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Biomedical subjects

T L Murphy

Publications and source records attributed to T L Murphy.

48 records · Page 3Linked to original sources

Pattern of isoaccepting transfer RNAs common to 26 patients with Hodgkin's disease.

The elution profiles of aminoacyl transfer RNAs from Hodgkin's tumors have been compared with the corresponding patterns from normal splenic tissue. Aminohexyl-Sepharose and reversed-phase 5 chromatography have been used in the fractionation studies. Three peaks of acceptor activity have been observed in phenylalanyl, histidyl, aspartyl, and asparaginyl transfer RNAs. A second peak was shown in the case of tyrosyl and methionyl transfer RNAs. Seryl transfer RNA showed no change in elution profile; namely, a single species was observed in both normal and tumor transfer RNAs. These observations are confirmation that Hodgkin's disease is a malignant disease. The uniformity of the extra species of tRNA suggests that there is a commonly occurring aberration in the cell of origin of the Hodgkin's tumor.

Chromatography↗

Role of platelet serotonin in the canine pulmonary response to endotoxin.

There is evidence suggesting a role for platelet serotonin (5-HT) in the immediate pulmonary response to endotoxin in the dog (J. Appl. Physiol. 23: 47, 1967). To further define this role, autologous canine platelets were labeled with 5-[14C]HT in vitro and then reinfused. Subsequently Escherichia coli endotoxin (0.55:B-5, Difco), 2.5 mg/kg, was injected. Within 5 min dynamic compliance (CL) fell by more than 50%, and nonelastic resistance (RL) increased by more than 200%. Despite a 95% decrease in platelet count, less than 10% of the platelet 5-HT was released as determined by changes in the radioactivity of platelet-poor plasma (PPP) prepared from both aortic and pulmonary artery blood. As a positive control, injected of bovine collagen produced a similar decrease in platelet count that was associated with a significant increase in the radioactivity of aortic and pulmonary artery PPP. FInally, rapid injection of a dose of 5-HT equivalent to 25% of the 5-HT in circulating platelets did not cause a change in CL or RL equivalent to that produced by endotoxin. From these data we conclude that endotoxin injection does not cause immediate massive platelet activation and that platelet 5-HT does not play a major role in the immediate pulmonary response to endotoxin.

Animals↗

Effect of methysergide on the acute lung mechanics response to endotoxin.

The effect of the serotonin antagonist methysergide on the acute lung mechanics response to endotoxin in anesthetized, paralyzed, mechanically ventilated dogs was investigated. In five dogs given 0.25 mg/kg Escherichia coli endotoxin only, the pulmonary nonelastic resistance (RL) increased to 238% of control and dynamic compliance (CL) decreased to 50% of control. In a second group of five dogs, methysergide (0.25 mg/kg) was shown to markedly attenuate the lung mechanics response to serotonin (0.04 mg/kg), which alone had produced changes in lung mechanics greater than endotoxin. In these same dogs endotoxin administered after injection of methysergide produced an increase in RL to 377% and a decrease in CL to 33% of control. In a third group of five dogs whose lung mechanics response to serotonin was also greater than to endotoxin alone, endotoxin administered after injection of saline produced an increase in RL to 168% and a decrease in CL to 58% of control. Since the response to endotoxin after injection of methysergide exceeded the response after saline, we conclude that serotonin is not a mediator of the acute lung mechanics response to endotoxin.

Animals↗

Endogenous anticoagulation during extracorporeal perfusion: generation of a heparinlike inhibitor.

Studies were done to define the coagulation defect that develops in hemodynamically stable anesthetized dogs perfused on our arteriovenous extracorporeal system without added heparin. After 45 min, the dogs developed whole blood clotting times (WBCT) greater than 24 h. There was an associated decrease in ADP-induced platelet aggregation and a drop in factor V, VIII, and X levels of 75.8, 33.5, and 46.8%, respectively. Despite an increase in fibrinogen degradation products, there was no significant change in fibrinogen level or platelet count. An inhibitor of thrombin and factor Xa clotting of plasma appeared that was "heparinlike", because it stimulated the inactivation of factor Xa by antithrombin III (ATIII) but not by O-methyl isoureamodified ATIII. Thrombin inhibition by ATIII was also stimulated. The inhibitor was heat stable, adsorbed by BaSO4, and neutralized by protamine. Infusion of protamine sulfate into two perfused dogs neutralized the inhibitor and brought the WBCT from greater than 24 h to less than control. Six dogs developed inhibitor levels equivalent to 0.98 to 6.15 U/ml heparin. Five eviscerated dogs in which the hepatic artery was ligated developed peak plasma inhibitor levels of 3.2 +/- 1.0 U/ml. Thus, the endogenous heparinlike inhibitor is a major contributor to the anticoagulated state induced with our perfusion system and may have an extrahepatic origin.

Animals↗

Transfer RNA and transfer RNA methylase activity in spleens of patients with Hodgkin's disease and histiocytic lymphoma.

tRNA levels, base composition, and tRNA methylase activities of normal and tumor tissue from the spleens of 24 patients (18 with Hodgkin's disease and 6 with histiocytic lymphoma) were studied. There were no significant differences in major base composition of normal and tumor tissue. Methylated guanosine was increased in tumor tissue of some patients, and tRNA methylase activities were increased in extracts from the tumors.

Hodgkin Disease↗

Carbohydrate-deficient transferrin in alcoholics with liver disease.

To assess the relationship between carbohydrate-deficient transferrin (CDT) and alcoholic liver disease, we measured the ratio of carbohydrate-deficient transferrin to total transferrin (rCDT) in 32 male alcoholics with liver disease (Child-Pugh class A, 8; B, 11; C, 13) and 14 male alcoholics without clinically evident liver disease. Twenty of 32 with liver disease and six of 14 without clinically apparent liver disease had recent abstinence. The 32 patients with liver disease were assessed, in addition to the Child-Pugh class, using a linear prognostic score, the Combined Clinical and Laboratory Index (CCLI). Transferrin and CDT were measured by isocratic anion exchange chromatography and a radio-immunoassay. When the total group (n = 46) was divided into those with recent abstinence (n = 26) and those without (n = 20), the rCDT was lower in the abstainers than non-abstainers (0.7 +/- 0.6 vs 2.9 +/- 2.4, P < 0.005). Similarly, abstainers with liver disease (n = 20) had a significantly lower rCDT than non-abstainers (n = 12) with liver disease (0.7 +/- 0.7 vs 3.5 +/- 2.8, P < 0.005). The rCDT in the 20 abstaining patients with liver disease did not differ significantly between Child-Pugh classes. Furthermore, there was no correlation between the CCLI and rCDT (r = 0.05). We conclude that the relationship between rCDT and alcohol abuse is not appreciably altered by the presence of clinically severe liver disease in male alcoholics.

Alcoholism↗