Cyclic GMP-dependent and cyclic AMP-dependent protein kinases,protein kinase modulators and phosphodieterases in arteries and veins of dogs Distribution and effects of arteriovenous fistula and arterial occlusion

Possible involvement of cyclic GMP-dependent and cyclic AMP-dependent protein kinases, protein kinase modulators and cyclic nucleotide phosphodiesterases in functions of vascular tissues were investigated in the dog. All of the above activities, localized in the smooth muscle-rich inner layer of the blood vessels, were found to be higher in the arteries than in the veins. The peripheral arteries were disproportionately richer in cyclic GMP-dependent protein kinase (as indicated by high ratios of cyclic GMP-dependent to cyclic AMP-dependent protein kinase) than were the veins, with the exception of the pulmonary artery, an atypical arterial tissue exposed to low blood pressure. Interestingly, the protein kinase ratio for the aorta, an artery with no significant role in blood pressure regulation, was not higher than that for the vena cava. Creation of femoral arteriovenous fistulae in the dogs led to preferential reductions in the cyclic GMP-dependent enzyme activity both in the proximal and distal arteries, whereas it was elevated in the stressed vein distal to the anastomotic site. The cyclic GMP-dependent enzyme was preferentially reduced in the saphenous artery distal to occlusion. Changes in the cyclic GMP-dependent enzyme activity appeared to precede gross atrophy or hypertrophy of the vessels. It is suggested that the vascular cyclic GMP-dependent protein kinase may be closely related to peripheral resistance and its regulation.     

Polyethyleneglycols and immunocamouflage of the cells tissues and organs for transplantation.

In allogenic transplant the immediate immune response is due to the recipient T cell recognition of non-self molecules presented on graft resident donor antigen presenting cells. An alternative to the transplantation tolerance paradigm is based on the development of strategies which distort alloimmune recognition of the graft by antigen reactive cells of the recipient. Immunocamouflage relies on the modification of the cell membrane surface with non-immunogenic molecules creating a barrier that prevents the recognition of antigenic sites by cells and antibodies of the recipient. Polymers can spontaneously bind to cell and tissues surfaces and sterically stabilize the underlying surface from interactions with other components in the surrounding. They can be adsorbed or chemically grafted to surfaces. Polyethylene glycol (PEG) seems to be the more effective at sterically stabilizing underlying surfaces. The outstanding protection provided by this polymer has been attributed to its molecular properties, such as its low interfacial energy, its conformation, hydrophilicity and high flexibility. The main advantage of immunocamouflage, is that it directly modify the inherent immunogenicity of the donor tissue itself, using means that are strictly physicochemical in nature and do not rely on the details of activation pathways, leaving fully competent, the immune system of the recipient.     

Extended type-1 chain glycosphingolipid antigens. Isolation and characterization of trifucosyl-Leb antigen (III4V4VI2Fuc3Lc6).

A Lewis-b-active glycosphingolipid containing a repetitive type-1 chain carbohydrate core was isolated from human colonic adenocarcinoma cell line Colo205. This glycosphingolipid was purified by HPLC and preparative high-performance thin-layer chromatography and its structure elucidated by positive-ion fast-atom-bombardment mass spectrometry with collision-induced disassociation, 1H-NMR spectroscopy and methylation analysis. The glycosphingolipid was found to be a trifucosylated derivative of this novel carbohydrate core, having the following structure: [formula; see text].     

Variability in response to UV-B among species and strains of Metarhizium isolated from sites at latitudes from 61 degrees N to 54 degrees S.

The effects of irradiances of 920 and 1200 mW m(-2) (biologically effective weighted irradiance) were examined in 2 Metarhizium album strains, 26 M. anisopliae strains, 1 M. flavoviride strain, and 1 M. taii strain isolated from sites located at latitudes from 61 degrees N to 54 degrees S. Conidia were exposed to UV-B from 1 to 6 h and subsequently examined for relative percentage culturability. Total dosage received at the end of the exposure periods ranged from 3.3 to 19.9 kJ m(-2) for the lower irradiance and from 4.3 to 25.9 kJ m(-2) for the higher irradiance. Both the irradiance values and the doses are environmentally realistic and can be observed even in temperate regions. The relationships between latitude of origin and UV-B tolerance were compared for the two levels of irradiance for the data from 1 and 2 h exposure. Exposure to both irradiances drastically reduced the relative percentage culturability of all strains. Tolerance to UV-B varied widely among strains and high variation was observed for both irradiances after all periods of exposure. After 1 h of exposure, a difference between the two irradiance levels was detectable, and this difference was magnified at longer irradiations. A significant quadratic relationship of decreasing UV-B tolerance with increasing latitude was observed after exposure of 1 and 2 h. The shape of the relationship did not differ for the two levels of irradiance. Also, we studied the effect of 1200 mW m(-2) irradiance on conidial germination time in 1 M. album strain, 7 M. anisopliae strains, and 1 M. taii strain. Exposure to UV-B delayed the germination of surviving conidia of all strains. In general, the delay in germination was directly proportional to the dose.     

Metabolic cost of generating muscular force in human walking: insights from load-carrying and speed experiments.

We sought to understand how leg muscle function determines the metabolic cost of walking. We first indirectly assessed the metabolic cost of swinging the legs and then examined the cost of generating muscular force during the stance phase. Four men and four women walked at 0.5, 1.0, 1.5, and 2.0 m/s carrying loads equal to 0, 10, 20, and 30% body mass positioned symmetrically about the waist. The net metabolic rate increased in nearly direct proportion to the external mechanical power during moderate-speed (0.5-1.5 m/s) load carrying, suggesting that the cost of swinging the legs is relatively small. The active muscle volume required to generate force on the ground and the rate of generating this force accounted for >85% of the increase in net metabolic rate across moderate speeds and most loading conditions. Although these factors explained less of the increase in metabolic rate between 1.5 and 2.0 m/s ( approximately 50%), the cost of generating force per unit volume of active muscle [i.e., the cost coefficient (k)] was similar across all conditions [k = 0.11 +/- 0.03 (SD) J/cm3]. These data indicate that, regardless of the work muscles do, the metabolic cost of walking can be largely explained by the cost of generating muscular force during the stance phase.     

The development of a population of spinal cord neurons and their axonal projections revealed by GABA immunocytochemistry in frog embryos

The development of a population of cerebrospinal-fluid-contacting neurons in the spinal cord of the Xenopus embryo ('Kolmer-Agduhr' cells) has been followed by using an immunocytochemical procedure that identifies GABA in fixed nervous tissue. Stained Kolmer-Agduhr cells containing GABA first appeared at stage 25 and their numbers increased steadily with the developmental age of the embryo. The Kolmer-Agduhr neurons had ascending ipsilateral axons that often terminated in growth cones. These axons and growth cones could be stained by the GABA antiserum from the earliest stages of outgrowth from the Kolmer-Agduhr cell body. We measured the angle of the earliest axons' outgrowth relative to the rostrocaudal axis of the spinal cord. The initial outgrowth of axons was always rostral over a narrow range of angles. This observation is inconsistent with the hypothesis of random initial outgrowth followed by later selection of the correct orientation, which would predict that axons would initially grow out over a wide range of angles. Instead, it suggests that, even from the earliest moments, axon outgrowth from the Kolmer-Agduhr cells is directed rostrally in a specific stereotyped manner.