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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 127 records · Page 7Linked to original sources
PubMed1992

Intestinal myxosarcoma in a thoroughbred mare.

A large fibrotic mass originating from the cecal base was discovered upon surgical exploration of the abdomen in a Thoroughbred mare with a history of chronic colic and weight loss. The mass protruded intraluminally resulting in partial obstruction. Surgical excision was not feasible due to the location of the mass and the inability to exteriorize it adequately from the abdominal cavity. The mass was fibrous with a shiny, gelatinous material present throughout the neoplasm. Histologically, large confluent spaces filled with mucopolysaccharides were identified by staining with Alcian blue. The diagnosis of myxosarcoma was based upon finding of atypical fibroblastic cells, mucinous stroma, local invasiveness, and metastasis to the regional lymph nodes. Myxomatous tumors have not previously been documented to occur in the equine intestinal tract.

Animals↗
PubMed1991

Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation.

High affinity binding of platelet-derived growth factor (PDGF) has been proposed to involve the interaction of the dimeric PDGF ligand with two receptor subunits, designated alpha and beta. We have cloned and expressed a human PDGF receptor cDNA which differs in sequence from the beta-subunit and which has the PDGF binding properties and monoclonal antibody recognition, predicted for the alpha-subunit. Scatchard analysis indicated that PDGF-AA and PDGF-AB bound to transfected alpha-subunits with affinities of Kd = 0.06 and 0.05 nM, respectively. PDGF-BB bound with a significantly lower affinity (Kd = 0.4 nM). Nevertheless, this affinity is still great enough to mediate substantial PDGF-BB binding at physiological concentrations and would be considered to be "high affinity." We have used wild-type and kinase-inactive human beta-subunits to show that PDGF binding promotes receptor subunit dimerization in intact cells. In addition, we found that PDGF stimulates tyrosine phosphorylation of the kinase-inactive beta-subunit when it is expressed with alpha-subunits. The kinase-inactive beta-subunits were phosphorylated at tyrosine 857 and 751, the major phosphorylation sites of the wild-type beta-subunit, indicating either that intra- and intermolecular phosphorylation occurs on the same sites, or that a significant fraction of receptor tyrosine phosphorylation is intermolecular.

Animals↗
PubMed1991

Failure of motor evoked potentials to predict neurologic outcome in experimental thoracic aortic occlusion.

Motor evoked potential monitoring was tested as an alternative to somatosensory evoked potential monitoring in evaluating spinal cord function during thoracic aortic occlusion in dogs. Twenty-seven animals underwent 60 minutes of cross-clamping of the proximal descending thoracic aorta with (n = 18) or without (n = 9) cerebrospinal fluid drainage. Spinal cord blood flow was measured with microspheres, and neurologic outcome was evaluated at 24 hours with Tarlov's scoring system. Cerebrospinal fluid drainage improved neurologic outcome (p less than 0.05). Motor evoked potentials recorded over the lumbar spinal cord were lost in 9 of 20 dogs with ischemic cord injury and were not lost in any of the 7 dogs that were neurologically normal. Somatosensory evoked potential were lost in 19 of 20 paraplegic/paraparetic dogs and lost in 3 of 7 normal dogs (p less than 0.01). After reperfusion, motor evoked potentials returned in all nine neurologically injured dogs that lost the potentials and were still present at 24 hours. Changes in amplitude, latency, or time until loss or return of motor evoked potentials or somatosensory evoked potentials did not predict neurologic injury. Loss of somatosensory evoked potentials had a high sensitivity (95%) but had low specificity (67%) because of peripheral nerve ischemia. Loss of motor evoked potentials recorded from the spinal cord had high specificity (100%) but a low sensitivity (46%) and was therefore not a reliable predictor of neurologic injury. Return of motor evoked potentials during reperfusion did not correlate with functional recovery. Motor evoked potentials stimulated in the cortex and recorded from the spinal cord had low overall accuracy (59%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Sepsis and septic shock. Deadly complications that are on the rise.

Most patients are already hospitalized when sepsis and septic shock develop, and in spite of therapy, at least 50% die. Although newer therapeutic agents are being evaluated, current management consists of antibiotics, fluids for volume resuscitation, inotropic agents, and surgery for septic foci. Greater emphasis on preventive measures is recommended.

Anti-Bacterial Agents↗
PubMed1991

Differences in the biological activities of transforming growth factor-beta and platelet-derived growth factor in vivo.

Transforming growth factor-beta 1 (TGF-beta 1 and recombinant platelet-derived growth factor-BB (rPDGF-BB) promoted an extensive, dose-dependent development of fibrous connective tissue when continuously delivered for 8 days by mini-osmotic pumps implanted subcutaneously in adult guinea pigs. Biochemical analyses demonstrated that TGF-beta 1 and rPDGF-BB stimulated dose-dependent increases in the dry weight, and protein, DNA, collagen, and glycosaminoglycan (GAG) contents of the fibrous connective tissue capsule that enveloped the pumps. The GAG/DNA mass ratio was markedly elevated by TGF-beta 1, but the collagen/DNA, protein/DNA, and collagen/protein ratios were not significantly increased. In contrast, rPDGF-BB generally decreased these mass ratios. Histological analyses suggested that this was due to the fact that rPDGF-BB induced a very cellular response with a marked influx of neutrophils and fibroblasts. TGF-beta 1 induced significantly less cellular response, which consisted primarily fibroblasts and macrophages. These results indicated that rPDGF-BB and TGF-beta 1 induced connective tissue deposition in vivo in a dose-dependent fashion, although the cellular nature of the responses as well as the structural composition of the extracellular matrices were clearly distinguishable between the two growth factors.

Animals↗
PubMed1991

Protamine-heparin-induced pulmonary hypertension in pigs: effects of treatment with a thromboxane receptor antagonist on hemodynamics and coagulation.

Adverse hemodynamic reactions after protamine neutralization of heparin are an infrequent but important clinical problem. Pre-treatment of swine with a thromboxane A2 receptor antagonist has been reported to prevent the pulmonary hypertensive response occasionally seen after protamine reversal of heparin anticoagulation. In the current study, a control group of pigs (n = 9) received intravenous heparin (300 IU/kg), followed after 10 min by a neutralizing dose of protamine (3 mg/kg). A treatment group of pigs (n = 11) was treated identically, except that the thromboxane A2 receptor antagonist L-670596 (2 mg/kg) was infused intravenously 2 min after the protamine infusion. Hemodynamic and coagulation profiles were monitored during these procedures. Pulmonary hypertension developed and reached a peak within 2 min of protamine administration, often at the same time that L-670596 was administered in the treatment group. There was no statistical difference between control and treatment groups' peak pulmonary arterial pressure and peak pulmonary vascular resistance. However, the interval for return of mean pulmonary artery pressure from peak to baseline values was 11.6 +/- 3.1 versus 5.5 +/- 1.9 min (mean +/- SD) for control and treatment groups, respectively (P less than 0.01). Thromboxane B2 plasma concentrations increased in both groups and were correlated with the pulmonary hypertensive response (r = 0.86, P less than 0.01). Platelet aggregation to collagen was inhibited by the thromboxane A2 receptor antagonist (P less than 0.05). Bleeding time was prolonged beyond normal range in 50% of L-670596-treated pigs. All other coagulation tests in both groups returned to baseline after reversal of heparin with protamine and were unaffected by L-670596.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hypothyroidism and respiratory insufficiency in a neonatal foal.

Hypothyroidism was diagnosed in a neonatal Thoroughbred foal that was weak, hypothermic, and septicemic. Administration of thyroid-releasing hormone elicited attenuated increases in concentrations of free and total triiodothyronine and thyroxine, as compared with a clinically normal, age-matched foal. The foal died of apparent respiratory insufficiency, pre- and postmortem findings compatible with hypothyroidism included hypothermia, large thyroid glands with distended, colloid-filled follicles, and severe, diffuse atelectasis, with thickened alveolar septae and degenerating alveolar squamous epithelial cells.

Animals↗
PubMed1990

Endoscopic evaluation of changes in gastric lesions of Thoroughbred foals.

Gastroendoscopic examinations were conducted on thirty-two 2- to 60-day-old Thoroughbred foals on 5 breeding farms. Repeat gastroendoscopic examinations were performed 35 to 135 days after the initial examination, with the age of foals ranging from 39 to 190 days. On initial endoscopic examination, lesions consisting of ulcers and/or erosions were most prevalent in the stratified squamous epithelial mucosa adjacent to the margo plicatus along the greater curvature of the stomach (15 of 32 foals), and were observed much less frequently at other sites within the stomach. In addition to ulcers and erosions, squamous epithelial desquamation at the margo plicatus was observed in 16 of 19 foals less than 30 days old and in 3 of 13 foals 30 to 60 days old, and was not seen in any foal on repeat endoscopy. At the time of repeat endoscopic examination, the frequency of ulcers and erosions at the margo plicatus was significantly (P less than 0.01) less than at initial examination (4 of 32 foals vs 15 of 32 foals). Lesions had healed in 14 of the 15 foals with lesions at the margo plicatus on the initial examination. Lesions were observed in the glandular mucosa of the fundus in 3 of 32 foals on initial examination and in 6 of 32 foals reexamined. Lesions in the glandular fundus observed on initial examination had healed in 2 of 3 foals, and of the 6 foals with glandular mucosal lesions on reexamination, 5 had developed lesions since the initial examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Examination of immune parameters and host resistance mechanisms in B6C3F1 mice following adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Adult female B6C3F1 mice were given a single ip dose of 0, 01, 1.0, or 10.0 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and examined for immune function and host resistance 7-10 d later. Exposure to TCDD resulted in a significant dose-related decrease in induction of both IgM and IgG antibody-forming cells. This suppression was noted for both T-dependent and T-independent antigens. TCDD at a dosage of 10 micrograms/kg was shown to suppress production of antibody to viral hemagglutinin. In contrast, TCDD exposure had no significant effect on natural killer cell function, production of interferon, or various parameters of macrophage function. Assessment of host resistance revealed a significant increase in susceptibility to fatal infection with influenza virus, but no significant alteration in susceptibility to infection with the bacterium Listeria monocytogenes.

Animals↗
PubMed1990

Endotoxin does not directly alter norepinephrine release or vasoactivity in dog pulmonary artery and portal vein.

The direct effect of Escherichia coli endotoxin on the release of norepinephrine (NE) and the contractile response consequent to the release of NE were studied in isolated, superfused segments of dog pulmonary artery and portal vein during resting conditions and during electrical stimulation (ES). High-pressure liquid chromatography with electrochemical detection was used to quantify the endogenous NE released and that remaining in the tissue after stimulation. Endotoxin (1 micrograms/ml and 10 micrograms/ml in superfusate) had no effect on the release of NE from either pulmonary artery or portal vein. Endotoxin also had no effect on vasoactivity in response to ES. Thus, in isolated pulmonary artery and portal vein, endotoxin, in the doses employed, does not directly affect release of NE from adrenergic nerve endings, nor does it affect the sequence of events that starts with transmitter-receptor interaction and ends with contraction of smooth muscle cells.

Adrenergic Fibers↗
PubMed1990

Prevalence of gastric lesions in foals without signs of gastric disease: an endoscopic survey.

Gastroendoscopic examinations were conducted on 75 Thoroughbred foals aged two to 85 days on seven breeding farms in England and Ireland. The foals showed no signs of gastric disease. There was no significant difference between lesion prevalence in foals in England (16 of 28 foals; 57 per cent) or Ireland (22 of 47 foals; 47 per cent). Neither was there any sex predilection (18 of 36 males; 20 of 39 females). Lesions were most prevalent in foals under 10 days old (8 of 9) and least prevalent in foals older than 70 days (3 of 10). Lesions occurred most frequently in the squamous mucosa immediately adjacent to the margo plicatus along the greater curvature (34 foals), whereas lesions in the squamous fundus, the glandular fundus, and the lesser curvature were observed in 11, six and three foals, respectively. Lesions were not observed in the squamous mucosa surrounding the cardia. Gastric lesions were more prevalent in foals with a previous disorder than in those without (68 vs 43 per cent) and particularly with a history of recent or concurrent diarrhoea (9 of 14).

Age Factors↗
PubMed1990

Intraoperative guidance for intrauterine procedures with transrectal sonography.

Transrectal sonography was used for intraoperative guidance in intrauterine tandem placement for intracavitary radiation therapy and in dilation and curettage procedures. The authors describe the method and three representative cases in which it was applied. It is concluded that the technique may prevent complications such as uterine perforation or bladder injury in tandem placement, and that it can facilitate dilation and curettage in complicated cases.

Aged↗
PubMed1990

Early signals in the mitogenic response of Swiss 3T3 cells: a comparative study of purified PDGF homodimers.

Platelet-derived growth factor (PDGF) occurs as three dimeric isoforms, AA, BB, and AB. Two distinct receptor subunits, alpha and beta, have been identified which bind either all three isoforms of PDGF (alpha) or PDGF-BB only (beta). Here, we have compared the effect of purified PDGF homodimers on the early intracellular signaling events and mitogenesis in Swiss 3T3 cells, which possess equivalent numbers of the alpha and beta subunits. Both PDGF-AA and PDGF-BB stimulated receptor phosphorylation, inositol phosphate formation, activation of protein kinase C, calcium mobilization, EGF receptor transmodulation, sodium uptake, arachidonic acid release, cyclic AMP accumulation, and c-fos induction in a comparable, dose-dependent manner (half-maximal values for all these response were in the 2-10 ng/ml range for both homodimers). At high concentrations of PDGF (greater than 10 ng/ml), the BB homodimer effect on early membrane and cytosolic signals was 20-30% greater than PDGF-AA, reflecting the greater number of available binding sites for PDGF-BB. DNA synthesis studies indicated that PDGF-AA and PDGF-BB were potent mitogens for Swiss 3T3 cells, displaying identical dose-response effects. Moreover, the mitogenic activities of both homodimers were equally potentiated in the presence of insulin. These results indicate that both PDGF-AA and PDGF-BB stimulate the full complement of molecular responses required for the synergistic interactions mediating long-term mitogenesis. We conclude that alpha and beta receptor subunits do not differ in their ability to transduce PDGF-mediated signals leading to DNA synthesis in Swiss 3T3 cells.

Animals↗
PubMed1990

Pain problems in the ICU.

To manage pain in an ICU setting effectively, one must first understand the unique features associated with the disease process for which patients are admitted. Although there are certain common denominators, a postoperative patient is different from a patient with an acute myocardial infarction. This article reviews the aspects of pain associated with the individual syndromes of patients admitted to an ICU.

Attitude of Health Personnel↗
PubMed1990

PDGF and FGF stimulate wound healing in the genetically diabetic mouse.

To examine the effects of recombinant growth factors in vivo, impaired wound healing was studied in genetically diabetic C57BL/KsJ-db/db mice. Large full-thickness skin wounds made on the backs of these mice exhibited significant delays in the entry of inflammatory cells into the wound, the formation of granulation tissue, and in wound closure when compared to their nondiabetic littermates. Recombinant human platelet-derived growth factor (rPDGF-BB, 1 or 10 micrograms), recombinant human basic fibroblast growth factor (rbFGF, 1 micrograms), or combinations of both were applied topically to the wounds for 5 to 14 days after wounding. Diabetic mouse wounds treated with rPDGF-BB or rbFGF had many more fibroblasts and capillaries in the wound bed at 10 and 21 days than did wounds treated with the vehicle alone. The animals treated with growth factors also had significantly greater wound closure at 21 days than those treated with the vehicle. Combinations of rPDGF-BB and rbFGF improved all parameters of healing but not to a greater extent than either growth factor alone. The effectiveness of rPDGF-BB and rbFGF suggest that recombinant growth factors may be useful in the treatment of patients with deficient wound repair.

Administration, Topical↗