Immunocytochemical demonstration of vasopressin binding in rat kidney
PubMed, Nov 1, 1990
We investigated the immunoperoxidase demonstration of vasopressin (VSP) bound to paraffin-embedde... more We investigated the immunoperoxidase demonstration of vasopressin (VSP) bound to paraffin-embedded sections of rat kidney and the effects of various fixatives. Slices of rat kidney from normal and 4-day water-deprived rats were incubated with 10(-7) M VSP, fixed, and embedded in paraffin. Hydrated sections of these tissues were again incubated with 10(-7) M VSP or 10(-7) M VSP and 10(-5) M oxytocin (OXY). VSP bound to the sections was demonstrated using rabbit anti-Arg8 VSP antiserum and peroxidase-labeled second antibody. In sections of kidney from both normal and water-deprived rats, immunoperoxidase labeling was most intense in the renal papilla and was restricted to the cells of the ducts of Bellini and loops of Henle. In the medulla, the collecting ducts and medullary thick ascending limbs of Henle were moderately stained. In the normal kidney sections there was no staining of the proximal tubules, distal convoluted tubules (DCT), and only slight staining of the cortical collecting ducts (CCD). However, in the water-deprived rats there was a considerable increase in the staining of the DCT and CCD. Simultaneous incubation in OXY and VSP resulted in reduced immunoperoxidase labeling of the tubules. Omission of VSP incubation led to a similar decrease in stain intensity, indicating a specificity for the sites of VSP binding. This technique allows the identification of cells responsible for the binding of VSP in the kidney.
Brain Banking in Psychiatric Disorders: The Amsterdam Experience
The growing number of sophisticated neurobiological techniques that can be applied on postmortem ... more The growing number of sophisticated neurobiological techniques that can be applied on postmortem brain obtained from psychiatric patients increases the pressure on brain banks to supply autopsy material to the scientific community. Brain banks that collect postmortem tissue from patients with psychiatric disorders form an important link between clinicians, scientists, and neuropathologists. The rapid autopsy system we set up in Amsterdam for collecting brain specimens for research on depression, bipolar disorders, and schizophrenia includes matching for several factors, both antemortem and postmortem. Antemortem factors include age, sex, agonal state, seasonal alterations, circadian variation, clock time of death, and medication. Postmortem factors include postmortem delay, fixation and storage time, and lateralization. The material and data collected by the Netherlands Brain Bank as presented in this chapter illustrate the wide variety of potentialities and pitfalls in the use of autopsy tissue for research on psychiatric disorders.
A brain bank is a prospective source of adequately collected and preserved tissues of the central... more A brain bank is a prospective source of adequately collected and preserved tissues of the central nervous system obtained via a donor program, which are supplied for neurobiological research. Brain tissue banks collect brains, serum and cerebro-spinal fluid from patients suffering from neurological disorders such as Alzheimer's diseases, Parkinson's disease and multiple sclerosis for diagnostic purposes and for the development of future diagnostic tests. To create and develop the right infrastructure underlying brain bank activities, one should have a medico-legal and ethical support according to local legislation. From an ethical point of view, brain bank activities can be divided into the following categories: a) factors related to the donor program; b) factors related to handling and management of organs; c) factors related to scientific research. The present paper deals with the above mentioned issues according to world-wide recognised ethical considerations and recommendations of several official statements, and specifies the objectives of the European Brain Bank Network (EBBN).
It is essential to examine brain materials for the understanding the cause and pathology of menta... more It is essential to examine brain materials for the understanding the cause and pathology of mental disorders. Recent methodological progress urges us to set up well qualified brain banks. Human tissue and Bio -banking is a complex field and the daily practice of brain banks needs to abide by several golden standards in order to avoid pitfalls in basic research : 1) A donor system in which informed consent is granted for the use of the samples for scientific research, including genetic analysis and access to medical records, 2) Rapid autopsy system, 3) Compatibility of protocols for procurement, management, handling and storage, 4) A generally accepted consensus on diagnostic criteria, 5) Quality control, 6) Abiding by local/international legal and ethical guidelines for work with human material, 7) Proper safety procedures. In the present review, the authors introduced the activities of European brain banks, and discussed on their current issues, and on the problems remain to be resolved.
Apoptosis is a tightly controlled process in which cell death is executed through activation of s... more Apoptosis is a tightly controlled process in which cell death is executed through activation of specific signalling pathways. Within cells, there are positive and negative regulatory pathways of apoptosis, hence it is targeted as 'Double-edged sword', the balance between these pathways dictates the cell fate. The past decade has seen intense focus on the mechanisms of apoptosis. Many important observations on the various signalling pathways mediating apoptotic cell death have been made and our understanding of the importance of apoptosis in both normal growth and development and pathophysiology has greatly increased. In addition, mechanisms of metal-induced toxicity continue to be of interest given the ubiquitous nature of these contaminants. The purpose of this review is to summarize our current understanding of the apoptotic pathways that are initiated by metals in Alzheimer's disease. Increased understanding of metal-induced (direct) and metal-amyloid-β (indirect) linked neuronal cell death through the formation of reactive oxygen species (ROS) is critical to illuminate mechanisms of metal-induced cell death, as well as the potential role of metal speciation in neurodegeneration.
The diagnosis of dementing disorders is severely hampered by the absence of reliable biomarkers t... more The diagnosis of dementing disorders is severely hampered by the absence of reliable biomarkers that can be measured in body fluids such as blood, urine and cerebro-spinal fluid (CSF). Searching for biomarkers is hampered by the huge variability between individuals; the use of autopsy specimens induces significant data fluctuation due to rapid post-mortem changes in the specimens. The search for biomarkers obtained from living donors has contributed already a vast amount of data. The role of amyloid and tau as early diagnostic markers in the pathology of dementia has been reported in differential involvement in Alzheimer's disease (AD), late onset Alzheimer disease (LOAD), Lewy Body dementia (DLBD), Vascular dementia, fronto-temporal lobar degeneration (FTLD), Mild cognitive impairment (MCI) and non neurological controls. In the coming decennia, brain/tissue/biobanks (BTB-banks) will have a major role in identifying the relevant biomarkers and will collect, preserve and type RNA and DNA extracted from brain/tissue/body fluids in order to update the pathological hallmarks of dementing disorders. The present paper reviews and compares the currently known/clinically applied biomarkers in dementia which can be identified and incorporated into clinical drug trials and elucidate proposed mechanisms of disease and drug action. Furthermore, the review screens a panel of biomarkers used for early and differential diagnosis and comments on the validity of these biomarkers in reflecting the typical hallmarks of neurological disorders.
Alzheimer's disease (AD) is a progressive dementia associated with loss of memory and cognitive d... more Alzheimer's disease (AD) is a progressive dementia associated with loss of memory and cognitive dysfunction. In a previous study, we demonstrated a decrease in b-series gangliosides along with a change in ganglioside molecular species in the hippocampal grey matter of patients with AD. The present study demonstrates the use of imaging mass spectrometry for analyzing the spatial arrangement of ganglioside GM1 (GM1) molecular species in the hippocampus. In AD patients, we found a decrease in the ratio of GM1(d20:1/C18:0) to GM1 d18:1/C18:0) in the outer molecular layer (ML) of the dentate gyrus. Because the outer ML is the region of main input into the hippocampus, our findings may have a direct relationship to the mechanism of dysfunction in AD.
Tauopathies such as Alzheimer disease (AD) probably involve a type of phosphorylation imbalance c... more Tauopathies such as Alzheimer disease (AD) probably involve a type of phosphorylation imbalance causing the accumulation of abnormally hyperphosphorylated tau in neurons and/or glias. Investigation of R406W tau mutation may provide insight into such abnormal tau hyperphosphorylation, since this mutation causes AD-like dementia and tauopathy in humans and because it has the unique ability to reduce tau phosphorylation in vitro and in cultured cells. Here we show that R406W mutation primarily disrupts tau phosphorylation at Ser404, a priming phosphorylation site of glycogen synthase kinase-3β (GSK-3β), thereby reducing subsequent GSK-3β-mediated phosphorylation at the PHF-1 site (mostly Ser396). In contrast, c-jun N-terminal kinase (JNK) as activated in the mitotic phase directly hyperphosphorylates R406W tau at the PHF-1 site. This was confirmed by PHF-1 hyperphosphorylation of R406W tau in mitotic cells, its association with cytoplasmic JNK activation, and its inhibition by a JNK inhibitor, SP600125. These data unveil the unknown mechanisms of physiological tau phosphorylation at the PHF-1 site and suggest that cytoplasmic JNK activation may play an important role in the abnormal tau hyperphosphorylation associated with R406W tau mutation and in AD.
Estrogen receptor α-immunoreactive astrocytes are increased in the hippocampus in Alzheimer's disease
Experimental Neurology, Oct 1, 2003
Postmenopausal estrogen use may decrease the risk, and delay the onset and progression, of Alzhei... more Postmenopausal estrogen use may decrease the risk, and delay the onset and progression, of Alzheimer’s disease (AD). By means of fluorescence immunocytochemistry, the present study investigated the distribution of estrogen receptor α (ERα) in the human hippocampus in controls and in AD cases. ERα immunoreactivity was observed in neurons and glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the hippocampus both
Activation of the human supraptic and paraventricular nucleus neurons with aging and in Alzheimer's disease as judged from increasing size of the Golgi apparatus
Brain Research, Dec 1, 1993
... possi-ble to retrieve the MG-160 antigen, marker of theGolgi Apparatus, from conventionally .... more ... possi-ble to retrieve the MG-160 antigen, marker of theGolgi Apparatus, from conventionally ... also indebted to HGP Blaauwgeersfrom the department of Pathology, Academic Medical Centre, Ams ... USA (NK Gonatas) and the Nether-lands Organization for Scientific Research (NWO ...
The effects of agonal status, postmortem delay, and age on human brain adenylyl cyclase activity ... more The effects of agonal status, postmortem delay, and age on human brain adenylyl cyclase activity were determined in membrane preparations of frontal cortex from a series of 18 nondemented subjects who had died with no history of neurological or psychiatric disease. Basal and guanosine 5'-U-(3-thiotriphosphate)-, aluminum fluoride-, and forskolinstimulated enzyme activities were not significantly reduced over an interval from death to postmortem of between 3 and 37 h and were also not significantly different between individuals dying with a long terminal phase of an illness and those dying suddenly. Basal and aluminum fluoride-stimulated enzyme activities showed a negative correlation with increasing age of the individual. In subsequent experiments, basal and guanosine 5'-0-(3-thiotriphosphate)-, aluminum fluoride-, and forskolin-stimulated enzyme activities were compared in five brain regions from a series of eight Alzheimer's disease and seven matched nondemented control subjects. No significant differences were observed between the groups for either basal activity or activities in response to forskolin stimulation of the catalytic subunit of the enzyme. In contrast, enzyme activities in response to stimulation with guanosine 5'-0-(3-thiotriphosphate) and aluminum fluoride
To correlate quantitative magnetic resonance (MR) imaging data (ie, relaxation times and magnetiz... more To correlate quantitative magnetic resonance (MR) imaging data (ie, relaxation times and magnetization transfer ratios [MTRs]) with histopathologic findings of demyelination and axonal disease in cervical spinal cord specimens from patients with multiple sclerosis (MS) and control subjects. Formaldehyde-fixed cervical spinal cord specimens from 11 patients with MS-three men and eight women (mean age at death, 66 years Ϯ 11.3 [standard deviation])-and two female control subjects without neurologic disease (83 and 41 years of age at death) were examined at 4.7 T. Relaxation time measurements and MTR mapping were performed. Analyses included the whole cord area and region-of-interest measurements. Histopathologic analyses included semiquantitative myelin and quantitative axonal analysis. Compared with control specimens (P Ͻ .001, analysis of variance), specimens from patients with MS had smaller cord areas (mean area, 59.0 mm 2 Ϯ 12.5 vs 72.7 mm 2 Ϯ 10.0), significant prolongation of T1 (mean prolongation, 30%) and T2 (mean prolongation, 13%), and decreased MTRs (mean, 10.5%). Within MS specimens, 58% of the white matter area displayed signal intensity abnormalities on intermediate-weighted MR images. The number of axons in normal-appearing white matter in MS specimens was, on average, 46% lower than the number of axons in white matter in control specimens. All quantitative MR parameters correlated well with demyelination; the correlation with T2 relaxation time was the strongest (r ϭ 0.77, Spearman and Kendall nonparametric correlations). By contrast, quantitative MR parameters correlated less well with axonal density; the correlation with T2 relaxation time was the strongest (r ϭ Ϫ0.44, Spearman and Kendall nonparametric correlations). Multilevel analysis, corrected for age and MS phenotype, could not result in a model explaining axonal density on the basis of quantitative MR parameters when myelin density was included as a predictor. Changes in quantitative MR imaging parameters in the cervical spinal cord in MS are mainly determined by demyelination and do not reflect axonal disease well.
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