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51.
52.
Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis 总被引:7,自引:2,他引:7
Li DY; Toland AE; Boak BB; Atkinson DL; Ensing GJ; Morris CA; Keating MT 《Human molecular genetics》1997,6(7):1021-1028
Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular
disease that affects the aorta, carotid, coronary and pulmonary arteries.
Previous molecular genetic data have led to the hypothesis that SVAS
results from mutations in the elastin gene, ELN. In these studies, the
disease phenotype was linked to gross DNA rearrangements (35 and 85 kb
deletions and a translocation) in three SVAS families. However, gross
rearrangements of ELN have not been identified in most cases of autosomal
dominant SVAS. To define the spectrum of ELN mutations responsible for this
disorder, we refined the genomic structure of human ELN and used this
information in mutational analyses. ELN point mutations co-segregate with
the disease in four familial cases and are associated with SVAS in three
sporadic cases. Two of the mutations are nonsense, one is a single base
pair deletion and four are splice site mutations. In one sporadic case, the
mutation arose de novo. These data demonstrate that point mutations of ELN
cause autosomal dominant SVAS.
相似文献
53.
Expression of Disrupted-In-Schizophrenia-1, a schizophrenia-associated gene, is prominent in the mouse hippocampus throughout brain development 总被引:4,自引:0,他引:4
DISC1 (Disrupted-In-Schizophrenia 1) has been associated with schizophrenia in multiple genetic studies. Studies from our laboratory have shown that Disc1, the mouse ortholog of DISC1, is highly expressed in the dentate gyrus of the hippocampus in the adult mouse brain. Because developmental dysfunction of the hippocampus is thought to play a major role in schizophrenia pathogenesis, and the dentate gyrus is a major locus for adult neurogenesis in the mouse, we investigated Disc1 expression during mouse brain development. Strikingly, Disc1 is strongly expressed in the hippocampus during all stages of hippocampal development, from embryonic day 14 through adulthood. Disc1 mRNA was detected in the dentate gyrus at all stages in which this structure was identifiable, as well as in the cornu ammonis (CA) fields of the hippocampus, the subiculum and adjacent entorhinal cortex, and the developing cerebral neocortex, hypothalamus, and olfactory bulbs, all of which also express Disc1 in the adult mouse brain. In addition, Disc1 mRNA was seen in regions of the developing mouse brain which do not express Disc1 during adulthood, regions including the bed nucleus of the stria terminalis, reticular thalamic nucleus and reuniens thalamic nucleus. These results demonstrate that Disc1 marks the hippocampus from its earliest stages, and suggest that developmental Disc1 dysfunction may lead to defects in hippocampal function that are associated with schizophrenia. 相似文献
54.
55.
Shumikhina S Guay J Duret F Molotchnikoff S 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2004,158(2):223-232
Synchronization of neuronal activity has been proposed as a binding mechanism for integration of image properties into one coherent percept. In the present study, we investigated the contextual modulation of synchronization to random dot patterns. Coherent motion of random dots evoked well synchronized responses in area 17 of anaesthetized cats when the stimulus was presented in the compound receptive field of recorded sites. Gradually changing the directional coherence of random dots in the surround while maintaining fully coherent motion of the stimulus in the receptive field significantly suppressed synchronization of neuronal activity for some stimulus conditions. However, usually one or two peaks of increased synchronization were found in the surround coherence tuning curves with low (8–12%) and/or moderate (25–50%) coherence in the surround. At the population level, synchronization was significantly depressed with incoherent motion in the receptive field and when both the surround and the receptive field were jointly stimulated with 0% coherence. The intriguing finding was the discovery of two distinct groups of cells with opposite synchronization changes dependent on the presence or absence of significant synchronization in their spontaneous activity. The latter group of neurons showed peaks of increased synchronization with lower surround coherence, thus probably being more sensitive to the direction of the surround motion. Overall, our findings support the notion that binding of stimulus properties can be achieved by synchronized activity of cortical cells. However, our findings go further than the original hypothesis of feature binding by synchrony to show that synchronization of cortical activity may be directly related to the decision making processes, which in turn are related to the threshold of perception of coherent motion. 相似文献
56.
Cognitive function in depression: a distinct pattern of frontal impairment in melancholia? 总被引:18,自引:0,他引:18
Austin MP Mitchell P Wilhelm K Parker G Hickie I Brodaty H Chan J Eyers K Milic M Hadzi-Pavlovic D 《Psychological medicine》1999,29(1):73-85
BACKGROUND: Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes. METHODS: Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate. RESULTS: The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired. CONCLUSIONS: Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate. 相似文献
57.
Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin protein expression 总被引:2,自引:1,他引:2
Manilal S; Recan D; Sewry CA; Hoeltzenbein M; Llense S; Leturcq F; Deburgrave N; Barbot J; Man N; Muntoni F; Wehnert M; Kaplan J; Morris GE 《Human molecular genetics》1998,7(5):855-864
Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been
studied both by DNA sequencing and by emerin protein expression. Fourteen
had mutations in the X-linked emerin gene, while three showed evidence of
autosomal inheritance. Twelve of the 14 emerin mutations caused early
termination of translation. An in-frame deletion of six amino acids from
the C-terminal transmembrane helix caused almost complete absence of emerin
from muscle with no localization to the nuclear membrane, although mRNA
levels were normal. This shows that mutant emerin proteins are unstable if
they are unable to integrate into a membrane. A 22 bp deletion in the
promoter region was expected to result in reduced emerin production, but
normal amounts of emerin of normal size were found in leucocytes and
lymphoblastoid cell lines. This shows that DNA analysis is necessary to
exclude emerin mutations in suspected X-linked EDMD. Emerin levels in
female carriers often deviated from the expected 50% and this was due, in
at least two families, to skewed emerin mRNA expression from the normal and
mutated alleles. In one family with a novel deletion of the last three
exons of the emerin gene, a carrier had a cardiomyopathy and very low
emerin levels (<5% of normal) due to skewed X-inactivation. In the three
autosomal cases of EDMD, emerin was normal on western blots of blood cells,
which suggests that autosomal EDMD is not caused by indirect reduction of
emerin levels.
相似文献
58.
Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception 总被引:3,自引:4,他引:3
McMahon CA; Ungerer JA; Beaurepaire J; Tennant C; Saunders D 《Human reproduction (Oxford, England)》1997,12(1):176-182
The aim of this study was to compare 70 couples who had conceived by in-
vitro fertilization (IVF) with 63 matched controls for the prevalence of
anxiety and quality of attachment to the baby during pregnancy. Results for
mothers showed no group differences using a global measure of anxiety, the
Spielberger State-Trait Anxiety Inventory. However, pregnancy-specific
measures revealed significantly higher levels of anxiety in IVF mothers
about the survival and normality of their unborn babies, about damage to
their babies during childbirth and about separating from their babies after
birth. When IVF mothers were differentiated according to the number of
treatment cycles, more differences in anxiety level were revealed, with
most increases occurring in mothers who had experienced two or more
treatment cycles. IVF fathers did not differ from controls on the global
anxiety measure. No data on pregnancy-specific anxiety were available for
fathers. Neither IVF mothers nor IVF fathers differed from controls on
measures of attachment to the baby during pregnancy. Results are discussed
in the context of the need for researchers to employ differentiated and
issue-specific measures to identify concerns that may be unique to IVF
couples. Clinical implications regarding the need for psychological support
during pregnancy are also discussed.
相似文献
59.
Alternative therapies, widely used by Americans, include yoga, relaxation techniques, and herbal medications, as well as less conventional and more experimental treatments. The AIDS Research Center in Seattle is conducting the largest study of alternative therapies. Many alternative therapies are used as complements to traditional treatments, and can make a disease easier to manage. Several categories of alternative medicines are detailed: acupuncture and other Chinese treatments, natural treatments including herbal medicine and aromatherapy, and mind-body treatments such as hypnosis and biofeedback. Patients are cautioned to avoid five dangerous therapies: chelation therapy, colonic irrigation, bee venom therapy, hydrogen peroxide injections, and unlabeled medicines. Contact telephone numbers for alternative therapies are listed. 相似文献
60.
Heritability of C-Reactive Protein and Association with Apolipoprotein E Genotypes in Japanese Americans 总被引:1,自引:0,他引:1
M. A. Austin C. Zhang S. E. Humphries W. L. Chandler P. J. Talmud K. L. Edwards D. L. Leonetti M. J. Mcneely W. Y. Fujimoto 《Annals of human genetics》2004,68(3):179-188
Numerous studies have demonstrated that increased C‐reactive protein (CRP) levels predict coronary heart disease, stroke, peripheral vascular disease, and diabetes, and are associated with features of the metabolic syndrome. Only three previous studies have investigated the heritability of CRP levels, primarily in samples of Caucasian families.The purpose of the present study was to estimate the magnitude of genetic influences on CRP levels, and to examine potential associations between variation in the APOE gene and CRP levels, using a sample of 562 individual Japanese Americans from 68 extended kindreds. In general, correlation coefficients between first‐degree relatives for CRP were approximately 0.2, and spouse correlations did not differ from zero, consistent with genetic influences. Heritability estimates were approximately 0.3 (p < 0.01), even with adjustment for factors known to influence CRP levels. A significant relationship was seen between unadjusted CRP levels and APOE genotypes (p = 0.02), with the highest mean CRP level among ?2 carriers (1.20 mg/L), and nearly the same mean levels among ?3/?3 subjects and ?4 carriers (0.72 and 0.74 mg/L, respectively). However, this relationship was diminished with adjustment for covariates (p = 0.07). These results demonstrate the presence of both genetic and environmental effects on CRP levels among Asian Americans, and additional studies are needed to determine if the APOE gene contributes to these genetic influences. 相似文献