMed2004

[Long-term effects of sildenafil in a patient with scleroderma-associated pulmonary hypertension and Raynaud's syndrome].

HISTORY: A 65-year-old woman was admitted because of dyspnea at rest and peripheral edema due to scleroderma-associated pulmonary fibrosis and hypertension, as well as Raynaud's phenomenon. DIAGNOSTIC FEATURES, TREATMENT AND COURSE: She had a marked restrictive ventilatory disorder with severe impairment of diffusion capacity. Right heart catheterization demonstrated a mean pulmonary artery pressure of 50 mmHg. She was able to walk only 220 m. All usual methods of treatment failed to give satisfactory results so that sildenafil (phospherodiesterase type-5 |PDE-5| inhibitor; Viagra ((R)) was given, even though it is not licensed for this indications ("off-label", as a therapeutic attempt. This achieved definite reduction in pulmonary arterial pressure and significantly improved the clinical symptoms. In particular, it drastically reduced the level of atrial natriuretic peptide, an important prognostic marker in right heart failure. Sildenafil also significantly raised peripheral perfusion and the signs of Raynaud's syndrome. CONCLUSION: PDE-5 inhibitors are efficacious in scleroderma-associated pulmonary hypertension and may also provide a new option in the treatment of Raynaud's disease.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Effect of smoking on MAP kinase-induced modulation of IL-8 in human alveolar macrophages.

Inflammatory cytokine production by alveolar macrophages (AMs) is regulated by transcriptional activation and may be increased by cigarette smoking. The smoking-induced regulation of interleukin (IL)-8 by extracellular signal-regulated kinase (ERK)-1 and -2, p38 mitogen-activated protein kinase (MAPK) and the transcription factor nuclear factor-kappaB (NF-kappaB) in lipopolysaccharide-stimulated AMs was assessed in nine smokers compared with nine healthy nonsmokers. IL-8 production was dependent on phosphorylation of ERK-1 and -2 and p38 MAPK, as examined by PD 098059 (10 microM), an inhibitor of the upstream activator of MAPK kinase (MKK)-1, and SB 203580 (10 microM), an inhibitor of p38 MAPK. IL-8 release and the inhibitory effect of PD 098059 were increased in AMs from smokers. Moreover, ERK-2 messenger ribonucleic acid expression, as examined by reverse transcriptase polymerase chain reaction and phosphorylation of ERK-2 using Western blots, were increased in AMs from smokers, indicating a smoking-induced modulatory role of ERK-1 and -2. Lipopolysaccharide-induced IL-8 production was dependent on activation of NF-kappaB, as examined by SN 50 (100 microM), an inhibitor of NF-kappaB translocation, and the specific NF-kappaB inhibitor kinase-2 inhibitor, AS 602868 (10 microM), with no differences in AMs from smokers and nonsmokers. SN 50 but not PD 098059 and SB 203580 blocked NF-kappaB deoxyribonucleic acid-binding, and this occurred to the same extent in AMs from smokers and nonsmokers, as examined by electromobility shift assay. It is concluded that cigarette smoking enhances mitogen-activated protein kinase activation more than nuclear factor-kappaB activation to increase lipopolysaccharide-induced interleukin-8 production in alveolar macrophages.

Adult↗
PubMed2003

Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-alpha agonists.

Peroxisome proliferator activated receptor (PPAR)-alpha controls the expression of multiple genes involved in lipid metabolism, and activators of PPAR-alpha, such as fibrates, are commonly used drugs in the treatment of hypertriglyceridemia and other dyslipidemic states. Recent data have also suggested a role for PPAR-alpha in insulin resistance and glucose homeostasis. In the present study, we have assessed the transcriptional and physiological responses to PPAR-alpha activation in a diet-induced rat model of insulin resistance. The two PPAR-alpha activators, fenofibrate and Wy-14643, were dosed at different concentrations in high-fat fed Sprague-Dawley rats, and the transcriptional responses were examined in liver using cDNA microarrays. In these analyses, 98 genes were identified as being regulated by both compounds. From this pool of genes, 27 correlated to the observed effect on plasma insulin, including PPAR-alpha itself and the leukocyte antigen-related protein tyrosine phosphatase (PTP-LAR). PTP-LAR was downregulated by both compounds, and showed upregulation as a result of the high-fat feeding. This regulation was also observed at the protein level. Furthermore, downregulation of PTP-LAR by fenofibric acid was demonstrated in rat FaO hepatoma cells in vitro, indicating that the observed regulation of PTP-LAR by fenofibrate and Wy-14643 in vivo is mediated as a direct effect of the PPAR agonists on the hepatocytes. PTP-LAR is one of the first genes involved in insulin receptor signaling to be shown to be regulated by PPAR-alpha agonists. These data suggest that factors apart from skeletal muscle lipid supply may influence PPAR-alpha-mediated amelioration of insulin resistance.

Animals↗
PubMed2001

Large cluster formation through multiple substitution with lanthanide cations (La, Ce, Nd, Sm, Eu, and Gd) of the polyoxoanion.

Several new large polyoxotungstates have been synthesized by reaction of lanthanide cations with the well-known "As(4)W(40)" anion, [(B-alpha-AsO(3)W(9)O(30))(4)(WO(2))(4)](28-) (1). The heteropolyanions [(H(2)O)(11)Ln(III)(Ln(III)(2)OH)(B-alpha-AsO(3)W(9)O(30))(4)(WO(2))(4)](20)(-) (Ln = Ce, Nd, Sm, Gd) (2-4) (Ln(3)As(4)W(40)) and [M(m)()(H(2)O)(10)(Ln(III)(2)OH)(2)(B-alpha-AsO(3)W(9)O(30))(4)(WO(2))(4)]((18-m)(-)) (Ln = La, Ce, Gd and M = Ba, K, none) (5-7) (Ln(4)As(4)W(40)) have been isolated as alkali metal and ammonium salts, respectively, and characterized by single-crystal X-ray analysis, elemental analysis, and IR and (183)W-NMR spectroscopy. The X-ray analyses revealed interanionic W-O-Ln bonds between adjacent Ln(x)()As(4)W(40) units forming a "dimer" for x = 3 and chains for x = 4. Upon dissolving in water these bonds hydrolyze and the monomeric species form. The straightforward syntheses which require the use of concentrated NaCl solutions (1-4 M) and the addition of stoichiometric amounts of Ba(2+) or K(+) reemphasize the importance of the presence of appropriate countercations for the assembly of large polyoxometalate structures.

Journal Article↗
PubMed2001

Estrogen modulates estrogen receptor alpha and beta expression, osteogenic activity, and apoptosis in mesenchymal stem cells (MSCs) of osteoporotic mice.

In the mouse, ovariectomy (OVX) leads to significant reductions in cancellous bone volume while estrogen (17beta-estradiol, E2) replacement not only prevents bone loss but can increase bone formation. As the E2-dependent increase in bone formation would require the proliferation and differentiation of osteoblast precursors, we hypothesized that E2 regulates mesenchymal stem cells (MSCs) activity in mouse bone marrow. We therefore investigated proliferation, differentiation, apoptosis, and estrogen receptor (ER) alpha and beta expression of primary culture MSCs isolated from OVX and sham-operated mice. MSCs, treated in vitro with 10(-7) M E2, displayed a significant increase in ERalpha mRNA and protein expression as well as alkaline phosphatase (ALP) activity and proliferation rate. In contrast, E2 treatment resulted in a decrease in ERbeta mRNA and protein expression as well as apoptosis in both OVX and sham mice. E2 up-regulated the mRNA expression of osteogenic genes for ALP, collagen I, TGF-beta1, BMP-2, and cbfa1 in MSCs. In a comparison of the relative mRNA expression and protein levels for two ER isoforms, ERalpha was the predominant form expressed in MSCs obtained from both OVX and sham-operated mice. Cumulatively, these results indicate that estrogen in vitro directly augments the proliferation and differentiation, ERalpha expression, osteogenic gene expression and, inhibits apoptosis and ERbeta expression in MSCs obtained from OVX and sham-operated mice. Co-expression of ERalpha, but not ERbeta, and osteogenic differentiation markers might indicate that ERalpha function as an activator and ERbeta function as a repressor in the osteogenic differentiation in MSCs. These results suggest that mouse MSCs are anabolic targets of estrogen action, via ERalpha activation. J. Cell. Biochem. Suppl. 36: 144-155, 2001.

Alkaline Phosphatase↗
PubMed2001

[Unilateral and bilateral recurrence of inferior laryngeal nerve paralysis].

Unilateral recurrent nerve paralysis leads to glottic insufficiency, causing a significant lack of vocal ability. In contrast, bilateral palsies present with stridor on inspiration due to glottic stenosis. Most of the underlying lesions are iatrogenic, with thyroid surgery being the single most important causative factor. However, a variety of different reasons can lead to such a condition. Whenever aetiology is uncertain a complete diagnostic work-up is mandatory. Indirect laryngoscopy confirms the diagnosis. Laryngeal electromyography is of great value because it differentiates between paralysis and ankylosis of the cricoarytaenoid joint. Moreover, in many cases laryngeal electromyography provides a reliable prognosis of clinical outcome. While unfavorable results can be predicted with high accuracy, correct prognosis of complete recovery is more difficult. Speech therapy is the treatment of choice in case of unilateral recurrent nerve palsy. Only if a significant glottal gap persists medialization procedures may become useful for voice improvement. Endoscopic as well as open approaches are available for this purpose. Bilateral recurrent nerve palsies need to be addressed surgically in the vast majority of cases. Today, a variety of endoscopic techniques for widening the glottic airway are available. Compared to permanent tracheostomy these procedures have much less impact on the patient's quality of life and should be preferred whenever possible. Inevitably, voice quality is traded for airway normalisation. However, modern surgical techniques accomplish very tolerable phonatory results.

Functional Laterality↗
PubMed2001

Chemokines and interleukin-18 are up-regulated in bronchoalveolar lavage fluid but not in serum of septic surgical ICU patients.

Our objective was to investigate the levels of chemokines (MIP1-alpha, MCP-1, and Gro-alpha), Interleukin-18 (IL-18), and Interleukin (IL-6) in bronchoalveolar lavage (BAL) fluid and serum at the onset and ongoing states of sepsis as defined by the American College of Chest Physicians/Society of Critical Care Medicine in septic surgical ICU patients. Our summary background data was to understand the significance of compartmentalized inflammatory mediator production in an immunologically active organ (lung) in comparison with levels in the systemic circulation. The study group consisted of 20 septic patients and 10 non-septic patients on surgical ICU. At the onset of sepsis, both BAL fluid and serum samples were taken and levels of MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 were measured by ELISA. Furthermore, over a subsequent 8-day period, levels of these mediators were determined in serum. In some experiments, IL-18 mRNA levels were determined in peripheral blood lymphocytes (PBL) of septic and non-septic patients. At the onset of sepsis, MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 levels were significantly up-regulated in BAL fluid as compared with non-septic controls. In marked contrast, with the exception of IL-18 mRNA and IL-6 peptide, there was no increase in serum levels of inflammatory mediators determined both at the onset and during the ongoing states of sepsis. Based on the present data, monitoring levels of serum chemokines and IL-18 protein as markers of sepsis might be misleading since despite their non-detection in serum, they were highly up-regulated in the lung tissue compartment. These data might underscore the role of MIP-1alpha, MCP-1, GRO-alpha, and IL-18 in the mediation of local tissue damage. Furthermore, these findings raise the notion that mediator measurement in immunologically active organs might serve as pivotal indicators of sepsis prior to the actual fulfillment of specific clinical criteria that defines the patient as being septic.

Bronchoalveolar Lavage Fluid↗
PubMed2001

Concurrent glottic and tracheal stenoses: restoration of airway continuity in end-stage malignant disease.

Six patients known to have inoperable esophageal carcinoma presented with stridor due to both malignant tracheal stenosis (with additional respiratory-digestive tract fistula in 2 patients) and bilateral vocal cord paralysis. Patency was restored by endotracheal stenting plus unilateral cordotomy. Four patients had immediate relief. Two patients required enlargement of the vocal cord incision. One of them declined reoperation and underwent tracheostomy. The stent function was uneventful, with no dislodgment or mucus impaction. The fistula seal was complete, with no aspiration through the newly shaped glottic orifice. The peak expiratory flow increased from 24.4% +/- 9.7% of predicted normal before the procedure to 40.5% +/- 13.7% after the procedure. Restoration of airway continuity in serial laryngotracheal stenoses by a combined approach is a feasible technique in end-stage cancer patients. It effectively relieves respiratory distress and ensures voice preservation. In addition, it may avoid the risks of tracheotomy.

Aged↗
PubMed2001

Atresia of the trachea following repeated percutaneous dilational tracheotomy.

Percutaneous dilational tracheotomy (PDT) and conventional tracheostomy are still competing methods to provide an airway for intensive care patients requiring assisted ventilation. Tracheal stenosis is a late complication for any tracheostomy and long-term intubation. However, late complications in PDT have not been extensively studied. This article is the first to report on total atresia of the subglottic larynx and cervical trachea after PDT. The dimension of the lesion is visualized by three-dimensional reconstructed CT scan. The etiology of this condition is discussed.

Dilatation↗
PubMed2000

Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor.

1-Ethyl-2-(4-hydroxyphenyl)pyrrolo[2,1,5-cd]indolizine (NNC 45-0095) is a novel compound which represents the parent pharmacophore structure of a series of pyrrolo[2,1,5-cd]indolizine derivatives with mixed estrogen agonist/antagonist properties. NNC 45-0095 binds with high affinity to the estrogen receptor (IC50=9.5 nM) and exhibits full protection of bone loss in the ovariectomized mouse model for post-menopausal osteoporosis.

Animals↗
PubMed2000

Malignant laryngotracheal obstruction: a way to treat serial stenoses of the upper airways.

BACKGROUND: Six patients known to have inoperable esophageal carcinoma presented with stridor due to both malignant tracheal stenosis (n = 6) and bilateral vocal cord paralysis. Two patients also had respiratory-digestive fistula. METHODS: Patency was restored by endotracheal stenting plus unilateral cordectomy. Four patients had immediate relief. Two patients required enlargement of the cord incision. One of them declined reoperation and underwent tracheotomy. RESULTS: Stent function was uneventful. There was no dislodgement or mucous impaction. Fistula seal was complete. There was no aspiration through the new-shaped glottic orifice. Peak expiratory flow increased from 24.4% +/- 9.7% predicted normal before to 40.5% +/- 13.7% after the procedure, whereas the dyspnea score decreased from 74.2 +/- 12.7 to 24.2 +/- 14.0. CONCLUSIONS: Restoration of airway continuity in serial laryngotracheal stenoses using a combined approach is a feasible technique in end-stage cancer patients. It effectively relieves respiratory distress and ensures voice preservation. In addition, it may avoid the risks of tracheotomy.

Aged↗
PubMed2000

Sensitivity to nitrogen mustard relates to the ability of processing DNA damage in Chinese hamster ovary cells.

The hallmark of the excision repair pathways is the removal of DNA adducts by excision of the damaged nucleotides. In the course of repair, transient DNA strand breaks occur, which can be measured by the Comet assay. We have investigated the processing of DNA damage, mediated by nitrogen mustard, in wild-type AA8 Chinese hamster ovary cells, and in UV5, UV20 and UV41 DNA repair deficient cell lines. Whereas DNA repair could not be detected by unscheduled DNA synthesis at nitrogen mustard doses below 10 microM, processing of nitrogen mustard-mediated DNA damage was observed by the Comet assay at a 100-times lower concentration. Wild-type Chinese hamster ovary AA8 cells were able to process nitrogen mustard-mediated DNA damage within 4-24 hr depending on the dose of nitrogen mustard (0.1-10 microM). None of the repair-deficient cell lines was able to completely process the DNA damage induced by 10 microM nitrogen mustard. At nitrogen mustard doses that conferred 10% colony forming ability, the repair-deficient cells had an altered processing of nitrogen mustard-mediated DNA damage: In the AA8, UV20, and UV41 cells, the amplitude of strand breaks peaked early (within 4 hr), the level of strand breaks in the nitrogen mustard exposed UV20 and UV41 cells did not return to the baseline of the unexposed reference culture, and the peak in strand breaks in the UV5 cell line occurred after 4 hr. Our results indicate that the single cell gel electrophoresis (Comet) assay is suitable for assessing repair capability of DNA alkylations.

Alkylating Agents↗