Reduced activity of the red-cell sodium-potassium pump in human obesity

Looking for evidence of reduced energy use in the cells of obese persons, we measured the numbers of sodium-potassium-pump units in erythrocytes from a group of 21 obese human subjects and found them to be reduced by 22 per cent as compared with those of nonobese controls (P <0.001). The cation-transport activity of the pump, as measured by 86rubidium uptake by the cells, we also reduced in parallel with decrease in pump units. An increased concentration of sodium in the red cells of obese subjectes was also found (9.6 +/- 0.7 vs. 7.1 +/- 0.6 mmol per liter of cells; P<0.01). This finding demonstrates independently the physiologic importance of reduced numbers of sodium-pump units and reduced pump activity as measured by ouabain binding and rubidium transport, respectively. The magnitude of the reduction in the number of pump units was found to be negatively correlated with the percentage of ideal body weight (r = 0.56, P<0.001); this observation suggests a possible role of abnormalities of the sodium pump in the pathophysiology of obesity.     

Mucin is produced by clara cells in the proximal airways of antigen-challenged mice

Airway mucus hypersecretion is a prominent feature of many obstructive lung diseases. We thus determined the ontogeny and exocytic phenotype of mouse airway mucous cells. In naive mice, ciliated (approximately 40%) and nonciliated (approximately 60%) epithelial cells line the airways, and > 95% of the nonciliated cells are Clara cells that contain Clara cell secretory protein (CCSP). Mucous cells comprise < 5% of the nonciliated cells. After sensitization and a single aerosol antigen challenge, alcian blue-periodic acid Schiff's positive mucous cell numbers increase dramatically, appearing 6 h after challenge (21% of nonciliated/nonbasal cells), peaking from Days 1-7 (99%), and persisting at Day 28 (65%). Throughout the induction and resolution of mucous metaplasia, ciliated and Clara cell numbers identified immunohistochemically change only slightly. Intracellular mucin content peaks at Day 7, and mucin expression is limited specifically to a Clara cell subset in airway generations 2-4 that continue to express CCSP. Functionally, Clara cells are secretory cells that express the regulated exocytic marker Rab3D and, in antigen-challenged mice, rapidly secrete mucin in response to inhaled ATP in a dose-dependent manner. Thus, Clara cells show great plasticity in structure and secretory products, yet have molecular and functional continuity in their identity as specialized apical secretory cells.     

Differentiation of primary cytomegalovirus infection from reactivation using the urea denaturation test for measuring antibody avidity

Cytomegalovirus (CMV) is probably the most common agent of prenatal infection of the newborn, and one of 20 congenitally infected newborns shows serious symptoms. It was therefore considered important to be able to differentiate primary CMV from reactivation in pregnant females. A urea denaturation test was used to distinguish primary from secondary rubella infection in which the urea is included in the wash step of the standard IgG ELISA. This resulted in the removal of low-avidity antibodies, which are the antibodies produced early in infection. A group of CMV IgM-negative and -positive sera were tested, and all but one showed moderate to high avidity, with an avidity index reading of more than 30%. Among a group of babies 3-12 months of age, who were CMV IgM positive, 55% (16 of 29) showed low-avidity CMV antibodies. A small group of renal transplant patients and patients with clinically and laboratory-confirmed CMV gave more or less predicted avidity index results. It appears that, with the method used at this laboratory, the urea denaturation test can be applied to CMV to determine primary infection or reactivation in the majority of cases.     

Comparative immunohistologic studies in an adoptive transfer model of acute rat cardiac allograft rejection

It has been shown that fulminant acute rejection of rat cardiac allografts across a full haplotype disparity may occur as a direct result of adoptive transfer of sensitized W3/25+ MRC OX8- SIg- T helper/DTH syngeneic spleen cells to sublethally irradiated recipients. In order to establish the immunohistologic parameters of this form of rejection, allografts and recipient lymphoid tissue were analyzed using a panel of monoclonal antibodies of known cellular distribution. These data were compared with those obtained following reconstitution of irradiated allograft recipients with unseparated sensitized spleen cells, with unreconstituted irradiated donor recipient pairs, with unmodified first-set rejection, and with induced myocardial infarction of syngeneic heart grafts transplanted to normal and to sublethally irradiated recipients. Rejecting cardiac allografts transplanted to all reconstituted irradiated recipients were characterized by extensive infiltration with MRC OX8+ (T cytotoxic-suppressor, natural killer) cells even when this subset was virtually excluded from the reconstituting inocula. A similar proportional accumulation of MRC OX8+ cells observed at the infarct margins of syngeneic heart grafts transplanted to irradiated unreconstituted recipients greatly exceeded that present in normal nonirradiated controls. These data provide evidence that under conditions of heavy recipient irradiation, MRC OX8+ cells may be sequestered within heart grafts in response to nonspecific injury unrelated to the rejection process. Although there was no significant degree of MRC OX8+ cellular repopulation within organized secondary lymphoid tissues of irradiated animals over the study period, the density of ileal mucosal MRC OX8+ lymphocytes approximated normal at 7 days post-irradiation, raising the possibility that these cells could share a common origin with those sequestered within the heart grafts. Carbon+ MRC OX6+ macrophages were a significant component of the infiltrate in all rejecting cardiac allografts, as well as in all infarcted syngeneic heart grafts--providing further evidence that macrophage "activation" with expression of class II determinants may occur in response to nonspecific injury. In unmodified first-set rejection there was an intense B cell reaction in recipient spleens and lymph nodes. In the adoptive transfer model, marked B cell expansion was exclusively confined to the parathymic lymph nodes of irradiated allograft recipients reconstituted with the sensitized W3/25+, MRC OX8-, SIg- T helper/DTH donor cell inocula.(ABSTRACT TRUNCATED AT 400 WORDS)     

High Case-Fatality Rate for Human Anthrax,Northern Ghana, 2005–2016

The human cutaneous anthrax case-fatality rate is ≈1% when treated, 5%–20% when untreated. We report high case-fatality rates (median 35.0%; 95% CI 21.1%–66.7%) during 2005–2016 linked to livestock handling in northern Ghana, where veterinary resources are limited. Livestock vaccination and access to human treatment should be evaluated.     

An inhibitory anti-factor IX antibody effectively reduces thrombus formation in a rat model of venous thrombosis

An inhibitory anti-factor IX/IXa antibody (BC2) has been investigated as an anti-thrombotic agent in a rat venous thrombosis model. The treatment of rats post-injury with a single bolus dose of BC2 (3 mg/kg, i.v.) resulted in an approximately 4 fold reduction in venous thrombus mass (P = 0.043). This efficacy was matched by a minimal (<2.5 fold) prolongation of the aPTT and had no effect on the prothrombin time (PT). Heparin by comparison, given as a bolus followed by continuous infusion, at doses comparable in efficacy at reducing thrombus formation, prolonged the aPTT >50 fold. These results demonstrate that the anti-factor IX/IXa antibody (BC2), when compared to heparin, can effectively reduce venous thrombosis with less disruptive consequences on blood clotting.