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Biomedical subjects

J Bohl

Publications and source records attributed to J Bohl.

At least 19 recordsLinked to original sources
PubMed2006

A new type of leukoencephalopathy with metaphyseal chondrodysplasia maps to Xq25-q27.

BACKGROUND: The authors report a three-generation family with four male patients presenting with a novel type of X-chromosomal leukoencephalopathy associated with skeletal abnormalities. METHODS: The index patient and his brother reached their early motor milestones in due time and had normal language development. Between the ages of 2 and 3 years, first signs of spastic paraplegia were noticed. Furthermore, the patients developed tremor, ataxia, optic atrophy, and spastic tetraparesis. Both boys had broad wrists and knees without significant contractures. A maternal uncle and a granduncle had the same disease. RESULTS: Leukoencephalopathy (MRI, MRS) and metaphyseal chondrodysplasia (X-ray, MRI) were diagnosed. MRS showed a reduction of choline-containing compounds in the white matter. An autopsy on one of the patients, who died at age 37 years, revealed an orthochromatic type of leukoencephalopathy. In bone and cartilage tissue, unspecific signs of a mild chondrodysplasia were found. At the PLP gene locus an obligate recombination was observed, which excludes the Pelizaeus-Merzbacher locus on Xq21-22. However, affected males share a fragment of the long arm of chromosome X. CONCLUSION: The authors report a new type of leukoencephalopathy associated with metaphyseal chondrodysplasia located on Xq25-q27.

Adult↗
PubMed2005

Spinocerebellar ataxias types 2 and 3: degeneration of the pre-cerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum.

The pre-cerebellar nuclei act as a gate for the entire neocortical, brainstem and spinal cord afferent input destined for the cerebellum. Since no pathoanatomical studies of these nuclei had yet been performed in spinocerebellar ataxia type 2 (SCA2) or type 3 (SCA3), we carried out a detailed postmortem study of the pre-cerebellar nuclei in six SCA2 and seven SCA3 patients in order to further characterize the extent of brainstem degeneration in these ataxic disorders. By means of unconventionally thick serial sections through the brainstem stained for lipofuscin pigment and Nissl material, we could show that all of the pre-cerebellar nuclei (red, pontine, arcuate, prepositus hypoglossal, superior vestibular, lateral vestibular, medial vestibular, interstitial vestibular, spinal vestibular, vermiform, lateral reticular, external cuneate, subventricular, paramedian reticular, intercalate, interfascicular hypoglossal, and conterminal nuclei, pontobulbar body, reticulotegmental nucleus of the pons, inferior olive, and nucleus of Roller) are among the targets of both of the degenerative processes underlying SCA2 and SCA3. These novel findings are in contrast to the current neuropathological literature, which assumes that only a subset of pre-cerebellar nuclei in SCA2 and SCA3 may undergo neurodegeneration. Widespread damage to the pre-cerebellar nuclei separates all three phylogenetically and functionally defined regions of the cerebellum, impairs their physiological functions and thus explains the occurrence of gait, stance, limb and truncal ataxia, dysarthria, truncal and postural instability with disequilibrium, impairments of the vestibulo-ocular reaction and optokinetic nystagmus, slowed and saccadic smooth pursuits, dysmetrical horizontal saccades, and gaze-evoked nystagmus during SCA2 and SCA3.

Adolescent↗
PubMed2005

Extended pathoanatomical studies point to a consistent affection of the thalamus in spinocerebellar ataxia type 2.

The involvement of the thalamus during the course of the currently known polyglutamine diseases is still a matter of debate. While it is well-known that this diencephalic nuclear complex undergoes neurodegeneration in some polyglutamine diseases such as Huntington's disease (HD), it has remained unclear whether and to what extent the thalamus is also involved in spinocerebellar ataxia type 2 (SCA2) patients. Encouraged by our recent post-mortem findings in one German SCA2 patient and the results of a recent nuclear magnetic resonance (NMR) study, we extended our pathoanatomical analysis to serial thick sections stained for lipofuscin granules and Nissl substance through the thalami of four additional German and Cuban SCA2 patients. According to this analysis the thalamus is consistently affected by the destructive process of SCA2. In particular, during our study we observed a consistent involvement of the lateral geniculate body, the lateral posterior, ventral anterior, ventral lateral, ventral posterior lateral, and ventral posterior medial thalamic nuclei as well as the extraterritorial reticular nucleus. In four of the SCA2 cases studied additional damage was seen in the inferior and lateral nuclei of the pulvinar, whereas in the minority of the patients a subset of the limbic nuclei of the thalamus (i.e. anterodorsal, anteroprincipal, laterodorsal, fasciculosus, mediodorsal, central lateral, central medial, cucullar, and paracentral nuclei, medial nucleus of the pulvinar) underwent neurodegeneration. These interindividual differences in the distribution pattern of thalamic neurodegeneration indicate that the thalamic nuclei differ in their proclivities to degenerate in SCA2 and may suggest that they become involved at different phases in the evolution of the underlying degenerative process.

Adult↗
PubMed2004

Contribution of diffusion tensor imaging to delineation of gliomas and glioblastomas.

PURPOSE: To determine if the diffusion tensor imaging (DTI) parameters fractional anisotropy (FA) and mean diffusivity (MD) can differentiate between accompanying edema and tumor cell infiltration of white matter (WM) beyond the tumor edge as defined from conventional MRI in low- and high-grade gliomas. MATERIALS AND METHODS: We examined 12 patients with high-grade gliomas/glioblastomas and eight patients with low-grade gliomas and compared them to 10 patients with meningiomas, in which no tumor infiltration is expected. The tumor was defined as the enhancing area in glioblastomas and meningiomas and as the area of increased T2-signal in low-grade gliomas. FA and MD were measured in the center of the tumor and in the adjacent WM. The contralateral WM and internal capsule were used as an internal standard. RESULTS: Comparing the WM areas of increased T2-signal adjacent to meningiomas and glioblastomas, we saw a trend (without significance) towards a reduction of FA, but not of MD, in glioblastomas. We found no changes of FA and MD in the WM adjacent to low-grade gliomas (without T2-signal increase) compared to the WM of the contralateral hemisphere. In meningiomas and high-grade gliomas/glioblastomas, a narrow rim of significantly (P < 0.01) increased FA and decreased MD values around the enhancing tumor area was seen, whereas in low-grade gliomas, such a rim could not be defined. There was no contribution of FA or MD to grading of gliomas. CONCLUSION: In glioblastomas, a reduction of FA in the edematous area surrounding the tumor may indicate tumor cell infiltration, but a reliable differentiation between infiltration and vasogenic edema is not yet possible on the basis of DTI. The additional finding of a narrow rim of increased FA and decreased MD at the edge of glioblastomas (as well as in meningiomas) may be caused by com-pressed WM fibers and/or increased vascularity, but does not contribute to exclude peripheral cellular infiltration.

Brain↗
PubMed2004

Flow-cytometric DNA analysis of intracranial tumors in children.

The objective of this study was to investigate flow-cytometric DNA values of pediatric intracranial tumors, and to establish DNA analysis as a potential prognostic parameter. Twenty-nine brain tumor specimens from 26 pediatric patients were cryo-preserved within a 3-year period. The DNA content was measured by flow cytometry. Six of the tumor specimens had aneuploid DNA patterns. The median of the proliferation index was lower in the survivor group compared with the non-survivor group (36.4% and 47.5%, respectively). Ten of the 26 patients are still alive, eight were lost to follow up, and eight died. Flow-cytometric DNA analysis may be a helpful tool for examining brain tumors in children. The small size of this study could not establish flow cytometry as a definite prognostic factor, but further prospective multicenter studies will evaluate the prognostic significance of flow-cytometric DNA analysis.

Adolescent↗
PubMed2001

Organisation and maturation of the human thalamus as revealed by CD15.

The distribution of the CD15 antigen (CD15, 3-fucosyl-N-acetyl-lactosamine, Lewis x) has been studied immunohistochemically in the fetal human thalamus. Its changing patterns could be related to three successive, but overlapping, periods primarily due to its association with radial glial cells, neuropil, and neural cell bodies, respectively. From 9 weeks of gestation (wg), a subset of CD15-positive radial glial cells distinguished the neuroepithelium of the ventral thalamus, a characteristic also seen in the developing mouse. Distal processes of the radial glial cells converged at the root of the forebrain choroid tenia, which was also CD15 positive. From 13 wg until approximately 20 wg, CD15-positive neuropil labeling marked the differentiation areas of prospective nuclei within the dorsal thalamus and progressively outlined their territories in a time sequence, which appeared specific for each nucleus. CD15 labeling of differentiating nuclei of the ventral, medial, anterior, and intralaminar thalamic divisions showed a transient topographic relationship with restricted areas of the ventricular wall. After 26 wg, CD15 immunoreactivity was observed in subpopulations of glial cells and neurons. Transient CD15 immunoreactivity was also found in delimited compartments within the subventricular region. The time of CD15 expression, its location, and cellular association suggest that CD15 is involved in segmentation of diencephalon, in the specification of differentiating nuclear areas and initial processes regarding the formation of intercellular contacts and cellular maturation.

Biomarkers↗
PubMed2001

[Bilateral progressive hearing loss as the first manifestation of metastatic carcinoma of the head of the pancreas. Case report].

We report the history of a patient who presented first with a progressive unilateral hearing loss and later with a bilateral deafness and an unilateral facial nerve palsy as first and only symptoms of a pancreatic adenocarcinoma. By means of magnetic resonance tomography tumor-suspect lesions in both internal auditory canals were detected. Referring to the results of further examinations these intracanalicular lesions are most probably due to rarely seen bilateral metastasis of a pancreatic adenocarcinoma in the temporal bone. In addition to this rarely diagnosed localisation of metastasis it is rather uncommon that this kind of primary malignoma had not been detected because of gastrointestinal symptoms or extracranial metastasis.

Adenocarcinoma↗
PubMed2001

Cooperative transformation and coexpression of bovine papillomavirus type 1 E5 and E7 proteins.

Productively infected bovine fibropapillomas were examined for bovine papillomavirus type 1 (BPV-1) E7 localization. BPV-1 E7 was observed in the cytoplasm of basal and lower spinous epithelial cells, coexpressed in the cytoplasm of basal cells with the E5 oncoprotein. E7 was also observed in nucleoli throughout the basal and spinous layers but not in the granular cell layer. Ectopic expression of E7 in cultured epithelial cells gave rise to localization similar to that seen in productive fibropapillomas, with cytoplasmic and nucleolar expression observed. Consistent with the coexpression of E7 and E5 in basal keratinocytes, BPV-1 E7 cooperated with E5 as well as E6 in an anchorage independence transformation assay. While E5 is expressed in both basal and superficial differentiating keratinocytes, BPV-1 E7 is only observed in basal and lower spinous epithelial cells. Therefore, BPV-1 E7 may serve to modulate the cellular response of basal epithelial cells to E5 expression.

Animals↗
PubMed2001

Development-related expression of AKAP79 in the striatal compartments of the human brain.

The expression of AKAP79 which tethers regulatory proteins within postsynaptic densities has been studied in the two striatal compartments, i.e. patches and matrix, at different stages of the developing human brain by means of immunohistochemistry. The two striatal compartments exhibit various intensities of diffuse immunolabelling and a different number of immunoreactive nerve cells. From the 14th to 20th gestational week a nearly homogeneous distribution of immunoreactive structures in the two compartments of the striatum is seen. Thereafter, a decrease in immunoreactive structures within the matrix is observed (22nd-25th week, intermediate stage). From the 27th week onwards the patch compartment contains distinctly more immunoreactive puncta and nerve cells. Thus, the patches stand out clearly in the immunopreparations. This distribution pattern does not change during proceeding development. AKAP79-immunoreactive nerve cells closely resemble those constituting the class of medium-sized inhibitory projection neurons that receive the dopaminergic input of the striatum. Literature data suggest that AKAP79 may be functionally attributed to dopaminergic inputs. Accordingly, the patterns of AKAP79 expression can at least in part be correlated with the sequential occurrence of dopaminergic innervation. The mature matrix containing a dopaminergic innervation being as dense as in the patches displays distinctly less AKAP79-immunoreactive neurons and puncta than the patches. This discrepancy might indicate that a subpopulation of matrix neurons may, despite dopaminergic input, not express AKAP79.

A Kinase Anchor Proteins↗
PubMed2001

Effect of fetal hydrocephalus on the distribution patterns of calcium-binding proteins in the human occipital cortex.

Neuronal pathology in the cerebral cortex (CC) of fetal hydrocephalus brains is quite subtle when applying routine Nissl staining. This study is aimed at investigating alterations of interneurons which can be immunolabelled by antibodies against the calcium-binding proteins calretinin (CR), calbindin (CB) and parvalbumin (PV). The subplate (SP) subjacent to the cortex anlage is included as this transient zone plays a pivotal role in the establishment of cortical connections. Nine occipital lobes from cases of fetal hydrocephalus and 9 controls were categorized according to age: 21-25 weeks of gestation (group 1) and 32-36 weeks (group 2). No differences in the distribution, number and morphology of CR-immunoreactive (ir) neurons are seen when comparing hydrocephalic with control brains of group 1. In severely altered hydrocephalic brains of group 2, the distribution and number of CR-, PV- and CB-ir nerve cells are not altered; however, they appear shrunken and processes are less immunolabelled. In extremely altered tissue PV-, CB-ir neurons cannot be detected, whereas the number of CR-ir somata is not reduced. The data indicate that subpopulations of interneurons of the CC may be differentially damaged. The alterations observed in the SP may implicate a possible impairment of transient neuronal circuitries that are essential for the development of cortical connections. On the whole, these neuronal alterations may account for residual deficits observed after shunting.

Calbindin 2↗
PubMed2001

Neurodegenerative diseases.

This article briefly discusses and illustrates the major important neurodegenerative diseases of adulthood and neurometabolic (neurodegenerative in a broader sense) diseases of childhood and their gross neuropathology. Macroscopic views of the brain including the cerebellum and the brain stem and the spinal cord are given by external inspection as well as gross sections after brain cutting. Histologic details and photographs are supplied to explain and corroborate certain gross findings. This article attempts to correlate nosologic and neuropathologic features as the basis for interpreting neuroimaging data.

Adult↗
PubMed2000

Competitive binding to a charged leucine motif represses transformation by a papillomavirus E6 oncoprotein.

E6 oncoproteins from HPV-16 and bovine papillomavirus type 1 (BPV-1) bind to similar leucine-rich peptides termed charged leucine motifs found on the cellular focal adhesion protein paxillin and the E3 ubiquitin ligase E6AP. BPV-1 E6 (BE6) mutants that do not bind to paxillin are defective at inducing cellular transformation. It is possible, however, that BE6 mutants that do not bind paxillin are defective for transformation for an unrelated reason than the ability to bind to charged leucine motifs. To address the role of BE6 interaction with charged leucine motifs, we fused a BE6-binding charged leucine motif to the amino terminus of BE6, thereby creating an autoinhibitory binding domain. We found that the fusion protein failed to bind to paxillin or transform murine C127 cells. Mutation of the amino terminal binding motif in the fusion protein restored both interaction with paxillin and transformation. This demonstrates that BE6 transformation requires binding to charged leucine motifs on particular cellular proteins and that transformation by papillomavirus oncoproteins can be repressed by competitive interactions with charged leucine motifs.

Amino Acid Sequence↗
PubMed2000

Distribution of SNAP-25 in transient neuronal circuitries of the developing human forebrain.

The distribution of SNAP-25 is demonstrated within prominent transient structures in the developing human forebrain. During early fetal development SNAP-25 is mainly expressed in axons of the intermediate zone and the internal capsule. The fibers appear directed towards the mantle zone of the ganglionic eminence and the perireticular nucleus located within the internal capsule. Cells of these two areas are shown to interact with SNAP-25 immunoreactive structures with the aid of double-labellings. The SNAP-25 immunoreactive fibers may represent corticofugal axons which contact the perireticular nucleus and ganglionic eminence which are regarded as intermediate targets providing a scaffold for growing axons. Anti-SNAP-25, thus, is an appropriate marker of intermediate targets which are involved in brain injuries of preterm infants.

Adult↗
PubMed2000

[Clinical aspects of "argyrophilic grain disease"].

Argyrophilic grain disease (AGD) is a frequently occurring degenerative illness of the aging human brain. It is accompanied by progressive pathological alterations of the cytsokeleton which are traceable to an abnormal phosphorylation of the microtubule associated tau protein. Histologically, it is possible with the help of suitable staining techniques to identify pathognomonic spindle-shaped cellular inclusions (argyrophilic grains). These cellular inclusions display a typical cortical as well as subcortical distribution pattern. The goal of the present study is the retrospective evaluation of the clinical findings from 53 individuals with neuropathologically demonstrable AGD-related changes of the brain. Nearly one-half of the cases (49%) was classifiable as demented in accordance with DSM IV-criteria. Moreover, the frequency of the dementia increased significantly in relation to the growing severity of the AGD-associated pathological cytoskeletal degeneration. These results confirm the assumption that AGD can cause degenerative changes ranging from cognitive impairment all the way to dementia. They also underscore the necessity of further prospective studies pertaining to the clinical aspects of this still enigmatic disease.

Aged↗
PubMed2000

Expression of MAP1a and MAP1b in the ganglionic eminence and the internal capsule of the human fetal brain.

The expression of microtubule-associated proteins 1a and 1b (MAP1a and 1b) were investigated in two transient structures, the ganglionic eminence (GE) being a prominent part of the telencephalic proliferative zone and the perireticular nucleus (PR) within the internal capsule (IC). Anti-MAP1a immunolabels PR neurons from 18 weeks of gestation (wg) onwards, whereas anti-MAP1b immunolabels long IC fibers between 18 and 22 wg. MAP1b is further present in thalamic fibers that seem to terminate at the medial margin of the GE, in a moderate number of cells of the GE and its medial extension, the gangliothalamic body (GTB). From 26 to 33 wg MAP1b is expressed in short fiber bundles of the IC, a few MAP1b-positive cells are seen in the GE. MAP1a has so far been described to appear in differentiated neurons and to be related to late developmental events. However, the transient PR being involved in axonal guidance as an intermediate target shows a precocious MAP1a-expression. The MAP1b-finding that thalamocortical fibers accumulate at the GE-margin indicates that this region represents an intermediate target for these fibers. The short MAP1b fiber bundles found in the IC are in accordance with cell culture experiments showing that MAP1b is concentrated in distal parts of outgrowing axons.

Cell Differentiation↗
PubMed2000

Transient expression of synaptogyrin in the ganglionic eminence of the human fetal brain.

The ganglionic eminence (GE) representing a conspicuous bulb-like elevation of the telencephalic proliferative zone has recently been shown to be involved in the establishment of cortical connections. This study demonstrates the presence of synaptogyrin-immunoreactivity in a large number of cell bodies of the human GE between 12 and 20 weeks of gestation. From the 20th week onwards synaptogyrin expression sharply declines. No immunoreactive structures are detectable in the 23rd week or later. As the GE persists nearly throughout the entire fetal period these results show that its neurochemical features change distinctly in the course of development. The synaptogyrin-immunoreactive GE-cells may form an early corticopedal connection which provides a scaffold for outgrowing cortical axons.

Abortion, Induced↗
PubMed2000

Pathological changes in the parahippocampal region in select non-Alzheimer's dementias.

The transentorhinal and entorhinal regions of the human brain extend over the ambient gyrus and anterior portions of the parahippocampal gyrus. They are important components of the limbic loop which receives its major afferents from the neocortical sensory association areas and generates powerful efferent projections both directly and via intermediary relay stations to the prefrontal cortex. The bilateral structural preservation of limbic loop components is a prerequisite for the maintenance of intact memory functions. In progressive neurodegenerative diseases, such as Alzheimer's disease, argyrophilic grain disease, Pick's disease, idiopathic Parkinson syndrome, and Huntington's disease, the transentorhinal and entorhinal regions are particularly susceptible to severe pathological changes. The transentorhinal region typically registers the initial alterations and becomes the most severely involved. From this transitional region of the mesocortex, the alterations usually invade with decreasing severity both the entorhinal region and temporal proneocortex. Each type of lesion that develops in the above-mentioned neurodegenerative disorders hampers or even interrupts data-transport from the sensory neocortex to the prefrontal neocortex, thereby contributing to the insidious development of progressive changes in personality, cognitive decline, and, ultimately, dementia.

Alzheimer Disease↗