CD38 protein deficiency induces autoimmune characteristics and its activation enhances IL-10 production by regulatory B cells.

CD38 is a transmembrane protein expressed in B lymphocytes, and is able to induce responses as proliferation, differentiation or apoptosis. Several reports propose that CD38 deficiency accelerates autoimmune processes in murine models of autoimmune diabetes, lymphoproliferation and rheumatoid arthritis. Other reports have shown elevated CD38 expression in B and T cells from patients with autoimmunity; however, the role of CD38 is still unclear in the development of autoimmunity. Recently, it has been characterized as CD1dhi CD5+ regulatory B cell subpopulation able to produce IL-10, and the loss of these cells exacerbates the autoimmunity in murine models. Here, we report that CD38-/- mice exhibited elevated titres of ANAS, anti-dsDNA autoantibodies from 12 months of age and were higher by 16 months of age and mice presented kidney damage. Interestingly, there is a reduction in the survival of CD38-/- mice compared to the WT. Furthermore, CD38 is highly expressed by CD1dhigh CD5+ regulatory B cells, and the agonistic anti-CD38 stimulus plus LPS was able to increase the percentage of this cell subset and its ability to induce IL-10 production. Together, these results suggest that CD38 could play a role in the control of autoimmune diseases through their expression on regulatory B cells.

Atypical carcinoid tumours of the lung: prognostic factors and patterns of recurrence.

BACKGROUND: Atypical carcinoids (AC) of the lung are rare intermediate-grade neuroendocrine neoplasms. Prognostic factors for these tumours are undefined. METHODS: Our cooperative group retrieved data on 127 patients operated between 1980 and 2009 because of an AC. Several clinical and pathological features were studied. RESULTS: In a univariable analysis, T-status (p=0.005), N-status (p=0.021), preoperative M-status (previously treated) (p=0.04), and distant recurrence developed during the outcome (p<0.001) presented statistically significant differences related to survival of these patients. In a multivariable analysis, only distant recurrence was demonstrated to be an independent risk factor for survival (p<0.001; HR: 13.1). During the monitoring, 25.2% of the patients presented some kind of recurrence. When we studied recurrence factors in a univariable manner, sublobar resections presented significant relationship with locoregional recurrence (p<0.001). In the case of distant recurrence, T and N status presented significant differences. Patients with preoperative M1 status presented higher frequencies of locoregional and distant recurrence (p=0.004 and p<0.001, respectively). In a multivariable analysis, sublobar resection was an independent prognostic factor to predict locoregional recurrence (p=0.002; HR: 18.1). CONCLUSIONS: Complete standard surgical resection with radical lymphadenectomy is essential for AC. Sublobar resections are related to locoregional recurrence, so they should be avoided except for carefully selected patients. Nodal status is an important prognostic factor to predict survival and recurrence. Distant recurrence is related to poor outcome.

Chronic inflammatory demyelinating polyradiculoneuropathy in a patient with systemic lupus erythematosus and good outcome with rituximab treatment.

A patient with chronic inflammatory demyelinating polyradiculoneuropathy and systemic lupus erythematosus arising after rubella vaccination was initially treated with plasmapheresis, corticosteroids and intravenous immunoglobulins, with partial response. After shift to rituximab, most clinical symptoms improved markedly, emphasizing the possible role of this monoclonal antibody in conventional therapy-resistant cases.

Oral health status and inequalities among ambulant older adults living in central Chile.

OBJECTIVE: To assess the oral health status and treatment needs of older adults, living in the Valparaiso Region of Chile. BASIC RESEARCH DESIGN: A random sample of 354 older adults, aged 60 years or older, living independently in the community were examined orally by calibrated examiners and underwent a structured oral health interview. Data collection extended from October 2006 to June 2007. RESULTS: This was a largely dentate population (80%) with a mean DMFT score of 21.6 (s.d. 5.7). While about 28% of the dentate sample had all their restorative needs unmet, 30.8% had all of their restorative needs met. Regarding periodontal health, 3.3% had sound periodontum; complex periodontal therapy (CPI 3-4) was needed by 43.1% of the sample. CONCLUSION: This study represents one of the largest data collections in oral health among older adults living in Chile. Participants seemed to have better oral health status than previously reported. Of particular relevance is the reduction of the decayed component and the increased number of sound teeth in the present sample. Participants also presented lower need for advance periodontal treatment. Yet, inequalities were apparent in the proportion of unmet restorative needs. Strategies to develop oral health care programmes focused on improving access to and use of preventive services for older adults are critical. Further research is indicated to get a more complete picture of the factors that shape the oral health of Chilean older adults.

Multiple primary cancer: an increasing health problem. Strategies for prevention in cancer survivors.

This study was set to look for associations between the sites of the first and subsequent tumours in patients with multiple primary cancer (MPC) diagnosed from 1975 to 2002 in the reference hospital of a Spanish northern region, and propose prevention strategies. Patient and tumour variables were measured. Crude and standardized incidence rates per 100 000 inhabitants were obtained, and the association between MPC incidence and time was analysed by means of lineal regression. Relative risks were calculated to analyse associations between tumour sites. A total of 2737 MPC cases were registered (male/female ratio = 2). The percentage of MPC with respect to the total cancer increased from 1.78% in the 1975-1979 period to 7.08% in the 2000-2002 period (R(2) = 0.92; P = 0.003). Great increase of incidence by time was found (R(2) = 0.90; P = 0.004). Breast, prostate and bladder cancers increase risk of second tumour in female genital organs [RR 4.78 (3.84-5.93)], urinary system [RR 3.69 (2.89-4.69)] and male genital organs [RR 3.76 (2.84-4.69)] respectively. The MPC incidence is increasing. Interventions for MPC prevention, according to the European Code against Cancer, should be implemented early after the first cancer principally if patients suffer breast, bladder, prostate, larynx and colon cancers.

Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia.

Axonal regeneration in the lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. In adult rats, olfactory ensheathing glia (OEG) transplants successfully led to functional and structural recovery after complete spinal cord transection. From 3 to 7 months post surgery, all OEG-transplanted animals recovered locomotor functions and sensorimotor reflexes. They presented voluntary hindlimb movements, they supported their body weight, and their hindlimbs responded to light skin contact and proprioceptive stimuli. In addition, relevant motor axons (corticospinal, raphespinal, and coeruleospinal) regenerated for long distances within caudal cord stumps. Therefore, OEG transplantation provides a useful repair strategy in adult mammals with traumatic spinal cord injuries. Our results with these cells could lead to new therapies for the treatment of spinal cord lesions in humans.

Regional-specific regulation of BDNF and trkB correlates with nigral dopaminergic cell sprouting following unilateral nigrostriatal axotomy.

Axotomy is a powerful stimulus of axon growth and plastic changes. We investigated the potential role of BDNF/trkB signaling in the sprouting of dopaminergic nigral axons in response to axotomy of the medial forebrain bundle. Tyrosine hydroxylase immunohistochemistry revealed the existence of sprouting mechanisms in the axotomized substantia nigra (SN). Time-course changes of trkB mRNA expression demonstrated a robust increase in an area projecting from the rostral tip of the SN to the glial scar, which coincided with evidence of nigral dopaminergic sprouting. In addition, we found an early loss of this messenger in areas related to the knife cut, which recovered by 7 days postlesion. TrkB down-regulation appeared to be associated to the lesion-induced local damage, as it was restricted to an area showing Fluoro-Jade B- and TUNEL positive cells. In trkB-depleted areas, an inverse correlation between mRNA expressions of BDNF and trkB was apparent. Specific induction of BDNF mRNA was mostly seen in border of areas devoid of trkB mRNA. In contrast, in the areas exhibiting trkB mRNA expression, no BDNF mRNA was detected. We suggest that trkB levels could be a determinant element in regulating BDNF expression. Finally, the search for molecules involved in either promoting or inhibiting axonal growth, demonstrated up-regulation of GAP-43 and Nogo-A mRNA at sites close to the knife transections as early as 1 day postlesion. However, overall, Nogo-A induction was more robust than that seen for GAP-43.

Clinical Outcomes of Sequential Intrastromal Corneal Ring Segments and an Extended Range of Vision Intraocular Lens Implantation in Patients with Keratoconus and Cataract.

PURPOSE: To evaluate efficacy, safety, and predictability of sequential Ferrara-type intrastromal corneal ring segments (ICRS) and an extended range of vision intraocular lens (IOL) implantation in patients with keratoconus and cataract. METHODS: This study comprised patients with keratoconus and cataract that had ICRS implantation followed 6 months later by extended range of vision IOL implantation. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and residual refractive errors, analysed using vector analysis, were recorded preoperatively, 6 months after ICRS implantation, and 6 months after IOL implantation, respectively. RESULTS: The study enrolled 17 eyes (11 patients). The mean UDVA (logMAR scale) was 1.15 ± 0.67 preoperatively, 0.88 ± 0.69 six months after ICRS implantation (P = 0.005), and 0.27 ± 0.18 six months after IOL implantation (P < 0.0001). The CDVA changed from 0.26 ± 0.15 (logMAR) before surgery to 0.17 ± 0.08 six months after Ferrara-type ICRS implantation (P = 0.002) and to 0.07 ± 0.06 six months after IOL implantation (P < 0.0001). The spherical equivalent and the refractive cylinder declined steeply after IOL implantation (P < 0.001). The magnitude of depth of focus was 2.60 ± 1.02 D. There were no statistically significant differences in visual acuity for a defocus range from +0.50 D to -0.50 D (P > 0.1). CONCLUSION: Sequential Ferrara-type ICRS and an extended range of vision IOL implantation provided good visual and refractive outcomes, being an effective, safe, and predictable procedure for the treatment of selected cases of patients with keratoconus and cataract. In addition, this approach provides an increase of tolerance to defocus.

Expression of HLA class I and II antigens in bronchogenic carcinomas: its relationship to cellular DNA content and clinical-pathological parameters.

We studied the presence of HLA class I antigens in 115 samples of bronchogenic carcinomas (66 frozen and 49 formalin-fixed and paraffin-embedded specimens) by the immunophosphatase alkaline and immunoperoxidase methods with antibodies against major histocompatibility complex antigens. We also studied HLA class II antigens on the 66 frozen tumor samples. Nonneoplastic lung tissue was also analyzed for purposes of comparison. Pneumocytes and epithelial respiratory cells expressed HLA class I and II antigens. The expression of class I antigens was totally lost in 29 tumors (25%). The defect in HLA gene expression affected both heavy chain and beta 2-microglobulin, as demonstrated by the null reactivity with specific antibodies. In 2 cases of 66 studied in cryostatic section, the selective loss of A locus was observed, and in three cases selective loss of B locus was detected. The expression of class I antigens was compared with clinical-pathological parameters such as histological type, degree of differentiation, and tumor stage, as well as tumoral ploidy. The absence of expression of HLA class I molecules was significantly associated with poorly differentiated and undifferentiated tumors (P less than 0.0001) and with aneuploid tumors (P less than 0.001), suggesting that some lung tumors may escape immune surveillance and become biologically more aggressive. Class II antigens were expressed in 13 cases of 66 studied (18%) in frozen specimens, and a clear relationship was observed with well-differentiated tumors (P less than 0.05).

Horizontal gaze palsy and progressive scoliosis in a patient with congenital esotropia and inability to abduct. A case report. / Parálisis de la mirada horizontal y escoliosis progresiva en un paciente con endotropia congénita y limitación de abducción. A propósito de un caso.

CASE REPORT: The case is presented on a 4- year-old child with congenital esotropia, limitation of abduction, cross-fixation, and thoracolumbar scoliosis. Genetic testing of ROBO3 gene confirmed the diagnosis of horizontal gaze palsy and scoliosis (HGPSS) DISCUSSION: HGPPS is a rare congenital disorder characterised by absence of conjugate horizontal eye movements and progressive scoliosis developed in childhood and adolescence. We highlight this motility disorder as a part of the differential diagnosis of early childhood esotropia with cross- fixation and limitation of abduction.

Female gender and wealth are associated to overweight among adolescents in La Paz, Bolivia.

OBJECTIVE: To describe the prevalence of overweight, obesity and being thin in adolescents of La Paz City, Bolivia. DESIGN: Cross-sectional study, clustered sampling. SETTING: La Paz, Bolivia, August-September 2003. SUBJECTS: Height and weight of 525 adolescents (mean age 16 y; s.d.+/-1.3) attending public and private schools were measured; sociodemographic characteristics were assessed with a short questionnaire. RESULTS: The present study reveals that 9.3% (+/-2.5) of the sample are thin adolescents; 19.8% (+/-3.4) is the overall prevalence of overweight and 2.3% (+/-1.3) the overall prevalence of obesity. The odds of being thin were higher among those working (P=0.03) and among those of higher age (P<0.001). The odds of being overweight were higher among female subjects (P<0.001). The odds of being obese were higher among younger adolescents (P=0.046) and among the more wealthy ones (P=0.044). CONCLUSIONS: A large prevalence of 22% overweight/obesity in adolescents from La Paz City was observed. The findings support the need of enhanced nutritional surveillance and interventions particularly in female adolescents.

Differential expression of microtubule-associated protein 1B phosphorylated isoforms in the adult rat nervous system.

Phosphorylated microtubule-associated protein 1B isoforms are thought to be involved in the plastic events taking place in neurons during development. However, little is known about their expression and possible role in the mature nervous system. To gain insight into the mechanisms underlying neuronal plasticity in the adult, we studied the pattern of expression of three microtubule-associated protein 1B isoforms in the entire adult rat nervous system. Accordingly, we performed western blots and immunohistochemistries using the antibodies 125, 150 and 531, which specifically recognize phosphorylated and unphosphorylated microtubule-associated protein 1B epitopes. Two electrophoretically distinct microtubule-associated protein 1B isoforms, slow-migrating and fast-migrating, were detected with the antibodies. The pattern of expression of these isoforms in the adult rat nervous system was region specific. Phosphorylated slow-migrating microtubule-associated protein 1B was expressed at all cellular compartments of primary sensory neurons in the central and peripheral nervous systems. In addition to primary sensory axons, slow-migrating microtubule-associated protein 1B was encountered at some other axons within the central nervous system. We discuss the correlation between slow-migrating microtubule-associated protein 1B axonal content and the regenerative potential of neurons. Phosphorylated fast-migrating microtubule-associated protein 1B was exclusively found in central nervous system dendrites where synaptic plasticity with morphological changes occurs in the adult. Unphosphorylated fast-migrating microtubule-associated protein 1B was the only isoform present in the bodies and dendrites of all motor neurons, and in peripheral and central nervous system glial cells of myelinated tracts with slow-migrating microtubule-associated protein 1B-containing axons. In summary, this report describes the pattern of expression of microtubule-associated protein 1B isoforms in the entire adult rat nervous system. In addition, it provides some information about the possible functional implications of phosphorylated microtubule-associated protein 1B isoforms in the adult.

Glial cells from adult rat olfactory bulb: immunocytochemical properties of pure cultures of ensheathing cells.

Three morphologically and immunohistochemically distinct types of cell were present in primary cultures of adult rat olfactory nerve and glomerular layers of the olfactory bulb. One cell type was multipolar and stained positively for glial fibrillary acidic protein; a second type had fried egg-like morphology and stained with antibodies to epitope ED1; the third cell type had fusiform morphology, reacted with antibodies to vimentin and laminin and was glial fibrillary acidic protein- and ED1-negative. Trypsinization of these primary cultures (3 min, 37 degrees C), detached multipolar and fusiform cells only. When detached cells were set up in secondary culture on a glass substrate, fusiform cells did not attach, resulting in a pure culture of multipolar cells. Multipolar cells were glial fibrillary acidic protein- and myelin basic protein-positive and had the properties of so-called ensheathing cells or Blanes' glia. Immunoreactivity with anti-nerve growth factor receptor and anti-fibronectin allowed us to identify four distinct populations of multipolar ensheathing cells. One population was nerve growth factor receptor-positive, fibronectin-negative. A second was nerve growth factor receptor-negative and fibronectin-positive. A third was positive for both markers and the remaining cells did not stain for either of them. The morphological and immunological characteristics of cultured cells from olfactory nerve and glomerular layers were similar to those of Schwann cells and the similarities could account for the permissivity to axonal growth of the olfactory bulb.

Usefulness of the codification of multiple causes of death in mortality statistics.

BACKGROUND: The codification of multiple causes of death began in the US in 1917 and systematic publication of this data started in 1984. In Spain this began in 1988, and the data from this year have been taken as the basis for investigation. They have also been studied for regional differences. METHODS: A representative sample (595) of Spanish Standard Death Certificates (DC) was collected in Asturias for the year 1988. All were coded according to the International Classification of Diseases and a separate coding was made for each nosological entity included in the certificate (coding of multiple causes). The median, mode and the multiple cause/underlying cause ratio were also calculated. RESULTS: More than 80% of the certificates studied contained more than one cause of death. Chronic diseases are those which are accompanied by a greater number of causes and acute diseases those which appear alone. The highest ratios appear for diseases which are ill defined and also in those which are chronic. CONCLUSIONS: Our data show that information is lost in the production of the statistics of mortality and there are repercussions for the usefulness of these statistics.

Cell therapy to repair injured spinal cords: olfactory ensheathing glia transplantation.

The absence of spontaneous axonal regeneration in the adult mammalian central nervous system cause devastating functional consequences in patients with spinal cord injuries. During the past decades several attempts have been made in order to find a strategy to repair injured spinal cords in experimental animals, that could provide a novel therapeutic approach in humans. Cell transplantation has been broadly used as an intervention to influence neuronal survival and axonal regeneration in the severed neuraxis. Of the cell types used for transplantation, olfactory ensheathing glia (OEG) promoted a dramatic functional improvement and anatomical repair after complete transection of the adult mammalian spinal cord. These cells can be easily obtained from adult donors opening the possibility of autologous transplantation. Grafting OEG to repair injured spinal cords offers some advantages compared to injections of other cell types. Therefore, OEG have become good candidates to bring about repair in damaged spinal cords. In this article we review OEG transplantation studies, discuss the properties that could account for their axonal growth-promoting ability, and the advantages of using OEG as a repair strategy.

Expression of 9-O-acetylated gangliosides during development of the rat olfactory system.

The expression of 9-O-acetylated gangliosides recognized by the Jones monoclonal antibody (mAb) correlates with cell migration and axonal outgrowth in the developing rat nervous system. We studied the expression of these gangliosides during the development and maturation of the rat olfactory system. Beginning on embryonic day 13 (E13) the olfactory epithelium and the migratory mass were intensely stained with Jones mAb. However, though this immunoreactivity disappeared from the olfactory epithelium at E19, it remained in a few fascicles and some glomeruli of the newborn and adult olfactory bulbs. We concluded that the expression of 9-O-acetylated gangliosides by olfactory axons and/or migrating cells may facilitate axonal outgrowth during development and might be involved in the formation of new glomeruli in the mature olfactory bulb.

Two modes of microtubule-associated protein 1B phosphorylation are differentially regulated during peripheral nerve regeneration.

Two major modes of MAP1B phosphorylation (I and II), respectively recognized by monoclonal antibodies 150 and 125, have been related to remodeling and formation of processes in the mature nervous system. To gain insight into the cytoskeletal modifications underlying peripheral nerve regeneration, the pattern of expression of both MAP1B phosphorylated modes was studied during this process. Sciatic nerves from adult Wistar rats were crushed and animals allowed to survive for 5, 7, 10 or 14 days. After those survival periods, damaged and undamaged sciatic nerves, dorsal root ganglia (DRG), and spinal cords, were subjected to immunohistochemistry and Western blot, using antibodies 150 and 125. At all survival periods analysed, MAP1B phosphorylated at mode I was concentrated at the distal region of regenerating nerves whereas mode II phosphorylation underwent an overall decrease in regenerating axons that was less evident in more proximal nerve regions. Very high levels of MAP1B phosphorylated at mode II were detected in the bodies of DRG neurons and in bodies and dendrites of spinal motor neurons. This phosphorylation mode was also encountered in some Schwann cells and oligodendroglia associated with more proximal regions of regenerating axons. In this study we conclude that MAP1B was differentially phosphorylated depending on the cell type, subcellular compartment and stage of the regenerative process and discuss the possible functional implications that differential expression of each MAP1B phosphorylation mode might have during nerve regeneration.

Knowledge of the European Code against Cancer in sixth-form pupils and teachers in Asturias (Spain).

Cancer is the second major cause of death in Spain and in most industrialized countries. It is also the main cause of premature death. The objective of this study was to evaluate what is known and practiced of the European Code against Cancer by students and teachers of the final course of secondary education in Asturias (Spain). Two questionnaires (the official one given by the European Code against Cancer and another, designed by us) were given to a representative sample of 695 students and 160 teachers. The mean score of knowledge for teachers and pupils, respectively, was 6.41 and 5.05, out of a possible maximum of 16 points. This difference was statistically significant (Student's t-test = 6.63; P > 0.0001). A relationship was also found in females between knowledge and practice in relation to food intake, tobacco and alcohol consumption, and cancer. Our results demonstrate a lack of knowledge and practice of the Code, which places at risk the main objective of the Europe against Cancer Programme to reduce cancer mortality by 15% by the year 2000. In our opinion more informational-educational programmes are therefore necessary.

Validation of a questionnaire to evaluate the attitude towards primary prevention advice from the European code against cancer.

Educative interventions to promote primary prevention of cancer (PPC) should be based on psychosocial models and be tailored to attitude. Attitude is a difficult variable to measure. The aim of this study was to draw up a questionnaire to evaluate the attitude to PPC of relatives of patients affected by cancer. An interview of 48 patients, who answered open questions, allowed 67 items to be drawn up. Three hundred and fifty-five people answered the self-administered questionnaire of 67 items (69 of them did it twice, with an interval of 2 weeks). The factorial analysis revealed five factors that explain the 36% total and the 115% common estimated variance. The Cronbach's alpha oscillated between 0.80 and 0.93. The intraclass correlation coefficient was 0.7721 (95% CI (confidence interval) 0.6311-0.8592, P<0.0001). The analysis based on Samejima's model ordered the items according to their discriminating power and the difficulty/ease with which people agree with the most preventive option. The average scores obtained in both surveys of 69 people did not show significant statistical differences (P=0.195). The definitive questionnaire obtained has 63 items that measure attitude to PPC behaviour in a reliable and stable way.

Olfactory ensheathing glia: properties and function.

The failure of regenerating axons to grow within the adult mammalian central nervous system (CNS) does not apply to the olfactory bulb (OB). In this structure, normal and transected olfactory axons are able to enter, regenerate, and reestablish lost synaptic contacts with their targets, throughout the lifetime of the organism. A remarkable difference between an axonal growth-permissive structure such as the OB and the remaining CNS resides in the presence of ensheathing glia in the former. These cells exhibit phenotypic and functional properties known to be involved in the process of axonal elongation that may explain the permissibility of the OB to axonal growth. In addition, transplants of ensheathing glia were successfully used to promote axonal regeneration within the injured adult CNS. The axonal growth-promoting properties of ensheathing glia make the study of this cell type interesting to provide an insight into the mechanisms underlying the process of axonal regeneration. Therefore, in this article we review the developmental, morphologic, immunocytochemical, and functional properties presented by this unique glial cell type, and correlate them with the axonal growth-promoting ability of ensheathing glia. In addition, we provide some evidence of the potentiality that ensheathing glia might have as a promoter of axonal regeneration within the injured nervous system.