Emergence and scattering of multiple neurofibromatosis (NF1)-related sequences during hominoid evolution suggest a process of pericentromeric interchromosomal transposition

Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase activating protein family and is considered to be a tumor suppressor gene. Its very high rate of de novo mutation in humans led us to study a specific feature of this gene: the presence of numerous NF1-related sequences. According to our results, the human genome contains at least 11 NF1-related sequences, nine of which are scattered near centromeric sequences of seven different chromosomes. These NF1-related sequences, whose extent is quite varied according to loci, are unprocessed copies of the NF1 gene, and bear numerous mutations. A phylogenetic analysis of the six largest sequences indicates that they are all derived from a common ancestor, which would have appeared 22-33 million years ago, and was subsequently duplicated several times during hominoid evolution. The most recent duplication and interchromosomal transposition occurred in the last million years suggesting that the process could still be ongoing. Intriguing similarities between the evolution of alpha- satellite DNA and NF1-related sequences suggest the involvement of a common genetic mechanism for the generation and pericentric spreading of these NF1 partial copies.      

Psychometric properties of the SUNYA revision of the psychosomatic symptom checklist

The Psychosomatic Symptom Checklist (PSC), a questionnaire assessing psychosomatic symptoms, was administered to two separate samples of college students. For Sample 1 (N=698),the questionnaire was readministered to three separate subsets at intervals of either 1 week (N=143),4 weeks (N=74),or 8 weeks (N=48).Each subset of subjects recompleted the PSC on only one of the three retest intervals. Based on the initial administration an analysis of the normative data revealed a mean total score of 23.7, suggesting a relatively low degree of psychosomatic symptoms in this group. Although total scores decreased slightly over time, test-retest correlations remained high (r>0.80, P<0.0001).Individual item correlations varied and also decreased across time; however, the majority of correlations was greater than r=0.50 throughout. Sample 2 (N=249)completed the PSC, Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI-X), and Rathus Assertiveness Scale (RAS), and intercorrelations were computed between these measures. This analysis revealed little overlap between the psychosomatic complaints assessed by the PSC and other commonly used measures of psychological distress. Finally, a factor analysis revealed one major factor on which all but 2 of the 17 questionnaire items loaded significantly. These results suggest that the PSC is sensitive to psychosomatic distress and remains reliable over time.This reaserch was supported in part by Grants NS-15235 and NS-16891 from NINCDS.     

Chromosomal assignment of human O6-methylguanine-DNA-methyltransferase gene by hamster-human somatic cell hybrids.

Using an in vitro assay to measure O6-methylguanine-DNA-methyltransferase (MT) activity in cell extracts from a panel of human-hamster cell hybrids, we were able to locate the human MT gene on chromosome 10. Chinese hamster cells have little or no MT activity and the presence of human chromosome 10 was a necessary condition for MT activity in cell hybrids. In some cell hybrids carrying chromosome 10, however, MT activity was not higher than that of hamster cells. As an explanation for this result, genetic determinants repressing MT expression and/or activity might be present in other human chromosomes carried by MT-negative cell hybrids. Partial hyperploidy of the hamster karyotype, variable activity of the parental human cell lines and changes during subculturing of the cell hybrids might also account for the lack of enzymatic activity in chromosome 10 containing hybrids.     

Dream recall after sleep interruption in brain-injured patients

Nineteen patients with unilateral hemispheric lesions of a vascular or neoplastic nature were studied. Before the onset of disease, these patients had experienced dream recall at least once a week. During hospitalization their dream recall was investigated using a morning diary for 10 consecutive days. During this period, seven patients reported having dreamed, whereas 12 had no dream recall. Subsequently, the patients' sleep was interrupted during both stage 2 NREM and REM sleep. With this method, 11 patients reported having dreamed at least once, whereas eight had no dream recall. Patients with lesions in the temporo-parieto-occipital region had a more frequent loss of dream recall than those with lesions outside this area. The agreement between the results obtained using the diary and those from provoked awakening was significant. The results obtained from compilation of a diary on morning awakening appear sufficiently reliable to reveal the presence or absence of dream recall in patients with focal cerebral lesions in the acute phase of the disease.     

XLMR genes: update 1992.

Up to now, we have identified 77 X-linked conditions in which mental retardation is the primary or a major component manifestation. These conditions were subdivided into 2 categories, designated respectively "X-linked mental retardation syndromes" and "Non-specific X-linked mental retardation". Forty genes have been regionally mapped onto the X chromosome. However, in several instances the data were derived from a single family and most lod scores were less than 3.0.     

Borderline HER‐2 breast cancer cases: Histochemical versus real‐time PCR analysis and impact of different cut‐off values

Seventy‐one cases that had resulted borderline for HER‐2 protein expression at conventional immunohistochemical assay (2+) were assessed for HER‐2 gene amplification by real‐time PCR and by FISH in accordance with the manufacturer's recommendations (gene amplification with ratio ?2 in both methods). Thirty‐three out of 71 cases (47%) resulted amplified at real‐time PCR analysis, whereas 15 cases resulted positive at FISH (21%). Apparently, PCR was more sensitive than FISH in HER‐2 determination, only 10 cases resulting amplified in both tests. When the mean ratio value obtained in all PCR experiments was adopted as threshold in determining HER‐2 gene amplification, the apparent sensitivity of PCR was reduced but correlation between PCR and FISH results was dramatically increased. Furthermore, when the mean PCR ratio value observed in the FISH‐positive group was chosen as threshold, the best agreement between PCR and FISH results was achieved. Therefore, we found that the proposed threshold ratio value of ?2 is not accurate in separating HER‐2 amplified and non‐amplified cases. We suggest that the threshold ratio value in PCR tests should be determined in each laboratory using FISH controlled cases. Finally, above certain in‐lab generated threshold values, PCR might be proposed as a highly predictive positive test in HER‐2 assessment.