Experimental infection of human volunteers with Haemophilus ducreyi does not confer protection against subsequent challenge.
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Two groups of human volunteers were inoculated with 2 doses of live Haemophilus ducreyi 35000HP. The reinfection group consisted of 7 subjects who previously had participated in experimental infection with 35000HP to the pustular stage of disease. The control group consisted of 7 naive subjects. Papules developed at 92.8% (95% confidence interval [CI], 66.1%-99.8%) of sites inoculated with live bacteria, in the reinfection group, and at 85.7% (95% CI, 57.2%-98. 2%) of sites in the control group. Sixty-nine percent (95% CI, 36. 8%-90.9%) of papules evolved into pustules in the reinfection group, compared with 41% (95% CI, 15.2%-72.3%) in the control group. The recovery rates of H. ducreyi from surface cultures and the histopathology of biopsies obtained from both groups were similar. Thus, experimental infection to the pustular stage of disease does not provide protective immunity against subsequent challenge. (+info)
13-(S)-hydroxyoctadecadienoic acid (13-HODE) incorporation and conversion to novel products by endothelial cells.
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13(S)-Hydroxy-[12,13-3H]octadecadienoic acid (13-HODE), a linoleic acid oxidation product that has vasoactive properties, was rapidly taken up by bovine aortic endothelial cells. Most of the 13-HODE was incorporated into phosphatidylcholine, and 80% was present in the sn -2 position. The amount of 13-HODE retained in the cells gradually decreased, and radiolabeled metabolites with shorter reverse-phase high-performance liquid chromatography retention times (RT) than 13-HODE accumulated in the extracellular fluid. The three major metabolites were identified by gas chromatography combined with mass spectrometry as 11-hydroxyhexadecadienoic acid (11-OH-16:2), 9-hydroxytetradecadienoic acid (9-OH-14:2), and 7-hydroxydodecadienoic acid (7-OH-12:2). Most of the radioactivity contained in the cell lipids remained as 13-HODE. However, some 11-OH-16:2 and several unidentified products with longer RT than 13-HODE were detected in the cell lipids. Normal human skin fibroblasts also converted 13-HODE to the three major chain-shortened metabolites, but Zellweger syndrome fibroblasts produced only a very small amount of 11-OH-16:2. Therefore, the chain-shortened products probably are formed primarily by peroxisomal beta-oxidation. These findings suggest that peroxisomal beta-oxidation may constitute a mechanism for the inactivation and removal of 13-HODE from the vascular wall. Because this is a gradual process, some 13-HODE that is initially incorporated remains in endothelial phospholipids, especially phosphatidylcholine. This may be the cause of some of the functional perturbations produced by 13-HODE in the vascular wall. (+info)
Collagen synthesis in rat skin and ileum fibroblasts is affected differently by diabetes-related factors.
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Untreated diabetes reduces wound strength: a concomitant reduction in collagen deposition has been found in cutaneous wounds but not in intestinal anastomoses. This raises the question if collagen synthesis in fibroblasts from skin and intestine reacts differently to the diabetic state. Fibroblast lines were established from healthy rat skin and ileum. Diabetic rat serum was collected from hyperglycaemic rats 3 days after intravenous injection of streptozotocin (200 mg/kg). Fibroblast cultures were grown to confluency in foetal calf serum and maintained in various concentrations of glucose, insulin, normal or diabetic rat serum. Collagen synthesis was measured by incorporation of [3H]-proline into Collagenase-Digestible-Protein. Collagen synthesis in fibroblasts from both skin and ileum was not affected by increasing glucose concentrations. Insulin strongly and specifically stimulated collagen synthesis in skin fibroblasts whereas in ileum fibroblasts only a nonspecific increase of total protein synthesis was observed. In skin fibroblasts, diabetic rat serum stimulated collagen synthesis to a significantly lesser extent than normal rat serum, whereas in ileum fibroblasts stimulation by serum was far less explicit and no difference was observed between normal and diabetic serum. The fact that ileum fibroblasts respond less strongly to culture in diabetic serum than skin fibroblasts may explain our prior finding that would collagen accumulation in intestinal anastomoses is virtually unaffected during diabetes and supports the existence of tissue-specific healing responses. (+info)
Disseminated Penicillium marneffei infection presenting as a right upper lobe mass in an HIV positive patient.
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A 35 year old HIV positive patient from Hong Kong presented with a fever, cough and a skin rash in association with a lung mass, all of which were due to disseminated Penicillium marneffei infection. He made a good response to antifungal therapy. The lung mass is a previously undescribed pulmonary manifestation of disseminated Penicillium marneffei infection. Infections with this fungus should be suspected in any patient with HIV and respiratory symptoms who has visited southeast Asia. (+info)
The potential role of chemokines and inflammatory cytokines in periodontal disease progression.
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Inflammation is regulated by the expression of mediators that cause a number of pleiotropic events culminating in the recruitment of inflammatory cells and release of biologic mediators by leukocytes. If the inflammation is transient in nature, it can protect the host by activating defense mechanisms and initiating wound repair. However, if the inflammation is inappropriate, it can lead to considerable tissue damage. My colleagues and I have investigated the role of chemokines, particularly monocyte chemoattractant protein 1, in various pathological processes and the role of the proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) in experimental periodontitis. I will discuss first the studies on chemokines and then the use of IL-1 and TNF blockers in inhibiting inflammation and bone loss in the periodontium. (+info)
Role of nitric oxide in the vascular effects of local warming of the skin in humans.
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Local warming of skin induces vasodilation by unknown mechanisms. To test whether nitric oxide (NO) is involved, we examined effects of NO synthase (NOS) inhibition with NG-nitro-L-arginine methyl ester (L-NAME) on vasodilation induced by local warming of skin in six subjects. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for delivery of L-NAME and sodium nitroprusside. Skin blood flow was monitored by laser-Doppler flowmetry (LDF) at microdialysis sites. Local temperature (Tloc) of the skin at both sites was controlled with special LDF probe holders. Mean arterial pressure (MAP; Finapres) was measured and cutaneous vascular conductance calculated (CVC = LDF/MAP = mV/mmHg). Data collection began with a control period (Tloc at both sites = 34 degrees C). One site was then warmed to 41 degrees C while the second was maintained at 34 degrees C. Local warming increased CVC from 1.44 +/- 0.41 to 4.28 +/- 0.60 mV/mmHg (P < 0.05). Subsequent L-NAME administration reduced CVC to 2.28 +/- 0.47 mV/mmHg (P < 0.05 vs. heating), despite the continued elevation of Tloc. At a Tloc of 34 degrees C, L-NAME reduced CVC from 1.17 +/- 0.23 to 0.75 +/- 0.11 mV/mmHg (P < 0.05). Administration of sodium nitroprusside increased CVC to levels no different from those induced by local warming. Thus NOS inhibition attenuated, and sodium nitroprusside restored, the cutaneous vasodilation induced by elevation of Tloc; therefore, the mechanism of cutaneous vasodilation by local warming requires NOS generation of NO. (+info)
Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase.
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The oligomeric IkappaB kinase (IKK) is composed of three polypeptides: IKKalpha and IKKbeta, the catalytic subunits, and IKKgamma, a regulatory subunit. IKKalpha and IKKbeta are similar in structure and thought to have similar function-phosphorylation of the IkappaB inhibitors in response to proinflammatory stimuli. Such phosphorylation leads to degradation of IkappaB and activation of nuclear factor kappaB transcription factors. The physiological function of these protein kinases was explored by analysis of IKKalpha-deficient mice. IKKalpha was not required for activation of IKK and degradation of IkappaB by proinflammatory stimuli. Instead, loss of IKKalpha interfered with multiple morphogenetic events, including limb and skeletal patterning and proliferation and differentiation of epidermal keratinocytes. (+info)
Transmembrane insertion of the Toxoplasma gondii GRA5 protein occurs after soluble secretion into the host cell.
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The intracellular parasite Toxoplasma gondii resides within a specialized compartment, the parasitophorous vacuole (PV), that resists fusion with host cell endocytic and lysosomal compartments. The PV is extensively modified by secretion of parasite proteins, including the dense granule protein GRA5 that is specifically targeted to the delimiting membrane of the PV (PVM). We show here that GRA5 is present both in a soluble form and in hydrophobic aggregates. GRA5 is secreted as a soluble form into the PV after which it becomes stably associated with the PVM. Topological studies demonstrated that GRA5 was inserted into the PVM as a transmembrane protein with its N-terminal domain extending into the cytoplasm and its C terminus in the vacuole lumen. Deletion of 8 of the 18 hydrophobic amino acids of the single predicted transmembrane domain resulted in the failure of GRA5 to associate with the PVM; yet it remained correctly packaged in the dense granules and was secreted as a soluble protein into the PV. Collectively, these studies demonstrate that the secretory pathway in Toxoplasma is unusual in two regards; it allows soluble export of proteins containing typical transmembrane domains and provides a mechanism for their insertion into a host cell membrane after secretion from the parasite. (+info)