Cytogenetic studies in couples experiencing repeated pregnancy losses

A computerized database generated from the literature on cytogeneticstudies in couples experiencing repeated pregnancy losses hasbeen set up at the University of Quebec at Chicoutimi. At thepresent time, it contains data on 22 199 couples (44 398 individuals).The statistical analyses showed a relationship between the distributionof the chromosome abnormalities and the number of abortions.An uneven distribution of the chromosomal structural rearrangementsaccording to the sex of the carrier was found (P < 0.05).Overall, 4.7% of the couples ascertained for two or more spontaneousabortions included one carrier. It also appeared that only translations(both reciprocal and Robertsonian) and inversions were associatedwith a higher risk of pregnancy wastage. Therefore, geneticcounselling should be offered to these couples and investigationsperformed on their extended families.     

Retinoids in embryonal development

The key role of vitamin A in embryonal development is reviewed. Special emphasis is given to the physiological action of retinoids, as evident from the retinoid ligand knockout models. Retinoid metabolism in embryonic tissues and teratogenic consequences of retinoid administration at high doses are presented. Physiological and pharmacological actions of retinoids are outlined and explained on the basis of their interactions as ligands of the nuclear retinoid receptors. Immediate target genes and the retinoid response elements of their promoters are summarized. The fundamental role of homeobox genes in embryonal development and the actions of retinoids on their expression are discussed. The similarity of the effects of retinoid ligand knockouts to effects of compound retinoid receptor knockouts on embryogenesis is presented. Although much remains to be clarified, the emerging landscape offers exciting views for future research.     

Functional expression of 4-1BB (CD137) in the inflammatory tissue in Crohn's disease

4-1BB ligand (L) expressed on antigen presenting cells (APC) interacts with 4-1BB, expressed on activated T cells and this interaction costimulates T cells to secrete cytokines and to proliferate. We investigated whether 4-1BB/4-1BBL interactions might be involved in the pathogenesis of Crohn's disease (CD). In immunohistochemistry, we found 4-1BB expression on lamina propria (LP) cells in inflamed and to a lesser extend in non-inflamed gut tissue from CD patients. mRNA levels for 4-1BB were also elevated in intestinal CD tissue. In contrast, only few 4-1BB-expressing cells were found in inflamed tissue from ulcerative colitis (UC) patients and almost no positive cells were found in control intestinal tissue. 4-1BB expression was better sustained on in vitro activated lamina propria T cells from CD patients compared to controls. Finally, agonistic anti-4-1BB antibody enhanced interferon-gamma (IFN-gamma) production and proliferation of lamina propria T cells from CD patients. Taken together, our data suggest that 4-1BB/4-1BBL interactions contribute to the persistence of gut inflammation in CD.     

Therapeutic apheresis in children: experience in a pediatric dialysis center

The use of apheretic procedures in pediatric patients has always been restricted by technical difficulties and the low incidence of diseases requiring this kind of treatment. The aim of the present study was to describe the solutions adopted to solve technical difficulties related to priming, vascular access and monitoring and then to evaluate clinical results. Between 1982 and 2000, 51 consecutive children (28 male, 23 female) with a mean age of 4.9 +/- 4.8 years (3 months-14.8 years) and a mean weight of 19.7 +/- 12.8 kg (5-52 kg), with renal and/or extra-renal diseases requiring apheretic procedures were selected for the study. The overall number of procedures performed were: 226 plasma-exchange (PE), 6 LDL-apheresis (LDL-A) and 8 protein A immunoadsorption (IAPA) sessions. Our therapeutic protocol involves hematic flux of 20-100 ml/min and ultrafiltration of 5-20 ml/min. In each 70-95 minute session we exchanged plasmatic volume with fresh frozen plasma or with a solution of 6% albumin in lactated Ringer's, using heparin (10-20 UI/kg/h). We used Paired Filtration Dialysis Monitor in PE and LDL-A; Citem 10 in IAPA. As plasma separator, we used a filter made of polypropylene, 0.2 m2 surface, 30 ml priming (Hemaplex BT 900). Hemolytic uremic syndrome was the most commonly treated disease (18/51 cases) with good results in 10/18 cases. We recorded, good results in vasculitis as well, in one girl with focal glomerulosclerosis in transplanted kidney and rapid improvement in all children with Guillaine-Barré Syndrome. PE treatment was effective in metabolic disorders such as tirosynemia and familiar hypercholesterolemia. Only 4/12 patients with acute liver failure due to viral hepatitis recovered. We had poor results in the remaining eight cases. Complications were rare and no viral infection was found in any patient. Our data show that it is possible to use these procedures in pediatric patients even though clinical indications and real effectiveness still need to be cleared up.     

Probiotic activities of Lactobacillus casei rhamnosus: in vitro adherence to intestinal cells and antimicrobial properties

The interest of probiotics as remedies for a broad number of gastrointestinal and other infectious diseases has gained wide interest over the last few years, but little is known about their underlying mechanism of action. In this study, the probiotic activities of a human isolate of Lactobacillus casei subsp. rhamnosus strain (Lcr35) were investigated. Using intestinal Caco-2 cell line in an in vitro model, we demonstrated that this strain exhibited adhesive properties. The inhibitory effects of Lcr35 organisms on the adherence of three pathogens, enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC) and Klebsiella pneumoniae, were determined. A decrease in the number of adhering pathogens was observed, using either preincubation, postincubation or coincubation of the pathogens with Lcr35. Moreover, the antibacterial activities of cell-free Lcr35 supernatant was examined against nine human pathogenic bacteria, ETEC, EPEC, K. pneumoniae, Shigella flexneri, Salmonella typhimurium, Enterobacter cloacae, Pseudomonas aeruginosa, Enterococcus faecalis and Clostridium difficile. The growth of all strains was inhibited, as measured by determining the number of viable bacteria over time, but no bactericidal activity was detected in this in vitro assay. Together, these findings suggest that this probiotic strain could be used to prevent colonization of the gastrointestinal tract by a large variety of pathogens.     

Non-adenomatous colorectal polyposis syndromes

Gastrointestinal polyps are common lesions that usually present singly or in small numbers. Although the term ‘multiple colorectal polyposis’ was originally applied to patients carrying at least 100 large intestinal adenomas, it has subsequently become broadened to include patients carrying multiple polyps regardless of their nature. Most of the non-adenomatous polyposis syndromes are hereditary. They can be classified according to the dominant type of polyp, their distribution in the gastrointestinal tract and their potential for the development of gastrointestinal cancers. This review summarises their main clinical, genetic and histopathological features.     

Human Peripheral Eosinophils with Receptors for IgM: Demonstration and Ultrastructural Morphology

Receptors for IgM were detected on peripheral blood human eosinophils by a rosette technique with ox red blood cells coated with the IgM fraction of the specific immunserum. Between 14 % and 43 % (mean 27 %) FcµR positive cells were found after an overnight incubation period at 37°C by using this technique. The specificity of the receptors for IgM was assessed by studying the inhibitory capacity of purified human IgM in the rosette assay. From an ultrastructural point of view, the EA^M rosette-forming cells are mature eosinophlic granulocytes characterized by a nucleus with a variable number of lobes and a certain number of «first type» granules partially or totally devoid of their content.     

The possible involvement of endogenous opioid peptides and catecholestrogens in provoking menstrual irregularities in women athletes

It is well known that women athletes engaged in strenuous physical exercise and endurance training may develop "athletic menstrual irregularities" (AMI). Although many studies have appeared dealing with the immediate endocrinological and physiological changes in these women, the underlying mechanisms have remained unknown to date. A number of hypotheses have been put forward, the most well-known among them, for example, defending the existence of a critical percent of body fat necessary to trigger or maintain normal menstruation. All these theories have, however, their own, sometimes numerous, methodological inaccuracies and a teleological way of investigation. Spectacular, and perhaps promising new developments concern the possible involvement of endogenous opioid peptides and catecholestrogens in these processes. In basal circumstances beta-endorphin, the most well-known endogenous substance with opiate-like activity, may decrease LH levels by suppressing hypothalamic GnRH. This phenomenon is, however, only observed during the estrogen-dominant late-follicular and mid-luteal phases. As for catecholestrogens, it appears essential to differentiate between, for example, the 2- and 4-hydroxy derivatives of both estrone and estradiol. While some of these catecholestrogens obviously seem to suppress LH levels, others seem to potentiate and induce the LH surge. In any case, similar to beta-endorphin, these activities of catecholestrogens appear to depend upon the essential presence of a sufficiently estrogenic environment. In addition, both endogenous opioid peptides and some of the catecholestrogens appear to be able to suppress prolactin release, probably by interfering with its inhibiting factor dopamine. Other effects of catecholestrogens may include the control of the luteolysis-potent prostaglandin F2 alpha. Although a number of studies have investigated the behaviour of beta-endorphin during and post-exercise, similar studies investigating catecholestrogens as to their relation to physical exercise are almost nonexistent. This, in association with the numerous methodological inaccuracies of various studies, makes it difficult to draw any firm conclusion. As to formulate new hypotheses, the only reasonable suggestion considers the possible existence of a complex feedback system including catecholestrogens and endogenous opioid peptides. Furthermore, recommendations made in this survey may be helpful in designing new, perhaps more firmly supported and appropriate future studies.     

Neutron therapy for locally advanced head and neck squamous cell carcinoma: optimum dose search

28 patients with locally advanced primary squamous cell carcinoma of the head and neck received neutron therapy and were randomized between two dose levels: 145 cGy n gamma x twelve fractions, three fractions per week (total 17.4 Gy n gamma). 155 cGy n gamma x twelve fractions, three fractions per week (total 18.6 Gy n gamma). Acute toxicity for skin, mucous membrane, salivary and subcutaneous tissues was graded using the EORTC/RTOG scoring system. Analysis indicates 17.4 Gy n gamma as "safe". A further twelve patients are to be assigned to the higher dose (18.6 Gy n gamma) before making a final dose selection.     

Epilepsy and the GABA-hypothesis a brief review and some examples

A brief review is given with regard to the GABAergic alterations in experimental and genetic models of epilepsy and human epilepsy, illustrating, among others, that agents exist, both convulsants and anticonvulsants, that are capable of interacting with GABA's synthesis, storage, extraneuronal release, presynaptic reuptake, postsynaptic destruction and activation. The so-called "GABA-hypothesis" of epilepsy implies that a reduction of GABA-ergic inhibition results in epilepsy while an enhancement of GABAergic inhibition results in an antiepileptic effect. The examples presented, in support of the "GABA-hypothesis", concern the effects of some exogenous [pentylenetetrazol (PTZ) and methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM)] and some endogenous convulsants on the postsynaptic GABAA receptor. The studied endogenous convulsants were the guanidino compounds which are known to increase in uremia and hyperargininemia. PTZ and DMCM dose-dependently reduced GABA responses on mouse neurons in cell culture. The benzodiazepine receptor antagonist CGS 9896 antagonized the DMCM- but not the PTZ-induced inhibition of GABA-responses. The guanidino compounds guanidine, methylguanidine, creatinine, guanidinosuccinic acid (increased in uremia) and arginine, homoarginine, alpha-keto-delta-guanidinovaleric acid and argininic acid (increased in hyperargininemia) decreased both GABA- and GLY-responses. The guanidino compounds were equally potent in decreasing GABA- and GLY-responses and CGS 9896 did not antagonize the guanidino compound-induced inhibition of GABA responses. The presented results indicate that the studied convulsants inhibit GABAergic inhibition through interaction with distinct sites at the postsynaptic GABAA receptor. The demonstrated effect might, in agreement with the "GABA-hypothesis", underlie the epileptogenicity of these compounds in animal models and might have pathophysiological importance in uremia and hyperargininemia.