Christoph Meissner - Academia.edu (original) (raw)
Papers by Christoph Meissner
Monatsschrift Kinderheilkunde, 1999
ABSTRACT
Clinical neuropathology
We report the case of a 20-year-old male driver who suffered from a trauma to the cervical verteb... more We report the case of a 20-year-old male driver who suffered from a trauma to the cervical vertebral column in a head-on collision with a tree. The injuries included subluxation of the 2nd and 3rd cervical vertebrae and fracture of the odontoid process of the axis with ventrally directed displacement of the proximal fragment and dorsally directed displacement of the distal fragment. Already at admission to hospital a space-occupying spinal subdural hematoma was diagnosed. Clinically, paraplegia was diagnosed with progressive loss of consciousness. Pneumonia led to death 40 days after the accident. Autopsy disclosed a total myelomalacia of the cervical spinal cord obviously resulting from an ischemia caused by a traumatic lesion of the dorsal truncus arteriosus spinalis as well as a compression by the spinal subdural hematoma.
Archiv für Kriminologie
The case history presented reports on three 30- to 40-years-old men, who were found dead in a par... more The case history presented reports on three 30- to 40-years-old men, who were found dead in a party like situation in the living room. The toxicological investigation proved alcohol and THC as well as therapeutic Flunitrazepam- and Pentobarbital levels and toxic 7- Amino-Flunitrazepam concentrations. The background of this surprising scene led up to the conclusion of an accidental death caused by a mixed intoxication.
Archiv für Kriminologie
The blood morphine concentrations in cases of heroin-associated fatalities can vary considerably.... more The blood morphine concentrations in cases of heroin-associated fatalities can vary considerably. Currently, a free-morphine concentration of > or = 100 ng/ml in blood is generally considered as potentially fatal. Moreover, it is a common observation that fatal cases of heroin-intoxication with blood morphine concentrations lower than 100 ng/ml occur. This poses the question of how the fatal cases with low blood morphine concentrations can be explained. In the study described here, 62 cases of morphine only intoxications were examined. The fatal cases were divided into two groups according to the free morphine concentrations measured in the blood of the heart (group I: free morphine concentration < 100 ng/ml, n = 21 cases; group II: free morphine concentration > or = 100 ng/ml, n = 41 cases). The two groups were compared as to circumstances of death, as well as to autopsy findings and histopathologic alterations. Overall, infections of the respiratory tract occurred significantly more often in group I (lower morphine concentrations) than in group II. In a second step, the group I cases were analyzed individually to get detailed information on the cause of death. In 19 of the 21 cases the authors could find a plausible explanation for death in combination with low free morphine concentrations in the blood.
Zeitschrift für Gerontologie + Geriatrie
There is a lot of evidence that age-associated alterations of the mitochondrial genome occur, esp... more There is a lot of evidence that age-associated alterations of the mitochondrial genome occur, especially in postmitotic tissues such as brain, heart and skeletal muscle. These alterations are supposed to be a result of an attack of free radicals generated as normal byproducts of oxidative phosphorylation and lead to damage of proteins, lipids, and DNA. The alterations of mtDNA include oxidative damage of base pairs, point mutations, large-scale deletions or duplications. The 4977 bp deletion or "common deletion" reveals an age-dependent accumulation in postmitotic tissues, but not in fast-dividing tissues such as blood cells. In addition, it is observed that a tissue-specific accumulation occurs with the highest abundance in the basal ganglia, followed by skeletal muscle, heart, and lowest in cerebellar tissue. Third, pathological alterations of specific tissue, like ischemia/reperfusion events, display a pronounced accumulation of the deletion compared to age-matched cont...
Journal of Forensic Sciences
The successive killing of three siblings by their biological mother at two-year intervals is desc... more The successive killing of three siblings by their biological mother at two-year intervals is described. The children were 367 days, 75 days and 3 years old. Although sudden infant death syndrome (SIDS) or interstitial pneumonia could not be ruled out as the cause of death in the two younger children, who were killed first, the third child exhibited discrete signs of violence in the mouth and throat area which were interpreted as proof of infanticide. All three children had petechiae of the skin of the face and throat, the upper thorax, the shoulders and the mucous membranes of the mouth. None of the children exhibited signs of a disease-related hemorrhagic tendency. After the mother was convicted of murdering the three-year-old boy by smothering in combination with compression of the thorax, she confessed to having killed the other two children in a similar manner. In the absence of hemostatic disease, the presence of petechiae of the skin extending over the entire drainage area of ...
Journal of Forensic Sciences
A 7-month-old previously healthy female infant was found dead in her crib by her mother shortly a... more A 7-month-old previously healthy female infant was found dead in her crib by her mother shortly after having been laid down to sleep following the noontime feeding. Because the child did not suffer from an acute illness and no other evidence pointed to a cause of death, it was initially assumed by the police that she had died of sudden infant death syndrome. At autopsy, however, the cause of death was determined to be cardiac arrhythmia secondary to fibroma of the heart.
Experimental and Toxicologic Pathology
Quantitative changes in nucleolus organizer regions (NORs) are known markers of proliferation tha... more Quantitative changes in nucleolus organizer regions (NORs) are known markers of proliferation that can be demonstrated by a specific silver staining technique on paraffin-embedded sections. Wounding of skin induces proliferation of basal epidermal cells at the wound margin. The degree of proliferation depends on the survival time and can be measured by morphometric assessment of argyrophilic NORs (AgNORs). Following incision wounding of the pinnae, rats were allowed to survive for different intervals (7 rats per interval) up to 120 hours. Before each sacrifice, biopsies were taken and incubated in a bromodeoxyuridine (BrdU) solution, embedded in paraffin, and stained with an antibody against BrdU. At the same time morphometric analysis of AgNOR counts was performed on sections made from the same material. BrdU incorporating nuclei were assessed by simple counting, whereas morphometric analysis of AgNOR counts was computer aided. Both methods revealed an increase in the number of pro...
Zeitschrift für Gerontologie und Geriatrie, 2007
Acta neuropathologica, 2003
To determine the value of imaging procedures such as computer tomography (CT) and magnetic resona... more To determine the value of imaging procedures such as computer tomography (CT) and magnetic resonance imaging (MRI) of the head in providing additional information of forensic relevance, we examined 17 cadavers of human victims of gunshot wounds to the head. Three of the victims briefly survived the gunshot wound. The weapons involved were all guns with low muzzle energy (<550 J), i.e., handguns and low-velocity rifles. In the majority of cases ( n=15) a penetrating wound to the head was found, only two cases showed the bullet lodged in the brain. In some cases, imaging of the skull and brain was performed prior to autopsy; in others imaging took place after autopsy on the isolated, formalin-fixed brain. The imaging findings were correlated with the criminological data and the results of macroscopic and microscopic examination of the brain. The findings on the bony structures of the head provided imaging criteria for differentiation between entrance and exit of the gunshot wounds,...
Medicine, science, and the law, 2000
Various hematogenous markers were used to differentiate and quantify the types of mononuclear cel... more Various hematogenous markers were used to differentiate and quantify the types of mononuclear cells present in subcutaneous haemorrhages. Fifty samples of subcutaneous bleeding with a survival time of a few minutes to more than 48 hours were studied. The various cell types were detected using the following stains: Naphthol AS-D chloracetate esterase for myeloid cells, including mast cells; (alpha1-antichymotrypsin for monocytes/macrophages; UCHL1 for T-lymphocytes; and L26 for B lymphocytes. The percentage of monocytes/macrophages was found to increase in dependence on survival time, whereas T-lymphocytes declined. Within minutes of injury neutrophilic granulocytes had emigrated into the surrounding tissue and mast cell degranulation had occurred within the haemorrhagic zone. Esterase-positive mononuclear cells, namely metamyelocytes, were detected within minutes after injury and were still present after survival times exceeding 48 hours; however, no dependence on survival time or c...
Mutation research, Jan 3, 1998
The 4977 bp deletion in mitochondrial DNA (mtDNA) is known to accumulate with age in various huma... more The 4977 bp deletion in mitochondrial DNA (mtDNA) is known to accumulate with age in various human tissues. Findings regarding its accumulation in blood, however, have so far been contradictory. We investigated the levels of the 4977 bp deletion in mtDNA from 100 intravital and postmortem blood samples. Applying an improved version of a PCR plus silver staining of polyacrylamide gels, we could detect the 4977 bp deletion in blood of healthy individuals over 20 years of age. While the 4977 bp deletion in blood is subject to a certain age dependence, it appears to be influenced by additional factors. A Primer-Shift-Assay amplifying four different deletion-specific fragments showed that the smaller fragments were amplified with a higher amplification efficiency than the larger fragments. The deletion-specific 389 bp fragment was demonstrated in 73% of individuals over 80 years of age, but in only 46% of individuals between 21 and 30 years old whereas the largest 802 bp deletion-specifi...
Journal of Alzheimer's disease : JAD, 2014
The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid deposits, intrac... more The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid deposits, intracellular neurofibrillary tangles (NFTs), and neuronal death. Hyperphosphorylation of tau is a key factor in the generation of NFTs. Mitogen activated protein kinase 1 (MAPK1) and protein kinase C beta (PRKCB) are thought to play a role in hyperphosphorylation, and PRCKB is thought to be involved in hypoxic stress and vascular dysfunction, and to trigger MAPK phosphorylation pathways. We performed single-cell analyses of neurons with different vulnerabilities to AD-related changes. Using quantitative PCR (qPCR), we measured the levels of MAPK1 and PRKCB transcript in CA1 (high vulnerability), CA2 pyramidal cells from the hippocampus, granule cells from the cerebellum (low vulnerability), and neurons from the brain stem (nucleus tractus spinalis nervi trigemini, characterized by early neurophysiological deficits) at progressive Braak stages compared to age-matched controls. The highly vulne...
Zeitschrift f�r Gerontologie und Geriatrie, 2001
ABSTRACT Eine Vielzahl von Untersuchungen belegt, dass die Funktion der Atmungskette der Mitochon... more ABSTRACT Eine Vielzahl von Untersuchungen belegt, dass die Funktion der Atmungskette der Mitochondrien in höherem Lebensalter, besonders in postmitotischen Geweben wie Gehirn, Herz oder Skelettmuskulatur, abnimmt. Dieser Funktionsverlust scheint Folge einer Schädigung durch freie Radikale zu sein, die als Nebenprodukte bei der oxidativen Phosphorylierung anfallen und Proteine, Fette und DNA schädigen können. Die Schädigung der mitochondrialen DNA (mtDNA) umfasst oxidative Schäden der Basenpaare, Punktmutationen, Deletionen oder Duplikationen. Die häufigste Deletion der mtDNA ist 4977bp lang und zeigt eine altersabhängige Zunahme in postmitotischen Geweben. Weiterhin wird eine gewebsspezifische Zunahme beobachtet, wobei die Deletion am stärksten in den Basalganglien akkumuliert, gefolgt von Skelettmuskulatur und Herzmuskulatur, während im Kleinhirngewebe kaum deletierte mtDNA nachzuweisen ist. Ferner wird eine stärkere Akkumulation in pathologisch verändertem Gewebe (z.B. bei Ischämie) gegenüber altersgleichen Kontrollgeweben beobachtet. Obwohl einige kritische Stimmen die Bedeutung der Mitochondrien in Bezug auf die Alterungsvorgänge und die Theorie der freien Radikale anzweifeln, sprechen doch die experimentellen Daten für die wichtige Rolle der Mitochondrien im Alterungsprozess. There is a lot of evidence that age-associated alterations of the mitochondrial genome occur, especially in postmitotic tissues such as brain, heart and skeletal muscle. These alterations are supposed to be a result of an attack of free radicals generated as normal byproducts of oxidative phosphorylation and lead to damage of proteins, lipids, and DNA. The alterations of mtDNA include oxidative damage of base pairs, point mutations, large-scale deletions or duplications. The 4977bp deletion or “common deletion” reveals an age-dependent accumulation in postmitotic tissues, but not in fast-dividing tissues such as blood cells. In addition, it is observed that a tissue-specific accumulation occurs with the highest abundance in the basal ganglia, followed by skeletal muscle, heart, and lowest in cerebellar tissue. Third, pathological alterations of specific tissue, like ischemia/reperfusion events, display a pronounced accumulation of the deletion compared to age-matched controls. Because there are many mtDNA mutations, further analysis of all alterations of mtDNA will elucidate its role in the phenomenon of aging. Despite some criticisms of this free radical theory of aging, there is a lot of experimental evidence to support the important role of mitochondria in organismal aging.
Zeitschrift für Gerontologie und Geriatrie, 2007
Proceedings of the National Academy of Sciences, 2008
Neuropediatrics, 2005
In cases of traumatic brain injuries in children it may be difficult to differentiate between phy... more In cases of traumatic brain injuries in children it may be difficult to differentiate between physical abuse and accidental occurrence. This review will shed light on discriminating epidemiological as well as biomechanical data, morphological findings, and clinical features. As a basic principle, simple injuries are caused by simple mechanisms like falls whereas life-threatening injuries should be attributed to abuse until proven otherwise. Implausibilities between reported events and mechanisms by caregivers as well as more than one explanation of injury indicate suspicion of child abuse. From reviewing the literature, it can be stated that falls from less than 1.5 m lead only in few cases to severe brain injuries. Children who experienced a fall at home seldom exhibit fractures of the skull but just minor intracranial injuries without neurological deficits. Regarding biomechanical aspects, multiple or complex skull fractures, depression fractures, additional fractures of the body, and intracranial hemorrhages as a consequence of an impact are the most important findings in child abuse. Moreover, additional specific morphological criteria give evidence of clinical and/or post-mortem diagnosis of the shaken baby syndrome. These include subdural hemorrhage and laceration of the brain and retinal bleeding, epidural hemorrhage of the cervical cord, gripping marks (bruises) on chest and/or shoulders, and tearing injuries of the throat and neck muscles. Post-mortem signs of recurrent shaken baby syndrome are indicated by iron-positive cells or microglial cells in neuronal or retinal tissue. A clinical diagnosis will be dependent on the one hand on the exclusion of coagulation diseases, on the other hand on the demonstration of a subdural hemorrhage by means of neuroimaging techniques, i.e., CT and MRI, as well as retinal hemorrhage. The shaken baby syndrome will usually be observed within the first year of life. The doctor has to manifest his diagnosis to the caregivers and - before informing the caregivers - he must be sure of his diagnosis.
Mechanisms of Ageing and Development, 2005
During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and other mutations... more During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and other mutations have been reported. These structural alterations of mtDNA are assumed to cause a reduction in the respiratory chain activity and may contribute to the ageing process. Therefore, the question arises if the accumulation of deleted mtDNA is compensated in vivo by an increase of mtDNA synthesis via a feedback mechanism. We designed two human mtDNA-specific oligonucleotide probes for quantitative mtDNA analysis of 5 different tissues from 50 individuals aged from 8 weeks to 93 years. The amount of mtDNA was approximately 1.1 +/- 0.5% (4617 +/- 2099 copies) in the caudate nucleus, 1.0 +/- 0.5% (4198 +/- 2099 copies) in the frontal lobe cortex, 0.3 +/- 0.2% (1259 +/- 840 copies) in the cerebellar cortex, 1.0 +/- 0.4% (4198 +/- 1679 copies) in skeletal muscle and 2.2+/-1.3% (9235 +/- 5457 copies) in heart muscle. We did not observe any significant change in the absolute copy number during ageing in five different tissues, and therefore, found no evidence for the postulated feedback mechanism. Our study indicates that mtDNA copy number is tissue-specific and depends on the energy demand of the tissue.
Legal Medicine, 2008
Opposite to clinical laboratory findings in experimental drowning of animals (erythrocytic lysis,... more Opposite to clinical laboratory findings in experimental drowning of animals (erythrocytic lysis, hyperkalemia, and final cardial fibrillation) are the observations in drowned humans (increase of pCO2, hypoxic encephalopathy), which leads to a different pathophysiological interpretation of the drowning process. This process, however, is recently discussed again, therefore an additional study seemed to be recommended. In a retrospective study, 31 cases of near-drowning (23 cases: fresh water; 8 cases: brackish water) clinical laboratory data were analysed. While 21 of the cases were fatal with a delay of up to 180 days, 10 individuals survived the accident, four cases with severe neurological deficits. Data of pH, potassium, sodium, chloride, hemoglobin and total protein were collected during the very early post-drowning period. Nearly all cases (96%) revealed a reduction of pH due to hypoxic acidosis, and only two cases (6.5%) exhibited a slight hyperkalemia. The hemoglobin level was normal in most of the cases (83%) and slightly reduced in the others (17%) while the protein level was slightly reduced in most of the fatalities (80%). As a result of our investigation we have to state the lack of hyperkalemia as well as of an increase of the hemoglobin level indicate that there is no distinct intravascular red cell lysis due to influx of water into the vascular compartment. Therefore the death by drowning in humans in most cases is the result of a hypoxic cerebral process. A comparison with animal experiments obviously is not helpful because the drowning process in humans leads to an aspiration of only 2-4 ml water/kg, while in animal experiments more than 10 ml water/kg will be artificially aspirated leading to red cell lysis as well as to electrolyte disturbances and cardial fibrillation.
Monatsschrift Kinderheilkunde, 1999
ABSTRACT
Clinical neuropathology
We report the case of a 20-year-old male driver who suffered from a trauma to the cervical verteb... more We report the case of a 20-year-old male driver who suffered from a trauma to the cervical vertebral column in a head-on collision with a tree. The injuries included subluxation of the 2nd and 3rd cervical vertebrae and fracture of the odontoid process of the axis with ventrally directed displacement of the proximal fragment and dorsally directed displacement of the distal fragment. Already at admission to hospital a space-occupying spinal subdural hematoma was diagnosed. Clinically, paraplegia was diagnosed with progressive loss of consciousness. Pneumonia led to death 40 days after the accident. Autopsy disclosed a total myelomalacia of the cervical spinal cord obviously resulting from an ischemia caused by a traumatic lesion of the dorsal truncus arteriosus spinalis as well as a compression by the spinal subdural hematoma.
Archiv für Kriminologie
The case history presented reports on three 30- to 40-years-old men, who were found dead in a par... more The case history presented reports on three 30- to 40-years-old men, who were found dead in a party like situation in the living room. The toxicological investigation proved alcohol and THC as well as therapeutic Flunitrazepam- and Pentobarbital levels and toxic 7- Amino-Flunitrazepam concentrations. The background of this surprising scene led up to the conclusion of an accidental death caused by a mixed intoxication.
Archiv für Kriminologie
The blood morphine concentrations in cases of heroin-associated fatalities can vary considerably.... more The blood morphine concentrations in cases of heroin-associated fatalities can vary considerably. Currently, a free-morphine concentration of &amp;amp;amp;gt; or = 100 ng/ml in blood is generally considered as potentially fatal. Moreover, it is a common observation that fatal cases of heroin-intoxication with blood morphine concentrations lower than 100 ng/ml occur. This poses the question of how the fatal cases with low blood morphine concentrations can be explained. In the study described here, 62 cases of morphine only intoxications were examined. The fatal cases were divided into two groups according to the free morphine concentrations measured in the blood of the heart (group I: free morphine concentration &amp;amp;amp;lt; 100 ng/ml, n = 21 cases; group II: free morphine concentration &amp;amp;amp;gt; or = 100 ng/ml, n = 41 cases). The two groups were compared as to circumstances of death, as well as to autopsy findings and histopathologic alterations. Overall, infections of the respiratory tract occurred significantly more often in group I (lower morphine concentrations) than in group II. In a second step, the group I cases were analyzed individually to get detailed information on the cause of death. In 19 of the 21 cases the authors could find a plausible explanation for death in combination with low free morphine concentrations in the blood.
Zeitschrift für Gerontologie + Geriatrie
There is a lot of evidence that age-associated alterations of the mitochondrial genome occur, esp... more There is a lot of evidence that age-associated alterations of the mitochondrial genome occur, especially in postmitotic tissues such as brain, heart and skeletal muscle. These alterations are supposed to be a result of an attack of free radicals generated as normal byproducts of oxidative phosphorylation and lead to damage of proteins, lipids, and DNA. The alterations of mtDNA include oxidative damage of base pairs, point mutations, large-scale deletions or duplications. The 4977 bp deletion or "common deletion" reveals an age-dependent accumulation in postmitotic tissues, but not in fast-dividing tissues such as blood cells. In addition, it is observed that a tissue-specific accumulation occurs with the highest abundance in the basal ganglia, followed by skeletal muscle, heart, and lowest in cerebellar tissue. Third, pathological alterations of specific tissue, like ischemia/reperfusion events, display a pronounced accumulation of the deletion compared to age-matched cont...
Journal of Forensic Sciences
The successive killing of three siblings by their biological mother at two-year intervals is desc... more The successive killing of three siblings by their biological mother at two-year intervals is described. The children were 367 days, 75 days and 3 years old. Although sudden infant death syndrome (SIDS) or interstitial pneumonia could not be ruled out as the cause of death in the two younger children, who were killed first, the third child exhibited discrete signs of violence in the mouth and throat area which were interpreted as proof of infanticide. All three children had petechiae of the skin of the face and throat, the upper thorax, the shoulders and the mucous membranes of the mouth. None of the children exhibited signs of a disease-related hemorrhagic tendency. After the mother was convicted of murdering the three-year-old boy by smothering in combination with compression of the thorax, she confessed to having killed the other two children in a similar manner. In the absence of hemostatic disease, the presence of petechiae of the skin extending over the entire drainage area of ...
Journal of Forensic Sciences
A 7-month-old previously healthy female infant was found dead in her crib by her mother shortly a... more A 7-month-old previously healthy female infant was found dead in her crib by her mother shortly after having been laid down to sleep following the noontime feeding. Because the child did not suffer from an acute illness and no other evidence pointed to a cause of death, it was initially assumed by the police that she had died of sudden infant death syndrome. At autopsy, however, the cause of death was determined to be cardiac arrhythmia secondary to fibroma of the heart.
Experimental and Toxicologic Pathology
Quantitative changes in nucleolus organizer regions (NORs) are known markers of proliferation tha... more Quantitative changes in nucleolus organizer regions (NORs) are known markers of proliferation that can be demonstrated by a specific silver staining technique on paraffin-embedded sections. Wounding of skin induces proliferation of basal epidermal cells at the wound margin. The degree of proliferation depends on the survival time and can be measured by morphometric assessment of argyrophilic NORs (AgNORs). Following incision wounding of the pinnae, rats were allowed to survive for different intervals (7 rats per interval) up to 120 hours. Before each sacrifice, biopsies were taken and incubated in a bromodeoxyuridine (BrdU) solution, embedded in paraffin, and stained with an antibody against BrdU. At the same time morphometric analysis of AgNOR counts was performed on sections made from the same material. BrdU incorporating nuclei were assessed by simple counting, whereas morphometric analysis of AgNOR counts was computer aided. Both methods revealed an increase in the number of pro...
Zeitschrift für Gerontologie und Geriatrie, 2007
Acta neuropathologica, 2003
To determine the value of imaging procedures such as computer tomography (CT) and magnetic resona... more To determine the value of imaging procedures such as computer tomography (CT) and magnetic resonance imaging (MRI) of the head in providing additional information of forensic relevance, we examined 17 cadavers of human victims of gunshot wounds to the head. Three of the victims briefly survived the gunshot wound. The weapons involved were all guns with low muzzle energy (<550 J), i.e., handguns and low-velocity rifles. In the majority of cases ( n=15) a penetrating wound to the head was found, only two cases showed the bullet lodged in the brain. In some cases, imaging of the skull and brain was performed prior to autopsy; in others imaging took place after autopsy on the isolated, formalin-fixed brain. The imaging findings were correlated with the criminological data and the results of macroscopic and microscopic examination of the brain. The findings on the bony structures of the head provided imaging criteria for differentiation between entrance and exit of the gunshot wounds,...
Medicine, science, and the law, 2000
Various hematogenous markers were used to differentiate and quantify the types of mononuclear cel... more Various hematogenous markers were used to differentiate and quantify the types of mononuclear cells present in subcutaneous haemorrhages. Fifty samples of subcutaneous bleeding with a survival time of a few minutes to more than 48 hours were studied. The various cell types were detected using the following stains: Naphthol AS-D chloracetate esterase for myeloid cells, including mast cells; (alpha1-antichymotrypsin for monocytes/macrophages; UCHL1 for T-lymphocytes; and L26 for B lymphocytes. The percentage of monocytes/macrophages was found to increase in dependence on survival time, whereas T-lymphocytes declined. Within minutes of injury neutrophilic granulocytes had emigrated into the surrounding tissue and mast cell degranulation had occurred within the haemorrhagic zone. Esterase-positive mononuclear cells, namely metamyelocytes, were detected within minutes after injury and were still present after survival times exceeding 48 hours; however, no dependence on survival time or c...
Mutation research, Jan 3, 1998
The 4977 bp deletion in mitochondrial DNA (mtDNA) is known to accumulate with age in various huma... more The 4977 bp deletion in mitochondrial DNA (mtDNA) is known to accumulate with age in various human tissues. Findings regarding its accumulation in blood, however, have so far been contradictory. We investigated the levels of the 4977 bp deletion in mtDNA from 100 intravital and postmortem blood samples. Applying an improved version of a PCR plus silver staining of polyacrylamide gels, we could detect the 4977 bp deletion in blood of healthy individuals over 20 years of age. While the 4977 bp deletion in blood is subject to a certain age dependence, it appears to be influenced by additional factors. A Primer-Shift-Assay amplifying four different deletion-specific fragments showed that the smaller fragments were amplified with a higher amplification efficiency than the larger fragments. The deletion-specific 389 bp fragment was demonstrated in 73% of individuals over 80 years of age, but in only 46% of individuals between 21 and 30 years old whereas the largest 802 bp deletion-specifi...
Journal of Alzheimer's disease : JAD, 2014
The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid deposits, intrac... more The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid deposits, intracellular neurofibrillary tangles (NFTs), and neuronal death. Hyperphosphorylation of tau is a key factor in the generation of NFTs. Mitogen activated protein kinase 1 (MAPK1) and protein kinase C beta (PRKCB) are thought to play a role in hyperphosphorylation, and PRCKB is thought to be involved in hypoxic stress and vascular dysfunction, and to trigger MAPK phosphorylation pathways. We performed single-cell analyses of neurons with different vulnerabilities to AD-related changes. Using quantitative PCR (qPCR), we measured the levels of MAPK1 and PRKCB transcript in CA1 (high vulnerability), CA2 pyramidal cells from the hippocampus, granule cells from the cerebellum (low vulnerability), and neurons from the brain stem (nucleus tractus spinalis nervi trigemini, characterized by early neurophysiological deficits) at progressive Braak stages compared to age-matched controls. The highly vulne...
Zeitschrift f�r Gerontologie und Geriatrie, 2001
ABSTRACT Eine Vielzahl von Untersuchungen belegt, dass die Funktion der Atmungskette der Mitochon... more ABSTRACT Eine Vielzahl von Untersuchungen belegt, dass die Funktion der Atmungskette der Mitochondrien in höherem Lebensalter, besonders in postmitotischen Geweben wie Gehirn, Herz oder Skelettmuskulatur, abnimmt. Dieser Funktionsverlust scheint Folge einer Schädigung durch freie Radikale zu sein, die als Nebenprodukte bei der oxidativen Phosphorylierung anfallen und Proteine, Fette und DNA schädigen können. Die Schädigung der mitochondrialen DNA (mtDNA) umfasst oxidative Schäden der Basenpaare, Punktmutationen, Deletionen oder Duplikationen. Die häufigste Deletion der mtDNA ist 4977bp lang und zeigt eine altersabhängige Zunahme in postmitotischen Geweben. Weiterhin wird eine gewebsspezifische Zunahme beobachtet, wobei die Deletion am stärksten in den Basalganglien akkumuliert, gefolgt von Skelettmuskulatur und Herzmuskulatur, während im Kleinhirngewebe kaum deletierte mtDNA nachzuweisen ist. Ferner wird eine stärkere Akkumulation in pathologisch verändertem Gewebe (z.B. bei Ischämie) gegenüber altersgleichen Kontrollgeweben beobachtet. Obwohl einige kritische Stimmen die Bedeutung der Mitochondrien in Bezug auf die Alterungsvorgänge und die Theorie der freien Radikale anzweifeln, sprechen doch die experimentellen Daten für die wichtige Rolle der Mitochondrien im Alterungsprozess. There is a lot of evidence that age-associated alterations of the mitochondrial genome occur, especially in postmitotic tissues such as brain, heart and skeletal muscle. These alterations are supposed to be a result of an attack of free radicals generated as normal byproducts of oxidative phosphorylation and lead to damage of proteins, lipids, and DNA. The alterations of mtDNA include oxidative damage of base pairs, point mutations, large-scale deletions or duplications. The 4977bp deletion or “common deletion” reveals an age-dependent accumulation in postmitotic tissues, but not in fast-dividing tissues such as blood cells. In addition, it is observed that a tissue-specific accumulation occurs with the highest abundance in the basal ganglia, followed by skeletal muscle, heart, and lowest in cerebellar tissue. Third, pathological alterations of specific tissue, like ischemia/reperfusion events, display a pronounced accumulation of the deletion compared to age-matched controls. Because there are many mtDNA mutations, further analysis of all alterations of mtDNA will elucidate its role in the phenomenon of aging. Despite some criticisms of this free radical theory of aging, there is a lot of experimental evidence to support the important role of mitochondria in organismal aging.
Zeitschrift für Gerontologie und Geriatrie, 2007
Proceedings of the National Academy of Sciences, 2008
Neuropediatrics, 2005
In cases of traumatic brain injuries in children it may be difficult to differentiate between phy... more In cases of traumatic brain injuries in children it may be difficult to differentiate between physical abuse and accidental occurrence. This review will shed light on discriminating epidemiological as well as biomechanical data, morphological findings, and clinical features. As a basic principle, simple injuries are caused by simple mechanisms like falls whereas life-threatening injuries should be attributed to abuse until proven otherwise. Implausibilities between reported events and mechanisms by caregivers as well as more than one explanation of injury indicate suspicion of child abuse. From reviewing the literature, it can be stated that falls from less than 1.5 m lead only in few cases to severe brain injuries. Children who experienced a fall at home seldom exhibit fractures of the skull but just minor intracranial injuries without neurological deficits. Regarding biomechanical aspects, multiple or complex skull fractures, depression fractures, additional fractures of the body, and intracranial hemorrhages as a consequence of an impact are the most important findings in child abuse. Moreover, additional specific morphological criteria give evidence of clinical and/or post-mortem diagnosis of the shaken baby syndrome. These include subdural hemorrhage and laceration of the brain and retinal bleeding, epidural hemorrhage of the cervical cord, gripping marks (bruises) on chest and/or shoulders, and tearing injuries of the throat and neck muscles. Post-mortem signs of recurrent shaken baby syndrome are indicated by iron-positive cells or microglial cells in neuronal or retinal tissue. A clinical diagnosis will be dependent on the one hand on the exclusion of coagulation diseases, on the other hand on the demonstration of a subdural hemorrhage by means of neuroimaging techniques, i.e., CT and MRI, as well as retinal hemorrhage. The shaken baby syndrome will usually be observed within the first year of life. The doctor has to manifest his diagnosis to the caregivers and - before informing the caregivers - he must be sure of his diagnosis.
Mechanisms of Ageing and Development, 2005
During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and other mutations... more During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and other mutations have been reported. These structural alterations of mtDNA are assumed to cause a reduction in the respiratory chain activity and may contribute to the ageing process. Therefore, the question arises if the accumulation of deleted mtDNA is compensated in vivo by an increase of mtDNA synthesis via a feedback mechanism. We designed two human mtDNA-specific oligonucleotide probes for quantitative mtDNA analysis of 5 different tissues from 50 individuals aged from 8 weeks to 93 years. The amount of mtDNA was approximately 1.1 +/- 0.5% (4617 +/- 2099 copies) in the caudate nucleus, 1.0 +/- 0.5% (4198 +/- 2099 copies) in the frontal lobe cortex, 0.3 +/- 0.2% (1259 +/- 840 copies) in the cerebellar cortex, 1.0 +/- 0.4% (4198 +/- 1679 copies) in skeletal muscle and 2.2+/-1.3% (9235 +/- 5457 copies) in heart muscle. We did not observe any significant change in the absolute copy number during ageing in five different tissues, and therefore, found no evidence for the postulated feedback mechanism. Our study indicates that mtDNA copy number is tissue-specific and depends on the energy demand of the tissue.
Legal Medicine, 2008
Opposite to clinical laboratory findings in experimental drowning of animals (erythrocytic lysis,... more Opposite to clinical laboratory findings in experimental drowning of animals (erythrocytic lysis, hyperkalemia, and final cardial fibrillation) are the observations in drowned humans (increase of pCO2, hypoxic encephalopathy), which leads to a different pathophysiological interpretation of the drowning process. This process, however, is recently discussed again, therefore an additional study seemed to be recommended. In a retrospective study, 31 cases of near-drowning (23 cases: fresh water; 8 cases: brackish water) clinical laboratory data were analysed. While 21 of the cases were fatal with a delay of up to 180 days, 10 individuals survived the accident, four cases with severe neurological deficits. Data of pH, potassium, sodium, chloride, hemoglobin and total protein were collected during the very early post-drowning period. Nearly all cases (96%) revealed a reduction of pH due to hypoxic acidosis, and only two cases (6.5%) exhibited a slight hyperkalemia. The hemoglobin level was normal in most of the cases (83%) and slightly reduced in the others (17%) while the protein level was slightly reduced in most of the fatalities (80%). As a result of our investigation we have to state the lack of hyperkalemia as well as of an increase of the hemoglobin level indicate that there is no distinct intravascular red cell lysis due to influx of water into the vascular compartment. Therefore the death by drowning in humans in most cases is the result of a hypoxic cerebral process. A comparison with animal experiments obviously is not helpful because the drowning process in humans leads to an aspiration of only 2-4 ml water/kg, while in animal experiments more than 10 ml water/kg will be artificially aspirated leading to red cell lysis as well as to electrolyte disturbances and cardial fibrillation.