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M J Alberts

Publications and source records attributed to M J Alberts.

68 records · Page 4Linked to original sources
PubMed1991

Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.

A genetic component in the etiology of Alzheimer disease (AD) has been supported by indirect evidence for several years, with autosomal dominant inheritance with age-dependent penetrance being suggested to explain the familial aggregation of affecteds. St. George Hyslop et al. reported linkage of familial AD (FAD) in four early-onset families (mean age at onset [M] less than 50 years). Subsequent studies have been inconsistent in their results; Goate et al. also reported positive lod scores. However, both Pericak-Vance et al.'s study of a series of mainly late-onset FAD families (M greater than 60 years) and Schellenberg et al.'s study failed to confirm linkage to chromosome 21 (CH21). These various studies suggest the possibility of genetic heterogeneity, with some families linked to CH21 and others unlocalized. Recently, St. George Hyslop et al. extended their analysis to include additional families. The extended analyses supported their earlier finding of linkage to CH21, while showing strong evidence of heterogeneity between early-onset (M less than 65 years) and late-onset (M greater than 60 years) FAD families. Because our families did not show linkage to CH21, we undertook a genomic search for an additional locus for FAD. Because of both the confounding factor of late age at onset of FAD and the lack of clear evidence of Mendelian transmission in some of our families, we employed the affected-pedigree-member (APM) method of linkage analysis as an initial screen for possible linkage. Using this method, we identified two regions suggesting linkage: the proximal long arm of chromosome 19 (CH19) and the CH21 region of FAD linkage reported by St. George Hyslop et al. Application of standard likelihood (LOD score) analysis to these data support the possibility of an FAD gene locate on CH19, particularly in the late-onset FAD families. These data further suggest genetic heterogeneity and delineate this region of CH19 as an area needing additional investigation in FAD.

Age Factors↗
PubMed1990

An analysis of time of presentation after stroke.

The recent development of potential therapies for acute stroke has focused attention on the time delay between stroke onset and presentation. We used the Duke/Veterans Administration stroke registry to collect data about this delay. Results were analyzed using Fisher's Exact Test and ridit analysis. Data from 457 patients at two hospitals were used. Only 42% (192/457) of patients presented within 24 hours of stroke onset, while 25% (116/457) presented within 48 hours and 33% (149/457) presented after 48 hours. Presentation time varied significantly with stroke type. A majority of patients with infarcts (64% [176/276]), stroke-in-evolution (54% [44/81]), and subarachnoid hemorrhage (54% [25/46]) did not present within 24 hours of stroke onset. Most patients with intracerebral hemorrhage (63% [34 of 54]) did present within 24 hours. Reasons for this delay may include patients' lack of awareness about the symptoms of stroke and lack of recognition of early signs by medical personnel. Because of this delay in presentation, a majority of patients may not be candidates for some therapies for acute stroke.

Acute Disease↗
PubMed1990

Genetics of cerebrovascular disease.

Stroke is a complex disease, with both genetic and environmental factors having a role in its pathogenesis. A review of past studies shows some evidence of genetic influences in the development of stroke. This is supported by studies of cardiovascular disease, which indicate major genetic influences at several levels including the development of risk factors. New approaches to phenotypic classifications, patient ascertainment, and genetic analysis will stimulate research into the role of genetics in cerebrovascular disease.

Cerebrovascular Disorders↗
PubMed1989

Diagnosis of acute stroke. How to relate presentation to vascular anatomy.

Stroke is a heterogeneous disease with many different causes and presentations. Ischemic strokes can be due to occlusion of large or small vessels by thrombi or emboli. Hemorrhagic strokes are due to rupture of small vessels within the brain or rupture of aneurysms at the base of the brain. An understanding of the vascular anatomy of stroke syndromes is essential to planning an efficient evaluation. The workup should be individualized for each patient and should rule out processes that can produce strokelike syndromes. Despite the availability of advanced imaging tools, the clinical evaluation is still of paramount importance.

Brain Ischemia↗
PubMed1989

Genetic linkage mapping of chromosome 17 markers and neurofibromatosis type I.

The von Recklinghausen neurofibromatosis (NF1) gene has been localized to the pericentromeric region of chromosome 17. We have screened six multigenerational families with multiple, tightly linked markers to aid in mapping this region of the chromosome. More than 150 members in six families were typed with probes including HHH202, D17Z1, EW203, EW206, EW207, EW301, pA10-41, D17S37, and D17S36. Two-point lod scores for NF1 versus all markers were calculated. HHH202 demonstrated the tightest linkage to NF1 with theta = .0, z = 3.86 (95% confidence limits [CL] of theta = .0-.13), suggesting that HHH202 be considered as a potential candidate marker for use in carrier detection and prenatal diagnosis. Pairwise marker-to-marker lod scores were used in examining the most likely order of subsets of the markers. Of those tested, the most likely order was (pter)-pA10-41-EW301-D17Z1-HHH202-NF1-E W206-EW207-EW203-(qter). In addition, we have ascertained an NF1 x NF1 half-cousin mating in which there are four affected family members who are potentially homozygous for the disease gene. Two of these four individuals have been sampled and typed for marker loci. When their D17Z1 genotypes are considered, the probability that both these individuals are heterozygous is 85%.

Chromosome Mapping↗
PubMed1989

Myotonic muscular dystrophy.

Myotonic muscular dystrophy is inherited as an autosomal dominant disease and affects many different organ systems. Genetic research has located the DM gene to chromosome 19. Using new DNA probes, highly accurate genetic counseling can be provided for families with DM. Isolation of the DM gene is expected in the near future and may allow planning of effective therapies.

Adult↗
PubMed1987

A multicenter study of anticoagulation parameters when using heparin and warfarin.

Anticoagulation with heparin and warfarin is used in the treatment of several diseases including cerebrovascular disease. While the most effective therapeutic range of anticoagulation is unclear, some investigators have found an increased risk of bleeding complications with more intense anticoagulation. Recent studies have suggested that lower levels of anticoagulation may be as efficacious as high levels but with a reduced incidence of bleeding complications. In order to better assess the anticoagulation parameters used by neurologists and house officers, we performed a questionnaire survey at six major medical centers. Responses were obtained from 30 attending neurologists and 52 house officers. Attending physicians and house officers selected mean partial thromboplastin times of 57.7 s and 63.3 s, respectively. The mean prothrombin time (PT) was 21.0 s for attending neurologists and 19.4 s for house officers. The average PT ratio was 1.82 for attending neurologists and 1.69 for house officers. Forty percent of attending neurologists and 17.7% of house officers specified PT ratios of 2.0 or greater. These results indicate that many physicians may be using warfarin in dosages above recommended guidelines.

Blood Coagulation Tests↗
PubMed1987

Genetic linkage studies of chromosome 17 RFLPs in von Recklinghausen neurofibromatosis (NF1).

Recent localization of the gene for von Recklinghausen neurofibromatosis (NF1) to chromosome 17 has led to studies to identify additional tightly linked probes that can be used in defining the primary genetic defect in NF1. We have examined and obtained blood for DNA linkage studies on over 250 individuals from 10 multigeneration neurofibromatosis families. We have analyzed 130 members in 7 families with the available chromosome 17 NF1 linked probes, pE51, D17S71, and D17Z1, as well as two probes generated from our own chromosome 17/19 enriched library (LDR92, LDR152A). Tight linkage was found between NF1 and the centromeric probe D17Z1 (theta = 0.04) and between NF1 and D17S71 (theta = 0.08). A definite recombinant was seen for the D17Z1 marker, which previously had not exhibited crossingover. Chromosome 17 DNA markers pE51, LDR92, and LDR152A gave slightly positive scores, which were not statistically significant.

Chromosomes, Human, Pair 17↗
PubMed1987

Linkage studies in peripheral neurofibromatosis.

Peripheral neurofibromatosis (NF) is one of the most common major genetic disorders in man. Its chromosomal location is unknown and questions regarding such factors as genetic heterogeneity remain unanswered. We have ascertained and sampled several large multi-generation families for linkage studies including one family of 66 subjects, 28 of whom were affected with NF. Recombinant DNA studies of several restriction fragment length polymorphisms (RFLPs) including C3, ApoC2, pBam34 (D19S6], HAUP[APRT], pE40-1 [D11521], Hp[Hp2 alpha], LDR92, and LDR111 failed to show a significant linkage (Z [lod score] greater than or equal to 3.00) in this family. In addition, the results excluded areas of the genome around the marker loci (Z greater than or equal to - 2.00) as potential sites for linkage. The maximum Z obtained with the markers was for Hp at theta (maximum recombination fraction) = 0.20 and Z = 0.399. We are now in the process of screening additional RFLPs and families for linkage to NF.

Genetic Linkage↗
PubMedDate not supplied

Familial clustering of intracerebral hemorrhage: a prospective study in North Carolina.

Few studies have assessed the frequency of familial clustering in intracerebral hemorrhage (ICH). Of 144 patients with ICH prospectively assessed, 14 (9.8%) had a positive family history of ICH (FH+). Four pedigrees had more than two affected family members. Comparisons between FH+ and FH- probands demonstrated no significant differences in race, age, sex, ICH type or location. An underlying genetic etiology may account for familial clustering in some ICH patients.

Aged↗