Kalirin inhibition of inducible nitric-oxide synthase

Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity.     

Theory of diaphragm structure and shape

The muscle bundles of the diaphragm form a curved sheet that extends from the chest wall to the central tendon. Each muscle bundle exerts a force in the direction of its curvature; the magnitude of this force is proportional to the curvature of the bundle. The contribution of this force to transdiaphragmatic pressure is maximal if the direction of bundle curvature is orthogonal to the surface and the curvature is maximal. That is, the contribution of muscle tension to transdiaphragmatic pressure is maximal if the muscle bundles lie along lines that are both geodesics and lines of maximal principal curvature of the surface. A theory of diaphragm shape is developed from the assumption that all muscle bundles have these optimal properties. The class of surfaces that are formed of line elements that are both geodescis and lines of principal curvature is described. This class is restricted. The lines that form the surface must lie in planes, and all lines must have the same shape. In addition, the orientation of the lines is restricted. An example of this class that is similar to the shape of the canine diaphragm is described, and the stress distribution in this example is analyzed.     

Evaluation of cardiac 31P magnetic resonance spectroscopy: reviewing NMR principles

Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia.     

Analytical development of electrospray and nanoelectrospray mass spectrometry in combination with liquid chromatography for the characterization of proteins

Microbial pathogens may be transmitted to humans via food animals and food animal products. A quick reference table is presented to provide easy access to food safety information related to the major food animal product areas. Included in the table are the pathogens, mode of transmission, public health impact, and control and prevention strategies for poultry, beef, dairy products, and pork.     

Human leukocyte derived interferon-alpha in a hydrophilic gel for the treatment of intravaginal warts in women: a placebo-controlled, double-blind study

Persistent polychlorinated biphenyl (PCB) metabolites were studied with respect to their interaction with the human glucocorticoid receptor (GR). 3-Methylsulphonyl-2,5,6,2',4',5'-hexachlorobiphenyl (3-MeSO2-CB149) was shown to compete with 3H-dexamethasone for binding to the GR, with an IC50 (concentration that inhibits 50%) of approximately 1 microM. Using GRAF cells expressing human GR, glucocorticoid responsive element, and a reporter enzyme, we demonstrated that 3-MeSO2-CB149 functionally acts as an antagonist at the GR (IC50 = 2.7 microM). In accordance with the receptor binding, the antagonism mainly appeared to be of a competitive nature. When studying the competitive binding of 24 methylsulfonyl PCBs (relative to dexamethasone) to GR from mouse liver cytosol, seven compounds had a higher affinity to GR than 3-MeSO2-CB149. Structure-activity relationship studies indicated that the presence of three chlorine atoms in the ortho-position and chlorine and methyl sulfone groups on either end of the molecule (4 and 4'-position) increased the affinity to GR. The relevance of this finding for human health is not known, but PCB methyl sulfones are ubiquitous pollutants present in mother's milk. The results stress the need for studying endocrine disruptors that affect hormonal systems other than sex and thyroidogenic hormones.     

Permanent open shunt as a reason for impotence or reduced potency after surgical treatment of priapism in 26 patients

A permanent open shunt as a cause of impotence or impaired potency after a shunt operation for priapism is an unusual situation. In this series we studied the persistence of an open shunt in 26 patients who had developed impotence or impaired potency after operative treatment for priapism. All patients had been examined by cavernosography on the suspicion of an open shunt, giving a positive finding in five of 26 cases, in all of which impotence was cured by closure of the shunt. In five patients without a permanent open shunt potency returned to normal only after 6-12 months.