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Biomedical subjects

S Albert

Publications and source records attributed to S Albert.

At least 19 recordsLinked to original sources
PubMed1999

Rate of memory decline in AD is related to education and occupation: cognitive reserve?

OBJECTIVE: To determine whether the rate of decline in performance on a memory test is more rapid in AD patients with higher versus lower educational and occupational attainment. BACKGROUND: Epidemiologic and imaging studies have suggested that, given comparable clinical severity of dementia, AD pathology is more advanced in patients with higher educational and occupational attainment. Because educational and occupational attainment should not influence the progression of AD pathology, and because severe AD pathology will eventually produce a mortality-causing condition, people with higher attainment might experience clinical AD for a shorter time and have a more rapid clinical progression. METHODS: A total of 177 AD patients were tested yearly for up to four study visits with the Selective Reminding Test (a memory test). Analysis of prospective change in the total recall score was performed by applying generalized estimating equations to regression analyses with repeated measures. RESULTS: At the initial visit, scores were comparable in the high- and low-education and the high- and low-occupation groups. Overall, memory scores declined by approximately 1 point yearly (p<0.01). There was a more rapid decline in memory scores in patients with higher educational (p<0.057) and higher occupational attainment (p<0.02). The authors then stratified patients based on their initial memory scores. The more rapid decline in memory scores associated with higher educational and occupational attainment was noted only in the group with low initial scores (p<0.05 for both). The full group and stratified group analyses were also repeated controlling for other potentially relevant variables including age, gender, race, ethnicity, and the presence of extrapyramidal signs, stroke, or at least one apolipoprotein E-epsilon4 allele. The results remained unchanged. CONCLUSIONS: Memory declined more rapidly in AD patients with higher educational and occupational attainment. This adds support to the idea that the discontinuity between the degree of AD pathology and the observed clinical severity of AD is mediated through some form of reserve.

Aged↗
PubMed1999

Two new members of a family of Ypt/Rab GTPase activating proteins. Promiscuity of substrate recognition.

Monomeric GTPases of the Ras superfamily have a very slow intrinsic GTPase activity which is accelerated by specific GTPase-activating proteins. In contrast to Ras- and Rho-specific GTPase-activating proteins (GAPs) that have been studied in great detail, little is known about the functioning of GAPs specific for Ypt/Rab transport GTPases. We have identified two novel Ypt/Rab-GAPs because of their sequence relatedness to the three known GAPs Gyp1p, Gyp6p, and Gyp7p. Mdr1/Gyp2p is an efficient GAP for Ypt6p and Sec4p, whereas Msb3/Gyp3p is a potent GAP for Sec4p, Ypt6p, Ypt51p, Ypt31/Ypt32p, and Ypt1p. Although the affinity of Msb3/Gyp3p for its preferred substrate Sec4p is low (K(m) = 154 microM), it accelerates the intrinsic GTPase activity of Sec4p 5 x 10(5)-fold. Msb3/Gyp3p appears to be functionally linked to Cdc42p-regulated pathway(s). The results demonstrate that in yeast there is a large family of Ypt/Rab-GAPs, members of which discriminate poorly between GTPases involved in regulating different steps of exo- and endocytic transport routes.

Amino Acid Sequence↗
PubMed1999

Identification of the catalytic domains and their functionally critical arginine residues of two yeast GTPase-activating proteins specific for Ypt/Rab transport GTPases.

Ypt/Rab proteins constitute the largest subfamily of the Ras superfamily of monomeric GTPases and are regulators of vesicular protein transport. Their slow intrinsic GTPase activity (10(-4)-10(-3) min(-1) at 30 degrees C) has to be accelerated to switch the active to the inactive conformation. We have identified the catalytic domain within the C-terminal halves of two yeast GTPase-activating proteins (GAPs), Gyp1p and Gyp7p, with specificity for Ypt/Rab GTPases. The catalytically active fragments of Gyp1p and Gyp7p were more active than the full-length proteins and accelerated the intrinsic GTP hydrolysis rates of their preferred substrates by factors of 4.5 x 10(4) and 7.8 x 10(5), respectively. The K(m) values for the Gyp1p and Gyp7p active fragments (143 and 42 microM, respectively) indicate that the affinities of those GAPs for their substrates are very low. The catalytic domains of Gyp1p and Gyp7p contain five invariant arginine residues; substitutions of only one of them (R343 in Gyp1p and R458 in the analogous position of Gyp7p) rendered the GAPs almost completely inactive. We suggest that Ypt/Rab-GAPs, like Ras- and Rho-GAPs, follow the same mode of action and provide a catalytic arginine ('arginine finger') in trans to accelerate the GTP hydrolysis rate of the transport GTPases.

Amino Acid Sequence↗
PubMed1999

The influence of smoking on the risk of Alzheimer's disease.

OBJECTIVE: To investigate the relationship between cigarette smoking and Alzheimer's disease (AD) in a prospective community-based study in northern Manhattan. BACKGROUND: Results from previous case-control studies suggest that there is a protective effect of smoking on AD. However, the recent prospective Rotterdam Study found that there was an increased risk of AD for smokers, particularly those without an apolipoprotein E (APOE)-epsilon4 allele. METHODS: The authors examined data from a community-based longitudinal study of local elders residing in northern Manhattan to determine whether tobacco use increases or decreases the risk of AD. Information regarding the frequency of tobacco use was obtained in structured interviews at the baseline assessment. Standardized clinical assessments were subsequently completed on each subject at annual visits during which incident cases of AD were identified. RESULTS: The relative risk (RR) of AD among former smokers was 0.7 (95% CI, 0.5 to 1.1). The RR among current smokers was 1.9 (95% CI, 1.2 to 3.0). Smokers without an APOE-epsilon 4 allele had the highest risk of AD (RR = 2.1; 95% CI, 2.1 to 3.7) compared with those with an APOE-epsilon 4 allele (RR = 1.4; 95% CI, 0.6 to 3.3). CONCLUSIONS: Our results are consistent with the observation that smoking increases the risk of AD. However, we found that among previous smokers who quit smoking, there may be a slight reduction in the risk of AD.

Aged↗
PubMed1999

The family of major royal jelly proteins and its evolution.

A cDNA encoding a new member of the gene family of major royal jelly proteins (MRJPs) from the honeybee, Apis mellifera, was isolated and sequenced. Royal jelly (RJ) is a secretion of the cephalic glands of nurse bees. The origin and biological function of the protein component (12.5%, w/w) of RJ is unknown. We show that the MRJP gene family encodes a group of closely related proteins that share a common evolutionary origin with the yellow protein of Drosophila melanogaster. Yellow protein functions in cuticle pigmentation in D. melanogaster. The MRJPs appear to have evolved a novel nutritional function in the honeybee.

Amino Acid Sequence↗
PubMed1999

Molecular characterization of MRJP3, highly polymorphic protein of honeybee (Apis mellifera) royal jelly.

Major proteins of honey bee (Apis mellifera) royal jelly are members of the MRJP protein family. One MRJP protein termed MRJP3 exhibits a size polymorphism as detected by SDS-PAGE. In this report we show that polymorphism of the MRJP3 protein is a consequence of the polymorphism of a region with a variable number of tandem repeats (VNTR) located at the C-terminal part of the MRJP3 coding region. We present the characterization of five polymorphic alleles of MRJP3 by DNA sequencing. By PCR analyses, at least 10 alleles of distinct sizes were found in randomly sampled bees. Studies with nurse bees from a single honeybee colony revealed both Mendelian inheritance and very high variability of the MRJP3 genomic locus. The high variability and simple detection of the MRJP3 polymorphism may be useful for genotyping of individuals in studies of the honeybee.

Alleles↗
PubMed1999

The EMB 506 gene encodes a novel ankyrin repeat containing protein that is essential for the normal development of Arabidopsis embryos.

The EMB 506 gene of Arabidopsis, required for the normal development of the embryo beyond the globular stage, has been cloned. The gene encodes a protein of predicted size 35 kDa that contains five ankyrin (ANK) repeats within the C terminal moiety. ANK repeats are conserved domains of 33 amino acids involved in specific recognition of protein partners. The EMB 506 protein was detected at different stages of silique development but accumulated preferentially in the mature cauline leaves. The rescue of homozygous emb 506 embryos by complementation with the wild-type sequence cDNA demonstrated that the emb mutation is a consequence of the T-DNA insertion and that integration and expression of the transgene occurred during gametogenesis and/or early embryo development. In addition to the drastic effect of the emb 506 mutation during embryo development, complementation experiments revealed another effect of the gene: emb 506 plants transformed with the wild-type EMB 506 sequence were able to produce viable seeds but showed a reduction of apical dominance and the presence of adventitious buds or bracts along the stem. This result supports the idea that genes essential for embryogenesis may also be required at other stages of the plant life cycle.

Amino Acid Sequence↗
PubMed1999

Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate and notochord.

The signalling molecule Sonic hedgehog (Shh) controls a wide range of differentiation processes during vertebrate development. Numerous studies have suggested that the absolute levels as well as correct spatial and temporal expression of shh are critical for its function. To investigate the regulation of shh expression, we have studied the mechanism controlling its spatial expression in the zebrafish. We employed an enhancer screening strategy in zebrafish embryos based on co-injection of putative enhancer sequences with a reporter construct and analysis of mosaic expression in accumulated expression maps. Enhancers were identified in intron 1 and 2 that mediate floor plate and notochord expression. These enhancers also drive notochord and floor plate expression in the mouse embryo strongly suggesting that the mechanisms controlling shh expression in the midline are conserved between zebrafish and mouse. Functional analysis in the zebrafish embryo revealed that the intronic enhancers have a complex organisation. Two activator regions, ar-A and ar-C, were identified in intron 1 and 2, respectively, which mediate mostly notochord and floor plate expression. In contrast, another activating region, ar-B, in intron 1 drives expression in the floor plate. Deletion fine mapping of ar-C delineated three regions of 40 bp to be essential for activity. These regions do not contain binding sites for HNF3beta, the winged helix transcription factor previously implicated in the regulation of shh expression, indicating the presence of novel regulatory mechanisms. A T-box transcription factor-binding site was found in a functionally important region that forms specific complexes with protein extracts from wild-type but not from notochord-deficient mutant embryos.

Animals↗
PubMed1998

A family of major royal jelly proteins of the honeybee Apis mellifera L.

The characterization of major proteins of honeybee larval jelly (49-87 kDa) was performed by the sequencing of new complementary DNAs (cDNAs) obtained from a honeybee head cDNA library, by the determination of N-terminal sequences of the proteins, and by analyses of the newly obtained and known sequence data concerning the proteins. It was found that royal jelly (RJ) and worker jelly (WJ) contain identical major proteins and that all the proteins belong to one protein family designated MRJP (from Major Royal Jelly Proteins). The family consists of five main members (MRJP1, MRJP2, MRJP3, MRJP4, MRJP5). The proteins MRJP3 and MRJP5 are polymorphic. MRJPs account for 82 to 90% of total larval jelly protein, and they contain a relatively high amount of essential amino acids. These findings support the idea that MRJPs play an important role in honeybee nutrition.

Amino Acid Sequence↗
PubMed1998

[Diagnosis of pneumonia in long-term ventilated patients. Value of digital luminescence radiography in comparison with clinical and microbiological monitoring].

PURPOSE: Pulmonary infection is one of the most feared complications in patients receiving long-term ventilation. We evaluated prospectively the diagnostic value of daily bedside chest radiography performed as digital luminescence radiography (DLR) in comparison to clinical findings and quantitative microbial culture. MATERIAL AND METHODS: Prospective evaluation of daily bedside chest radiography (DLR) and clinical parameters such as blood count, body temperature, and microbiological monitoring (quantitative culturing, microscopy) of 20 patients receiving long-term ventilation was undertaken. Altogether 325 chest radiographs were evaluated. RESULTS: 96% of the routine radiographs showed abnormal findings. Nosocomial pneumonia was suspected in 31% of all 330 days of observation by means of clinical and microbiological findings. DLR showed correct findings in 80% of this days (right-positive interpretation); a false-positive interpretation was resulted in 16 radiographs. Most common finding in nosocomial pneumonia was an alveolar pattern with air bronchogram. Fever and leucocytosis often precede radiological evidence of pneumonia. CONCLUSION: Daily bedside chest radiography performed as DLR shows abnormal finding in a high percentage. Bedside chest radiograph is in accordance to clinical and microbiological finding of nosocomial pneumonia in 80%.

Adult↗
PubMed1997

[Unstable angina pectoris in intermittent left bundle branch block].

We present a case report of a 57 year old woman with recurrent chest pain, initially exclusively at exercise and later also at rest. This led to an emergency hospitalization for suspected myocardial infarction. As there were no enzymatic and electrocardiographic signs of acute infarction she was treated, as unstable angina pectoris. Coronary angiography revealed but a modest coronary atheromatosis without significant coronary stenosis. Therefore her symptoms were interpreted as primary manifestation of an intermittant Left Bundle Branch Block (LBBB) with changing heart-rate dependency. A majority of patients with LBBB and chest pain have a relevant Coronary Artery Disease (CAD). There is a small number of reports in literature about patients with intermittant LBBB without significant CAD but with both typical (exercise-induced) and atypical (at rest) chest pain. Special features of our case are presentation of LBBB as unstable angina, documentation of an intermittant LBBB with changing heart-rate dependency and heart-rate-dependent supranormal conduction in the left bundle branch. We review some important aspects of LBBB with regard to this case.

Angina, Unstable↗
PubMed1997

Isolation and characterization of the droPIK57 gene encoding a new regulatory subunit of phosphatidylinositol 3-kinase from Drosophila melanogaster.

Mammalian phosphatidylinositol 3-kinase (PI 3-kinase) plays an important role in the regulation of various cellular, receptor tyrosine kinase-mediated processes, such as mitogenesis and transformation. PI 3-kinase is composed of a 110-kDa catalytic subunit and a regulatory subunit of 85 kDa or 55 kDa. We have cloned a gene for a regulatory subunit from Drosophila melanogaster, named droPIK57, from head-specific cDNA libraries. The droPIK57 gene encodes a protein containing two SH2 domains with significant sequence homology to those in p85 and p55. Like the p55 subunits, DroPIK57 is missing the SH3 domain and the bcr homology region of the p85 subunit. The short N-terminus as well as the C-terminus of the DroPIK57 protein show no identity to the known PI 3-kinase subunits, suggesting that it is a new member in the family of regulatory subunits. In-situ hybridization and Northern blot analysis indicate a widespread function of this gene during embryogenesis and in the CNS.

Amino Acid Sequence↗
PubMed1997

The absence of an apolipoprotein epsilon4 allele is associated with a more aggressive form of Alzheimer's disease.

We investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE epsilon4 allele. The rate of decline in modified Mini-Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE epsilon4 alleles compared with patients with other genotypes. Compared with patients without an APOE epsilon4 allele, the risk of mortality was also decreased in patients with at least one epsilon4 allele (RR = 0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE epsilon4 is associated with a less aggressive form of AD.

Age of Onset↗
PubMed1997

Intensity Measurements of Deltal > 1 Transitions of Several Isotopomers of HCN

The intensities of the forbidden Q-branch transitions 02(2f)0-00(0)0, 12(2f)0-00(0)0, and 02(2f)1-00(0)0 for HCN have been measured. The intensities of the 02(2f)0-00(0)0 transitions of DCN, D13C15N, and H12C15N were also measured, as well as the 02(2f)1-00(0)0 transitions of H12C15N and H13C15N. These Q-branch transitions are forbidden even when the effects of l-type resonance are considered so they must get their intensity from some other Coriolis interactions. The much stronger P- and R-branch lines for the e levels of these same vibrational transitions were also measured and they are shown to get most of their intensity from l-type resonance. However, the same Coriolis resonance that gives intensity to the Q-branch transitions seems to affect the DeltaJ = &plusmn;1 transitions as shown by the difference in the intensities of the DeltaJ = +1 and DeltaJ = -1 transitions. Measurements of the intensity of the 03(3e)0-00(0)0 and 03(3f)0-00(0)0 transitions shows that they derive most, but perhaps not all, of their intensity from l-type resonance. An unsuccessful search for forbidden DeltaJ = 0, e-e transitions for the strong 10(0)0-00(0)0 band shows that there is no detectable mixing of the e and f levels. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Role of quantitative cultures and microscopic examinations of endotracheal aspirates in the diagnosis of pulmonary infections in ventilated patients.

Endotracheal aspirates (EA) from 20 intubated patients in a surgical intensive care unit (mean ventilation time/patient = 16.5 days) were investigated serially by performing quantitative cultures using growth of 10(5) cfu/mL as a cut-off point. Microscopic examinations were made using Giemsa's stain for polymorphonuclear neutrophils (PMN). The spectrum of pathogens encountered was determined and compared with clinical data to distinguish colonization from infection of the lower respiratory tract. Out of 301 EA cultures, 156 (51.8%) were positive and 145 (48.2%) were below the cut-off point. Counts of PMN were significantly higher in samples which gave positive cultures. Seventy-five different bacterial strains were isolated (64% were Gram-negative bacilli). Seventeen patients (85%) were colonized with Gram-negative bacteria. Nine patients (45%) developed nosocomial pneumonia (NP), five (25%) had no signs of pneumonia, and six (30%) had an uncertain status. Main causative agents for NP were Pseudomonas aeruginosa, Enterobacteriaceae and Staphylococcus aureus. Quantitative EA cultures had a sensitivity of 81.5%, a specificity of 64.8%, a positive predictive value of 55% and a negative predictive value of 87%. Our results suggest that EA quantitative cultures (cut-off value 10(5) cfu/mL), species identification and microscopic examination of EA may help to differentiate tracheobronchial colonization and infection, especially when bronchoscopic techniques are not available.

Adult↗
PubMed1997

BANYULS, a novel negative regulator of flavonoid biosynthesis in the Arabidopsis seed coat.

A mutant of Arabidopsis that accumulates a high level of red pigments within the seed coat has been isolated from a population of T-DNA-transformed plants. Genetic analysis revealed that the mutation is recessive and affects maternal seed tissues only. Due to the color of the immature seeds, this mutation was named banyuls (ban). Pigments accumulated continuously from early seed development to the desiccation stage in the seed coat of the mutant. The phenotype of the double mutant banyuls/ transparent testa confirmed the flavonoid nature of the pigments and enabled assignment of the regulatory TT (Transparent Testa) genes to two groups according to their epistatic relationship to ban. The flavonoid content of germinated ban and wild-type seedlings was similar. Plants harbouring the ban mutation had a normal formation of trichomes and root hairs and were not affected in their responses to light. The seeds of ban plants exhibited reduced germination compared to wild-type which may be a direct consequence of the high level of pigments. These results suggest that BANYULS functions as a negative regulator of flavonoid biosynthesis that prevents accumulation of pigments in the seed coat during early embryogenesis in Arabidopsis.

Anthocyanins↗