Canine granulocytic ehrlichiosis in the UK.
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Biomedical subjects
Publications and source records attributed to S Shaw.
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Lymphocytes need rigidity while in circulation, but must abruptly become deformable to undergo transmigration into tissue. Previously, the control of leukocyte deformability has been attributed to microfilaments or microtubules, but the present studies demonstrate the greater importance of vimentin intermediate filaments (IFs). In circulating T lymphocytes, IFs form a distinctive spherical cage that undergoes a rapid condensation into a juxtanuclear aggregate during chemokine-induced polarization. Measurements of the resistance of peripheral blood T lymphocytes to global deformation demonstrate that their rigidity is primarily dependent on intact vimentin filaments. Microtubules, in contrast, are not sufficient to maintain rigidity. Thus, vimentin IFs are a primary source of structural support in circulating human lymphocytes, and their regulated collapse is likely to be an essential element in chemokine-induced transendothelial migration.
We have completed a genome scan of a 12-generation, 3,400-member pedigree with schizophrenia. Samples from 210 individuals were collected from the pedigree. We performed an "affecteds-only" genome-scan analysis using 43 members of the pedigree. The affected individuals included 29 patients with schizophrenia, 10 with schizoaffective disorders, and 4 with psychosis not otherwise specified. Two sets of white-European allele frequencies were used-one from a Swedish control population (46 unrelated individuals) and one from the pedigree (210 individuals). All analyses pointed to the same region: D6S264, located at 6q25.2, showed a maximum LOD score of 3.45 when allele frequencies in the Swedish control population were used, compared with a maximum LOD score of 2.59 when the pedigree's allele frequencies were used. We analyzed additional markers in the 6q25 region and found a maximum LOD score of 6.6 with marker D6S253, as well as a 6-cM haplotype (markers D6S253-D6S264) that segregated, after 12 generations, with the majority of the affected individuals. Multipoint analysis was performed with the markers in the 6q25 region, and a maximum LOD score of 7.7 was obtained. To evaluate the significance of the genome scan, we simulated the complete analysis under the assumption of no linkage. The results showed that a LOD score >2.2 should be considered as suggestive of linkage, whereas a LOD score >3.7 should be considered as significant. These results suggest that a common ancestral region was inherited by the affected individuals in this large pedigree.
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We here report that aging increases expression of endothelin-1 and NO synthases in the vasculature and kidney of normotensive rats in vivo. Expression of preproendothelin-1 mRNA was quantified by RT-PCR and in situ hybridization, and endothelin-1 protein was determined by radioimmunoassay/HPLC. Vascular mRNA expression of NO synthase isoforms II and III was analyzed by RT-PCR. In young animals, vascular endothelin-1 protein was differentially expressed (aorta < renal artery < carotid artery) and increased with aging in all vascular beds (P < 0.05). In the intact aorta of aged rats, mRNA expression of preproendothelin-1, "inducible" NO synthase II, and endothelial cell NO synthase III gene was up-regulated (P < 0.05). Moreover, preproendothelin-1 mRNA expression increased in glomeruli and tubulointerstitial cells (P < 0.05). To our knowledge this is the first study demonstrating local vascular up-regulation of the trophic factor endothelin under physiological conditions. Activation of vascular endothelin and NO synthases may be important, pressure-independent factors contributing to structural and functional abnormalities of age-dependent diseases, including atherosclerosis.
BACKGROUND/AIMS: Hepatic stellate cells (HSC) are involved in the pathogenesis of liver fibrosis; although ET-1 is increased in cirrhosis, its pathophysiological role in fibrogenesis and portal hypertension remains controversial. The aim of this study was to investigate splanchnic hemodynamics and to correlate them with changes in ET-1 expression and HSC activation in bile duct ligated (BDL) rats. METHODS/RESULTS: Expression of the ET-1 gene was increased early as measured by quantitative reverse transcriptase-polymerase chain reaction (6-fold 3 days after BDL) whereas ET-1 peptide measured by RIA increased significantly only in the late phase (30-fold at 28 days). There was a linear correlation between portal pressure and the amount of ET-1 in the portal vein (r = 0.66; P = 0.003), as well as between ET-1 and the volume fraction of myofibroblasts (r = 0.80, P < 10(-7)) as assessed by morphometry and immunohistochemical staining using alpha-smooth muscle actin. CONCLUSIONS: During chronic liver injury activation of HSCs and of preproET-1 mRNA is accentuated in the early phase after BDL. The late increase in ET-1 peptide may indicate that this peptide is only secondarily involved in HSC activation. The correlation between ET-1 in portal vein and portal pressure suggests that ET-1 may play an important role in the development of portal hypertension.
A hallmark of modern biology is the realization of the fundamental unity of biological processes in all life forms. Consequently, the complete genome sequencing of various bacteria, yeast (Saccharomyces cerevisiae), fly (Drosophila melanogaster) and worm (Caenorhabditis elegans) over the past five years has already had an impact on all of biology. "Model organisms" have contributed a great deal to immunology; for example, the Toll receptors of the fly provided the impetus for the investigation of Toll-like receptors, which proved to be fundamental elements in the mammalian innate immune system. The recent release of a draft sequence of the human genome provides the first panoramic view of the 30000-35000 human genes in the human genetic blueprint and provides a plethora of new details, the significance of which will take some time to appreciate. The over-riding concepts that emerge from these studies relate primarily to general evolutionary processes that are equally as relevant to immunology as they are to other disciplines of biology.
The most recent Human Leucocyte Differentiation Antigen Workshop ("HLDA7") took place in 2000 in Harrogate, UK and the proceedings are about to be published (Leucocyte Typing VII). New Sections were introduced in this Workship (Dendritic cells, Stem/progenitor cells, Erythroid cells and Carbohydrate Structures) and monoclonal antibodies were selected for which at least some molecular data were already available (to avoid "blind" screening of reagents against known specificities). A total of more than 80 new CD specificities were established (previously the average was less than 30 new CD specificities per Workshop) and these are listed in this article. There is already evidence for the existence of many new leucocyte surface molecules for study at the next HLDA Workshop (in Adelaide in 2004), and we have listed in this article a number of such potential CD candidates (identified following the production of monoclonal antibodies or via gene cloning). There are also today an increasing number of lineage- and/or stage-restricted leucocyte-associated molecules localised within the cell cytoplasm (or nucleus): they will certainly prove of intense in the future for many laboratories studying human haematopoietic cells (regardless of whether a new "intracellular CD" categorisation scheme is devised for such molecules).
The purpose of this study was to determine the frequency of responses to selected fragrance materials in patients who were fragrance sensitive. 178 patients were evaluated in 8 centers worldwide with a fragrance mix (FM) and 20 other fragrance materials. Reaction to the fragrance mixture (FM) occurred in 78.7% of the subjects. Substances reacting at a rate of 2% or higher included jasmine absolute, geranium oil bourbon, l-citronellol, spearmint oil, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran, omega-6-hexadecenlactone, dimethyltetrahydrobenzaldehyde (isomer mixture), and alpha-amylcinnamaldehyde. These chemicals should be furthur evaluated to corroborate their allergenicity. We are constantly looking for new fragrance allergens to extend the diagnostic capability of the fragrance mix (FM).
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Clostridium novyi has recently been identified as the causative organism responsible for the deaths of 35 heroin addicts who had injected themselves intramuscularly. We present two heroin addicts who developed C. botulinum infection following intramuscular or subcutaneous injection of heroin. Like C. novyi, this grows under anaerobic conditions and clinical presentation may be similar; however, descending motor or autonomic signs are invariably present in botulism. The prognosis is good if the diagnosis is made early and appropriate treatment commenced.
BACKGROUND: There is a growing awareness that some individuals exhibit heightened skin sensitivity, particularly on the face, and have a high incidence of adverse reactions to cosmetics and toiletries. OBJECTIVES: To carry out an epidemiological study to assess the prevalence of sensitive skin and cosmetic-related adverse events in a U.K. population, and to examine possible factors that may be associated with sensitive skin. METHODS: Self-assessment questionnaires were sent out to 3300 women and 500 men, randomly selected, who were over the age of 18 years and lived within a 10-mile radius of High Wycombe (Bucks.). Fifty non-responder women were also questioned by telephone to ensure that the postal responders were representative of the population as a whole. RESULTS: The response rates were 62% for women and 52% for men, with the incidence of self-reported skin sensitivity being 51.4% and 38.2%, respectively. Ten per cent of women and 5.8% of men described themselves as having very sensitive skin. Fifty-seven per cent of women and 31.4% of men had experienced an adverse reaction to a personal product at some stage in their lives, with 23% of women and 13.8% of men having had a problem in the last 12 months. Among the women, symptoms of cosmetic-induced subjective sensory skin discomfort (burning, stinging, itching etc.) occurred more commonly in the sensitive skin cohort (53%) than in those who regarded themselves as non-sensitive (17%). An atopic diathesis in women did not appear to be a predictive factor for sensitive skin, the incidence of self-perceived sensitive skin being equivalent for atopics (49%) and non-atopics (51%). Furthermore, some 34% of atopic women described themselves as being non-sensitive. Nevertheless, the incidence of atopy was higher among the women in the sensitive skin group (49%) than among those in the non-sensitive group (27%). Dry skin and a predilection for blushing/flushing were associated factors for sensitive skin. CONCLUSIONS: Our survey indicates that sensitive facial skin is a common problem for women and men in the U.K. and points to the need for the development of personal products designed for this skin phenotype.
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