Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

In the present study, we address the role of the gene for catechol-O-methyltransferase (COMT), a key modulator of dopaminergic and noradrenergic neurotransmission, in the genetic predisposition to obsessive-compulsive disorder (OCD). We show that a common functional allele of this gene, which results in a 3- to 4-fold reduction in enzyme activity, is significantly associated in a recessive manner with susceptibility to OCD, particularly in males. This association is further supported by psychiatric evaluation of patients who carry microdeletions encompassing the comt gene. The mechanism underlying this sex-selective association remains to be defined and may include a sexual dimorphism in COMT activity, although close linkage with a nearby disease susceptibility locus cannot be excluded at this point.     

Knowledge, attitudes and practices about blood donation. A sociological study among the population of Lomé in Togo]

GOALS: 1) analyse the knowledge, attitudes and practices of Lome population about blood donation; 2) identify obstacles to blood donation among the population of Lome; 3) suggest some solutions to improve the performance of the National Blood Transfusion Centre (CNTS). METHODOLOGY: We have conducted a sample survey among the population of Lome from the 6th to 21st October 2003. Three hundred persons filled a questionnaire. RESULTS: In the sample, 183 (61%) were males. Their age ranged from 18 to 67 years with 2/3 of young peoples between 18 and 37 years. Pupils/students were 24,33%, wage-earners, 55% and the unemployed, 17,67%. More than the half of the investigated persons (54,67%) were unmarried and 96, 33% persons were literate. Nearly all the people (96,33%) knew about blood donation in Lome and they have received information mainly from friends, media and sensitization by the CNTS. Sixty-one percent of the investigated knew where blood is donated. All the investigated were unanimous about the vital role of blood. Whatever their religion, they recognized its sacred nature. The majority of the investigated (85%) were willing to donate blood. Only 95 people were donors. The reasons for non-donation were mainly related to the fear of catching diseases (31,71%) especially the HIV (9,76%), the lack of information (25,37%), the religious beliefs (19,51%) and the fear of knowing the result of one's HIV test. 277 people (92,33%) said that blood should be donated without remuneration. CONCLUSION: There is a growing interest in the blood donation among the population of Lome but new strategies must be elaborated to inform the population and motivate blood donors.     

Iodine status in vegans consuming a living food diet

The dietary intake and urinary output of iodine and the thyroid activity was measured in 12 living food eaters (people consuming uncooked, Lactobacilli rich vegan food) and omnivores. Seven day food record was used for calculating the dietary iodine intake, instrumental neutron activation analysis for measuring the urinary iodine output and RIA for determining of the thyroid hormones (TSH and FT4). The living food eaters were divided into two groups according to urinary iodine output: high iodine group (≥900 ug/d) and low iodine group (<200 ug/d). Thyroid activity in both groups was with in normal range. Dietary intake of iodine was dependent on the the use of seaweed. The highest amounts of dietary iodine observed in the present study, as assessed by the the urinary iodine output, can be harmful for susceptible subjects. On the other hand the calculated intake of iodine by living food eaters didn't fill the RDA. As an conclusion on a living food diet one has to ensure the sufficient intake of iodine by consuming seaweed or Kelp tablets daily. However the intake of these preparations needs to be kept at reasonble limits due to their possible high iodine content. More information of the iodine content of different seaweeds and seaweed products is needed.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

Tibiotalocalcaneal arthrodesis with retrograde intramedullary nailing

Nineteen patients (20 feet) with severe hindfoot and ankle deformity underwent tibiotalocalcaneal fusion with a retrograde locked intramedullary nail as a limb-salvage procedure. The purpose of this study was to compare the complication rates of this procedure in diabetic versus nondiabetic patients. There were 8 men and 11 women with preoperative diagnoses including Charcot neuroarthropathy, primary osteoarthritis, rheumatoid arthritis, equinocavovarus, posttraumatic osteoarthritis, gouty arthritis, and ankle malunion. Ten of 20 procedures were performed in patients with diabetes. The average patient age was 56 years, and the average postoperative follow-up was 19.8 months. Nineteen of 20 ankles (95%) achieved successful fusion with an average time of 4.1 months. Four patients (21%) required either a fracture brace or an ankle foot orthosis at final follow-up. Five patients (25%) had major complications and 11 patients had minor complications. Major complications included osteomyelitis (n = 2), Charcot arthropathy (n = 2), failure of fixation (n =1), soft-tissue necrosis (n = 1), cardiac arrest (n = 1), cerebral vascular accident (n = 1), and fatal pulmonary embolus (n = 1). All patients with major complications were diabetic, and 14 of 20 combined major and minor complications occurred in patients with diabetes. The complication rate was found to be high in diabetic patients with end-stage deformity undergoing a limb salvage     

Bovine parathyroid cells: cultures maintained for more than 140 population doublings.

Primary cultures of bovine parathyroid cells were developed using Coon's modified Ham's F-12 medium containing low (0.3 mM) concentrations of calcium and supplements of bovine hypothalamic extract, bovine pituitary extract, epidermal growth factor, insulin, transferrin, selenous acid, hydrocortisone, triiodothyronine, retinoic acid, and galactose. These cells were cultured serially on serum-coated dishes for 140 population doublings before signs of senescence were detected. The cells were epithelioid and maintained a high degree of differentiation as evidenced by calcium regulation of both growth and secretion and by prostaglandin E1 stimulation of cAMP formation and hormone release.     

Follicular lymphoma cell lines,an in vitro model for antigenic selection and cytokine-mediated growth regulation of germinal centre B cells

In the periphery, B cells differentiate in germinal centres (GCs) of secondary lymphoid organs. Isolated GC cells die quickly in vitro by apoptosis. Therefore, cell lines originating from follicular lymphomas, which are the malignant counterparts of GC B cells, would provide a stable in vitro model to study the immunobiology of GC B cells. We have established three novel human follicular lymphoma cell lines that were characterized with special reference to immunophenotypic features, response to B-cell receptor (BCR) triggering, response to cytokines and cytokine mRNA expression. One of the cell lines, HF-1A3, has a phenotype of a centrocyte. It expresses surface immunoglobulin G (sIgG) and dies by apoptosis following BCR cross-linking. Co-stimulation with interleukin-6 (IL-6), IL-15 or interferon-gamma (IFN-gamma) rescues HF-1A3 cells from BCR-induced apoptosis. The second cell line, HF-28, also represents phenotypically an IgG+ centrocyte. Ligation of its BCR leads to the cell-cycle arrest at G1 instead of apoptosis. HF-28 cells express both CD45RA and RO isoforms, which is unusual in B lymphocytes apart from plasma cells, thus suggesting a transition to plasma cell phenotype. The third cell line, HF-4.9, which phenotypically represents an sIgM+ centroblast, responds by proliferation to BCR cross-linking. These cell lines offer a unique in vitro model to study antigenic selection and cytokine-mediated growth regulation of human GC B cells.     

A two-stage study on multiple sclerosis susceptibility and chromosome 2q33

We have performed a two-stage study to analyse the association of polymorphism on chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in stage-1 in 134 Finnish MS families and the observed associations were tested in stage-2 in 186 MS families. We did not find previously reported allelic or haplotype associations with CTLA4. We obtained a weak signal of two distinct predisposing genes, one proximal the other distal of CTLA4. The putative proximal gene was associated with the marker rs3977 in families lacking HLA-DR2 (P=0.02 and 0.02) and the other distal gene was associated with D2S1271 in families from a high-risk region in western Finland (P=0.02 and 0.01). Based on the >3 cM distance and the lack of linkage disequilibrium between these loci, we conclude that the two association signals are independent. Our results provide preliminary evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.