Showing papers by "Joanne E. Martin published in 1991"
TL;DR: It is concluded that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms.
Abstract: Antibodies to ubiquitin have been used to search for evidence of abnormal protein degradation in amyotrophic lateral sclerosis—motor neuron disease (ALS). Anterior horn cell ubiquitin-immunoreactive (IR) inclusions were present in all of 31 ALS cases but in none of 23 neurologically normal and in only 1 of 22 neurologically abnormal controls. These inclusions, which were present in familial and sporadic ALS cases, and in cases with dementia, took the form of dense rounded or irregular ubiquitin-IR cytoplasmic inclusions (dense bodies), or loosely arranged bundles (‘skeins’) of filamentous-appearing material. The presence of ubiquitin-IR inclusions corresponded to the pattern of selective neuronal vulnerability in ALS, although inclusions in pyramidal neurons of the motor cortex were infrequent and were noted in only a minority of cases. Ubiquitin-IR inclusions were more prevalent than Bunina Bodies. The latter were present in 67% of ALS cases but were seldom labelled by antibodies to ubiquitin. Intranuronal inclusions resembling Lewy bodies were present in 23% of ALS cases and were often identified by antibodies to ubiquitin. We conclude that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms. Ubiquitin-IR inclusions in ALS differ from ubiquitinated inclusions in other neuronal degenerations in that they are not readily identified by antibodies to cytoskeletal proteins. They may represent accumulations of altered or abnormal neuronal proteins resistant to degradation via the ubiquitin proteolytic pathway.
344 citations
TL;DR: A newly identified myopathy of the internal anal sphincter is described in this paper, which causes severe proctalgia fugax and rectal evacuation difficulty, and the maximum anal canal pressure was usually increased with marked low wave activity.
118 citations
TL;DR: Although ubiquitin, HSP72 and p57 are stress–induced proteins, they are expressed differently and might therefore have different significance in neuronal degeneration.
Abstract: The expression of two heat shock proteins, HSP72 and p57, in addition to ubiquitin, has been studied immunocytochemically in nine amyotrophic lateral sclerosis (ALS) cases and 10 agematched controls. HSP72 and p57 antibodies did not identify the characteristic ubiquitinimmunoreactive inclusions present in anterior horn cells in ALS spinal cord. Antibodies to HSP72, but not to p57 or ubiquitin, strongly labelled structures corresponding to polyglucosan bodies in spinal grey matter. Such immunoreactive profiles were more abundant in ALS cases, although they were also present in control material. They were sometimes identified by haematoxylin and eosin and periodic acid Schiff reaction, but were not labelled by phosphotungstic acid haematoxylin or by antibodies to glial fibrillary acidic protein. Although ubiquitin, HSP72 and p57 are stress–induced proteins, they are expressed differently and might therefore have different significance in neuronal degeneration.
36 citations
TL;DR: Clinical and histological features in a case of myopathy with tubular aggregates is reported and heat shock proteins have a role in the modulation of the tertiary structure of proteins and may be involved in the pathogenesis of tubular aggregation and other microtubular abnormalities in muscle.
Abstract: Tubular aggregates may be found in a variety of conditions and have been associated with a wide range of chemical and ischemic insults. We report clinical and histological features in a case of myopathy with tubular aggregates. The structure of these tubular aggregates was examined using antibodies to cytoskeletal proteins and heat shock proteins. Epitopes of the 72 kD heat shock protein were expressed in the areas of abnormality in this case and in a case of hypokalemic periodic paralysis with tubular aggregates. Heat shock proteins have a role in the modulation of the tertiary structure of proteins and may be involved in the pathogenesis of tubular aggregates and other microtubular abnormalities in muscle.
36 citations
TL;DR: Small bodies expressing epitopes of the 72 kD heat shock protein (HSP) have been identified in the brain and spinal cord in normal and neurologically abnormal individuals.
Abstract: Small bodies expressing epitopes of the 72 kD heat shock protein (HSP) have been identified in the brain and spinal cord in normal and neurologically abnormal individuals. These bodies resemble the 'pre-corpora amylacea' (pre-CA), thought to be the primary structure in the development of the mature body. Corpora amylacea are laminated hyaline bodies composed of polyglucosans. They are found in larger numbers with increasing age in the brain and spinal cord. Mature, histologically 'classical', corpora amylacea express epitopes of HSP chiefly at the periphery of the corpus, whilst smaller immature 'pre-corpora' stain intensely throughout the entire structure. A heat shock or stress response in neurons and glial cells may be part of the cellular reaction to accumulation of abnormal products.
32 citations
TL;DR: High-dose intraperitoneal BAPN in the rat causes Purkinje cell changes, but no other central nervous system abnormalities, and Immunohistochemical studies of phosphorylated neurofilaments and the 72 kDa heat shock protein were normal and no intraneuronal ubiquitinated inclusions were seen.
Abstract: Compounds causing neurolathyrism are putative aetiological agents in neurodegenerative disorders including amyotrophic lateral sclerosis.β-Aminopropionitrile (BAPN) is one such compound. We have administered this lathyrogenic agent at a dose of 1 g/kg by the intraperitoneal route in experiments in adult Sprague-Dawley rats during a period of 10 weeks. The rats developed marked kyphoscoliosis, ataxia with paralysis and muscle wasting of the hind limbs. Vacuolation and loss of Purkinje cells developed, but no anterior horn cell degeneration was noted. Immunohistochemical studies of phosphorylated neurofilaments and the 72 kDa heat shock protein were normal and no intraneuronal ubiquitinated inclusions were seen. High-dose intraperitoneal BAPN in the rat causes Purkinje cell changes, but no other central nervous system abnormalities.
16 citations
TL;DR: Investigation of immunohistochemical studies of heat shock protein (HSP) expression in the frontal cortex of three patients with dialysis dementia revealed punctate granules in most endothelial cells of cortical vessels in patients with Dialysis encephalopathy, suggesting that these stress granules represent a toxic response of endothelial Cells in the brain to aluminium.
Abstract: Dialysis encephalopathy, a complication of long-term haemodialysis, is a syndrome characterized by progressive dementia, myoclonus, dysarthria and ataxia associated with high serum and brain levels of aluminium. Expression of heat-shock or stress proteins, including ubiquitin can be induced in cell culture experiments by aluminium. We report immunohistochemical studies of heat shock protein (HSP) expression in the frontal cortex of three patients with dialysis dementia. Immunolabelling with antibody to the 72 kD heat shock protein revealed punctate granules in most endothelial cells of cortical vessels in patients with dialysis encephalopathy. These granules, 1-5 microns in diameter, aggregated to form inclusions that resembled stress-granules, typically induced in plant or animal cell culture by repeated insult. These granules did not express epitopes of ubiquitin. They were rare in endothelial cells in the brains of subjects dying with other neurological disorders or of non-neurological causes. We suggest that these stress granules represent a toxic response of endothelial cells in the brain to aluminium.
4 citations