The H-2 dm1 mutation and Qa antigens

The effect of the H-2dm1 mutation on Qa-m2 expression was examined. The mutant strain B10.D2-H-2dm1 showed a fourfold increase in Qa-m2 expression when compared with the parental strain B10.D2. Qa-m2 molecules immunoprecipitated from B10.D2-H-2dm1, C57BL/10, and B10.D2 spleen cells were identical by two-dimensional (2-D) gel electrophoresis [isoelectric focusing (IEF) followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE]). It is likely therefore that the increased Qa-m2 expression is not due to gross structural alterations of the Qa-m2 molecule; in the present study, alternative explanations are discussed.     

Monoclonal anti-idiotype induces protection against the cytotoxicity of the trichothecene mycotoxin T-2

An IgG1 mAb, designated HD11, specific for the trichothecene mycotoxin T-2 and capable of neutralizing its cytotoxicity was used to generate a syngeneic monoclonal anti-Id antibody. The generated anti-Id mAb, designated DE8, specifically bound to HD11 anti-T-2 mAb, and not to IgG1 mAb of irrelevant specificity or to normal mouse Ig. DE8 inhibited the binding of HD11 anti-T-2 to T-2-BSA-coated plates, whereas a control anti-Id mAb did not, suggesting recognition of an Id determinant associated with the T-2 binding site of HD11. Moreover, the binding of HD11 to DE8 and that of DE8 to HD11 were specifically inhibited by free T-2 mycotoxin. DE8 mAb was efficient in abrogating the protective effect of HD11 in the cytotoxicity of T-2 on the human epidermoid carcinoma cell line Hep-2. In vivo immunization of BALB/c mice with DE8 conjugated to KLH induced an anti-T-2 antibody titer comparable to that obtained with T-2-OVA immunization, whereas immunization with unconjugated DE8 resulted in a lower titered anti-T-2 response. Immunization with DE8-keyhole limpet or with unconjugated DE8 induced anti-T-2 antibody responses characterized by expression of "HD11-like" Id and by protection against T-2 cytotoxicity. However, the T-2-OVA-induced anti-T-2 response lacked the HD11+ Id and was only partially protective against T-2 cytotoxicity. This represents the first demonstration of the use of an anti-Id based vaccine in the in vivo induction of a protective antibody response against the cytotoxicity of a nonproteinaceous, small m.w. biologic toxin, whose very toxic nature precludes its use as the immunogen.     

Plasma LH and testosterone in Zebu crossbred bulls after exposure to an estrous cow and injection of synthetic GnRH

Plasma hormone levels were examined in 4 mature Zebu bulls of normal libido (HL) and 4 which were sexually inactive (LL). When used in an artificial insemination programme the 8 bulls had similar fertility. Basal levels of LH and testosterone (T) estimated from 8 sequential blood samples at 30 minute intervals were not different in HL and LL bulls. Exposure of the animals to an estrous cow did not stimulate LH release. Following sexual stimulation plasma T levels actually decreased by an average (±S.E) of 2.9 (±1.9) ng/ml in the HL group and increased by 3.9 (±1.6) ng/ml in the LL group. An injection of 1 mg GnRH (Hoechst) caused LH release of similar magnitude in HL and LL bulls. The elevation of plasma T which followed GnRH injection was significantly larger in HL bulls.Low libido was not associated with a deficiency of basal LH or T, nor with the ability of the pituitary to respond to GnRH.     

Tea2p is a kinesin-like protein required to generate polarized growth in fission yeast

Cytoplasmic microtubules are critical for establishing and maintaining cell shape and polarity. Our investigations of kinesin-like proteins (klps) and morphological mutants in the fission yeast Schizosaccharomyces pombe have identified a kinesin-like gene, tea2(+), that is required for cells to generate proper polarized growth. Cells deleted for this gene are often bent during exponential growth and initiate growth from improper sites as they exit stationary phase. They have a reduced cytoplasmic microtubule network and display severe morphological defects in genetic backgrounds that produce long cells. The tip-specific marker, Tea1p, is mislocalized in both tea2-1 and tea2Delta cells, indicating that Tea2p function is necessary for proper localization of Tea1p. Tea2p is localized to the tips of the cell and in a punctate pattern within the cell, often coincident with the ends of cytoplasmic microtubules. These results suggest that this kinesin promotes microtubule growth, possibly through interactions with the microtubule end, and that it is important for establishing and maintaining polarized growth along the long axis of the cell.     

Radiothérapie interne vectorisée par 177Lu-PSMA-617 de l’adénocarcinome prostatique métastatique résistant à la castration : à propos d’un cas et revue de la littérature

The prostate-specific membrane antigen (PSMA) is a type II glycoprotein which is over-expressed in prostate cancer tissue, especially in high grade tumours, metastatic disease, as an effect of androgen-deprivation therapies and in castrate-resistant prostate cancer (CRPC). Recent studies about radioligand therapy using PSMA ligands labeled with lutetium-177 (¹⁷⁷Lu) in CRPC patients have suggested its interest as a third line of treatment after second generation anti-androgens and chemotherapy by taxane. We present the case of a CRPC patient who was treated by iterative radioligand therapy using PSMA-617 ligand labeled with ¹⁷⁷Lu. This case illustrates on the one hand the efficacy of the treatment, and on the other hand the fragility of the patients who are at an advanced stage of their disease. Then we present a short review of the literature on this topic, focusing on the published efficacy and tolerance of ¹⁷⁷Lu-PSMA radioligand therapy of CRPC patients.