CD69 downregulates autoimmune reactivity through active transforming growth factor-beta production in collagen-induced arthritis

CD69 is induced after activation of leukocytes at inflammatory sites, but its physiological role during inflammation remains unknown. We explored the role of CD69 in autoimmune reactivity by analyzing a model of collagen-induced arthritis (CIA) in WT and CD69-deficient mice. CD69-/- mice showed higher incidence and severity of CIA, with exacerbated T and B cell immune responses to type II collagen. Levels of TGF-beta1 and TGF-beta2, which act as protective agents in CIA, were reduced in CD69-/- mice inflammatory foci, correlating with the increase in the proinflammatory cytokines IL-1beta and RANTES. Local injection of blocking anti-TGF-beta antibodies increased CIA severity and proinflammatory cytokine mRNA levels in CD69+/+ but not in CD69-/- mice. Moreover, in vitro engagement of CD69 induced total and active TGF-beta1 production in Concanavalin A-activated splenocyte subsets, mouse and human synovial leukocytes, and Jurkat stable transfectants of human CD69 but not in the parental CD69 negative cell line. Our results show that CD69 is a negative modulator of autoimmune reactivity and inflammation through the synthesis of TGF-beta, a cytokine that in turn downregulates the production of various proinflammatory mediators.     

Reference range thyroid-stimulating hormone is associated with physical activity energy expenditure in overweight and obese postmenopausal women: a Montreal-Ottawa New Emerging Team Study

Clinical and, to a lesser extent, subclinical hypothyroidism is associated with a variety of metabolic abnormalities, including increased body mass index, unfavorable lipoprotein profile, and increased biomarkers for atherosclerosis. Energy expenditure could act as a confounding factor in the association reported between thyroid-stimulating hormone (TSH) levels and cardiometabolic risk factors. The objective of the study was to investigate the relationship between reference range plasma TSH and energy expenditure as well as blood pressure, lipid, and inflammation parameters in women. One hundred four postmenopausal, overweight and obese, spontaneously euthyroid women were included in the study. We evaluated total energy expenditure by doubly labeled water, resting energy expenditure by indirect calorimetry, physical activity energy expenditure (PAEE = [total energy expenditure × 0.90] − resting metabolic rate), body weight, and percentage of fat mass by dual-energy x-ray absorptiometry. Blood pressure, plasma lipoproteins profile, and high-sensitivity C-reactive protein levels were also measured. Mean TSH was 2.39 ± 1.09 mIU/L. We observed that high-density lipoprotein cholesterol (r = −0.20, P ≤ .05) was negatively associated with TSH, whereas systolic blood pressure (r = 0.21, P ≤ .05) and apolipoprotein B (r = 0.22, P ≤ .05) were positively correlated with TSH. However, these correlations were no longer significant after controlling for PAEE. A significant negative correlation was found between TSH and PAEE (r = −0.23, P ≤ .05). Our results suggest that, although TSH in the reference range is associated with some cardiometabolic risk factors, this is in large part explained by lower PAEE. In turn, lower PAEE could increase the cardiometabolic risk.     

Impairment of rapid repetitive finger movements and visual reaction time in patients with essential tremor

Background and purpose:  The question whether patients with essential tremor (ET) have slowed movements as part of their clinical manifestations is still a matter of controversy. We analyzed basic motor function in patients with ET and in healthy matched controls.
Methods:  We studied 61 patients with ET and 122 age- and sex-matched controls. Evaluation included four timed tests (pronation-supination, finger tapping and movement between two points, all with both hands, and walking test); and three tests performed on a personal computer (speed for pressing repetitively a key – frequency, visual reaction time and movement time, all with both hands).
Results:  Essential tremor patients showed higher mean values for right and left finger tapping, left movement between two points; and with right and left frequency and reaction time. In the logistic regression study, ET patients showed significantly higher values than controls for right and left finger tapping; mean, SD, maximum and rank values of right and left frequency; and mean, SD, minimum, maximum and rank values of right and left visual reaction time. Tremor severity was not correlated with the altered values.
Conclusions:  Patients with ET showed impaired motor performance, at least in some tasks, such as rapid repetitive finger movements (finger tapping and frequency) and visual reaction time (impairment was not related with tremor severity). This probably means that patients with ET have some degree of bradykinesia.     

Nonsynonymous Polymorphisms of Histamine-Metabolising Enzymes in Patients with Parkinson’s Disease

Objective To analyze genetically based impairment in histamine-metabolising enzymes in patients with Parkinson’s disease (PD). Methods Leukocytary DNA from 214 PD patients and a control group of 295 unrelated healthy individuals was studied for nonsynonymous histamine N-methyltransferase (HNMT) and diamine oxidase (ABP1) polymorphisms by using amplification–restriction analyses. Results An association of the HNMT Thr105Ile polymorphism, but not of the ABP1 His645Asp polymorphism, with PD was observed. Patients with PD showed a higher frequency of homozygous HNMT genotypes leading to high activity with a gene-dose effect (P < 0.001), as compared to healthy subjects. These findings were independent of gender, but the association with the HNMT polymorphism is higher among patients with late-onset PD (P < 0.0001). Conclusion These results, combined with previous findings indicating alterations in histamine levels in patients with PD, suggest that alterations of histamine homeostasis in the SNC are associated with the risk for PD.     

The Nonsynonymous Thr105Ile Polymorphism of the Histamine <Emphasis Type="Italic">N</Emphasis>-Methyltransferase is Associated to the Risk of Developing Essential Tremor

Objective We analyzed in patients with essential tremor (ET) the Thr105Ile polymorphism of the Histamine N-methyltransferase (HNMT) enzyme that is associated to Parkinson’s disease (PD) risk. Methods Leukocytary DNA from 204 ET patients and a control group of 295 unrelated healthy individuals was studied for the nonsynonymous HNMT Thr105Ile polymorphism by using amplification-restriction analyses. Results Patients with ET showed a higher frequency of homozygous HNMT 105Thr genotypes leading to high metabolic activity (p < 0.015) with a statistically significant gene-dose effect, as compared to healthy subjects. These findings were independent of gender, and of tremor localization, but the association of the HNMT polymorphism is more prominent among patients with late-onset ET (p < 0.007). Conclusion These results, combined with previous findings indicating alterations in the frequency for the HNMT Thr105Ile polymorphism in patients with PD, suggest that alterations of histamine homeostasis in the SNC are associated with the risk of movement disorders.     

Imaging in spinal vascular disease

Spinal vascular diseases are rare and constitute only 1% to 2% of all vascular neurologic pathologies. In this article, the following vascular pathologies of the spine are described: spinal arterial infarcts, spinal cavernomas, and arteriovenous malformations (including perimedullary fistulae and glomerular arterivenous malformations), and spinal dural arteriovenous fistulae. This article gives an overview about their imaging features on MRI, MR angiography, and digital subtraction angiography. Clinical differential diagnoses, the neurologic symptomatology, and the potential therapeutic approaches of these diseases, which might vary depending on the underlying pathologic condition, are given.     

Infant mortality and air pollution: modifying effect by social class

Studies link air pollution with increased mortality; however, information on infants is scarce and inconclusive. OBJECTIVE: We studied short-term PM10 exposure, relating to increased respiratory-related infant mortality, and estimated for poor living conditions. METHODS: A case-crossover approach modeled the relationship between infant mortality (1 month-1 year of age), and ambient PM10 levels on days before death in Ciudad Juarez, Mexico (1997-2001). Socioeconomic level (SES) of the deceased was defined by residence location. RESULTS: Overall air pollutants did not affect infant mortality (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.94-1.11 for PM10, lag1) but low SES increased risk. Each 20 microg/m3 in PM10 (24-hour average, lag1, cumulative over 2 previous days) increased respiratory-related mortality (OR = 1.61, 95% CI = 0.97-2.66; OR = 2.56; 95% CI = 1.06-6.17, respectively). Ozone levels did not affect infant mortality for any SES. CONCLUSIONS: Worse living conditions among lower SES concurred with increased mortality.