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Biomedical subjects

M Carroll

Publications and source records attributed to M Carroll.

At least 163 records · Page 9Linked to original sources

Effect of vitamin D3, other drugs altering serum calcium or phosphorus concentrations, and desoxycorticosterone on the distribution of Tc-99m pyrophosphate between target and nontarget tissues.

Radioactive imaging agents are chemically designed for selective distribution. Another approach to selectivity is to find stable compounds that favorably influence this distribution. Using a rat model of myocardial necrosis, we studied effects of various stable compounds (as a single, large dose or fractionated into short series) on the ratio, uptake of Tc-99m pyrophosphate (PPi) by the target lesion/uptake by the principal nontarget, bone (L/B). Vitamin D3s ability to increase L/B was mediated by the hypercalcemia and hyperphosphatemia that it caused. The hypercalcemia was accompanied by increased [Ca] in the lesion. In contrast, pulse doses of desoxycorticosterone acetate (DOCA) at 7 and 6 hr before killing increased uptake by lesion, increasing L/B from 0.19 +/- 0.03 to 0.45 +/- 0.08 (p less than 0.01), with no change in serum [Ca] and minimal changes in serum [P], [Na], and [K]. DOCA also increased the lesion-to-blood ratio from 6.5 +/- 0.07 to 15.4 +/- 3.9 (p less than 0.05). These results encourage further study of DOCA's effect and investigation of other stable drugs that may influence distribution of other imaging agents.

Animals↗

Isoenzymes of membrane-bound beta-glucosidase of human spleen.

Normal human spleen contains two forms of membrane-bound beta-glucosidase, distinguishable by their thermostability and kinetic properties. The spleen from a patient with adult Gaucher's disease was deficient in the major, thermolabile, form of the enzyme.

Cell Membrane↗

Studies of uptake of the bretylium analogue, iodobenzyltrimethylammonium iodide, by non-primate, monkey and human hearts.

Uptake of (+/-)-[3H]-noradrenaline, [14C]-bretylium and [125I]-o-iodobenzyltrimethylammonium iodide (RIBA) by rat heart was studied by the Langendorff technique. All three compounds showed significant uptake. 2 Corticosterone and 17-beta-oestradiol inhibited the uptake of all three compounds by rat heart, a finding consistent with extraneuronal uptake (uptake2). 3 [131I]-RIBA was injected intravenously into pigs and monkeys (M. speciosus). Myocardial samples taken from pigs killed 1 and 2 h after injection showed significant uptake. No significant uptake was found in myocardial samples of monkeys killed 10 min, 2 h and 24 h, respectively, after injection. 4 Four normal human volunteers received [125I]-RIBA intravenously and the image of the precordial area was followed by means of scintillation camera for the first 4 h after injection. In two of the subjects, the scintigrams were repeated at 22 and 23 h after injection, respectively. No evidence of myocardial uptake was observed. 5 These results suggest the possibility that man and at least one other primate species may differ from lower species with regard to uptake.

Adult↗

Characterization of proteins structurally related to human N-acetyl-beta-D-glucosaminidase.

Those proteins of human liver that cross-reacted with antibodies raised to apparently homogenous hexosamindases A and B were detected by immunodiffusion. Cross-reacting proteins with high molecular weights (greater than 2000000) and intermediate molecular weights (70000--200000) were present both in the unadsorbed fraction and in the 0.05--0.2M-NaCl eluate obtained by DEAE-cellulose chromatography at pH7.0. The unadsorbed fraction also contained a cross-reacting protein of low molecular weight (10000--70000). The possible structural and functional relationships between hexosaminidase and the cross-reacting proteins are discussed. An apparently cross-reacting protein present in the 0.05M-NaCl eluate from the DEAE-cellulose column was serologically unrelated to hexosaminidase, but it gave a reaction of immunological identify with one of the apparently cross-reacting proteins having the charge and size characteristics of hexosaminidase A. It is suggested that immunochemical methods may provide criteria for the homogeneity of enzyme preparations superior to those of conventional methods.

Acetylglucosaminidase↗

Hereditary hemochromatosis. Diagnosis in siblings and children.

We studied five patients with clinically manifest hemochromatosis and 19 of their siblings and children to define better the diagnostic criteria for stages of the disease. The earliest detectable abnormalities were an increase in hepatic-parenchymal-cell stainable iron, hepatic iron concentration, transferrin saturation and serum iron concentration. In contrast, urinary iron excretion after deferoxamine and serum ferritin concentration were usually normal in early iron loading. In either latent or clinically manifest disease, hepatic-parenchymal-cell stainable iron was Grade 3 or 4; hepatic iron concentration was greater than 250 microng per 100 mg; serum iron was greater than 170 microng per 100 ml; transferrin saturation was greater than 70 per cent; urinary iron excretion exceeded 2.2 mg per 24 hours; and serum ferritin usually exceeded 1000 ng per ml. Estimation of liver iron is the most sensitive method for detecting early disease. Urinary iron excretion and serum ferritin estimate the total body burden of iron in latent and clinically manifest disease.

Adolescent↗

A radioiodinated bretylium analog as a potential agent for scanning the adrenal medulla.

Studies with radioiodinated bretylium analogs (RIBA) suggested that the p-isomer was capable of concentrating in adrenal medulla. The present studies with 125I-p-RIBA in rats and dogs confirm this property and show its marked and persistent affinity for the adrenal medulla. Analogous studies with 14C-p-IBA indicate that it is the quaternary form of the drug that is retained by the adrenal and that high thyroidal radioactivity following 125I-p-RIBA administration is due to in vivo deiodination of the drug.

Adrenal Gland Diseases↗

A low-molecular-weight protein cross-reacting with human liver N-acetyl-beta-D-glucosaminidase.

Antisera were raised to preparations of hexosaminidase isoenzymes A and B purified from human liver. Protein that cross-reacted with the liver hexosaminidase was detected by an antibody-consumption method. A cross-reacting protein with a low molecular weight (20000) was partially characterized and purified from control human liver. This protein is also present in the liver of patients with Tay-Sachs disease or with Sandhoff's disease. Hexosaminidases A and B gave an immunological reaction of partial identity with the low-molecular-weight protein. The possible identity of the low-molecular-weight cross-reacting protein as a subunit of hexosaminidase is discussed.

Acetamides↗

Separation and properties of human brain hexosaminidase C.

Hexosaminidase C was separated from human brain supernatant by immunoadsorption of the A and B forms on to a column of immobilized antibody followed by preparative starch-block electrophoresis. There were some differences in the properties of hexosaminidase C preparations after each of these stages, shown by comparison of their heat-inactivation characteristics and filtration through Bio-Gel P-200. The C form prepared by both separation steps had properties which differed markedly from those of the A and B isoenzymes; its molecular weight was much larger, greater than 200000, it had optimum activity between pH6 and 7 and could not be successfully eluted from DEAE-cellulose, even with high salt concentrations, or from Sephadex G-200. These results seem to support the proposal that the C form is under a separate genetic control from the others.

Adsorption↗