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M Albert

Publications and source records attributed to M Albert.

At least 37 records · Page 2Linked to original sources
PubMed2003

The role of APOE-epsilon4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging.

BACKGROUND: While a genetic risk factor for late-onset AD, the effects of the epsilon4 allele of the APOE gene on cognitive functioning more generally remain unclear. OBJECTIVE: To assess the role of the epsilon4 allele of the APOE gene in longitudinal cognitive decline. METHODS: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline. Subjects were 965 Caucasian and African American men and women from Durham NC, East Boston, MA, and New Haven, CT, aged 70 to 79 years, recruited in 1988 through 1989, who completed two follow-up evaluations, one at 3 years and another at 7 years. RESULTS: At the first follow-up, modest but significant declines in naming and spatial ability were associated with the APOE-epsilon4 genotype. By the second follow-up, more pronounced and significant associations were noted between the APOE-epsilon4 genotype and cognitive decline from six of the eight cognitive outcomes. After 7 years, APOE-epsilon4 allele carriers were twice as likely to have declined on a global cognitive score (odds ratio = 2.0; 95% CI: 1.1, 3.6) as noncarriers. CONCLUSIONS: APOE-epsilon4 is associated with cognitive decline among a high-functioning elderly cohort, with effects most pronounced after 7 years of follow-up. Hence, the epsilon4 allele either may function as a risk factor for cognitive impairment in normal aging across a broad spectrum of domains or may exert detectable effects early in a long prodromal AD trajectory.

Aged↗
PubMed2003

AES and SIMS investigation of diffusion barriers for copper metallization in power-SAW devices.

Barrier layers for Cu-metallization in surface acoustic wave (SAW) devices were investigated by AES and SIMS depth profiles. Two layered systems on LiNbO(3) substrate have been analyzed after annealing in air up to 400 degrees C. The investigated systems were (A) Ta(20 nm)/Cu(150 nm)/Ti(30 nm), deposited by electron beam evaporation, and (B) Ta(30)Si(18)N(52)(50 nm)/Cu(150 nm)/Ta(30)Si(18)N(52)(50 nm) deposited by magnetron sputtering. In system A the Ta layer shows oxidation in air for T>or=300 degrees C. Ti from the buffer layer diffuses into the Cu at about 100 degrees C, and segregates at the Ta/Cu interface for T>or=200 degrees C. Oxidation of the Ti layer starts at 300 degrees C. But no remarkable amounts of oxygen could be found in the Cu film. The depth profiles show that the TaSiN layer in system B operates as a more effective barrier for the Cu-SAW technology up to more than 300 degrees C.

Journal Article↗
PubMed2003

Mycobacterium xenopi and drinking water biofilms.

The ability of Mycobacterium xenopi to colonize an experimental drinking water distribution system (a Propella reactor) was investigated. M. xenopi was present in the biofilm within an hour following its introduction. After 9 weeks, it was always present in the outlet water (1 to 10 CFU 100 ml(-1)) and inside the biofilm (10(2) to 10(3) CFU cm(-2)). Biofilms may be considered reservoirs for the survival of M. xenopi.

Biofilms↗
PubMed2002

Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging.

OBJECTIVE: To investigate whether plasma interleukin-6 (IL-6) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population-based sample of nondisabled elderly people. METHODS: A prospective cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted. Regression modeling was used to investigate whether baseline IL-6 levels (classified by tertiles) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up) and from 1988 to 1995 (7-year follow-up). RESULTS: Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function (i.e., scores below the median), independent of demographic status, social status, health and health behaviors, and other physiologic variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third tertile (OR = 2.03; 95% CI: 1.30, 3.19) were at increased risk of cognitive decline even after adjusting for all confounders. At 7 years of follow-up, only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all confounders. CONCLUSIONS: The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function. These findings are consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasma IL-6, and neuropathologic disorders.

Aged↗
PubMed2002

Association between the APOE genotype and psychopathologic symptoms in Alzheimer's disease.

BACKGROUND: Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results. OBJECTIVE: To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD. METHODS: Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years (mean 5.5 years) for development of delusions, illusions, hallucinations, behavioral symptoms, and depression. Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology (outcome) in relation to APOE genotype (predictor). RESULTS: The presence of one epsilon4 allele carried a 2.5-fold risk, whereas the presence of two epsilon4 alleles carried a 5.6-fold risk for development of delusions. The associations remained significant even when age, ethnicity, sex, education, duration of disease, and cognitive and functional performance were controlled for. The presence of two epsilon4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only. No significant associations were detected between APOE genotype and the incidence of illusions, behavioral symptoms, or depression. CONCLUSION: The presence of one or more epsilon4 alleles is a significant predictor for the incidence of delusions in the course of AD.

Aged↗
PubMed2002

Prenatal diagnosis of brain abnormalities in Wolf-Hirschhorn (4p-) syndrome.

OBJECTIVES: Although there have been occasional reports of prenatal diagnosis of this syndrome, most cases are diagnosed postnatally. The objective was to evaluate the presence of brain abnormalities in the prenatal diagnosis of Wolf-Hirschhorn syndrome. METHODS: Prenatal ultrasound and MRI examination of the fetal brain were performed in a case of Wolf-Hirschhorn syndrome. A comprehensive review of Wolf-Hirschhorn syndrome reported between 1960 and 2000 in the literature was carried out. RESULTS: The late diagnosis of a growth-retarded fetus with normal amniotic fluid volume, normal Doppler and negative infection screen calls for a detailed examination of the fetal brain and heart. Multifocal white matter lesions and periventricular cystic changes, which are often attributed to perinatal distress, are possible prenatal features causing suspicion of 4p- syndrome in an IUGR fetus. CONCLUSION: Subtle abnormalities on ultrasound may suggest a chromosomal problem. Standard cytogenetics cannot always demonstrate a microdeletion. High-resolution banding and molecular analysis can help to confirm the diagnosis.

Abnormalities, Multiple↗
PubMed2002

Prenatal diagnosis of a 45,X male with a SRY-bearing chromosome 21.

Male phenotype associated with a 45,X karyotype is an infrequent finding. We present a case diagnosed prenatally on amniocentesis performed for maternal age. The male phenotype was associated with a translocation of a distal part of Yp including the pseudoautosomal SHOX gene and SRY gene on the short arm of a chromosome 21. By DNA analysis we could show that the X chromosome was of maternal origin and that the breakpoint was in interval 3 of the Y chromosome. Mechanisms and genetic counselling are discussed based on a review of published cases of 45,X and XX males.

Adult↗
PubMed2002

Fetal gender: antenatal discrepancy between phenotype and genotype.

Sexual discrepancy is reported in both 46,XY females and 46,XX males, and most diagnoses of sex reversal are made in the postpubertal period. We report three cases of sexual discrepancy, which were revealed by karyotyping following genetic amniocentesis, chorionic villus sampling and fetal blood sampling. The etiologies of 46,XX male, 45,X male and 46,XY female subjects are reviewed. When sexual discrepancy between fetal karyotype and ultrasonographic fetal phenotype is encountered, sample error and placental mosaicism should be excluded. A detailed fetal ultrasound examination should be performed to check for syndromic gender discrepancy. When repeat karyotyping is indicated, localization of the Sox related Y chromosome gene should be carried out.

Abnormalities, Multiple↗
PubMed2002

One-generation reproduction toxicity study of Dithane M-45 (mancozeb) and lead acetate.

The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of diet. The three treatment groups received, in addition to the above doses of lead acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals decreased significantly before the pregnancy period. This tendency was also seen in males after the combination treatment. At the two high dose levels a remarkable body weight increase was seen in the female animals during the lactation period. As a result of treatment, decreased body weight of offspring was measured during the lactation period. No gross pathological changes were seen. Histological examination showed general tubulonephrosis in the experimental animals. It can be established that the administration of Dithane M-45 did not enhance the reproductive toxicity of lead acetate.

Animals↗
PubMed2001

Does histologic grade have a role in the management of head and neck cancers?

PURPOSE: High histologic grade is usually associated with a greater propensity to distant metastases (DM). Its role to predict DM in head and neck cancer is not yet defined. The aim of this study is to evaluate the role of histologic grade as an independent predictor of DM and to determine a subgroup of patients who may benefit from systemic chemotherapy. PATIENTS AND METHODS: This is a retrospective study of 1,266 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy. All stages and subsites of head/neck were included. DM rates were evaluated by the Kaplan-Meier method with a subsequent Cox analysis. RESULTS: There is a strong correlation of grade with N stage (P <.000001). The metastases-free survival (MFS) was 98%, 90%, and 72% for grades 1, 2, and 3, respectively (P <.000001). In patients with N0 stage, MFS is always greater than 90%, whatever the grade. In the 222 N1 patients, MFS was more than 90% in grade 1 and 2 but dropped to 75% for grade 3 (P =.001). In patients with N2 and N3, MFS was 91%, 79%, and 59% for grades 1, 2, and 3, respectively (P =.008). The same conclusion is applicable when only patients with neck control are analyzed. In a Cox model, grade was an independent predictor of DM (P =.000001) as well as T stage (P =.003), N stage (P =.000001), and neck failure (P =.0003). Higher grade was also an independent predictor of survival (P =.02). CONCLUSION: Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.

Aged↗
PubMed2001

Canine ocular onchocercosis in Hungary.

An adult male mongrel dog that had spent its entire life in Hungary, was found to have infection with filaroid nematodes of the genus Onchocerca. The gravid male and female parasites were embedded in bean-sized granulomatous masses on the conjunctiva and the sclera of both eyes. The cuticle of females consisted of two separated layers in longitudinal sections, the external layer bearing ridges and the internal layer showing striations. The ridges were marked, rounded in shape, and the ratio of body diameter to the distance between ridges varied between 7:1 and 10:1. At midbody of the worms, two striations could be seen between each pair of ridges: one under every ridge and one between neighbouring ridges. Numerous exceptionally small (96.4 microm x 6.4 microm) microfilariae were seen in the uteri of females and the surrounding tissues and isolated from skin biopsy materials. The morphology and location of the parasite and histopathological lesions of the Hungarian case were similar to that described in dogs in the United States. This case is the first documented ocular Onchocerca infection in dogs outside the western United States. Thus, onchocercosis should be considered in the differential diagnosis of ocular and periocular nodules in dogs also in Europe.

Animals↗
PubMed2001

An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease.

BACKGROUND: Studies of patients meeting clinical and pathologic criteria for Alzheimer disease (AD) have not consistently found associations between the presence of Lewy bodies (LBs) at postmortem examination and a higher frequency during life of the clinical features of dementia with LBs. OBJECTIVE: To evaluate the clinical correlates of LBs in patients with AD. DESIGN AND METHODS: Fifty-one patients were diagnosed as having probable AD during life and met pathologic criteria for AD. Semiquantitative ratings for LBs were obtained in 4 brain regions: substantia nigra, cingulate, insular cortex, and hippocampus. The patients had been followed up semiannually for up to 9.9 years before death, and clinical features associated with dementia with LBs, including extrapyramidal signs and visual hallucinations, were assessed at each study visit. Logistic regression analyses determined whether patients who had LBs were more likely than those without LBs to express specific clinical signs during follow-up. Cox analyses determined whether patients with LBs developed clinical signs or died earlier. Generalized estimating equations were used to compare rates of cognitive or functional change. RESULTS: Nineteen of the 51 patients had at least 1 LB in one of the studied regions. In no case was a significant relation noted between LBs and the presence of a measured clinical sign. No LB measure was associated with an increased risk of developing any of the evaluated clinical signs earlier in the disease. There was no association between the presence of LBs and more rapid mortality or more rapid disease progression. CONCLUSIONS: In patients diagnosed as having AD during life, we did not observe a relation of LBs noted during postmortem examination with the presence of any clinical feature that we assessed or with the rapidity of disease progression. The relation between LBs and specific clinical manifestations may be tenuous in these patients.

Aged↗
PubMed2001

Outcome of patients treated with cobalt and 6 MV in head and neck cancers.

BACKGROUND: Since 1992, we have been using a 6-MV linear accelerator instead of a cobalt machine. The aim of the study is to evaluate the impact of this on neck control, particularly on postoperative patients in which subcutaneous tissues are at risk. METHOD: A retrospective study including all of 1,452 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All stages and subsites of the head/neck were included. Local and neck control were evaluated by the Kaplan Meier method, and comparisons were made between the cobalt and the 6-MV subgroups with a subsequent Cox analysis. For neck control analysis, the postoperative patients were divided in low and high risk (extracapsular extension [ECE], >two nodes, or T4). RESULTS: Radical radiotherapy: A better local control (LC) is observed with 6 MV than with cobalt, but neck control was similar. Postoperative radiotherapy: A better LC is observed with 6 MV. In high-risk patients, the neck control was higher for the cobalt group (79%) vs 60% for the 6-MV group (p = .09 and .03 in a Cox model). CONCLUSION: In postoperative patients at high risk for neck relapse, cobalt seems to give a better neck control. We are currently doing a prospective study in which a bolus is added for half the treatment when patients at high risk for neck relapse are treated with 6 MV.

Adult↗
PubMed2001

Immunocytological localization of the HNK-1 carbohydrate in murine cerebellum, hippocampus and spinal cord using monoclonal antibodies with different epitope specificities.

The HNK-1 carbohydrate, an unusual 3'-sulfated glucuronic acid epitope characteristic of many neural recognition molecules, serves as a ligand in neural cell interactions and is differentially expressed in the quadriceps and saphenous branches of the femoral nerve in the PNS of adult mice. Based on these observations, we investigated the possibility that the HNK-1 carbohydrate may be differentially distributed in neurons and fiber tracts also in the CNS thereby contributing to different targeting and guidance mechanisms. We have used antibodies with different HNK-1 epitope specificities to probe for subtle differences in expression patterns. In the adult mouse cerebellum the HNK-1 carbohydrate is detectable in stripe-like compartments in the molecular and Purkinje cell layers, whereas N-CAM and its associated alpha2,8 polysialic acid does not show this compartmentation. In the adult hippocampus, the HNK-1 carbohydrate localizes to perineuronal nets of inhibitory interneurons and marks the inner third of the molecular layer of the dentate gyrus. In the adult spinal cord, HNK-1 labeling is most pronounced in gray matter areas. White matter enriched regions show differential labeling with regard to fiber tracts and antibody specificity. Whereas the different antibodies do not show differences in staining in the cerebellum and the hippocampus, they show differences in staining pattern of fiber tracts and motoneurons in the spinal cord. The HNK-1 expression pattern also differed in the adult spinal cord from that observed at embryonic day 14 and postnatal day 14. Our observations suggest a functional role in the specification of functionally discrete compartments in different areas of the CNS and during development.

Animals↗
PubMed2001

Social relationships, social support, and patterns of cognitive aging in healthy, high-functioning older adults: MacArthur studies of successful aging.

This study examines the relationship of social ties and support to patterns of cognitive aging in the MacArthur Studies of Successful Aging (see L. F. Berkman et al., 1993), a cohort study of 1,189 initially high-functioning older adults. Baseline and longitudinal data provide information on initial levels as well as changes in cognitive performance over a 7.5-year period. Linear regression analyses revealed that participants receiving more emotional support had better baseline performance, as did those who were unmarried and those reporting greater conflict with network members. Greater baseline emotional support was also a significant predictor of better cognitive function at the 7.5-year follow-up, controlling for baseline cognitive function and known sociodemographic, behavioral, psychological, and health status predictors of cognitive aging. The findings suggest the potential value of further research on the role of the social environment in protecting against cognitive declines at older ages.

Aged↗
PubMed2001

Yersinia enterocolitica invasin triggers phagocytosis via beta1 integrins, CDC42Hs and WASp in macrophages.

The Yersinia outer surface protein invasin binds to beta1 integrins on target cells and has been shown to trigger phagocytic uptake by macrophages. Here, we investigated the role of the actin regulator Wiskott-Aldrich syndrome protein (WASp), its effector the Arp2/3 complex and the Rho-GTPases CDC42Hs, Rac and Rho in invasin/beta1 integrin-triggered phagocytosis. During uptake of invasin-coated latex beads, the alpha5beta1 integrin, WASp and the Arp2/3 complex were recruited to the developing actin-rich phagocytic cups in primary human macrophages. Blockage of beta1 integrins by specific antibodies, inhibition of Arp2/3 function by microinjection of inhibitors or the use of WASp knockout macrophages inhibited phagocytic cup formation and uptake. Furthermore, microinjection of the dominant negative GTPase mutants N17CDC42Hs, N17Rac or the Rho-specific inhibitor C3-transferase into macrophages greatly attenuated invasin-induced formation of cups. These data suggest that during invasin-triggered phagocytosis beta1 integrins activate actin polymerization via CDC42Hs, its effector WASp and the Arp2/3 complex. The contribution of Rac and Rho to phagocytic cup formation also suggests a complex interplay between different Rho GTPases during phagocytosis of pathogens.

Actin-Related Protein 2↗
PubMed2001

Pathogenesis of primary respiratory disease induced by isolates from a new genetic cluster of bovine viral diarrhea virus type I.

The pathogenesis of infection induced by cytopathogenic isolates from the newly identified genetic cluster Id of bovine viral diarrhea virus (BVDV) type I was studied in two experimental infections of previously seronegative, immunocompetent calves. Experiment 1 focused on the evaluation of clinical patterns, viremia, and serological responses. All infected calves in this experiment developed respiratory symptoms and seroconverted to BVDV positivity. Contact calves also contracted a respiratory tract infection following exposure to infected animals. Viremia was demonstrated between postinfection days 2 and 17, and the virus was detected in organ specimens of all but one each of the infected and contact calves. In experiment 2, the distribution of BVDV in various tissues of calves euthanized at defined days postinfection was studied. In two of these calves recurrent shedding of BVDV in nasal secretions was shown. BVDV was detected in various tissues of all infected calves throughout the experiment and also following seroconversion and the clearance of BVDV from the circulatory system. Despite the widespread distribution of the virus in various organs, significant tissue damage was found mainly in respiratory tract and lymphoid tissues. These experiments revealed that viruses from cluster Id of BVDV are able to induce primary respiratory disease in previously seronegative, immunocompetent calves. Contact transmission and virus recurrence, contrary to observations from acute experimental infections with noncytopathogenic BVDV, are likely to reflect differences in biological features of these cytopathogenic isolates. Virus shedding and its presence in tissues following peripheral clearance and in the presence of antibodies may have implications in the diagnosis, pathogenesis, and epidemiology of BVDV-induced syndromes in cattle.

Animals↗