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Biomedical subjects

J Ryan

Publications and source records attributed to J Ryan.

At least 307 records · Page 17Linked to original sources

Screening for breast cancer by mammography: an Australian experience.

Four years' experience of screening well women for breast cancer by mammography is described. Twenty-six cancers were detected in 11,927 women (2-2 per 1,000), of which 20 were unsuspected by the patient and 12 were impalpable. Of the 26 cancers detected, 18 had no histological evidence of tumour in axillary lymph nodes, and 10 were impalpable and had unaffected axillary nodes. Four patients whose mammograms did not suggest malignant disease were subsequently found to have cancer, within 12 months.

Adenocarcinoma↗

Response of transplanted AKR leukemia to combination therapy with amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea: dose and schedule dependency.

A number of different amphotericin B (AmB)-1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) treatment regimens were evaluated with our model of transplantable AKR leukemia. We found that dose levels and treatment schedules were critical in determining the number of survivors. A 4-day treatment regimen of 0.5 mg AmB/mouse on days 1, 2, 3, and 4 and 0.2 mg BCNU/mouse on day 4 was found to be the most effective and has been chosen as our standard regimen. The efficacy of the treatment regimen depended on the presence of a large tumor burden, and the response was abolished when the mice were preirradiated or treated with the immunosuppressive agent, cyclophosphamide. These results, as well as others which we discuss, supported our notion that AmB affected host immune response to the tumor.

Amphotericin B↗

Effect of vasoactive intestinal polypeptide on basal and cholecystokinin-induced gallbladder pressure.

Studies were conducted in vivo to examine the pressure response of the opossum gallbladder to vasoactive intestinal polypeptide (VIP) alone and in combination with cholecystokinin (CCK). The following observations were made (1) VIP alone produced dose-related decreases in basal gallbladder pressure; (2) VIP eliminated spontaneous contractile activity when present; (3) VIP significantly antagonized the expected pressure response to CCK infusion. These observations lend further support to our proposal that the regulation of gallbladder motor function depends upon the actions and interactions of the gastrointestinal hormones on gallbladder smooth muscle.

Animals↗

Technetium-99m-labeled n-(2,6-dimethylphenylcarbamoylmethyl) iminodiacetic acid (tc-99m HIDA): a new radiopharmaceutical for hepatobiliary imaging studies.

An easily formulated, stable kit preparation of technetium-99m HIDA, suitable for use in humans, was developed and tested in mice and dogs. The tracer was cleared rapidly from the blood and excreted predominantly by the liver in both species. In dogs, the hepatobiliary clearance of Tc-99m HIDA was significantly greater than that of C-14 HIDA and Sn-113 HIDA. The LD50 for HIDA in mice, 168 mg/kg, exceeded the average human dose by a factor of 1000 on a per-weight basis. Blood clearance curves for Tc-99m HIDA in 12 normal subjects were biexponential with half-times of 4.6 +/- 1.0 min and 31.5 +/- 7.0 min, and cumulative 90-min urine samples contained 14.2 +/- 1.8% of the injected dose. Images in normal subjects and nonjaundiced patients showed rapid concentration of tracer by the liver and activity was present within the biliary system in 10-20 min. In jaundiced patients, the tracer blood clearance was delayed and urinary excretion increased, but intestinal activity, indicating biliary patency, was imaged in those patients without complete focal obstruction of the common duct. Technetium-99m HIDA is a nontoxic radiopharmaceutical useful for clinical evaluation of hepatobiliary disorders in humans.

Acetanilides↗

Elemental analysis of biological specimens in air with a proton microprobe.

The unique capabilities of the proton microprobe in an atmospheric environment as a biological tool are illustrated in studies of arsenic and mercury distributions in siingle strands of hair from poisoning victims and of the distributions of several abundant elements in frozen hydrated eye and kidney specimens from rats.

Animals↗

The HLB dependency for detergent solubilization of hormonally sensitive adenylate cyclase.

The HLB dependency for the solubilization of membrane proteins and adenylate cyclase activity from a plasma membrane-enriched fraction from rat liver has been determined. The HLB (hydrophilic/lipophilic/balance) number of a detergent is an empirical measure of its relative hydrophobicity. Detergent HLB numbers vary systematically with the length of the ethylene oxide chain for a homologous series of detergents such as the Triton X series. These detergents have a constant hydrophobic moiety, octylphenyl, and a variable polar portion, polyethoxyethanol. Basal-NaF-epinephrine-, and glucagon-stimulated adenylate cyclase activities were solubilized in the HLB range of 16.8-17.4. Solubilization was most effective in 0.01 M Tris buffers at pH 7.5 containing 1-5 mM mercaptoethanol, 1 mM MgCl2, and 0.1% Triton X-305. The detergent to membrane protein ratio used in these studies was 3:1. Criteria for solubilization included lack of sedimentation at 100,000 X g, the absence of particulate material in the supernatant when examined by electron microscopy, and inclusion of hormonally sensitive adenylate cyclase activity in Sephadex G-200 gels. The apparent molecular weight of the solubilized enzyme was approximately 200,000 in the presence of Triton X-305. The solubilized enzyme was stimulated 5-fold by NaF, 7-fold by glucagon, and 20-fold by epinephrine compared to the particulate enzyme used in this study which was stimulated 10-fold, 3.4-fold, and 4-fold by NaF, epinephrine, and glucagon, respectively. The solubilized enzyme is stable for several weeks when stored at -60 degrees C.

Adenylyl Cyclases↗

Renal echography.

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Adolescent↗

Interaction of gastrin I, secretin, and cholecystokinin on gallbladder smooth muscle.

The effect of cholecystokinin (CCK), the octapeptide of cholecystokinin (CCK-OP), gastrin I, and secretin was studied on guinea pig gallbladder smooth muscle in vitro. Both CCK and CCK-OP stimulated gallbladder contraction, with CCK-OP being more potent. Gastrin I, over a wide dose range, had no effect on gallbladder contractility. Secretin alone also showed no effect on gallbladder smooth muscle but in combination with CCK-OP it produced a noncompetitive type of inhibition. Michaelis-Menten kinetics showed the calculated maximum response of the secretin plus CCK-OP interaction to be less than with CCK-OP alone. There was no change in the dose required to achieve half-maximal response, D50. These studies indicate that: a) CCK-OP has a greater effect on gallbladder contractility than CCK, b) gastrin I has no effect on gallbladder muscle tone, and c) secretin acts as a noncompetitive antagonist of CCK-OP. These findings suggest that gallbladder motor function may be determined in part by the interaction of secretin and CCK rather than solely in response to CCK.

Animals↗

Gallbladder pressure-volume response to gastrointestinal hormones.

The pressure-volume (PV) response of the opossum gallbladder was studied under basal conditions and after the continuous intravenous infusion of gastrin I, secretin, and cholecystokinin (CCK). The hormone effects were examined individually and in combination. The unstimulated gallbladder was capable of accommodating increases in intraluminal volume with only slight changes in intraluminal pressure. Cholecystokinin significantly increased the pressure recorded from the gallbladder. The pressure generated depended on the concentration of CCK and the intraluminal volume. Gastrin I had no independent effect on the PV response of the gallbladder but reduced the stimulatory affect of CCK. Secretin, alone, decreased the PV response of the gallbladder. Secretin also antagonized the stimulatory response to CCK. These findings suggest that the regulation of gallbaldder motor function and pressure generation exclusive of neural input, may depend on the interaction of CCK with gastrin and secretin and the intraluminal volume of the organ at the time of stimulation.

Animals↗

A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog.

Intravenous dose-response data obtained from renal clearance studies in anesthetized dogs indicated that bumetanide was approximately 30-fold more potent than furosemide in enhancing sodium excretion. After the administration of 0.01 mg/kg of bumetanide or 1.0 mg/kg of furosemide, the relationship between i.v. diuretic activity and tissue distribution was evaluated. In dog renal clearance experiments, bumetanide and furosemide significantly enhanced urine flow, sodium and potassium excretion. Inulin clearance as an estimate of glomerular filtration rate was not altered by either drug, but sodium reabsorption was decreased with bumetanide (13%) and furosemide (12%). At these diuretic doses, both compounds were bound to dog plasma protein to about the same extent (86-91%), although total plasma levels were 100-fold higher for furosemide. Within 1/2 hour after the i.v. administration of 14C-bumetanide or 14C-furosemide, 86 to 99% of the 14C in urine, plasma, kidney, and liver appeared as unchanged drug. One minute after maximal diuresis bumetanide was found to have a higher affinity (3-fold) for kidney compared to furosemide. These data offer a possible explanation for the i.v. diuretic potency difference between these two compounds. Furthermore, the lack of significant difference in plasma protein binding and the absence of urinary metabolites of either drug suggest that other factors may also contribute to the marked differences in diuretic activity between bumetanide and furosemide.

Animals↗

Circulatory turnover of pancreatic amylase.

Radiolabeled amylase and unlabeled pancreatic amylase were infused into pigs in order to determine the plasma half-life of the enzyme. Regardless of the parameter measured (radioactivity, enzyme activity or concentration), the plasma removal curves could be resolved into three components when subjected to tracer analysis. The plasma half-life was estimated to be approximately 3 hr. Through the use of a recently developed radioimmunoassay specific for porcine pancreatic amylase, the plasma concentration of amylase was calculated at 2.4 mug/ml. Knowing the plasma concentration and half-life of amylase we determined the circulatory turnover of the enzyme. Over a 2.4-hr period, 9.6 mug of pancreatic amylase/ml of plasma must re-enter the circulation to maintain the enzyme at constant levels.

Amylases↗