Intraperitoneal administration of an I125 labelled monoclonal antibody for localization of human colorectal cancer in the nude mouse

The monoclonal antibody (MoAb) HMGF-1 was evaluated in the radioimmunodetection of human colonic cancer transplanted intraperitoneally (i.p.) into athymic nude mice. This antibody reacts with a component of the human milkfat globule, as well as a wide range of epithelial cells and adenocarcinomas of various origins. Purified MoAb was iodinated with 125I and administered i.p. into nu/nu mice bearing (i.p.) xenografts of human colonic adenocarcinoma (X56). Differential tissue counts of radioactivity demonstrated preferential localization of the antibody in i.p. and subcutaneous (s.c.) tumor tissue as compared to normal tissues. Maximum per cent dose per g of tumor (25.17 +/- 1.37), maximum tumor: blood ratio (4.45 +/- 0.14) and maximum tumor: tissue ratios (34.2 +/- 0.12) were obtained at the optimal labelling time of 5 days after antibody injection. Selective localization to tumor was confirmed with a control anti-hepatitis virus MoAb of the same isotype and by localization studies in non-tumor bearing athymic mice. Half lives of the persistence of the iodine 125 in the tumor bearing and non tumor bearing mice were 5 and 7 days, respectively, indicating approximate antibody half lives. Whole body scans showed distinct tumor images without the use of subtraction techniques. This pilot experimental study demonstrates the feasibility of i.p. administration of labelled antitumor MoAb in the imaging of i.p. tumors in an athymic mouse system. Whether or not these observations are applicable to the human situation remains to be carefully established.     

A prospective,double-blind,randomized study of high-versus low-dose OKT3 induction immunosuppression in cadaveric renal transplantation

We undertook a prospective, double-blind study of high-(5-mg) versus low-(2-mg) dose OKT3 for induction immunosuppression (12 days) in cadaveric renal allograft transplantation. Maintenance immunosuppression was identical in both groups and consisted of azathioprine and prednisone initially, with cyclosporine beginning on the 5th postoperative day. Twenty-six patients were randomized. The groups were similar in terms of age, kidney ischemia time, peak PRA, and latest PRA. There were more diabetics and women in the high-dose group. Patient survival at 12 months was 100% in both groups. Graft survival at 12 months was 92% and 100% in the high- and low-dose groups, respectively. Infections were mostly minior and equal in frequency in the two groups. All patients receiving high- or low-dose OKT3 had manifestations of the cytokine release syndrome; these were delayed in onset in the low-dose group. Eleven patients (85%) in each group produced anti-OKT3 andtibodies. Lymphocyte depletion after 1 day was major (>98%) and identical in both groups. CD3 antigens were removed more slowly in the low-dose group but eventually at equal rates in both groups. Cost was significantly lower in the low-dose group. We conclude that while both doses of OKT3 were effective and safe for induction immunosuppression, it may be prudent to use a lower dose of OKT3 for induction immunosuppression because of its potential to reduce cytokine-mediated effects and to avoid the complications of overimmunosuppression and because of the lower costs associated with it.     

Active listening: task-dependent plasticity of spectrotemporal receptive fields in primary auditory cortex

Listening is an active process in which attentive focus on salient acoustic features in auditory tasks can influence receptive field properties of cortical neurons. Recent studies showing rapid task-related changes in neuronal spectrotemporal receptive fields (STRFs) in primary auditory cortex of the behaving ferret are reviewed in the context of current research on cortical plasticity. Ferrets were trained on spectral tasks, including tone detection and two-tone discrimination, and on temporal tasks, including gap detection and click-rate discrimination. STRF changes could be measured on-line during task performance and occurred within minutes of task onset. During spectral tasks, there were specific spectral changes (enhanced response to tonal target frequency in tone detection and discrimination, suppressed response to tonal reference frequency in tone discrimination). However, only in the temporal tasks, the STRF was changed along the temporal dimension by sharpening temporal dynamics. In ferrets trained on multiple tasks, distinctive and task-specific STRF changes could be observed in the same cortical neurons in successive behavioral sessions. These results suggest that rapid task-related plasticity is an ongoing process that occurs at a network and single unit level as the animal switches between different tasks and dynamically adapts cortical STRFs in response to changing acoustic demands.     

Nitric oxide modulates vascular endothelial growth factor and receptors in chronic cyclosporine nephrotoxicity

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in angiogenesis, wound healing, and inflammation and exerts its effect via tyrosine kinase receptors, fms-like tyrosine kinase (Flt-1) and fetal liver kinase (Flk-1 or KDR). We have previously shown that VEGF is up-regulated in a model of chronic cyclosporine (CsA) nephrotoxicity and that l-arginine (l-Arg) improved while N-nitro-l-arginine-methyl ester (L-NAME) worsened fibrosis. We examined the role of nitric oxide modulation on VEGF in this model. METHODS: Pair-fed salt-depleted rats were administered CsA, CsA + L-NAME, CsA +l-Arg, vehicle (VH), VH + L-NAME or VH +l-Arg and were sacrificed at 7 or 28 days. Physiologic and histologic changes were studied in addition to the mRNA expression of VEGF and its receptors Flt-1 and KDR/Flk-1 by Northern blot and the protein expression of VEGF by Western blot and immunohistochemical staining. RESULTS: While L-NAME worsened renal function and histology, l-Arg had the opposite beneficial effect in CsA-treated rats. VEGF mRNA and protein expressions increased with CsA, further increased with L-NAME and became significantly reduced with L-Arg. Flt-1 expression was similar in all groups. On the other hand, KDR/Flk-1 mRNA expression was modulated in a fashion similar to VEGF. Also, nitric oxide modulation did not have an effect on VH-treated rats. CONCLUSIONS: VEGF expression in chronic CsA nephrotoxicity is increased by nitric oxide blockade and decreased by nitric oxide enhancement. Moreover, VEGF probably exerted its effect via the KDR/Flk-1 receptor. The actions of VEGF in this model remain speculative, but it is probable that VEGF plays a role, either independently or through nitric oxide, in CsA-induced fibrosis.     

Lipid Profile In Transplant Patients: A Clinical Study

15 renal transplant recipients were studied for their lipid profile. The patients were on regular post transplant follow up and had non clinical or laboratory evidence of graft dysfunction, intercurrent infection or post transplant diabetes mellitus for at least 3 months prior to the study. The mean duration of transplant was 15 ± 9.5 months (range 3-32 months). Majority (86%) were on triple immunosuppression therapy and received a mean prednisolone dose of 10.5 mg. An equal number of healthy subjects were randomly selected and studied for their lipid profile and served as control for the study group. There was no significant change in the HDL-cholesterol level as compared with controls. However, these patients showed a significantly higher LDL-cholesterol and total cholesterol levels. Further, a significant inverse correlation was observed between triglycerides and total cholesterol levels and transplant duration.Key Words: Lipid profile, Renal transplant