Rapid eye movement sleep behavior disorder in parkinsonism with parkin mutations

Rapid eye movement sleep behavior disorder (RBD) in the setting of parkinsonism or dementia often reflects an underlying synucleinopathy. Lewy bodies, intraneuronal aggregates containing abnormal alpha-synuclein, are absent in most cases of parkinsonism with parkin mutations (Park2). We performed clinical history and video-polysomnography in 10 Park2 patients (seven men; age, 51.2 +/- 11.6 years; parkinsonism duration, 18.3 +/- 11.2 years) and found RBD in 6. In all instances, RBD followed the onset of motor symptoms by several years. Our study shows that RBD is frequent in Park2, suggesting that mechanisms other than synuclein deposition can cause RBD in neurodegenerative disorders.     

Gender-related differences among Turkish patients with obsessive-compulsive disorder

The purpose of the present study was to investigate gender-related sociodemographic and clinical differences among Turkish patients with obsessive-compulsive disorder (OCD). A total of 169 patients diagnosed with OCD by DSM-III-R or DSM-IV criteria were included in this study. Male (n = 73) and female (n = 96) OCD patients were compared with respect to the demographic variables and the scores obtained from the Hamilton Rating Scale for Anxiety (HRSA), the Hamilton Rating Scale for Depression (HRSD) and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). We found a significantly earlier age at onset in male patients. No significant difference in terms of HARS, HDRS, and Y-BOCS scores was detected between the two groups. We observed a significantly higher frequency of contamination obsessions in females, and that of aggression and sexual obsessions in males. There was no significant difference in terms of the frequency of compulsions between the two groups. We also found that compulsion severity on obsessions/compulsions was higher in females and comorbidity rates of social phobia and schizophrenia were higher in males. Considering our results in combination with those of other studies, similarities rather than differences in gender-related sociodemographic and clinical characteristics of OCD patients across different populations seem to be present.     

Conversion and somatization disorders; dissociative symptoms and other characteristics

OBJECTIVE: There is a difference in classification of conversion disorder in ICD-10 and DSM-IV. Conversion disorder is included in dissociative disorders in ICD-10. In view of this, we aimed to clarify this discrepancy in the classification of this diagnosis. METHODS: We assessed 87 patients with conversion disorder and 71 patients with somatization disorder for sociodemographic characteristics, suicide ideation, psychiatric symptoms and dissociative symptoms using the Patient Information Form, the Dissociative Experience Scale (DES), the Symptom Check List (SCL-90-R) and the Suicide Ideation Scale. RESULTS: The number of the high school graduates, singles and students with conversion disorders was higher than the number of patients with the same characteristics who have somatization disorder. In conversion disorder, the SCL-90-R total score and the score in paranoid ideation, psychoticism subgroups were higher than the scores in somatization disorders. There were no statistical differences in suicide ideation and the total score of dissociative symptoms between the two disorders. The number of patients whose total DES score of 30 and above was higher in conversion disorders. DISCUSSION: As a result of this present study, we concluded that to enlighten the concepts of conversion, further somatization and dissociation studies are necessary.     

In vitro activity of dimethylarsinic acid against human leukemia and multiple myeloma cell lines

PURPOSE: Arsenic trioxide (As(2)O(3)), an inorganic arsenic compound, has recently been approved for the treatment of relapsed or refractory acute promyelocytic leukemia. However, systemic toxicity associated with As(2)O(3) treatment remains a problem. Inorganic arsenic is detoxified in vivo by methylation reactions into organic arsenic compounds that are less toxic. METHODS AND RESULTS: We investigated the antiproliferative and cytotoxic activity of dimethylarsinic acid (DMAA), an organic arsenic derivative and major metabolic by-product of As(2)O(3), against a panel of eight leukemia and multiple myeloma cell lines. As(2)O(3) was tested in comparison. In clonogenic assay, the average concentration of DMAA that suppressed cell colony growth by 50% was 0.5-1 m M, while for As(2)O(3) it was on average 1-2 microM. At those concentrations DMAA and As(2)O(3) had significantly less effect on colony growth of normal progenitor cells. Cytotoxic doses of DMAA and As(2)O(3) in 3-day trypan blue dye exclusion assay experiments were similar to doses effective in clonogenic assay. Assessment of apoptosis by annexin V assay revealed a high rate of apoptosis in all cell lines treated with DMAA and As(2)O(3), but significantly less effect on normal progenitor cells. DMAA, unlike As(2)O(3), had no effect on the maturation of leukemic cells. CONCLUSIONS: DMAA exerts differential antiproliferative and cytotoxic activity against leukemia and multiple myeloma cells, with no significant effect on normal progenitor cells. However, concentrations of DMAA needed to achieve such efficacy are up to 1000 times those of As(2)O(3). Evaluation of novel organic arsenic that would combine the high efficacy of As(2)O(3) and the low toxicity of DMAA is warranted.     

P53 codon 72 polymorphism in breast cancer

Increased and deregulated proliferative activity due to abnormalities in the cell cycle modulators are frequently observed in cancer. A sequence polymorphism at codon 72 of the p53 gene results in either a proline or an arginine and may induce different functional activities. This polymorphism has been shown to have varying ethnic and geographical distribution. It has been reported that the p53 Arg homozygous genotype could be a potential genetic risk factor for cancer. However, not all investigations have been consistent and this hypothesized association remains controversial. The purpose of this study was to investigate the genotype frequencies and association of the p53 codon 72 polymorphism with breast cancer in Turkish patients. A group of 115 patients with breast cancer and a control group of 76 healthy individuals were enrolled in the study. A significantly higher prevalence of homozygosity for the p53 Arg allele was observed in the patients as compared to the controls. Statistical analysis suggested a strong association between the Arg/Arg genotype and breast cancer.     

A4T mutation in the SOD1 gene causing familial amyotrophic lateral sclerosis

We report the clinical and laboratory findings in the largest kindred so far recorded with familial amyotrophic lateral sclerosis due to an A4T mutation in the SOD1 gene. The age of onset ranged from 32 to 60 years, with a mean of 46 years. Weakness in the legs was the most frequent early symptom and there was a predominance of lower motor neuron signs. The mean time from onset of symptoms to death was 14 months. One man with onset at the age of 37 has shown a slowly developing form and is currently alive 76 months after diagnosis (October 2002), although severely affected. The A4T mutation, with one exception, was of similar severity to the A4V mutation.     

A study on the genotoxic activities of some new benzoxazoles

The Bacillus subtilis rec assay has been specially developed to detect DNA-damaging potential in chemicals, with the rationale based on the relative difference of survival of a DNA repair combination proficient strains and its deficient strain, which is interpreted as genotoxicity. The genotoxic activities of newly (1–6) and previously (7–18) synthesized various benzoxazoles and benzimidazoles were analyzed via the B. subtilis rec assay. Newly obtained benzoxazole and benzimidazole derivatives (1–6) were synthesized in the presence of polyphosphoric acid (PPA) and 6 N HCl, respectively to detect their DNA-damaging activities. Among the tested compounds, 6-methyl-2-(o-chlorophenyl)benzoxazole (9), 5-amino-2-(p-methylbenzyl)benzoxazole (4), 5-(p-fluorobenzamido)-2-phenylbenzoxazole (13), and 2-(p-methylaminophenyl)benzoxazole (18) showed genotoxic activities having Rec₅₀ values of 1.85, 1.74, 1.60, and 1.50 or S-probit values of 0.534, 0.482, 0.460, and 0.357, respectively. On the other hand, 2-(p-bromobenzyl)-5-methylbenzimidazole (6) and 2-benzyl-5-(p-fluorophenylacetamido)-benzoxazole (15) were exhibited a reverse effect that displayed a bacterial growth in the rec ^- strains while there was no any bacterial growth in rec ⁺ strains at the same concentration.     

Atypical epithelial changes and mutant p53 gene expression in ovarian endometriosis

It has been reported that cases of ovarian endometriosis those with epithelial cytological atypia have potential for malignant transformation. This study was planned to determine the incidence of atypical endometriosis and its cytological criteria, to evaluate the malignant potential of atypical endometriosis via immunohistochemical methods (p53). In this study we evaluated 140 samples obtained from 120 cases of ovarian endometriosis and 10 ovarian endometrioid carcinomas that have been previously diagnosed histopathologically. We re-evaluated endometriosis cases with respect to their epithelial and stromal features, existence of acute or chronic inflammatory cells in endometriotic epithelium or stroma and other accompanying histological findings. We observed atypia in 7 (5.8%) cases; reactive atypia in 37 (30.8%) cases, no atypia in 76 (63.4%) cases. We evaluated immunohistochemical p53 expression in 7 atypical cases, 37 reactive atypical cases, and in 10 of those without atypia and in 10 endometrioid carcinoma cases. We noted no staining in cases with atypia, reactive atypia and without atypia while 3 cases of endometrioid carcinoma had positive staining for p53. We concluded that prominent nucleolus and angulation of nuclear contour could be added to criteria of atypia that were mentioned before in the literature. In our study, even though p53 expression could not be shown with immunohistochemical methods in atypical endometriotic cases; it can not be determined that atypical endometriosis lesions are not premalignant. Still, endometriosis cases should be evaluated carefully by the pathologist for foci of cytological atypia and it should be kept in mind that malignant transformation might occur in these atypical endometriosis cases.