Low expression of collagen receptors in moderate and poorly differentiated colorectal adenocarcinomas.
Explore the source record for details and available documents.
Adenocarcinoma↗
Biomedical subjects
M E Smith
Publications and source records attributed to M E Smith.
Selective and non-selective loss of immunoregulatory molecules (HLA-A,B,C antigens and LFA-3) in transitional cell carcinoma.
The expression of the major histocompatibility complex (MHC) class I and II antigens and lymphocyte function-associated antigen-3 (LFA-3) was investigated using immunohistochemical staining of bladder tissue sections from 18 patients with transitional cell carcinoma (TCC) and two normal bladder specimens. The expressions of HLA-A,B,C antigens varied greatly between different tumours. Complete loss was observed in one of 18 cases. Moderate to strong expression of HLA-A,B,C antigens was observed in 10 of 18 cases with the remaining seven cases showing either weak expression or expression on only a proportion of the tumour cells. Selective loss of HLA-Bw6 was seen in one of 18 cases. In many cases heterogenous and often focal expression of HLA-D products was seen. In one case tumour cells not expressing HLA-DR antigens were adjacent to strongly HLA-DR expressing non-neoplastic bladder epithelium, indicating a lack of inducible HLA-DR in the tumour cells. LFA-3 was undetectable in two of 18 cases with the remaining 16 cases showing moderate to strong expression of the molecule. These findings indicate that a substantial proportion of bladder tumours have one or more of a wide range of different alterations in the expressions of immunoregulatory molecules that could contribute to escape from immune surveillance.
Adult↗
p53 mutations in colorectal cancer.
Immunohistological staining of primary colorectal carcinomas with antibodies specific to p53 demonstrated gross overexpression of the protein in approximately 50% of the malignant tumors examined. Benign adenomas were all negative for p53 overexpression. To determine the molecular basis for this overexpression we examined p53 protein expression in 10 colorectal cancer cell lines. Six of the cell lines expressed high levels of p53 in ELISA, cell-staining, and immunoprecipitation studies. Direct sequencing and chemical-mismatch-cleavage analysis of p53 cDNA by using the polymerase chain reaction in these cell lines showed that all cell lines that expressed high levels of p53 were synthesizing mRNAs that encoded mutant p53 proteins. In two of those four cell lines where p53 expression was lower, point mutations were still detected. Thus, we conclude that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by a simple immunohistochemical analysis. Mutation of the p53 gene is one of the commonest genetic changes in the development of human colorectal cancer.
Adenocarcinoma↗
Neuronal activity in the human medial temporal lobe during recognition memory.
Human medial temporal lobe neuronal activity and event-related potentials were recorded during the following behaviours: contextual recognition of words and faces, semantic discrimination of nonwords from words, and discrimination of stimulus classes based on perceptual attributes. Three distinct classes of behavioural correlates of unit activity were demonstrated by visual inspection of peristimulus histograms and by nonparametric statistics: (1) neuronal excitation during a keypress related to the subject's choice; (2) specific and nonspecific excitation to words; (3) excitation or inhibition to rare stimuli in a sensory discrimination task. Responses specifically to familiar (as opposed to unfamiliar) words or faces, or to tasks requiring recent memory per se were never seen. Keypress excitation was relatively common (32/76 units) and occurred regardless of whether the keypress target was a repeated or nonrepeated word, or the task required recent or remote semantic memory. In a more complex recognition task utilizing two responses and an imperative cue for the patient's response, units with prior keypress excitation failed to generate the response. This suggests that keypress excitation is not strictly tied either to response choice or to generation. The onset latencies and temporal relationship to event-related potentials of the nonspecific and specific excitation to words and the excitation to rare stimuli suggest that they represent contextual encoding of stimuli. Similar evidence suggests that the inhibition to rare stimuli represents inhibitory processes terminating contextual encoding. Thus human medial temporal lobe neurons seem to contribute information during successive stages of a cognitive stimulus-response task: contextual encoding, closure and response-selection.
Action Potentials↗
An enquiry into the use of financial compensation for severe injury.
Explore the source record for details and available documents.
Activities of Daily Living↗
Disintegration of mercury disc cells in simulated gastric juice: implications for management of disc cell ingestion.
The disintegration of charged alkaline mercury button cells in simulated gastric fluid over a 24 h period has been studied. The integrity of the cells and the amount of mercury that can leak out of them were assessed. The cells raised the pH of the incubating solutions. Disruption was seen in five out of 18 cells tested in 0.1 mol/L hydrochloric acid and one out of nine in 0.9% saline. Five of the six disrupted cells were made by the same manufacturer. Major leakage of mercury only occurred after complete disintegration of the cells. The implications of these findings for the management of patients who have ingested mercury-containing button cells are discussed.
Animals↗
Cellular expression of lymphocyte function associated antigens and the intercellular adhesion molecule-1 in normal tissue.
A detailed immunohistological analysis of normal tissues for the distribution of lymphocyte function-associated antigens (LFA) and the intercellular adhesion molecule-1 (ICAM-1) showed several hitherto unrecognised patterns of LFA-3 and ICAM-1 expression. The widespread, but not ubiquitous, distribution of LFA-3 contrasted with the more restricted distribution of ICAM-1. Among epithelial cells, all tissues which were ICAM-1 positive were also LFA-3 positive with the single exception that thymic cortical epithelium, in contrast to previous reports, expressed only ICAM-1. It was striking that LFA-3 molecules were absent in some tissues which are considered to be sites of immunological privilege (such as brain and testis), suggesting an additional mechanism by which these microenvironments maintain immunological autonomy. Furthermore, the unexpected finding that LFA-3 is strongly expressed on intercalated discs of cardiac muscle may possibly be related to a non-immune function, or indicate a structurally similar epitope expressed by an unrelated molecule within this tissue.
Antigens, Surface↗
The effects of phonosurgery on laryngeal vibration: Part I. Theoretic considerations.
Surgical manipulation of the laryngeal framework (phonosurgery) is rapidly gaining interest and attention. To date, however, a comparative objective evaluation of the various phonosurgical techniques has not been reported. A theoretic model of the larynx, a four-mass model based on the work of Ishizaka (J Acoust Soc Am 1976;60:1193-8) and Koizumi et al. (J Acoust Soc Am 1987;82:1179-92), was developed and adapted to simulate laryngeal biomechanical behavior, as understood by current research. The model was then applied to a comparative evaluation of phonosurgical techniques. Input parameters that correlate laryngeal function and model simulation were developed. Surgical procedures were categorized according to their effect on these parameters. A model simulation of these techniques allowed comparison and prediction of the results of phonosurgery and a better understanding of the issues involved with surgical alteration of the voice.
Computer Simulation↗
Proopiomelanocortin-derived peptides in mice with motoneurone disease.
beta-Endorphin and alpha-melanotropin immunoreactivity was detected in motor nerves in histological sections of murine skeletal muscle, using the peroxidase-antiperoxidase technique. In mice of the wobbler strain, which can inherit motoneurone disease, a significantly higher proportion of the intramuscular nerves in soleus, extensor digitorum longus and diaphragm muscles of the diseased mice were immunoreactive than in the corresponding muscles of their healthy littermates.
Aging↗
Angiolymphoid hyperplasia with eosinophilia of the orbit associated with obstructive airway disease.
Two patients with angiolymphoid hyperplasia with eosinophilia isolated to the orbit had eyelid swelling, a superior orbital mass, and histories of intermittent obstructive airway disease. One patient later developed a transient peripheral blood eosinophilia as high as 36%. One lesion recurred 38 months postoperatively and responded to systemic corticosteroid therapy.
Aged↗
Regulation of expression of the gene encoding the major surfactant protein (SP-A) in human fetal lung in vitro. Disparate effects of glucocorticoids on transcription and on mRNA stability.
We previously observed that dexamethasone had a biphasic effect on the levels of mRNA encoding the major surfactant protein (SP-A) in human fetal lung in vitro; at concentrations of 10(-10) and 10(-9) M, dexamethasone caused an increase in the levels of SP-A mRNA, whereas at concentrations of greater than 10(-8) M, the steroid had a pronounced inhibitory effect on SP-A mRNA levels. It was also found that dexamethasone antagonized the stimulatory effect of dibutyryl cyclic AMP (Bt2cAMP) on SP-A mRNA levels in human fetal lung in vitro. It was our objective, in the present study, to characterize further the effects of dexamethasone and Bt2cAMP on SP-A mRNA levels in human fetal lung tissue and to determine whether such effects are associated with comparable changes in the transcriptional activity of the SP-A gene. We found that the action of dexamethasone (10(-7) M) to reduce the levels of SP-A mRNA in control and Bt2cAMP-treated fetal lung explants was evident within 2 h of its addition to the culture medium; SP-A mRNA was reduced to barely detectable levels in control and in Bt2cAMP-treated tissues after 24 h of dexamethasone treatment. The action of dexamethasone to reduce SP-A mRNA levels was not prevented by co-incubation with either actinomycin D or cycloheximide. In contrast to its dose-related biphasic effects on the levels of SP-A mRNA, we found that dexamethasone caused a dose-dependent stimulation of SP-A gene transcription. Bt2cAMP also increased the transcriptional activity of the SP-A gene in the human fetal lung in vitro. In fetal lung explants incubated in the presence of dexamethasone plus Bt2cAMP, a synergistic induction of SP-A gene transcription was observed at concentrations of dexamethasone of 10(-9)-10(-7) M. Our findings are indicative that the stimulatory effects of dexamethasone (10(-10)-10(-9) M) on SP-A mRNA levels are reflective of a stimulatory effect of the steroid on SP-A gene transcription, whereas the inhibitory effects of dexamethasone (10(-7) M) on SP-A mRNA levels are the result of a dominant effect of the steroid in elevated concentrations to reduce SP-A mRNA stability.
Bucladesine↗
Classification of lung cancer patients and controls by chromatography of modified nucleosides in serum.
A wide spectrum of modified nucleosides has been quantified by high-performance liquid chromatography in serum of 49 male lung cancer patients, 35 patients with other cancers, and 48 patients hospitalized for nonneoplastic diseases. Data for 29 modified nucleoside peaks were normalized to an internal standard and analyzed by discriminant analysis and stepwise discriminant analysis. A model based on peaks selected by a stepwise discriminant procedure correctly classified 79% of the cancer and 75% of the noncancer subjects. It also demonstrated 84% sensitivity and 79% specificity when comparing lung cancer to noncancer subjects, and 80% sensitivity and 55% specificity in comparing lung cancer to other cancers. The nucleoside peaks having the greatest influence on the models varied dependent on the subgroups compared, confirming the importance of quantifying a wide array of nucleosides. These data support and expand previous studies which reported the utility of measuring modified nucleoside levels in serum and show that precise measurement of an array of 29 modified nucleosides in serum by high-performance liquid chromatography with UV scanning with subsequent data modeling may provide a clinically useful approach to patient classification in diagnosis and subsequent therapeutic monitoring.
Biomarkers, Tumor↗
Dissociation of GFAP intermediate filaments in EAE: observations in the lumbar spinal cord.
Acute experimental allergic encephalomyelitis (EAE) in the Lewis rat is a cell-mediated autoimmune disease of central nervous system myelin. The lesion has been characterized by breakdown of the blood-brain barrier, edema, and periventricular infiltration of macrophages and lymphocytes. At the early stage of the disease, the astrocytes show a marked increase in immunostaining for glial fibrillary acidic protein (GFAP). A corresponding increase in GFAP content, however, cannot be demonstrated. Electron microscopic examination of the early lesion shows a typical reactive astrocytic response expressed by an enlarged watery cytoplasm, particularly at the level of the processes surrounding neurons and blood vessels and in the neuropil itself. The astroglial processes contain numerous glycogen particles (aggregates and single particles). Glial filaments are also conspicuous and are arranged in small bundles or loose thin filaments adjacent to the bundles. The glial filaments that normally appear as tight bundles have expanded and appear less dense. We suggest that the increase in GFAP immunostaining of the astrocytes in the early lesion is due in part to edema, which causes dissociation of the filaments and thereby exposes more antigenic sites to the antibodies.
Animals↗
Effects of food and antacid on oral absorption of misoprostol, a synthetic prostaglandin E1 analog.
Misoprostol, a synthetic PGE1 analog with mucosal protective and antisecretory properties, is rapidly and essentially completely metabolized to its active metabolite, misoprostol acid. Relative to fasting conditions administration of misoprostol with antacid resulted in reduced bioavailability, as manifested by lower AUC(0-4) values from (mean +/- SD; n = 12) 417 +/- 135 to 349 +/- 108 pg.hr/ml (P less than 0.05), without significant changes in the rate of absorption (tmax = 14 +/- 8 [fasting] vs. 20 +/- 14 min [with antacid]). The observed Cmax values were also reduced (from 811 +/- 317 to 689 +/- 315 pg/ml), however, the difference was not statistically significant. Drug administration with a high-fat content meal resulted in a marked slowing in the absorption rate without a substantial decrease in the extent. Relative to fasting conditions food decreased misoprostol acid Cmax from 811 +/- 317 to 303 +/- 176 pg/ml (P less than 0.05) and increased tmax from 14 +/- 8 to 64 +/- 79 min (P less than 0.05): the AUC changes remained statistically insignificant from 417 +/- 135 to 373 +/- 111 pg.hr/ml. Administration of misoprostol with food could potentially decrease the incidence of systemic side effects by reducing the early high peak plasma concentrations of misoprostol acid.
Administration, Oral↗
Safety of axial traction.
Explore the source record for details and available documents.
Cervical Vertebrae↗
Dissociation of recognition memory components following temporal lobe lesions.
It has been proposed that recognition decisions are based on contextual retrieval of specific trace information, in addition to an assessment of item strength. The retrieval component is maximal after a single presentation, whereas the strength component increases with multiple repetition. We report that unilateral anterior temporal lobectomy (ATL) in the language dominant (left) hemisphere impairs initial recognition accuracy without affecting the rate at which repetition improves performance. The implication that the temporal lobe contributes to retrieval rather than strength during recognition is supported by simultaneous event-related potential (ERP) recordings. In normal subjects, the large ERP difference between repeated and nonrepeated words does not increase with increasing study and is associated with contextual integration in other tasks. Thus, the lack of a repetition-induced ERP difference after left-ATL reported here provides converging evidence for a critical role of the temporal lobe in contextual retrieval during recognition.
Adult↗
Loss of HLA-A,B,C allele products and lymphocyte function-associated antigen 3 in colorectal neoplasia.
The expression of HLA-A,B,C antigens and lymphocyte function-associated antigen 3 in human colorectal adenomas and adenocarcinomas was studied by immunohistochemistry. None of 10 adenomas and only 1 of 30 carcinomas had lost expression of all HLA-A,B,C molecules. On the other hand, focal loss of an HLA-B product was seen in 2 of the adenomas, and complete losses of tumor cell HLA-A2 (in 7 of 13 cases), HLA-Bw4 (in 4 of 13 cases), and HLA-A3 (in 1 of 6 cases) were seen in the carcinomas. No complete losses of HLA-A1 (in 6 cases) or HLA-Bw6 (in 22 cases) occurred in the carcinomas. In addition, 1 of 20 adenocarcinomas totally lacked lymphocyte function-associated antigen 3. Because a loss of tumor cell HLA-A,B,C antigen or lymphocyte function-associated antigen 3 could be selected for through an advantage in escape from cytotoxic T-lymphocyte attack, our results suggest that immunoselection may be a more important mechanism in tumor progression than has previously been assumed.
Adenocarcinoma↗
Variation in HLA expression on tumors: an escape from immune response.
Explore the source record for details and available documents.
Adenocarcinoma↗