Basic Mechanisms in the Healing Cutaneous Wound

The process of wound healing can be divided into substrate, proliferative, and remodeling phases. The basic biologic and physiologic events which transpire during these stages are examined in detail. Particular emphasis is placed on the interactions between platelets, macrophages, and other inflammatory cells, and fibroblasts in the healing wound. Recent advances in the roles played by interleukins, fibronectin, and epidermal growth factor are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72810/1/j.1524-4725.1986.tb02099.x.pd

KIC 4247791: A SB4 system with two eclipsing binaries (2EBs)

KIC 4247791 is an eclipsing binary observed by the Kepler satellite mission. We wish to determine the nature of its components and in particular the origin of a shallow dip in its Kepler light curve that previous investigations have been unable to explain in a unique way. We analyze newly obtained high-resolution spectra of the star using synthetic spectra based on atmosphere models, derive the radial velocities of the stellar components from cross-correlation with a synthetic template, and calculate the orbital solution. We use the JKTEBOP program to model the Kepler light curve of KIC 4247791. We find KIC 4247791 to be a SB4 star. The radial velocity variations of its four components can be explained by two separate eclipsing binaries. In contradiction to previous photometric findings, we show that the observed composite spectrum as well as the derived masses of all four of its components correspond to spectral type F. The observed small dip in the light curve is not caused by a transit-like phenomenon but by the eclipses of the second binary system. We find evidence that KIC 4247791 might belong to the very rare hierarchical SB4 systems with two eclipsing binaries.Comment: 6 pages, 8 figures, 2 table

Epidermolysa bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene

BACKGROUND Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. RESULTS Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. CONCLUSIONS Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock

PCR clonality detection in Hodgkin lymphoma

B-cell clonality detection in whole tissue is considered indicative of B-cell non-Hodgkin lymphoma (NHL). We tested frozen tissue of 24 classical Hodgkin lymphomas (cHL) with a varying tumor cell load with the multiplex polymerase chain reaction (PCR) primer sets for IGH and IGK gene rearrangement (BIOMED-2). A clonal population was found in 13 cases with the IGH FR1 and/or FR2/FR3 PCRs. Using the IGK-VJ and IGK-DE PCRs, an additional six cases had a dominant clonal cell population, resulting in a detection rate of 79% in frozen tissue. Of 12 cases, also the formalin-fixed and paraffin-embedded (FFPE) tissue was tested. Surprisingly, in eight of the 12 FFPE cases with acceptable DNA quality (allowing PCR amplification of >200 nt fragments), the IGK multiplex PCRs performed better in detecting clonality (six out of eight clonal IGK rearrangements) than the IGH PCRs (four out of nine clonal rearrangements), despite a rather large amplicon size. There was no evidence of B-cell lymphoma during follow-up of 1 to 6 years and no correlation was found between the presence of a clonal result and Epstein–Barr virus in the tumor cells. Our results indicate that the present routine PCR methods are sensitive enough to detect small numbers of malignant cells in cHL. Therefore, the presence of a clonal B-cell population does not differentiate between cHL and NHL

Three Potential Sources of Microfungi in a Treated Municipal Water Supply System in Sub-Tropical Australia

Some microfungi are known to be opportunistic human pathogens, and there is a body of scientific opinion that one of their routes of infection may be water aerosols. Others have been implicated as causative agents of odours and off-tastes in drinking water. This study was undertaken to investigate three potential sources of microfungi in a treated, oligotrophic municipal water supply system in sub-tropical Australia. Formation of the microfungal component of developing biofilm on hard surfaces in water storage reservoirs was also assessed. Inside and outside air samples were collected from two reservoirs using two types of Burkard air samplers. Biofilm and soft sediment samples were collected from the inner surfaces of asbestos cement water pipes and from pipe dead ends respectively. These were analysed for microfungal growth and sporulation using Calcofluor White stain and epifluorescent microscopy. Artificial coupons of glass, PVC and concrete were immersed in two reservoirs to assess microfungal biofilm formation. This was analysed periodically using Calcofluor White stain and epifluorescent microscopy, cultures of coupon swabs and scanning electron microscopy. Fungal spores were recovered from all air samples. The number of colonies and the genera were similar for both inside and outside air. Microfungal filaments and sporulating structures were recovered from most of the pipe inner surface biofilm and dead end sediment samples, but were sparser in the biofilm than in the sediment samples. No recognisable, vegetative filamentous fungi were found in the slowly developing biofilm on coupons. This study indicates that airborne spores are an important potential source of microfungi found in water storage reservoirs. It has also demonstrated conclusively that filamentous microfungi grow and sporulate on water pipe inner surfaces and in soft sediments within the water distribution system

Incidence and Distribution of Microfungi in a Treated Municipal Water Supply System in Sub-Tropical Australia

Drinking water quality is usually determined by its pathogenic bacterial content. However, the potential of water-borne spores as a source of nosocomial fungal infection is increasingly being recognised. This study into the incidence of microfungal contaminants in a typical Australian municipal water supply was carried out over an 18 month period. Microfungal abundance was estimated by the membrane filtration method with filters incubated on malt extract agar at 25 °C for seven days. Colony forming units were recovered from all parts of the system and these were enumerated and identified to genus level. The most commonly recovered genera were Cladosporium, Penicillium, Aspergillus and Fusarium. Nonparametric multivariate statistical analyses of the data using MDS, PCA, BEST and bubble plots were carried out with PRIMER v6 software. Positive and significant correlations were found between filamentous fungi, yeasts and bacteria. This study has demonstrated that numerous microfungal genera, including those that contain species which are opportunistic human pathogens, populate a typical treated municipal water supply in sub-tropical Australia

Anti-HIV Activity Mediated by Natural Killer and CD8+ Cells after Toll-Like Receptor 7/8 Triggering

We previously found that triggering TLR7/8 either by single stranded HIV RNA or synthetic compounds induced changes in the lymphoid microenvironment unfavorable to HIV. In this study, we used selective TLR7 and 8 agonists to dissect their contribution to the anti-HIV effects. While triggering TLR7 inhibited efficiently HIV replication in lymphoid suspension cells from tonsillar origin, its effect was inconsistent in peripheral blood mononuclear cells (PBMC). In contrast, triggering TLR8 showed a very prominent and overall very consistent effect in PBMC and tonsillar lymphoid suspension cells. Depletion of dendritic cells (DC), Natural killer cells (NK) and CD8+ T-cells from PBMC resulted in the reversal of TLR8 induced anti-HIV effects. Especially noteworthy, depletion of either NK or CD8+ T-cells alone was only partially effective. We interpret these findings that DC are the initiator of complex changes in the microenvironment that culminates in the anti-HIV active NK and CD8+ effector cells. The near lack of NK and the low number of CD8+ T-cells in tonsillar lymphoid suspension cells may explain the lower TLR8 agonist's anti-HIV effects in that tissue. However, additional cell-type specific differences must exist since the TLR7 agonists had a very strong inhibitory effect in tonsillar lymphoid suspension cells. Separation of effector from the CD4+ target cells did not abolish the anti-HIV effects pointing to the critical role of soluble factors. Triggering TLR7 or 8 were accompanied by major changes in the cytokine milieu; however, it appeared that not a single soluble factor could be assigned for the potent effects