The LRRK2 G2019S mutation is associated with Parkinson disease and concomitant non-skin cancers.

OBJECTIVE: In view of the fact that cancer patterns in patients with Parkinson disease (PD) differ from the general population, we aimed to verify whether patients with PD with LRRK2 mutations have an increased risk for particular cancer types. METHODS: In this cross-sectional study, eligible consenting Jewish patients with PD were genotyped for the predominant LRRK2 G2019S mutation. Oncologic data were obtained by personal interview and reviewing patients' files. Stepwise logistic regression was applied to model the probability of cancer occurrence in carriers vs noncarriers. RESULTS: Overall, 79/490 (16.1%) genotyped patients carried the G2019S mutation. Seventy-seven (16%) were diagnosed with cancer; of those, 67 (14%) with a non-skin cancer. Eighteen (23%) carriers vs 49 (12%) noncarriers had a non-skin cancer (p = 0.01, odds ratio [OR] = 2.18, 95% confidence interval [CI] 1.19-3.99). A significant ethnicity effect was noted (p = 0.045, OR = 1.84, 95% CI 1.02-3.34). Among Ashkenazi patients, age and LRRK2 emerged as significant using stepwise logistic regression including age, gender, and LRRK2 status as explanatory variables. The OR for LRRK2 mutation carriers adjusted for age was 3.38 (95% CI 1.64-6.97, p = 0.0009). CONCLUSIONS: Ashkenazi Jewish patients with PD who harbor the G2019S LRRK2 mutation are more likely to have a concomitant non-skin cancer than noncarriers.

[Age-related characteristics of the natural cytotoxicity system in patients with multiple sclerosis and their possible relation to the pathogenesis of the disease]. / Vozrastnye osobennosti sistemy estestvennoi tsitotoksichnosti u bol'nykh rasseiannym sklerozom i ikh vozmozhnaia sviaz' s patogenezom zabolevaniia.

A study was made of the cytotoxic activity of natural killers (NK) against 3H-uridine labeled K-562 cells and its variability. 56 patients suffering from multiple sclerosis (MS), 33 healthy donors of different age and 34 patients with remitting MS and MS of different standing were entered into the study. The most remarkable lowering of the NK activity was seen in patients aged 41 to 50 years. In patients aged 51 to 59 years, the NK activity was not different from that in a group of healthy donors. The most pronounced increase of the variability index (VI) was recorded in patients aged 41 to 50 years. In the senior age group (from 51 to 59 years), the VI of the NK activity was 1.7 to 2.8 times as reduced as compared to the healthy control. It has been revealed that the changes in the NK activity and its variability in the respective patients' groups are of concomitant nature and that the estimates undergo fluctuations in the counterphase. During studies of the NK activity as dependent on the disease standing, NK deficiency was found to be associated with the gravity of the patient's clinical status and long disease standing. A possible relation of the changes in the NK activity and its variability to the disease pathogenesis is under discussion as are the compensation mechanisms that get triggered during depletion of the system according to the secondary deficiency type.

[Interferon-producing and cytotoxic activity of natural killer cells in multiple sclerosis patients]. / Interferonprodutsiruiushchaia i tsitotoksicheskaia aktivnost' estestvennykh kletok-killerov u bol'nykh rasseiannym sklerozom.

Examination of 22 patients with multiple sclerosis (MS) has revealed a decrease in the cytotoxic activity of natural killer cells (NKC), in the production of endogenic interferon (EI) in the system of NK--target cells, and in the production of alpha- and gamma-interferon by stimulated lymphocytes. Some patients showed dissociation of the cytotoxic and interferon-producing activity of NKCs. Possible mechanisms responsible for changes in NKC activity are discussed. The authors have concluded that disturbances in the NKC-EI system are manifestations of the total regulatory imbalance in the immune system.

[Experience in using T-activin in multiple sclerosis patients]. / Opyt primeneniia T-aktivina u bol'nykh rasseiannym sklerozom.

Forty patients with multiple sclerosis of a differing course, duration and severity were treated in this series. T-activin was employed as an immunocorrective agent (AFT-6 fraction). The immunological status was assessed in all patients observed prior to, during and after the treatment. Good clinical response was noted in patients with a secondary progressive course; the effect of a short course of treatment with T-activin on the state of patients with a prolonged progressive course or at the stage of stabilization in the presence of severe organic symptomatology was less prominent. AFT-6 showed a beneficial effect on the immunological status of patients, largely on the T-immunity system. Following the treatment, most patients displayed the normalization of the total lymphocyte count and of the proportional content of T-cells with their activity rising.

[Clinico-electrophysiologic, immunologic and biochemical studies of multiple sclerosis patients]. / Kliniko-élektrofiziologicheskie, immunologicheskie i biokhimicheskie issledovaniia bol'nykh rasseiannym sklerozom.

Immunological blood indices, neutral lipid fractions, level of daily urine C21-corticosteroid excretion, free amino acid spectrum of the blood were studied in 72 patients with disseminated sclerosis. The EEG, EMG and REG data were analyzed. Healthy persons of the same age formed the control group. The data obtained may favour more differentiated treatment (in particular, the use of immunodepressants or immunostimulants) according to the disease pattern and stage. The study is important for early diagnosis and estimation of the process acuity and drug efficacy.

[Role of immunoregulatory cells and natural killers in the pathogenesis of multiple sclerosis]. / Rol' immunoreguliatornykh kletok i estestvennykh killerov v patogeneze rasseiannogo skleroza.

Simultaneous investigations of the immunoregulatory cells and the natural killers were carried out in patients with different stages of multiple sclerosis in an attempt to determine a relationship between these organisms and the clinical stage of the disease. The quantities of E- and EAC-RFC in patients of all groups were within normal. The amount of T gamma-cells was decreased in the progressive phase of the disease and was significantly higher than normal during remission. The activity of the natural killers in the progressive phase of disease did not differ from control but was significantly depressed during remission with all effector/target ratios. The activity of the natural killers and the amount of T gamma-cells were found to be reversely correlated both in the progressive and remission phases of the disease. A quantitative reduction in the 0 population of lymphocytes was accompanied by a sharp suppression of natural killer activity.