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Biomedical subjects

M Holzer

Publications and source records attributed to M Holzer.

77 records · Page 5Linked to original sources
PubMedDate not supplied

Phosphorylation of tau, Abeta-formation, and apoptosis after in vivo inhibition of PP-1 and PP-2A.

Chronic inhibition of protein phosphatases 1 and 2A in vivo was induced by infusion of okadaic acid into lateral ventricles of rat brain for up to 4 months. Cytoskeletal pathology, alterations of the amyloid precursor protein, and apoptotic cell death induced by this treatment followed a certain sequence and spatial distribution. Changes in the expression, phosphorylation, and subcellular distribution of neurofilament proteins and tau, as well as first signs of apoptotic cell death, occurred already after about 2 weeks. The distribution of apoptotic cells, however, was different from those revealing a high accumulation of hyperphosphorylated tau, indicating that those cytoskeletal pathology had no obvious sequelae for the viability of these neurones. A continuation of treatment for longer than 2 weeks induced diffuse deposits of both hyperphosphorylated tau and A beta-amyloid-immunoreactive material in white matter areas that increased in size and number over time. Because tau-phosphorylation is a regulator of the dynamic stability of microtubules, the pathology observed in the present experimental paradigm in the white matter might be viewed as an indication of a disturbed axonal transport. It is hypothesized that perturbations of the axonal transport might also be critically involved in the formation of paired helical filaments and amyloid deposits in Alzheimer's disease.

Amyloid beta-Peptides↗
PubMedDate not supplied

Progression of neurofibrillary changes and PHF-tau in end-stage Alzheimer's disease is different from plaque and cortical microglial pathology.

In terminal Alzheimer's disease (AD) the frequency of plaques was found to be reduced in single cases. To test this finding in a larger sample, and in order to determine whether the number of plaques labeled with different markers and the distribution of neurofibrillary tangles are correlated positively to each other and to the degree of dementia, a sample of 134 autopsy brains with and 15 without AD-related pathology has been examined. All of the cases were staged according to Braak and Braak. Both the frequency of plaques immunopositive for beta-amyloid, amyloid precursor protein, and apolipoprotein E and that of microglial cells in the cortex and in the white matter were determined semiquantitatively. The content and distribution of PHF-tau was ascertained by ELISA and immunohistochemistry. Both the clinical dementia rating and the global deterioration scale were used as clinical parameters retrospectively. Correlation coefficients were calculated for all parameters and differences were evaluated statistically. With progressive distribution of neurofibrillary tangles and increasing content of PHF-tau the plaque stages and the degree of cortical microglia reaction increased up to the Braak-stages IV and V, thereafter showing a slightly decreasing tendency in the investigated regions. In end-stage AD resorption of beta-amyloid seems to surpass its deposition. The microglial reaction in the white matter correlated neither with the Braak-stage nor with the accumulation of amyloid. With regard to the degree of dementia, both scales correlated well with the pathological changes. Our data show that neuronal cytoskeletal alterations progressively increase with progressive dementia until the end stage of AD in contrast to the frequencies of plaques and cortical microglial cells, and are therefore preferable for staging purposes.

Aged↗
PubMedDate not supplied

Postmortem changes in the phosphorylation state of tau-protein in the rat brain.

The phosphorylation state of tau-protein is crucial for the regulation of neuronal microtubule organization. Functional conclusions on tau-protein require an accurate assessment of phosphorylated sites. Therefore, the in vivo distribution and postmortem preservation of some phospho-epitopes on tau-protein were examined in the rat brain under different fixation and preparation conditions. Detection of tau-protein with a phosphorylation-independent antiserum revealed both axonal and somatodendritic localizations, which were not influenced by a postmortem interval of 30 min. The phospho-epitopes recognized by 12E8, AT8, and PHF-1 were mainly localized in the somatodendritic compartment. The binding sites of AT8 and PHF-1 were rapidly dephosphorylated postmortem, whereas the Tau-1 epitope was unmasked in the somatodendritic region. The axonally located phospho-epitope of AT270 and the nuclear epitope of AT100 were still detectable after a postmortem interval of 30 min. Postmortem dephosphorylation and inhibition of this process by PP1 and/or PP2A was further demonstrated on Western blot. In conclusion, rapid processing of tau-protein is essential for the correct assessment of investigations on phospho-isoforms.

Animals↗
PubMedDate not supplied

Successful automatic external defibrillator operation by people trained only in basic life support in a simulated cardiac arrest situation.

OBJECTIVE: To show whether in an in-hospital cardiac arrest, early defibrillation can also be performed by hospital staff trained only in basic life support. BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR) endorses the concept that in many settings non-medical individuals should be allowed and encouraged to use defibrillators. METHODS: Five different groups of hospital staff were evaluated whether they were able to correctly operate an automatic external defibrillator in a simulated sudden cardiac arrest situation without any prior instruction. The participants were assigned either to the 'basic life support-trained' group (BLS, n = 40, or to the 'advanced life support-trained' group (ALS, n = 40). RESULTS: All persons of the 'only BLS-trained' group delivered the three sequential ('stacked') shocks with the automatic external defibrillator when persistent ventricular fibrillation was simulated. The 'ALS-trained' persons successfully delivered the three shocks with the automatic external defibrillator in 98% of the cases. When this group used a conventional defibrillator, only 88% were able to deliver the three shocks, however they were able to do it significantly more quickly. CONCLUSION: Using an automatic defibrillator without any prior instruction, even persons trained only in BLS were able to deliver three sequential shocks in a simulated persistent ventricular fibrillation cardiac arrest.

Adult↗