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71.
Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease 总被引:11,自引:4,他引:11
Cruts M; van Duijn CM; Backhovens H; Van den Broeck M; Wehnert A; Serneels S; Sherrington R; Hutton M; Hardy J; St George-Hyslop PH; Hofman A; Van Broeckhoven C 《Human molecular genetics》1998,7(1):43-51
Two closely related genes, the presenilins ( PS ), located at chromosomes
14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer
disease (AD) with onset age below 65 years (presenile AD). We performed a
systematic mutation analysis of all coding and 5'-non-coding exons of PS -1
and PS -2 in a population-based epidemiological series of 101 unrelated
familial and sporadic presenile AD cases. The familial cases included 10
patients of autosomal dominant AD families sampled for linkage analysis
studies. In all patients mutations in the amyloid precursor protein gene (
APP ) had previously been excluded. Four different PS -1 missense mutations
were identified in six familial cases, two of which where autosomal
dominant cases. Three mutations resulted in onset ages above 55 years, with
one segregating in an autosomal dominant family with mean onset age 64
years (range 50-78 years). One PS -2 mutation was identified in a sporadic
case with onset age 62 years. Our mutation data provided estimates for PS
-1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively.
When family history was accounted for mutation frequencies for PS -1 were
9% in familial cases and 18% in autosomal dominant cases. Further,
polymorphisms were detected in the promoter and the 5'-non-coding region of
PS -1 and in intronic and exonic sequences of PS -2 that will be useful in
genetic association studies.
相似文献
72.
Cindy L Ehlers David A Gilder Tamara L Wall Evelyn Phillips Heidi Feiler Kirk C Wilhelmsen 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2004,(1):110-115
Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain elusive. This study's aims were to map susceptibility loci for DSM-III-R alcohol dependence and two narrower alcohol-related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM-III-R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians. 相似文献
73.
74.
Madan Jagasia Jennifer Giglia Wichai Chinratanalab Sheri Dixon Heidi Chen Haydar Frangoul Brian Engelhardt Stacey Goodman John Greer Adetola Kassim David Morgan Katherine Ruffner Friedrich Schuening 《Biology of blood and marrow transplantation》2007,13(10):1207-1215
Chronic graft-versus-host disease (cGVHD), a common complication after stem cell transplant (SCT), has an impact on morbidity and survival. Previous classification of cGVHD has not been reproducible or prognostic for nonrelapse mortality (NRM). Recently the National Institutes of Health (NIH) consensus criteria were proposed, but the ability of this classification to predict outcome of various subtypes of cGVHD is unknown. Patients (N = 110) undergoing an SCT for a hematologic malignancy and surviving until day 100 posttransplant from 2001 to 2003 were studied. The overall survival (OS) using a landmark analysis at day 100 was 44% versus 66% (no GVHD vs. GVHD, P = .026). The OS of patients with various types of GVHD as proposed by the NIH criteria were significantly different (P < .0001). In a univariate analyses, this was more apparent when patients with any acute features of GVHD were compared to classic cGVHD (3-year OS 46% vs. 68%, P = .033). The 3-year NRM for the entire cohort was 21%, and was not affected by presence or absence of GVHD or subtypes of GVHD. In a multivariable analysis, extensive cGVHD (hazard ratio [HR] 0.35, P = .015) and having any acute feature of GVHD after day 100 (HR 3.36, P = .0144) were significant independent predictors of survival. The OS with different NIH subtypes of GVHD after day 100 from SCT varies, and is superior for patients with classic cGVHD. 相似文献
75.
Designing immunotoxins for cancer therapy 总被引:5,自引:0,他引:5
Immunotoxins are the rapeutic agents with a high degree of specificity and unique mechanism of action. An immunotoxin is achimeric
protein consisting of a targeting moiety linked to a toxin. The targeting moiety selectively binds to a tumor cell and targets
it for death via the attached toxin. Generally, immunotoxins are specifically potent against cancer cells in vitro and in
animal models of human malignancies. However, immunotoxins can be limited clinically by immunogenicity, toxicity, and instability.
In this review, weofferwaysto overcome these limitations to create “ideal immunotoxins” for cancer therapy. These include
producing single chain targeting/toxin fusion proteins of fully human origin that are extracellularly stable but once internalized,
can be cleaved by intracellular proteases to free the toxin and facilitate its translocation to the cytosol. 相似文献
76.
Mucosal pseudolipomatosis of the colon 总被引:1,自引:0,他引:1
Twenty-four cases of a lesion characterized by unlined spaces in the colorectal lamina propria are presented. While lesions such as this have been reported previously as "lipomatosis" of the colon, histochemical and ultrastructural examination reveals that they are not, in fact, composed of adipocytes. It appears that they may be composed of gas trapped in the lamina propria. Because of their gross and microscopical similarity to fat, however, the term "pseudolipomatosis" is proposed. 相似文献
77.
Laura D Seligman Thomas H Ollendick Audra K Langley Heidi Bechtoldt Baldacci 《Journal of clinical child and adolescent psychology》2004,33(3):557-565
We evaluated the ability of the Revised Children's Manifest Anxiety Scale (RCMAS), the State-Trait Anxiety Inventory for Children (STAIC), and the Child Behavior Checklist (CBCL) to (a) discriminate between youth with an anxiety disorder and youth without a disorder, (b) discriminate between youth with an anxiety disorder and youth with either externalizing disorders or affective disorders, and (c) measure treatment change. In addition, variables, including age and sex, were explored as possible moderators of instrument utility. A meta-analysis of 43 articles was conducted. A large effect size was found when the instruments were used to compare youth with an anxiety disorder to youth without a disorder. When comparing anxious youth to psychiatric control groups, the picture was mixed; the instruments were found to be useful when discriminating between youth with an anxiety disorder and youth with an externalizing disorder, but not between youth with an anxiety disorder and children and adolescents with an affective disorder. The RCMAS, STAIC, and CBCL were found to be moderately sensitive to treatment gains. 相似文献
78.
The role of EEG in the study of the dementias is to help in the differential diagnosis of the multiple causes of this syndrome. EEG is useful in differentiating early on between treatable and as of now untreatable forms of dementia. Space-occupying lesions that give rise to dementia are reliably detected by EEG. Infectious, toxic, and metabolic processes are associated with early and severe electroencephalographic abnormalities. The "slow virus" infections show characteristic electrical patterns that reliably distinguish them from the cortical or subcortical dementias. Finally, the EEG may contribute to distinguishing between Alzheimer's disease and MID, two commonly occurring forms of dementia. The paucity of substantial early EEG abnormalities in Alzheimer's disease, although helping to differentiate it from other dementias, leaves us without a currently available physiologic test that provides positive evidence for this condition. Recent studies of EPs, however, suggest that some intermediate latency VEP components may be delayed in patients with Alzheimer's disease when compared with normal subjects. This is encouraging, as latencies in VEPs are more reliable and less variable than amplitude that has previously been reported as "abnormal" in some early Alzheimer patients. Long latency ERPs and CNV also show early abnormalities in Alzheimer's disease. Tests of eye movements such as ERPs are psychophysiologic tests requiring some degree of patient cooperation. Performance on tests of ocular smooth pursuit correlate highly with severity of the dementia syndrome in Alzheimer's disease. In contrast, smooth pursuit testing is usually normal in elderly patients with pseudodementia of depression, suggesting this test may be of some value in differentiating these two clinical disorders. Some evidence exists that smooth pursuit eye movements are also normal, at least in the early and middle stages, in Pick's disease, again suggesting that eye movement testing may prove to have some utility in differentiating this form of dementia from Alzheimer's disease. Ocular scanpaths are abnormal in dementia. They typically are poorly organized and at times perseveratory. In addition, the average durations of eye fixations during directed visual search are altered in dementia as compared with normals. The average eye fixation durations are longer with Alzheimer's disease and briefer in patients with frontal lobe tumors as compared with elderly normal controls. These group differences suggest differing scanning strategies for these two forms of dementia.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
79.
Motivation to provide care is a significant predictor of informal caregiving among family caregivers of persons with dementia. Adequate support is an important source of help and relief to caregivers, but fragmentation of dementia care services is common and better ways of supporting these caregivers are needed. Knowledge of adult-child caregivers' motivation and how this motivation is influenced by community healthcare services is lacking. The aim of this study is therefore to describe and explore adult children's experiences with community healthcare services for their home-dwelling parent with dementia and how these influence their caregiver motivation. The study applied a qualitative design based on three focus group interviews with 15 of these caregivers (40–69 years) in Norway in 2017. The study results indicate three categories supporting adult children's sustained motivation as caregivers: (a) caregivers prioritize their parent's need for healthcare services over their own need for support; (b) caregivers need acknowledgement through respect and involvement; and (c) caregivers need timely information and competence as the dementia progresses. To stimulate collaboration among adult-child caregivers, their parents with dementia, and community healthcare services, we claim that a relationship-centred care framework could be emphasised as a way of supporting sustained motivation among caregivers to parents with dementia as part of community healthcare services. 相似文献
80.
Approximately 1 million persons are now infected with human immunodeficiency virus (HIV) in the United States. Evidence exists that psychiatric disorders are common in patients with HIV and that these patients may not receive optimal care because their psychiatric disorders are a barrier to medical care, communication with clinicians, and adherence to medical recommendations. We describe herein a complex case seen at The Johns Hopkins Hospital with several psychiatric conditions that are common in our HIV clinic population. We describe the collaborative treatment of the patient by a multidisciplinary team including both medical and mental health practitioners. We briefly describe a coherent diagnostic and treatment approach to patients in HIV clinics and the supporting rationale from the literature. We discuss the need for comprehensive evaluation, a multidisciplinary treatment team, and therapeutic optimism. 相似文献