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Biomedical subjects

Paul Martin

Publications and source records attributed to Paul Martin.

At least 91 records · Page 5Linked to original sources
PubMed2004

New aspects regarding evolution and virulence of Listeria monocytogenes revealed by comparative genomics and DNA arrays.

Listeria monocytogenes is a food-borne bacterial pathogen that causes a wide spectrum of diseases, such as meningitis, septicemia, abortion, and gastroenteritis, in humans and animals. Among the 13 L. monocytogenes serovars described, invasive disease is mostly associated with serovar 4b strains. To investigate the genetic diversity of L. monocytogenes strains with different virulence potentials, we partially sequenced an epidemic serovar 4b strain and compared it with the complete sequence of the nonepidemic L. monocytogenes EGDe serovar 1/2a strain. We identified an unexpected genetic divergence between the two strains, as about 8% of the sequences were serovar 4b specific. These sequences included seven genes coding for surface proteins, two of which belong to the internalin family, and three genes coding for transcriptional regulators, all of which might be important in different steps of the infectious process. Based on the sequence information, we then characterized the gene content of 113 Listeria strains by using a newly designed Listeria array containing the "flexible" part of the sequenced Listeria genomes. Hybridization results showed that all of the previously identified virulence factors of L. monocytogenes were present in the 93 L. monocytogenes strains tested. However, distinct patterns of the presence or absence of other genes were identified among the different L. monocytogenes serovars and Listeria species. These results allow new insights into the evolution of L. monocytogenes, suggesting that early divergence of the ancestral L. monocytogenes serovar 1/2c strains from the serovar 1/2b strains led to two major phylogenetic lineages, one of them including the serogroup 4 strains, which branched off the serovar 1/2b ancestral lineage, leading (mostly by gene loss) to the species Listeria innocua. The identification of 30 L. monocytogenes-specific and several serovar-specific marker genes, such as three L. monocytogenes serovar 4b-specific surface protein-coding genes, should prove powerful for the rapid tracing of listeriosis outbreaks, but it also represents a fundamental basis for the functional study of virulence differences between L. monocytogenes strains.

Biological Evolution↗
PubMed2004

Differentiation of the major Listeria monocytogenes serovars by multiplex PCR.

A new multiplex PCR assay was developed to separate the four major Listeria monocytogenes serovars isolated from food and patients (1/2a, 1/2b, 1/2c, and 4b) into distinct groups. The PCR test, which constitutes a rapid and practical alternative to laborious classical serotyping, was successfully evaluated with 222 Listeria strains.

Base Sequence↗
PubMed2004

Parallels between tissue repair and embryo morphogenesis.

Wound healing involves a coordinated series of tissue movements that bears a striking resemblance to various embryonic morphogenetic episodes. There are several ways in which repair recapitulates morphogenesis. We describe how almost identical cytoskeletal machinery is used to repair an embryonic epithelial wound as is involved during the morphogenetic episodes of dorsal closure in Drosophila and eyelid fusion in the mouse foetus. For both naturally occurring and wound-activated tissue movements, JNK signalling appears to be crucial, as does the tight regulation of associated cell divisions and adhesions. In the embryo, both morphogenesis and repair are achieved with a perfect end result, whereas repair of adult tissues leads to scarring. We discuss whether this may be due to the adult inflammatory response, which is absent in the embryo.

Animals↗
PubMed2004

Advances in liver transplantation. New strategies and current care expand access, enhance survival.

Liver transplantation revolutionized the management of liver disease. Although the number of patients who could benefit from a transplant far exceeds the number of available cadaveric donors, new strategies, such as splitting cadaveric organs and using living donors, have expanded access to transplantation. Here, a team of transplant physicians highlights these new strategies, as well as the long-term management issues of special relevance to primary care physicians caring for transplant recipients.

Cadaver↗
PubMed2004

Effect of aminoglycoside otic drops on isolated cochlear outer hair cells with and without liver extract activation.

OBJECTIVE: To assess the ototoxicity of commercially available Gentacidin and TobraDex ear drops with and without liver extract activation using isolated cochlear outer hair cells (OHCs). MATERIAL AND METHODS: OHCs from adult chinchilla cochleae were exposed to standard bathing solution (SBS), liver extract alone and Gentacidin and TobraDex ear drops with and without liver extract. All experiments were performed at an osmolality of 305 +/-5 mOsm, at room temperature and for up to 60 min. OHC images were recorded using an inverted microscope and analyzed electronically. Time to cell death and changes in cell length were measured. RESULTS: The time to cell death and the percent change in cell length were significantly shorter in the Gentacidin+liver extract group than in the Gentacidin alone group (p < 0.05). The TobraDex+liver extract group showed a significantly decreased time to cell death compared to the SBS control group (p < 0.05). There were no significant differences in cell length or time to cell death between the TobraDex+liver extract group and the TobraDex alone group (p > 0.05). CONCLUSION: This study suggests that the cytotoxicity of aminoglycoside ear drops to isolated OHCs in vitro requires

Aminoglycosides↗
PubMed2004

Leading by example.

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Community Health Nursing↗
PubMed2003

Targeting connexin43 expression accelerates the rate of wound repair.

The repair of tissue damage is a key survival process in all organisms and involves the coordinated activation of several cell types. Cell-cell communication is clearly fundamental to this process, and a great deal is known about extracellular communication within the wound site via cytokines. Here we show that direct cell-cell communication through connexin 43 (Cx43) gap junction channels also plays a major role in the wound healing process. In two different wound healing models, incisional and excisional skin lesions, we show that a single topical application of Cx43 antisense gel brings about a transient downregulation of Cx43 protein levels, and this results in a dramatic increase in the rate of wound closure. Cx43 knockdown reduces inflammation, seen both macroscopically, as a reduction in swelling, redness, and wound gape, and microscopically, as a significant decrease in neutrophil numbers in the tissue around the wound. One long-term consequence of the improved rate of healing is a significant reduction in the extent of granulation tissue deposition and the subsequent formation of a smaller, less distorted, scar. This approach is likely to have widespread therapeutic applications in other injured tissues and opens up new avenues of research into improving the wound healing process.

Animals↗
PubMed2003

Wound healing in the PU.1 null mouse--tissue repair is not dependent on inflammatory cells.

Damage to neonatal and adult tissues always incites an influx of inflammatory neutrophils and macrophages. Besides clearing the wound of invading microbes, these cells are believed to be crucial coordinators of the repair process, acting both as professional phagocytes to clear wound debris and as a major source of wound growth factor signals. Here we report wound healing studies in the PU.1 null mouse, which is genetically incapable of raising the standard inflammatory response because it lacks macrophages and functioning neutrophils. Contrary to dogma, we show that these "macrophageless" mice are able to repair skin wounds with similar time course to wild-type siblings, and that repair appears scar-free as in the embryo, which also heals wounds without raising an inflammatory response. The growth factor and cytokine profile at the wound site is changed, cell death is reduced, and dying cells are instead engulfed by stand-in phagocytic fibroblasts. We also show that hyperinnervation of the wound site, previously believed to be a consequence of inflammation, is present in the PU.1 null wound, too.

Animals↗
PubMed2003

Nuclear gene sequences from a late pleistocene sloth coprolite.

The determination of nuclear DNA sequences from ancient remains would open many novel opportunities such as the resolution of phylogenies, the sexing of hominid and animal remains, and the characterization of genes involved in phenotypic traits. However, to date, single-copy nuclear DNA sequences from fossils have been determined only from bones and teeth of woolly mammoths preserved in the permafrost. Since the best preserved ancient nucleic acids tend to stem from cold environments, this has led to the assumption that nuclear DNA would be retrievable only from frozen remains. We have previously shown that Pleistocene coprolites stemming from the extinct Shasta sloth (Nothrotheriops shastensis, Megatheriidae) contain mitochondrial (mt) DNA from the animal that produced them as well as chloroplast (cp) DNA from the ingested plants. Recent attempts to resolve the phylogeny of two families of extinct sloths by using strictly mitochondrial DNA has been inconclusive. We have prepared DNA extracts from a ground sloth coprolite from Gypsum Cave, Nevada, and quantitated the number of mtDNA copies for three different fragment lengths by using real-time PCR. We amplified one multicopy and three single-copy nuclear gene fragments and used the concatenated sequence to resolve the phylogeny. These results show that ancient single-copy nuclear DNA can be recovered from warm, arid climates. Thus, nuclear DNA preservation is not restricted to cold climates.

Animals↗
PubMed2003

HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen.

Allogeneic blood or marrow transplantation (BMT) is a curative therapy for chronic myeloid leukemia (CML). We have previously reported that the pharmacologic targeting of busulfan combined with cyclophosphamide (TBU/CY) can minimize regimen-related toxicity while preserving antileukemic effects. We report here on 131 consecutive chronic-phase CML patients treated with allogeneic related BMT using a TBU/CY preparative regimen, where the busulfan dose was targeted to achieve a steady-state plasma concentration of at least 900 ng/mL. The median age of the patients was 43 years (range, 14-66 years). Estimates of the probabilities of nonrelapse mortality, relapse, survival, and disease-free survival 3 years after transplantation were 14%, 8%, 86%, and 78%, respectively. Age had no statistically significant effect on survival. Although approximately 60% of the patients developed clinically extensive chronic graft-versus-host disease, the median Karnofsky score at last contact date among survivors was 95%. Of surviving patients, 11% were molecularly positive for the bcr-abl mRNA at last contact, with a median level of bcr-abl transcripts of 4.6 copies/microg RNA. These data suggest that TBU/CY is a very effective preparative regimen for CML in chronic phase, associated with an expected survival at 3 years of approximately 85%, with most patients being in molecular remission.

Adolescent↗
PubMed2003

Role for keratins 6 and 17 during wound closure in embryonic mouse skin.

Injury to adult skin triggers a response designed to restore its vital barrier function. A conserved aspect of this response is a rapid switch in gene expression whereby the type II keratin 6 (K6) and type I keratins 16 and 17 (K16, K17) are induced in epithelial cells at the wound edge. This induction occurs at the expense of the keratins normally expressed during terminal differentiation and correlates with the activation of epithelial cells at the wound edge, ahead of their migration into the wound site. Here, we show that the capacity to enact this switch is already acquired in E11.5 stage mouse embryos. Such early timing is well ahead of the onset of differentiation-specific gene expression (approximately E13.5) and the acquisition of barrier formation by developing epidermis (approximately E16.5). Induction of K6, K16, and K17 correlates with changes in the morphology of epithelial cells at the wound edge. The closure of embryonic wounds is significantly delayed in K17 null embryos, but not embryos null for K6. These observations significantly extend the correlation between K6, K16, and K17 expression and epithelial wound closure, and provide direct evidence that expression of these keratins, K17 in particular, is important for the timeliness of this process.

Animals↗
PubMed2003

6-thioguanine can cause serious liver injury in inflammatory bowel disease patients.

BACKGROUND & AIMS: Thioguanine (6-TG) has been studied as an alternative thiopurine in inflammatory bowel disease (IBD). Short-term safety and efficacy data were favorable. Experience with 6-TG in patients with acute lymphoblastic leukemia raised long-term safety concerns when implicated in nodular regenerative hyperplasia (NRH) of the liver and portal hypertension. The aim of this study was to describe the association between 6-TG and NRH in IBD. METHODS: Liver chemistries and complete blood counts were monitored, and patients were encouraged to undergo liver biopsy. Clinical data were collected by chart review, and associations were tested by univariate and multivariable analyses. Patients were classified based on the presence (group 1) or absence (group 2) of laboratory abnormalities. RESULTS: Laboratory abnormalities occurred in 29 of 111 patients (26%). Elevations of liver enzymes and a decrease in platelet counts (<200,000) were most commonly observed. Male gender (odds ratio, 2.9; 95% CI, 1.1-7.3; P < 0.03) and preferential 6-methylmercaptopurine production on 6-mercaptopurine/azathioprine (odds ratio, 3.0; 95% CI, 1.2-7.4; P < 0.04) were independently associated with laboratory abnormalities. No association was seen with duration of 6-TG treatment, cumulative dose, or 6-TG nucleotide levels. The median increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels was 39, 30, and 75 U/L, respectively, in group 1, and the median decrease in platelet count was 115,000 in group 1 versus 7000 in group 2 (P < 0.001). NRH occurred in 76% of patients undergoing biopsy in group 1 and 33% in group 2. CONCLUSIONS: NRH is a common finding in 6-TG-treated patients with IBD. The progression or reversibility of NRH remains unknown. Our findings suggest that 6-TG should not be considered as therapy for patients with IBD.

Adolescent↗