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Biomedical subjects

A Dodson

Publications and source records attributed to A Dodson.

11 recordsLinked to original sources
PubMed2002

Prostatic stem cells.

Multipotent cells within the epithelial compartment, together with phenotypically 'plastic' mesenchyma cells (stromal stem cells), provide a repository of protected genetic information from which the structure, stability and functionality of the prostate gland can be maintained. However, mere preservation of cells in a non-dividing state is insufficient to provide the necessary reservoir of information from which the structure and function of the prostate gland can be retained or recreated. Rather, there is a constant dynamic interaction, at the level of information exchange, between stem cells (whether epithelial or mesenchymal) and their surrounding environment (both humoral and physical). Thus, with respect to epithelial stem cells, these reside within environmental 'niches' which allow their controlled and limited proliferation while preserving genomic integrity. Similar 'mesenchymal niches' are also predicted to occur, although not yet identified, thus providing the multipotent source from which the full spectrum of stromal phenotypes might be regenerated. Recent data from studies of the haematopoietic and hepato-biliary systems indicate that the potential scope of stem cells far exceeds the immediate phenotypic complement of those tissues within which they originate, being dependent upon their precise environment as well as their genomic integrity.

Cell Differentiation↗
PubMed2001

Detailed tissue expression of bcl-2, bax, bak and bcl-x in the normal human pancreas and in chronic pancreatitis, ampullary and pancreatic ductal adenocarcinomas.

BACKGROUND: The aim of this study was to evaluate expression of the bcl-2 family of apoptosis regulating proteins in normal and diseased human pancreatic tissues. METHOD: Expression of bcl-2, bax, bcl-x, bak and p53 was determined in formalin-fixed paraffin wax-embedded archival specimens of normal pancreatic tissue (n = 7), chronic pancreatitis (n = 7), pancreatic ductal adenocarcinoma (n = 23) and ampullary cancer (n = 7) by immunohistochemistry using specific antibodies. RESULTS: In normal pancreas and chronic pancreatitis tissues, bcl-2, bax and bcl-x were predominantly expressed in ductal epithelial cells while p53 was not detected. In pancreatic ductal adenocarcinoma and ampullary cancer, bcl-2 was not detected compared with expression seen in normal acini (p < 0.01), minor (p < 0.001) and major ducts (p < 0.01), bax expression was reduced with respect to minor ducts (p < 0.01) but no different from normal acini or major ducts. bak and bcl-x were more strongly expressed in malignant epithelia compared with acini and major ducts but reduced when compared with minor ducts (p < 0.01). Overexpression of p53 was identified in 11 (48%) of 23 pancreatic adenocarcinomas and 4 (57%) of 7 ampullary cancers. Differential survival of individual patients was predicted by the relative level of bcl-x expression but not bax or bak, such that strong expression of bcl-x was associated with a median postoperative survival of 171 days when compared with 912 days for diminished expression (p < 0.001) of bcl-x. CONCLUSION: Pancreatic and ampullary cancer are associated with absent bcl-2 expression. bax, bak and bcl-x expression was reduced compared with normal minor ducts whilst bak and bcl-x expression was increased when compared with major ducts. bcl-x expression correlates with survival following resection and may represent a potential prognosis marker.

Adenocarcinoma↗
PubMed1999

Protein kinase C isoenzyme patterns characteristically modulated in early prostate cancer.

Expression of protein kinase C (PKC) isoenzymes -alpha, -beta, -delta, -epsilon, -gamma, -iota, -lambda, -mu, -theta, and -zeta, and of their common receptor for activated C-kinase (RACK)-1, was determined immunohistochemically using specific antibodies in formalin-fixed and paraffin-embedded specimens of early prostatic adenocarcinomas (n = 23) obtained at radical prostatectomy. Expression of each isoenzyme by malignant tissues was compared with nonneoplastic prostate tissues removed at radical cystectomy (n = 10). The most significant findings were decreased PKC-beta expression in early neoplasia when compared to benign epithelium (P < 0.0001), together with a reciprocal increase in expression of PKC-epsilon (P < 0.0001). Detectable levels of PKC-alpha and PKC-zeta were also significantly increased in the cancers (P = 0.045 and P = 0.015 respectively) but did not correlate with either PKC-beta or PKC-epsilon for individual cases. Alterations in the levels of the four PKC isoenzymes occurred specifically and consistently during the genesis and progression of human prostate cancer. PKC-delta, -gamma, and -theta were not expressed in the epithelium of either the benign prostates or the cancers. Levels of expression for PKC-A, -iota, -mu, and RACK-1 were not significantly different between the benign and malignant groups. Although changes in PKC isoenzyme expression may assist in explaining an altered balance between proliferation and apoptosis, it is likely that changes in activity or concentrations of these isoenzymes exert important modulating influences on particular pathways regulating cellular homeostasis. The findings of this study raise an exciting possibility of novel therapeutic intervention to regulate homeostatic mechanisms controlling proliferation and/or apoptosis, including expression of the p170 drug-resistance glycoprotein, intracellular Ca2+ concentrations, and enhanced cellular mobility resulting in the metastatic dissemination of human prostate cancer cells. Attenuation of PKC-beta expression is currently being assessed as a reliable objective adjunct to morphological appearance for the diagnosis of early progressive neoplasia in human prostatic tissues.

Disease Progression↗
PubMed1989

New aspects of the pathology of neurodegenerative disorders as revealed by ubiquitin antibodies.

Ubiquitin has previously been identified as a component of neuronal inclusions in neurodegenerative disorders. In this investigation, we examined tissue from cases of Alzheimer's disease (AD), Pick's disease, Parkinson's disease (PD), and progressive supranuclear palsy (PSP) to identify previously unrecognized ubiquitinated structures and to assess the evolution of neuronal inclusions. In AD, approximately 60% of neurofibrillary tangles (NFTs) that were stained with an anti-paired helical filaments (PHF) serum were identified by the ubiquitin antibodies. Extracellular NFTs were not labelled with anti-PHF but were unlabelled or weakly labelled with anti-ubiquitin antibodies. In Pick's disease, most Pick bodies were strongly labelled by the ubiquitin antibodies, and in addition some hippocampal CA1 neurones contained granular or strand-like ubiquitin-immunoreactive (IR) inclusions associated with more typical Pick bodies. Typical Lewy bodies in PD cases showed an unlabelled central core with an outer ring intensely labelled by ubiquitin antibodies. Pale bodies in pigmented substantia nigra neurones appeared as large well-defined, rounded structures without an identifiable core or peripheral zone. Some pale bodies were unlabelled by ubiquitin antibodies, but others showed labelling of variable intensity. Pale bodies which were labelled by ubiquitin antibodies tended also to be labelled by BF10, a monoclonal antibody against phosphorylated neurofilaments. We suggest that pale bodies in PD may represent stages in the formation of Lewy bodies. In addition, we observed numerous spindle-shaped ubiquitin-IR swellings of dendrites of pigmented substantia nigra neurones. In contrast to inclusions of AD and Pick's disease, the PHF-positive fibrillary neuronal inclusions of PSP were either unlabelled or only weakly labelled by ubiquitin antibodies. No ubiquitinated structures were seen in neurones from corresponding areas in aged controls. Identification of ubiquitinated proteins in neurodegenerative disorders may provide insights into molecular events associated with cell death.

Aged↗
PubMed1989

Cytoskeletal abnormalities in motor neuron disease. An immunocytochemical study.

Immunocytochemistry with antibodies against cytoskeletal proteins has been used to search for molecular differences in the spinal cord from patients with motor neuron disease (MND) of amyotrophic lateral sclerosis type and normal spinal cord. Monoclonal antibodies which recognize phosphorylated neurofilament epitopes diffusely labelled a proportion of normal and MND anterior horn cells, but did not permit differentiation between normal and MND tissue. However, in some MND and control anterior horn cells, dense 'floccular' accumulations were labelled by antibodies recognizing phosphorylated neurofilament epitopes. These accumulations of phosphorylated neurofilaments suggest abnormalities of cytoskeletal regulation, but were neither a common nor a specific feature of MND. Axonal spheroids, which were as common in normal as in MND tissue, were labelled by all antineurofilament antibodies. Normal-appearing axons, but not spheroids, in MND and control tissue were identified by an antiactin antibody, indicating that actin may be absent from the cytoplasmic domain which gives rise to spheroids. In summary, we have not found specific posttranslational changes of cytoskeletal proteins in MND and, in particular, phosphorylated neurofilament epitopes are common to both MND and control anterior horn cells.

Adult↗
PubMed1988

Ubiquitin deposits in anterior horn cells in motor neurone disease.

A polyclonal antiserum to ubiquitin, a low molecular weight protein involved in the ATP-dependent removal of abnormal cytoplasmic proteins, has been used to stain spinal cord from 10 cases of motor neurone disease and from 12 control spinal cords. All 10 cases of motor neurone disease exhibited antiubiquitin-immunoreactive deposits in a proportion of the surviving anterior horn cells but these deposits were not seen in any of the 12 controls. These ubiquitin deposits do not correspond to previously described neuronal inclusions in motor neurone disease. The ubiquitin deposits represent, therefore, a new neuronal inclusion which possibly reflects previously unrecognised degradative events occurring in the vulnerable neurones.

Humans↗
PubMed1987

Monoclonal antibodies against plant proteins recognise animal intermediate filaments.

Four monoclonal antibodies were raised against polypeptides present in a high-salt detergent-insoluble fraction from cells of Chlamydomonas reinhardtii. Indirect immunofluorescence microscopy of fibroblasts and epithelial cells grown in culture using these plant antibodies revealed staining arrays identical to those obtained with well characterised antibodies to animal intermediate filaments. Immunofluorescence microscopy of Chlamydomonas with these monoclonal antibodies and a monoclonal antibody that recognises all animal intermediate filaments (anti-IFA) gave a diffuse, patchy cytoplasmic staining pattern. Both the plant antibodies and anti-IFA stained interphase onion root tip cells in a diffuse perinuclear pattern. In metaphase through to telophase, the labelling patterns colocalised with those of microtubules. Labelling of the phragmoplast was also detected but not staining of the preprophase band. On Western blots of various animal cell lines and tissues, all the antibodies labelled known intermediate filament proteins. On Western blots of whole Chlamydomonas proteins, all the antibodies labelled a broad band in the 57,000 Mr range, and three antibodies labelled bands around 66,000 and 140,000 Mr but with variable intensities. On Western blots of whole onion root tip proteins, all the antibodies labelled 50,000 Mr (two to three bands) polypeptides and a diffuse band around 60,000 Mr and three of the antibodies also labelled several polypeptides in the 90,000-200,000 Mr range. The consistent labelling of these different bands by several different monoclonal antibodies recognising animal intermediate filaments makes these polypeptides putative plant intermediate filament proteins.

Antibody Specificity↗
PubMed1979

Stresses involved in wearing PVC supplied-air suits: a review.

A side effect of the growth and development of industrial technology is the ever increasing number of hostile environments encountered by man. This situation has resulted in the development of impermeable clothing as a barrier protection against the external environment. Unfortunately, although specific government standards concerning the design and engineering requirements of the impermeable suit have been stated, little or no standardized evaluation of the majority of available suits has been attempted. This review was undertaken to provide an in-depth summary of the physiological effects of a PVC protective suit while working. It was concluded that it was necessary to develop a standardized performance test to determine the protective and stressful characteristics of the individual manufacturer's designed suit. Recommendations of specific criteria for the test were obtained.

Body Water↗