Biomedical subjects

M Beck

Publications and source records attributed to M Beck.

At least 73 records · Page 4Linked to original sources

PubMed2002

Electrocardiographic signs of hypertrophy in fabry disease-associated hypertrophic cardiomyopathy.

AIMS: Fabry disease results from deficient activity of the lysosomal enzyme alpha-galactosidase A. Progressive accumulation of the major substrates leads, in both men and women, to progressive hypertrophic cardiomyopathy. We aimed to evaluate the utility of different electrocardiographic (ECG) parameters for assessing the degree and severity of hypertrophic cardiomyopathy in patients with Fabry disease. METHODS: A total of 166 ECGs of 94 hemi- and heterozygous patients with Fabry disease were analysed and compared with echocardiographic-estimated left ventricular mass (LVM). RESULTS: There was a significant (p < 0.0001) correlation between QRS duration (R2 = 0.59), 12-lead amplitude/duration product (R2 = 0.61), Sokolow-Lyon voltage/duration product (R2 = 0.52) and LVM. Analysis of receiver operating characteristics revealed that the 12-lead amplitude/duration product had the highest sensitivity-specificity relationship (p < 0.01 compared with the Cornell index). CONCLUSION: In general, ECG signs of left ventricular hypertrophy correlated well with LVM as revealed by echocardiography. Of the parameters studied, the 12-lead amplitude/duration product was the most successful at describing the severity of cardiac involvement in Fabry disease. These data suggest that ECG parameters have potential for use as a simple and cost-effective means of screening for hypertrophic cardiomyopathy in patients with Fabry disease.

Adolescent↗

PubMed2002

Progressive sudomotor dysfunction in amyotrophic lateral sclerosis.

Autonomic dysregulation is part of the complex degenerative process in amyotrophic lateral sclerosis (ALS). To investigate this, sweating was examined at rest in 39 patients with ALS in comparison with a control group. Sweat was collected over a 30 second period over the thenar and hypothenar eminences and on the sole of the foot, using a commercial device based on vapour pressure gradient. The measurements were repeated after three and six months in 10 patients for longitudinal analysis. In early ALS, patients had significantly higher skin water loss than control subjects over the thenar and the hypothenar eminences. In advanced disease stages, sweating was decreased at all sites compared with controls. A significant decline in sweat secretion of about 40% was found over a six month period. The findings suggest an abnormal sympathetic activity with hyperhidrosis in early ALS and a reduction in sweat production as the disease progresses.

Adult↗

PubMed2001

Joint quantum measurement using unbalanced array detection.

We have measured the joint Q-function of a highly multimode field using unbalanced heterodyne detection with a charge-coupled device array detector. We use spectral interferometry between a weak signal field and a strong, 100 fs duration local oscillator pulse to reconstruct the joint quadrature amplitude statistics of about 25 temporal modes. By adjusting the time delay between the signal and local oscillator pulses we are able to shift all the classical noise to modes distinct from the signal. This obviates the need to use a balanced detector.

Journal Article↗

PubMed2001

Investigating the microenvironments of inhomogeneous soft materials with multiple particle tracking.

We develop a multiple particle tracking technique for making precise, localized measurements of the mechanical microenvironments of inhomogeneous materials. Using video microscopy, we simultaneously measure the Brownian dynamics of roughly one hundred fluorescent tracer particles embedded in a complex medium and interpret their motions in terms of local viscoelastic response. To help overcome the inherent statistical limitations due to the finite imaging volume and limited imaging times, we develop statistical techniques and analyze the distribution of particle displacements in order to make meaningful comparisons of individual particles and thus characterize the diversity and properties of the microenvironments. The ability to perform many local measurements simultaneously allows more precise measurements even in systems that evolve in time. We show several examples of inhomogeneous materials to demonstrate the flexibility of the technique and learn new details of the mechanics of the microenvironments that small particles explore. This technique extends other microrheological methods to allow simultaneous measurements of large numbers of probe particles, enabling heterogeneous samples to be studied more effectively.

Journal Article↗

PubMed2001

Evaluation of the energetic position of the lowest excited singlet state of beta-carotene by NEXAFS and photoemission spectroscopy.

In carotenoids the lowest energetic optical transition belonging to the pi-electron system is forbidden by symmetry, therefore the energetic position of the S(1) (2(1)A(g)) level can hardly be assessed by optical spectroscopy. We introduce a novel experimental approach: For molecules with pi-electron systems the transition C1s-->2p(pi*) from inner-atomic to the lowest unoccupied molecular orbital (LUMO) appears in X-ray absorption near edge spectra (NEXAFS) as an intense, sharp peak a few eV below the carbon K-edge. Whereas the peak position reflects the energy of the first excited singlet state in relation to the ionization potential of the molecule, intensity and width of the transition depend on hybridization and bonding partners of the selected atom. Complementary information can be obtained from ultraviolet photoelectron spectroscopy (UPS): At the low binding energy site of the spectrum a peak related to the highest occupied molecular orbital (HOMO) appears. We have measured NEXAFS and UPS of beta-carotene. Based on these measurements and quantum chemical calculations the HOMO and LUMO energies can be derived.

Electron Probe Microanalysis↗

PubMed2001

Microinjection and growth of bacteria in the cytosol of mammalian host cells.

Most facultative intracellular bacteria replicate in specialized phagosomes after being taken up by mammalian cells. Relatively few intracellular bacteria escape the phagosomal compartment with the help of cytolytic (pore-forming) proteins and replicate in the host cell cytosol. Without such toxins, intracellular bacteria cannot reach this cellular compartment. To circumvent the requirement of an "escape" step, we developed a procedure allowing the efficient direct injection of bacteria into the cytosol of mammalian cells. With this technique, we show that most bacteria, including extracellular bacteria and intracellular pathogens that normally reside in a vacuole, are unable to replicate in the cytosol of the mammalian cells. In contrast, microorganisms that replicate in the cytosol, such as Listeria monocytogenes, Shigella flexneri, and, to some extent, enteroinvasive Escherichia coli, are able to multiply in this cellular compartment after microinjection. Further L. monocytogenes with deletion in its PrfA-regulated hpt gene was found to be impaired in replication when injected into the cytosol. Complementation of the hpt mutation with a plasmid carrying the wild-type hpt gene restored the replication ability in the cytosol. These data indicate that cytosolic intracellular pathogens have evolved specific mechanisms to grow in this compartment of mammalian cells.

Animals↗

PubMed2001

Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient.

Sialidosis is a lysosomal storage disease caused by the deficiency of alpha-N-acetylneuraminidase (NEU1; sialidase), the key enzyme for the intralysosomal catabolism of sialylated glycoconjugates. We have identified a homozygous transversion in the last intron (IVSE +1 G>C) in neu1 of a sialidosis patient. Sequencing of the truncated cDNA revealed an alternatively spliced neu1 transcript which lacks the complete sequence of exon 5. Skipping of exon 5 leads to a frameshift and results in a premature termination codon. This is the first description of an intronic point mutation causing a complete deficiency of the lysosomal neuraminidase activity.

Amino Acid Sequence↗

PubMed2001

Towards time-resolved, coupled structure-function information on carotenoid excited state processes: X-ray and optical short-pulse double resonance spectroscopy.

A novel soft X-ray and optical short-pulse double resonance spectroscopic technique tailor-made to elucidate processes involving the optically forbidden S1 (2(1)A(g)) state of carotenoids in native biological samples (e.g., photosynthetic antenna complexes) is described. The principle relies on probing the near carbon K-edge absorption of the optically excited sample with soft X-rays generated by a laser-induced plasma. A first application concerns location of the 2(1)A(g) state of beta-carotene in vitro. Further applications are proposed.

Biophysics↗

PubMed2001

[Diagnosis and therapy of Gaucher disease. Current recommendations of German therapy centers in the year 2000].

BACKGROUND: Gaucher's disease is the autosomally recessively inherited deficiency of the lysosomal enzyme glucocerebrosidase. Increasing storage of glucocerebrosides leads to a multisystem disease, the prevalence of which is about 1:40,000 in central Europe and up to 1:2,000 in some other countries (e.g. Israel). The acute and chronic neuronopathic forms of the disease (formerly defined as Gaucher types 2 and 3) account for only 5 to 10% of all Gaucher patients in Central Europe and Germany and are thus less frequent than the non-neuronopathic disease (formerly defined as Gaucher type 1). Gaucher's disease is usually associated with spleno- and hepatomegaly, fatigue, skeletal complications, and several corresponding hematological and laboratory abnormalities. In 5 to 10% of the patients there are also central nervous symptoms such as myoclonic seizures, oculomotoric apraxia and a slight mental retardation. METHODS: Four specialized centers care for more than 2/3 of all German Gaucher patients today. These centers present their consensus recommendations for state-of-the-art diagnosis and treatment of Gaucher's disease. RESULTS: Recent epidemiological data indicate that only 10 to 20% of all Gaucher patients are correctly diagnosed (and treated) in Germany. The diagnosis today can be done in all patients by noninvasive methods, i.e. determination of the glucocerebrosidase activity in peripheral leukocytes and of the genetic defect. The current enzyme replacement therapy with glucocerebrosidase has proven effective to improve and often normalize hematological abnormalities, hepatosplenomegaly, skeletal complications and quality of life, provided that the therapy is started early and is given at adequate dosages. CONCLUSION: In view of the availability of an effective therapy, efforts should be made to increase the awareness of Gaucher's disease in differential diagnosis, to help to diagnose the disease with noninvasive techniques at early stages, and to provide practical guidelines for adequate treatment.

Chromosome Aberrations↗

PubMed2001

Molecular genetic alterations in glioblastomas with oligodendroglial component.

Glioblastoma multiforme is the most malignant astrocytic glioma and usually resistant to chemotherapy. A small fraction of glioblastomas may contain areas with histological features of oligodendroglial differentiation. To determine the molecular genetic alterations in such "glioblastomas with oligodendroglial component", we investigated 13 of these tumors for genetic alterations and/or expression of the TP53, CDKN2A, PTEN, and EGFR genes. In addition, we performed microsatellite analyses for loss of heterozygosity (LOH) on chromosome arms 1p, 19q and 10q. None of tumors showed evidence for LOH on 10q. LOH on 1p was detected in 3 tumors, 1 of which additionally showed LOH on 19q. The 3 tumors with LOH on 1p showed neither TP53 mutations nor nuclear p53 accumulation. In contrast, 9 of 10 tumors without demonstrated losses on 1p showed nuclear p53 accumulation. TP53 mutations were identified in 3 of these cases. Further aberrations detected were epidermal growth factor receptor (EGFR) overexpression (3 of 13 tumors), homozygous CDKN2A deletion (2 of 11 tumors), and PTEN mutation (1 of 13 tumors). Taken together, our results indicate that "glioblastomas with oligodendroglial component" carry heterogeneous genetic alterations. LOH on 10q, PTEN mutation, and homozygous CDKN2A deletion appear to be less common in these tumors as compared to ordinary glioblastomas. Furthermore, a subset of these tumors demonstrates LOH on 1p, i.e., an alteration that has recently been linked to chemosensitivity and good prognosis in anaplastic oligodendrogliomas.

Adult↗

PubMed2001

Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B.

An inherited deficiency in beta-galactosidase can result in GM1 gangliosidosis, with several phenotypes of generalized or chronic psychomotor deterioration, as well as in Morquio disease type B, a characteristic mucopolysaccharidosis free of neurological symptoms. We performed mutation analyses in 17 juvenile and adult patients from various European regions with a deficiency in beta-galactosidase and skeletal abnormalities. Fifteen of these had the Morquio B phenotype and have remained neurologically healthy until now while the two others exhibited psychomotor retardation of juvenile onset. A two-base substitution (851-852TG-->CT; W273L) was present in 14 of the 15 Morquio B cases. Even if one excludes alleles from patients with possible common descent, there was a much higher frequency (79%) among those with Morquio B phenotype for the W273L mutation than previously reported in the literature (37%). That the Morquio phenotype is also expressed in heterozygotes for W273L and alleles typically found in GM1 gangliosidosis makes it possible to predict the phenotype and reliably detect heterozygotes. A single French patient had a novel missense point mutation (Q408P) together with a known mutation (T500A) while the mentally retarded patients were both heterozygous for two mutations known in chronic GM1 gangliosidosis together with two novel missense point mutations (Y270D and H281Y) in the vicinity of W273L. Our results confirm the high impact of Trp 273 for the function of beta-galactosidase and the expression of the Morquio B phenotype. In addition, a second domain around the amino acids 400-500 may also be of significance.

Adolescent↗

PubMed2001

Two distinct reproductive strategies are correlated with an ovarian phenotype in co-existing parthenogenetic strains of a parasitic wasp.

The question whether different organisms are able to compete for the same resource is of fundamental importance to evolutionary biology. Sympatric co-existence of similar species on a single resource has long been claimed to be unstable. However, indirect evidence suggests that parasitic wasps exhibit evolutionarily stable mixtures of life-history strategies. Here we describe genetically distinct strains of a parthenogenetic wasp Venturia canescens, with different ovarian phenotypes that affect egg numbers in oviducts. Wasp females with large egg load search for caterpillars and deposit eggs immediately after host encounter, whereas females with fewer eggs delay parasitism. Since the outcome of interlarval competition within super-parasitized caterpillars depends on the age distribution of competing larvae, the two egg deposition strategies may co-exist under conditions that favor super-parasitism.

Journal Article↗

PubMed2001

TP53 gene mutations, nuclear p53 accumulation, expression of Waf/p21, Bcl-2, and CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma multiforme.

Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain tumor with a median survival of less than one year despite multimodal treatment regimens. However, a small subgroup of GBM patients has a better clinical outcome, with a small number of patients surviving several years. Apoptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signaling pathways, cancer cells may escape apoptosis, despite carrying irreversible DNA damage. In the present study, we have analyzed tumors of two age-matched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 54), and 'long-term' for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs. The percentage of alterations in genes/proteins involved in the apoptotic pathway investigated here was virtually identical in the two groups of clinically different GBM patients. Thus, our data imply that none of these alterations investigated per se has a strong impact on the overall survival of GBM patients.

Adult↗

PubMed2001

Variable clinical presentation in lysosomal storage disorders.

Extensive clinical heterogeneity is seen in lysosomal storage disorders, regarding the age of onset and severity of symptoms, the organs involved, and effects on the central nervous system. A broad phenotypic spectrum is seen, for example, in mucopolysaccharidosis type I (Hurler/Scheie disease), Gaucher disease, the several forms of GM2-gangliosidosis and the different manifestations of beta-galactosidase deficiency (GM1-gangliosidosis and Morquio disease type B). Variable clinical expression of the same enzyme defect is not well understood. The presence of different mutations is only part of the explanation, as intrafamilial variability is observed in many cases. Other mechanisms, for example the effect of specific activators, may also have an influence on phenotype.

Disease Progression↗

PubMed2001

Anderson-Fabry disease: clinical manifestations of disease in female heterozygotes.

Anderson-Fabry disease is a rare, X-chromosomal lipid storage disorder caused by a deficiency of lysosomal alpha-galactosidase A. Clinical manifestations of Anderson-Fabry disease include excruciating pain in the extremities (acroparaesthesia), skin vessel ectasia (angiokeratoma), corneal and lenticular opacity, cardiovascular disease, stroke and renal failure, only renal failure being a frequent cause of death. Heterozygote female carriers have often been reported as being asymptomatic or having an attenuated form of the disease. To evaluate the spectrum of clinical signs in heterozygotes, a comprehensive clinical examination was performed on 20 carriers of Anderson-Fabry disease. This revealed that, in addition to the skin manifestation, various other clinical manifestations of the disease are present, including acroparaesthesia, kidney dysfunction, cerebrovascular disease, and gastrointestinal and heart problems. It therefore appears that Anderson-Fabry disease affects both hemizygotes and heterozyotes and therefore should be considered to be an X-linked dominant disease.

Adolescent↗

PubMed2001

Limited impact of lifestyle education in patients with Type 2 diabetes mellitus and microalbuminuria: results from a randomized intervention study.

AIMS: To assess the effect of intensified education on lifestyle (diet, exercise and smoking) as part of an intensified multifactorial intervention over a 4-year period in patients with Type 2 diabetes mellitus with microalbuminuria. METHODS: Patients, aged 45-65 years, were randomly assigned either to an intensive group focusing on change of behaviour as well as polypharmacological treatment (n = 80) or to a control group receiving conventional treatment (n = 80). Diet intervention focused on dietary fat and carbohydrate. Food intake was estimated by dietary history interviews and nutrients were calculated from food tables. Exercise and smoking habits were evaluated by interviews. RESULTS: Mean follow-up was 3.8 (SD 0.3) years. The decrease in total fat intake (% of energy intake) was larger in the intensive group as compared to the control group (41.2 (6.2) to 34.2 (6.0) vs. 41.9 (6.5) to 38.3 (6.4)%, P = 0,0001). The decrease in saturated fatty acids (% of total fat intake) was from 47 (4) to 44 (6)% with intensive therapy vs. 45 (5) to 46 (5)%, P = 0.001 and the increase in polyunsaturated fatty acids was from 14 (4) to 18 (6) vs. 16 (5) to 14 (4)%, P < 0.0001. Also the increase in carbohydrate was larger with intensive therapy. However, changes in exercise and smoking habits did not differ between groups. CONCLUSION: Despite the many resources invested in behaviour modification in this study, only modest changes were obtained in nutrient intake. Further studies are required to determine the best method of inducing long-lasting changes in behaviour in Type 2 diabetic patients.

Aged↗

PubMed2001

Total hip arthroplasty in young adults after failed triple innominate osteotomy.

This study compared the results of total hip arthroplasty (THA) in 11 patients with 13 hips who underwent THA after a failed triple innominate osteotomy (TIO) with an age-matched and sex-matched group of patients who underwent THA without prior TIO. The average age at the time of THA was 37 years (range, 16-50 years). The average follow-up of the patients who underwent THA for failed TIO was 36 months and for the control group was 28 months. One hip in each group underwent revision for dislocation. At final follow-up, the average Harris hip score in the study group was 76, whereas in the control group it was 88 (P <.05). The pain component of the Harris hip score in the study group averaged 32, whereas in the control group it averaged 40 (P <.05). Functional scores between the 2 groups were similar. Radiographically, there was no difference between the 2 groups. Estimated blood loss for the hips performed for failed TIO averaged 721 mL, whereas in the control group the estimated blood loss averaged 448 mL (P <.05). There was no difference in operative time. The results of this study indicated that although the radiographic results of THA after TIO are equivalent to THA without prior TIO, clinical results in terms of pain relief and the technical difficulty of THA are not equivalent to results in young adult patients who undergo THA without prior TIO.

Adolescent↗

PubMed2001

Anesthetic efficacy of ropivacaine in maxillary anterior infiltration.

OBJECTIVE: The purpose of this prospective, randomized double-blind study was to evaluate and compare the anesthetic efficacy of 0.5% ropivacaine with 1:200,000 epinephrine, of 0.5% ropivacaine, and of 0.5% bupivacaine with 1:200,000 epinephrine in maxillary lateral incisor infiltrations. STUDY DESIGN: Forty subjects randomly received, in a double-blind manner, 3 infiltrations at 3 separate appointments, in a repeated-measures design. The injections consisted of an infiltration of 1.8 mL of 0.5% ropivacaine plain, an infiltration of 1.8 mL of 0.5% ropivacaine with 1:200,000 epinephrine, and an infiltration of 1.8 mL of 0.5% bupivacaine with 1:200,000 epinephrine (control solution). The maxillary lateral incisor pulpal anesthesia was evaluated with an electric pulp tester at 2-minute cycles for 90 minutes after injection. No response from the subject to the maximum output (80 reading) of the pulp tester was used as the criterion for pulpal anesthesia. Anesthesia was considered successful when 2 consecutive 80 readings were obtained. The duration of pulpal anesthesia was recorded as the last 80 reading. RESULTS: One hundred percent of the subjects had lip numbness with all solutions. The anesthetic success rates for ropivacaine plain, ropivacaine with epinephrine, and bupivacaine with epinephrine were 68%, 75%, and 80%, respectively. There were no significant differences (P >.05) among the solutions. The duration of pulpal anesthesia (80 readings) for ropivacaine plain, ropivacaine with epinephrine, and bupivacaine with epinephrine was 13 minutes, 33 minutes, and 33 minutes, respectively. Ropivacaine plain had a significantly shorter duration of pulpal anesthesia than ropivacaine with epinephrine. CONCLUSIONS: We concluded that 0.5% ropivacaine with 1:200,000 epinephrine was equivalent to 0.5% bupivacaine with 1:200,000 epinephrine in pharmacologic action. The duration of pulpal anesthesia was less for ropivacaine without epinephrine. Ropivacaine with epinephrine has the potential to replace bupivacaine with epinephrine in clinical dental practice because of the decreased potential for cardiac and central nervous system toxicity.

Adult↗