Chronic obstructive pulmonary disease: current burden and future projections.
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Biomedical subjects
Publications and source records attributed to V Schmid.
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The analysis of the geographical distribution of disease on the scale of geographic areas such as administrative boundaries plays an important role in veterinary epidemiology. Prevalence estimates of wildlife population surveys are often based on regional count data generated by sampling animals shot by hunters. The observed disease rate per spatial unit is not an useful estimate of the underlying disease prevalence due to different sample sizes and spatial dependencies between neighbouring areas. Therefore, it is necessary to account for extra-sample variation and spatial correlations in the data to produce more accurate maps of disease incidence. The detection of spatial patterns is complicated by missing data in many of the geographical areas as the complete coverage of all areas is nearly impossible in wildlife surveys. For this purpose a hierarchical Bayesian model in which structured and unstructured over dispersion is modelled explicitly in terms of spatial and non-spatial components was implemented by Markov chain Monte Carlo methods. The model was empirically compared with the results of a non-spatial beta-binomial model using surveillance data of pseudorabies virus infections of European wild boars (Sus scrofa scrofa L.) in the Federal State of Brandenburg, Germany.
To clarify the relationship between axial patterning in cnidarians and bilaterians, we have investigated the embryonic development of the hydrozoan Podocoryne carnea. The expression of Hox-like homeobox genes was analyzed by RT-PCR and in situ hybridization. Cnox1-Pc, an anterior Hox gene, is a maternal message. It is present throughout larval development, first weakly in all blastomeres and later restricted mostly to the anterior pole of the planula. Gsx, an anterior ParaHox gene, is first seen in the anterior endoderm but also extends into posterior regions. Cnox4-Pc, an orphan Hox-like gene, is expressed in the egg as a ring-shaped cloud around the germinal vesicle. After fertilization, the message remains in most animal blastomeres. When the embryo elongates in late blastula, staining is restricted to a few cells at the posterior pole where gastrulation will start. However, once gastrulation starts, the Cnox4-Pc signal disappears and is absent in later stages of larval development. Phylogenetic analysis shows that not all cnidarian Hox-like genes have recognizable orthologues in bilaterian groups. However, the expression analysis of Cnox1-Pc and Gsx correlates to some extent with the expression pattern of cognate genes of bilaterians, confirming the conservation of genes involved in organizing animal body plans and their putative common ancestral origin.
Among the basal animal phyla, the Cnidaria display many characteristics similar to the Bilateria (the higher Metazoa). However, the relation of that outgroup phyla to the Bilateria is still equivocal. Additionally to morphological and genetic data, studies on cnidarian embryogenesis are essential to clarify the Cnidaria-Bilateria relationship. We analyzed cellular differentiation during planula larvae development of the jellyfish Podocoryne carnea. Within 24 to 30 h postfertilization, the diploblastic body structure and all cell types found in polyps have already differentiated in the larva. Whereas the differentiating smooth muscles, RFamide-positive nerve cells, or nematocytes (stinging cells) express no axial polarity, a newly discovered tyrosine-tubulin-positive nervous system develops gradually in repetitive patterns from anterior to posterior. These data demonstrate that part of the cnidarian nervous system develops from anterior to posterior in serially repeated patterns. This developmental mechanism seems to follow the bilaterian pattern and would have antedated the Cambrian explosion.
We have isolated an integrin-beta and -alpha subunit from Podocoryne carnea (Cnidaria, Hydrozoa) and studied their expression in the life-cycle and during cell migration, in vitro transdifferentiation and regeneration. Comparison of the integrin expression pattern with a Podocoryne talin homologue by RT-PCR demonstrates that all three genes are maternal messages and continuously expressed in the life-cycle, in medusa development and in all medusae tissues. In situ hybridisation experiments confirm co-expression of both integrin subunits in the different life-stages. Integrin expression was furthermore studied in isolated striated muscle induced to transdifferentiate to new cell types, or grafted on ECM where the muscle adheres and migrates. Integrin expression was maintained continuously throughout both processes. These results suggest that in Podocoryne carnea processes such as cell migration and differentiation are not controlled by up- or downregulation of alternative integrin subunits, but by a single integrin heterodimer which activates different downstream signalling cascades.
The basic helix-loop-helix (bHLH) transcription factor Twist is highly conserved from Drosophila to vertebrates and plays a major role in mesoderm specification of triploblasts. The presence of a Twist homologue in diploblasts such as the cnidarian Podocoryne carnea raises questions on the evolution of mesoderm, the third cell layer characteristic for triploblasts. Podocoryne Twist is expressed in the early embryo until the myoepithelial cells of the larva differentiate and then again during medusa development. There, the gene is detected first when the myoepithelial cells of the polyp dedifferentiate to form the medusa bud and later Twist is found transiently in the entocodon, a mesoderm-like cell layer which differentiates into the smooth muscle and striated muscle of the bell. On the other hand, in later bud stages and the medusa, expression is seen where non-muscle tissues differentiate. Experimental analysis of in vitro transdifferentiation and regeneration demonstrates that Twist activity is not needed when isolated striated muscle regenerate medusa organs. Developmental roles of Twist are discussed with respect to early animal evolution from a common ancestor of cnidarians and bilaterians.
The marine jellyfish Podocoryne carnea (Cnidaria, Hydrozoa) has a metagenic life cycle consisting of a larva, a colonial polyp and a free-swimming jellyfish (medusa). To study the function of HOX genes in primitive diploblastic animals we screened a library of P. carnea cDNA using PCR primers derived from the most conserved regions in helix 1 and helix 3 of the homeobox. A novel gene, Cnox2-Pc, has been isolated and characterized. Cnox2-Pc is a HOX cluster-like gene, and its homeodomain shows similarity to the Deformed subfamily of HOM-C/HOX genes. In situ hybridization revealed that Cnox2-Pc is expressed in the anterior region of the larva, the polyp head, and the most apical ectoderm of the differentiating bud during medusa development. In adult medusa expression is restricted to the gastrovascular entoderm. The results suggest that Cnox2-Pc is involved in establishment of an anterior-posterior axis during development in primitive metazoans.
We characterized a Pax gene from the hydrozoan Podocoryne carnea. It is most similar to cnidarian Pax-B genes and encodes a paired domain, a homeodomain and an octapeptide. Expression analysis demonstrates the presence of Pax-B transcripts in eggs, the ectoderm of the planula larva and in a few scattered cells in the apical polyp ectoderm. In developing and mature medusae, Pax-B is localized in particular endodermal cells, oriented toward the outside. Pax-B is not expressed in muscle cells. However, if isolated striated muscle tissue is activated for transdifferentiation, the gene is expressed within 1 h, before new cell types, such as smooth muscle and nerve cells, have formed. The expression data indicate that Pax-B is involved in nerve cell differentiation.
In many bilaterian animals members of the Otx gene family are expressed in head or brain structures. Cnidarians, however, have no clearly homologous head and no distinct brain; but an Otx homolog from the jellyfish Podocoryne carnea is highly conserved in sequence and domain structure. Sequence similarities extend well beyond the homeodomain and Podocoryne Otx can be aligned over its entire length to human OTX1, OTX2, and CRX. The overall structure of Otx is better conserved from Podocoryne to deuterostomes while protostomes appear to be more derived. In contrast, functions seem to be conserved from protostomes to vertebrates but not in Podocoryne or echinoderms. Podocoryne Otx is expressed only during medusa bud formation and becomes restricted to the striated muscle of medusae. Cnidaria are the most basal animals with striated muscle. Podocoryne polyps have no striated muscle and no Otx expression; both appear only during the asexual medusa budding process. The common ancestor of all animals that gave rise to cnidarians, protostomes, and deuterostomes already had an Otx gene more similar to today's Podocoryne and human homologs than to Drosophila otd, while the head-specific function appears to have evolved only later.
Cnidaria are the most basal animal phylum in which smooth and striated muscle cells have evolved. Since the ultrastructure of the mononucleated striated muscle is similar to that of higher animals, it is of interest to compare the striated muscle of Cnidaria at the molecular level to that of triploblastic phyla. We have used tropomyosins, a family of actin binding proteins to address this question. Throughout the animal kingdom, a great diversity of tropomyosin isoforms is found in non-muscle cells but only a few conserved tropomyosins are expressed in muscle cells. Muscle tropomyosins are all similar in length and share conserved termini. Two cnidarian tropomyosins have been described previously but neither of them is expressed in striated muscle cells. Here, we have characterized a new tropomyosin gene Tpm2 from the hydrozoan Podocoryne carnea. Expression analysis by RT-PCR and by whole mount in situ hybridization demonstrate that Tpm2 is exclusively expressed in striated muscle cells of the medusa. The Tpm2 protein is shorter in length than its counterparts from higher animals and differs at both amino and carboxy termini from striated muscle isoforms of higher animals. Interestingly, Tpm2 differs considerably from Tpm1 (only 19% identity) which was described previously in Podocoryne carnea. This divergence indicates a functional separation of cytoskeletal and striated muscle tropomyosins in cnidarians. These data contribute to our understanding of the evolution of the tropomyosin gene family and demonstrate the recruitment of tropomyosin into hydrozoan striated muscles during metazoan evolution. J. Exp. Zool. (Mol. Dev. Evol.) 285:378-386, 1999.
We have investigated, by RT-PCR and in situ hybridization, expression of genes encoding regulatory and structural proteins in migrating mononucleated striated muscle cells of the medusa Podocoryne carnea. Expression of the three homeobox genes Otx, Cnox1-Pc, and Cnox3-Pc; a specific splice variant of the myosin heavy chain gene (Myo1); and a tropomyosin (Tpm2) is stable in isolated and cultured striated muscle tissue. When grafted onto cell-free extracellular matrix (ECM), muscle cells of the tissue fragments leave their native ECM and migrate as a coherent tissue onto a host ECM until a stretched cell monolayer is formed. Shortly after the first cells of the grafted isolate have made contact with the host ECM, Otx and Cnox1-Pc expression is completely turned off in all cells of the graft, including those still adhering to their native ECM. Myo1 message disappears with a delay while the expression level of Tpm2 is strongly reduced. However, expression of the homeobox gene Cnox3-Pc, a msh-like gene, and of the ubiquitously expressed elongation factor 1 alpha is not affected by the migration process. All genes are reexpressed after 12-24 h, once migration of the cells has ceased. Our results demonstrate that the first few migrating cells induce a change in gene expression which is rapidly communicated throughout the entire tissue. Furthermore, we showed that commitment of striated muscle cells remains stable despite the transient inactivation of cell-type-specific regulatory and structural genes.
Studies on morphogenesis and regeneration in cnidarians have a long history, and the importance of cell-ECM (extracellular matrix) interactions for these processes has been well recognized and studied since the middle of the 20th century. Cnidarians have a life cycle with a larva, a polyp, and often a medusa generation. In the medusa, the ECM (mesoglea) is very prominent and essentially shapes the animal. In the larva and the polyp, the ECM is a thin layer. Some of the ECM components known from vertebrates have been identified in cnidarians by immunohistochemistry, electron microscopy, rotary shadowing, biochemistry, and molecular cloning. In vivo and in vitro experiments suggest that the cnidarian ECM plays a role in cell migration and morphogenesis comparable to that known from other developmental systems. In the fresh water polyp Hydra, regeneration of body patterns and migration of nematocytes seems to require the presence of ECM ligands and the corresponding cell receptors. In hydrozoan medusae, DNA replication and the stability of the differentiated state of isolated tissue can be influenced by altering the properties of the ECM substrate. When cultured, most cnidarian cells survive only when attached to ECM substrates, they rarely divide and die within short times.
BACKGROUND: The impact of response to treatment on subsequent symptoms, quality of life, health care consumption, and absence from work in functional dyspepsia is unknown. METHODS: Patients with functional dyspepsia from Denmark, France, Germany, The Netherlands, Hungary, and Poland (n = 567 (215 men), 18-80 years old) were followed up for 3 months after a 4-week treatment trial with omeprazole (20 mg or 10 mg) or placebo. The patients were blinded to the initial treatment. Dyspeptic symptoms and quality of life were assessed, and dyspepsia-related costs were calculated in terms of number of clinic visits, days on medication, and absence from work. RESULTS: Responders had fewer clinic visits than non-responders (1.5 versus 2.0 mean visits) and fewer days on medication (mean, 9 days versus 23 days) over the 3-month period (both, P < 0.001). The quality of life in responders was better at study entry and persisted over 3 months (all, P < 0.001). When analysed country by country, health care costs due to clinic visits and medications were significantly lower in responders in all countries (P < 0.05), except Denmark and The Netherlands. CONCLUSION: Symptom resolution in patients with functional dyspepsia has a positive impact on quality of life and reduces the subsequent costs over a 3-month period after cessation of initial treatment.
Metalloproteinases of the astacin family such as tolloid play major roles in animal morphogenesis. Cnidarians are thought to be evolutionary simple organisms and, therefore, a metalloproteinase from the marine hydrozoan Podocoryne carnea was analysed to evaluate the role of this conserved gene familiy at the base of animal evolution. Surprisingly, the proteinase domain of Podocornyne PMP1 is more similar to human meprin than to HMP1 from another hydrozoan, the freshwater polyp Hydra vulgaris. However, PMP1 and HMP1 both contain a small C-terminal domain with six cysteines that distinguishes them from other astacin-like molecules. Similar domains have been described only recently from sea anemone toxins specific for potassium channels. This toxin homology (Tox1) domain is clearly distinct from epidermal growth factor (EGF)-like domains or other cysteine-rich modules and terminates with the characteristic pattern CXXXCXXC with three out of six cysteines in the last eight residues of the protein. PMP1 is transiently expressed at various sites of morphogenetic activity during medusa bud development. In the adult medusa, however, expression is concentrated to the manubrium, the feeding organ, where the PMP1 gene is highly induced upon feeding. These disparate expression patterns suggest a dual role of PMP1 comparable to tolloid in development and, like astacin in the crayfish, also for food digestion. The Tox1 domain of PMP1 could serve as a toxin to keep the pray paralysed after ingestion, but as a sequence module such Tox1 domains with six cysteines are neither restricted to cnidarians nor to toxins.
BACKGROUND: The efficacy of H2-receptor antagonists in functional dyspepsia is equivocal and the therapeutic place of proton pump inhibitors in functional dyspepsia is unknown. AIM: To evaluate the efficacy of proton pump inhibitor therapy in functional dyspepsia. METHODS: Patients (n = 1262) with a clinical diagnosis of functional dyspepsia (persistent or recurrent epigastric pain or discomfort for at least 1 month and a normal upper gastrointestinal endoscopy) were randomized to receive omeprazole 20 mg, 10 mg or identical placebo, for 4 weeks. Symptoms were assessed using validated measures. Helicobacter pylori status was determined pre-entry by a 13C-urea breath test. RESULTS: On an intention-to-treat analysis (n=1248), complete symptom relief was observed in 38% on omeprazole 20 mg, compared with 36% on omeprazole 10 mg and 28% on placebo (P = 0.002 and 0.02, respectively). Among those with ulcer-like and reflux-like dyspepsia, complete symptom relief was achieved in 40% and 54% on omeprazole 20 mg, and 35% and 45% on omeprazole 10 mg, respectively, compared with 27% and 23% on placebo (all P < 0.05, except omeprazole 10 mg in ulcer-like dyspepsia, P = 0.08). There was no significant benefit of omeprazole over placebo in dysmotility-like dyspepsia. Symptom relief was similar in H. pylori-positive and negative cases. CONCLUSIONS: Omeprazole is modestly superior to placebo in functional dyspepsia at standard (20 mg) and low doses (10 mg) but not in patients with dysmotility-like dyspepsia.
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Ultrasonography was used to compare adhesions induced by two different methods of gastropexy in 16 dogs. An incisional gastropexy technique was used in eight dogs (group 1) and a 'modified' gastropexy technique in the remaining eight (group 2). The length and thickness of the gastropexy and the peristaltic activity of the stomach were measured ultrasonographically and compared between groups. Measurements for the two groups were taken in the early postoperative interval (two to four days), intermediate postoperative interval (eight to 20 days) and late postoperative interval (57 to 79 days). Both techniques were equally successful in forming permanent adhesions at two months postoperatively and there was no recurrence of gastric dilatation and volvulus. The length and thickness of the gastropexy were similar for both groups at two months postoperatively and there were no surgical complications with either technique. The modified gastropexy provides a technique that can easily be performed by a single surgeon, with no increased operative time or duration of anaesthesia, and with the formation of a permanent adhesion.