Carboxy-terminal peptides from the B subunit of Shiga toxin induce a local and parenteral protective effect

Two synthetic peptides corresponding to overlapping sequences from the C-terminus of the B chain of Shiga toxin were prepared and characterized. These peptides consisted of residues 54-67 and 57-67 in the protein sequence. This region coincides with the major peak of surface area residues, as predicted from a computer-derived plot. For the purpose of immunization, the peptides were either conjugated with a protein or a synthetic carrier, or were polymerized. Polyclonal antibodies against these peptides derivatives, induced in rabbits, recognized the homologous peptides and cross-reacted with the intact toxin. These antibodies were capable of neutralizing the various biological activities of the toxin, namely the cytotoxic, enterotoxic and neurotoxic activities. Active immunization of mice with the peptide derivatives protected them from the lethal effect of the toxin. Moreover, oral immunization of rats led to inhibition of fluid secretion in ligated ileal loops into which toxin was injected. This effect was paralleled by the induction of high levels of specific anti-peptide IgA antibodies in the serum after bile duct ligation.     

Improved selective medium for the isolation of lipase-positive Clostridium botulinum from feces of human infants.

Isolation of lipase-positive Clostridium botulinum from fecal specimens establishes the diagnosis of infant botulism, contributes to the diagnosis of food-borne botulism, and is most easily accomplished by use of selective media. Modification of an available selective medium, C. botulinum inhibitory medium (CBI), enabled more rapid isolation of C. botulinum. The modified medium (botulinum selective medium [BSM] contained (per liter) 25 g of dehydrated heart infusion broth, 20 g of agar, 30 ml of egg yolk suspension, 250 mg of cycloserine, 76 mg of sulfamethoxazole, 4 mg of trimethoprim, and 100 IU of thymidine phosphorylase at pH 7.4. The two media were compared by using 15 fresh fecal specimens from infant botulism patients (10 type A and 5 type B) and a C. botulinum isolate that had been obtained from an infant botulism patient and that was mixed into a fresh stool specimen from a healthy human infant. In comparison to CBI, BSM always provided better suppression of the nonbotulinum fecal flora and earlier emergence of lipase-positive colonies. Diagnosis of infant botulism was accomplished sooner with BSM than with CBI because isolation of lipase-positive C. botulinum was easier.     

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.     

Childhood Cancer and the Risk of ESKD

BackgroundIncreasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.MethodsTo assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.ResultsOf the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).ConclusionsChildhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.     

Osteoid osteoma: a diagnostic problem

A 32-year-old patient is presented to draw the attention of physical therapists to the diagnosis of osteoid osteorna, particularly in patients after an athletic injury. Osteoid osteorna is a benign neoplasm, but it can cause substantial pain and disability. This paper is not intended to add another case to the 400 already published, but rather to point out the difficulty in diagnosing osteoid osteorna despite modern laboratory findings and a classical history of pain responsive to salicylates only. Surgical excision of an osteoid osteorna, if diagnosed and present, is always indicated. It brings complete relief and eliminates any further need for physical therapy. In order to be certain that the nidus is excised, an x-ray of the specimen should be taken. J Orthop Sports Phys Ther 1983;5(1):33-35.     

Increased risk of salivary gland tumors after low-dose irradiation

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.     

Early fulminant leukaemia post autologous bone marrow transplantation in non-hodgkin’s lymphoma patients

Although autologous bone marrow transplantation (ABMT) is a curative option for about 50% of the patients with progressive or relapsing Symphomas, considerable concern has been raised recently over the emerging rates of secondary malignancies following ABMT. A 15% cumulative incidence of myelodyspfasia 5 years after BMT is of major concern. We hereby describe a unique form of leukaemia occuring 4–6 weeks post ABMT for non-Hodgkin’s iymphoma patients. The possible etiology for this phenomenon as well as its relation to the classical MDS post ABMT is discussed.