Germline mutation analysis of the androgen receptor gene in Finnish patients with prostate cancer

PURPOSE: Steroid hormones, particularly androgens, are suspected to have a major role in prostate carcinogenesis. Since androgen receptor mediates androgenic effects on cells and recent studies suggest that the androgen receptor gene is a putative prostate cancer susceptibility locus, we screened the coding region of the androgen receptor gene for germline mutations using the genomic DNA of patients with prostate cancer. MATERIALS AND METHODS: DNA samples from 38 patients with early onset prostate cancer and 36 from Finnish prostate cancer families showing no male-to-male transmission of prostate cancer were analyzed for mutations in the androgen receptor gene using single strand conformation polymorphism analysis and subsequent sequencing. RESULTS: R726L substitution in the hormone binding region of androgen receptor was found in 1 prostate cancer family but no previously uncharacterized germline mutations were detected. CONCLUSIONS: Our results indicate that constitutional androgen receptor mutations explain only a small fraction of familial and early onset prostate cancer cases in Finland.     

Life events, social support, and onset of major depressive episode in Finnish patients

We investigated differences in life events and social support between subgroups of depressed patients and the distribution of life events in phases preceding or during depression. In the Vantaa Depression Study, 269 psychiatric patients with DSM-IV major depressive disorder were diagnosed with Schedule for Clinical Assessment in Neuropsychiatry, Version 2.0, and Structured Clinical Interview for DSM-III-R personality disorders (SCID-II). Life events during the 12 months preceding the interview were investigated with the Interview for Recent Life Events, and social support with the Interview Measure of Social Relationships and the Perceived Social Support Scale-Revised. Nearly all patients (91%) reported life events, on average 4.1 per preceding year. No major differences between sociodemographic or clinical subgroups were found; the frequency of events was somewhat greater among the younger subjects, whereas those with comorbid alcoholism or personality disorders perceived less social support. Although events were distributed evenly between the time preceding depression, the prodromal phase, and the index major depressive episode, two thirds of the patients attributed their depression to some event. Despite clinical and sociodemographic heterogeneity, patients with major depressive disorder are fairly homogeneous in terms of life events during the preceding year. Events do not cluster in any particular phase of the progression to an episode.     

How xylitol-containing products affect cariogenic bacteria

BACKGROUND: The authors examined the effect of xylitol, a naturally occurring sweetener, on levels of Streptococcus mutans and S. sobrinus. They also investigated xylitol's mechanism of action. METHODS: The authors compared cariogenic bacteria levels before and after exposure to xylitol products in children and adults. In the first study, 187 children received xylitol-containing snacks in school for four weeks. In the second study, two adults received xylitol candy for four weeks. Unstimulated saliva samples were taken from all subjects. Gingival samples also were taken from the adults. The authors plated the samples on selective microbiological media. Individual isolates were plated on media with varying concentrations of xylitol, and were identified using specific DNA probes. Genetic relatedness was determined via pulse-field gel electrophoresis. RESULTS: The children's salivary S. mutans levels remained stable before and after xylitol exposure. Further analysis of the S. mutans isolates was conducted for seven children. Bacteria from five of these children grew with 10 percent or less xylitol at baseline, while the bacteria from all seven children grew with 15 percent xylitol after exposure to the xylitol-containing snacks, suggesting that the S. mutans increased in tolerance to xylitol during exposure. Six children had isolates with the same genotype at both time points. S. mutans and S. sobrinus levels were reduced in one of the adults as a result of xylitol exposure, and the bacterial isolates became more xylitol tolerant. In the second adult, S. mutans and S. sobrinus levels increased, while the subject maintained the same proportion of susceptible and tolerant strains as that at baseline. CONCLUSIONS: Overall, consumption of xylitol-containing snacks and candy did not reduce S. mutans levels. However, bacteria from five children and one adult became more xylitol tolerant. CLINICAL IMPLICATIONS: These results provide a basis on which xylitol-containing products can be recommended and xylitol's mechanism of action can be explained to patients.     

Lignan precursors from flaxseed or rye bran do not protect against the development of intestinal neoplasia in ApcMin mice

Phytoestrogens, like isoflavonoids and lignans, have been postulated as possible colorectal cancer protective constituents. To investigate this hypothesis, two high-fiber sources rich in lignan precursors, i.e., rye bran and flaxseed, were tested for their ability to modulate intestinal tumor development in ApcMin mice. Test diets consisted of a control diet (a Western-style diet, adjusted for fiber and/or phytate content) supplemented with 5% flaxseed or 30% rye bran. Chemical analysis of diets and blood samples confirmed the enhanced systemic exposure of mice fed the test diets to the major lignan precursors, i.e., secoisolariciresinol and matairesinol. No statistically significant difference was observed in the incidence and multiplicity of small intestinal and colon tumors at terminal sacrifice between mice fed the control diet or the diet supplemented with 5% flaxseed. With the rye bran diet a statistically significant enhancement of the number of small intestinal tumors in female mice was observed. The number of colon tumors, however, was comparable between the control and rye bran-fed mice of either sex. Furthermore, no activating point mutations in the K-ras oncogene nor positive immunohistochemical staining for the p53 gene were observed in a set of 48 colon tumors. In conclusion, our results demonstrate that increased intake of lignan precursors from flaxseed or rye bran, administered in a Western-style diet, does not protect against intestinal tumor development in an appropriate animal model for intestinal neoplasia such as the ApcMin mice.     

18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images

PURPOSE: To study brain MRI findings in patients with 18q- syndrome and to correlate these findings with the results of the molecular breakpoint analysis. MATERIALS AND METHODS: Brain MR images of 17 patients with 18q- syndrome were evaluated. Segregation analysis was performed with 15 microsatellite markers to determine the deletion breakpoints and whether the deletion included the myelin basic protein (MBP) gene. RESULTS: One patient had an interstitial deletion of 18q which spared the MBP gene. He was the only one with normal brain MRI. All 16 patients with deletions including the MBP gene had abnormal white matter in MRI. The main finding was poor differentiation of gray and white matter on T2-weighted images due to increased white matter signal intensity. In addition, measured signal intensity of the white matter was significantly increased in patients compared with controls. CONCLUSIONS: Poor differentiation of gray and white matter on T2-weighted images is the most typical MRI finding of the 18q- syndrome. These results support the postulation that abnormal myelination in 18q- syndrome is due to haploinsufficiency at or near the MBP locus.     

Regional cerebral glucose metabolism in monozygotic twins discordant for Alzheimer's disease

We investigated regional cerebral glucose metabolic rates (rCMRgluc) with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in 7 monozygotic twin pairs discordant for Alzheimer's disease (AD). Ten healthy volunteers with comparable mean age and educational level served as controls. In the hippocampus, the mean +/- SD rCMRgluc were 0.20 +/- 0.03 micromol/ml/min for the demented twins, 0.21 +/- 0.03 micromol/ml/min for their non-demented co-twins, and 0.23 +/- 0.02 micromol/ml/min for the controls. The mean hippocampal rCMRgluc was reduced in the demented twins (p = 0.006), compared with the controls. In the lateral temporal cortex, the mean +/- SD rCMRgluc were 0.27 +/- 0.05, 0.28 +/- 0.04, and 0.32 +/- 0.02 micromol/ml/min, respectively. These mean rates were reduced both in the demented (p = 0.02) and the non-demented (p = 0.01) twins, compared with the controls. In conclusion, in the demented twins, the reduction of rCMRgluc was detected in the hippocampus and lateral temporal cortex, i.e. the 2 brain areas which show early changes in pathological and imaging studies in AD. Their non-demented co-twins showed milder reductions, which may be an indication of genetic susceptibility for dementia, and an early sign of a dementing illness in them.     

CHEK2 variants associate with hereditary prostate cancer

Recently, variants in CHEK2 gene were shown to associate with sporadic prostate cancer in the USA. In the present study from Finland, we found that the frequency of 1100delC, a truncating variant that abrogates the kinase activity, was significantly elevated among 120 patients with hereditary prostate cancer (HPC) (four out of 120 (3.3%); odds ratio 8.24; 95% confidence interval 1.49-45.54; P=0.02) compared to 480 population controls. Suggestive evidence of segregation between the 1100delC mutation and prostate cancer was seen in all positive families. In addition, I157T variant had significantly higher frequency among HPC patients (13 out of 120 (10.8%); odds ratio 2.12; 95% confidence interval 1.06-4.27; P=0.04) than the frequency 5.4% seen in the population controls. The results suggest that CHEK2 variants are low-penetrance prostate cancer predisposition alleles that contribute significantly to familial clustering of prostate cancer at the population level.     

Generalized anxiety disorders three to four months after ischemic stroke

BACKGROUND AND OBJECTIVE: The main objective of our study was to detail the frequency and clinical determinants of poststroke generalized anxiety disorders in a large, well-defined stroke cohort. METHODS: A total of 277 stroke patients aged 55-85 were subjected to a comprehensive psychiatric evaluation between 3 and 4 months after ischemic stroke. Primary generalized anxiety disorder or generalized anxiety disorder due to stroke were diagnosed according to DSM-IV symptom criteria. RESULTS: The frequency of any generalized anxiety disorder was 20.6% (n = 57). According to a logistic model, any generalized anxiety disorder was associated with a history of epilepsy, comorbid depressive disorder, severity of depression, severity of anxiety, and the use of anxiolytic drugs. A discriminant analysis identified four factors that distinguished the two diagnostic subgroups from one another: the level of psychosocial functioning (worse score in patients with generalized anxiety due to stroke), a history of migraine, anterior circulation stroke localization (more frequent in patients with generalized anxiety disorder due to stroke), and a history of insomnia (more frequent in patients with primary generalized anxiety disorder). CONCLUSIONS: Clinically significant anxiety is common in ischemic stroke patients and may hamper their rehabilitation.     

Growth hormone-insulin-like growth factor-1 axis,leptin and sleep in anorexia nervosa patients

The present study characterizes the relationships between severe malnutrition, sleep, growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, and leptin levels in anorexia nervosa (AN) patients before and after weight gain. Eleven restricting-type anorectic females (mean age = 19.7 years) with severe starvation state [mean body mass index (BMI) = 13.3] were studied using polysomnography and spectral power analysis. The hormone levels were measured in the morning after sleep recording. Eleven normal-weight, age- and gender-matched healthy volunteers without a history of any eating disorder served as controls. After nutritional treatment for about 2 months (65.7 +/- 6.4 days), sleep examinations and blood tests were repeated. At this stage, the study group consisted of 5 patients (mean BMI = 15.6). Higher IGF-1 and leptin levels were associated with longer and deeper sleep among anorectics. The sleep parameters including the percentages of stage 1 sleep and SWS as well as IGF-1 tended to normalize after only limited weight gain. Sleep disturbances in anorectics may be mediated through changes in the levels of the GH-IGF-1 axis hormones, as well as the levels of leptin.