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R Prior

Publications and source records attributed to R Prior.

34 records · Page 2Linked to original sources
PubMed1991

Localization of Alzheimer beta A4 amyloid precursor protein at central and peripheral synaptic sites.

We have recently shown that the amyloid beta A4 precursor protein (APP) is synthesized in neurons and undergoes fast axonal transport to synaptic sites [Koo et al., Proc. Natl. Acad. Sci. U.S.A., 87 (1990) 1561-1565]. Using immunofluorescence, laser confocal microscopy and immunoelectron microscopy with simultaneous detection of APP and synaptophysin, we now report a preferential localization of APP at synaptic sites of human and rat brain and at neuromuscular junctions. APP is further found on vesicular elements of neuronal perikarya, dendrites and axons. The synaptic localization of APP implies (1) a role of APP in physiological synaptic activity and (2) a potential and early impairment of central synapses when synaptic APP is converted to beta A4 amyloid during the pathological evolution of Alzheimer's disease and Down's syndrome.

Amyloid beta-Protein Precursor↗
PubMed1991

Quantitative changes in the amyloid beta A4 precursor protein in Alzheimer cerebrospinal fluid.

The major three secretory isoforms of Alzheimer beta A4 amyloid precursor protein (APP) were quantified in cerebrospinal fluid (CSF) using (1) a newly developed enzyme-linked immunosorbent assay (ELISA) and (2) densitometric analysis of CSF Western blots. The protease inhibitor-containing APP751/770 isoforms represented an average of 10.5% of total APP in CSF of patients with Alzheimer's disease (AD, n = 22), multi-infarct dementia (MID, n = 5) and normal controls (n = 10). APP levels in CSF did not depend on total CSF protein. Both findings are inconsistent with a hematogeneous origin of APP in CSF and suggest an intracerebral source. Total APP, APP695 and APP751/770 were significantly decreased in the AD and in the MID groups, but were not correlated to the ages of patients or controls.

Aged↗
PubMed1991

Mechanisms of amyloid deposition in Alzheimer's disease.

At the cellular level, Alzheimer's disease (AD) must be the result of neuronal dysfunction and degeneration leading to a reduction in synaptic density. Filamentous deposits of amyloid, which define the disease at the molecular level, occur within perikarya, axons, dendrites, and terminals of neurons as neurofibrillary tangles (NFT), in the extracellular neuropil as amyloid plaques (APC), and around blood vessels as amyloid congophilic angiopathy (ACA). These fibrillar amyloid protein aggregates are also found in the brain of all individuals with Down's syndrome after the age of 30 years. The amyloid deposits apparently occur in the terminal zones of neurons that develop NFT. It is suggested that amyloid deposition is of fundamental significance in AD and that a thorough understanding of amyloid formation will eventually lead to successful therapeutic intervention in AD. As elucidation of the reasons behind amyloid deposition must shed some light on the pathogenesis of AD, we review the current state of knowledge on the nature of the AD amyloid protein, its origin, and its formation. Although there is yet no agreement about the chemical nature of the amyloid protein of NFT, the major constituent of both APC and ACA has been shown to be a 4.5-kD amyloid protein originally termed "beta-protein" or "amyloid A4" which we now denote as "beta A4." Amyloid beta A4 protein is proteolytically derived from a transmembrane protein termed amyloid precursor protein (APP) which is encoded by a widely expressed gene on chromosome 21. Our present results are consistent with the possibility that amyloid formation requires membrane damage or APP molecules that are not or are incorrectly integrated into membranes. To allow the generation of the C-terminus of beta A4, one proteolytic cleavage step has to occur in the sequence that normally forms the transmembrane domain of the APP proteins. This cleavage is crucial for amyloid formation because we could show that the ability of synthetic beta A4 to form amyloid depositions is mainly based on hydrophobic parts of the sequence that have to interact with each other and build up large aggregates under physiologic conditions. Membrane association of APP is expected to interfere with this cleavage and the process of aggregation.

Aging↗
PubMed1990

Synthesis and secretion of Alzheimer amyloid beta A4 precursor protein by stimulated human peripheral blood leucocytes.

Alzheimer amyloid precursor proteins (APP) are actively secreted by stimulated human peripheral mononuclear blood leucocytes (PMBLs). Induction of APP transcription, translation and secretion was observed with several T cell mitogens but was highest with phytohemagglutinin. The time course of induction is similar to that reported for IL-2 and IL-2 receptor. We suggest that APP may play an important role in the construction of the immunological network and the differentiation of T cells.

Amyloid beta-Peptides↗
PubMed1990

Transferrin receptor expression in tumours of the human nervous system: relation to tumour type, grading and tumour growth fraction.

The expression of transferrin receptor (Tr) was investigated by means of immunohistochemistry in 101 tumours of the human central and peripheral nervous system. The results were compared with the proliferative activity of the tumours, determined by immunostaining for the proliferation-associated antigen Ki-67. In addition to immunostaining of normal and proliferated blood vessel endothelium and of a fraction of tumour infiltrating lymphocytes, we observed staining for Tr in a variable fraction of neoplastic cells of all histological tumour types. Immunoreactivity in the majority of tumour cells was found only in anaplastic tumours such as glioblastomas. Furthermore, a positive correlation between Tr expression and the Ki-67 growth fraction was established for gliomas. Non-glial tumours strongly expressing Tr included one metastatic rhabdomyosarcoma, one intracerebral malignant lymphoma, two of four plasmocytomas and seven of nine metastatic carcinomas. Our results indicate that immunohistochemistry for Tr and Ki-67 can provide additional information about the biological behaviour of nervous system tumours, thus complementing conventional histopathological criteria for anaplasia.

Antigens, Surface↗
PubMed1990

Does prostaglandin E1 and superoxide dismutase prevent ischaemic spinal cord injury after thoracic aortic cross-clamping?

The beneficial use of prostaglandin E1 (PGE1) and superoxide dismutase (SOD) on the tolerance to ischaemia of the spinal cord was evaluated following thoracic aortic cross-clamping in dogs. Aside from spinally evoked somatosensory potential (SEP) by means of a bipolar epidural catheter, postoperative evaluation of motor deficits was used to determine the efficiency of pharmacological protection when compared with controls. The animals were divided into four groups. Group I (n = 12) served as controls. The dogs of Group II (n = 12) were treated with PGE1 (100 ng/kg/min) during clamping and the first hour after declamping. In the third group (n = 12) SOD was given as an intra-arterial bolus (1 mg/kg) prior to declamping which was followed by a continuous perfusion (0.4 mg/kg/min) into the carotid artery for 25 min. In Group IV (n = 12) the dogs were treated with a combination of PGE1 and SOD in the same manner as in Groups 3 and 4. Results after pharmacological protection were significantly better than controls. In Group I all animals but one (92%) were paraplegic, as were five in Group II (42%) and eight in Group III (67%). In contrast no dog in Group IV developed paraplegia. There was a close correlation of SEP and postoperative recovery. The group with combination therapy (PGE1 plus SOD) was characterised by a loss of the evoked potential for a mean of 15 min, the PGE1 group for 45.8 min and the SOD group for 58.5 min. While the control group was characterised by a loss of 72.7 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1990

Hormonal dependency of cerebral meningiomas. Part 1: Female sex steroid receptors and their significance as specific markers for adjuvant medical therapy.

Female sex steroid receptors were examined in 50 human cerebral meningiomas. For estrogen receptors, high-affinity binding sites (dissociation constant (Kd): 0.05 to 0.2 nM) were found in the cytosolic fraction with a capacity of less than 4 fmol/mg protein in 10 meningiomas using a dextran-coated charcoal (DCC) assay. In the same cytosolic fraction, the solid-phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol/mg protein. However, in the nuclear compartment, none of the tumors stained positively for estrogen receptors with immunohistochemical techniques. In addition, the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid (mRNA). In none of the 50 meningiomas was the expression of estrogen mRNA coding for the estrogen receptor detected. For progesterone receptors, high-affinity binding sites (Kd: 0.3 to 2.6 nM) were found in 49 of the 50 tumors using a DCC assay. In the same cytosols, solid-phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors. However, in the nuclear compartment, only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques. Within the confines of this study, it is concluded that: 1) the estrogen receptor is generally absent in meningioma tissue, and 2) the progesterone receptor is mainly absent in the nuclear compartment, leading to the conclusion that the cytosolic progesterone receptor may be an inactive form. This study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas.

Adult↗
PubMed1990

Ultrastructural localization of the putative precursors of the A4 amyloid protein associated with Alzheimer's disease.

Any explanation of the causes of Alzheimer's disease and of its unique cerebral pathologic features must take into account the distribution and ultrastructural localization of the pre-A4 amyloid proteins in tissues and organs. The authors have analyzed the expression of the pre-A4 amyloid proteins in several tissues by immunogold electron microscopy and by immunofluorescence. For this purpose, they have used a mouse monoclonal antibody and a guinea pig antiserum raised against two synthetic peptides corresponding to two different sequences common to all the full-length forms of the A4 amyloid precursors. They observed a tissue-specific distribution of the secreted and the transmembrane form of the precursors. The authors could determine that the secreted form is generated in vivo within the cytoplasm. In the salivary glands and in the adenohypophysis, all the immunoreactivity is associated with the process of secretion, whereas in the muscle, a staining pattern compatible with the presence of the pre-A4 amyloid proteins in the sarcoplasmic reticulum has been observed. This difference in the localization may reflect tissue-specific processing pathways and suggests that posttranslational modifications such as proteolytic removal of the transmembrane and cytoplasmic domains contribute to the structural and thus functional diversity of the A4 amyloid precursors.

Alzheimer Disease↗
PubMed1989

Epidermal growth factor receptor expression and growth fraction in human tumours of the nervous system.

100 tumours of the human nervous system were investigated by means of immunohistochemistry in order to determine the expression of epidermal growth factor receptor (EGFr) and the proliferative activity as evaluated by demonstration of the proliferation-associated Ki-67 antigen. Epidermal growth factyr receptor immunoreactivity was present in 79% (23/29) of the high-grade malignant gliomas examined but in only 9% (2/22) of the low-grade gliomas. Besides the gliomas, EGFr-expression was detectable in smaller amounts in most (13/15) meningiomas, in one anaplastic neurinoma and in individual tumour cells of one medulloblastoma. In addition, EGFr-expression was found in 50% (6/12) of metastatic carcinomas. Seven of eight medulloblastomas, two cerebral primitive neuroectodermal tumours (PNETs), three benign neurinomas, one ganglioneuroma, one metastatic intracerebral malignant melanoma, three spinal plasmacytomas and one immunocytoma showed no detectable EGFr-expression. Our results indicate that (1) the expression of EGFr in human tumours of the nervous system depends on the histological tumour type and (2) in the glioma group is related to the grade of malignancy. A close correlation between EGFr-expression and proliferative activity as evaluated by Ki-67 staining could not, however, be established.

Cell Division↗
PubMed1989

Nerve growth factor receptor in tumours of the human nervous system. Immunohistochemical analysis of receptor expression and tumour growth fraction.

The expression of nerve growth factor receptor (NGFr) was investigated by means of immunohistochemistry in 135 tumours of the human central and peripheral nervous system. The results were compared to the proliferative activity of the tumours as determined by immunostaining for the proliferation-associated antigen Ki-67. Immunoreactivity for NGFr was most consistently observed in tumours derived from the neural crest such as neurinomas, neurofibromas and ganglioneuromas. In tumours of the central nervous system, NGFr-immunostaining was particularly strong in pilocytic astrocytomas while the majority of other gliomas were either NGFr-negative or contained only a minor fraction of NGFr-positive tumour cells. Among all other investigated tumours including medulloblastomas, pituitary adenomas and meningiomas only exceptional cases demonstrated a significant number of positive tumour cells. Choroid plexus papillomas and metastatic carcinomas were always NGFr-negative. Our results indicate that NGFr-expression in tumours of the human nervous system is heterogenous with respect to tumour type and appears to be unrelated to proliferative activity.

Humans↗
PubMed1985

Parkinson's disease in the district of the Northampton Health Authority, United Kingdom. A study of prevalence and disability.

The study of a population of 208,000 in a Midlands district of England has shown the prevalence of idiopathic Parkinson's disease to be 108.4 per 100,000. This is comparable with past studies in Carlisle, England, Rochester, Minnesota, and South-West Finland. Parkinsonism associated with cerebrovascular disease is evidently recognised and differentiated by general practitioners; post-encephalitic parkinsonism is not encountered and drug-induced parkinsonism is not common in this district. The major functional disability of a carefully assessed randomly selected group was found to relate to walking and hygiene. Nevertheless, the essential physical needs of those with Parkinson's disease appear to be well met in general.

Age Factors↗
PubMedDate not supplied

[Immunocytochemical and biochemical studies of an Ewing sarcoma cell line: evidence for neural differentiation in vitro].

A cell line established from a Ewing's sarcoma removed from the fibula of a 19-year-old female was investigated for morphology and hormone sensitivity. Cells in culture expressed neurofilaments and showed positive immunostaining for neuron-specific enolase (NSE), Leu-7-antigen (HNK-1) and S-100 protein. The cells also contained PAS-positive, diastase-digestible cytoplasmic material, indicative of glycogen inclusions. Moreover, the cells responded to dopamine as well as to beta-adrenergic agonists and prostaglandins to stimulate cyclic AMP synthesis and 3H-glycogen hydrolysis. In conclusion, the morphological and biochemical data show evidence for a neural differentiation pattern of Ewing's sarcoma cells in vitro.

Antigens, Differentiation↗