Search PubMed⌕ Search

Biomedical subjects

Friedrich P Paulsen

Publications and source records attributed to Friedrich P Paulsen.

At least 19 recordsLinked to original sources
PubMed2007

MUC16 in the lacrimal apparatus.

The aim of the present study was to determine the possible expression of the mucin MUC16 in the lacrimal apparatus. Expression and distribution of MUC16 in lacrimal gland, accessory lacrimal glands, and nasolacrimal ducts was monitored by RT-PCR and immunohistochemistry. MUC16 was expressed and detected in all tissues investigated. Comparable to conjunctiva and cornea it was membrane-anchored in accessory lacrimal glands whereas in lacrimal gland acinar cells and columnar cells of the nasolacrimal ducts it was stored in intracytoplasmic vesicles without membrane-association. Subepithelial serous glands of the nasolacrimal ducts revealed staining of the secretion product. Intracelluar production of MUC16 is present in lacrimal gland and epithelial cells of the nasolacrimal ducts but it is not clear whether this MUC16 is secreted. MUC16 seems to be shedded or secreted from the epithelial surface of subepithelial serous glands of the nasolacrimal ducts. Our results show that MUC16 is present in the whole lacrimal apparatus. Its distribution pattern suggests different physiological functions with regard to tear film physiology and tear outflow. Moreover, the results demonstrate the existence of so far not recognized qualitative differences in the secretion product of main lacrimal gland and accessory lacrimal glands (glands of Krause).

Aged↗
PubMed2006

Mucins and TFF peptides of the tear film and lacrimal apparatus.

The three-dimensional organization of the tear film, which is produced and drained by the different structures of the ocular adnexa, is essential for maintainance and protection of the ocular surface. This is facilitated by a class of large, highly glycosylated, hydrophilic glycoproteins, the mucins, which are usually expressed in association with a class of peptides having a well-defined, structurally conserved trefoil domain, the mammalian trefoil factor family (TFF) peptides. In this review, the latest information regarding mucin and TFF peptide function and regulation in the human lacrimal system, the tear film and the ocular surface is summarized with regard to mucous epithelia integrity, rheological and antimicrobial properties of the tear film and tear outflow, age-related changes and certain disease states such as dry eye, dacryostenosis and dacryolith formation.

Aging↗
PubMed2006

TFF peptides and mucins are major components of dacryoliths.

PURPOSE: The study was performed to determine whether trefoil factor peptides (TFF) and/or mucins are components of dacryoliths and to gain further insight into dacryolith composition and formation. METHODS: Twenty dacryoliths found in lacrimal surgery in patients suffering from primary acquired nasolacrimal duct obstruction were analyzed for the presence of TFF peptides (TFF1, 2, 3), mucins (MUC1, 2, 3, 4, 5AC, 5B, 6, 7, 8), defense cells (T- and B lymphocytes, macrophages, neutrophils), and antimicrobial substances (alpha defensins 1-3, secretory phospholipase A(2)) by means of light microscopy, histochemistry, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. RESULTS: All dacryoliths except one revealed clear immunoreactivity for all three TFF peptides. The immunohistochemical distribution of mucins was inhomogeneous throughout the different dacryoliths. However, in some dacryoliths all mucins investigated were detected. MUC8 showed reactivity in 14 out of 15 dacryoliths analyzed by immunohistochemistry. Most dacryoliths contained alpha defensins 1-3 as the secretory product of neutrophils. T and B lymphocytes, macrophages and secretory phospholipase A(2) were only present in single dacryoliths. Quantification of TFF peptide expression supported the immunohistochemical finding that all three TFF peptides are augmented in dacryoliths. CONCLUSIONS: Dacryoliths consist partly of secreted mucins comparable with the mucin spectrum of the epithelium of healthy nasolacrimal ducts. Beside TFF1 and TFF3, both of which are produced under healthy circumstances, TFF2 is additionally induced and secreted in cases of dacryolithiasis. All three TFF peptides appear to be augmented in dacryoliths. With regard to their rheologic properties, TFF peptides may play a functional role in dacryolith formation. However, our results raise the question of whether TFF peptides per se influence dacryolith formation or whether their secretion, as in secretion of mucins and alpha defensins 1-3, is merely a secondary phenomenon.

Adult↗
PubMed2006

Prognostic value of mucins in the classification of ampullary carcinomas.

The ampulla of Vater is of high clinical relevance with regard to influx of chyme, ascending inflammation, intubation during diagnostic and therapeutic endoscopic investigation, therapeutic papillotomy, and especially to malignant transformation. Little is known about the distribution of mucins in the ampulla. In this study, we have investigated the mucin distribution in the normal ampulla of Vater and compared it to duodenal mucosa and Brunner glands. Expression of mucins in the ampulla of Vater and duodenum was monitored by reverse transcription-polymerase chain reaction and localization of the products by immunohistochemistry. The samples investigated originated from 30 autopsy cases. Mucins MUC1, MUC3, MUC4, MUC5AC, MUC5B, MUC6, MUC7, and MUC8 were expressed in the ampulla of Vater. Immunohistochemistry revealed production of MUC4, MUC5AC, MUC5B, and MUC6. The mucin composition varied in comparison with the duodenum referring to MUC2, MUC7, and MUC8. Detected mucins contribute to innate immunity, epithelial restitution, and protection against the aggressive secretions of the liver, gall bladder, and pancreas. By cross-linking, they influence the rheological properties of the secretions in the ampulla and facilitate unidirectional flow into the duodenum. Knowledge of their pattern of expression has prognostic value with regard to the detection of malignancy. The observed differences in the mucin distribution between the duodenum and the ampulla of Vater support the use of MUC2, MUC7, and MUC8 as useful tool in the classification of ampullary carcinomas.

Adult↗
PubMed2005

Differential expression of vascular endothelial growth factor implies the limbal origin of pterygia.

OBJECTIVE: To study the distribution of isoforms of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 in pterygia and to compare it with that in healthy conjunctivas. DESIGN: Nonrandomized comparative (cadaver controlled) study with histopathologic correlations. METHODS: Tissue specimens from 75 patients treated for primary pterygia were analyzed using immunohistochemical studies as well as different molecular biological examinations. Healthy conjunctivas from 33 patients treated for cataracts as well as specimens from the conjunctiva, limbus, and lens of both eyes of 12 body donors served as controls. TESTING: Surgical specimens of pterygia and normal conjunctiva specimens were processed with paraffin, sectioned, stained using specific antibodies against VEGF and its receptors, and examined by light microscopy. The other part of both groups of specimens as well as specimens from body donors were prepared and analyzed by means of reverse-transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, enzyme-linked immunosorbent assay, and Western blots. MAIN OUTCOME PARAMETERS: Vascular endothelial growth factor and VEGFR1 and VEGFR2 were analyzed to indentify the splice variants of VEGF as well as the distribution and amount of VEGF and both receptors in pterygia and the control tissues. RESULTS: In analysis of specimens from pterygium patients as well as normal conjunctivas, VEGF121 and VEGF165 were identified as the only VEGF splice forms expressed. In addition to VEGF, VEGFR1 and VEGFR2 were detected in pterygia and conjunctivas and immunostained within the epithelium of pterygia and conjunctivas and on intrapterygial and intraconjunctival endothelial cells. Levels of VEGFR1 and VEGFR2 mRNA were lower in pterygia than in conjunctivas but similar in limbal and pterygium samples. Vascular endothelial growth factor levels were higher in pterygia than in conjunctivas, but were similar in the limbus and pterygia. CONCLUSIONS: The results reveal similar behaviors in limbal and pterygium epithelial cells in terms of VEGF and VEGFR expression, with the presumption that pterygia arise from limbal epithelial cells and that human conjunctivas are not a suitable control for the analysis of pterygia. Moreover, the results suggest that VEGF might play an active role in the physiology of conjunctival epithelial cells.

Blotting, Western↗
PubMed2004

Production of endogenous antibiotics in articular cartilage.

OBJECTIVE: Defensins are broad-spectrum antimicrobial peptides that are components of innate immunity. To date, only epithelial surfaces and blood cells have been shown to produce these cationic peptides in bactericidal concentrations when challenged with microorganisms or inflammatory cytokines. Infections caused by gram-negative pathogens occur only infrequently in association with joint surgery. The present study was undertaken to investigate whether this may be explained by intraarticular production of gram-negative-specialized antimicrobial peptides. METHODS: Healthy articular cartilage and cultured T/C-28a2 chondrocytes were assessed, by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, for expression of various antimicrobial peptides. The expression of human beta-defensin 2 (HBD-2) was studied in cultured chondrocytes after exposure to bacterial supernatants and proinflammatory cytokines and was assayed by real-time RT-PCR and immunoblot analysis. A septic arthritis mouse model was used to investigate the regulation of the murine homolog of HBD-2 in articular cartilage after bacterial inoculation. RESULTS: Healthy articular cartilage and T/C-28a2 chondrocytes were able to produce different antimicrobial peptides. After exposure to gram-negative bacteria and proinflammatory cytokines, expression of cartilage-derived HBD-2 strongly increased. Immunoblot analysis revealed up-regulation of the gram-negative-specialized HBD-2 in microbicidal doses. Immunohistochemistry analysis revealed induction of the murine homolog of HBD-2 in vivo after intraarticular injection of bacteria. CONCLUSION: This study demonstrated a previously unrecognized function of human chondrocytes. In addition to its biomechanical properties, articular cartilage has the ability to produce antimicrobial substances when challenged with microorganisms. The expression of HBD-2 in microbicidal doses suggests that antimicrobial peptides may contribute to host defense mechanisms in articular joints.

Adult↗
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↗
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↗
PubMed2003

Loss of tear duct-associated lymphoid tissue in association with the scarring of symptomatic dacryostenosis.

OBJECTIVE: To determine whether organized mucosa-associated lymphoid tissue (MALT) is a normal component of the human efferent tear ducts or is acquired in reaction to chronic inflammation. DESIGN: Nonrandomized comparative (cadaver controlled) study with histopathologic correlations. MATERIALS: Tissue specimens from nasolacrimal ducts of 38 patients undergoing endonasal dacryocystorhinostomy in postinflammatory dacryostenosis with signs of chronic inflammation were analyzed using histologic examination and immunohistochemical studies. Only tissue specimens revealing proliferative sclerotic forms of chronic fibrosis were chosen for the study. Eighty specimens from the lacrimal systems of body donors served as controls. TESTING: Tissue specimens from each lacrimal system were prepared and processed with paraffin, sectioned, stained using different histologic methods with an array of specific antibodies, and examined by light microscopy. MAIN OUTCOME PARAMETERS: The distribution of intraepithelial and subepithelial defense cells was analyzed to identify plasma cells, secretory immunoglobulins, lymphocytes, dendritic cells, and organized mucosa-associated lymphoid tissue. RESULTS: The presence of secretory immunoglobulin A was demonstrated in subepithelial plasma cells and in the cytoplasm of apical epithelial cells in both chronically inflamed and healthy lacrimal systems. In more than one third of cases from body donors, but in only a few biopsy specimens from patients, organized lymphoid tissue was found with the cytomorphologic and immunophenotypical features of MALT. All other cases showed a diffuse infiltrate of defense cells within the lamina propria. CONCLUSIONS: The development of tear duct-associated lymphoid tissue (TALT) is a common feature that is often found in symptomatically normal nasolacrimal ducts. Because TALT seems to be lost associated with the scarring of symptomatic dacryostenosis, it is unlikely that the presence per se of TALT leads to scarring. Future studies are needed to explain the development of TALT.

Adult↗
PubMed2003

Drainage of tears: impact on the ocular surface and lacrimal system.

The human efferent tear ducts are part of the lacrimal system. Because little knowledge exists concerning the physiology of the nasolacrimal system, and hence its patho- physiology, the nasolacrimal system has received almost no consideration as a possible factor in dry eye. The human nasolacrimal ducts consist of the upper and the lower lacrimal canaliculus, the lacrimal sac, and the nasolacrimal duct. As a draining and secretory system, the efferent tear ducts play a role in tear transport and nonspecific immune defense. Moreover, components of tear fluid are absorbed in the nasolacrimal passage and are transported into a surrounding vascular system. This system is similar to a cavernous body that is subject to autonomic control and regulates tear outflow. Tear duct-associated lymphoid tissue (TALT) is present in the efferent tear ducts, displaying the cytomorphological and immunophenotypic features of mucosa-associated lymphoid tissue (MALT). Under normal conditions, tear fluid components are constantly absorbed into the blood vessels of the surrounding cavernous body. These vessels are connected to the blood vessels of the outer eye and could act as a feedback signal for tear fluid production, which ceases if these tear components are not absorbed. In this way, dry eye could be initiated. Defective stimulation of TALT could result in abnormal immune deviation at the ocular surface, leading to an autoimmunological response that causes dry eye pathology.

Journal Article↗
PubMed2003

Characterization of mucins in human lacrimal sac and nasolacrimal duct.

PURPOSE: Mucins are polymers that may reduce drag and enhance tear outflow. Mucin expression and distribution in human efferent tear ducts were tested in the physiological state, and potential differences in the expression pattern were investigated in the presence of primary acquired dacryostenosis (PANDO). METHODS: Expression of mucins in human lacrimal sac and nasolacrimal ducts was monitored by reverse transcription-polymerase chain reaction analysis. The presence and distribution of MUC1, -2, -4, -5AC, -5B, -6, and -7 in epithelia of the efferent tear duct passage are assessed with antisera to mucin peptide cores. Twenty normal tissues from cadavers and surgical specimens from 20 patients with PANDO were tested. RESULTS: mRNAs for all mucins investigated were detected in healthy human lacrimal sacs and nasolacrimal ducts. MUC6 mRNA was detected in only about half of the investigated samples. A reduced level of MUC2, -5AC, and -5B mRNAs was observed in PANDO. Immunohistochemistry revealed MUC2 in goblet cells and single epithelial cells. Both MUC5AC and -5B were detected in goblet cells forming intraepithelial mucous glands. MUC7 was present only in columnar epithelial cells of the efferent tear duct system. No immunoreactivity was observed with antibodies against MUC1, -4, and -6 peptide cores. CONCLUSIONS: Human efferent tear ducts express and produce a broad spectrum of mucins that is partly comparable with that in the conjunctiva and the salivary glands. The mucin diversity of the efferent tear ducts could enhance tear transport and antimicrobial defense. Reduced levels of mucin mRNA in a nonfunctioning though patent segment of the lacrimal passage, which is associated with epiphora, suggests that mucins ease tear flow through the efferent tear ducts.

Adult↗
PubMed2003

The cavernous body of the human efferent tear ducts contributes to regulation of tear outflow.

PURPOSE: To test the hypothesis that the surrounding vascular plexus of the lacrimal sac and the nasolacrimal duct contributes to the regulation of tear outflow. METHODS: Experiments in 30 probands aged between 15 and 37 years were performed in both nasolacrimal systems of each subject by observing with an endoscope the transit time of an applied tear drop containing fluorescein dye until its entry into the inferior meatus of the nose. Four different experiments were performed to determine the median transit time under normal conditions and the influence on transit time of a decongestant drug, a foreign body on the ocular surface, and a decongestant drug applied together with a foreign body on the ocular surface. Comparisons were made between the right and left nasolacrimal system, in males and females, eyeglass wearers and non-eyeglass wearers, and the different experiments and the results statistically analyzed. RESULTS: The tear transit time was independent of side (right or left), gender, or eyeglass wear. It showed great individual variability. Application of a decongestant drug or placement of a foreign body on the ocular surface both prolonged the dye transit time significantly. Application of a decongestant drug simultaneously with placement of a foreign body shortened the dye transit time significantly compared with the effect of the decongestant drug alone but revealed no significant difference compared with application of a foreign body alone. CONCLUSIONS: The cavernous body of the lacrimal sac and nasolacrimal duct plays an important role in the physiology of tear outflow regulation. It is subject to autonomic control and is integrated into a complex neuronal reflex feedback mechanism starting with the dense innervation of the cornea. Moreover, its function can be pharmacologically influenced.

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

Impact of vocal cord paralysis on cricoarytenoid joint.

To demonstrate structural changes in the cricoarytenoid joint after recurrent laryngeal nerve paralysis, we performed a laboratory investigation of fixed arytenoid cartilages from adult humans obtained during laser surgical arytenoidectomy in cases of bilateral vocal fold paralysis, analyzing the articular cartilage, the joint capsule, and the attached laryngeal musculature. Ten arytenoid cartilages from adult humans were studied by means of histology, as well as scanning and transmission electron microscopy. After long-standing denervation (>6 months), all arytenoid cartilages showed degenerative changes in their joint surface structure at various levels of intensity. The articular surface revealed fibrillation in some places, demasking of collagen fibrils next to the joint surface, and formation of chondrocyte clusters near the joint surface. All specimens also showed muscle atrophy. We conclude that long-standing recurrent laryngeal nerve paralysis does not result in ankylosis of the cricoarytenoid joint, as assumed, but the articular cartilage undergoes structural changes comparable to those in osteoarthritis. Structural changes in the articular cartilage and in the surrounding musculature hamper efforts at joint function recovery, as do procedures aiming solely at either medialization or lateralization of the vocal fold.

Adolescent↗
PubMed2002

Animal model for the absorption of lipophilic substances from tear fluid by the epithelium of the nasolacrimal ducts.

PURPOSE: To compare the nasolacrimal tissues of several species to see how closely they resemble the human and to measure nasolacrimal absorption of a substance, to show that an absorption pathway exists for substances placed in the external eye, other than directly through the cornea or conjunctiva. METHODS: The nasolacrimal systems of six different vertebrates were investigated by light microscopy to find a species with a nasolacrimal system comparable to that of humans, for use in absorption experiments. In addition to primates, rabbits were revealed by histology to have a lacrimal system closely comparable to that of humans. The rabbit lacrimal system had a stratified epithelium consisting of two layers. Subepithelially, the lamina propria was composed of two strata: loose connective tissue containing elastic fibers and lymphatic cells and a rich venous plexus comparable to a cavernous body. Rabbits were therefore chosen for the absorption experiments. (3)H-cortisol was dropped into the eyes of female rabbits. After 21, 43, or 146 minutes, the rabbits were killed, the blood collected, and the nasolacrimal systems prepared and embedded for histologic examination. Serum was obtained from the clotted blood, and radioactivity was counted. Autoradiographs of sections of rabbit nasolacrimal duct were also prepared. RESULTS: Uptake of radioactivity into the serum was high and increased with time. After 21 minutes, maximum incorporation of the applied radioactivity into the blood the level was 7.1%; after 43 minutes, 12.4%; and after 146 minutes, 15.5%. Transport of radioactivity was visualized in autoradiographs of rabbit nasolacrimal systems. CONCLUSIONS: (3)H-cortisol is incorporated from the nasolacrimal ducts into the blood of rabbits. The comparable morphology of rabbits and humans suggests that absorption of cortisol would also take place in humans. Future investigations of the nasolacrimal passage are needed to understand whether absorption of normal tear fluid components in the nasolacrimal ducts is a physiological function that also plays a role in pathologic conditions such as dry eye. The similarities between rabbit and human nasolacrimal ducts support the use of the rabbit for such studies.

Absorption↗