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Biomedical subjects

K Schäfer

Publications and source records attributed to K Schäfer.

At least 19 recordsLinked to original sources

Plasminogen activator inhibitor-1 and its cofactor vitronectin stabilize arterial thrombi after vascular injury in mice.

BACKGROUND: The origin and contribution of plasminogen activator inhibitor-1 (PAI-1) and its cofactor vitronectin (VN) to arterial thrombosis/thrombolysis in vivo is controversial. METHODS AND RESULTS: Ferric chloride was used to induce carotid artery injury in 97 wild-type (WT), 84 PAI-1-/-, and 84 VN-/- mice. Complete thrombotic occlusion was observed in 70% of PAI-1-/- mice versus 92% of WT (P:<0.001) and 87% of VN-/- (P:=0.015) mice. In vessels that occluded, mean times to occlusion were significantly longer in PAI-1-/- than in WT or VN-/- mice. The initial thrombotic response of VN-/- mice was similar to that of WT mice, but their thrombi were unstable and frequently embolized. As a result, the patency rate of carotid vessels 30 minutes after injury was as high in VN-/- mice (36%) as in PAI-1-/- mice (which demonstrate progressive thrombolysis) and significantly higher than that of WT mice (12%; P:=0.013). Histochemical and reverse transcription-polymerase chain reaction studies revealed an early upregulation of PAI-1 mRNA and protein expression in the thrombus and the vessel wall, which persisted for >/=1 week. VN protein also accumulated after injury, but VN mRNA levels remained low at all times. CONCLUSIONS: PAI-1 and VN participate in the thrombotic response to arterial injury by preventing premature thrombus dissolution and embolization. The accumulation of PAI-1 in the thrombus/vessel wall after injury may result, at least in part, from local synthesis, whereas the VN protein appears to be derived from plasma.

Actins↗

Incorporation of dietary linoleic and conjugated linoleic acids and related effects on eggs of laying hens.

In the present study, laying hens received 29 g per kg diet of a preparation containing either 70% linoleic acid (LA) or approximately the same amount of conjugated linoleic acid (CLA) in the control and experimental treatments, respectively. The CLA preparation consisted predominantly of cis-9,trans-11 and trans-10,cis-12 fatty acid isomers as free fatty acids in a ratio of 1:1. The diets were fed for 8 wk to determine the effect of dietary CLA on quality characteristics of eggs. In addition, the fatty acid composition of liver and heart was analyzed. Performance parameters (egg weight, feed efficiency) were not significantly affected by feeding the diets supplemented with CLA. The overall amount of CLA that was incorporated into yolk was 7.95 g CLA/100 g total fatty acids, or approximately 400 mg CLA/egg. The transfer efficiency of the cis-9,trans-11 isomer was higher than that of the trans-10,cis-12 isomer; however, the transfer rate of CLA isomers into yolk and tissues was significantly lower than that of linoleic acid. Dietary CLA increased the concentration of saturated fatty acids in yolk and tissues at the expense of monounsaturated fatty acids. The proportions of myristic, palmitic, and stearic acids in yolk lipids were also changed by dietary CLA. Additionally, long-chain polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) were decreased without changing the balance of the n-6/n-3 ratio in egg yolk. The inclusion of CLA in layer diets altered the shape of the yolk and various egg parameters (albumen height, foam index, and yolk index). The results of this study indicate that CLA induces various changes in lipid and fatty acid metabolism of laying hens and affects quality characteristics of eggs.

Animal Feed↗

Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity.

Obesity is associated with increased cardiovascular morbidity and mortality and with elevated circulating levels of the satiety factor leptin. This study provides evidence for a direct link between leptin and the risk for thrombotic complications in obese individuals. For example, although arterial injury provokes thrombosis in both lean and obese (ob/ob) mice, the time to complete thrombotic occlusion is significantly delayed in the ob/ob mice, and the thrombi formed are unstable and frequently embolize. The ob/ob mice lack leptin, and intraperitoneal administration of leptin to these mice before injury restores the phenotype of lean mice by shortening the time to occlusion, stabilizing the thrombi, and decreasing the patency rate. The thrombi that form when leptin receptor-deficient obese (db/db) mice are injured also are unstable. However, in this instance, leptin has no effect. Platelets express the leptin receptor, and leptin potentiates the aggregation of platelets from ob/ob but not db/db mice in response to known agonists. These results reveal a novel receptor-dependent effect of leptin on platelet function and hemostasis and provide new insights into the molecular basis of cardiovascular complications in obese individuals. The results suggest that these prothrombotic properties should be considered when developing therapeutic strategies based on leptin.

Adenosine Diphosphate↗

Virtual anthropology: the digital evolution in anthropological sciences.

The discovery and explanation of differences among organisms is a major concern for evolutionary and systematic biologists. In physical anthropology, the discrimination of taxa and the qualitative and quantitative description of ontogenetic or evolutionary change require, of course, the analysis of morphological features. Since the 1960s, a remarkable amount of fossil material was excavated, some of it still awaiting a detailed first analysis, some of it requiring re-examination by more developed methods. While the fossil record grew continuously, a revolution in anthropological research took place with advances in computer technology in the 1980s: a handful of innovative researchers working in specialized anthropology laboratories or medical departments developed the methodological inventory needed to extract critical information from subjects in vivo and from fossilized remains. A considerable part of this information is preserved in the physically heretofore inaccessible interior of anatomical structures. Virtual Anthropology (VA) is a means of making them visible and measurable. Thus, VA also allows access to 'hidden' landmarks; in addition, the large number of semilandmarks accessible on the form enhances the power of Geometric Morphometrics analysis. Furthermore, the density information in volume data allows manipulations such as segmentation, impossible with the real, physical object. Moreover, metric body measurements generally, and cranial measurements specifically, are also an important source of information for the analysis of the ontogenetic development of the skeletal system, and--last but not least--for clinical use (e.g., operation planning, operation simulation, prosthetics). Thus, there developed a fruitful interdisciplinary cooperation between statistics, medicine, and physical anthropology.

Anthropology, Physical↗

An illustrated identification key to four different species of adult Dinoderus (Coleoptera: Bostrichidae), commonly attacking dried cassava chips in West Africa.

Bostrichids of the genus Dinoderus are commonly found as pests of dried cassava chips in West Africa. An illustrated key facilitating the identification of the four most frequent African species, i.e. D. bifoveolatus (Wollaston), D. minutus (Fabricius), D. porcellus Lesne, and D. oblongopunctatus Lesne is presented.

Journal Article↗

Construction and characterization of a gridded cattle BAC library.

A bovine genomic large-insert bacterial artificial chromosome (BAC) library has been constructed from leukocytes of a Holstein-Friesian male. Size fractionated DpnII-digested genomic DNA was ligated to the dephosphorylated BamH1 ends of a pBACe3.6 vector. Approximately 8.3 x 10(4) individual BAC clones were picked into 384-well plates. Two-hundred and sixty-seven randomly chosen clones were characterized by pulsed-field gel electrophoresis (PFGE). The average insert size was 104 kb with a frequency of clones without inserts of 5.5%. Thirty-four BAC clones were mapped by fluorescence in situ hybridization (FISH) to cattle chromosomes. Three showed signals at more than one location, one of them on the centromeric regions of all autosomes, indicating that the clone contains centromeric repeats. A subset of these BAC clones was used for the development of sequence tagged sites. Both subcloning and direct sequencing of the BACs were used for generating sequence tagged site information. The clones from the library were gridded onto high-density membranes, and PCR superpools were produced from the same set of clones. Membranes and superpools are available through the Resource Centre of the German Human Genome Project in Berlin (http:// www.rzpd.de).

Animals↗

Methicillin-resistant Staphylococcus aureus in a teaching hospital: investigation of nosocomial transmission using a matched case-control study.

In early 1996 a hospital-wide methicillin-resistant Staphylococcus aureus (MRSA) epidemic was recognized in a 900-bed university hospital. In order to investigate hospital-specific transmission routes, a case-control study was carried out. Cases and controls were matched for age (+/- 10 years), sex, admission date (+/- 10 days) and clinical department on admission. Data on potential risk factors, were retrieved by chart review. Between June 1996 and February 1997, 67 patients with hospital-acquired MRSA were identified. Molecular typing showed that 85% of the cases carried an indistinguishable strain. The average time at risk for cases and controls was 17.3 and 23.7 days, respectively (P= 0.01). Seventeen patients (25.4%) developed infection. Conditional multivariate regression analysis showed that intensity of care (P= 0.002), number of transfers (P= 0.019), and fluoroquinolone therapy (P= 0.025) were independently associated with acquisition of MRSA. Intensity of care can be considered as a surrogate marker for a number of manipulations which represent the main risk factors for MRSA transmission. Frequent transfers within the hospital hinder, not only the epidemiological analyses, but also efforts to bring an outbreak under control. Our findings give epidemiological support to recent molecular studies which suggest that fluoroquinolone use may increase the transmissibility of MRSA in hospitals.

Adult↗

Decrease of cholestasis under "continuous extracorporeal stool transport (CEST)" in prematures and neonates with stomas.

According to recent studies, the percentage of neonates suffering a combination of very low birth weight (VLBW) and intestinal malformation or diseases that require surgery has increased. As opposed to mature newborn, split stoma is the therapy of choice in VLBW infants. These neonates and patients with other causes for a congenital or acquired short-bowel syndrome usually require parenteral nutrition and have a high risk of a cholestasis. Until 1993, stoma patients were treated with a special diet in our department, but depending of the stoma site often required parenteral nutrition, while the non-used distal bowel was irrigated with an isotonic electrolyte solution. With this regime, up to 38.5% of the treated patients (10126) were found to have a hyperbilirubinemia (> 3 mg/dl) after the 21st day of life. 1994, we started to use a device that continuously transfers the intestinal chylus from the proximal into the aboral bowel via a pump like a continuous extracorporeal stool transport (CEST). In this study, we evaluated the risk of cholestasis by comparison of the prospectively investigated group (CEST-group 1994-1998) of 33 infants with the results of the retrospectively studied group of 26 patients operated on between 1987 and 1993. We found a significantly lower risk of cholestasis in the CEST-Group (12.9% versus 38.5%; p<0.04). Only 3% of our patients with CEST (one patient) required permanent parenteral nutrition, compared to 50% of the conventionally treated patients.

Bilirubin↗

Orofacial analysis on the Adriatic Islands: 1. The island of Hvar as a model for odontogenetic researches.

This paper presents a preliminary orofacial analysis of a subadult population of Hvar, a Croatian island in the Adriatic. Its population represents one of the last genetic isolates in Europe and has therefore been the object of intensive crossdisciplinary research over the last 30 years. We focussed on the coefficient of endogamy on the one hand and malocclusal-related caries on the other hand, and expected differences in the latter between subgroups of the population. We analyzed 224 dental casts from children all over the island and found multiple caries in approximal surfaces in 55 percent of the children, but no significant differences between the subpopulations. Instead, significantly more caries affection was found in the boys than in the girls. The percentage of general caries affection is fairly high, even when compared to other isolated populations; it may be due to environmental influence. This would be consistent with the other results, which have putatively been caused by complex environmental influences and not solely by genetic components.

Adolescent↗

Comparing frontal cranial profiles in archaic and modern homo by morphometric analysis.

Archaic and modern human frontal bones are known to be quite distinct externally, by both conventional visual and metric evaluation. Internally this area of the skull has been considerably less well-studied. Here we present results from a comparison of interior, as well as exterior, frontal bone profiles from CT scans of five mid-Pleistocene and Neanderthal crania and 16 modern humans. Analysis was by a new morphometric method, Procrustes analysis of semi-landmarks, that permits the statistical comparison of curves between landmarks. As expected, we found substantial external differences between archaic and modern samples, differences that are mainly confined to the region around the brow ridge. However, in the inner median-sagittal profile, the shape remained remarkably stable over all 21 specimens. This implies that no significant alteration in this region has taken place over a period of a half-million years or more of evolution, even as considerable external change occurred within the hominid clade spanning several species. This confirms that the forms of the inner and outer aspects of the human frontal bone are determined by entirely independent factors, and further indicates unexpected stability in anterior brain morphology over the period during which modern human cognitive capacities emerged. Anat Rec (New Anat): 257:217-224, 1999.

Biometry↗

Immune response to human papillomavirus 16 L1E7 chimeric virus-like particles: induction of cytotoxic T cells and specific tumor protection.

Expression of human papillomavirus type 16 (HPV 16) fusion proteins LI deltaCE7(1-55) and LI deltaCE7(1-60) (carboxy-terminal deletion of LI replaced by 55 or 60 amino-terminal amino acids of E7) leads to formation of chimeric papillomavirus-like particles (CVLPs). After "infection" of cells by CVLPs, the chimeric proteins can be detected in the cytosol and the endoplasmic reticulum (ER), suggesting that they are intracellularly processed via the MHC class I pathway and, therefore, able to activate cytotoxic T lymphocytes (CTLs). To investigate the cytotoxic immune response against HPV 16 LI deltaCE7(1-60) and LI deltaCE7(1-55) CVLPs, we immunized C57Bl/6 mice with various CVLP doses without adjuvant. Two weeks after immunization, spleen cells were prepared and stimulated in vitro using HPV 16 E7-expressing transfectants of the tumor cell line RMA. In 51Cr-release cytotoxicity assays, spleen cells of mice vaccinated with LI deltaCE7(1-60) CVLPs specifically lysed the RMA-E7 transfectants as well as RMA cells loaded with the peptide E7(49-57), which represents an H2-Db-restricted CTL epitope. This demonstrates that CVLPs induce an E7-specific CTL response in mice in the absence of an adjuvant. Furthermore, immunization with CVLPs prevented outgrowth of E7-expressing tumor cells even if inoculation of cells was performed 2 weeks before vaccination. We conclude from our data that CVLPs show promise for therapy of HPV-associated lesions.

Animals↗

Effects of somatostatin, octreotide and cortistatin on ischaemic neuronal damage following permanent middle cerebral artery occlusion in the rat.

This study investigated whether peptides acting at somatostatin receptors, such as somatostatin-14, octreotide or cortistatin-14, can influence the extent of brain damage after focal ischaemia in rats. The intracerebroventricular application of 0.1 or 1.0 nmol somatostatin-14 5 min after middle cerebral artery occlusion significantly reduced the infarct size assessed 7 days after the insult (by 47% and 57% of the saline control), whereas 10.0 nmol had no significant protective effect (9% reduction). A similar dose/response relationship was obtained after intracerebroventricular injection of octreotide. The lower doses of 0.1 or 1.0 nmol afforded significant neuroprotection (reduction of the infarct size by 72 and 57%), whereas 10 nmol actually increased the infarct size up to 348%. Cortistatin-14 (10 nmol) decreased the ischaemic damage by 52%. For comparison with the neuropeptides acting on somatostatin receptors, the kappa opiate agonist enadoline (10 nmol) also had a significant protective effect against the development of focal ischaemia; the extent of the brain damage was reduced by 60% after intracerebroventricular injection.

Animals↗

Virtual reality and anthropology.

Since the discovery of the Tyrolean Iceman in 1991 advanced imaging and post processing techniques were successfully applied in anthropology. Specific techniques include spiral computed tomography and 3-dimensional reconstructions including stereolithographic and fused deposition modeling of volume data sets. The Iceman's skull was the first to be reproduced using stereolithography, before this method was successfully applied in preoperative planning. With the advent of high-end graphics workstations and biomedical image processing software packages, 3-dimensional reconstructions were established as a routine tool for analyzing volume data sets. These techniques opened totally new insights in the field of physical anthropology. Computed tomography became the ideal research tool to access the internal structures of various precious fossils without damaging or even touching them. Many of the most precious specimens from the species Autralopithecus (1.8-3.5 Myears), Homo heidelbergensis (200-600 kyears) or Homo neanderthalensis (40-100 kyears) were scanned during the last 5 years. Often the fossils are filled with a stone matrix or other materials. During the postprocessing routines highly advanced algorithms were used to remove virtually these incrustations. Thus it was possible to visualize the morphological structures that lie beneath the matrix. Some specimen were partially destroyed, so the missing parts were reconstructed on computer screen in order to get estimations of the brain volume and endocranial morphology, both major fields of interest in physical anthropology. Moreover the computerized form of the data allows new descriptions of morphologic structures by the means of 'geometric morphometrics'. Some of the results may change aspects and interpretations in human evolution. The introduction of new imaging and post processing techniques created a new field of research: Virtual Anthropology.

Algorithms↗

Early specification of limb muscle precursor cells by the homeobox gene Lbx1h.

During vertebrate embryogenesis, myogenic precursor cells of limb muscles delaminate from the ventro-lateral edge of the somitic dermomyotome and migrate to the limb buds, where they congregate into dorsal and ventral muscle masses. It has been proposed that the surrounding connective tissue controls muscle pattern formation in limbs. Regulatory molecules such as receptor tyrosine kinases like c-Met ( ref. 6) and those encoded by homeobox-containing genes, including c-Met (ref. 6), Tbx1 (ref. 7), Mox2 (ref. 8), Six1 and Six2 (ref. 9), Pitx2, Pax3 (refs 10,11) and Lbx1h (refs 12,13), are expressed in migrating limb precursor cells. The role of these genes in the patterning of limb muscles is unknown, although mutation of Pax3 or Met causes disruption of limb muscle development at an initial step, disturbing the epithelial-to-mesenchymal transition of the somitic epithelium. No limb muscle cells form in these mutants, and the early loss of myogenic precursor cells prevented an analysis of later functions of these genes during limb muscle development. Based on quail-chick chimaera studies, it was assumed that a cell-autonomous contribution of myogenic cells to the formation of individual limb muscles is negligible, and that an instructive role of limb mesenchyme is critical in this process. Here we show that Lbx1h determines migratory routes of muscle precursor cells in a cell-autonomous manner, thereby leading to the formation of distinct limb muscle patterns. Inactivation of Lbx1h, which is specifically expressed in migrating muscle precursor cells, led to a lack of extensor muscles in forelimbs and an absence of muscles in hindlimbs. The defect was caused by the failure of all muscle precursor cells of hindlimbs and of precursor cells of extensor muscles of forelimbs to migrate to their corresponding muscle anlagen. Our results demonstrate that Lbx1h is a key regulator of muscle precursor cell migration and is required for the acquisition of dorsal identities of forelimb muscles.

Animals↗