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Biomedical subjects

M E Perry

Publications and source records attributed to M E Perry.

At least 37 records · Page 2Linked to original sources
PubMed1996

Expression of adhesion molecules on the microvasculature of the pharyngeal tonsil (adenoid).

We have examined the vasculature of 12 human adenoids and the expression and distribution of four endothelial adhesion molecules, ICAM-1, VCAM-1, P-selectin and E-selectin, in tissue sections using histology, immunocytochemistry and immunoelectron microscopy (IEM). The connective tissue septa and septula contained arterioles, veins and efferent lymphatics. Branches of arterioles supplied lymphoid follicles and divided into sub- and intraepithelial capillary plexuses which drained into interfollicular venules, mostly high endothelial venules (HEV), before joining larger veins. No afferent lymphatics were observed entering the adenoid. Although ICAM-1 was widely distributed in the tissue, it was preferentially expressed on luminal aspects of HEV. E-selectin was found only in a few areas on HEV and subepithelial capillaries, whereas P-selectin was strongly expressed on segments of HEV, adjacent small venules and a few follicular capillaries. IEM showed the localisation of VCAM-1 on the components of the perivascular sheath, but not on the endothelium, of some HEV and capillaries. Its strongest expression was on follicular dendritic cells (FDC). These findings showed that in addition to HEV, lymphocyte-binding molecules are expressed on other segments of adenoid vasculature and their distribution and intensity of expression varies. In the non-inflamed adenoid, the VCAM-1 does not seem to participate in the adhesive mechanism of recirculating lymphocytes to the endothelium which, in this study, lacked the expression of VCAM-1 in all vessels.

Adenoids↗
PubMed1995

Selective binding of peripheral blood lymphocytes to the walls of cerebral vessels in frozen sections of human brain.

In order to identify the factors that control the binding of blood leucocytes to cerebral blood vessels we have modified and applied the frozen section assay of Stamper and Woodruff to the study of human brain. Cryostat sections of brain tissue obtained at post mortem were overlaid with blood lymphocytes and experimental conditions were defined which permitted optimum binding of the cells to transected blood vessel walls. The maximal binding of lymphocytes to cerebral vessels occurred when 6 x 10(6) lymphocytes were overlaid onto brain sections for 30 min at 7 degrees C with gentle agitation. Only a small proportion (0.01%) of the added lymphocytes bound to exposed cerebral vessels. However, lymphocytes were far more adherent than monocytes and polymorphonuclear cells (7-fold and 11-fold respectively: p < 0.001) and activation of lymphocytes with IL-2 enhanced their binding to blood vessel walls (mean 130% increase; p < 0.03). Further analysis revealed that CD4-positive T lymphocytes were the predominant cell population binding to the blood vessels. Antibody blocking studies showed that lymphocyte binding to cerebral blood vessels was inhibited by pretreating the lymphocytes with anti-CD11a, anti-CD18 or anti-CD49d (p < or = 0.02) and immunohistochemical studies revealed the presence of the counter-receptors ICAM-1 (CD54) and VCAM-1 (CD106) for these adhesion molecules in addition to the presence of E-selectin (CD62E) and P-selectin (CD62P) on the cerebral blood vessels. The establishment of a technique in situ which measures selective binding of CD4-positive peripheral lymphocytes to sections of cerebral blood vessels will assist in the molecular characterization of factors that control the interaction of leucocytes with the blood-brain barrier in health and disease.

Adult↗
PubMed1995

The distribution and abnormal morphology of plasma cells in rheumatoid synovium.

This study assessed the distribution and structural features of plasma cells in rheumatoid synovial tissue. Plasma cells were found to be the predominant infiltrating mononuclear cells (mean 40%) in relation to lymphocytes and monocytes, and there was a direct relationship between their number in the infiltrates and the total number of mononuclear leucocytes (P = 0.007). Plasma cells were also seen in intimate contact with macrophages intermixed with synovial lining cells, and closely associated with small blood vessels. They often surrounded these blood vessels and sometimes were seen lying within the vessel walls themselves. Ultrastructural analysis revealed that many synovial plasma cells were considerably larger than plasma cells of a normal size and possessed a marked distension of the cisternae of rough endoplasmic reticulum. Furthermore, plasma cells in close proximity to blood vessels often appeared to be undergoing migration. These observations imply that in rheumatoid synovium, plasma cells are metabolically very active and occupy a pivotal position for the secretion of antibodies into both the vascular and the extravascular compartments.

Aged↗
PubMed1995

General practice referral letters to a regional ophthalmic accident and emergency department.

A significant proportion of patients seen in ophthalmic Accident and Emergency departments are referred by other medical practitioners. Two hundred and twenty-six referral letters from general practitioners to the Accident and Emergency Department of a large regional ophthalmology centre were examined. Information that was poorly recorded in the referral letters included social and personal background details, examination findings, management plans and investigation results. Analysis revealed that 50-70% of referrals did not constitute accidents or urgent conditions and could have been more properly assessed within usual secondary referral outpatient clinics. Ophthalmic Accident and Emergency is therefore providing a service for general practitioner referrals in excess of its defined function. The impact on purchaser/provider arrangements if appropriate redirection to outpatients were to occur would be significant.

Correspondence as Topic↗
PubMed1994

The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis.

The p53 tumour-suppressor gene is mutated in 60% of human tumours, and the product of the gene acts as a suppressor of cell division. It is thought that the growth-suppressive effects of p53 are mediated through the transcriptional transactivation activity of the protein. Overexpression of the p53 protein results either in arrest in the G1 phase of the cell cycle or in the induction of apoptosis. Both the level of the protein and its transcriptional transactivation activity increase following treatment of cells with agents that damage DNA, and it is thought that p53 acts to protect cells against the accumulation of mutations and subsequent conversion to a cancerous state. The induction of p53 levels in cells exposed to gamma-irradiation results in cell cycle arrest in some cells (fibroblasts) and apoptosis in others (thymocytes). Cells lacking p53 have lost this cell cycle control and presumably accumulate damage-induced mutations that result in tumorigenesis. Thus, the role of p53 in suppressing tumorigenesis may be to rescue the cell or organism from the mutagenic effects of DNA damage. Loss of p53 function accelerates the process of tumorigenesis and alters the response of cells to agents that damage DNA, indicating that successful strategies for radiation therapy may well need to take into account the tissue of origin and the status of p53 in the tumour.

Animals↗
PubMed1994

Comparison of venography, duplex imaging, and bilateral impedance plethysmography for diagnosis of lower extremity deep vein thrombosis.

Twenty-four consecutively hospitalized patients with clinical evidence of lower extremity deep vein thrombosis (DVT) had blinded ipsilateral ultrasonographic duplex imaging (US), contrast venography (VG), and a one-time bilateral impedance plethysmography (IPG) examination. The cases of eight (33%) of the study patients were thought to be complicated due to a prior history of DVT or the presence of ipsilateral inguinal adenopathy. Interpretable test results were obtained for 100% of the US examinations, 88% of the VG studies, and 75% of the IPGs. One additional subject, included in our study for statistical analysis, had an unblinded false-negative US examination; in this case DVT was shown by VG but could not be seen on US despite the radiologist's prior knowledge. The sensitivities, specificities, and 95% confidence intervals for the three studies were as follows: US, 92% (81% to 103%) sensitivity, 100% (99% to 101%) specificity; VG, 100% (99% to 101%) sensitivity, 75% (58% to 96%) specificity; IPG, 50% (30% to 70%) sensitivity, 83% (68% to 98%) specificity. Of the six indeterminate IPG studies, four (67%) occurred in complicated cases. These data suggest that US should be the first-line noninvasive screening study done for evaluation of suspected DVT, especially in complicated cases.

Adult↗
PubMed1994

The specialised structure of crypt epithelium in the human palatine tonsil and its functional significance.

Material from 25 human palatine tonsils was studied by light microscopy, immunocytochemistry, scanning and transmission electron microscopy. Special attention was focused on the structure of the epithelium lining the tonsillar crypts in the context of its ascribed immunological functions. This epithelium was not uniform and contained patches of stratified squamous nonkeratinising epithelium and patches of reticulated sponge-like epithelium. The degree of reticulation of the epithelial cells and the infiltration of nonepithelial cells varied. Reticulated patches were associated with disruptions in the continuity of basement membrane, and often also with desquamation of the upper cell layers, and contained numerous small blood vessels. The epithelial cells showed considerable variation in their morphology when surrounded by infiltrating cells. The rearrangement of their cytoskeleton and redistribution of desmosomal contacts indicate the responsiveness and dynamic nature of such epithelium. Cytoplasmic glycogen granules, located in the upper strata, suggest the possibility of energy-demanding functions such as absorption and secretion. The numerous membrane-coating granules may have contributed to cell membrane thickening and possibly also to tonsillar mucosal protection. Some areas contained a few keratohyalin granules but there was little evidence of keratinisation. The presence, and sometimes the predominance, of nonepithelial cells was characteristic of the reticulated epithelium. T and B cells often infiltrated the whole epithelial thickness, and many plasma cells were located around intraepithelial vessels, while macrophages and interdigitating cells showed a patchy distribution. It is proposed that the major functions of the reticulated epithelium are: (1) to provide a favourable environment for the intimate contact between the effector cells of immune responses; (2) to facilitate direct transport of antigens; (3) to synthesise the secretory component continually; and (4) to contain a pool of immunoglobulins. Thus the reticulated epithelium lining the tonsillar crypts represents a specialised compartment, important in the immunological functions of the tonsil as a whole.

Adolescent↗
PubMed1994

P53 and mdm-2: interactions between tumor suppressor gene and oncogene products.

The p53 tumor suppressor gene is the most commonly mutated gene in human cancers and, although mutation leads to loss of p53 suppression of cell growth, it can also result in new functions which enhance tumorigenicity. These mutations often lead to loss of p53 transcriptional activation activity, which is likely to account for the loss of growth control. The p53 protein induces expression of the GADD45 and mdm-2 genes, and the respective roles of the products of these two genes in the regulation of growth control, apoptosis, amplification, and the response to DNA damage remain to be determined. Although some facts are clear at this juncture, we can surely expect some surprises in the future, including additional functions for the p53 tumor suppressor gene product and a constant reevaluation of our present concepts. The study of the p53 regulatory pathway, however, should lead us to additional important genes and proteins central to an explanation of the origins of cancer.

Amino Acid Sequence↗
PubMed1993

The mdm-2 gene is induced in response to UV light in a p53-dependent manner.

Irradiation of mammalian cells with UV light results in a dose-dependent accumulation of the p53 tumor-suppressor gene product that is evident within 2 hr. UV treatment causes a dramatic increase in p53-specific transcriptional transactivation activity and an increase in expression of the p53-responsive gene mdm-2. UV-stimulated mdm-2 expression is not directly correlated with the level of p53 protein in a cell because mdm-2 induction is delayed at high UV doses even though p53 levels rise almost immediately. Cells lacking p53 protein do not respond to UV by increasing their expression of mdm-2. The delayed induction of mdm-2 at high UV doses suggests that, in addition to p53 protein levels, other factors contribute to the regulation of mdm-2 expression following UV treatment. The time of induction of mdm-2 in cells treated with UV light correlates with recovery of normal rates of DNA synthesis, presumably after DNA repair. These data indicate a possible role for mdm-2 in cell cycle progression.

3T3 Cells↗
PubMed1993

Immuno-electron microscopic analysis of the distribution of ICAM-1 in human inflammatory tissue.

An immuno-electron microscopic analysis was undertaken to determine ICAM-1 expression on vascular endothelium in human tonsils and in synovia from patients with rheumatoid arthritis. ICAM-1 was preferentially expressed on high endothelial venules (HEV) located in the parafollicular regions of the tonsils and HEV located in the villous processes of the synovia. On both tissues, these areas contained the greatest number of perivascular lymphocytes. In contrast, ICAM-1 was only weakly expressed on the low endothelium lining capillaries, venules and sinusoids. In both tonsils and synovia, ICAM-1 was confined to the luminal and lateral surfaces of the endothelial cells and absent from the abluminal surfaces adjacent to the basement membrane. We propose that in inflammatory tissues, ICAM-1 mediates the interaction of circulating lymphocytes with the high endothelial cells, but may not have a major role in promoting their migration through the whole thickness of the blood vessel wall.

Arthritis, Rheumatoid↗
PubMed1993

Tumor-suppressor p53 and the cell cycle.

The p53 tumor suppressor is a transcription factor that can activate the expression of some genes and repress the transcription of others. The protein appears to be dispensable for normal murine development, although mice lacking p53 develop tumors at an early age and their fibroblasts are genetically unstable in culture. Human and murine cells lacking wild-type p53 loose the ability to arrest in the G1 phase of the cell cycle in response to gamma-irradiation. Therefore, p53 may be a cell-cycle checkpoint protein that regulates the cycle under adverse conditions.

Animals↗
PubMed1993

Immunoelectronmicroscopical demonstration of major histocompatibility class II antigen: expression on endothelial and perivascular cells but not Schwann cells in human neuropathy.

A pre-embedding technique for identifying major histocompatibility (MHC) class II antigen with monoclonal antibody LN3 at the electron microscope level by immunogold silver enhancement was applied to sections from 12 human nerve biopsies. Many perivascular mononuclear cells in the epineurium, perineurium and endoneurium expressed MHC class II antigen and had the morphological appearance of macrophages. Cell processes expressing MHC class II antigen extended throughout the endoneurium, often close to Schwann cells. No MHC class II expression was identified on myelinating or non-myelinating Schwann cells. The endothelial cells of epineurial blood vessels expressed MHC class II antigen on their luminal surfaces more often and more strongly than those of the endoneurial vessels. These observations indicate that perivascular cells in both the endoneurium and perineurium commonly express the molecules necessary to present antigen to CD4+ T lymphocytes, but Schwann cells do not.

Adult↗
PubMed1993

Formation of the tonsillar corpuscle.

In this study of the human palatine tonsil we examined epithelial structures found always in the vicinity of the crypts and closely resembling thymic Hassall's corpuscles. We propose that in the reactive tonsillar lymphoid tissue these corpuscles form as a result of occlusion of fine microcrypts by the expanding lymphoid follicles during antigenic stimulation. The reticulated epithelial cells lining these microcrypts may then loose their polarisation, and gradually degenerate deep in the parenchyma, forming concentrically arranged parakeratotic pearls, rather than desquamate at the free epithelial surface. The structural similarities of the tonsillar and Hassall's corpuscles may be explained by endodermal embryological origin of the primordia of both organs, and by the specific degenerative properties of epithelia in the lymphoepithelial immune organs.

Adolescent↗
PubMed1992

Simian virus 40 large tumor antigen alone or two cooperating oncogenes convert REF52 cells to a state permissive for gene amplification.

Gene amplification is characteristic of tumors and continuous cell lines but not of primary, normal, diploid, senescing cells. However, the rat cell line REF52, which resembles primary cells in requiring expression of cooperating oncogenes for transformation, is unusual among cell lines as it is not permissive for amplification. REF52 cells did not form colonies in N-(phosphonacetyl)-L-aspartate (PALA), a drug for which the only known mechanism of resistance is amplification of the carbamoylphosphate synthetase/aspartate transcarbamoylase/dihydroorotase (CAD) gene. Colonies did form in a low concentration of methotrexate but did not contain amplified dihydrofolate reductase genes. Expression of two cooperating oncogenes in REF52 cells converted them to a state permissive for amplification. Cells expressing only the 12S E1A mRNA of adenovirus 5 did not give rise to PALA-resistant colonies, but expression of an activated ras gene together with E1A readily allowed the cells to form resistant colonies in which the CAD gene was amplified. Cells expressing E1A plus ras were fully transformed, but expression of simian virus 40 large tumor antigen alone converted REF52 cells to a state permissive for amplification without transforming them fully. The ability to manipulate gene amplification in REF52 cells by expression of oncogenes should contribute to an understanding of the nature of the permissive state.

Adenovirus Early Proteins↗
PubMed1992

Ultrastructural identification and distribution of the adhesion molecules ICAM-1 and LFA-1 in the vascular and extravascular compartments of the human palatine tonsil.

Immunohistological analysis of sections prepared from human palatine tonsils revealed marked differences in the distribution of the adhesion molecule, leucocyte function antigen-1 (LFA-1) and its counter receptor, intercellular adhesion molecule-1 (ICAM-1). Light microscopy showed that LFA-1 was restricted to the leucocytes, particularly the lymphocytes. In contrast, staining of ICAM-1 was predominantly confined to the vascular endothelium with the greatest expression seen on the morphologically distinct high endothelial venules in the parafollicular areas; these are the sites that appear to support lymphocyte migration. Electron microscopy revealed that ICAM-1 was present on the luminal and lateral surfaces of the high endothelium and absent from the abluminal surface supported by basal lamina. The ICAM-1 was also absent from those surfaces of the endothelium that were in close contact with intravascular lymphocytes. Other cells stained by the anti-ICM-1 antibody included dendritic cells, plasma cells and epithelial cells in the reticulated crypt epithelium and in the upper strata of the non-keratinised stratified squamous epithelium. The high expression of LFA-1 was most prominent on lymphocytes, low on antigen-presenting cells and activated lymphoid cells, and not detectable on plasma cells, epithelial and endothelial cells. We propose that LFA-1/ICAM-1 binding participates in mediating the transendothelial migration of lymphocytes across the high endothelial venules of palatine tonsil.

Adolescent↗
PubMed1992

Induction of gene amplification by 5-aza-2'-deoxycytidine.

Treatment of Syrian hamster kidney cells with the demethylating agent 5-aza-2'-deoxycytidine (azadC) increased both the frequency and the rate of gene amplification appreciably. AzadC caused substantial DNA demethylation, which is likely to be responsible. The magnitude of the increases depended on the concentrations of both azadC and the drug used for selection. A transient stress response is not responsible since the increases were not dependent on cytotoxicity and were still apparent after several weeks. We discuss mechanisms by which azadC treatment may induce amplification by rendering DNA more prone to this process or by increasing the transcription of genes whose protein products stimulate amplification.

Animals↗
PubMed1992

The effect of intermediate altitude on the Army Physical Fitness Test.

Official physical training records of personnel stationed at intermediate altitude (elevation 5,280 feet) for at least 1 year were reviewed to gauge the effect of altitude on 2-mile running performance. An average of 48 additional seconds (a 5% increase in time) was required to complete the run compared to sea-level values in the same subjects. Run times gradually diminished during the first 9 months of assignment to altitude before stability was established. These data indicate that acclimatization occurs over several months. Even with acclimatization, substantial loss of performance is associated with habitation at intermediate altitude.

Adult↗