Biomedical subjects
Publications and source records attributed to M Reardon.
Strychnine poisoning is reported in a patient who was the victim of attempted homicide in his home and in a General hospital. The diagnosis proved to be an elusive one over five months. The question of a primary psychiatric diagnosis, raised by the patient's wife proved to be an attempt by her to cover her crime. Medico-legal issues relating to the management of attempted homicide in hospital are discussed.
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The effect of growth phase on enzymatic activities of the de novo and salvage pathways for purine and pyrimidine nucleotide synthesis was studied in a hepatocyte-derived cell line from the rat. The cells were in lag phase after plating for 36 h; log phase started at 48 h and persisted up to 120 h of culture. Then the cells stopped growing and entered into plateau phase (144 h). In non-proliferating cells (144 h of culture) the basal activities of the enzymes of purine de novo biosynthesis were 1.7- to 6.8-fold higher than in normal rat liver, those of pyrimidine de novo synthesis showed 0.6- to 30-fold increase in activity. The purine salvage enzymes were unchanged, and the pyrimidine salvage enzymes were 3.1- to 7.4-fold higher compared to normal liver. During the growth cycle all enzymes except the purine salvage enzymes, which did not change, showed a peak in activity at 72 h of culture (log phase). The increase in activity in log phase compared to plateau phase was 1.3- to 2.4-fold for purine de novo synthetic enzymes, 1.1- to 2.4-fold for pyrimidine de novo enzymes, and 1.4- to 4.7-fold for pyrimidine salvage enzymes. The specific activities of the enzymes in exponentially growing cells were comparable either to that in 24-h regenerating liver, or to that in hepatomas of low or medium growth rate. It was concluded that the enzymatic pattern and metabolic state of the cells shared some features with regenerating liver, others with tumors, although they were not tumorigenic after transplantation into athymic nude mice.
UNLABELLED: We wondered if the inverse changes in airway conductance (Gaw) and functional residual capacity (FRC) during histamine (H) and acetylcholine (ACH) challenge are interrelated or occur at random. In 14 normal and 14 asthmatic subjects, we determined FRC and Gaw changes corresponding to changes in specific airway conductance (SGaw) around -40 percent produced by an aerosol of H or ACH inhaled quantitatively and with measured lung deposition. We also assessed the elastic recoil following H inhalation (5A). We found that in 11 normal and nine asthmatic subjects, after H or nine normal and 11 asthmatic subjects after ACH, Gaw and 1/FRC were linearly and directly related (p less than 0.05). The steepness of this slope was directly related to the resting Gaw values. A similar relation was uncovered in the literature for asthmatic patients at rest or during recovery from natural asthma. As the elastic recoil was normal and did not change after H, it could not explain delta FRC at delta SGaw of -40 percent. IN CONCLUSION: (1) during H or ACH challenge, Gaw-FRC relationship in normal or asthmatic subjects tends to be hyperbolic and dependent on resting Gaw; (2) such a relationship is seemingly present in other bronchoconstrictor responses with a different pathogenesis; and (3) during bronchoconstriction, as Gaw vs FRC is no longer linear, SGaw becomes volume dependent.
We evaluated the adequacy of regional and transmural blood flow during exercise and rapid pacing after 1 wk of hypoxemia. Seven mature mongrel dogs were made hypoxemic (mean O2 saturation = 72.4%) by anastomosis of left pulmonary artery to left atrial appendage. Catheters were placed in the left atrium, right atrium, pulmonary artery, and aorta. Atrial and ventricular pacing wires were placed. An aortic flow probe was placed to measure cardiac output. Ten nonshunted dogs, similarly instrumented, served as controls. Recovery time was approximately 1 wk. Cardiac output, mean aortic pressure, and oxygen saturation were measured at rest, with ventricular pacing, atrial pacing, and with treadmill exercise. Ventricular and atrial pace and exercise were at a heart rate of 200. Right ventricular free wall, left ventricular free wall, and septal blood flow were measured with radionuclide-labeled microspheres. Cardiac output, left atrial blood pressure, and aortic blood pressure were similar between the two groups of dogs in all testing states. Myocardial blood flow was significantly higher in the right and left ventricular free wall in the hypoxemic animals during resting and exercise testing states. Myocardial oxygen delivery was similar between the two groups of animals. Pacing resulted in an increase in myocardial blood flow in the control animals but not the hypoxemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence was provided that in rat liver synthase II activity, amount and turnover were regulated primarily by insulin. When rats were starved, synthase II activity and the immunotitratable enzyme amount markedly decreased; refeeding restored enzyme activity and amount to normal range. The changes in activity and amount were paralleled with alterations in the level of circulating insulin in the plasma. When starved rats were treated with anti-insulin serum before and during refeeding, the animals consumed the food, but the rise in synthase II activity was prevented. In diabetic rats, the activity and amount of synthase II in the liver markedly decreased and insulin treatment restored them to normal range. Actinomycin treatment prevented the refeeding and the insulin-induced rise in synthase II activity and amount. Study of the turnover of synthase II showed that in starvation the rate of synthesis decreased and refeeding restored the enzyme synthetic and degradation rates to normal range. In the diabetic rat, synthase II synthetic rate markedly decreased, and the degradation rate increased. Insulin returned the synthetic and catabolic rates to normal livers. In rapidly growing rat hepatoma 3924A, synthase II activity and amount were elevated 9- to 10-fold. Turnover studies showed that the synthetic rate in hepatoma 3924A was approximately 10-fold higher than that of normal liver. The catabolic rates of synthase II were similar in the liver and hepatoma. Thus, the increased activity and amount of synthase II in the hepatoma was due primarily to an increased rate of enzyme biosynthesis. Evidence was presented that in starvation and diabetes and on refeeding and insulin administration there is very little or no change in the enzymic activity, amount and turnover of hepatoma synthase II. The marked contrast between the turnover rate of hepatoma 3924A synthase II activity and that of the normal liver enzyme in starvation and in diabetes is under investigation. This overview of the behavior of activity, amount and turnover of synthase II in liver and hepatoma 3924A provides evidence of the important role of insulin in regulation of liver synthase II and of the apparent lack of responsiveness of the hepatoma enzyme to insulin concentrations. The precise details of the experimental procedures and the enzymic results will be published elsewhere.
The mechanism for the marked reduction in hepatic triglyceride secretion when rats are fed fish oils was explored in studies with isolated rat hepatocytes. Hepatocytes obtained from Sprague-Dawley rats fed either chow or fish oil or safflower oil were incubated in the presence of [3H]-glycerol to estimate triglyceride formation. In some experiments, various fatty acids, complexed to albumin, were added to the incubations. Similar experiments were carried out with hepatocytes from a genetic strain of hypertriglyceridemic, obese rats. In the absence of added fatty acid, hepatocytes from fish oil-fed rats produced and secreted substantially less triglyceride than cells from safflower oil-fed rats. However, the addition of 2 mmol/L Na oleate stimulated triglyceride formation similarly in both types of hepatocytes. When hepatocytes from chow fed rats were incubated with fatty acids of increasing chain length and unsaturation (oleate, linolenate, arachidonate, eicosapentaenoate, and docosahexaenoate), the latter two, which characterize the fish oil used, almost totally suppressed triglyceride formation. Coincubation with oleate partly reversed this effect. Hepatocytes from the hypertriglyceridemic rats synthesized significantly more triglyceride than hepatocytes from normal rats; however triglyceride formation was markedly reduced also in this strain of rat by feeding fish oil or by adding docosahexaenoate to hepatocytes in vitro. These studies confirm previous conclusions with perfused livers from fish oil-fed rats that showed diminished triglyceride production and secretion. These findings suggest that diversion of polyenoic acids from pathways of esterification is a major factor in the triglyceride lowering effect of fish oils.(ABSTRACT TRUNCATED AT 250 WORDS)
We wanted to determine whether the competitive radioimmunoassay for IgE is influenced by various combinations of three monoclonal IgE (IgEND, IgEPS, IgESHA) used as tracer or standard, and anti-IgEND and anti-IGEPS as first antibody. When the immunogen for the first antibody was identical with the monoclonal tracer or standard IgE, the latter two bound preferentially to the first antibody. These unusual assays led to inhibition curves that ran in parallel to those produced by usual assays, i.e. assays in which the tracer and the immunogen were different monoclonal IgE and the standard was a polyclonal IgE. When serum samples were analyzed for their IgE content, the unusual assay produced values that were linearly related to those produced by a usual or another, unusual, assay. However, the values of IgE produced by a usual assay were, in general, significantly different from those obtained by unusual assays. We conclude that as suspected, but never demonstrated before, the competitive assay for IgE requires the use of two different monoclonal IgE as tracer and immunogen; application of unusual assays requires their prior calibration against a usual assay.
The kinetics of the major apoproteins of high density lipoproteins (HDL), A-I(apoA-I) and A-II(apoA-II), were studied from the specific activity-time curves of these apoproteins, after reinjection of radioiodine-labeled HDL. In all 20 subjects, HDL apoprotein kinetics conformed to a two-pool model. The total fractional removal rates for the two apoproteins were similar, although the irreversible fractional removal rate appeared to be slightly greater for apoA-I. The mean transport for A-I and A-II was 12.2 mg/kg/day and 5.0 mg/kg/day, respectively. The mass of the apoprotein pools was strongly correlated with apoprotein production rate and also, to a lesser degree and inversely, with the irreversible fractional catabolic rate. Transport was directly correlated with body weight. Higher fractional catabolic rates, including the transfer rates between the two pools, were observed in five hypertriglyceridemic subjects; in contrast, five subjects with familial hypercholesterolemia tended to show lower fractional catabolic rates. These findings were supported by (1) a strongly positive correlation between the transport rates of HDL A-I and of very low density lipoprotein (VLDL) apoB, determined simultaneously in 10 subjects; and (2) a significant inverse correlation between the irreversible fractional removal rate of HDLA-I and the concentration of low density lipoprotein (LDL) apoB, measured in 15 subjects. These observations underline the metabolic interrelationships of the major lipoprotein classes. Two subjects with familial hyperalphalipoproteinemia showed enlarged pool sizes, but normal transport, with irreversible fractional removal rates that were in the lower range for the group of 20 subjects.
The fate of cholesteryl esters in high density lipoprotein (HDL) was studied to determine whether the transfer of esterified cholesterol from HDL to other plasma lipoproteins occurred to a significant extent in man. HDL cholesteryl ester, labelled in vitro with [3H] cholesterol, was injected into human subjects. Labelling of cholesteryl esters in very low density (VLDL) occurred rapidly and by 3 h, the esterified cholesterol in VLDL reached peak specific radioactivity. The removal rate of cholesteryl esters from HDL appeared to be exponential and of the order of 0.2/h; calculation of the apparent flux was about 150 mg/h which approximates reported values for total cholesterol esterification in human plasma in vivo. The rapid rate of labelling of VLDL from HDL suggests that the transfer of HDL cholesteryl esters to VLDL may represent a significant pathway for the disposal of HDL cholesterol.
Dietary sucrose has been shown to increase triglyceride transport in very-low-density lipoproteins (VLDL), but it is not known whether the metabolism of the entire particle is affected. Measurements were therefore carried out on VLDL-B apoprotein flux and removal rate before and after the consumption of high sucrose diets (55% of calories). Autologous 125I-labeled VLDL were injected and the specific activity-time curves analyzed by two-pool kinetics. Two kinds of response to sucrose were seen. In two subjects, the pool of VLDL-B apoprotein decreased by 20% and 14% (despite increased fluxes) due to substantial increases in removal rates of 42% and 116%. In four subjects, pool size expanded by 154%, 426%, 50% and 105%, primarily as the result of decreased removal rates (decreases of 55%, 67%, 30%, and 43%). Changes in flux were inconstant, suggesting that accumulation of VLDL particles was related to delayed clearance rather than to increased formation. This may reflect the longer time required to remove the larger load of triglyceride from each particle. The catabolic rate of low-density lipoprotein (LDL) was also measured in five subjects: in four, the clearance of LDL increased with sucrose and was associated with decreases in LDL-B apoprotein and plasma cholesterol.
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Glaucoma is one of the leading causes of irreversible blindness in the world and is characterized by elevated intraocular pressure, optic nerve atrophy, and progressive visual field loss. Primary open angle glaucoma (POAG) is the most common subtype of glaucoma in the United States. Recently, Stoilova and coworkers [Genomics 1996;36:142-150] identified a locus for POAG on chromosome 2 (2cen-q13) in families primarily located in the United Kingdom. We examined families with POAG identified within the US for linkage to the 2cen-q13 locus. A total of 18 families with POAG were used in the analysis. Of 77 family members, 46 were classified as affected and 31 were either glaucoma suspects or considered normal. Eight highly polymorphic and informative markers flanking and distributed throughout the region were used. Parametric lod score analysis was performed using both a dominant and recessive low penetrance or 'affecteds-only' model. Multipoint affected sibpair exclusion mapping was also performed. Lod score (both models) and sibpair analysis excluded linkage of the POAG phenotype to the 2cen-q13 region in these families. These data suggest that the chromosome 2cen-q13 locus does not explain a substantial amount of genetic variation in familial POAG.