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S Hedges

Publications and source records attributed to S Hedges.

At least 19 recordsLinked to original sources
PubMed2005

Phylogeography, genetic structure, and diversity in the dhole (Cuon alpinus).

The Asiatic wild dog or dhole was once very widely distributed across Asia but now has a very fragmented range. In this first genetic study of this little-known species, we obtained information on genetic diversity, phylogeography, and social structure using both mitochondrial control region sequencing and microsatellite genotyping of noninvasive faecal samples from wild populations, as well as from museum and captive samples. A pattern largely consistent with isolation by distance across the Asian mainland was observed, with no clear subspecies distinctions. However, two major phylogeographical groupings were found across the mainland, one extending from South, Central, and North India (south of the Ganges) into Myanmar, and the other extending from India north of the Ganges into northeastern India, Myanmar, Thailand and the Malaysian Peninsula. We propose a scenario involving glaciation events that could explain this pattern. The origin of the dhole populations in Sumatra and Java is enigmatic and requires further study. Very low levels of genetic diversity were observed among wild dholes from Baluran National Park in Java, Indonesia, but in contrast, high levels were observed in Mudumalai Wildlife Sanctuary in South India.

Animals↗
PubMed2000

The secreted effector protein of Salmonella dublin, SopA, is translocated into eukaryotic cells and influences the induction of enteritis.

Salmonella-induced enteritis is associated with the induction of an acute intestinal inflammatory response and net fluid secretion into the lumen of infected mucosa. Proteins secreted by the Inv/Spa type III secretion system of Salmonella play a key role in the induction of these responses. We have demonstrated recently that the Inv/Spa-secreted SopB and SopD effector proteins are translocated into eukaryotic cells via a Sip-dependent pathway and act in concert to mediate inflammation and fluid secretion in infected ileal mucosa. Mutations of both sopB and sopD significantly reduced, but did not abrogate, the enteropathogenic phenotype. This indicated that other virulence factors are involved in the induction of enteritis. In this work, we characterize SopA, a secreted protein belonging to the family of Sop effectors of Salmonella dublin. We demonstrate that SopA is translocated into eukaryotic cells and provide evidence suggesting that SopA has a role in the induction of enteritis.

Amino Acid Sequence↗
PubMed1998

Clonidine does not potentiate the antipsychotic effects of neuroleptics in chronically ill patients.

Clonidine is a centrally acting antihypertensive and has been prescribed widely for more than 20 years. Because it decreases central norepinephrine activity, clonidine has been investigated as an antipsychotic. In most of the preliminary studies, clonidine was tested as the sole antipsychotic agent. We performed a double-blind, placebo-controlled, crossover study to compare a placebo plus a neuroleptic to clonidine plus a neuroleptic in a group of 16 chronically psychotic patients. Of these 16, 3 dropped out secondary to side effects of the clonidine and 1 withdrew from the study. The clonidine dosage varied from 0.2 to 0.6 mg per day. The concurrent neuroleptic (one of the following: haloperidol, thiothixene, thioridazine, mesoridazine, or fluphenazine) averaged 34 mg per day of haloperidol equivalents. Symptoms were monitored using the Psychiatric Symptoms Assessment Scale. The data provided evidence that a clonidine/neuroleptic combination was not more effective than a neuroleptic alone in this group of patients. These data suggest that the central antinorepinephrine activity of a neuroleptic is not potentiated further by clonidine.

Adjuvants, Pharmaceutic↗
PubMed1998

Identification of a pathogenicity island required for Salmonella enteropathogenicity.

Salmonella spp. interact with ileal mucosa and disrupt normal intestinal function, which results in an acute inflammatory cell influx, fluid secretion and enteritis. We have recently characterized SopB, a novel secreted effector protein of Salmonella dublin, and presented evidence that SopB is translocated into eukaryotic cells via a sip-dependent pathway to promote fluid secretion and inflammatory responses. Here, we show that sopB is located on a large DNA fragment unique to the Salmonella chromosome. This locus is conserved in Salmonella and maps at approximately 20 centisome of the S. typhimurium chromosome. Sequence analysis revealed that this Salmonella-specific DNA fragment is flanked by DNA sequences with significant sequence similarity to the Escherichia coli K-12 genes, tRNA1ser (serT) on one side and copS/copR on the other. Thus, this Salmonella-specific DNA fragment has features characteristic of 'pathogenicity islands' and, therefore, it was denoted SPI-5 (Salmonella pathogenicity island-5). SPI-5 was sequenced and was found to contain five novel genes, pipA, pipB, pipC, pipD (pathogenicity island-encoded proteins) and orf, in addition to sopB. The effect of mutations in pipA, pipB and pipD on the induction of fluid secretion and an acute inflammatory cell influx was assessed in bovine ligated ileal loops. The effect of mutations in SPI-5-encoded genes on systemic salmonellosis was assessed in mice. The results of these experiments suggest that SPI-5-encoded genes contribute to enteric but not to systemic salmonellosis.

Amino Acid Sequence↗
PubMed1997

A secreted effector protein of Salmonella dublin is translocated into eukaryotic cells and mediates inflammation and fluid secretion in infected ileal mucosa.

Enteritis induced by non-typhoid pathogenic Salmonella is characterized by fluid secretion and inflammatory responses in the infected ileum. The inflammatory response provoked by Salmonella initially consists largely of a neutrophil (PMN) migration into the intestinal mucosa and the gut lumen. The interactions between Salmonella and intestinal epithelial cells are known to play an essential role in inducing the inflammatory response. Upon interaction with epithelial cells salmonellae are able to elicit transepithelial signalling to neutrophils. This signalling is recognized as a key virulence feature underlying Salmonella-induced enteritis. However, the nature and mechanism of such signalling has not been clarified to date. Here, we characterize SopB, a novel secreted effector protein of Salmonella dublin, and present data implying that SopB is translocated into eukaryotic cells via a sip-dependent pathway to promote fluid secretion and inflammatory responses in the infected ileum.

Amino Acid Sequence↗
PubMed1995

Magnetic resonance versus computed tomographic imaging in acute stroke.

BACKGROUND AND PURPOSE: This study was an attempt to determine whether CT and MRI are comparable or if one is superior to the other in the early detection of ischemic stroke or hematoma. METHODS: Patients with acute stroke were sought within 3 hours of onset for clinical examination and prospective evaluation by concurrently performed CT and MRI. Repeated clinical and imaging studies were undertaken when possible immediately after imaging and at 24 hours, 3 to 5 days, and 3 months. The study neurologists were blinded to the results of imaging, as were the study radiologists to the clinical findings. The study radiologists read the scans in sequence, mapping each imaging on standard templates before viewing a later scan. No retrospective revisions of imaging mapping of earlier images were undertaken. RESULTS: Sixty-eight patients were recruited within 4 hours and an additional 12 patients within 24 hours. Seventy-five strokes were due to infarction and five to hemorrhage. The median time to first scan was 132 minutes. Although some of the infarctions in 75 patients were detected within 1 hour, the fraction of positive first scans approached an asymptote at 2 to 3 hours. Overall, with the use of conventional non-contrast-enhanced CT and T1- and T2-weighted MRI, neither was superior in the very early detection of either hematoma or infarction. There was a marginally significant correlation between early positive brain imaging and the severity of the stroke. Some patients had initially positive CT and/or MRI scans, but their neurological examination had returned to normal by 24 hours. Overall, CT was better than baseline MRI at predicting 24-hour outcome. After 24 hours, both CT and MR more conspicuously defined the lesion limits than they did at baseline. CONCLUSIONS: With the technology available through 1991, neither CT nor MRI proved superior in the detection of the earliest signs of stroke.

Adolescent↗
PubMed1994

Bacterial adherence and mucosal cytokine production.

1. Uropathogenic E. coli adhere to mucosal sites. 2. In the urinary tract, adherence is followed by inflammation, including a mucosal cytokine response. 3. Bacteria activate epithelial cells to secrete IL-6 and IL-8. IL-6 may cause the fever and acute phase response that accompany systemic urinary tract infections. IL-8 may function as a neutrophil chemoattractant. 4. E. coli up-regulate adhesion molecule expression on epithelial cell lines and neutrophil migration through epithelial cell monolayers. This process is inhibited by antibodies to CD18 and ICAM-1. 5. Cytokines released by nonepithelial cells (T cells and monocytes) modify the epithelial cell cytokine response to bacteria.

Bacterial Adhesion↗
PubMed1994

Suppressed antibody and interleukin-6 responses to acute pyelonephritis in pregnancy.

This study examined the effect of pregnancy on the host response to acute pyelonephritis. Urine and serum samples were obtained at the time of diagnosis and after two weeks, from non-pregnant and pregnant women with acute pyelonephritis. The samples were analyzed for interleukin-6 (IL-6) and specific antibody activity to antigens extracted from the Escherichia coli strain infecting each patient. The host response to infection was further quantitated as fever, C-reactive protein, and renal concentrating capacity. Acute pyelonephritis in non-pregnant and pregnant women was accompanied by a significant serum and urine antibody response. The serum antibody response was significantly lower in the pregnant group. The IL-6 levels in serum and urine at diagnosis were significantly higher in the non-pregnant compared to the pregnant women. These results demonstrate that the immunosuppression of pregnancy includes the mucosal IL-6 and specific antibody responses to acute pyelonephritis caused by E. coli.

Acute Disease↗
PubMed1994

Uroepithelial cells are part of a mucosal cytokine network.

This study compared the cytokine production of uroepithelial cell lines in response to gram-negative bacteria and inflammatory cytokines. Human kidney (A498) and bladder (J82) epithelial cell lines were stimulated with either Escherichia coli Hu734, interleukin 1 alpha (IL-1 alpha), or tumor necrosis factor alpha (TNF-alpha). Supernatant samples were removed, and the RNA was extracted from cells at 0, 2, 6, and 24 h. The secreted cytokine levels were determined by bioassay or immunoassay; mRNA was examined by reverse transcription-PCR. The two cell lines secreted IL-6 and IL-8 constitutively. IL-6 and IL-8 mRNA were constitutively produced in both cell lines; IL-1 beta mRNA was detected in J82 cells. IL-1 alpha induced significantly higher levels of IL-6 secretion than did E. coli Hu734 or TNF-alpha. IL-1 alpha and TNF-alpha induced significantly higher levels of IL-8 secretion than did E. coli Hu734. Secreted IL-1 beta was not detected; IL-1 alpha and TNF-alpha were not detected above the levels used for stimulation. IL-1 alpha, IL-1 beta, IL-6, and IL-8 mRNAs were detected in both cell lines after exposure to the stimulants. TNF-alpha mRNA was occasionally detected in the J82 cell line after TNF-alpha stimulation. Cytokine (IL-6 and IL-8) and control (glyceraldehyde 3-phosphate dehydrogenase [G3PDH] and beta-actin) mRNA concentrations were quantitated with internal PCR standards. Cytokine mRNA levels relative to beta-actin mRNA levels were the highest in E. coli-stimulated cells. In comparison, the cytokine mRNA levels relative to G3PDH mRNA levels were the highest in IL-1 alpha-stimulated cells. beta-Actin mRNA levels decreased after bacterial stimulation but not after cytokine stimulation, while G3PDH mRNA levels increased in response to all of the stimulants tested. These results suggested that E. coli Hu734 lowered the beta-actin mRNA levels in uroepithelial cells, thus distorting the IL-6 and IL-8 mRNA levels relative to this control. In summary, E. coli IL-1 alpha and TNF-alpha were found to activate the de novo synthesis and secretion of IL-6 and IL-8 in uroepithelial cells. These results emphasize the role of epithelial cells in cytokine-mediated responses during the early stages of infection.

Actins↗
PubMed1993

Cyclosporin A does not inhibit IL-1 alpha-induced epithelial cell IL-6 secretion.

Trauma and infection activated a murine mucosal IL-6 response in different ways: the IL-6 response to bacteria was sensitive to Cyclosporin A (CsA); the IL-6 response to trauma was not. The aim of the present study was to identify possible activators of the CsA-insensitive IL-6 secretion at the epithelial cell level. Two human epithelial cell lines from the kidney (A498) and bladder (J82) were exposed to Escherichia coli Hu734, interleukin-1 alpha (IL-1 alpha) and tumour necrosis factor alpha (TNF-alpha). The E. coli strain had been used for the in vivo experiments which led to this study, and IL-1 alpha and TNF-alpha were likely to be released during infections and trauma. The secretion of IL-6 into the supernatants was compared between cells stimulated in the presence or absence of CsA. E. coli Hu734, IL-1 alpha and TNF-alpha stimulated an IL-6 response in the two epithelial cell lines. The IL-1 alpha-induced IL-6 response was rapid, and the secreted IL-6 levels were significantly higher than those induced by E. coli Hu734 or TNF-alpha. The IL-6 response to IL-1 alpha was insensitive to CsA. By contrast, the IL-6 response to E. coli Hu734 and TNF-alpha was inhibited by CsA. These results demonstrated that the inhibitory effect of CsA depends on the stimulus triggering the IL-6 response. IL-1 alpha may play a role in the induction of trauma-associated CsA-insensitive IL-6 secretion.

Animals↗
PubMed1993

Selective cytokine production by epithelial cells following exposure to Escherichia coli.

This study compared the repertoire of cytokines produced by epithelial cell lines and human peripheral blood monocytes in response to Escherichia coli. The A-498 and J82 urinary tract epithelial cell lines and human peripheral blood monocytes were exposed to E. coli Hu734. The cytokine content of single cells was detected by indirect immunofluorescence using monoclonal antibodies to interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF-alpha), TNF-beta, IL-6, IL-8, and granulocyte macrophage-colony-stimulating factor, and the number of positive cells was used to quantitate the response. The J82 bladder cell line stained positive for IL-6, IL-8, and IL-1 alpha. The IL-8 and IL-6 response peaked at 2 h, while the number of IL-1 alpha-positive cells reached a peak 6 h after E. coli stimulation. The A-498 kidney cell line stained for IL-8 with a peak at 2 h and IL-6 with a peak at 6 h after E. coli stimulation. Peripheral blood monocytes stained for the cytokines IL-1 alpha, IL-1 beta, IL-8, IL-6, and TNF-alpha but not for TNF-beta and granulocyte macrophage-colony-stimulating factor after stimulation with E. coli. The results demonstrated that bacteria activated a cytokine response in the epithelial cell lines and monocytes. The epithelial cell lines had a more limited cytokine response profile than circulating monocytes, which may serve to limit the consequences of microbial exposure at the mucosal surface and help maintain the integrity of other tissue compartments.

Adult↗