Biomedical subjects

M Kasper

Publications and source records attributed to M Kasper.

At least 55 records · Page 3Linked to original sources

PubMed2000

Constipation and the use of laxatives: a comparison between transdermal fentanyl and oral morphine.

Constipation and the use of laxatives were investigated in patients with chronic cancer pain treated with oral morphine and transdermal fentanyl in an open sequential trial. Forty-six patients were treated with slow-release morphine 30-1000 mg/day for 6 days and 39 of these patients were switched to transdermal fentanyl 0.6-9.6 mg/day with a conversion ratio of 100:1. Median fentanyl doses increased from 1.2 to 3.0 mg/day throughout the 30-day transdermal treatment period. Twenty-three patients completed the study. Two patients died from the basic disease while treated with transdermal fentanyl, 12 patients were excluded for various reasons, and not enough data for evaluation were available for two patients. Mean pain intensity decreased slightly after conversion although the number of patients with breakthrough pain or requiring immediate-release morphine as a rescue medication was higher with transdermal fentanyl. The number of patients with bowel movements did not change after the opioid switch but the number of patients taking laxatives was reduced significantly from 78-87% of the patients per treatment day (morphine) to 22-48% (fentanyl). Lactulose was used mainly and was reduced most drastically, but other laxatives were also used less frequently. In this study transdermal fentanyl was associated with a significantly lower use of laxatives compared to oral morphine. The difference in the degree of constipation between the two analgesic regimens should be confirmed in a randomized double-blind study that takes into account both constipation and use of laxatives.

Administration, Cutaneous↗

PubMed2000

Cognitive impairment and its influence on pain and symptom assessment in a palliative care unit: development of a Minimal Documentation System.

Symptom assessment in the palliative care unit must consider the reduced physical and mental status of the patients. Standardized instruments are often not completed by patients with cognitive impairment. We tried to combine minimal burden for patients and staff with sufficient information content in a Minimal Documentation System (MIDOS) for pain and symptom assessment in palliative care patients. From January to July 1998, 108 patients (123 consecutive admissions) with a mean age of 63 years (range 32-87 years) were admitted to the palliative care unit. Pain was reported as the reason for admission in 70% of the patients, and 71% were treated with opioids. Using a cut-off point of 20/21, 35% of the patients were impaired in the Mini Mental State Examination (MMSE). The number of missing values in the Brief Pain Inventory (BPI) and the quality-of-life questionnaire SF-12 correlated highly with each other and with the MMSE sum score, but not with the summary scores of BPI or SF-12. Only 31 patients completed the SF-12 quality-of-life questionnaire. Age was not correlated to MMSE scores, and neither were opioid doses for 26 patients with slow-release oral morphine or for 20 patients with transdermal fentanyl. Only a minority of patients was able to use the numerical scale for symptoms other than pain, though most patients were able to score symptom intensity on the verbal categorical scale. Pain and symptom assessments were performed by the physician for 17% of the patients at admission, and for 16% of the follow-up controls because self-assessment was not possible. In this study, cognitive impairment prevented symptom assessment with longer and more complicated instruments such as the SF-12 in a large number of the patients admitted to the palliative care unit. Assessment instruments for patients with advanced disease must provide simple categorical scales and the possibility of being administered by interview.

Adult↗

PubMed1999

Experimental induction of AGEs in fetal L132 lung cells changes the level of intracellular cathepsin D.

The effect of the carbonyl compound glyoxal on the induction of advanced glycation end products (AGEs) in the fetal epithelial lung cells L132 was investigated using immunohistochemical, immunoelectron microscopic, and biochemical methods. It was found that glyoxal treatment resulted in morphological changes of the cells and in the membranous and cytosolic localization of AGEs such as methyl-glyoxal-derived compounds, N-(carboxymethyllysine) (CML) and imidazolone. The formation of AGEs was accompanied with a change in the intracellular expression of cathepsin D and a loss of enzymatic activity.

Antibodies↗

PubMed1999

Re: Alterations in cytokeratin expression by the alveolar lining epithelial cells in lung tissues from patients with idiopathic pulmonary fibrosis.

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Animals↗

PubMed1999

Differential immunolocalization of VEGF in rat and human adult lung, and in experimental rat lung fibrosis: light, fluorescence, and electron microscopy.

Vascular endothelial growth factor (VEGF) is a cytokine with main angiogenetic functions in embryonic development and tumor-formation. In the adult lung, reports of the localization of VEGF were controversial. A precise cell typing of VEGF-positive pulmonary cells is still lacking. Nothing is known about a potential role in pulmonary fibrosis. Immunohistochemistry (IH), double immunofluorescence microscopy (DIF), and immunoelectron microscopy (IEM) were used to study the differential distribution of VEGF in paraffin-embedded (IH, DIF) and in cryo-substituted, Lowicryl-embedded (IEM) specimens of normal rat and human lungs and fibrotic rat lungs. Fibrosis was induced by intratracheal bleomycin treatment. IH and DIF showed that VEGF was present in surfactant protein (SP) D-positive alveolar type II pneumocytes, bronchiolar Clara cells, smooth muscle (SM) cells, and alpha-SM actin-positive myofibroblasts of normal rat and human lungs. Fibrotic lesions in bleomycin-treated rat lungs were rich in VEGF-positive cells presenting with a heterogeneous phenotype (mainly SP-D-positive type II pneumocytes, alpha-SM actin-positive myofibroblasts). There were no signs of angiogenesis. Post-embedding immunogold labeling using protein A-gold and IgG-gold technique revealed a specific localization of VEGF to mitochondria, Clara cell secretory granules, and capillary interendothelial cell junctions. The predominant localization of VEGF to bronchiolar and alveolar epithelial and alpha-SM actin-positive cells, and the marked increase of VEGF-positive type II pneumocytes and myofibroblasts in fibrotic lung lesions, indicate that in adult lungs VEGF is involved in processes other than angiogenesis.

Adult↗

PubMed1999

Immunohistochemical investigations on the differentiation marker protein E11 in rat calvaria, calvaria cell culture and the osteoblastic cell line ROS 17/2.8.

Until now, many extracellular matrix proteins, e.g. osteopontin and osteonectin, have been used to determine a cell's osteogenic maturation. The disadvantage in evaluation of these proteins is their relative wide-ranging appearance throughout the osteogenic differentiation process. Thus, the aim of this study was to establish an immunohistochemical setup using E11, a marker that binds selectively to cells of the late osteogenic cell lineage. In addition, the histochemical expression of the bone matrix proteins osteonectin, osteopontin and fibronectin was compared to that of E11 using monoclonal antibodies. For light microscopical detection of osteogenic markers in cultured cells we developed a simple paraffin technique using a fibrin glue as embedding medium. This allows the handling of cultured cells such as a tissue sample and includes the use of stored biological specimens for further immunohistochemical experiments. We used newborn rat calvariae for whole tissue preparations and for isolation and cultivation of bone cells. In addition, we included the rat osteosarcoma cell line ROS 17/2.8 in this study. For the first time, we have localised E11 in osteocytes of rat calvaria preparations at the electron microscopical level. E11 was detected at plasma membranes of osteocytes and their processes, but not at those of osteoblasts. Accompanying experiments with cultured newborn rat calvaria cells and ROS 17/2.8 cells revealed E11 reactivity on a subset of cells. The results obtained confirm the suitability of the differentiation marker E11 as a sensitive instrument for the characterisation of bone cell culture systems.

Animals↗

PubMed1999

Characterisation of caveolins from cartilage: expression of caveolin-1, -2 and -3 in chondrocytes and in alginate cell culture of the rat tibia.

This study was performed to determine if rat articular chondrocytes express caveolin, the structural protein of caveolae, and to determine differences in the distribution of the caveolin subtypes 1, 2 and 3 in knee joints of newborn and adult rats. All three subtypes of caveolin were detected in adult cartilage by immunocytochemical staining. In newborn rats, only caveolin-1 was found in the hyaline cartilage. Caveolin-1, -2 and -3 messenger RNA and protein were also detected in chondrocyte cell cultures. Ultrastructural investigations of cell culture and cartilage tissue revealed the presence of caveolae at the plasma membrane of chondrocytes. These findings represent the first report on the different expression of caveolin isoforms, in particular the expression of the muscle cell-specific caveolin-3 in chondrocytes. There is evidence that caveolin-2 and -3 are upregulated during growth and development of articular cartilage, suggesting a role for caveolins in chondrocyte differentiation.

Alginates↗

PubMed1999

Alterations in the immunohistochemical distribution patterns of vascular endothelial growth factor receptors Flk1 and Flt1 in bleomycin-induced rat lung fibrosis.

To investigate the role of vascular endothelial growth factor (VEGF) in fibrogenesis, the distribution patterns of the VEGF receptors Flt1 and Flk1 were studied by immunohistochemistry, double immunofluorescence, and immunoelectron microscopy in normal (n=2) and bleomycin-treated (n=21) adult rats. Lungs were studied at 5, 24, 28, 35, and 42 days after treatment (p.t.). Flt1, Flk1, and VEGF immunoreactivity localised predominantly to the pulmonary epithelium. In control lungs, Flt1 immunoreactivity was present in ciliated bronchial epithelium and type 2 pneumocytes, Flk1 in Clara cells, and VEGF in Clara cells and type 2 pneumocytes. Flk1 localised to mast cells, present in the peribronchovascular and pleural interstitium only. Flt1- and Flk1-mRNAs were observed in Clara cells and type 2 pneumocytes. Bleomycin-induced fibrogenesis was characterised by a decrease in Flk1 immunoreactivity of Clara cells, and an increase in VEGF-immunoreactive myofibroblasts and type 2 pneumocytes by day 5 p.t., followed by a progressive accumulation of Flk1-immunoreactive mast cells by day 24 p.t. in fibrotic lesions containing VEGF-immunoreactive myofibroblasts. After 42 days, fibrotic regions were densely populated by mast cells. Since mast cells are known to be chemotactically attracted by VEGF, we suggest that VEGF/Flk1 represents the molecular link between proliferation of myofibroblasts, accumulation of mast cells, and the burst of fibrosis at sites of initial lesions in bleomycin-induced fibrosis.

Animals↗

PubMed1999

Distribution of cytokeratin filaments and vimentin in developing human taste buds.

Taste buds in humans originate from approximately the 8th postovulatory week under the influence of ingrowing nerve fibers. Since they develop from local epithelium, it is of interest whether or not prospective taste cells maintain or develop characteristics of epithelial cells that are different from those of the adjacent epithelium during differentiation. The aim of this study was to monitor changes of the distribution of the cytokeratin filaments (CKs) 8, 18, 19 and 20 ("gastrointestinal" type), CK 7 ("ductal" type), and CK 13 (maturation "mucosa type"), as well as vimentin in developing human taste buds and adjacent squamous epithelium. With the exception of CK13, which remains negative in taste bud anlagen and adult taste buds, all cytokeratins tested were present in taste cells. With the progress of development, the distribution of CKs becomes more and more restricted to taste cells and salivatory ducts as well as Ebner gland cells. Only CK20 is exclusively specific to taste bud anlagen and sometimes to individual bipolar cells occurring in early stages (week 8-9). Vimentin was located mainly in mesodermal derivatives but also in perigemmal epithelial cells during all stages of development. The occurrence of vimentin in "borderline" epithelia that interface with underlying connective tissue, i.e., in a region of discontinuity, may be associated with particular events in development, cell migration or even dedifferentiation.

Adult↗

PubMed1999

Immunohistochemical localization of the differentiation marker E11 in dental development of rats.

E11 antigen, originally characterized in a rat osteosarcoma cell line, is known to be expressed during late stages of the osteogenic cell lineage both in vitro and in vivo. The aim of the present study was to monitor the occurrence and distribution patterns of the E11 antigen using monoclonal antibodies (mAb E11 and MEP-1) during different stages of tooth germ development of new-born rats by means of immunohistochemistry. Both antibodies strongly bound to plasma membranes of ameloblasts in presecretory and secretory stages. In addition, odontoblasts and cells of the periodontium were immunoreactive for E11 and MEP-1. During maturation, the immunoreactivity of ameloblast plasma membranes decreased significantly. Our data suggest that E11 and MEP-1 might be important as markers for cell differentiation and mineralization processes during tooth germ development.

Ameloblasts↗

PubMed1999

Ultrastructural identification of caveolae and immunocytochemical as well as biochemical detection of caveolin in chondrocytes.

Using fluorescence immunocytochemistry, transmission electron microscopy and Western blotting, we have shown that caveolae and caveolin are abundant on chondrocytes of different cartilaginous structures of newborn and adult rat knee joints. Caveolin was detected in chondrocytes of the outer layer of articular cartilage, in the fibrocartilage of the menisci, and in fibrocartilage-like cells at tendon and ligament insertions. Electron microscopical studies revealed caveolae-like invaginations along the plasmalemmal membrane of articular chondrocytes and fibrocartilage cells. Immunoblot analysis demonstrated caveolin in detergent-insoluble and soluble complexes isolated from cultured rat chondrocytes.

Age Factors↗

PubMed1999

Monoclonal antibody 2G13, a new axonal growth cone marker.

Growth cones are specialized sensorimotor structures at the tips of neurites implicated in pathfinding decisions and axonal outgrowth during neuronal development. We generated a mouse monoclonal antibody (mAb 2G13) against chick tectum and found that the antibody exclusively labelled axonal growth cones, particularly their filopodia and lamellipodia, in developing rat CNS and in embryonic neurons in culture. The high fidelity of the staining of growth cones by mAb 2G13 means that the antibody will be a useful marker for identifying growth cones. In growth cones of cultured neurons, mAb 2G13 labelling is intracellular and mainly associated with the filamentous actin cytoskeleton. Experiments with cytochalasins, which depolymerise filamentous actin, showed that 2G13p (the protein recognised by mAb 2G13) is physically associated with filamentous actin in growth cones. These properties of 2G13p suggest a role in growth cone motility.

Actins↗

PubMed1999

Keratinocyte growth factor-induced hyperplasia of rat alveolar type II cells in vivo is resolved by differentiation into type I cells and by apoptosis.

Keratinocyte growth factor (KGF) is a potent mitogen of alveolar epithelial type II cells (AEII). AEII hyperplasia is resolved within several days following intratracheal instillation of KGF by unknown mechanism(s). AEII hyperplasia was induced in rat lungs by intrabronchial instillation of 5 mg recombinant human (rh)KGF x kg body weight(-1) or an equivalent amount of diluent. Epithelial architecture, cell proliferation, transformation of AEII into type I cells (AEI) and apoptosis were investigated by means of immunohistochemistry, stereology, double immunofluorescence microscopy, electron microscopy and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) technique in lungs fixed 1, 2, 3 and 7 days after treatment. After 1 day of rhKGF instillation, an increase was observed in the nuclear antigen Ki-67, a proliferation marker detected by the antibody MIB-5-expressing surfactant protein (SP)-B, -C, -D-positive AEII. The incidence of mitosis was increased by day 2, resulting in AEII micropapillae with intense basolateral expression of the exon 6 containing isoform (v6) of CD446 (CD44v6), a marker for AEII. By day 3, monolayers of AEII exhibiting lateral CD44v6 covered 45% of the alveolar surface. After 7 days, there were numerous intermediate AEII/AEI cells characterized by a flat elongated shape, staining for SP-D, apical appearance of AEI marker Lycopersicon esculentum lectin and lateral staining for AEII marker CD44v6. Increased numbers of TUNEL-positive epithelial cells were seen at days 2-7. In conclusion, restoration of normal alveolar epithelium after instillation of recombinant human keratinocyte growth factor is accomplished by terminal differentiation and apoptosis of hyperplastic alveolar epithelial type II cells in vivo.

Animals↗

PubMed1998

Loss of caveolin expression in type I pneumocytes as an indicator of subcellular alterations during lung fibrogenesis.

Caveolin is a major structural protein of caveolae, also known as plasmalemmal vesicles, which are particularly abundant in type I pneumocytes and capillary endothelial cells of lung parenchyma. Here we demonstrate that caveolin expression in the alveolar epithelium of rats and mini pigs is strikingly downregulated after irradiation-induced lung injury. Indirect immunoperoxidase staining with polyclonal anti-caveolin antibodies, confirmed by double fluorescence studies with type I cell-specific monoclonal anti-cytokeratin antibodies or lectins, revealed a dramatic loss of caveolin immunoreactivity in type I pneumocytes. In contrast, caveolin expression increased in endothelial cells. Immunoblotting of lung homogenates from normal and irradiated rats using specific anti-caveolin antibodies confirmed the presence of caveolin in normal tissue and its marked decrease of expression in fibrotic tissue. The loss of caveolin as an important structural protein of caveolae in alveolar epithelial cells may be an early indicator of serious type I cell injury during fibrogenesis. The increase of caveolin immunoreactivity in endothelia of blood vessels may indicate that different types of caveolae and/or different regulatory mechanisms of caveolin expression exist.

Animals↗

PubMed1998

Immunohistochemical distribution of CD44 and some of its isoforms during human taste bud development.

Taste buds are accumulations of elongated bipolar cells situated on lingual papillae. The factors that determine the sites where a taste bud may develop are largely obscure, although it is known that the early invasion of nerve fibers plays one of the key roles in taste bud development and maturation. The conditions under which taste bud primordium cells develop are influenced by the interaction between epithelial cells and extracellular matrix molecules of the mesenchyma, such as hyaluronan. Thus, we investigated immunohistochemically the distribution pattern of the receptor for hyaluronan, CD44s, and its epithelial variant isoforms CD44v6 and CD44v9, in taste buds of human embryonic, fetal, perinatal, and adult tongues. Furthermore, we wanted to determine the temporal and spatial relationships of CD44 to sensory innervation of taste bud primordia. In early gestational stages (weeks 7-9), CD44 and its isoforms are expressed on membranes of apical perigemmal (marginal) cells covering taste bud primordia. It seems that CD44 serves as a marker for marginal cells (perigemmal cells) in early developmental stages. The expression of CD44 follows rather than precedes the invasion of sensory nerve fibers and the development of taste bud primordia (weeks 7-8). In new-born and adult taste bud cells, only the standard molecule, CD44s, is expressed; the variant isoforms, CD44v6 and CD44v9, occur only in the adjacent epithelium. From these results it is likely that marginal cells are of the utmost importance for the development and maturation of taste buds. We presume that CD44 is involved in local binding, reuptake, and degradation of hyaluronan in the early stages of taste bud formation. CD44 probably does not induce the transformation of epithelial cells into taste bud primordial cells. What is more, CD44 may change its function in the course of developmental events.

Adult↗

PubMed1998

Gasless videoendoscopic implantation of aortobifemoral vascular prostheses via transperitoneal versus extraperitoneal approach in an animal model.

BACKGROUND: The goal of this acute experimental study was to demonstrate the practicability and reproducibility of aortobifemoral bifurcational prosthesis implantations via either a transperitoneal or extraperitoneal approach using gasless videoendoscopic instrumentation. The endoscopically sutured end-to-side aortic anastomoses were also examined for fluid tightness. METHODS: Eighteen of the 20 domestic pigs in this experimental study received aortobifemoral vascular prostheses in a gasless videoendoscopic procedure. Bursting pressures and leakage (ml/min) were compared for the endoscopically sutured aortic end-to-side anastomoses versus those sutured in conventional techniques using 6-h-old porcine aortas and 6-mm prostheses. RESULTS: The surgical procedures averaged 4 h for the transperitoneal approach (n = 9) and 4.5 h for the extraperitoneal approach (n = 9). However, these times were significantly reduced with increasing routine. Average aortic occlusion times were 1 h for the transperitoneal approach and 1 h 15 min for the extraperitoneal approach; the average iliacofemoral occlusion time ranged from 1 h 45 min with the transperitoneal approach to 1 h 15 min with the extra-peritoneal approach, depending on which side was involved: There were no significant differences in in vitro bursting pressure or leakage amounts between endoscopic and conventionally sutured aortic end-to-side anastomoses. CONCLUSIONS: Gasless videoendoscopic implantation of aortobifemoral vascular prostheses in animal subjects is both practicable and reproducible using either a transperitoneal or extraperitoneal approach. The extraperitoneal approach has proven advantages over the transperitoneal approach. The in vitro fluid tightness achieved with endoscopically sutured aortic end-to-side anastomoses is comparable to conventionally sutured anastomoses.

Anastomosis, Surgical↗

PubMed1998

Cytomegalovirus-specific IFNgamma and IL-4 are produced by antigen expanded human blood lymphocytes from seropositive volunteers.

The cytokine responses to cytomegalovirus (CMV) antigen in seropositive and seronegative individuals were measured using a combination of antigenic expansion and intracellular staining. Intracellular IFNgamma and IL-4 were produced in a dose-dependent manner by T cells in response to CMV only in the seropositive population. The potential for individual cells to produce both Th1 and Th2 cytokines simultaneously was clear, as IL-4 was most often produced in those cells with the highest IFNgamma production. The cytokine-specific nature of this response was demonstrated by fluorescence microscopy, which showed granular cytoplasmic staining, and at the mRNA level by ribonuclease protection assays. These methods expand our ability to evaluate the immune response to CMV, and can now be correlated to a number of clinical conditions.

Adult↗

PubMed1998

Characterization of the gap junction protein connexin37 in murine endothelium, respiratory epithelium, and after transfection in human HeLa cells.

Affinity-purified antibodies to oligopeptides derived from two different regions of the carboxyterminus and cytoplasmic loop or to the last 103 C-terminal amino acids of mouse connexin37 (Cx37) were used to characterize expression of this gap junctional protein in endothelium of several murine tissues. Cx37 was expressed in endothelium of large blood vessels in brain, liver, kidney, spleen, heart, and lung, but not in capillaries. In addition, weak Cx37 immuno-signals were observed in lung respiratory epithelium of small bronchi and in alveolar epithelial cells of bronchioli. The ratios of Cx37 protein to Cx37 mRNA in adult and embryonic kidney as well as skin were 29-303-fold larger than in lung, suggesting that Cx37 mRNA was translated at different efficiencies in kidney and skin versus lung. Cx37 protein was more abundant in embryonic kidney and lung than in the corresponding adult tissues. After differential centrifugation of plasma membrane fractions in sucrose gradients, we found that Cx37-containing gap junctions in lung were much smaller than Cx32 and Cx26 aggregates from liver. HeLa cells were transfected with mouse Cx37 cDNA. In these cells, mouse Cx37 protein was phosphorylated mainly at serine, less at tyrosine, and very little at threonine residues. Three conductance states were resolved at 110, 240, and 315 pS.

Animals↗