Genetics of Autoantibodies in Relation to Disease

ABSTRACT. Familial occurrence of three types of autoantibodies, viz. rheumatoid factors, antinuclear antibodies and thyroid autoantibodies, was investigated in two population series: twins from the Finnish Twin Registry representing the adult twin population living in an urban area (76 monozygotic and 82 dizygotic same-sex twin pairs) and siblings from a middle-aged rural population subject to an ongoing epidemiological study (311 sibling groups comprising 801 subjects and 584 married couples). The observations were compatible with the concept of two components in the above autoantibody system. The major component is determined predominantly by environmental factors and is manifested with increasing age. The autoantibodies belonging to the minor, familial component occur in somewhat higher titers, exhibit certain specificity features of their own (RF reacting with rabbit gamma globulin), and are associated with “autoimmune” diseases.     

Differences in Recent Life Events between Alcoholic and Depressive Nonalcoholic Suicides

The purpose of this study was to investigate the main differences in recent life events preceding suicide between alcoholic and depressive nonalcoholic suicide victims, how much these differences were sex- and age-dependent, and how social support varied between these groups.
Using the psychological autopsy method, retrospective best-estimate diagnoses by DSM-III-R criteria were assigned to a randomized 16.4% sample ( n = 229) of suicide victims drawn from a 1-year total nationwide suicide population ( n = 1,397) in Finland. Life events during the last 3 months (32 items) and social support (6 items) of 75 suicide victims with alcohol abuse/dependence diagnoses were compared with those of 69 nonalcoholic depressive victims.
Among male suicides, the alcoholics had experienced more separations and family discord, financial trouble, and unemployment, whereas the depressives had experienced more somatic illness. Among females, adverse interpersonal events had been common in both alcoholic and depressive victims. Among the alcoholics, unlike the depressives, the number of adverse interpersonal life events had not diminished with increasing age. Living alone had been twice as common among the alcoholic suicides and, in these cases, recent separation, unemployment, and financial trouble were remarkably common, suggesting a concurrent stressor effect.
Our results confirm and extend the earlier findings of excess interpersonal stressors among alcoholic suicides compared with depressive suicides. The findings suggest that multiple adverse life events and living alone need to be taken into account in clinical practice when assessing psychosocial stress and suicidal danger in alcoholism.     

Magnetic Resonance Imaging and Magnetization Transfer in Experimental Myonecrosis in the Rat

Experimental myonecrosi–induced by injection of notexin into rat tibialis anterior muscle–and subsequent regeneration were studied from 1 h to 20 days postinjury with magnetic resonance imaging using conventional and magnetization transfer sequences, and these findings were correlated with histopathology. MR images revealed necrosis within 1 h postinjection. Histopathologically, necrotized fibers enlarged and intercellular spaces widened, indicating intracellular and extracellular edema, which began to decrease after 48 h, whereafter the formation of new myofibers predominated. T₂ increased progressively until 7.5 h, while T₁ increased until 24 h. Magnetization transfer contrast (MTC) and magnetization transfer rate (R_wm) decreased rapidly postinjection; the decrease in R_wm lasted longer than in MTC (96 h versus 48 h, respectively). Spin echo, inversion recovery and magnetization transfer sequences revealed the lesions equally effectively. MR images and relaxation parameters reflect well the extent of histopathological injury and edema in the acute phase, whereas specific tissue changes in the regenerative phase were not detectable by MRI. MT imaging and especially magnetization transfer rate are as sensitive as conventional T2 contrast to alterations in water imbalance.     

Pancreatitis associated protein as an early marker of acute pancreatitis.

BACKGROUND--A study was conducted to evaluate the prevalence of metronidazole resistant Helicobacter pylori strains among the Chinese in Hong Kong. The efficacy of the triple therapy that contains metronidazole as one of the anti-microbial agents in eradication of the metronidazole susceptible and the metronidazole resistant strains was also assessed. METHODS--Culture for H pylori was attempted from antral biopsy specimens of 70 peptic ulcer and 51 control subjects. Successfully cultured H pylori strains were tested for metronidazole susceptibility. Twenty six peptic ulcer disease subjects who had received a course of triple therapy were also reassessed four to six weeks later for successful eradication of H pylori infection. RESULTS AND CONCLUSIONS--H pylori was successfully cultured from antral biopsy specimens in 69 of 80 (86%) of the infected subjects. The overall metronidazole resistance rate was 53.5% (37 of 69). There was a significantly higher metronidazole resistance rate among H pylori isolates from the asymptomatic controls (20 of 25) than the peptic ulcer disease subjects (17 of 44) (p = 0.0007). Twenty three of 32 (73%) women and 14 of 37 (38%) men harboured the metronidazole resistant strains. There was no sex or age difference as far as the prevalence of metronidazole resistant strains were concerned within each study group. Pre-treatment metronidazole susceptible H pylori were significantly more likely to respond to the triple therapy used than those with the metronidazole resistant ones (14 of 15 v five of 10) (p = 0.021).     

Stability of vocational outcome in adulthood after moderate to severe preschool brain injury.

We studied how moderate to severe childhood traumatic brain injury (TBI) affects vocational outcome with time. This is the second follow-up of patients who were injured as preschoolers in traffic accidents. In the first follow-up the mean age was 23 years and in the present study the average age of the 27-patient cohort was 40 years. Twenty-two patients were assessed clinically by a neuropsychologist, neurologist and a social worker. Five patients, although not able or willing to participate in the clinical study, were contacted by telephone and interviewed on their vocational outcome. Compared to the first follow-up, 20/27 patients in total had no change in their vocational status. Nine out of the 27 patients were working full-time, two had subsidized jobs and 16 were not working. Twenty-four of 27 patients were independent in daily living. In the neuropsychological tests of executive functions, preserved flexibility associated with full-time work status. In conclusion, 1/3 of the patients were still employed full-time over 30 years after the TBI. This suggests that favorable vocational outcome, reached by young adulthood, is maintained at least until middle age.     

Ultrastructural studies of the retina in infantile neuronal ceroid-lipofuscinosis

A 9-year-old boy who had died of infantile neuronal ceroid-lipofuscinosis had experienced retina-derived visual failure. Ophthalmologically and morphologically, his retina was severely atrophic and scarred by a dense fibrillary gliosis while photoreceptor cells had completely disappeared, cells of the bipolar layer had decreased in number and had become atrophic beyond cytologic recognition. Retinal pigment epithelial cells had undergone either atrophy or proliferation. Disease-specific granular lipopigments had accumulated in perikarya and processes of remaining cells and were infrequently associated with melanin within huge melanolipofuscin bodies and RPE cells of sessile and migrating nature, and within cells of the atrophic retina, among them glial cells. The ubiquitous lipopigment accumulation in the retina of this patient was identical to that seen in other childhood forms of NCL and to that observed in canine NCL while the retinopathy likewise resembled that encountered in childhood NCL, and in primary human and canine retinopathia pigmentosa.     

Binding of progestins to the glucocorticoid receptor: Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes

A number of physiological and synthetic progestins were tested for their ability to compete with [³H]dexamethasone for the binding to the glucocorticoid receptor of human mononuclear leukocytes and their ability to elicit glucocorticoid-like effects on the same cells. As compared to the reference compound dexamethasone (relative receptor binding affinity defined as 100%), two potent synthetic progestins with a pregnane-type structure, megestrol acetate and medroxyprogesterone acetate, were found to display a considerable binding affinity towards the receptor (46 and 42%, respectively). The relative binding affinity of the naturally occurring ligand, cortisol, to the receptor was clearly lower (25%). The effective binding of medroxyprogesterone acetate to the glucocorticoid receptor was confirmed by direct binding studies utilizing a tritiated derivative of this steroid. No evidence for the existence of a specific progesterone receptor in human mononuclear leukocytes was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [³H]Org 2058 was used. Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the lymphocyte functions. These included inhibition of the proliferative responses to the T-cell mitogens concanavalin A and phytohaemagglutinin and an enhanced accumulation of immunoglobulin secreting cells in pokeweed mitogen-stimulated cultures. The progestin effect appears to be mediated through a radiosensitive (suppressor) subpopulation of T lymphocytes. In contrast, the synthetic progestins related structurally to 19-nortestosterone, norethisterone and d-norgestrel, were virtually devoid of binding affinity towards the glucocorticoid receptor nor did they measurably influence the in vitro lymphocyte functions. These studies demonstrate that certain progestins in common clinical use probably possess inherent glucocorticoid activity and suggest that side effects attributable to this character (e.g. suppression of the pituitary-adrenal axis) might be expected when these compounds are used in pharmacological doses.     

Effects of aripiprazole on alcohol intake in an animal model of high-alcohol drinking

AIMS: This study examined the effects of aripiprazole, a novel atypical antipsychotic drug with partial agonist properties at dopamine D2 receptors, on the voluntary limited access alcohol drinking of alcohol-preferring AA (Alko, Alcohol) rats. METHODS: AA rats were taught to drink 10% alcohol in a 4 h limited access paradigm. Effects of acute aripiprazole (0, 0.3, 1.0, and 3.0 mg/kg) on the limited access alcohol drinking were studied. In repeated treatment experiment, aripiprazole (0, 1.0, and 6.0 mg/kg) was administered once daily over five successive days. To reveal any effect by aripiprazole not selective for alcohol drinking, 0.025% saccharin solution was substituted for alcohol during the 4 h limited access, and acute treatments were repeated. The effects of aripiprazole on ambulatory locomotor activity were tested with doses that were used in the acute experiments. RESULTS: Acute aripiprazole at the doses of 0.3, 1.0, and 3.0 mg/kg had no effect on alcohol drinking. Repeated treatment with the aripiprazole dose of 6.0 mg/kg significantly diminished alcohol drinking at the 1 h time point. This dose had no effect on saccharin drinking when given acutely. Acute aripiprazole at the doses of 1.0, 3.0, and 6.0 mg/kg significantly suppressed locomotor activity. CONCLUSIONS: Aripiprazole decreased limited access alcohol drinking in AA rats, but only at a high dose that also strongly suppressed locomotor activity.