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Biomedical subjects

H J Gertz

Publications and source records attributed to H J Gertz.

At least 19 recordsLinked to original sources
PubMed2000

Aberrant expression of nNOS in pyramidal neurons in Alzheimer's disease is highly co-localized with p21ras and p16INK4a.

Aberrancies of growth and proliferation-regulating mechanisms might be critically involved in the processes of neurodegeneration in Alzheimer's disease (AD). Expression of p21ras and further downstream signalling elements involved in regulation of proliferation and differentiation as, for example, MEK, ERK1/2, cyclins, cyclin-dependent kinases and their inhibitors such as those of the p16INK4a family, are elevated early during the course of neurodegeneration. Activation of p21ras can also directly be triggered by nitric oxide (NO), synthesized in the brain by various isoforms of nitric oxide synthase (NOS) that might be differentially involved into the pathomechanism of AD. To study the potential link of NO and critical regulators of cellular proliferation and differentiation in the process of neurofibrillary degeneration, we analyzed the expression pattern of NOS-isoforms, p21ras and p16INK4a compared to neurofibrillary degeneration in AD. Additionally to its expression in a subtype of cortical interneurons that contain the nNOS-isoform also in normal brain, nNOS was detected in pyramidal neurons containing neurofibrillary tangles or were even unaffected by neurofibrillary degeneration. Expression of nNOS in these neurons was highly co-localized with p21ras and p16INK4a. Because endogenous NO can activate p21ras in the same cell which in turn leads to cellular activation and stimulation of NOS expression [H.M. Lander, J.S. Ogiste, S.F.A. Pearce, R. Levi, A. Novogrodsky, Nitric oxide-stimulated guanine nucleotide exchange on p21 ras, J. Biol. Chem. 270 (1995) 7017-7020], the high level of co-expression of NOS and p21ras in neurons vulnerable to neurofibrillary degeneration early in the course of AD thus provides the basis for an autocrine feedback mechanism that might exacerbate the progression of neurodegeneration in a self-propagating manner.

Aged↗
PubMed2000

[Diminution of hand writing area and D2-dopamine receptor blockade. Results from treatment with typical and atypical neuroleptics].

Beside the typical extrapyramidal motor symptoms such as rigidity, tremor, and dyskinesia, a reduction in handwriting area may occur under neuroleptic therapy. To date, the nature of the relationship between a reduction in handwriting area and striatal D2 dopamine receptor occupancy has remained unclear, and it is not known whether such a reduction also occurs under treatment with atypical neuroleptic drugs. In 23 schizophrenic patients treated with haloperidol, haloperidol decanoate, risperidone, and clozapine, the handwriting are was examined using a planimetric computer program. 123I-iodobenzamide (IBZM) single photon emission tomography (SPET) was used to measure the D2 dopamine receptor occupancy. A statistically significant correlation was found between a reduction in handwriting area and D2 dopamine receptor occupancy (r = 0.86; P < 0.0001). The curve derived from the plotted data resulted in a hyperbolic function. The regression was present regardless of whether the patients were treated with typical or atypical neuroleptic drugs.

Adult↗
PubMed2000

Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer's disease.

We have examined the relationships between dementia, loss of synaptic proteins, changes in the cytoskeleton, and deposition of beta-amyloid plaques in the neocortex in a clinicopathologically staged epidemiological cohort using a combination of biochemical and morphometric techniques. We report that loss of synaptic proteins is a late-stage phenomenon, occurring only at Braak stages 5 and 6, or at moderate to severe clinical grades of dementia. Loss of synaptic proteins was seen only after the emergence of the full spectrum of tau and beta-amyloid pathology in the neocortex at stage 4, but not in the presence of beta-amyloid plaques alone. Contrary to previous studies, we report increases in the levels of synaptophysin, syntaxin, and SNAP-25 at stage 3 and of alpha-synuclein and MAP2 at stage 4. Minimal and mild clinical grades of dementia were associated with either unchanged or elevated levels of synaptic proteins in the neocortex. Progressive aggregation of paired helical filament (PHF)-tau protein could be detected biochemically from stage 2 onwards, and this was earliest change relative to the normal aging background defined by Braak stage 1 that we were able to detect in the neocortex. These results are consistent with the possibility that failure of axonal transport associated with early aggregation of tau protein elicits a transient adaptive synaptic response to partial de-afferentation that may be mediated by trophic factors. This early abnormality in cytoskeletal function may contribute directly to the earliest clinically detectable stages of dementia.

Alzheimer Disease↗
PubMed1999

Positive correlation between reduction of handwriting area and D2 dopamine receptor occupancy during treatment with neuroleptic drugs.

We investigated the relationship between fine extrapyramidal-motor symptoms (reduction of handwriting area) and D2 dopamine receptor occupancy under neuroleptic treatment. The handwriting of 18 schizophrenic patients before and during treatment with typical (haloperidol, haloperidol decanoate) and atypical (clozapine, risperidone) neuroleptic drugs was examined. Data analysis of the handwriting's examination was carried out with a planimetric computer programme. At the time of the second test of handwriting, D2 receptor occupancy was determined with single photon emission tomography (SPET) using [(123)I]iodobenzamide ((123)I-IBZM). In all patients, a reduction of handwriting area and a D2 receptor occupancy were found. The correlation between reduction of handwriting area and D2 receptor occupancy for typical and atypical neuroleptic drugs was linear and statistically significant (r=0.9; P > 0.001). Our findings point to the possibility that the reduction of handwriting area may be used as a clinical indicator of D2 receptor occupancy under treatment with neuroleptic drugs.

Adult↗
PubMed1999

Power of theta waves in the EEG of human subjects increases during recall of haptic information.

Several studies have reported a functional relationship between spectral power within the theta-band of the EEG (theta-power) and memory load while processing visual or semantic information. We investigated theta power during the processing of different complex haptic stimuli using a delayed recall design. The haptic explorations consisted of palpating the structure of twelve sunken reliefs with closed eyes. Subjects had to reproduce each relief by drawing it 10 s after the end of the exploration. The relationship between mean theta power and mean exploration time was analysed using a regression model. A linear relationship was found between the exploration time and theta power over fronto-central regions (Fp1, Fp2, F3, F7, F8, Fz, C3) directly before the recall of the relief. This result is interpreted in favour of the hypothesis that fronto-central theta power of the EEG correlates with the load of working memory independent of stimulus modality.

Adolescent↗
PubMed1999

Cortical load of PHF-tau in Alzheimer's disease is correlated to cholinergic dysfunction.

To assess a potential relationship between cortical neurofibrillary degeneration and cortical cholinergic deafferentation, the load of PHF-tau was analysed in eight cortical regions and in the basal nucleus of Meynert in 12 cases with Alzheimer's disease by means of a sensitive ELISA employing the monoclonal antibody B5-2. The activity of choline acetyltransferase was determined on identical tissue samples. The results demonstrate a highly correlative relationship between the cortical distribution of the amount of PHF-tau, mainly present in neuropil threads, and cholinergic depletion early during the course of the disease. This relationship was less strong in more advanced stages. The results support the suggestion that the formation of PHF-tau in cholinergic axon terminals which might result in a loss of cholinergic synapses and a cholinergic dysconnection of the cortex, is an early event in AD. During the progression of the disease, formation of PHF-tau appears to spread over the cortex which results in a more even distribution of neuropil threads and a progressive involvement of non-cholinergic neurons.

Aged↗
PubMed1999

[Haptic perception and EEG changes in anorexia nervosa].

OBJECTIVES: We predicted that due to diminished somatosensory integrative ability, the anorectic patients would have problems reproducing haptic stimuli. In addition we sought to determine whether EEGs from anorectic patients (AN) and the healthy controls (CO) would show discrepancies between the two groups during haptic explorations in theta-power over the right parietal region. METHOD: EEG power (theta-power) data of AN (n = 13) and CO (n = 13) were analyzed during haptic exploration tasks and rest intervals. The haptic explorations consisted of palpating the structure of six sunken reliefs in sequence with both hands, eyes closed. After each exploration the structure was drawn on a piece of paper. RESULTS: The reproductions of haptic stimuli submitted by the anorectic patients were of notably poorer quality than those of the healthy controls. During rest intervals and haptic explorations, spectral power was generally lower in the AN group in comparison to the healthy controls. Significant theta-power differences between groups showed over the right parietal cortex during haptic explorations. The decrease in EEG power in the anorectic patients in the theta bands across the right parietal region during haptic exploration tasks could be interpreted as a minor activation of visuo-spatial regions. The results of the haptic explorations as well as the EEG-power changes indicate a cortical dysfunction and deficits in somatosensory integration processing in anorexia nervosa patients.

Adolescent↗
PubMed1998

The prognosis of mild cognitive impairment in the elderly.

PURPOSE: To determine whether or not subtypes of intellectual functioning are suitable to predict further cognitive decline in individuals with mild cognitive impairment. DESIGN: Naturalistic longitudinal study (mean interval 2.7 years). PATIENTS: 41 subjects with mild cognitive impairment who attended a memory clinic. METHODS: SIDAM, CT, SPECT, and ApoE genotype. RESULTS: At follow-up, 8 out of 41 patients (19.5%) with MCI had progressed to dementia, 8 patients (19.5%) had improved to normal levels of cognitive functioning, 25 patients (61%) had remained stable within the MCI group. At baseline the two prognostic groups differed significantly with regard to age, memory functions, orientation, and the degree of atrophy of the left medial temporal lobe on CT scan. CONCLUSION: The majority of MCI patients in this study remained cognitively stable within the observation period. Patients with older age, poorer test performance on memory tasks and orientation deficits are at higher risk of progressive decline to dementia. CT measures of medial temporal lobe atrophy may be a sensitive parameter of group discrimination.

Aged↗
PubMed1998

Examination of the validity of the hierarchical model of neuropathological staging in normal aging and Alzheimer's disease.

The neuropathological staging model of Alzheimer's disease proposed by Braak and Braak [Acta Neuropathol (1991) 82:259] requires that the evolution of neurofibrillary pathology follows a predictable pattern that can be ordered in a regular regional hierarchy. We have operationalized the neuropathological staging system to permit testing of its validity. Forty-two cases were derived from an epidemiological study of cognitive function in an elderly population for which post-mortem brain tissue was collected. Cases with neuropathological diagnoses other than Alzheimer's disease and normal aging were excluded. Neurofibrillary tangle counts were determined in all cortical laminae and regions used for staging. There was a significant correlation between the overall extent of neurofibrillary pathology and the number of regions affected. There were frequent order violations in the proposed hierarchy: 19 instances (45%) involving entorhinal and transentorhinal cortices, and 16 instances (38%) involving CA1 of hippocampus and entorhinal cortex. Only 6 out of 42 cases conformed in all regions to the expected hierarchy. Nevertheless, 90% of the cases had 2 order violations or less, supporting the approximate validity of the hierarchy.

Aging↗
PubMed1998

Cortical distribution of neurofibrillary tangles in Alzheimer's disease matches the pattern of neurons that retain their capacity of plastic remodelling in the adult brain.

The formation of neurofibrillary tangles in Alzheimer's disease shows a preferential involvement of certain cytoarchitecturally defined cortical areas suggesting systematic differences in regional neuronal vulnerability. The cellular and molecular nature of this selective neuronal vulnerability that follows a certain hierarchy of structural brain organization is largely unknown. In the present study, we compared the regional pattern of tangle density in Alzheimer's disease with systematic regional differences in neuronal plasticity that can be observed both during ageing and in Alzheimer's disease. Changes in dendritic length and arborization of Golgi-impregnated pyramidal neurons were analysed after three-dimensional reconstruction in 12 cortical areas. The intensity of dendritic remodelling that was observed during ageing as well as in Alzheimer's disease was regionally different and decreased in the following order: transentorhinal region > limbic areas (entorhinal region, hippocampus) > non-primary association areas (37, 40, 46) > primary sensory association areas (7, 18, 22) > primary sensory and motor cortex (17, 41, 4). These regional differences of neuronal plasticity follow the same pattern as the regional vulnerability to tangle formation in Alzheimer's disease. The results of the present study provide evidence that a high degree of structural neuronal plasticity might predispose neurons to tangle formation.

Adult↗
PubMed1996

The relationship between clinical dementia and neuropathological staging (Braak) in a very elderly community sample.

The neuropathological staging model proposed by Braak and Braak (1991) implies that the evolution of neurofibrillary pathology follows a predictable sequence and can be ordered in a regular regional hierarchy. A total of 42 cases of an elderly population sample, which had been prospectively clinically assessed, were examined. Clinical diagnosis was made according to the CAMDEX criteria, and the sample reported here did not include cases were vascular dementia according to the criteria proposed by Chui et al. (1991). The neuropathological staging procedure was applied as originally proposed by Braak and Braak (1991). In addition, in all cortical laminae and regions which are essential for the staging model neurofibrillary tangles were quantified. Demented cases had significantly more areas involved and more advanced neuropathological stages. Cases with stages 1-3 tended to be non-demented, and cases with stages 4-6 tended to be demented. However, there was a considerable degree of overlap and no clear-cut threshold could be established. This brings into question the diagnostic value of the staging model.

Aged↗
PubMed1994

Stability of cell size and nucleolar size in Lewy body containing neurons of substantia nigra in Parkinson's disease.

Samples of 9 brains of autopsied patients suffering from Parkinson's disease were examined. In H & E stained 20 microns thick sections of substantia nigra 10 Lewy body containing and 20 unaffected pigmented nerve cells of substantia nigra per case were measured for size of the perikarya and nucleolar size utilizing an interactive image processing unit. In affected cells the size of Lewy bodies was measured too. There was no significant difference in the size of the perikarya and nucleolar size between affected and unaffected cells. In Lewy body bearing cells nucleolar size was not correlated with the size of the Lewy bodies. There was a significant negative correlation between nucleolar size of substantia nigra neurons and the duration of the disease. Since nucleolar volume can serve as indicator of RNA synthesis of a cell, Lewy bodies do not seem to disturb nerve cell metabolism.

Aged↗
PubMed1992

[Brief depressive affect].

A 59-year-old patient suffered during three months from depressive episode. Thereafter he developed depressive attacks of 30 to 60 minutes duration, reoccurring weekly to every third week. The patient could be treated successfully with Carbamacepine.

Carbamazepine↗
PubMed1991

Tangle-bearing neurons show more extensive dendritic trees than tangle-free neurons in area CA1 of the hippocampus in Alzheimer's disease.

To elucidate the pathogenetic significance of neurofibrillary tangles in Alzheimer's disease, the dendritic tree of tangle-bearing and unaffected pyramidal cells of area CA1 of the hippocampus was morphometrically examined. Golgi-stained neurons were assessed which were deimpregnated and counterstained with Congo red to visualize neurofibrillary tangles. The study revealed that tangle-bearing neurons have more extensive apical dendritic trees than tangle-free neurons. It is concluded that metabolic processes associated with the formation of neurofibrillary tangles may increase neurotrophic activity on a single cell level and counteract the cellular degeneration process.

Aged↗
PubMed1991

Low melanin content of substantia nigra in a case of neuroleptic malignant syndrome.

A 19-year-old man suffering from a first episode of schizophrenia developed a neuroleptic malignant syndrome (NMS) after administration of haloperidol and levomepromazine. After five weeks of neuroleptic treatment he died of an unknown cause. Histological examination of the brain revealed a low melanin content in neurons in the substantia nigra (SN). Since neuromelanin in SN is the end-product of nonenzymatic dopamine degradation, the amount of melanin probably depends on the overall amount of dopamine produced during life. Thus, dopamine production must have been low in the reported case. In addition, ectopic neurons were found in subcortical white matter.

Adult↗
PubMed1991

Pathological changes in dendrites of substantia nigra neurons in Parkinson's disease: a Golgi study.

Neurons of the substantia nigra show severe morphological changes in Parkinson's disease. Pathological alterations of cell bodies have been described, whereas those of neuronal processes have hardly been investigated. Golgi impregnation has been the chosen method for demonstrating neuronal processes and dendritic and somatic spines. We therefore used the Golgi-Braitenberg method to qualitatively and semi-quantitatively study the substantia nigra of eight patients with Parkinson's disease compared with eight control cases. Golgi impregnation of substantia nigra neurons was good in all control cases. In full agreement with the analysis of Braak and Braak (1986) three neuronal types within the substantia nigra were found. In cases of Parkinson's disease, severe pathological changes such as decrease of dendritic length, loss of dendritic spines and several types of dendritic varicosities were found only in the melanin-containing pars compacta neurons. Pars reticulata nerve cells were intact. These findings support the predominant role played by the dopaminergic efferent pathway in the degenerative process. The afferent pathway was not affected. This suggests that the substantia nigra lesion is primary in Parkinson's disease. Loss of neurons found in H & E sections corresponded to a lesser amount of impregnated pars compacta neurons in cases with Parkinson's disease when compared to controls. Evidences exist that the duration of the disease may be related to the extent of pathologically altered Golgi-impregnated pars compacta cells. The amount of Lewy bodies in H & E sections corresponded to the quantity of round varicosities in impregnated pars compacta neurons. These round dendritic varicosities were considered to be Lewy body inclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗