Biomedical subjects

M Beck

Publications and source records attributed to M Beck.

At least 55 records · Page 3Linked to original sources

PubMed2000

Quantum state tomography with array detectors.

I propose a method for measuring the quantum state of an optical field that occupies a mode having a complicated spatial structure. The technique uses array detectors and a single, plane-wave local oscillator beam. The advantage of using array detectors is that the local oscillator is not mode matched to the field being measured, yet the deleterious effects of this mismatch on the effective detection efficiency are greatly reduced compared to using single detectors. Indeed, when the spatial mode of the signal field is describable by a real function, the effective mode-matching efficiency is unity.

Journal Article↗

PubMed2000

Mid-infrared quantum cascade lasers for flow injection analysis

A Fabry-Perot quantum cascade laser (QCL) was used as a powerful light source for mid infrared (MIR) detection in flow injection analysis. The QCL lased at several wavelengths close to each other within a few wavenumbers (990-1010 cm-1), hence fitting well to the broad absorption bands of molecules in liquid phase. As compared with that of a state-of-the-art Fourier transform spectrometer, the signal-to-noise ratio could be improved by a factor of 50. Additionally, by using a QCL as the light source, optical path lengths of more than 100 microns could be used even in aqueous matrixes which reduced the danger of cell clogging. In the example shown here phosphate was determined in Diet Coke samples. The flow injection system used allowed the measurement of the sample at two pH values (5 and 13) at which the analyte was present as H2PO4- and PO4(3-), respectively. As the analytical readout the difference in IR absorption of H2PO4- and PO4(3-) at the laser wavelengths was taken. The FIA-QCL measurements were corroborated by ion chromatography which was used as a reference method.

Journal Article↗

PubMed2000

Altered phosphofructokinase mRNA levels but unchanged isoenzyme pattern in brains from patients with Alzheimer's disease.

In order to find out whether the increased phosphofructokinase (PFK) activities observed in brains from Alzheimer's disease (AD) patients are associated with alterations in PFK mRNA levels, we determined total PFK mRNA and the three different PFK isoenzyme mRNAs in AD and control patients by ribonuclease protection assay (RPA) and quantitative RT-PCR. PFK mRNA levels were found increased in some brain areas in AD patients. While all three PFK isoenzyme mRNAs were detectable in every studied brain sample, no changes of the PFK isoenzyme pattern were observed in patients with AD.

Alzheimer Disease↗

PubMed2000

Potential role of LIF as a modifier gene in the pathogenesis of amyotrophic lateral sclerosis.

Leukemia inhibitory factor (lif) is a potent survival factor for motoneurons in cell culture and in vivo. The authors screened 104 patients with ALS and 338 control subjects for mutations in the LIF gene. In four ALS patients, but in no control subject, a G-to-A point mutation at position 3400 was identified, which leads to an amino acid exchange of valine to methionine at position 64 of the mature lif protein. This region of the lif protein (AB loop) interacts with the lif receptor. The authors suggest that LIF could act as a modifier gene which, in combination with other genetic predispositions, might lead to motoneuron disease.

Adult↗

PubMed2000

Developmental motoneuron cell death and neurotrophic factors.

During the development of higher vertebrates, motoneurons are generated in excess. In the lumbar spinal cord of the developing rat, about 6000 motoneurons are present at embryonic day 14. These neurons grow out axons which make contact with their target tissue, the skeletal muscle, and about 50% of the motoneurons are lost during a critical period from embryonic day 14 until postnatal day 3. This process, which is called physiological motoneuron cell death, has been the focus of research aiming to identify neurotrophic factors which regulate motoneuron survival during this developmental period. Motoneuron cell death can also be observed in vitro when the motoneurons are isolated from the embryonic avian or rodent spinal cord. These isolated motoneurons and other types of primary neurons have been a useful tool for studying basic mechanisms underlying neuronal degeneration during development and under pathophysiological conditions in neurodegenerative disorders. Accumulating evidence from such studies suggests that some specific requirements of motoneurons for survival and proper function may change during development. The focus of this review is a synopsis of recent data on such specific mechanisms.

Animals↗

PubMed2000

Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons.

Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Abeta sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM-10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Abeta in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.

Amyloid beta-Peptides↗

PubMed2000

Guinea-pig primary cell cultures provide a model to study expression and amyloidogenic processing of endogenous amyloid precursor protein.

Until now guinea-pigs have been rarely used to investigate formation and deposition of Alzheimer's disease-associated amyloid beta peptides despite the sequence identity of human and guinea-pig amyloid beta peptides being known, and the overall similarity of human and guinea-pig amyloid precursor protein. We now describe a primary cell culture system of mixed fetal guinea-pig brain cells, which we have applied to characterize endogenous amyloid precursor protein processing and amyloid beta formation. These cell cultures were established at embryonic day 24 of guinea-pigs after comparison of selected stages of guinea-pig ontogenetic development with the known ontogeny of rats, and were characterized by immunocytochemical detection of neuronal and glial marker proteins. Amyloid precursor protein expression, processing and amyloid beta formation increased in parallel with cellular maturation during cultivation and reached a stable phase after approximately 14 days in vitro therefore providing a suitable time for analysis. Aged cultures display strong neuronal amyloid precursor protein immunoreactivity and an altered profile of amyloid precursor protein isoform messenger RNA expression due to glial proliferation as single neurons were shown to retain their typical pattern of amyloid precursor protein expression. We show that amyloid precursor protein in guinea-pig cells is processed by different protease activities which most likely represent alpha- and beta-secretase, leading to the generation of soluble amyloid precursor protein derivatives. Furthermore, endogenous amyloid precursor protein processing leads to production of substantial amounts of amyloid beta-peptides which accumulate in conditioned culture medium. Amyloid beta was readily detectable by western blot analysis and was shown to consist of approximately 80-90% amyloid beta(1-40). We suggest that primary guinea-pig cell cultures provide a valuable tool in amyloid research that resembles amyloid precursor protein processing under physiological concentrations and, therefore, the situation in humans more closely than current rodent models. It should be especially useful in screening experiments for secretase inhibiting compounds.

Amyloid↗

PubMed2000

Anesthetic efficacy and heart rate effects of the intraosseous injection of 1.5% etidocaine (1:200,000 epinephrine) after an inferior alveolar nerve block.

OBJECTIVE: The purpose of this study was to determine the anesthetic efficacy and heart rate effects of an intraosseous (IO) injection of 1.5% etidocaine with 1:200,000 epinephrine after an inferior alveolar nerve block. STUDY DESIGN: In a repeated-measures designed study, 48 subjects randomly received 2 combinations of injections at 2 separate appointments. The combinations were an inferior alveolar nerve (IAN) block (with 3% mepivacaine) + IO injection with 1.8 mL of 1.5% etidocaine hydrochloride containing 1:200,000 epinephrine, and an IAN + mock IO injection. The first molar was blindly tested with a pulp tester at 2-minute cycles for 60 minutes after the injection. Anesthesia was considered successful when 2 consecutive 80 readings (no subject response) were obtained. Heart rate (pulse rate) was measured with a pulse oximeter. RESULTS: Lip numbness occurred in 100% of the subjects with both the techniques. For the first molar, anesthetic success for the IAN + mock IO and the IAN + IO etidocaine hydrochloride groups, respectively, were 81% and 100%. The differences were significant (P <.05) when the IAN + IO etidocaine hydrochloride technique was compared with the IAN + mock IO. A mean increase in heart rate of 32 beats/min occurred in 90% of the subjects with the IO injection of the etidocaine hydrochloride solution. In 89% of these subjects, the heart rate returned to within 5 beats of baseline values 4 minutes or less after solution deposition. CONCLUSIONS: The IO injection of 1.8 mL of 1.5% etidocaine hydrochloride with 1:200,000 epinephrine, when used to augment an inferior alveolar nerve block, significantly increased anesthetic success in the first molar. The majority of subjects receiving the IO injection of the etidocaine hydrochloride solution had a transient increase in heart rate.

Adult↗

PubMed2000

Anesthetic efficacy and heart rate effects of the intraosseous injection of 3% mepivacaine after an inferior alveolar nerve block.

OBJECTIVE: The purpose of this study was to determine the anesthetic efficacy and heart rate effects of an intraosseous injection of 3% mepivacaine after an inferior alveolar nerve block. STUDY DESIGN: Through use of a repeated-measures design, each of 48 subjects randomly received 2 combinations of injections at 2 separate appointments. The combinations were (1) an inferior alveolar nerve block (with 1.8 mL of 3% mepivacaine) + intraosseous injection with 1.8 mL of 3% mepivacaine and (2) an inferior alveolar nerve (with 1. 8 mL of 3% mepivacaine) + mock intraosseous injection. The first molar was blindly pulp tested at 2-minute cycles for 60 minutes postinjection. Anesthesia was considered successful with 2 consecutive 80 readings. Heart rate (pulse rate) was measured with a pulse oximeter. RESULTS: All subjects had lip numbness with both of the inferior alveolar nerve + intraosseous techniques. Anesthetic success for the first molar was significantly increased for 30 minutes with intraosseous injection of mepivacaine in comparison with the inferior alveolar nerve block alone (mock intraosseous injection). Subjects receiving the intraosseous injection of mepivacaine experienced minimal increases in heart rate. CONCLUSIONS: The intraosseous injection of 1.8 mL of 3% mepivacaine, when used to augment an inferior alveolar nerve block, significantly increased anesthetic success for 30 minutes in the first molar. The 3% mepivacaine had a minimal effect on heart rate and would be useful in patients with contraindications to epinephrine use.

Adult↗

PubMed2000

Analysis of the molecular heterogeneity of the microtubule-associated protein tau by two-dimensional electrophoresis and RT-PCR.

The microtubule-associated protein tau is a member of a group of proteins, promoting assembly and stabilization of microtubules. In several tauopathic neurodegenerative disorders, namely Alzheimer's and Pick's disease and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP 17) this protein is converted into fibrilar polymers which form the component of insoluble proteanous deposits such as neurofibrillary tangles. The formation of these fibrils is believed to interrupt the physiological function of neurons resulting in degeneration and cell death. Tau protein exists as a family of heterogeneous isoforms derived by both, differential splicing of tau-mRNA and posttranslational modification of the protein. Since the role of the different isoforms during the process of neurodegeneration is not well understood and as their balance might be altered in some cases of tauopathies (Spillantini et al., Proc. Natl. Acad. Sci. USA 1998;95:7737-7741), the detailed analysis of the molecular heterogeneity gained outstanding interest. The method presented here allows the analysis of both, differential splicing and phosphorylation of tau protein by the application of two-dimensional (2D) electrophoresis and Western blot detection. Tau protein isoforms could be identified from the 2D pattern of dephosphorylated tau in concordance with the results of tau-mRNA analysis by RT-PCR. The protocol presented was successfully applied to analysis of tau isoforms of human brain (Janke et al., FEBS Lett. 1996;379:222-226) and of several species, revealing a phylogenetic correlation of tau protein patterns in mammals (Janke et al., Mol. Brain Res. 1999;68:119-128). The present paper provides a detailed description of the technique and discusses its prospects and limits.

Animals↗

PubMed2000

Molecular analysis of the PTEN, TP53 and CDKN2A tumor suppressor genes in long-term survivors of glioblastoma multiforme.

Despite multimodal therapy, glioblastoma multiforme (GBM) is associated with a poor prognosis with a median survival of less than 1 year. However, a small number of patients with GBM shows survival times of several years. Although clinical features like age and performance status at diagnosis are well known prognostic parameters, molecular markers for prognosis of overall survival are still lacking. Therefore, we compared 2 age- and gender-matched groups of GBM patients with different post-operative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 21), and 'long-term' for TTP of more than 24 months (n = 21) for genetic alterations of the PTEN, CDKN2A and TP53 genes as well as overexpression of the EGFR, p53 and Mdm2 proteins. For the GBMs with 'short-term' TTP vs. 'long-term' TTP, the studies revealed PTEN mutations in 4/21 vs. 2/21, TP53 mutations in 5/21 vs. 8/21, homozygous deletion of the CDKN2A gene in 5/21 vs. 6/21, overexpression of EGFR in 7/20 vs. 10/20, accumulation of p53 protein in 9/20 vs. 7/20 and of Mdm2 protein in 0/20 vs. 1/20 cases studied. Taken together, our data indicate that mutations of the PTEN and TP53 tumor suppressor genes, homozygous deletion of the CDKN2A gene as well as overexpression of the EGFR, p53 and Mdm2 proteins lack prognostic significance for overall survival time in patients with GBMs.

Adult↗

PubMed2000

Specificity determinants for bacteriophage Hong Kong 022 integrase: analysis of mutants with relaxed core-binding specificities.

The integrase (Int) proteins encoded by bacteriophages HK022 and lambda catalyse similar site-specific integration and excision reactions between specific DNA regions known as attachment (att) sites. However, the Int proteins of HK022 and lambda are unable to catalyse recombination between non-cognate att sites. The att sites of both phages contain weak binding sites for Int, known as 'core-type' sites. Negatively acting nucleotide determinants associated with specific core sites (lambda B', HK022 B', HK022 C) are responsible for the barrier to non-cognate recombination. In this study, we used challenge phages to demonstrate that the lambda and HK022 Ints cannot bind to core sites containing non-cognate specificity determinants in vivo. We isolated mutants of the HK022 Int, which bind the lambda B' core site. Two mutants, D99N and D99A, have changed a residue in the core-binding (CB) domain, which may be directly contacting the core site DNA. We suggest that binding to the lambda B' site was accomplished by removing the negatively charged aspartate residue, which normally participates in a conflicting interaction with the G4 nucleotide of the lambda B' site. We showed that, although our mutants retain the ability to recombine their cognate att sites, they are unable to recombine lambda att sites.

Amino Acid Sequence↗

PubMed2000

Constitutive overactivation of protein kinase C in guinea pig brain increases alpha-secretory APP processing without decreasing beta-amyloid generation.

Whilst it is generally accepted that the activation of protein kinase C (PKC) increases amyloid precursor protein (APP) secretion in vitro, the role of PKC in the regulation of APP processing and beta-amyloid generation in vivo is still not well understood. In order to address this question, we established the animal model of neocortical microencephalopathy in guinea pigs caused by in utero treatment with methylazoxymethanol acetate, a DNA-methylating substance that eliminates proliferating cells of neuroepithelial origin. The induction of this neocortical malformation is accompanied by constitutive overactivation of PKC in the neocortex of the offspring. In the cortical and hippocampal tissues of juvenile microencephalic guinea pigs (postnatal day 30), we observed significant increases in basal (by 58% and 74%, respectively,) and phorbol ester-stimulated PKC enzyme activity (by 47% and 71%) as compared to age-matched control animals. In the same cortical/hippocampal preparations of methylazoxymethanol-treated animals, there was increased alpha-secretion of APP by 35% and 30% as measured by Western blot analysis using the antibody 6E10, whilst total APP secretion as well as APP mRNA expression remained unaltered. This upregulation of APP alpha-secretion was limited to brain areas that displayed elevated PKC activity. However, constitutive overactivation of neocortical PKC did not affect the generation of beta-amyloid peptides 1-40 or 1-42 as measured by ELISA, suggesting that only the alpha-secretase pathway of APP processing is affected by chronic PKC overactivation in vivo.

Amyloid Precursor Protein Secretases↗

PubMed2000

Abnormal somatosensory evoked potentials indicate compressive cervical myelopathy in mucopolysaccharidoses.

Compressive myelopathy at the cranio-cervical junction is a complication of mucopolysaccharidoses (MPS). To detect cervical myelopathy we recorded median and posterior tibial nerve SEPs in 15 patients aged 2.4-33.4 years (median 8.8 years) with MPS I-S (n = 3), MPS IVA (n = 8) and MPS VI (n = 4). In addition to the cortical waveforms we recorded the subcortical median nerve SEPs N13b and P13 generated near the cranio-cervical junction and the lemniscal P30 after posterior tibial nerve stimulation. MRI studies in 13 subjects revealed spinal cord compression at the cranio-cervical junction in 10 patients; 5 patients had an increased signal intensity on the T2-weighted initial MRI indicating high cervical myelomalacia and 4 patients had clinical signs of cervical myelopathy. We did not find a relationship between the SEPs and spinal cord compression. Abnormal SEPs were found in the patients with MRI evidence of myelomalacia (sensitivity 1.0, specificity 1.0) and correspondingly in the patients with clinical signs (sensitivity 1.0, specificity 0.91). The SEPs consequently deteriorated in 2 subjects of 7.3 and 10.3 years of age. Abnormal SEPs indicated subclinical cervical myelopathy in 3 subjects. Cervical cord compression may be present before occurrence of clinical or electrophysiological evidence of myelopathy. However, we feel that the SEP analysis is useful to detect functional impairment of the cervical cord in patients with MPS.

Adolescent↗

PubMed2000

[Limits and possibilities of 2D video analysis in evaluating physiological and pathological foot rolling motion in runners].

Three-dimensional movements of the lower extremities in support phases are usually evaluated with the help of video analysis. This analysis is mainly done two-dimensionally in a frontal and sagittal plane. Usually, the temporal ankle of the achilles tendon respectively rear foot are analysed in the frontal plane, the knee and upper ankle angle in the sagittal plane, because their values are made responsible for different sport injuries. However, so far a correlation between different injuries and biomechanical parameters could not be proven. Often, small changes in 2D video data are discussed without considering the reliability of this method of measurement. It was the aim of this study to evaluate these parameters in 2D video analyses (2D-VA) which characterize the support phases of the foot. A second goal was to find out whether a connection between these angles and chronic achillodynia can then be sensibly proven. 32 male test persons consisting of a control group (KO, n = 14) without injuries and a group with chronic achillodynia (AD, n = 18), have been examined with the test/retest method in weekly intervals. The biomechanical running analysis was done with the help of 2D-VA in the frontal and sagittal plane on a treadmill at a speed of 80% of the individual anaerobic threshold with different shoes. The test/retest variability was for all measuring points not at all satisfying. Both groups showed big mean variations in both shoes and minimal differences in the measured angles. Because of the poor capability of reproduction of the 2D-VA for angles in the frontal plane this measuring method is only usable with restrictions for the evaluation of the support phase.

Achilles Tendon↗

PubMed2000

Effect of trephination on postoperative pain and swelling in symptomatic necrotic teeth.

OBJECTIVE: The purpose of this prospective, randomized, blinded study was to determine the effect of trephination on postoperative pain and swelling in symptomatic necrotic teeth. STUDY DESIGN: Fifty emergency patients participated, and each had a clinical diagnosis of a symptomatic necrotic tooth with associated periapical radiolucency. After endodontic treatment, patients randomly received either a trephination or mock trephination procedure. The trephination procedure used an intraosseous perforator to provide an initial opening in the cortical bone that was enlarged with files (No. 25 through No. 70) and an endodontic spoon. After surgery, each patient received ibuprofen; acetaminophen with codeine (30 mg); and a 7-day diary to record pain, percussion pain, swelling, and number and type of pain medication taken. RESULTS: The majority of patients with symptomatic necrotic teeth had significant postoperative pain and required analgesics to manage this pain. The use of a trephination procedure with an intraosseous perforator, files, and a spoon excavator did not significantly reduce pain, percussion pain, swelling, or the number of analgesic medications taken in symptomatic necrotic teeth with periapical radiolucencies (P >.05). CONCLUSION: We cannot recommend the routine use of a trephination procedure, as used in this study, for relief of pain in symptomatic necrotic teeth with radiolucencies.

Adult↗

PubMed2000

Effect of systemic penicillin on pain in untreated irreversible pulpitis.

OBJECTIVE: The purpose of this prospective, randomized, double-blind study was to determine the effect of penicillin on pain in untreated teeth diagnosed with irreversible pulpitis. STUDY DESIGN: Forty emergency patients participated, and each had a clinical diagnosis of an irreversible pulpitis. Patients randomly received a 7-day oral dose (28 capsules, 500 mg each, to be taken every 6 hours) of either penicillin or a placebo control in a double-blind manner. No endodontic treatment was performed. Each patient also received ibuprofen; acetaminophen with codeine (30 mg); and a 7-day diary to record pain, percussion pain, and number and type of pain medication taken. RESULTS: The administration of penicillin did not significantly (P >.05) reduce pain, percussion pain, or the number of analgesic medications taken by patients with untreated irreversible pulpitis. The majority of patients with untreated irreversible pulpitis had significant pain and required analgesics to manage this pain. CONCLUSION: Penicillin should not be prescribed for untreated irreversible pulpitis because penicillin is ineffective for pain relief.

Adult↗

PubMed2000

Free nerve endings in the ligamentum capitis femoris.

We report the presence of free nerve endings (FNE) in the ligamentum capitis femoris (LCF). Qualitative and quantitative measurements on the incidence of FNE, as assessed by immuno-histochemistry for the S-100 protein, were obtained from 18 patients undergoing hip surgery. We found FNE in all LCF, with no association to age. The presence of FNE in the LCF suggests a role in noci-/proprioception of the hip.

Adolescent↗