A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette's/chronic tic disorders.

The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.

Population-based, multi-generational family clustering study of social anxiety disorder and avoidant personality disorder.

BACKGROUND: We aimed to provide unbiased estimates of familial risk and heritability of social anxiety disorder (SAD) and avoidant personality disorder (AVPD). METHOD: We identified 18 399 individuals diagnosed with SAD and 2673 with AVPD in the Swedish National Patient Register between 1997 and 2009. Risks (odds ratios; OR) for SAD in all biological and non-biological relatives of probands, compared to relatives of unaffected individuals were calculated. We also estimated the risks for AVPD in relatives of probands with SAD. RESULTS: The risk for SAD among relatives of SAD probands increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives [OR 4.74, 95% confidence interval (CI) 4.28-5.25] were significantly higher than for second-degree and third-degree relatives. Second-degree relatives (OR 2.30, 95% CI 2.01-2.63) had significantly higher risk than third-degree relatives (OR 1.72, 95% CI 1.52-1.94). Relatives at similar genetic distances had similar risks for SAD, despite different degrees of shared environment. Heritability was estimated to be approximately 56%. There were no significant sex differences in the familial patterns. The risk of AVPD in relatives of SAD probands was significantly elevated, even after excluding individuals with both diagnoses (first-degree OR 3.54, second-degree OR 2.20, third-degree OR 1.62). Non-biological relatives (spouses/partners) also had elevated risks for both SAD (OR 4.01) and AVPD (OR 3.85). CONCLUSIONS: SAD clusters in families primarily due to genetic factors. SAD and AVPD are aetiologically related and may represent different expressions of the same vulnerability. The strong marital concordance observed in SAD/AVPD may indicate assortative mating but the exact mechanisms and implications require further investigation.

Induction and isolation of frameshift mutants in cultured Chinese hamster DON cells.

Induction, isolation and characterization of frameshift mutants were studied by using a Chinese hamster Don (CHD) cell line. ICR-191, known to be a potent frameshift mutagen, was used for the induction of frameshift mutations. The drug (10(-5) M), as well as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and ethyl methanesulfonate (EMS), increased significantly the frequency of forward mutations from 8-azaguanine (8-AG) sensitivity (8-AGs) to resistance (8-AGr) over the untreated control to an extent of about 100-fold. 21 8-AGr mutants were isolated from the AP-01 (a sub-line of CHD) cells after treatment with appropriate concentrations of ICR-191 (10(-5) and 1.36 X 10(-5) M), and subsequently several reclonal mutants were tested for their ability to revert to 8-AG susceptibility after treatment with the three mutagens and a carcinogen, 2-nitrofluorene (2-NF), known to be a frameshift mutagen. Among the 8-AGr mutants tested, clone ICR-014 or ICR-172 showed a significant increase in reversion frequency over the control level only after treatment with ICR-191 or 2-NF, respectively; but not with the other two mutagens. These results suggest that each of these two kinds of mutant has a different frameshift mutation in one of the loci controlling 8-AG resistibility. It was also found that the hypoxanthine--guanine phosphoribosyl transferase (HGPRT) activities in clones ICR-014 and ICR-172 were 1.9 and 34% of that of the original AP-01 cells, respectively.

Induction of mutations and chromosome aberrations in lung cells following in vivo exposure of rats to nitrogen oxides.

In order to investigate the mutagenic effects of nitrogen oxides ( NOx ), induced mutations and chromosome aberrations were examined using primary lung cells obtained from rats exposed in vivo to NO2 and NO. Rats were exposed to nitrogen oxide gases at concentrations of 8-27 ppm for 3 h in a stainless steel chamber. Over the range 15-27 ppm, NO2 significantly increased mutation to ouabain resistance. Over a similar dose range, NO significantly increased mutation only at the highest concentration (27 ppm). Following NO2 exposure, chromosome aberrations (mainly chromatid type) were induced in chromatid breaks, 2.5-11.6-fold over the control at 8 and 27 ppm, respectively.

Quantitative and functional changes in platelets and their preservation during extracorporeal circulation.

Platelet count, ADP-aggregation and adhesiveness of platelets, fibrinogen, FDP, and prothrombin time were examined in 50 patients who had undergone open cardiac surgery. Ticlopidine (250 mg/day) and Dipyridamole (1-2 mg/day) were administered prior to the extracorporeal circulation and the platelet inhibitory effects were compared. Platelet count was reduced markedly with the initiation of bypass and the low level was maintained until the 3rd postoperative day. Hyperthrombocythemia was found after a week. ADP induced platelet aggregation and platelet adhesiveness were markedly depressed by the ACC. Fibrinogen showed low level during the ECC but the hyper-fibrinogenemic state was observed in postoperative course. FDP showed an abnormally high value in nearly half the cases, particularly in the cases of valvular replacement. Ticlopidine markedly depressed the ADP-aggregation and Dipyridamole reduced platelet adhesiveness and thus both drugs showed a prophylactic effect in the reduction of platelets.

Effects of exercise on mice exposed to ozone.

The effects of exercise on response to ambient levels of ozone exposure were studied by using a sensitive indicator of the pulmonary effect of ozone, viz., the elevation of reduced glutathione levels in the lungs. Mice were exposed to 0.2, 0.5, or 1.0 ppm ozone for 3 hr daily for 4 days. For exercise study, animals were placed in a rotating cage in which they were alternately exercised and rested every 15 min during exposure periods. The susceptibility of mice to the pulmonary effects of ozone was found to be approximately tripled by concurrent exercise. The results indicate the importance of exercise in the evaluation of health hazards from photochemical smog.

A collaborative study of stroke incidence in Japan: 1975-1979.

A Japan Collaborative Study of Stroke covering 20 regional and occupational population groups was conducted with the support of the Ministry of Health and Welfare. In this study 17,423 males and 16,856 females, aged 40 to 69, were followed up prospectively from 1975 to 1979. The average annual incidence of all types of stroke was 3.94 for men and 2.52 for women per 1,000 population. The incidence of cerebral hemorrhage for men and women stood at 1.26 and 0.59 and that of cerebral infarction at 1.87 and 1.10 respectively. The difference in incidence between the sexes was large particularly in the age range of 40-49. The incidence of all types of stroke, cerebral hemorrhage and cerebral infarction increased with age. The incidence of all strokes in Japan during the period 1975-1979 appears to have decreased in comparison with that in 1960-1969, but tended to be still higher than that in Western countries.