Peptide-antibody conjugates for tumour therapy: A MHC-class-II-restricted tetanus toxin peptide coupled to an anti-IG light chain antibody can induce cytotoxic lysis of a human B-cell lymphoma by specific CD4 T cells

Anti-idiotype antibody therapy of B-cell lymphomas, despite numerous promising experimental and clinical studies, has so far met with limited success. Tailor-made monoclonal anti-idiotype antibodies have been injected into a large series of lymphoma patients, with a few impressive complete tumour remissions but a large majority of negative responses. The results presented here suggest that, by coupling to anti-lymphoma idiotype antibodies a few molecules of the tetanus toxin universal epitope peptide P2 (830–843), one could markedly increase the efficiency of this therapy. We show that after 2-hr incubation with conjugates consisting of the tetanus toxin peptide P2 coupled by an S-S bridge to monoclonal antibodies directed to the X light chain of human immunoglobulin, human B-lymphoma cells can be specifically lysed by a CD4 T-lymphocyte clone specific for the P2 peptide. Antibody without peptide did not induce B-cell killing by the CD4 T-lymphocyte clone. The free cystein-peptide was also able to induce lysis of the B-lymphoma target by the T-lymphocyte clone, but at a molar concentration 500 to 1000 times higher than that of the coupled peptide. Proliferation assays confirmed that the antibody-peptide conjugate was antigenically active at a much lower concentration than the free peptide. They also showed that antibody-peptide conjugates required an intact processing function of the B cell for peptide presentation, which could be selectively inhibited by leupeptin and chloroquine. It is reasonable to expect that, in vivo, the anti-idiotype antibodies will selectively transport the tetanus toxin peptides to the B-lymphoma cells, which will process the conjugates and present the peptides to the patients' CD4 T-cell repertoire. Our tetanus-toxoid-vaccinated population has T cells specific for the immunogenic peptide and these, in principle, could be further expanded prior to injection of the conjugate.     

Acute renal failure in a neonate due to pelviureteric candidal bezoars successfully treated with long-term systemic fluconazole

Systemic candidiasis with renal involvement is a rare but well-recognized complication during intensive care treatment in very-low-birth-weight infants. We report a term neonate who developed anuria associated with bilateral bezoar formation in the renal pelvis and candidemia. The treatment consisted of placement of a nephrostomy tube in the left kidney, short-term irrigation with amphotericin B and iv, and later, oral administration of fluconazole.     

Is injectable collagen truly safe?

Most patients have no response to injectable collagen or silicone, but some cases may have positive or 'undersea' (= clinically negative but immunologically positive) response to collagen. From the results of the Macrophage migration inhibition test, the relative immunogenicity was augmented most when we used implants with the following combination. The first immunization was collagen and the second one was collagen with silicone. The augmented antigenicity might be enough to cause an allergic reaction to the patients who had no response to each implant alone.     

An approach to the nasal septum in children

Surgery of the nasal septum has long been discouraged in the pediatric population. Concerns about growth and development of the nose have led surgeons to adopt an extremely cautious attitude toward the correction of nasal septal deformities in childhood. More recently, studies have shown that with proper preservation of septal cartilage, surgery can be safely undertaken in this area. Frequently, however, exposure to the nasal septum is limited in small children due to the size of the nasal vestibule. Sublabial septoplasty has been safely carried out now in ten patients ranging in age from 4 to 9 years. This approach allows for complete access to the nasal septum while avoiding any external cosmetic deformity. The nasal septum has been preserved in all cases through morsalization and repositioning. Growth and development of the nose has been followed for up to 60 months without evidence of deformity or alteration. Sublabial septoplasty would, therefore, appear to be a safe and cosmetically acceptable approach to the correction of severe nasal septal deformities of childhood.     

The Clinical Significance of Endometrial Prolactin

Prolactin (PRL) is produced not only by the anterior pituitary gland but also by human endometrium. That decidual stromal cells secrete PRL from day 22 of the menstrual cycle is demonstrated by: 1) nett accumulation of PRL during in vitro culture; 2) PRL accumulation is prevented by inhibitors of protein synthesis; and 3) identification of PRL mRNA within endometrial decidua. Endometrial PRL is biologically and immunologically equipotent with pituitary PRL and its amino acid sequence is very similar. In human pregnancy, decidual PRL binds to receptors on the fetal chorion and amnion and thereby passes into amniotic fluid in high concentration. Three putative functions of uterine PRL are suggested from current studies: a) a PRL receptor defect is present in the chorion laeve of patients with pregnancies complicated by chronic polyhydramnios and this deficiency in chorionic receptors for endometrial PRL may result in the development of excessive amniotic fluid; b) decidual PRL may modulate prostaglandin synthesis not only within the endometrium prior to menstruation, but also within the chorion and amnion to allow labour to proceed in a timely manner; and c) amniotic fluid PRL may pass into the fetal tracheo-bronchial system to promote surfactant production. Unlike pituitary PRL with distant target organs, decidual PRL appears to have paracrine or cybernetic functions in the human uterus, placental membranes and the fetus.     

Behavioral avoidance test for childhood obsessive-compulsive disorder: a home-based observation

Obsessive-compulsive disorder (OCD) is one of the most debilitating of the anxiety disorders. As our knowledge about this childhood condition continues to grow, there is a need for controlled treatment-outcome trials with precise assessments that are sensitive to treatment change, to guide the development of effective interventions. To evaluate the efficacy of a treatment protocol, it is necessary to have reliable and sensitive measures of OCD symptoms, including measures of obsessions, compulsions, and related levels of distress and avoidance. Whilst structured diagnostic interviews, semistructured clinical interviews, and self-report measures have been widely used in the assessment of childhood OCD, related levels of behavioral distress and avoidance have not been measured in treatment-outcome trials. This study investigated the sensitivity of a behavioral avoidance test (BAT), conducted in the home environment, in assessing treatment-outcome effects for children and adolescents with OCD following a 14-week cognitive-behavioral therapy (CBT) family intervention, in comparison to children in an 8-week "waitlist" control group. The results of the current study strongly support the sensitivity of a standardized BAT in assessing treatment-related changes in children and adolescents with OCD. Implications and future directions for research are discussed.