Biomedical subjects

J Bohl

Publications and source records attributed to J Bohl.

At least 37 records · Page 2Linked to original sources

PubMed1998

Evolution of Alzheimer's disease related cortical lesions.

Alzheimer's disease is an immutably progressing dementing disorder. Its major pathologic hallmark is the gradual development of neurofibrillary changes in a few susceptible nerve cell types. The cortical changes do not occur inevitably with advancing age. Once the disease has begun, spontaneous recovery or remissions are not observed. The initial changes develop in poorly myelinated areas of the temporal lobe. The destructive process then follows a predictable pattern as it extends into other cortical areas. Advanced age is not a prerequisite for the evolution of the lesions. Alzheimer's disease is thus an age-related, but not an age-dependent disease. The spread of the neurofibrillary changes resembles the process of cortical myelination, however in reverse order.

Aging↗

PubMed1998

Monoclonal antibodies SMI 311 and SMI 312 as tools to investigate the maturation of nerve cells and axonal patterns in human fetal brain.

Neurofilaments, which are exclusively found in nerve cells, are one of the earliest recognizable features of the maturing nervous system. The differential distribution of neurofilament proteins in varying degrees of phosphorylation within a neuron provides the possibility of selectively demonstrating either somata and dendrites or axons. Non-phosphorylated neurofilaments typical of somata and dendrites can be visualized with the aid of monoclonal antibody SMI 311, whereas antibody SMI 312 is directed against highly phosphorylated axonal epitopes of neurofilaments. The maturation of neuronal types, the development of area-specific axonal networks, and the gradients of maturation can thus be demonstrated. Optimal immunostaining with SMI 311 and SMI 312 is achieved when specimens are fixed in a mixture of paraformaldehyde and picric acid for up to 3 days and sections are incubated free-floating. Neurons, with their dendritic domains immunostained by SMI 311 in a Golgi-like manner, can be completely visualized in relatively thick sections. The limitations of Golgi-preparations, such as glia-labeling, artifacts, and the staining of only a small non-representative percentage of existing neurons, are not apparent in SMI preparations, which additionally provide the possibility of selectively staining axonal networks. The results achieved in normal fetal brain provide the basis for studies of developmental disturbances.

Abortion, Induced↗

PubMed1998

Transient features of the thalamic reticular nucleus in the human foetal brain.

The architectonic organization and neuronal types of the human foetal reticular nucleus (RN)--with special reference to transient characteristics--have been investigated using antisera against calretinin, parvalbumin and neurofilament epitopes of somata and dendrites (SMI 311). The RN consists of four subdivisions (clearly distinguishable in the 6/7th gestational month): The main portion appears as a prominent structure on account of its extension and high packing density of neurons which coexpress calretinin and parvalbumin. These two calcium-binding proteins are also expressed by the perireticular nucleus forming a conspicuous grey within the internal capsule. Perireticular cells form clusters which are in continuity with the main portion, globus pallidus, ganglionic eminence and pregeniculate nucleus. In double-labellings, a medial subnucleus stands out distinctly as it only expresses calretinin. SMI 311-immunopreparations show neurons revealing a high degree of diversification and elaborated dendritic trees. Several transient characteristics become obvious: the perireticular nucleus, not visible in the adult, represents a distinct entity in the human foetal brain. The main portion and the pregeniculate nucleus appearing as prominent greys are dramatically reduced in size later on. The percentage of RN-neurons expressing calretinin, the diversity of neuronal types and elaborated dendritic trees are reduced. The transient features can be correlated with the RN's putative functional roles in development: early RN-afferents to the dorsal thalamus may represent pioneer fibres providing guiding cues for outgrowing axons from or into the thalamus. Moreover, the RN may serve as an intermediate target for growing axons which are sorted and directed towards different final targets.

Antibodies, Monoclonal↗

PubMed1998

Transient architectonic features in the basolateral amygdala of the human fetal brain.

The architectonical differentiation in the basolateral nuclei of the human fetal amygdala - with special reference to transient structures - was studied using series of relatively thick Nissl-stained sections. These architectonic features were correlated with the process of migration. Radial glial fibers providing the scaffold of migratory routes can reliably be marked with the aid of antivimentin. In the 5th gestational month a transient feature is conspicuous in the inferior portions of the basolateral nuclei bordering upon the ganglionic eminence (proliferative zone): columnar cell clusters, separated by cell-sparse septa, extend from the poliferative zone to the nuclei. The width of the cell columns vary considerably between the different nuclei. In vimentin immunopreparations fibers are found inside these cell columns. So they most probably reflect clustered migratory streams. Two months later, instead of this merging area between the ganglionic eminence and the amygdaloid nuclei a cell-free capsule envelopes the nuclei and clearly separates them from the ganglionic eminence. Changes in cytoarchitectonics are accompanied by a distinct rearrangement of radial glial fibers. A basket-like arrangement of the vimentin-immunoreactive fibers around the cell columns inside the cell sparse septa is found. Towards the end of pregnancy radial glial fibers gradually vanish. A comparison of Nissl and vimentin preparations reveals that transient architectonic characteristics as visible in relatively thick Nissl sections may be correlated with migrational routes.

Amygdala↗

PubMed1997

Neurofibrillary tangles and neuropil threads as a cause of dementia in Parkinson's disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities. In AD susceptible neurons produce neurofibrillary changes, while in Parkinson's disease, they develop Lewy bodies. In AD six developmental stages can be distinguished on account of the predictable manner in which the neurofibrillary changes spread across the cerebral cortex. During the course of PD numerous limbic determined parts of the brain undergo specific lesions regulating endocrine and autonomic functions. In general, the extranigral destructions are in themselves not sufficient to produce overt intellectual deterioration. Fully developed Parkinson's disease with concurring incipient Alzheimer's disease is likely to cause impaired cognition.

Dementia↗

PubMed1997

Cerebral haemorrhage in long-term survivors of childhood acute lymphoblastic leukaemia.

Modern treatment of childhood acute lymphoblastic leukaemia (ALL) has dramatically improved the prognosis for children with this disease. Therapeutic approaches consist of multimodal chemotherapy and radiotherapy with significant long-term side-effects. We report on 4 children out of a group of 120 newly diagnosed patients with ALL, who survived the disease for more than 2 years and developed a cerebral haemorrhage after chemotherapy and fractionated cranial irradiation. Following a period of 2-12 years the four children presented with acute neurological signs and symptoms. i.e. seizures, ataxia and hemiparesis. CT and MRI revealed intracerebral mass lesions, interpreted as haemorrhage. After neurosurgery the patients neurological state improved. Histological examination confirmed the suspected diagnosis of bleeding cavernous haemangioma or capillary telangiectases. There are two possibilities to explain these rare alterations: they may be pre-existent to the disease and therapy or they may be caused by irradiation. CONCLUSION Acute neurological symptoms in patients treated for ALL may be caused by spontaneous cerebral haemorrhaging of cavernous haemangiomas or capillary telangiectases induced by chemotherapy and/or radiotherapy.

Adolescent↗

PubMed1997

High proportion of dementia with Lewy bodies in the postmortems of a mental hospital in Germany.

OBJECTIVE: Dementia with Lewy bodies (DLB) is under-recognized in Germany. No data on the number of patients suffering from this condition in Germany are available at present. We were interested in the proportion of DLB in the postmortems of demented inpatients in the care of a psychogeriatric service. DESIGN: In a retrospective study we examined consecutive postmortems of inpatients who died in one mental hospital. SETTING: A suburban and rural old age psychiatry service in Germany. PATIENTS: 103 consecutive postmortems had been performed from 9/1987 to 6/1995. Fifty-nine (57.3%) of all cases warranted the clinical diagnosis of dementia (DSM-III-R). MEASURES: The causes of dementia were examined histologically. Lewy bodies (LBs) were detected with ubiquitin immunohistochemistry. RESULTS: DLB was the third most frequent cause of dementia (13.6% of demented), after dementia of Alzheimer's type (DAT) (35.6%) and mixed DAT and vascular dementia (15.3%), but ahead of 'pure' vascular dementia (MID). The DLB group showed a male preponderance compared with the DAT, MID and mixed group of our series. The DLB patients died younger than the DAT patients. The differences, however, were not statistically significant. All DLB cases showed neurofibrillary and amyloid pathology sufficient to warrant an additional diagnosis of DAT. Cases with 'pure' LB pathology had not been detected in our series. CONCLUSIONS: Our results indicate that by using appropriate methods, ie ubiquitin immunohistochemistry, a considerable number of DLB cases can be detected in postmortems of demented patients from German mental hospitals.

Adult↗

PubMed1996

Age, neurofibrillary changes, A beta-amyloid and the onset of Alzheimer's disease.

Intraneuronal neurofibrillary changes and extracellular A beta-amyloid deposits are neuropathologic hallmarks of Alzheimer's disease. Examination of numerous non-selected autopsy cases demonstrates that they are by no means normal concomitants of brain aging. Rather, the initial neurofibrillary changes indicate the beginning of Alzheimer's disease. A small proportion of cases displays particularly early development of the intraneuronal changes, indicating that advanced age is not a prerequisite for the evolution of the lesions. However, the mean of stages in the development of the specific neurofibrillary pathology increases with age. Alzheimer's disease is thus an age-related, not an age-dependent disease.

Adult↗

PubMed1996

Apolipoprotein E polymorphism is associated with both senile plaque load and Alzheimer-type neurofibrillary tangle formation.

Recent work provided evidence that the apolipoprotein (apo) E polymorphism is associated with late-onset sporadic Alzheimer's disease. The major histological hallmarks of Alzheimer's disease are the extraneuronal deposition of A4/beta-amyloid and the intraneuronal formation of neurofibrillary tangles, the latter correlating strongly with the psychometric status. We examined the relationship between the apo E polymorphism and Alzheimer's disease-related histological changes using a staging system which accounts for the progression of the disease over time and correlates well with the cognitive decline ante mortem. We observed a significant positive correlation between both neurofibrillary changes and A4/beta-amyloid deposits and the epsilon 4 gene dose. We estimated that the presence of one apo E4 allele leads to an earlier onset of the histopathological process of about one decade. The association of both types of Alzheimer's disease-related changes with the prevalence of the epsilon 4-allele suggests that the apo E polymorphism causally contributes to the development of Alzheimer's disease.

Aging↗

PubMed1996

New aspects of pathology in Parkinson's disease with concomitant incipient Alzheimer's disease.

Alzheimer's disease and Parkinson's disease are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities which gradually develop in only a small number of neuronal types. In Alzheimer's disease, susceptible neurons produce neurofibrillary tangles and neuropil threads, while in Parkinson's disease, they develop Lewy bodies and Lewy neurites. The specific lesional pattern of both illnesses accrues slowly over time. Presently available data support the view that fully developed Parkinson's disease with concurring incipient Alzheimer's disease is likely to cause impaired cognition.

Alzheimer Disease↗

PubMed1996

Pattern of brain destruction in Parkinson's and Alzheimer's diseases.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities which gradually develop in only a small number of neuronal types. In AD, susceptible neurons produce neurofibrillary tangles (NFTs) and neuropil threads (NTs), while in PD, they develop Lewy bodies (LBs) and Lewy neurites (LNs). The specific lesional pattern of both illnesses accrues slowly over time and remains remarkably consistent across cases. In AD, six developmental stages can be distinguished on account of the predictable manner in which the neurofibrillary changes spread across the cerebral cortex. The pathologic process commences in the transentorhinal region (clinically silent stages I and II), then proceeds into adjoining cortical and subcortical components of the limbic system (stages III and IV - incipient AD), and eventually extends into association areas of the neocortex (stages V and VI - fully developed AD). During the course of PD, important components of the limbic system undergo specific lesions as well. The predilection sites include the entorhinal region, the CA2-sector of the hippocampal formation, the limbic nuclei of the thalamus, anterior cingulate areas, agranular insular cortex (layer VI), and - within the amygdala - the accessory cortical nucleus, the ventromedial divisions both of the basal and accessory basal nuclei, and the central nucleus. The amygdala not only generates important projections to the prefrontal association areas but also exerts influence upon all non-thalamic nuclei which in a non-specific manner project upon the cerebral cortex and upon the nuclei regulating endocrine and autonomic functions. All these amygdala-dependent structures themselves exhibit severe PD-specific lesions. In general, the extranigral destructions are in themselves not sufficient to produce overt intellectual deterioration. Similarly, AD-related pathology up to stage III may be asymptomatic as well. Fully developed PD with concurring incipient AD, however, is likely to cause impaired cognition. Presently available data support the view that the occurrence of additional lesions in the form of AD stage III (or more) destruction is the most common cause of intellectual decline in PD.

Aging↗

PubMed1996

Functional anatomy of human hippocampal formation and related structures.

Data on the internal organization, and neuronal connections of the human hippocampal formation and related structures of the limbic system are briefly reviewed. In the healthy brain, somatosensory, visual, and auditory input proceeds through neocortical core and belt fields to a variety of association areas, and from here the data is transported via long corticocortical pathways to the extended prefrontal association cortex. Tracts generated from this highest organization level of the brain guide the data via the frontal belt (premotor cortex) to the frontal core (primary motor area). The striatal and cerebellar loops provide the major routes for this data transfer. The main components of the limbic system (the hippocampal formation, the entorhinal region, and the amygdala) maintain a strategic position between the sensory and the motor association areas. Part of the stream of data from the sensory association areas to the prefrontal cortex branches off and eventually converges on the entorhinal region and the amygdala, These connections establish the afferent leg of the limbic loop. In addition, the limbic centers receive substantial input from nuclei processing viscerosensory information. The entorhinal region, the hippocampal formation, and the amygdala are densely interconnected. Important among these connections is the perforant path, which originates in the entorhinal cortex and projects to the hippocampal formation (fascia dentata, Ammon's horn, and subiculum). The subiculum projects to the amygdala, entorhinal region, mamillary nuclei, and anterior and midline thalamic nuclei. The hippocampal formation, the entorhinal region, and the amygdala generate the efferent leg of the limbic loop, which is directed toward the prefrontal cortex. Additional projections reach the key nuclei that control endocrine and autonomic functions. Furthermore, the amygdala exerts influence on all nonthalamic nuclei projecting in a nonspecific manner to the cerebral cortex (ie, the cholinergic magnocellular forebrain nuclei, the histaminergic tuberomamillary nucleus, the dopaminergic nuclei of the ventral tegmentum, the serotonergic anterior raphe nuclei, and the noradrenergic locus ceruleus). The limbic loop centers thus are in the unique strategic position to perform integration of exteroceptive sensory data of various sources with interoceptive stimuli from autonomic centers. Their efferent projections exert influence on both the prefrontal association cortex and the key centers controlling endocrine and autonomic functions.

Hippocampus↗

PubMed1995

Correlation of virus replication, cytokine (TNF-alpha and IL-1) producing cells, neuronal necrosis and inflammation after intranasal infection of mice with herpes simplex virus strains of different virulence.

The number of TNF-alpha and IL-1 beta producing cells was investigated during the acute replication phase of herpes simplex virus (HSV) in trigeminal ganglia after intranasal infection with strains of different virulence. The highly virulent strain WAL replicated strongly and induced many cytokine producing cells early in the ganglia. The low virulent strain HFEM replicated less, only few cytokine producing cells were detected late. The thymidine-kinase negative (TK-) virus 1301 did not replicate but produced some lymphocytic inflammation. The higher the virulence of strains of HSV-1 or -2 was, the stronger was the extent of histopathological lesions; moreover, a dissociation in time between replication and cellular reaction (granulocytic and lymphocytic) could be observed after infection with strains HFEM and TK- virus 1301. CD4 and CD8 positive cells could be detected mainly at the rim of necrotic areas, TNF-alpha and IL-1 beta producing cells, however, were scattered throughout the ganglia.

Administration, Intranasal↗

PubMed1995

Apolipoprotein E polymorphism influences not only cerebral senile plaque load but also Alzheimer-type neurofibrillary tangle formation.

Only recently, evidence was provided that apolipoprotein E allele epsilon 4 located on Chromosome 19 is associated with late onset (i.e. senile) sporadic Alzheimer's disease. Histologically, Alzheimer's disease is associated with intraneuronal neurofibrillary changes and extraneuronal A4/beta-amyloid deposition. We set out with a histological staging system which considers the gradual development of Alzheimer's disease-related histological changes over time and correlates highly with the cognitive decline ante mortem. Our analysis revealed that both the mean stage for A4/beta-amyloid deposits and the mean stage for neurofibrillary tangles get significantly shifted upwards in epsilon 4-carriers. This represents an earlier onset of the histopathological process of about one decade. The fact that both types of Alzheimer's disease-related changes correlate positively with the prevalence of the epsilon 4-allele suggests for a causal relationship between the apolipoprotein E polymorphism and the development of Alzheimer's disease.

Age Factors↗

PubMed1995

Close-meshed prevalence rates of different stages as a tool to uncover the rate of Alzheimer's disease-related neurofibrillary changes.

The speed of progression of Alzheimer's disease-related neurofibrillary changes is unknown. One reason for this is the impossibility to histopathologically follow-up one and the same individual over decades of their life. The present approach takes advantage of a recently introduced classification system which allows for a ranking of Alzheimer's disease-related neurofibrillary changes into six stages [Braak and Braak Acta Neuropath (1991) 82, 239-259] and analyses a staged sample of 887 brains obtained from routine autopsy. It sets out to interpret these cross-sectional data in dynamic longitudinal terms, in order to estimate the rate of passing through the various stages. The time needed to attain respective stages of pathology for 5% of a given cumulative sample is determined. The resulting fifth centiles are a measure of the average rate by which the disease-related changes progress assuming that the underlying stages represent a sequence of events and do not independently emerge. Advancing age and the prevalence of Alzheimer's disease-related changes of a given stage show a nonlinear positive correlation with only slight acceleration above the age of 65 years. Statistically, it takes at least 16 years from stage I to stage II, about 14 years pass by from stage II to III, 13 years from stage III to IV and five years from stage IV to V (= Alzheimer's disease) for 5% of a given cumulative sample. Thus, the deep roots of Alzheimer's disease-related neurofibrillary changes can be traced about 50 years back and may even extend into adolescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Dissection of the internal carotid artery after chiropractic manipulation of the neck.

A 29-year-old woman died from a right hemispheric infarction caused by dissection and subsequent thrombosis of the internal carotid artery after chiropractic manipulations of the neck. Pathologic study of several arteries of muscular and elastic type revealed a mediolytic arteriopathy with widespread mucoid degeneration and cystic transformation of the vessel wall caused by segmental degeneration of smooth muscle cells of the tunica media. We hypothesize that mediolytic arteriopathy was a predisposing factor for the dissection of the internal carotid artery after chiropractic manipulations in our patient.

Adult↗

PubMed1994

[Clinical, neurophysiologic and biopsy findings in neurotoxic amiodarone syndrome].

PATIENTS: Three patients complained of proximal weakness and paraesthesia of the legs and difficulties in walking during amiodarone treatment. Examination showed signs of a predominantly distal sensory neuropathy, a proximal myopathy, and a cerebellar gait disorder. All had amiodarone dosages of 600 mg per day, amiodarone serum levels above 2.7 mg/l and a total amount of amiodarone ingestion of 300 to 500 g. The clinical symptoms subsided within six to eleven months after treatment was stopped. RESULTS: The neurophysiologic investigations showed slowing of sensory and motor nerve conduction velocities with dissociation of the action potentials and delay of SEP latencies. With discontinuation of the drug these abnormalities were progressive in one patient. The biopsy (muscle, nerve and skin) in the most severely affected patient showed numerous intracellular lysosomal inclusions in cells of different tissues. It is supposed that the storage of amiodarone in muscle cells results in a predominantly proximal myopathy whereas storage in Schwann cells results in a secondary neuropathy. A similar storage in Purkinje cells may be responsible for the cerebellar gait disorder. CONCLUSION: The clinical picture should be termed a neurotoxic amiodarone syndrome rather than amiodarone neuropathy.

Amiodarone↗

PubMed1994

Adenylyl cyclase activity in Alzheimer's disease brain: stimulatory and inhibitory signal transduction pathways are differently affected.

Adenylyl cyclase (AC) activity was studied in post mortem hippocampus and cerebellum from eight patients with Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) and seven non-demented control patients. AC was stimulated via stimulatory guanine nucleotide binding proteins (Gs) using guanosine triphosphate (GTP) and GppNHp (both 10(-4) M) or directly with either forskolin (10(-4) M) or Mn2+ (10(-2) M). Inhibition of AC via A1-receptors was performed with N6-cyclohexyladenosine (CHA) under basal conditions and in the presence of forskolin (10(-5) M). In both brain regions AC activity was significantly reduced in AD/SDAT when compared to controls. Under basal conditions and after stimulation via Gs mean reduction in hippocampus and cerebellum was 47.7% and 58.2%, respectively. The reduction was less pronounced after direct activation of the AC, amounting to 21.8% in hippocampus and 28.1% in cerebellum. CHA inhibited basal and forskolin-stimulated AC concentration-dependently by about 20% (basal) and 30% (forskolin). Inhibition by CHA was similar in hippocampus and cerebellum and tended to be more pronounced in AD/SDAT than in controls. Since the reduction of AC activity in AD/SDAT is greater after stimulation via Gs than after direct activation of the catalytic subunit, we suggest that both Gs and the catalytic subunit seem to be impaired. The fact that CHA-mediated inhibition of AC is not significantly different in AD/SDAT and controls, indicates that in contrast to Gs-, inhibitory G-proteins (Gi) coupling to AC remains intact in Alzheimer's disease.

Adenosine↗