Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation

Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre- BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.     

Asymptomatic metachronous metastatic renal cell adenocarcinoma to the gallbladder

Summary A case of asymptomatic metachronous metastatic unilateral renal cell adenocarcinoma to the gallbladder detected five years after resection of the primary renal neoplasm is reported here. The lesion was diagnosed by contrast enhancement of a gallbladder mass on abdominal computerized tomography scan and by color Doppler sonographic study of the gallbladder, both of which demonstrated the vascular supply to the intraluminal gallbladder mass. The biological behavior of renal cell adenocarcinoma is reviewed. Guidelines for the evaluation of intraluminal gallbladder masses are suggested.     

Immune privilege in the gut: the establishment and maintenance of non-responsiveness to dietary antigens and commensal flora

Summary:  Immune privilege in the gut is the result of a complex interplay between the gut microbiome, gut luminal antigens, and the intestinal epithelial barrier. Composed of both physical and immunochemical components, the intestinal barrier secretes immunoregulatory mediators that promote the generation of tolerogenic antigen-presenting cells, phagocytic innate immune cells characterized by 'inflammatory anergy', and regulatory cells of the adaptive immune system. Innate immune cells mediate controlled transepithelial transport of luminal antigens as far as the mesenteric lymph nodes, where the intestinal and peripheral immune systems intersect. This promotes the generation of adaptive regulatory lymphocytes that actively suppress effector cell responses against gut luminal antigens and flora. The net result is the generation of tolerance to dietary antigens and the maintenance of gut homeostasis. Dysregulation of this complex immunoregulatory network leads to diseases such as food allergy and inflammatory bowel disease. Future therapies for these diseases will likely involve the functional restoration of the barrier and regulatory cell functions at the epithelial/luminal interface.     

Introduction: the Israeli high-risk study

The literature on theories of the etiology of schizophrenia (the "nature-nurture dilemma") is reviewed, and the rationale is explicated for a study comparing the development and outcome of kibbutz- and town-reared children of schizophrenic parents. Various possible outcomes of the kibbutz-rearing experience in vulnerable children are discussed. The research team and the time table are described.     

Specific nonsurgical therapy in male infertility

Although the objective of this article was to discuss the specific medically treatable causes of male infertility, the reader will be impressed by the fact that many of the treatments seem less than "specific." The need to treat infections to improve fertility is ill defined. The utilization of a scrotal cooling device as "specific" nonsurgical treatment for varicocele is yet to be defined. Immunologic suppression is indeed a specific form of therapy for a measurable phenomenon; unfortunately, the significance of that phenomenon as well as the best means and location of its assessment are undergoing significant reevaluation. An exciting frontier is the prospect of preventing infertility in the patient undergoing therapy for cancer, thus obviating the need for treatment of the ensuing infertility. Before specific therapies can be anticipated to have a predictable beneficial effect, these areas require active investigation to define the problem more clearly.     

Forfeiture of the proceeds of drug trafficking

The Hodgson Committee in its report on "The Profits of Crime and Their Recovery", which is being examined by the Government of the United Kingdom of Great Britain and Northern Ireland, made a number of recommendations relating to forfeiture and confiscation of the proceeds of crimes. The Committee, inter alia, recommended that the criminal courts should have the power to order the confiscation of the proceeds of crimes but that there should be a prescribed minimum amount below which no confiscation order could be made. This article comments on those recommendations relating to the proceeds of drug crimes, and suggests three possible ways of developing international cooperation to secure the tracing or confiscation of illegally acquired assets held abroad. The alternatives suggest either extending national laws to deal with these problems, in accordance with the provisions of the Single Convention on Narcotic Drugs; or following the example of Canada, where it is understood to be an offence to receive or possess the proceeds of crime irrespective of whether or not that crime took place in Canada; or developing a more extensive extra-territorial jurisdiction, for which there are precedents in the field of terrorism. One of the two annexes to this article describes recent initiatives within the Council of Europe to promote co-operation in tracing, freezing and confiscation of assets arising from drug trafficking, and the other provides an example of bilateral agreement (Cayman Islands) on disclosure of banking arrangements.