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.      

Will immunogenicity limit the use, efficacy, and future development of therapeutic monoclonal antibodies?

While monoclonal antibodies show promise for use in the treatment of a variety of disease states, including cancer, autoimmune disease, and allograft rejection, generation of anti-antibody responses still remains a problem. For example, 50% of the patients who receive OKT3 produce blocking antibodies that interfere with its binding to T cells, thus decreasing the therapeutic effect (51). HAMA responses have also interfered with tumor imaging (39,40) and radioimmunotherapy (56). The generation of an anti-antibody response is dependent on many factors. These include the dose of antibody, the number of injections of antibody, the immunogenicity of the antibody, the form of the antibody, and the immunocompetence of the recipient. Predictably, both the number of injections of antibody and the dosage are influential in the generation of an anti-antibody response. It is apparent that human antibodies, chimeric antibodies, and mouse Fab fragments are much less likely to induce anti-antibody responses than intact mouse monoclonal antibodies or mouse F(ab')2 fragments when one injection is administered. Injections of human or chimeric antibodies appears to reduce immunogenicity, but the probability that anti-antibody responses can still be induced on multiple injections must be considered and appropriately evaluated. Several areas demand extensive investigation to enhance the clinical utility of monoclonal antibodies. First, results of thorough clinical trials with human or chimeric antibodies need to be evaluated for the induction of anti-antibodies after multiple injections of antibodies. Second, less immunogenic forms of antibodies (Fab, Fv) need to be studied for their clinical efficacies and for their abilities to induce anti-antibody responses.     

CORTICAL SLOW POTENTIAL CHANGES IN MAN RELATED TO INTERSTIMULUS INTERVAL AND TO PRE TRIAL PREDICTION OF INTERSTIMULUS INTERVAL

Two experiments were performed to explore further the relationship between the cortical slow potential change known as the “contingent negative variation” (CNV) and the concept of “expectancy.” In Experiment I, 24 male Ss were presented click pairs, with inter-click intervals of 800, 1600 and 4800 msec (2 blocks of 10 trials each, counterbalanced between Ss for order), and instructed to press a key after the second click. Interval by order by trials analysis of variance showed interval to be the only significant factor: CNVs were lower and RTs longer as interval increased. In Experiment II, 8 female Ss given 60 pairs of clicks, 30 each with separations of 1200 and 2400 msec, were instructed to respond as in Experiment I, and were asked to make a pretrial prediction of the interval they would next receive. Analysis of variance of RTs showed that Ss responded slower when the interval was other than that predicted. Prediction by reception by subjects analysis of variance of CNV amplitude at the 1200 msec point gave a significant F only for prediction, mean amplitude for short being higher than for long. A similar design applied to CNV amplitudes at both the 1200 and 2400 msec points when Ss received the long interval yielded a significant measurement point by interval predicted interaction; at the 1200 msec point, short predictions were followed by higher CNVs than were long predictions; at 2400 msec, the opposite was found. These data combine with those already in the literature to indicate that the relationship between “expectancy” and the CNV is far from simple, and that cognitive and motivational factors play a significant role in determining CNV amplitude.     

Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.     

Impact of an organ donor and tissue donor advocacy program on community hospitals

A crucial shortage of organ donors exists in the United States. The majority of donor referrals come from large (greater than 500) beds) hospitals and trauma centers. To determine whether a significant number of donors who are not being recognized or referred also existed in medium-sized (300 beds) community hospitals, a Donor Advocacy Program was instituted at Francis Scott Key Medical Center in May 1987. This team developed policies and procedures to identify potential donors and conducted educational programs for physicians and nurses. A designated "Donor Advocate" made daily rounds on the inpatient units to maintain donor awareness and facilitate potential donations. After the first year, the program was evaluated. In comparison to the average of the previous three years, donor referrals increased by approximately 400 per cent and tissue donations increased over 500 per cent. Four organs were retrieved from two donors. It is concluded that an increase in referrals and tissue donations can be achieved at community hospitals through a structured donor awareness program. Recommendations are made to further examine the age group most often eligible for organ and tissue donations in community hospitals and target educational efforts accordingly. Commitment of hospital administration is vital to a positive outcome in such a program.     

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