Secretion of vascular endothelial growth factor/vascular permeability factor from human luteinized granulosa cells is human chorionic gonadotrophin dependent

Vascularization is a prominent event during corpus luteum formation, providing low density lipoproteins for steroid biosynthesis and enabling transport of secreted steroids. The process of vascularization is controlled by specific regulators. Vascular endothelial growth factor (VEGF), otherwise named vascular permeability factor (VPF), induces endothelial cell proliferation as well as angiogenesis in vivo and increases capillary permeability. Here we report the expression of VEGF/VPF mRNA by cultured human luteinized granulosa cells (GC) for at least 10 days. Without HCG VEGF/VPF expression declined after day 4 and by day 10 was reduced to approximately 30% of the value at day 4. However, after culture in the presence of 1 U/ml human chorionic gonadotrophin (HCG), expression of VEGF/VPF mRNA by GC was four times greater than control experiments by day 10, and increased 100% from day 4 to day 10. Simultaneously, HCG supplementation increased VEGF/VPF secretion by GC. Medium VEGF/VPF on day 3 was 13 pM without and 11 pM with HCG. Medium VEGF/VPF on day 10 was 6 pM without HCG and 29 pM with HCG. These results suggest that vascularization of the corpus luteum is induced by HCG-mediated effects of VEGF/VPF.      

Contraction history affects the in vivo quadriceps torque-velocity relationship in humans

We hypothesized that the history of contraction would affect the in vivo quadriceps torque-velocity relationship. We examined the quadriceps torque-velocity relationship of the human knee extensors at the descending and ascending limb of the torque-position relationship by initiating the knee extension at a knee angle position of 1.39 rad (80°) or 0.87 rad (50°) over a 0.52 rad (30°) range of motion under conditions of constant or linearly increasing velocity. Maximal voluntary isometric knee extension torque (M₀) was measured at 1.87 rad, 0.87 rad, and 0.35 rad, and concentric torque was measured. The subjects carried out ten maximal knee extensions at ten distinct velocities, each velocity ranging between 0.52 rad·s^–1 to 5.24 rad·s^–1 in steps of 0.52 rad·s^–1. Peak concentric torque was measured and mean torque calculated from the respective torque-time curves. Peak or mean torque, computed from the individual torque-time curves, and velocity data were fitted to the Hill equation under the four experimental conditions and the curve parameters computed. The M₀ was similar at 0.87 rad and 1.39 rad, but it was significantly lower at 0.35 rad. In the low-velocity domain of the torque-velocity curve where a plateau normally occurs, peak torque was always lower than M₀. Peak and mean torque were significantly greater under linearly increasing velocity conditions and the 1.39 rad starting knee position. Mean torque but not peak torque data could be well fitted to the Hill equation and the two computations resulted in significantly different Hill curve parameters including the concavity ratio, peak power, and maximal angular velocity. We concluded that the history of contraction significantly modifies the in vivo torque-velocity relationship of the human quadriceps muscle. Muscle mechanics and not neural factors may have accounted for the inconsistencies in the human torque-velocity relationships reported previously. Electronic Publication     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

Identification of active-site residues of the adenovirus endopeptidase.

Multiple sequence alignment of the 12 adenovirus endopeptidases known to date identified a number of conserved residues which might be important for enzyme activity. Eleven mutants were created in the cloned gene by site-directed mutagenesis to identify the active site of this thiol endopeptidase. Analysis of the proteolytic activity in a crude system using viral precursor proteins, as well as in a purified system with activated proteinases using a new chromophoric octapeptide substrate, yielded results consistent with Cys-104 and His-54 being two members of the active site. This result was confirmed by the carboxymethylation of the reactive Cys-104 and its prevention by the active-thiol-specific agent E64. Although Cys-122 and Cys-126 were also reactive cysteines, mutation of these residues did not affect enzyme activity. Replacement of the active-site Cys-104 by serine converted the enzyme into a serine-like proteinase, sensitive to serine proteinase inhibitors. The absence of homology to other proteinases, particularly at the active-site cysteine, coupled with the requirement for activation by a substrate cleavage fragment, indicates that the adenovirus endoproteinase may represent a new subclass of cysteine proteinases.