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M Becher

Publications and source records attributed to M Becher.

18 recordsLinked to original sources

The neuropathology of CAG repeat diseases: review and update of genetic and molecular features.

Classification of inherited neurodegenerative diseases is increasingly based on their genetic features, which supplement, clarify, and sometimes replace the older clinical and pathologic schemata. This change has been particularly rapid and impressive for the CAG repeat disorders. In Huntington's disease, X-linked spinobulbar muscular atrophy, dentatorubropallidoluysian atrophy, and a series of autosomal dominant cerebellar atrophies, genetic advances have resolved many nosologic issues, and opened new avenues for exploration of pathogenesis. In this review, we summarize classic and current concepts in neuropathology of these CAG repeat diseases.

Genetic Linkage↗

Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin.

Huntington's disease (HD) is an inherited neurodegenerative disorder associated with expansion of a CAG repeat in the IT15 gene. The IT15 gene is translated to a protein product termed huntingtin that contains a polyglutamine (polyGln) tract. Recent investigations indicate that the cause of HD is expansion of the polyGln tract. However, the function of huntingtin and how the expanded polyGln tract causes HD is not known. We investigate potential protein-protein interactions of huntingtin using affinity resins. Huntingtin from brain extracts is retained on calmodulin(CAM)-Sepharose in a calcium-dependent fashion. We purify rat huntingtin to apparent homogeneity using a combination of DEAE-cellulose column chromatography, ammonium sulfate precipitation, and preparative SDS/PAGE. Purified rat huntingtin does not interact with CAM directly as revealed by 125I-CAM overlay. Huntingtin forms a large CAM-containing complex of over 1,000 kDa in the presence of calcium, which partially disassociates in the absence of calcium. Furthermore, an increased amount of mutant huntingtin from HD patient brains is retained on CAM-Sepharose compared to normal huntingtin from control patient brains, and the mutant allele is preferentially retained on CAM-Sepharose in the absence of calcium. These results suggest that huntingtin interacts with other proteins including CAM and that the expansion of polyGln alters this interaction.

Animals↗

On-line solid-phase extraction of piroxicam prior to its determination by high-performance liquid chromatography.

A direct method for the determination of piroxicam in plasma is described. Plasma is directly injected onto the extraction column (10 mm x 2 mm I.D., packed with 40-microns Bond Elut C2) where proxicam is separated from the plasma concomitants using a solid-phase extraction procedure. Using a laboratory-made on-line column-switching system, the drug is quantitatively transferred and separated on the analytical column (15 cm x 4.6 mm I.D., Supelcosil LC18 DB, 5 microns) followed by determination using ultraviolet absorption at 331 nm. Validation of the method demonstrated a good recovery (100%), sensitivity (limit of determination 0.2 microgram/ml, based on a 20-microliters sample volume), accuracy and precision (better than 5%). The developed method has been adopted for studying the steady-state pharmacokinetics of the drug.

Chromatography, High Pressure Liquid↗

[Quantitative study of the dendritic spins of lamina V pyramidal neurons of the frontal lobe in children with severe mental retardation].

An altered morphology and number of dendritic spines on neurons of the human cortex has been shown to be associated with aging and neuropsychiatric diseases. Proceeding on this assumption specimens from the area 10 of the frontal cortex collected out of 9 children and adolescents with severe mental retardation, aged 6 to 24 years and also 7 non-neuropsychiatric age-matched controls were processed according to the Golgi-Kopsch method. The number of dendritic spines on the apical dendrite of layer V pyramidal neurons was counted on consecutive segments 50 microns long from the cellular body. Mushroom-shaped, stubby and short, thin spines occur normally, but many apical dendrites could be found with predominantly stubby and thin spines without head in infantile brain damage. Neither spine density (spines/microns) nor spine distribution (number of spines as a function of the distance from cellular body) in the cases with infantile brain damage allowed to state a dependence on ages. Compared with controls the spine density was significant lesser in the affected children and adolescents (p less than 0.05). The spine distribution also along apical dendrite displayed a significant diminution of the number of spines in children from 100 to 500 microns from the cellular body and in adolescents in range from 100 to 250 microns only. A remarkable result was a decreased spine density about 40% in normal adolescents compared with unaffected childrens. This results seems to point out the phenomenon of a spine-overshoot. The spine density of both hemispheres was different significantly in 4 brains of the retardates and in 5 brains of the controls, resulted from right-left-comparisons. A prevalence of the right hemisphere was observed (6 brains). The changes revealed in infantile brain damage are similar to those reported in Down's syndrome, Alzheimer's disease and alcoholism and represent perhaps a morphological correlate to the mental dysfunction.

Adolescent↗

[Correlation between clinical and paraclinical findings in brain tumors in comparison with the operation site].

On the basis of clinical material consisting of 147 brain tumors, the authors carry out a comparative investigation involving the site of the ensuing operation to ascertain the accuracy of the clinical and paraclinical diagnoses. Computed tomographic findings were deliberately excluded with the intention of focusing on the accuracy attainable by traditional means. Clinical findings, X-ray examination of the skull, ophthalmological findings, electroencephalographic and echoencephalographic data, nuclear diagnosis, and angiographic findings were all taken into account.

Brain↗

[Lumbar lipomeningocele (case report)].

The authors describe a case of spinal lipomeningocele at the L2 to L4 level, detailing the properties of growth, clinical characteristics, diagnosis, and surgical therapy of such types of swelling.

Female↗

[Idiopathic adrenal cortex dystrophy with the clinical picture of Addison's disease].

Clinical and autopsy findings are reported of three cases of Addisons disease due to idiopathic dystrophy of the adrenal cortex as seen in two women, 20 and 37 years of age respectively as well as a boy of 14 years. Idiopathic dystrophy of the adrenal cortex as a cause of Addisons disease has become aware of more and more frequently for some years. Its classification as an auto-aggression disease has been made a subject for discussion. Morphological findings and immunological investigations with three own cases confirm this conception. This disease should be reminded of with regard to the problem of clinically diagnosing it and the fatal prognosis of untreated cases.

Addison Disease↗

[Correlation between reflex behavior and EEG in a brain-stem tumor].

In a female patient with a tumour of the brain stem the e.e.g. showed signs of increasing general functional disorders and additional transient high voltage monographic waves with bilateral frontal and central accentuation, which we regarded as brain stem disturbances. At the same time the authors observed a characteristic inhibition of the amplitude of brain reflexes as well as high phases of a polyphasic stimulation--response potential with stimulation of the tibial nerve. Beside these inhibition phenomena, signs of disinhibition were verified (nociceptive, trigemino-trigeminal reflex, polyphasic disinhibited brain reflex?). The photostimulation was without influence on the sensitivity of motoneurons.

Adolescent↗

Hydrogen storage in carbon nanotubes.

The article gives a comprehensive overview of hydrogen storage in carbon nanostructures, including experimental results and theoretical calculations. Soon after the discovery of carbon nanotubes in 1991, different research groups succeeded in filling carbon nanotubes with some elements, and, therefore, the question arose of filling carbon nanotubes with hydrogen by possibly using new effects such as nano-capillarity. Subsequently, very promising experiments claiming high hydrogen storage capacities in different carbon nanostructures initiated enormous research activity. Hydrogen storage capacities have been reported that exceed the benchmark for automotive application of 6.5 wt% set by the U.S. Department of Energy. However, the experimental data obtained with different methods for various carbon nanostructures show an extreme scatter. Classical calculations based on physisorption of hydrogen molecules could not explain the high storage capacities measured at ambient temperature, and, assuming chemisorption of hydrogen atoms, hydrogen release requires temperatures too high for technical applications. Up to now, only a few calculations and experiments indicate the possibility of an intermediate binding energy. Recently, serious doubt has arisen in relation to several key experiments, causing considerable controversy. Furthermore, high hydrogen storage capacities measured for carbon nanofibers did not survive cross-checking in different laboratories. Therefore, in light of today's knowledge, it is becoming less likely that at moderate pressures around room temperature carbon nanostructures can store the amount of hydrogen required for automotive applications.

Adsorption↗