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Biomedical subjects
Publications and source records attributed to A Richardson.
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The size of the poly(A) segment of poly(A)+RNA extracted from hepatocytes isolated from 4- to 30-month-old rats was determined using polyacrylamide-agarose gel electrophoresis. The average size of the poly(A) segment isolated from newly synthesized poly(A)+RNA was 150 nucleotides, and the average size of the poly(A) segment isolated from the steady state pool of cytoplasmic poly(A)+RNA was 70 nucleotides. No significant age related change in either the size or the heterogeneity of the newly synthesized poly(A) segment was found. The translational activity of poly(A)+RNA isolated from livers of 4- to 30-month-old rats was determined using wheat germ extract and rabbit reticulocyte lysate cell-free systems. No age-related change in the translational activity of the poly(A)+RNA was observed. The effect of aging on the cap structure was also studied by measuring the inhibition of cell-free translation by 7-methyl guanosine-5'-monophosphate. No age-related change in the sensitivity of the poly(A)+RNA preparations to inhibition of translation by 7-methyl guanosine-5'-monophosphate was observed. Therefore, the results of this study demonstrate that no major age-related change occurs in the structure of the poly(A) segment, the translational activity, or the cap structure of poly(A)+RNA from rat liver.
The influence of age on the mixed function oxidase system from a non-human primate was studied. Microsomes were isolated from the livers of female Macaca nemestrina ranging from 2 to 21 years of age. No significant age-related change was observed in either the cytochrome P-450 content or the NADPH cytochrome c reductase activity. In addition, the ability of the microsomes to metabolize benzo [a]pyrene did not change significantly with age. These observations contradict studies with liver tissue from laboratory rodents in which an age-related decline in the mixed function oxidase system is generally observed. The lipid composition of the liver microsomes was studied also. Both the cholesterol and total phospholipid content of the liver microsomes increased significantly with age; however, the ratio of cholesterol to phospholipid remained constant. The percentage of individual phospholipids in the microsomes changed only slightly with age. These results provide new information on the effect of age on the mixed function oxidase system and indicate that one must be cautious in extrapolating from studies with liver tissue from laboratory rodents to primates.
The influence of age and food restriction on kidney protein synthesis was studied in Fischer F344 rats. The rate of total protein synthesis by suspensions of kidney cells declined 60% between 4 and 31 months of age. The rate of protein synthesis by kidney cells isolated from 19-month old rats fed a restricted diet (60% of diet consumed by rats fed ad libitum) was 45% higher than the rate of protein synthesis by kidney cells isolated from 19-month old rats fed ad libitum. The excretion of protein in the urine was measured to assess the effect of the age related decline in protein synthesis on kidney function. A dramatic increase in proteinuria was observed with increasing age, and rats fed the restricted diet excreted significantly less protein in the urine than rats fed ad libitum.
Lymphocyte proliferation induced by lectins declines drastically with age. It has been suggested that the reduction of interleukin production by lymphocytes from old individuals is responsible for the decline in proliferation. In this study, lymphocyte proliferation was stimulated by the calcium ionophore, A23187. A23187 induced the proliferation of spleen lymphocytes from rats through an interleukin-independent pathway; depletion of spleen lymphocytes of macrophages, addition of exogenous interleukin 2 (IL 2), and addition of anti-IL 2 monoclonal antibodies had no effect on the proliferation stimulated by A23187. Spleen lymphocytes from male Fischer F344 male rats of 5, 13, 22, and 30 months of age were stimulated with either concanavalin A (Con A) or A23187. A 50% decrease in Con A- and A23187-induced proliferation was observed between 5 months and 13 months of age. A23187-induced proliferation decreased only slightly between 13 months and 30 months of age (14%), while Con A-induced proliferation decreased by 34%. This is the first report to show that the induction of lymphocyte proliferation through an interleukin-independent pathway decreases with increasing age. In addition, these results suggest that a decrease in the responsiveness of cells to calcium ions might be an important factor in the age-related decline in lymphocyte proliferation.
Mitochondria isolated from heart tissue after a 1-min perfusion with Hanks medium were found to have significantly lower rates of State-3 respiration and respiratory control ratios compared to mitochondria isolated from non-perfused hearts. Examination of the mitochondrial preparations by electron microscopy revealed that a large proportion of the mitochondria isolated from perfused heart tissue were swollen and broken compared to mitochondria from non-perfused hearts.
At 6 wk of age, male Fischer F344 rats were fed a purified, casein-based diet either ad libitum or in the amount of 60% of the diet consumed by the rats fed ad libitum (restricted diet). Hepatocytes were isolated from the rats between 2.5 and 19 mo of age. The protein content of the hepatocytes isolated from the rats fed the restricted amount of diet was significantly lower than that of hepatocytes isolated from rats fed ad libitum. The DNA and RNA content of the hepatocytes were similar for the rats fed the two dietary regimens. The absolute rate of protein synthesis for hepatocytes isolated from rats fed ad libitum decreased 55% between 2.5 and 19 mo of age. However, the rate of protein synthesis by hepatocytes from rats fed the restricted amount of diet decreased only slightly with increasing age. At 19 mo of age, the rate of protein synthesis by hepatocytes from the rats fed the restricted amount of diet was significantly higher than the rate of protein synthesis for hepatocytes from rats fed ad libitum. Therefore, dietary restriction retards the age-related decline in liver protein synthesis.
Eight cases of major haemobilia have been seen by the Surgical Hepatobiliary service at Westmead Hospital between 1979 and 1984. Two occurred following blunt abdominal trauma, three after percutaneous biliary drainage or liver biopsy, two in association with postoperative haemorrhagic pancreatitis and one because of an abscess complicating hepatic hydatid disease. Coeliac and superior mesenteric angiography were carried out in all patients, and false aneurysms were demonstrated in seven of the eight. A marked coagulopathy was present in the remaining patient, in whom bleeding stopped without intervention when the coagulopathy was reversed. Those with false aneurysms were treated by radiologically controlled transarterial embolization with gelfoam, acrylate or Gianturco coils, and bleeding was controlled in all. There was one death from overwhelming sepsis in the patient with the hepatic abscess. It is concluded that percutaneous radiologically controlled embolization is the treatment of choice for most cases of haemobilia, except when there is major hepatic sepsis.
The ability of the beta 1 partial agonists prenalterol and corwin , to displace the binding of [3H]dihydroalprenolol to the heterogeneous populations of beta-adrenoceptors on rat and rabbit lung membranes was compared. Both drugs exhibited higher affinity for the binding sites in rabbit lung (predominant beta 1) as compared to rat lung (predominant beta 2). Curve fitting analysis of the displacement curves into high affinity (beta 1) and low affinity (beta 2) components indicates that both drugs exhibit beta 1 selective affinity. Further competition experiments performed in the presence of carefully calculated concentrations of highly selective beta 1 (atenolol) or beta 2 (ICI 118,551) antagonists to produce homogeneous receptor subtype populations in rat and rabbit lung membranes respectively, confirmed this beta 1 selective affinity. These results suggest an approximate selective affinity ratio (beta 1 to beta 2) of ten and forty fold for prenalterol and corwin respectively.
Ultraviolet-induced unscheduled DNA synthesis was studied as a function of age in hepatocytes isolated from 6- to 32-months-old rats. Unscheduled DNA synthesis was measured by both DNA specific activity and autoradiography. Using both procedures, a significant decline in unscheduled DNA synthesis was observed after 14 months of age.
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A primigravida with severe kyphoscoliosis developed cardio-respiratory failure in pregnancy. Cardiac arrest occurred 10 days after Caesarean section; gastric acid was aspirated then and was followed by the development of adult respiratory distress syndrome. Initial recovery, with clearing of peripheral oedema, was followed by a recurrence of respiratory distress associated with infection. Profound hypoxaemia and oliguria unresponsive to diuretics were relieved by the infusion of prostacyclin combined with fluid removal by ultrafiltration. This treatment may be of value in the management of respiratory distress syndrome when pulmonary oedema is the dominant feature.
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Urine samples from 6- to 31-month-old male Fischer F344 rats were analyzed using a high performance liquid chromatograph and a unique computer-based data analysis and quality control system in order to discover substances that could be used as markers in the aging process. Metabolic profiles of the organic acids from these urines yielded 42 peaks whose areas could be measured reliably. Of the 42 peaks, 10 were found by analysis of variance to vary significantly (p less than 0.05) with age. Rats from the four ages could also be distinguished using a multivariate statistic (discriminant analysis).
The diurnal rhythms of body temperature and serum thyrotrophin (TSH) levels in euthyroid individuals behaved inversely to one another. An artificially induced rise in the body temperature of these individuals was accompanied by a fall in serum thyrotrophin levels, the amplitudes of their respective rhythms decreasing simultaneously. There was a marked correlation between the degrees of change in body temperature and circulating thyrotrophin levels respectively during warming. In normal subjects manipulation of the diurnal rhythm of body temperature brings about inverse alterations in the thyrotrophin rhythm.
The responses of circulating catecholamines, TSH, thyroid hormones and prolactin to 30 min of acute cold exposure (4 degrees C) were measured in eight normal volunteers over a 2 h period. There was a rise in circulating noradrenaline, TSH, T4 and T3 levels and a fall in circulating prolactin in the subjects studied, but no change in circulating adrenaline levels nor any alteration in the T4/T3 ratio. The thyroid axis of normal individuals can respond rapidly to acute cold exposure. In addition, the increased plasma noradrenaline levels accompanied by unaltered adrenaline levels suggest that the stimulus exerted by cold does not evoke a generalised stress response, but rather that the sympathetic nervous system is selectively stimulated.
A patient with vertebral artery injury from penetrating neck trauma was treated by percutaneous transluminal embolization.