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Biomedical subjects

D Kasper

Publications and source records attributed to D Kasper.

10 recordsLinked to original sources
PubMed2006

Biochemical response to bisphosphonate therapy in pagetic patients with skull involvement.

The aims of this study were to compare the response to therapy in disease activity in pagetic patients with and without skull involvement and the usefulness of bone markers in the evaluation of these patients. Forty patients with Paget's disease treated with tiludronate and 26 healthy controls were included. Serum total and bone alkaline phosphatases (TAP, BAP), procollagen I N propeptide (PINP), and urinary N- and C-terminal cross-linking telopeptides of collagen I (NTX, alpha-alpha CTX, and beta-beta CTX) were measured at baseline and 6 months after therapy. The extent of the disease was evaluated using the Coutris' index. Pagetic patients were classified into three groups: patients with skull involvement (G-I, n = 12), patients without skull involvement (G-II, n = 28), and a subgroup of patients from G-II without skull involvement but with similar disease extent to G-I (G-III, n = 10). At baseline, patients from G-I showed significantly higher values in most markers compared to G-II. alpha-alpha CTX was the marker with the highest values in all groups. Moreover, monostotic patients with skull involvement showed higher serum baseline values of TAP per unit of affected area than monostotic patients without skull involvement. After therapy, the percentage of patients with markers within the normal range was lower in G-I than in G-II and G-III. In conclusion, pagetic patients with skull involvement showed a marked increase in bone turnover and a lower response to therapy.

Adult↗
PubMed2002

[Clinical manifestations of diffuse idiopathic skeletal hyperostosis (DISH)].

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH, Forestier disease) is in most cases a harmless, asymptomatic disease characterized by a massive, noninflammatory ossification with intensive formation of osteophytes affecting ligaments, tendons, and fasciae, especially of the spinal column. If the disease becomes symptomatic at all, the leading complaints will usually be dysphagia in the sense of a lump in the throat and difficulty in swallowing. However, in rare cases the osteophytes may influence the laryngeal function ranging from hoarseness and immobility of the vocal cord to life-threatening inspiratory stridor. Such laryngeal manifestations are almost unknown. PATIENTS AND METHOD: We report on three patients, two female and one male, suffering not only from chronic dysphagia but also from increasing inspiratory stridor and difficult breathing. RESULTS: Especially one case illustrates how difficult it can be to establish the etiological relationship between a cancer-like ulcer in the postcricoid region and a bilateral inactivity of the vocal cord on the one hand and DISH on the other hand. Only the resistance of the ulceration to any therapy as well as rare case reports in the literature confirmed our suspicion that the ulcer and disturbance of laryngeal function were caused by chronic pressure exerted by the huge vertebral osteophytes. In all three patients surgical resection of the osteophytes resulted in complete relief of complaints. CONCLUSION: Uni- or bilateral immobility of the arytenoids, possibly associated with chronic inflammatory hyperplasia of the tissue of the arytenoids and the postcricoid region, may be a symptom of an unusual manifestation of DISH.

Aged↗
PubMed2001

The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein.

Sortilin belongs to a growing family of multiligand type-1 receptors with homology to the yeast receptor Vps10p. Based on structural features and sortilin's intracellular predominance, we have proposed it to be a sorting receptor for ligands in the synthetic pathway as well as on the cell membrane. To test this hypothesis we examine here the cellular trafficking of chimeric receptors containing constructs of the sortilin tail. We report that sorting signals conforming to YXX and dileucine motifs mediate rapid endocytosis of sortilin chimeras, which subsequently travel to the trans-Golgi network, showing little or no recycling. Furthermore, we found that cation-independent mannose 6-phosphate receptor (MPR300)-sortilin chimeras, expressed in mannose 6-phosphate receptor knockout cells, were almost as efficient as MPR300 itself for transport of newly synthesized beta-hexosaminidase and beta-glucuronidase to lysosomes, and established that the sortilin tail contains potent signals for Golgi-endosome sorting. Finally, we provide evidence suggesting that sortilin is the first example of a mammalian receptor targeted by the recently described GGA family of cytosolic sorting proteins, which condition the Vps10p-mediated sorting of yeast carboxypeptidase Y.

Adaptor Proteins, Vesicular Transport↗
PubMed2001

Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.

Chloride channels play important roles in the plasma membrane and in intracellular organelles. Mice deficient for the ubiquitously expressed ClC-7 Cl(-) channel show severe osteopetrosis and retinal degeneration. Although osteoclasts are present in normal numbers, they fail to resorb bone because they cannot acidify the extracellular resorption lacuna. ClC-7 resides in late endosomal and lysosomal compartments. In osteoclasts, it is highly expressed in the ruffled membrane, formed by the fusion of H(+)-ATPase-containing vesicles, that secretes protons into the lacuna. We also identified CLCN7 mutations in a patient with human infantile malignant osteopetrosis. We conclude that ClC-7 provides the chloride conductance required for an efficient proton pumping by the H(+)-ATPase of the osteoclast ruffled membrane.

Adenosine Triphosphatases↗
PubMed2001

[Clinical aspects of tracheopathia osteoplastica].

Tracheopathia osteoplastica is a rare condition of the tracheobronchial tree characterized by the formation of multiple osseous or cartilaginous submucosal nodules which protrude into the lumen. Clinical features, pathological-anatomical, and radiological findings are described and discussed on the basis of three recent cases and a literature review.Two female patients (age 56 and 62 years) and one male (age 44 years) presented with recurrent tracheobronchitis, a "difficult intubation" at the time of an emergency situation requiring tracheostomy. The diagnosis was confirmed by tracheoscopy. CT scans showed radiodense nodular thickening of the tracheal wall compromising the lumen in all patients, whereas plain chest radiography revealed scalloped linear calcification in only one case. Histologically the nodules consisted of lamellar-type bone covered by normal mucosa. None of the patients needed therapeutic measures as there was no impairment of ventilatory function. The long-term observations (>15 years) of a few authors suggest that the disease is of benign course and does not deteriorate.

Adult↗
PubMed2001

Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.

Hereditary rippling muscle disease (RMD) is an autosomal dominant human disorder characterized by mechanically triggered contractions of skeletal muscle. Genome-wide linkage analysis has identified an RMD locus on chromosome 3p25. We found missense mutations in positional candidate CAV3 (encoding caveolin 3; ref. 5) in all five families analyzed. Mutations in CAV3 have also been described in limb-girdle muscular dystrophy type 1C (LGMD1C; refs. 6,7), demonstrating the allelism of dystrophic and non-dystrophic muscle diseases.

Caveolin 3↗
PubMed2000

The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress.

In Alzheimer's disease (AD) brains, selected populations of neurons degenerate heavily, whereas others are frequently spared from degeneration. To address the cellular basis for this selective vulnerability of neurons in distinct brain regions, we compared gene expression between the severely affected inferior temporal lobes and the mostly unaffected fronto-parietal cortices by using an mRNA differential display. We identified seladin-1, a novel gene, which was downregulated in large pyramidal neurons in vulnerable regions in AD but not control brains. Seladin-1 is a human homolog of the DIMINUTO/DWARF1 gene described in plants and Caenorhabditis elegans. Its sequence shares similarities with flavin-adenin-dinucleotide (FAD)-dependent oxidoreductases. In human control brain, seladin-1 was highly expressed in almost all neurons. In PC12 cell clones that were selected for resistance against AD-associated amyloid-beta peptide (Abeta)-induced toxicity, both mRNA and protein levels of seladin-1 were approximately threefold higher as compared with the non-resistant wild-type cells. Functional expression of seladin-1 in human neuroglioma H4 cells resulted in the inhibition of caspase 3 activation after either Abeta-mediated toxicity or oxidative stress and protected the cells from apoptotic cell death. In apoptotic cells, however, endogenous seladin-1 was cleaved to a 40 kDa derivative in a caspase-dependent manner. These results establish that seladin-1 is an important factor for the protection of cells against Abeta toxicity and oxidative stress, and they suggest that seladin-1 may be involved in the regulation of cell survival and death. Decreased expression of seladin-1 in specific neurons may be a cause for selective vulnerability in AD.

Aged↗
PubMed1996

Neither type of mannose 6-phosphate receptor is sufficient for targeting of lysosomal enzymes along intracellular routes.

Mouse embryonic fibroblasts that are deficient in the two mannose 6-phosphate receptors (MPRs) MPR 46 and MPR 300 missort the majority (> or = 85%) of soluble lysosomal proteins into the medium. Human MPR 46 and MPR 300 were expressed in these cells to test whether overexpression of a single type of MPR can restore transport of lysosomal proteins to lysosomes. Only a partial correction of the missorting was observed after overexpression of MPR 46. Even at MPR 46 levels that are five times higher than the wild-type level, more than one third of the newly synthesized lysosomal proteins accumulates in the secretions. Two-fold overexpression of MPR 300 completely corrects the missorting of lysosomal enzymes. However, at least one fourth of the lysosomal enzymes are transported along a secretion-recapture pathway that is sensitive to mannose 6-phosphate in medium. In control fibroblasts that express both types of MPR, the secretion-recapture pathway is of minor importance. These results imply that neither overexpression of MPR 46 nor MPR 300 is sufficient for targeting of lysosomal proteins along intracellular routes.

Animals↗