Biomedical subjects

M Albert

Publications and source records attributed to M Albert.

At least 37 records · Page 2Linked to original sources

PubMed2001

Pharmacologic interventions in suicide prevention.

Suicide rates vary by country and by mental disorder. What does not vary, though, is that the number of suicides per year is not declining and that a person with a mental disorder is more likely to commit suicide than one without such an illness. Although many pharmacologic interventions have been reported to reduce the risk of suicide among mentally ill patients, especially those with bipolar disorder, the effects of such interventions are inconsistent at best. Lithium is the only medication for which the evidence consistently shows an antisuicidal effect.

Antidepressive Agents↗

PubMed2000

Role of non-covalent enzyme-substrate interactions in the reaction catalysed by cellobiose phosphorylase from Cellulomonas uda.

Steady-state kinetic studies of the enzymic glucosyl transfer to and from phosphate catalysed by cellobiose phosphorylase from Cellulomonas uda have shown that this enzyme operates by a ternary-complex kinetic mechanism in which beta-cellobiose binds before phosphate, and beta-D-glucose and alpha-D-glucopyranosyl phosphate are released in that order. alpha-D-Glucopyranosyl fluoride (but not beta-D-glucopyranosyl fluoride) serves as alternative glucosyl donor for beta-cellobiose synthesis with a specificity constant that is one-ninth that of the corresponding enzymic reaction with alpha-D-glucopyranosyl phosphate (approximately 20000 M(-1).s(-1) at 30 degrees C). The kinetic parameters for a complete series of deoxy and deoxyfluoro analogues of D-glucose have been determined and the data yield estimates of the net strengths of hydrogen-bonding interactions with the non-reacting hydroxy groups of D-glucose at the transition state (0.8-4.0 kcal/mol, where 1 cal identical with 4.184 J) and enable the prediction of the polarities of these hydrogen bonds. Each hydroxy group functions as donor of a hydrogen for bonding to probably a charged (at 3-OH) or neutral (at 2-OH and 6-OH) acceptor group on the enzyme. The equatorial 1-OH is essential for enzyme activity. Derivatives of D-glucose in which the 1-OH or the reacting 4-OH were replaced by hydrogen or fluorine have been tested as inhibitors to measure their affinities for the sugar-binding subsite +1 (numbered from the bond-cleaving/forming site). The data show that hydrogen-bonding interactions between the 1-OH and 4-OH and charged groups on the enzyme stabilize the ground-state ternary complex of the enzymic synthesis of beta-cellobiose by 2.3 and 0.4 kcal/mol, respectively, and assist the precise positioning of beta-D-glucose for catalysis.

Actinomycetales↗

PubMed2000

Chiral determination of amino acids by capillary electrophoresis and laser-induced fluorescence at picomolar concentrations.

In this publication we present results on the determination of enantiomers of amino acids at very low concentrations. A fluoresceine-based chiral dye was synthesized to allow the separation of diastereoisomers of D- and L-amino acids. We used capillary electrophoresis with different non-ionic surfactants (Brij). The separation parameters were optimized and separations of D- and L-isovaline, an unusual terrestrial amino acid, were obtained. The sensitivity limits were also determined using a commercial laser-induced fluorescence detector. The quantitation of these amino acids is very important to understand the process of chiral selection on Earth.

Amino Acids↗

PubMed2000

Simultaneous detection of different glycosidase activities by 19F NMR spectroscopy.

A fast method for the simultaneous detection of different glycosidolytic activities in commercially available enzyme preparations and crude culture filtrates was found in using, as substrate, a mixture of different glycosyl fluorides and 19F NMR spectroscopy as a screening technique. Accompanying studies regarding the hydrolytic stability of these fluorides in various buffer systems, as well as conditions of their long-term storage, were carried out. A simple procedure for the preparation of beta-D-mannopyranosyl fluoride in gram quantities is given.

Fluorine↗

PubMed2000

Transglycosylation reactions with a crude culture filtrate from Thermoascus aurantiacus.

Some characteristics of regioselectivity and acceptor tolerance in transglycosylation reactions, catalysed by a crude culture filtrate from Thermoascus aurantiacus, were examined by employing methanol and monosaccharides as acceptors. When beta-D-mannopyranosyl fluoride was employed as the donor, the anomeric configuration of the newly formed bond was found to depend on the structure of the acceptor used.

Ascomycota↗

PubMed2000

Synthesis of deoxyfluoro sugars from carbohydrate precursors.

Results obtained over the past decade concerning the introduction of the fluorine atom into carbohydrate molecules, either by nucleophilic substitution or electrophilic addition reactions, are summarised. The first section mainly deals with the triflate/fluoride tandem sequence and the DAST-reaction. In the discussion, emphasis is given to the dependency of the reaction course on the stereochemical and protecting group features. Possible reaction pathways are direct substitution (with inversion or retention of configuration), rearrangement (combined with substitution and inversion of configuration at both of the centres involved) and elimination. Based on the assumption of cyclic transition states or transient intermediates (formed through participation of neighbouring groups), far-reaching mechanistic generalisations were made. On this basis, isolated examples from the literature, which are not in accordance with these generalisations, are specifically brought to attention. Results from the recently introduced reaction of safe and easy to handle N-F fluorinating agents with glycals are also reported. This approach allows the simple and stereoselective access to a series of 2-deoxy-2-fluoro aldopyranoses, as well as the synthesis of various C-1-substituted derivatives by an easy one-pot reaction. However, the same method applied to furanoid glycals is rather poor with respect to stereoselectivity. Finally, considerations on the importance of fluorine-specific reactions of the S(N)-type in related fields of organic synthesis are made.

Carbohydrates↗

PubMed2000

Predicting conversion to Alzheimer disease using standardized clinical information.

OBJECTIVE: To identify aspects of a standardized clinical assessment that can predict which individuals within the category of "questionable" Alzheimer disease (AD) have a high likelihood of converting to AD over time. DESIGN: Detailed semistructured interviews were performed at baseline and annually for 3 years. SETTING: University-based gerontology research program. PATIENTS: The patient population consisted of 165 individuals 65 years and older: 42 of the participants had a Clinical Dementia Rating (CDR) of normal cognition (CDR rating, 0.0) and 123 had a rating of questionable AD (CDR rating, 0.5). After 3 years of follow-up, 23 of the 123 subjects with questionable AD were diagnosed with probable AD. MAIN OUTCOME MEASURES: The interview was used to generate a summary measure based on the sum of 6 CDR categories, known as the Total Box Score. The responses to 32 selected questions from the interview also were examined. RESULTS: Likelihood of progression to AD during the follow-up period was strongly related to the Total Box Score. For example, more than 50% of individuals with a Total Box Score of 2.0 or higher at baseline developed AD during the follow-up interval, whereas about 10% of individuals with a Total Box Score of 1.0 or lower developed AD during this same period. Selected questions from the standardized clinical interview also were highly predictive of subsequent conversion to AD among the study population. Eight selected questions from the clinical interview at baseline, combined with the CDR Total Box Score, identified 88.6% of such individuals accurately (questionable group, 82/91; converter group, 19/23). CONCLUSIONS: A standardized clinical assessment can be used to identify the subgroup of individuals within the category of questionable AD who have a high likelihood of converting to AD over time. Subjects who met the criteria for questionable AD had a variety of trajectories during a 3-year follow-up, suggesting that diverse factors may influence the functional changes observed in this population.

Aged↗

PubMed2000

Isolation and characterisation of two sperm membrane proteins recognised by sperm-associated antibodies in infertile men.

Antisperm antibodies eluted from the surface of spermatozoa obtained from infertile men recognised several common epitopes. We tested whether these epitopes were relevant to fertility by isolating the immunodominant 37/36 and 19/18 protein zones. These protein zones were cut out of preparative slab gels and electro-eluted. The isolated proteins, P36 and P18, were used for biochemical characterisation and to produce specific antibodies in rabbits. The specific reactivity of P36 and P18 with WGA and AAL lectins, respectively, indicated the presence of lactosaminyl structures with sialic acid termini in P36 and of fucosylated residues in P18. Isoelectric focusing showed that the two proteins consist of several polypeptides. Some of these polypeptides were recognised by both human and rabbit antibodies: the pl of these epitopes was around 5.5 for P36 and 8.3-10.3 for P18. Rabbit antibodies detected the corresponding proteins on the sperm heads of methanol-fixed and of live acrosome-reacted spermatozoa. Anti-P36 antibodies bound mainly to the equatorial segment. They reduced the binding and, consequently, the penetration of zona-free hamster oocytes by human spermatozoa. Anti-P18 antibodies gave more diffuse staining of the acrosomal and post-acrosomal regions and reduced sperm-oocyte penetration without a significant effect on sperm binding. These results suggest that P36 and P18 antigens located in different compartments of the sperm head may participate in the sperm-oolemma interaction. We are currently investigating the physiological role of these antigens by sequencing the proteins isolated from the gels.

Animals↗

PubMed2000

Simultaneous measurements of temperature and pH in vivo using NMR in conjunction with TmDOTP5-.

NMR techniques for temperature and pH measurements have attracted increasing interest in recent years, motivated in part by the growing importance of medical hyperthermia for the treatment of cancer. The chemical shifts of thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetrakis(methylene phosphonate) (TmDOTP5-) have been studied as a function of temperature and pH. The results demonstrate that TmDOTP5- resonance shifts are highly sensitive to temperature (approximately 1.0 ppm/degrees C) and pH (approximately 3.2 ppm/pH unit) at clinically relevant field strengths. A new method is presented which utilizes two magnetically non-equivalent protons in TmDOTP5- for simultaneous NMR measurements of both temperature and pH. The difference in the chemical shift values of pairs of 1H resonances provides a temperature sensitivity of about 1.6 ppm/ degrees C. The technique is demonstrated in live rats undergoing ultrasound-induced hyperthermia therapy.

Animals↗

PubMed2000

The extracellular matrix molecule tenascin-R and its HNK-1 carbohydrate modulate perisomatic inhibition and long-term potentiation in the CA1 region of the hippocampus.

Perisomatic inhibition of pyramidal cells regulates efferent signalling from the hippocampus. The striking presence of HNK-1, a carbohydrate expressed by neural adhesion molecules, on perisomatic interneurons and around somata of CA1 pyramidal neurons led us to apply monoclonal HNK-1 antibodies to acute murine hippocampal slices. Injection of these antibodies decreased GABAA receptor-mediated perisomatic inhibitory postsynaptic currents (pIPSCs) but did not affect dendritic IPSCs or excitatory postsynaptic currents. The decrease in the mean amplitude of evoked pIPSCs by HNK-1 antibodies was accompanied by an increase in the coefficient of variation of pIPSC amplitude, number of failures and changes in frequency but not amplitude of miniature IPSCs, suggesting that HNK-1 antibodies reduced efficacy of evoked GABA release. HNK-1 antibodies did not affect pIPSCs in knock-out mice deficient in the extracellular matrix molecule tenascin-R which carries the HNK-1 carbohydrate as analysed by immunoblotting in synaptosomal fractions prepared from the CA1 region of the hippocampus. For control, HNK-1 antibody was applied to acute sections of mice deficient in the neural cell adhesion molecule NCAM, another potential carrier of HNK-1, and resulted in decrease of pIPSCs as observed in wild-type mice. Reduction in perisomatic inhibition is expected to promote induction of long-term potentiation (LTP) by increasing the level of depolarization during theta-burst stimulation. Indeed, LTP was increased by HNK-1 antibody applied before stimulation. Moreover, LTP was reduced by an HNK-1 peptide mimic, but not control peptide. These results provide first evidence that tenascin-R and its associated HNK-1 carbohydrate modulate perisomatic inhibition and synaptic plasticity in the hippocampus.

Animals↗

PubMed2000

Linear response theory for detectors consisting of discrete arrays.

The optical transfer function (OTF) and the noise power or Wiener spectrum are defined for detectors consisting of a lattice of discrete elements with the assumptions of linear response, Gaussian statistics, and stationarity under the discrete group of translations which leave the lattice fixed. For the idealized classification task of determining the presence or absence of a signal under signal known exactly/background known exactly (SKE/BKE) conditions, the Wiener spectrum, the OTF, along with an analog of the gray-scale transfer characteristic, determine the signal-to-noise ratio (SNR), which quantifies the ability of an ideal observer to perform this task. While this result is similar to the established result for continuous detectors, such as screen-film systems, the theory of discrete lattices of detectors must take into account the fact that the lattice only supports a bounded but (in the limit of a detector of arbitrarily great extent) continuous range of frequencies. Incident signals with higher spatial frequencies appear in the data at lower aliased frequencies, and there are pairs of signals which are not distinguishable by the detector (the SNR vanishes for the task of distinguishing such signals). Further, the SNR will in general change if the signal is spatially displaced by a fraction of the lattice spacing, although this change will be small for objects larger than a single pixel. Some of the trade-offs involved in detectors of this sort, particularly in dealing with signal frequencies above those supported by the lattice, are studied in a simple model.

Fourier Analysis↗

PubMed1999

Clinical and quantitative pathologic correlates of dementia with Lewy bodies.

OBJECTIVES: To examine the distribution of cortical Lewy bodies (LB) and their contribution to the clinical syndrome in dementia with LB (DLB) and to address their relationship to the pathologic markers of AD and PD. METHODS: We studied 25 cases meeting neuropathologic criteria for DLB: 13 cases without AD (Braak stage I or II) and 12 cases with concomitant AD changes (Braak stages III to V). Age at onset, disease duration, and clinical symptoms were reviewed for each case. We quantified the regional distribution of LB in substantia nigra, paralimbic areas (cingulate gyrus, insula, entorhinal cortex, and hippocampus), and neocortex (frontal and occipital association areas) using anti-alpha-synuclein immunostaining. We compared the LB pathology between groups of patients with different symptoms at onset or with specific clinical phenotypes. RESULTS: There were no significant differences in clinical symptoms or LB density between cases with or without concomitant AD. LB density showed a consistent gradient as follows: substantia nigra > entorhinal cortex > cingulate gyrus > insula > frontal cortex > hippocampus > occipital cortex. LB density in substantia nigra and neocortex was not significantly different in cases that started with parkinsonism compared with those that started with dementia. There were no significant differences in LB density in any region among patients with or without cognitive fluctuations, visual hallucinations, delusions, recurrent falls, or parkinsonism. Duration of the disease correlated with a global LB burden for each case (p = 0.02) but did not correlate with LB density in any individual area. Paralimbic and neocortical LB density were highly correlated with each other (p<0.0001), but neither of these correlated well with the number of LB in substantia nigra. LB density did not correlate with Braak stage or frequency of neuritic plaques. CONCLUSIONS: There is a consistent pattern of vulnerability to LB formation across subcortical, paralimbic, and neocortical structures that is similar for DLB cases with or without concomitant AD. Paralimbic and neocortical LB do not correlate with LB in substantia nigra, suggesting that DLB should not be considered just a severe form of PD. LB density correlates weakly with clinical symptoms and disease duration.

Age of Onset↗

PubMed1999

Bone mineral density in sixty adult patients with Marfan syndrome.

Sixty adult patients (40 women, 20 men) with Marfan syndrome (MFS) according to the Berlin criteria had a full clinical examination and bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry of the hip and nondominant forearm. BMD was expressed as a Z-score and compared with the reference population of the Hologic database. In MFS men, BMD (g/cm(2)) was compared with the BMD of 45 normal tall Caucasian adults. Osteocalcin was measured by radioimmunoassay. In patients with MFS, BMD was compared between patients with and without previous fractures and according to the phenotypic severity of MFS. The mean age of the patients was 32.9 +/- 9.3 years (women 32.5 +/- 9.7, men 33.4 +/- 8.6), mean height was 180.3 +/- 10.3 cm (women 176.3 +/- 9.2, men 188.1 +/- 7.5) and mean body mass index 20.9 +/- 3.6 kg/m(2) (women 20.8 +/- 3.4, men 20.95 +/- 3.97). Hyperlaxity score (Beighton criteria) was 6.9 +/- 1. 1. Six patients (10%) had a previous fracture. Thirty per cent of patients had had at least one previous operation for scoliosis, aortic dilatation or eye problems. BMD values in the 60 patients were as follows: Z-score of the hip, -1.26 +/- 0.93, p<10(-9) (neck, -0.93 +/- 1.09, p<10(-9); trochanter, -1.31 +/- 0.85, p<10(-9); intertrochanter, -1.39 +/- 0.99, p<10(-9); Ward's triangle, -0.93 +/- 1.88, p<10(-9)); Z-score of the radius: -1.6 +/- 1.06, p<10(-9) (1/3 proximal, -1.29 +/- 1.03; mid-radius, -1.94 +/- 1.04; ultradistal, -0.68 +/- 1.1, p<10(-9)). The decrease in BMD was similar in men and women at both the hip and the radius. BMD in MFS patients was significantly decreased at cortical compared with trabecular sites (radius 1/3 proximal vs ultradistal, p<0.0001; total femur vs Ward's triangle, p<0.0005). No difference in BMD was found between MFS patients with or without previous fractures and those with severe or less severe phenotypic expression of MFS. An influence of height and weight in MFS on BMD is suspected. Osteocalcin was not increased in our group of MFS patients. Thus both men and women with MFS have a significant deficit of BMD at the hip and radius. The decrease in BMD is present equally in both sexes and is more pronounced at predominantly cortical sites. In our group of patients we found no increase in fractures and no relation between decreased BMD and phenotypic expression of the syndrome.

Absorptiometry, Photon↗

PubMed1998

Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells.

Cells from the bone marrow can present peptides that are derived from tumors, transplants, and self-tissues. Here we describe how dendritic cells (DCs) process phagocytosed cell fragments onto major histocompatibility complex (MHC) class II products with unusual efficacy. This was monitored with the Y-Ae monoclonal antibody that is specific for complexes of I-Ab MHC class II presenting a peptide derived from I-Ealpha. When immature DCs from I-Ab mice were cultured for 5-20 h with activated I-E+ B blasts, either necrotic or apoptotic, the DCs produced the epitope recognized by the Y-Ae monoclonal antibody and stimulated T cells reactive with the same MHC-peptide complex. Antigen transfer was also observed with human cells, where human histocompatibility leukocyte antigen (HLA)-DRalpha includes the same peptide sequence as mouse I-Ealpha. Antigen transfer was preceded by uptake of B cell fragments into MHC class II-rich compartments. Quantitation of the amount of I-E protein in the B cell fragments revealed that phagocytosed I-E was 1-10 thousand times more efficient in generating MHC-peptide complexes than preprocessed I-E peptide. When we injected different I-E- bearing cells into C57BL/6 mice to look for a similar phenomenon in vivo, we found that short-lived migrating DCs could be processed by most of the recipient DCs in the lymph node. The consequence of antigen transfer from migratory DCs to lymph node DCs is not yet known, but we suggest that in the steady state, i.e., in the absence of stimuli for DC maturation, this transfer leads to peripheral tolerance of the T cell repertoire to self.

Animals↗

PubMed1998

The stereochemical course of the reaction mechanism of trehalose phosphorylase from Schizophyllum commune.

Phosphorolysis of alpha,alpha-trehalose catalyzed by trehalose phosphorylase from the basidiomycete Schizophyllum commune proceeds via net retention of anomeric configuration and yields alpha-D-glucose 1-phosphate and alpha-D-glucose as the products. In reverse reaction, only the alpha-anomers of D-glucose 1-phosphate and D-glucose are utilized as glucosyl donor and acceptor, respectively, and give exclusively the alpha,alpha-product. Trehalose phosphorylase converts alpha-D-glucose 1-fluoride and phosphate into alpha-D-glucose 1-phosphate, a reaction requiring the stereospecific protonation of the glucosyl fluoride by a Brønsted acid. The results are discussed with regard to a plausible reaction mechanism of fungal trehalose phosphorylase.

Glucose↗

PubMed1998

[Value of multidisciplinary consultation in diagnosis and survival of Marfan syndrome].

OBJECTIVES: To facilitate diagnosis, define a strategy for prevention and treatment and obtain further insight concerning Marfan's disease, we conducted a series of multidisciplinary consultations in French clinics. PATIENTS AND METHODS: Five specialists (a genetics specialist, a pediatrician or a rheumatologist, an ophthalmologist, and a psychologist) saw all the patients successively in the same clinic. A synthesis of the clinical files was prepared for analysis. Since the first consultation on 1 January 1995 and the study end on 30 June 1997, 494 patients (67% adults) participated in primary consultations, 143 were seen at follow-up consultations. RESULTS: The diagnosis of Marfan's disease was affirmed in 41% of the patients, disaffirmed in 48% and uncertain in 11%. Among the Marfan's patients, 75% were seen again within the framework of a multidisciplinary follow-up consultations. Annual work-up included cardiology (echocardiography with measurement of the proximal aorta diameter in search for indication for beta-blocker therapy or preventive valve replacement), ophthalmology (lens, retina) and rheumatology examinations (skeletal involvement). CONCLUSION: Early diagnosis and rigorous follow-up can help prevent ocular and cardiac complications in Marfan's disease. The multidisciplinary approach provides more precise data for diagnosis and possible phenotype-genotype correlations.

Adult↗

PubMed1998

Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset.

The efficacy of thalidomide (alpha-phthalimido-glutarimide) therapy in leprosy patients with erythema nodosum leprosum is thought to be due to inhibition of tumor necrosis factor alpha. In other diseases reported to respond to thalidomide, the mechanism of action of the drug is unclear. We show that thalidomide is a potent costimulator of primary human T cells in vitro, synergizing with stimulation via the T cell receptor complex to increase interleukin 2-mediated T cell proliferation and interferon gamma production. The costimulatory effect is greater on the CD8+ than the CD4+ T cell subset. The drug also increases the primary CD8+ cytotoxic T cell response induced by allogeneic dendritic cells in the absence of CD4+ T cells. Therefore, human T cell costimulation can be achieved pharmacologically with thalidomide, and preferentially in the CD8+ T cell subset.

Antibodies, Monoclonal↗

PubMed1998

A study of the efficacy of a comprehensive memory enhancement program in healthy elderly persons.

Well educated, high functioning older adults (ages 60-90) were given a comprehensive memory enhancement training program to determine the effectiveness of the program in increasing cognitive performance and positively influencing self-assessments of memory efficacy. The 68 subjects who participated in the memory enhancement training were compared to 74 subjects who were enrolled in a video control group. Between subject differences were analyzed prior to the interventions and at three time points following the interventions (immediately post, 3 months and 6 months). Only one cognitive measure, assessing verbal memory, revealed a significant difference between the groups, with participants in the memory enhancement group showing less decline from baseline than the video control group immediately following the intervention but with no difference between groups at 6 months post-intervention. Several self-report measures showed that the memory enhancement training subjects experienced improved memory functioning and decreased memory concerns relative to the video control group. The self-reported effects of the training were sustained over the 6-month follow-up period.

Adult↗