Spinal cord compression in myelofibrosis--a case report.
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Aged↗
Biomedical subjects
G Cook
Publications and source records attributed to G Cook.
Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion.
The granulomas of mice infected with Schistosoma mansoni for 8 wk have macrophages that secrete somatostatin 1-14 (SOM). Within the granuloma, SOM has no known function. To uncover the possible significance of SOM produced within this granulomatous inflammation, we sought SOM receptors on distinct cellular components of the granuloma to identify cells targeted for SOM action. [125I]SOM 1-14 bound to dispersed granuloma inflammatory cells specifically and reversibly. Scatchard analysis suggested one receptor type (kDa 4.28 x 10(-9) M). Octreotide, a stable SOM derivative, displaced radioligand (kDa 1.01 x 10(-10) M), but SOM 1-28, substance P, and vasoactive intestinal peptide did not. The SOM receptor localized exclusively to a subset of granuloma CD4+ T lymphocytes. Using IL-5 and IFN-gamma ELISA, it was shown that granuloma T cells can secrete appreciable IL-5 and IFN-gamma when stimulated with Ag or mitogen. Both SOM and octreotide at concentrations as low as 10(-10) M substantially decreased IFN-gamma secretion from Ag or mitogen-stimulated T cells, but at concentrations as high as 10(-6) did not affect IL-5 production. Octreotide administered to animals in vivo decreased the intensity of the granulomatous response. Thus, some granuloma T cells have SOM 1-14 receptors. SOM 1-14, a product of granuloma macrophages, may participate in regulation of the granulomatous response by modulating the secretion of some lymphokines. Octreotide, a clinically useful SOM analog, mimics the action of SOM on the immune system.
Animals↗
An evaluation of Technegas as a ventilation agent compared with krypton-81 m in the scintigraphic diagnosis of pulmonary embolism.
A ventilation agent that provides good quality lung images, which is cheap, easy to use and non-toxic, with a low radiation dose, has long been sought. Technegas, an ultrafine aerosol of technetium-99m-labelled carbon, was developed with these qualities in mind. We have studied Technegas in a clinical setting to evaluate some of these qualities. Twenty-five patients referred with a diagnosis of suspected pulmonary embolism were investigated during the same study using both krypton-81 m and Technegas as ventilation agents in conjunction with 99mTc-macroaggregated albumin as a perfusion agent. Technegas provided images which were of satisfactory quality. Images were obtained relatively easily and without discomfort to the patient, and Technegas has the advantage of always being available. A semi-quantitative regional assessment was employed which showed a good correlation (r = 0.499, P less than 0.001) between Technegas and krypton-81 m ventilation. We report on an effect not previously found to be significant, that is lung regions were better ventilated with Technegas than with krypton-81 m. This altered the diagnostic probability rating of pulmonary embolism in a number of patients (n = 3, 12%) compared with krypton-81 m. This effect was also noted in a further 8 patients (32%) without a change in the diagnostic probability. We offer possible explanations for this phenomenon.
Female↗
Failure of d-cycloserine to reverse cognitive disruption induced by scopolamine or phencyclidine in primates.
The partial glycine agonist d-cycloserine may be of therapeutic use as a cognitive enhancer. We examined the ability of d-cycloserine (3-14 mg/kg i.m.) to reverse cognitive impairments induced by scopolamine (0.03 mg/kg) or PCP (0.25 mg/kg). There was no evidence for a dose-related improvement in visuospatial memory using retention intervals of 2,10 or 20 sec. A possible explanation for these findings is that central glycine function cannot be adequately increased using systemic administration of d-cycloserine in this dose range.
Animals↗
Psychomotor activity and cognitive disruption attributable to NMDA, but not sigma, interactions in primates.
We have compared the ability of phencyclidine (PCP)-like or sigma ligands to induce psychomotor effects in primates. In squirrel monkeys, administration of MK-801 (0.001-0.1 mg/kg), PCP (0.03-0.3 mg/kg), (+)-SKF10047 (0.001-3.0 mg/kg) or (-)-SKF10047 (0.1-10 mg/kg) induced ataxia, head weaving and bradykinesia. In contrast, treatment with the selective sigma ligand (+)-pentazocine using doses up to 20 mg/kg failed to induce any overt behaviours. The order of potency for induction of these behaviours was: MK-801 greater than PCP greater than (+)-SKF10047 greater than (-)-SKF10047 much greater than (+)-pentazocine. In rhesus monkeys treatment with MK-801 (0.01-0.04 mg/kg), PCP (0.05-0.2 mg/kg), (+)-SKF10047 (0.75-3.0 mg/kg) or (+)-pentazocine (1-10 mg/kg), disrupted performance of a spatial delayed response task. The potency to induce cognitive disruption was positively correlated with affinity for [3H]MK-801, but not [3H](+)-SKF10047, binding sites in vitro. These findings indicate that the psychomotor and cognitive effects of PCP-like and sigma ligands in primates are mediated through interactions at NMDA, not sigma, receptors.
Animals↗
Cell-cell repulsion: clues from the growth cone?
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Animals↗
Health and social inequities in Ireland.
This paper attempts to discuss the shape of inequalities in health in the Republic of Ireland by focusing on social class, gender and regional inequalities in health outcomes as shown in annual publications of vital statistics and in various research studies. The Republic of Ireland has a demographic profile of rapid population increase, unique in Europe. While the birth rate is the highest in Europe, the infant mortality rate is relatively low, yet the perinatal mortality rate is relatively high. Attempts are made to analyse social class variations in mortality and morbidity rates but, except for psychiatric care, Irish data on health by social class are scarce. There exist more data on gender inequalities which pinpoint the particular vulnerability of Irish women to ischaemic heart disease and certain types of cancer. Regional analysis of vital statistics reveals the vulnerability of people in urban areas (compared to rural areas) to cancer of the trachea, bronchus and lung, cirrhosis of the liver, tuberculosis of the respiratory system, pneumonia, and bronchitis, emphysema and asthma. In comparison to several European countries, Irish standardized mortality rates were the worst for urban women dying from lung cancer, and for urban men and women, Irish standardized mortality rates were the worst for non-rheumatic heart disease and respiratory tuberculosis. Various studies of morbidity of the elderly clearly reveal the hidden clinical iceberg of symptoms which are not presented to the health care system. Unfortunately, there is relatively little evidence of the health situation of disabled people, the travelling community or the long term unemployed.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Segmentation and the development of the vertebrate nervous system.
1. Recent experiments on the development of neural segmentation in chick embryos are reviewed. 2. Segmentation of the spinal peripheral nerves is governed by a subdivision of the somite-derived sclerotome into anterior and posterior halves. Migrating neural crest cells and outgrowing motor axons are confined to the anterior sclerotome as a result, in part, of inhibitory interactions with posterior sclerotome cells. 3. The sclerotomal distribution of certain molecules known to influence growing nerve cells in vitro, namely laminin, fibronectin, N-CAM, N-Cadherin and J1/tenascin/cytotactin, suggest that these molecules play no critical role in determining the preference of nerve cells for anterior sclerotome. 4. Peanut agglutinin (PNA) recognises cell surface-associated components on posterior cells which, when incorporated into liposomes, cause the abrupt collapse of sensory growth cones in vitro. The PNA receptor(s) may be inhibitory for nerve cells in vivo. 5. The chick hindbrain epithelium is segmented early in its development. Each branchiomotor nucleus in the series of cranial nerves V, VII and IX derives from a pair of segments lying in register with an adjacent branchial arch. Neurogenesis of motor and reticular axons begins in alternate segments, suggesting parallels with insect pattern formation.
Animals↗
Renal transplantation in older patients on peritoneal dialysis.
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Age Factors↗
Monoclonal antibody ELISA for cotinine in saliva and urine of active and passive smokers.
The value of a monoclonal antibody-based ELISA for measuring cotinine in saliva and urine of active and passive smokers was assessed. Cotinine (mean +/- SEM) was detected in all 26 saliva (392 +/- 74 ng/ml) and 27 urine (4264 +/- 508 ng/mg creatinine; 2566 +/- 364 ng/ml) samples from smoking parents, but in only two of 36 salivas and one of 37 urines from nonsmokers (P less than 0.001). Similarly, mean cotinine levels in 30 salivas (4.67 +/- 1.10 ng/ml) and 33 urines (35.5 +/- 8.8 ng/mg creatinine; 25.3 +/- 8.1 ng/ml) from passively exposed children were significantly higher (P less than 0.001) than in fluids of 36 unexposed children. Children's levels showed a strong correlation (P less than 0.001) with the number of cigarettes smoked in the home, but only when data from nonsmoking households were included in the analysis. In adult smokers there was a positive correlation between salivary and urinary cotinine (P = 0.002) and a close relationship between urinary cotinine and cigarettes smoked per day (P = 0.066). The ELISA gives a reliable quantitative measure of cotinine as an indicator of active and passive exposure to tobacco smoke. However, correlations with cotinine can be overestimated if large numbers of nonsmokers are included in the comparison.
Adult↗
The sensitized patient. A single center study.
1. In a 20-year period from 1966 to 1986, 650 renal transplants have been performed at the Toronto Western Hospital (University of Toronto). The 10-year actuarial patient survival is 62% and the actuarial graft survival is 35%. 2. A multivariant analysis using the Cox proportional hazard model indicated recipient age, donor source, graft number and time period were factors which independently influenced patient survival and that age and time period were variables which independently effected graft outcome. 3. Sensitization alone, using either peak or current PRA, did not significantly influence graft survival. Sensitization interacting with gender did affect graft survival, which was significantly lower in female patients with a high current PRA. Sensitization interacting with age produced different effects in the younger and older patients. The highly sensitized older patient has a better survival than the highly sensitized younger patient. However, for less sensitized patients the reverse was found; younger patients had a better survival than older patients. Also increasing levels of sensitization correlated with decreased survival in younger patients. 4. Predictive models based on the survivorship analysis of Kalbfleisch and Prentice were constructed to illustrate the impact of these variables on outcome.
Actuarial Analysis↗
Comparison of monoclonal and polyclonal antibodies to cotinine in nonisotopic and isotopic immunoassays.
Monoclonal antibodies (McAb) were used to develop nonisotopic and radioimmunoassays (RIA) for quantitative determination of the major nicotine metabolite, cotinine, in physiological fluids. ELISAs and fluorescence immunoassays were carried out in microtiter plate wells coated with a conjugate of cotinine 4'-carboxylic acid bound covalently to poly-L-lysine. The detection systems were horseradish peroxidase (HRP)-labeled staphylococcal protein A, HRP-streptavidin-biotin, and biotinylated alkaline phosphatase-4-methylumbelliferyl phosphate. With the three McAb tested, I50 values ranged between 0.024-0.063 ng cotinine and as little as 0.005-0.015 ng gave 15% inhibition. These assays were 5-20 times more sensitive than similar assays using six rabbit antisera. With McAb the standard inhibition curves were steeper and complete inhibition of immune binding was achieved with approximately 1 ng cotinine. In contrast, 100-500 ng cotinine failed to give greater than 80-90% inhibition with rabbit antibodies either in the plate assays or in RIA using a 125I-labeled tyramine derivative of cotinine as the tracer. In this RIA, the sensitivity with McAb (mean I50 of 0.55 ng cotinine) was over three-fold greater than with rabbit antisera (mean I50 of 1.84 ng). The presence of antibodies directed to the amide linkage group common to the polylysine conjugate. 125I-tyramine derivative and the immunogen likely accounts for the inferior quality of assays using rabbit antisera. Consistent with this conclusion, superimposable inhibition curves were obtained in the RIA when monoclonal or rabbit antibodies were used with [3H]cotinine. Cotinine levels in saliva, serum and plasma from smokers and non-smokers determined with McAb-based assays showed a strong correlation with values obtained by RIA using rabbit antisera or by gas chromatography. Properly selected McAb offer distinct advantages over conventional antisera in nonisotopic immunoassays and RIAs for cotinine as a biochemical marker of active or passive smoking.
Antibodies↗
Isolation and characterization of a pentameric amino acid from elastin.
An unknown amino acid was purified from bovine ligament elastin. The compound was shown by proton NMR to have a pyridinium ring structure similar to isodesmosine, yet containing an olefinic double bond on one additional side chain which was not attached to the pyridinium ring. Mass spectral analysis confirmed the NMR data and indicated a parent compound with a mass of 653. A structure is proposed that is derived from the condensation of five lysine residues. The trivial name of pentasine is proposed for this compound.
Amino Acids↗
Domiciliary services in Victoria.
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Aged↗
Alberta Hunter: a celebration in blues (and licensed practical nursing).
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History, 20th Century↗
Stereospecific monoclonal antibodies to nicotine and cotinine and their use in enzyme-linked immunosorbent assays.
Stereospecific monoclonal antibodies (McAb) have been prepared against the tobacco alkaloid (S)-(-)-nicotine and its major metabolite (S)-(-)-cotinine. Nine anti-nicotine and 4 anti-cotinine hybridomas, selected by a screening procedure that utilized immunoprecipitation of the 3H-labeled natural isomers of nicotine or continine, were grown in the ascites fluid of pristane-primed syngeneic BALB/c mice. Antibodies in concentrations up to 7.5 mg/ml ascites and with binding affinities that generally exceeded 10(8) M-1 were obtained. Enzyme-linked immunosorbent assays (ELISAs) were developed in which nicotine or cotinine derivatives bound covalently to poly-L-lysine were coated onto wells of polyvinyl chloride microtiter plates. Coated wells were incubated sequentially with McAb in the presence or absence of inhibitor, rabbit anti-mouse immunoglobulin, then horseradish peroxidase-labeled protein A (HRP-SpA) before addition of substrate. The antibodies are highly specific and show minimal cross-reactivity with several nicotine metabolites and other structurally related compounds. In the respective assays, only 0.25 ng (S)-(-)-nicotine and 0.12 ng (S)-(-)-cotinine are required to give 50% inhibition of antibody binding, and as little as 0.05 ng nicotine and 0.02 ng cotinine give 15% inhibition. These assays are 5-10 times more sensitive than analogous ELISAs developed with rabbit antisera and HRP-SpA or conventional radioimmunoassays (RIAs) that utilize the rabbit antisera and 3H-labeled ligands. There was good correlation between the levels of nicotine (r = 0.967) and cotinine (r = 0.981) found in saliva samples from smokers and non-smokers assayed by McAb-based ELISAs and conventional RIAs.
Antibodies, Monoclonal↗
In vitro reversibility of cadmium-induced inhibition of phagocytosis.
Cadmium chloride, administered chronically in the drinking water of CBA/H mice, produced a delayed clearance of particles and soluble material bearing Fc fragments (D. W. Knutson, D. L. Vredevoe, K. R. Aoki, and L. Levy, 1980, Immunology, 40, 17-26; D. L. Vredevoe, L. Levy, D. Knutson, G. Cook, and P. Cohen, 1985, Environ. Res. 37, 373-382). The inhibition was reversed upon removal of the cadmium from the water, even though a tissue load of cadmium persisted. An in vitro system was developed to analyze the mechanism of the inhibition. Binding and ingestion of sheep red blood cells (E) treated with IgG (for measurement of Fc receptor activity) or IgM and complement (C) (for measurement of complement receptor activity) were studied in resident and elicited murine peritoneal macrophages in vitro. Elicited macrophages provided the most definitive test system. With this system, there was significant inhibition of ingestion of E-IgG and E-IgMC. Binding of both types of erythrocytes was not inhibited, except at the highest concentration (10(-4) M) of CdCl2 at which binding of only E-IgMC was affected. These effects were reversible upon removal of cadmium. Migration of Fc and C receptors on the macrophage surface was not significantly affected by cadmium. In general, cadmium did not alter the expression or the binding of Fc or C receptors on macrophages. The mechanism for delayed clearance appears to be due to inhibited internalization of the particles. This is consistent with the interpretation that cadmium is a membrane active agent.
Animals↗