Biomedical subjects

Philipp Steven

Publications and source records attributed to Philipp Steven.

6 recordsLinked to original sources

PubMed2004

VEGF expression in adult permanent thyroid cartilage: implications for lack of cartilage ossification.

Vascular endothelial growth factor (VEGF) has been shown to play an important role during endochondral bone formation in hypertrophic cartilage remodeling, ossification, and angiogenesis, but it is not expressed in normal adult articular cartilage. Thyroid cartilage undergoes only partial ossification beginning at the age of about 20. Because it never completely ossifies, we investigated a possible role of VEGF and its receptors (VEGFRs) as well as the angiogenetic inhibitor endostatin in this permanent cartilage. In analysis of cartilage samples from all specimens evaluated, VEGF121 and VEGF165 were identified as the only VEGF splice forms expressed. In addition to VEGF, VEGFR-2 (kinase domain region/fetal liver kinase 1), but not VEGFR-1 (fms-like tyrosine kinase 1), was detectable by RT-PCR in cartilage. However, VEGFR-2 expression was only detectable up to the age of 19 years. Deposition of VEGF and VEGFR was confirmed by immunohistochemistry. VEGF concentrations measured by ELISA in thyroid cartilage increased with age in males but decreased in females. Endostatin concentrations measured by ELISA in thyroid cartilage were three times lower than in articular cartilage and showed no change with age, either in females or males. VEGF was immunostained within the intra- and pericellular matrices of some but not all chondrocytes. Thus, apart from its production in hypertrophic chondrocytes of growth plates, VEGF is also produced in single chondrocytes of thyroid cartilage. The data allow us to speculate that thyroid cartilage persists in an embryological state until it has reached its final size. After reaching its final size at the end of the second decade, VEGFR-2 is downregulated and ossification starts in the posterior part of the thyroid cartilage, proceeding ventrally. Both proteins, VEGF121 and VEGF165, should contribute to this process. VEGF concentration is high and changes in an age-related and sex-specific manner. Therefore, we postulate that VEGF is at least one of the key factors that is important for the lifelong ossification in thyroid cartilage.

Base Sequence↗

PubMed2004

TFF peptides in the human false vocal folds of the larynx.

TFF peptides (formerly P domain peptides, trefoil factors) are typical secretory products of mucin-producing cells and are thought to influence the rheological properties of mucous gels. We investigated the localization of these peptides in the human false vocal folds of the larynx, also known as the ventricular folds or vestibular folds. An analysis of TFF peptide mRNA by RT-PCR and TFF protein by Western blot detected TFF1 and TFF3, but not TFF2. Immunohistochemistry revealed TFF1 to be associated with the secretory product of goblet cells and mucous parts of subepithelial seromucous glands. TFF3 occurred in columnar epithelial cells of the mucosa and in serous cells and excretory duct cells of seromucous glands. These peptides may play a role in the rheological function of mucus secreted onto the true vocal folds and are thus important constituents of vocal production.

Adult↗

PubMed2004

Aberrant lens fiber differentiation in anterior subcapsular cataract formation: a process dependent on reduced levels of Pax6.

PURPOSE: TGFbeta can induce development in lenses of opaque subcapsular fibrotic plaques that have many features of human subcapsular cataracts. To understand further the events associated with the onset and progression of TGFbeta-induced cataract, several different models for anterior subcapsular cataract (ASC) were used and characterized. METHODS: Anterior subcapsular plaques were induced in rat lenses cultured with TGFbeta and in transgenic mice overexpressing TGFbeta in the lens. ASC was also examined in lenses of mice haploinsufficient for Pax6, as well as in human biopsy specimens. Immunofluorescence and in situ hybridization labeling were used to examine changes in patterns of gene expression associated with cataract formation in these models. RESULTS: Examination of TGFbeta-induced cataract in transgenic mice established that the subcapsular plaques are composed of a heterogenous cell population: a population of myofibroblastic cells as well as a population of lens-fiber-like cells. Further support for phenotypic change comes from the observation that the cells in these plaques no longer expressed lens epithelial markers, such as Pax6 and Connexin43. Subsequent examination of human biopsy specimens of ASC, as well as lenses from Pax6-deficient mice, showed that the anterior subcapsular plaques in both cases were also composed of a heterogenous population of cells. In contrast, anterior subcapsular plaques that developed in vitro in response to TGFbeta did not have this same cellular heterogeneity, as no fiber-like cells were present. CONCLUSIONS: These findings suggest that in vivo, during TGFbeta-induced cataract formation, some lens epithelial cells transform into myofibroblastic cells, whereas others differentiate into fiber cells. As this pathologic change is accompanied by altered expression of genes characteristic of the normal lens epithelial cell phenotype and as lenses from Pax6-deficient mice exhibit development of anterior subcapsular plaques closely resembling those induced by TGFbeta in transgenic mice, the authors propose that a reduction in Pax6 levels may be essential for this pathologic process to progress. Furthermore, it is clear from these in vitro studies that TGFbeta alone cannot reproduce the same morphologic and molecular changes associated with ASC formation in vivo, indicating that additional molecule(s) in the eye are important in this process.

Actins↗

PubMed2003

Region-specific immunological response of the different laryngeal compartments: significance of larynx-associated lymphoid tissue.

The occurrence of primary extranodal marginal-zone B-cell lymphoma [of the mucosa-associated lymphoid tissue (MALT) type] has only been described in the supraglottic region, implying that preexistent organized lymphoid tissue is present at that site only. To date, studies have not established clearly whether organized MALT shows a site-related distribution in the larynx. The supraglottic region of the false vocal folds and the subglottis from 87 unselected cadavers with no known history of nasal, oral, pharyngeal, laryngeal, tracheal, or esophageal disease were examined for the presence of organized MALT. Organized lymphoid tissue was found with the cytomorphological and immunophenotypic features of MALT in 100% of false vocal folds of children and in more than 90% of adolescents, decreasing to 7.1% in persons in their sixth decade, whereas MALT was completely absent in the subglottis in all age groups. The results explain why primary extranodal marginal-zone B-cell lymphoma has only been described in the supraglottic region but is absent in the subglottis. Moreover, the results suggest a region-specific immunological response of the different laryngeal areas as reflected in clinical observations and animal studies. However, the impact on presence or absence of laryngeal MALT awaits clarification.

Adolescent↗

PubMed2002

Upper airway epithelial structural changes in obstructive sleep-disordered breathing.

The etiology of upper airway collapsibility in patients with snoring and obstructive sleep apnea (OSA) remains unclear. Structural mucosal changes could be contributory factors. The objective of this study was to determine whether pathologic changes in the epithelium or the epithelial-connective tissue interface are present in patients with snoring and/or OSA by means of scanning electron microscopy and immunohistochemistry. Uvulae were obtained by uvulopalatopharyngoplasty from three patients with habitual snoring and nine patients with mild to severe OSA, as well as by dissection from 43 nonsnoring body donors. Scanning electron microscopy revealed structural changes in the epithelial-connective tissue boundary that significantly differed from age-related changes in the control subjects. The immunohistochemical staining with antibodies against epithelial cytokeratins showed differences in the expression pattern of cytokeratin 13 between patients and control subjects. No differences were found in the distribution pattern of laminin. Analysis of defense cells revealed a significant diffuse infiltration of leukocytes, mainly T cells, inside the lamina propria of the patient group, which was not observed in the control group. In conclusion, these results support the hypothesis that progressive structural changes in the mucosa caused by the trauma of snoring are a possible contributory factor to upper airway collapsibility.

Adult↗

PubMed2002

The human false vocal folds -- an analysis of antimicrobial defense mechanisms.

Inflammatory processes often lead to pathologic changes in the area of the larynx. A moistening function of the false vocal folds has been described frequently. Up to now we have little knowledge of the role of the false vocal folds in protection against pathogenic agents. The present study analyzes the structures of the false vocal folds in their relations to antimicrobial defense mechanisms. Investigations were performed on false vocal folds of larynges from 34 cadavers using histologic, histochemical and immunohistochemical methods. Seromucous glands, together with epithelial and goblet cells of the folds, synthesize a complex mucus layer. In all of the investigated samples this layer contains carbohydrates including N-acetyl-glucosamine, N-acetyl-galactosamine, galactose, mannose, fucose, and sialic acids. Furthermore, antimicrobial peptides like lactoferrin, lysozyme, alpha and beta defensins are also found in these structures. IgA, produced by plasma cells in the false vocal folds, is frequently integrated in the secretory product. Synthesized mucins, antimicrobial peptides and immunoglobulins form a specialized protective substance that is secreted mainly at the true vocal folds. Here the layer functions to lubricate the true vocal folds, resulting in positive functional consequences during vocal production. Moreover, together with immunocompetent cells, the protective layer seems to play a major role in antigen defense and prevents invasion of pathogenic agents.

Aged↗