Efficient tumor eradication by adoptively transferred cytotoxic T-cell clones in allogeneic hosts

Tumor-specific cytotoxic T cells (CTLs) can play an important role against cancer as illustrated by the observation that adoptive transfer of tumor-specific CTLs can mediate potent anti-tumor effects. Although such CTLs can be detected at the tumor site, relatively little is known about the mechanisms by which they enter the tumor. In this study, the role of major histocompatibility complex (MHC) class 1 molecules on vascular endothelium in the tumor in entry of, and tumor eradication by, tumor-specific CTL was investigated. Two H-2Db-restricted CTL clones recognizing peptide VNIRNCCYI on human adenovirus type 5 early region 1-(Ad5E1)-induced tumors were used to test whether CTLs were able to cross the vascular endothelium lacking the restricting MHC molecule. One CTL clone recognizes peptide VNIRNCCYI in the context of both H-2Db and H-2Dbm14 molecules. The other CTL clone recognizes this peptide only in the context of H-2Db. Adoptive transfer of these CTLs leads to eradication of Ad5E 1-induced, H-2Db-expressing tumors in B6(H-2Db+) and Bm14(H-2Db-) nude mice. Our data show that presentation of tumor-derived peptides by MHC molecules on endothelial cells of blood vessels in a tumor do not play a major role in eradication of tumors by adoptively transferred CTL in combination with interleukin-2. Moreover, our data show that successful adoptive CTL immunotherapy is possible across allogeneic barriers, without inducing severe side effects, provided the tumor expresses the MHC class 1-peptide complex recognized by the CTLs.     

The immunogenic effect of purified antigens of B. alexandrina against Schistosoma mansoni in experimental animals (I) as measured by worm load and viability of ova

Current stratigies for the control of schistosomiasis are based primarily on chemotherapy but successful vaccination against infection has been also demonstrated in several host parasite models. In this study, the immunogenic effect of two purified antigens (Fiv 20-29 000 daltons & Fv 20-24 000 daltons) extracted from non infected hepatopancreas of B. alexandrina as measured by worm load, state of copulation and viability of ova in tissues. The antigens were prepared using gel filtration chromatography and their molecular weights were estimated through sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Four dilutions from each antigen were prepared and injected in two groups (33 each) of Swiss albino mice at weekly intervals. A control group was injected with phosphate buffer saline (PBS) in the same manner. All mice were injected with 100 cercariae using immersion method. Sacrification was done regularly after 7 weeks of injection. On the basis of worm load, Fiv gave protection of 44% while Fv gave only 36%. The number of worms in copula was significantly reduced and they became delicate, fragile, stunted and malformed. Both antigens gave a significant reduction in total viable eggs in tissues.     

Cell-seeding and in vitro biocompatibility evaluation of polymeric matrices of PEO/PBT copolymers and PLLA

Higher lipid content in gall bladder bile of sheep and goats as compared with monogastric species was due to higher proportion of glycerides. The volume of bile per gall bladder was higher in sheep than in goats. Bile from sheep and goats has a higher content of proteins and lower contents of dry matter, cholesterol and phospholipids compared with monogastric species. Biliary proteins partially purified by the ammonium sulfate precipitation method were characterized and quantified by polyacrylamide gel electrophoresis (PAGE), fast protein liquid chromatography (FPLC) and immunodiffusion. FPLC and PAGE profiles indicate that biliary proteins of sheep and goats are mainly of low mol. wt. of upto 65 KDa. Proportions of immunoglobulin (Ig) like molecules in biliary proteins precipitated by ammonium sulfate of different degrees of saturation, were 10.4 to 26.7 and 21.9 to 30.7 per cent of total proteins in bile of goats and sheep. IgG and IgA like molecules were the predominant Ig and lacked carbohydrates. On immunodiffusion such Ig like molecules did not show cross reactivity with humoral Ig. It was concluded that sheep and goats appear to secrete Ig into bile after deglycosylation and partial degradation. The proteins of smaller molecular weight may be secretory fragments or degradation products of Ig.     

Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach

A library of thioamide derivatives of leflunomide 1a and of its bioactive metabolite 1b has been synthesised on solid phase. Thus, para-substituted phenylacetic acids were coupled to TentaGel and were subsequently reacted with aromatic isothiocyanates. Treatment of the resulting enaminothioamides with hydroxylamine led to their simultaneous cyclisation and cleavage from the resin affording 2-25. Their in vitro profiling demonstrated that the amide-thioamide isologous substitution was detrimental of the biological activity.     

Botulinum toxin type A treatment of cosmetically disturbing masseteric hypertrophy]

Two patients, a woman aged 21 and a man aged 29, with asymmetrical swellings of both mandibular angles and a painful, heavy sensation in the masticatory muscles (and in the woman also round the maxillary joint), were diagnosed as having hypertrophy of the masseter muscles. Both had the habit of jaw clenching and tooth grinding. Treatment consisted not of the traditional surgical debulking which also allows correction of overdeveloped osseous mandibular angles, but of injections with botulinum toxin type A. Injection of 40-60 IU (product: Botox) per muscle was followed by some atrophy; cosmetically satisfactory results were achieved after repetition of the treatment a few months later. Reduction of muscle volume was confirmed by a quantitative volumetric assessment of MRI scans. In the female patient, the pain also abated.     

Ultrasound diagnosis of fetal diaphragmatic hernia and complex congenital heart disease at 12 weeks' gestation--a case report

Congenital diaphragmatic hernia is commonly associated with congenital heart disease. Their coexistence indicates a poor prognosis. Prenatal diagnosis of these conditions in early pregnancy allows the option of pregnancy termination. We present a case of left-sided fetal diaphragmatic hernia and complex congenital heart disease diagnosed by ultrasound examination at 12 weeks' gestation.