Modification of collagen matrices for enhancing angiogenesis

The vascularization of engineered tissues in many cases does not keep up with the ingrowth of cells. Nutrient and oxygen supply are not sufficient, which ultimately leads to the death of the invading cells. The enhancement of the angiogenic capabilities of engineered tissues therefore represents a major challenge in the field of tissue engineering. The immobilization of angiogenic growth factors may be useful for enhancing angiogenesis. The most potent angiogenic growth factor specific to endothelial cells, vascular endothelial growth factor (VEGF), occurs in several splice variants. The variant with 165 amino acids both has a high angiogenic activity and a high affinity for heparin. We therefore incorporated heparin molecules into collagen matrices by covalently cross-linking them to amino functions on the collagen. Physical binding of VEGF to the heparin may then prevent a rapid clearance from the implant, while the release rate may become coupled to the degradation of the collagen matrix. The modified matrices were characterized by determination of the extent of the heparin immobilization, the in vitro degradation rate by collagenase. For testing the angiogenic properties, non-modified and heparinized collagen specimens were--either loaded with VEGF or non-loaded--subcutaneously implanted on the back of rats. Specimens were explanted after varying periods of implantation, the dry weights and the hemoglobin contents, as well as immunostained histological sections were evaluated: heparinized collagen matrices loaded with VEGF are vascularized to a substantially higher extent as compared to non-modified matrices.     

Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18

Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type.     

Influenza: Diagnosis,epidemiology, prophylaxis

Sans résumé     

The mast cell: distribution and maturation in the peritoneal cavity of the adult rat.

In the peritoneal cavity of the adult rat mast cells at the four stages of progressive maturation (and corresponding increase of sulphation of granules) are best demonstrated in free peritoneal fluid. Of the 0.1-0.2x10(6) cells in the free fluid, 26% are at stage 1 of maturation (all granules are stained by Alcian blue). 24% at stage 2 (majority of granules are stained by Alcian blue, minority by safranin), 20% at stage 3 (majority of granules are safranin-positive), and 30% at stage 4 (all granules are safranin-positive). Peritoneal washings yield a mean of about 1.3-1.8x10(6) mast cells of which 16% are at stage 1, 24% at stage 2, 34% at stage 3 and 26% at stage 4. The greater number recovered by washing, compared with the number in free peritoneal fluid, suggests that a substantial number of mast cells lie on the surface of the peritoneal membranes.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

1. Download : Download high-res image (202KB)
2. Download : Download full-size image

     

Der Einfluss von Trematoden auf den Gasstoffwechsel von Stagnicola palustris Müll.

Zusammenfassung 1. Der Sauerstoffverbrauch pro mg nichtinfizierter Stagnicola palustris ist, statistisch gesichert, dem Gesamtgewicht nicht linear proportional. Bei den infizierten Tieren scheinen ähnliche Verhältnisse zu herrschen.2. Nach dem X²-Verfahren von Pearson kann ein Unterschied im Sauerstoffverbrauch zwischen nichtbefallenen und befallenen Schnecken statistisch gesichert werden.Die nichtbefallenen veratmen pro Gewichtseinheit mehr Sauerstoff als die befallenen Tiere.3. Der geringeren Sauerstoffverbrauch der befallenen Schnecken wird auf deren verringerte Bewegungsaktivität zurückgeführt.4. Die Sporocysten sind in der Lage, sowohl Glukose wie Glykogen aus dem sie umgebenden Medium aufzunehmen und zu veratmen.5. Lichteinwirkung aktiviert die Kriechbewegungen der in der Sporocyste zu etwa einem Drittel vorhandenen Cercarien. Gleichsinnig damit erhöht sich der respiratorische Quotient, wenn den Tieren Glukose geboten wird.6. Der Parasit ist in den Stoffwechsel seines Wirts so eingefügt, daß sich hinsichtlich des Gasstoffwechsel, sowohl qualitativ wie quantitativ kein nennenswerter Unterschied ergibt.Mit 10 TextabbildungenMeinem sehr verehrten Lehrer, Herrn Prof. Dr. W. Neuhaus, danke ich für die Überlassung des Themas und seine stetige, freundliche Unterstützung in allen Fragen.     

Clinical and epidemiological aspects of human bocavirus infection

Human bocavirus was recently described as a novel member of the Parvoviridae to infect humans. Based on accumulating clinical and epidemiological data the virus is currently being associated with respiratory infections in young children and infants and is furthermore discussed as causative agent of gastrointestinal illness.     

Erratum: Sodium channel gene (SCN5A) mutations in 44 index patients with brugada syndrome: Different incidences in familial and sporadic disease

In supplementation of previously published cardiac sodium channel (SCN5A) gene mutations that were cited in the text, in Table 2 and in Figure 2 we here apply an updated gene mutation nomenclature (Human Genome Variation Society, 2005) to facilitate mutation annotation comparison (SCN5A cDNA reference: NM_198056.1 or GI: 37622906; amino acid reference sequence: SWISS‐PROT entry Q14524, long splice variant, 2,016 amino acids): Mutation: c.2602delC Amino acid change: p.Glu868X Mutation: c.2581_2582delTT Amino acid change: p.Phe861Trp fsX90 Mutation: c.4477_4479delAAG Amino acid change: p.Lys1493del Mutation: c.5425C>A Amino acid change: p.Ser1812X