Absence of N addition facilitates B cell development, but impairs immune responses

The programmed, stepwise acquisition of immunocompetence that marks the development of the fetal immune response proceeds during a period when both T cell receptor and immunoglobulin (Ig) repertoires exhibit reduced junctional diversity due to physiologic terminal deoxynucleotidyl transferase (TdT) insufficiency. To test the effect of N addition on humoral responses, we transplanted bone marrow from TdT-deficient (TdT−/−) and wild-type (TdT+/+) BALB/c mice into recombination activation gene 1-deficient BALB/c hosts. Mice transplanted with TdT−/− cells exhibited diminished humoral responses to the T-independent antigens α-1-dextran and (2,4,6-trinitrophenyl) hapten conjugated to AminoEthylCarboxymethyl-FICOLL, to the T-dependent antigens NP19CGG and hen egg lysozyme, and to Enterobacter cloacae, a commensal bacteria that can become an opportunistic pathogen in immature and immunocompromised hosts. An exception to this pattern of reduction was the T-independent anti-phosphorylcholine response to Streptococcus pneumoniae, which is normally dominated by the N-deficient T15 idiotype. Most of the humoral immune responses in the recipients of TdT−/− bone marrow were impaired, yet population of the blood with B and T cells occurred more rapidly. To further test the effect of N-deficiency on B cell and T cell population growth, transplanted TdT-sufficient and -deficient BALB/c IgMa and congenic TdT-sufficient CB17 IgMb bone marrow were placed in competition. TdT−/− cells demonstrated an advantage in populating the bone marrow, the spleen, and the peritoneal cavity. TdT deficiency, which characterizes fetal lymphocytes, thus appears to facilitate filling both central and peripheral lymphoid compartments, but at the cost of altered responses to a broad set of antigens

Alcohol use disorders are associated with venous thromboembolism.

Moderate alcohol consumption has been suggested to protect against venous thromboembolism (VTE). However, it is not known how alcohol abuse and its associated somatic complications affect the risk of VTE. The present study determined the risk of pulmonary embolism (PE) and deep vein thrombosis (DVT) of the lower extremities in patients with alcohol use disorders (AUDs) in Sweden. All inpatients with AUDs in 2002-2010 without a previous VTE event (72,024 patients) were matched to five controls without AUD and followed until the end of follow-up (December 31, 2010), death, emigration or a VTE event. Cox regression was used to determine adjusted hazard ratios (HRs) for VTE. AUD patients were further divided into those without alcohol-related somatic complications (AUD-) and those with alcohol-related somatic complications (AUD+, i.e., encephalopathy, epilepsy, polyneuropathy, myopathy, cardiomyopathy, gastritis, liver disease, acute pancreatitis, and chronic pancreatitis). The adjusted HR for VTE was significantly increased for both AUD- (HR 1.70, 95 % CI 1.55-1.87) and AUD+ (HR 1.73, 95 % CI 1.37-2.19) patients. The risk of DVT was increased in both AUD+ and AUD- patients (HR 1.62, 95 % CI 1.45-1.83 and HR 1.99, 95 % CI 1.53-2.59, respectively). However, the risk of PE was only significantly increased in AUD- patients (HR 1.87, 95 % 1.59-1.20) and not in AUD+ patients (HR 1.16, 95 % 0.70-1.91). In conclusion, the present study shows that AUD increases the risk of VTE, even in the absence of alcohol-related somatic complications. Our findings suggest that severe alcohol abuse increases the risk of VTE

Kinetics of HDL Cholesterol and Paraoxonase Activity in Moderate Alcohol Consumers

Background: The inverse association between moderate drinking and coronary heart disease mortality is well established. This study was performed to investigate the kinetics of the alcohol-induced increases in apo A-1, HDL cholesterol, and paraoxonase (PON) activity, as well as to study whether the alcohol-induced increases in PON activity differ within different PON polymorphisms, and to investigate whether moderate alcohol consumption has similar effects on the outcome measures in postmenopausal women as in middle-aged men. Methods: In a randomized, diet-controlled, crossover study, 10 middle-aged men and 9 postmenopausal women, all apparently healthy, nonsmoking, and moderate alcohol drinkers, consumed beer or no-alcohol beer (control) with evening dinner during two successive periods of 3 weeks. During the beer period, alcohol intake equaled 40 and 30 g/day for men and women, respectively. The total diet was supplied to the subjects and had essentially the same composition during these 6 weeks. Before each treatment was a 1-week washout period, in which the subjects were not allowed to drink alcoholic beverages. Results: Moderate alcohol consumption significantly increased serum apo A-I level after 5 days (3.7%, p < 0.05); after 10 days, serum HDL cholesterol level was increased (6.8%, p < 0.001), and after 15 days serum PON activity was increased (3.7%, p < 0.05), all compared with no alcohol consumption. Gene polymorphisms did not modulate the alcohol effect on PON. Conclusions: Serum apo A-I, HDL cholesterol, and PON activity were significantly increased during 3 weeks of moderate alcohol consumption as compared with no alcohol consumption. Moreover, the results suggest that there is a sequence in induction of these parameters. After an increase in apo A-I, HDL cholesterol is increased followed by an increase in PON activity. Increased serum HDL cholesterol level and PON activity may be a mechanism of action not only in healthy middle-aged men but also in post-menopausal women, underlying the reduced coronary heart disease risk in moderate drinkers. Chemicals/CAS: Apolipoprotein A-I; Aryldialkylphosphatase, EC 3.1.8.1; Cholesterol, HDL; Esterases, EC 3.1