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Biomedical subjects

E A Jones

Publications and source records attributed to E A Jones.

At least 19 recordsLinked to original sources

Central mu-opioid receptors are down-regulated in a rat model of cholestasis.

Ameliorations of the pruritus of cholestasis by opioid antagonists are consistent with this form of pruritus being centrally mediated by the opioid system. To determine whether the central opioid system is altered in cholestasis, the specific binding of a selective mu-opioid receptor ligand, 3H-DAMGO, to mu-opioid receptors was studied in rats with acute cholestasis due to bile duct resection. Using whole brain membranes and subcellular mitochondrial-synaptosomal fractions the density of mu-receptor sites was 30% (p less than 0.01) and 22% (p = 0.03) less in bile-duct-resected rats than in sham-resected rats. Using membranes from individual brain regions specific binding of 3H-DAMGO was reduced by 43-53% in the cerebral cortex, hippocampus and caudate nucleus of bile-duct-resected rats. Thus mu-opioid receptors in the brain are down-regulated in a classical model of cholestasis. This alteration of the central opioid system could be a consequence of increased exposure of opioid receptors to endogenous opioids in cholestasis and may reflect an important mechanism in the pathogenesis of the pruritus of cholestasis.

Animals

Alpha-1-antitrypsin phenotypes in rheumatoid arthritis and systemic lupus erythematosus.

Alpha-1-antitrypsin phenotypes were determined in 37 patients with rheumatoid arthritis and 40 patients with systemic lupus erythematosus. No significant increase in non-MM phenotypes was found. It appears that alpha-1-antitrypsin phenotypes neither predispose to the development nor enhance the severity of the two rheumatic diseases.

Arthritis, Rheumatoid

Changes in the activity of lactose synthetase in the goat udder during pregnancy.

The lactose synthetase activity of homogenates and particulate fractions prepared from the udders of goats killed at various stages of pregnancy were determined. Both components of the enzyme, galactosyltransferase and alpha-lactalbumin, became detectable about half way through the gestation period, at the time when rapid proliferation of mammary epithelial tissue commences. Throughout the second half of pregnancy the udder possessed a high level of lactose synthetase activity though the lactose content of the tissue did not increase. These findings are discussed in relation to the endocrine control of lactogenesis in the goat and possible mechanisms for the induction of milk production at parturition.

Animals

Selective hepatic uptake of human beta-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells.

Intravenously administered (125)I-labeled human beta-hexosaminidase A (beta-N-acetylglucosaminidase; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30) was rapidly cleared from the circulation of rats and accumulated in the liver. When hepatic cells were subsequently isolated, the label was recovered from both sinusoidal cells and, to a lesser extent, hepatocytes. Clearance was inhibited by the simultaneous infusion of mannan but not by a galactose-terminated glycoprotein. Studies in vitro, in which (125)I-beta-hexosaminidase was incubated with isolated hepatic cells, detected no uptake of the labeled ligand by hepatocytes. In contrast, uptake by sinusoidal cells was shown to be temperature dependent and approached saturability. Prior treatment of sinusoidal cells with Pronase resulted in markedly decreased uptake of (125)I-beta-hexosaminidase by these cells. Mannan and partially deglycosylated glycoproteins bearing terminal nonreducing N-acetylglucosamine or mannose residues were shown to be potent inhibitors of the cellular uptake of (125)I-beta-hexosaminidase; native orosomucoid and desialylated (galactoseterminated) orosomucoid were not inhibitory. Of six simple sugars tested, including N-acetylglucosamine, only mannose was an effective inhibitor of the cellular uptake of (125)I-beta-hexosaminidase. The kinetics of uptake of beta-hexosaminidase and mannose-terminated orosomucoid by sinusoidal cells were shown to be similar. These findings suggest that the hepatic uptake of the lysosomal glycosidase beta-hexosaminidase A is mediated by a receptor on sinusoidal cells which recognizes and binds mannose-terminated glycoproteins.

Acetylglucosaminidase

Mammary growth during pregnancy in hypophysectomized or bromocriptine-treated goats.

Mammogenesis in primiparous hypophysectomized goats has been assessed between days 60 and 120 of gestation and compared with that found in untreated goats and goats treated with 5 mg bromocriptine/day. There were fivefold increases in the weight of lobulo-alveolar tissue in the hypophysectomized and bromocriptine-treated goats and a tenfold increase in the untreated goats. Histological examination of the mammary glands at 120 days showed normal structure, and determinations of lactose, lactose synthetase, cytosol enzymes, protein, DNA and RNA indicated qualitatively normal initiation of milk synthetic capabilities in both the hypophysectomized and bromocriptine-treated goats. Bromocriptine treatment lowered the plasma concentration of placental lactogen as well as that of prolactin. The results indicate that placental lactogen has important mammogenic effects during pregnancy.

Animals

The chronic sequelae of non-A, non-B hepatitis.

Twenty-six of 388 patients (6.7%) followed prospectively after open-heart surgery developed non-A, non-B hepatitis. Of these 26, 12 had an elevated (often fluctuating) serum alanine aminotransferase (SGPT) for greater than 1 year. Liver biopsy, done in eight of 12, showed chronic active hepatitis in six and chronic persistent hepatitis in two; one patient with chronic active hepatitis had early cirrhosis. Anicteric patients with peak SGPT greater then 300 IU/L were at greatest risk of developing chronic hepatitis. Chronic non-A, non-B hepatitis was symptomatically mild and unaccompanied by physical signs or laboratory evidence of autoimmune disease or severe chronic liver disease. In all 12 patients there was spontaneous improvement in serum transaminase over a period of 1 to 3 years, and four patients had sustained normalization of SGPT. Thus chronic active hepatitis is a common sequela of acute non-A, non-B hepatitis but may have a better prognosis than chronic active hepatitis of other causes.

Acute Disease

Hepatocellular injury with distinctive mitochondrial changes induced by lergotrile mesylate: a dopaminergic ergot derivative.

Increased serum activities of the enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) occurred in 12 out of 19 patients with idiopathic parkinsonism when they were treated with the ergot derivative lergotrile at an oral dose varying from 50 to 150 mg daily. Hepatocellular injury was confirmed by microscopic examination of liver biopsies obtained from 3 of these patients when the serum activities of ALT and AST were appreciably elevated. Light microscopy revealed features of mild acute hepatocellular injury, and electron microscopy showed proliferation of the smooth endoplasmic reticulum and apparently unique mitochondrial changes in hepatocytes. This is the first report of pathological changes in the liver associated with the therapeutic use of an ergot derivative. The presence of a potentially reactive cyanide group in the lergotrile molecule could be causally related to the observed hepatocellular injury. It is suggested that serum ALT and AST activities should be monitored carefully when the therapeutic potential of any new ergot derivative is assessed.

Adolescent

The significance of secretory IgA in middle ear fluid.

Studies of immunoglobulin levels in middle ear fluid in children with chronic otitis media show that MEF (middle ear fluid) IgA levels are proportionately higher than serum levels. Disproportionately elevated MEF IgA levels may be due to secretory IgA. Finding secretory IgA in MEF suggests the presence of a secretory epithelium and may define the etiology of chronic inflammation. Resolution of the secretory epithelium may be hastened with adequate ventilation of the middle ear space.

Acute Disease

Monocyte functional capacity in chronic neutropenia.

The bactericidal activity of monocytes from a child with chronic benign granulocytopenia who has had virtual absence of neutrophils yet minimal infections since birth was examined against Escherichia coli and Staphylococcus aureus and compared with that of monocyte and neutrophils from 20 control subjects. Studies on monocyte function in this patient with no neutrophils revealed normal monocyte kill of both organisms when compared with control monocytes. Monocyte and neutrophil killing of both organisms was similar in control subjects at bacteria to phagocyte ratios of 1:1. When ratios of 3:1 were employed, however, control neutrophils were more effective than control and patient monocytes in reducing the number of viable organisms. These findings support the neutrophil as the more effective blood phagocyte but stress the importance of monocyte functional capacity in patients compromised by granulocytopenia or neutrophil functional defects.

Agranulocytosis