Infection of the Laboratory Mouse with the Intracellular Pathogen Ehrlichia chaffeensis

To determine the basis of susceptibility and resistance to human monocytic ehrlichiosis (HME), immunocompetent and immunocompromised mice were infected with Ehrlichia chaffeensis and bacterial loads were measured by PCR and by immunohistochemistry. Immunocompetent (C.B-17 and C57BL/6) mice cleared the bacteria within 10 days, but immunocompromised SCID and SCID/BEIGE mice developed persistent infection in the spleen, liver, peritoneal cavity, brain, lung, and bone marrow and became moribund within 24 days. Both immunocompromised strains lack T and B lymphocytes, but the SCID/BEIGE strain is also deficient in natural killer (NK) cell function. During advanced stages of disease, the infections were associated with wasting, splenomegaly, lymphadenopathy, liver granulomas and necroses, intravascular coagulation, and granulomatous inflammation. Histochemical and immunohistochemical localization studies confirmed the presence of bacteria in tissues, and viable bacteria were cultured from infected animals. The data reveal that T and/or B cells play an essential role during resistance of immunocompetent mice to infection with E. chaffeensis and demonstrate the utility of immunocompromised mice as an experimental model for the study of HME.     

Membrane depolarization of isolated rat liver mitochondria attenuates permeability transition pore opening and oxidant production

It has been suggested that one key feature of mitochondrial permeability transition (PT) regulation is its control by the proton electrochemical gradient and that depolarization favors pore opening, swelling, and reactive oxygen species (ROS) production. Moreover, ROS have been suggested to facilitate the process of mitochondrial PT pore opening. The aim of this study was to show that collapsing the mitochondrial membrane potential with the mitochondrial uncoupler, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), at concentrations of up to 10 microM, does not induce mitochondrial swelling and, in fact, stabilizes mitochondria exposed to oxidant, protecting them from tert-butyl hydroperoxide (TBH)-induced high-amplitude swelling. FCCP decreased polyethylene glycol-induced mitochondrial contraction following exposure to TBH, indicating closing of the PT mega-channel. In the presence of the calcium uniporter inhibitor ruthenium red, FCCP induced PT due to suppression of calcium efflux. Under PT-favorable conditions, ROS production was evaluated in mitochondria following treatments with TBH, inorganic phosphate, or FCCP (with or without ruthenium red). FCCP alone and in combination with ruthenium red attenuated mitochondria-derived ROS production. FCCP also decreased the augmented ROS production induced by inorganic phosphate. It is concluded that mitochondrial depolarization protects and prevents high-amplitude swelling and PT-derived ROS production.     

Failure of ureteral stents subject to extrinsic ureteral obstruction and stent occlusions

International Urology and Nephrology - To quantify the occurrence of stent failure and the dynamic behavior of urine flow in ureter-stent systems, including the relative flow in the ureter and...     

Sweet's syndrome and subacute thyroiditis

A 63 year old woman developed biopsy documented lesions of acute febrile neutrophilic dermatosis (Sweet's syndrome) one week after the onset of subacute thyroiditis. This is only the second reported case of such an association. The role of cytokines in the development of both subacute thyroiditis and Sweet's syndrome may be the link between these two conditions.     

Two-stage reconstruction of the severely deficient alveolar ridge: bone graft followed by alveolar distraction osteogenesis

Distraction osteogenesis for the augmentation of severe alveolar bone deficiency has gained popularity during the past two decades. In cases where the vertical bone height is not sufficient to create a stable transport segment, performing alveolar distraction osteogenesis (ADO) is not possible. In these severe cases, a two-stage treatment protocol is suggested: onlay bone grafting followed by ADO. An iliac crest onlay bone graft followed by ADO was performed in 13 patients: seven in the mandible and six in the maxilla. Following ADO, endosseous implants and prosthetic restorations were placed. In all cases, the onlay bone graft resulted in inadequate height for implant placement, but allowed ADO to be performed. ADO was performed to a mean total vertical augmentation of 13.7 mm. Fifty-two endosseous implants were placed. During a mean follow-up of 4.85 years, two implants failed, both during the first 6 months; the survival rate was 96.15%. In severe cases lacking the required bone for ADO, using an onlay bone graft as a first stage treatment increases the bone height thus allowing ADO to be performed. This article describes a safe and stable two-stage treatment modality for severely atrophic cases, resulting in sufficient bone for implant placement and correction of the inter-maxillary vertical relationship.     

Directing exocrine secretory vesicles to the apical membrane by actin cables generated by the formin mDia1

The final stage in exocrine secretion involves translocation of vesicles from their storage areas to the apical membrane. We show that actin-coated secretory vesicles of the exocrine pancreas travel this distance over bundles of specialized actin cables emanating from the apical plasma membrane. These bundles are stable structures that require constant G-actin incorporation and are distinct from the actin web that surrounds the exocrine lumen. The murine mammalian Diaphanous-related formin 1 (mDia1) was identified as a generator of these cables. The active form of mDia1 localized to the apical membrane, and introduction of an active form of mDia1 led to a marked increase in bundle density along the lumen perimeter. Compromising formation of the cables does not prevent secretion, but results in disorganized trafficking and fusion between secretory vesicles. Similar apical secretory tracks were also found in the submandibular salivary glands. Together with previous results that identified a role for Diaphanous in apical secretion in tubular organs of Drosophila, the role of Diaphanous formins at the final stages of secretion appears to be highly conserved.