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Biomedical subjects

C Burke

Publications and source records attributed to C Burke.

At least 73 records · Page 4Linked to original sources
PubMed1988

Phorbol esters inhibit adenylate cyclase activity in cultured collecting tubular cells.

Activators of protein kinase C, a calcium- and phospholipid-dependent protein kinase, inhibit vasopressin-stimulated water flow in toad bladder. To determine the biochemical mechanisms of this inhibition, we examined the effects of activators of protein kinase C on arginine vasopressin (AVP)-stimulated adenylate cyclase activity in cultured rabbit cortical collecting tubular cells. The phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA), the diacylglycerol, 1-oleyl-2-acetyl glycerol (OAG), and the diacylglycerol kinase inhibitor, R59022, all rapidly activate protein kinase C in collecting tubular cells. Pretreatment with PMA produces a delayed inhibition (greater than or equal to 4 h) of AVP-stimulated adenylate cyclase activity. The 4-h time lag suggests that the effects of protein kinase C are mediated indirectly, possibly as a consequence of stimulating cell proliferation. PMA does not inhibit cholera toxin- or forskolin-stimulated adenylate cyclase activity, suggesting an effect on the vasopressin receptor or coupling of the receptor to the stimulatory guanine nucleotide regulatory protein. Neither prostaglandins nor the inhibitory guanine nucleotide regulatory protein appear to mediate this effect. In contrast, treatment with either OAG or R59022 produces a rapid inhibition of both AVP- and forskolin-stimulated adenylate cyclase activity suggesting a prominent distal site of action, presumably at the catalytic subunit of adenylate cyclase. The results demonstrate that different activators of protein kinase C inhibit AVP-stimulated adenylate cyclase activity by distinctly different mechanisms possibly by altering the substrate specificity or activating multiple forms of the kinase. These results have important implications when using different activators to study the biological effects of protein kinase C.

Adenylyl Cyclase Inhibitors↗
PubMed1987

Structural and dynamical comparison of alpha, beta and gamma forms of murine epidermal growth factor.

Reversed-phase high-performance liquid chromatography of mouse epidermal growth factor (mEGF) purified by the method of Savage and Cohen allows resolution of four forms of the protein hormone: alpha, beta, gamma and delta. alpha-mEGF, the major form isolated by HPLC, is the parent mEGF originally sequenced by Savage and Cohen, and beta-mEGF is des-asparaginyl1-alpha-mEGF. Proton nuclear magnetic resonance spectroscopy has been used to investigate structural and dynamical differences among the alpha, beta and gamma forms of the peptide. Based on these data, gamma-mEGF can be tentatively identified as des-Asn1, Ser2-mEGF. Comparative nuclear Overhauser experiments on amide and aromatic proton resonances suggest that there are significant conformational changes in the peptide structure on cleavage of the N-terminal residues. Backbone amide proton/deuteron exchange rates in gamma-mEGF and beta-mEGF are significantly faster than those in alpha-mEGF suggesting that structural dynamics are enhanced in the minor forms; this interpretation is supported by the decrease in Tyr(2,6)-(3,5) intraresidue NOE magnitudes on going from alpha to beta to gamma forms. These data suggest that the average conformations of beta and gamma-mEGF favor a more open or denatured state of the protein and that the N terminus is critical to the structural integrity of the parent protein.

Animals↗
PubMed1987

Arachidonic acid-induced pleurisy (ARIP): an in vivo model for testing 5-lipoxygenase inhibition.

Arachidonic acid-induced pleurisy in the rat was evaluated for testing inhibitors of arachidonic acid (AA) metabolism. The model involves the administration of AA intrapleurally and the determination of LTB4 and PGE2 as indicators of 5-lipoxygenase and cyclooxygenase activities in the exudate/wash. This model is suitable for the in vivo evaluation of potential inhibitors of the 5-lipoxygenase pathway but not the cyclooxygenase pathway of AA cascade.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

Treatment of osteoarthritis in the hand and wrist. Nonoperative treatment.

Osteoarthritis should initially be treated conservatively with the use of oral medication, intra-articular steroid injections, hand therapy, and splinting. The reduction of pain and the resultant increase in function to the patient are the ultimate goals of this treatment.

Activities of Daily Living↗
PubMed1986

Indiscretion enteritis. A Rabelaisian syndrome.

A 76-year-old man had small bowel obstruction and organic small bowel disease following a series of bizarre massive gustatory insults that involved food, medications, and mega-mineral-vitamin supplements. Intestinal obstruction required partial small bowel resection. The dietary indiscretions resulted in severe enteritis (indiscretion enteritis). The sequence has been termed a Rabelaisian syndrome after the great French writer and physician, Francois Rabelais, who vividly described bizarre gustatory habits. Gut injury may result from unwise oral intake of various foods and mineral supplements.

Aged↗
PubMed1985

Effect of a hydantoin prostaglandin analogue, BW245C, during oral dosing in man.

Following an open pilot study, the effects of repeated oral doses of BW245C, a hydantoin prostaglandin analogue, were studied in man. Six healthy volunteers received 150 micrograms BW245C or placebo 6-hourly for 5 days according to a double blind randomised balanced design with 7 days interval between treatments. Measurements of headache, facial flushing, heart rate, blood pressure, systolic time intervals, ECG, platelet aggregation responses to ADP and of subjective effects were made before and 1 and 3 h after the first dose of BW245C/placebo on days 1, 3 and 5 of dosing. BW245C produced significantly (p less than 0.05) higher headache scores than placebo on days 3 and 5; facial flushing, nasal stuffiness and abdominal discomfort were more frequent on BW245C than placebo. Heart rate, derived from the ECG, was significantly (p less than 0.05) higher and pre-ejection period significantly (p less than 0.05) shorter on BW245C at 1 h after dosing on each day. Left ventricular ejection time index, QS2 index, PR interval, QRS duration and T wave height were unchanged. Heart rate, counted at the radial pulse, and systolic and diastolic blood pressure, all measured lying and standing, were similar for BW245C and placebo. Platelet aggregation responses were not significantly different between the two treatments. The results indicate that repeated oral doses of BW245C, sufficient to cause moderately uncomfortable subjective effects, do not inhibit platelet aggregation.

Adenosine Diphosphate↗
PubMed1984

Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial.

Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001).

Acyclovir↗
PubMed1984

Oral acyclovir in herpes zoster.

Forty-one patients with herpes zoster were treated with acyclovir or placebo at a dosage of 400 mg five times a day by mouth for five days in a double-blind randomized domiciliary study. Acyclovir was shown to reduce the days of new lesion formation within the effected dermatome after day 0 (P = 0.049). No other statistical difference was demonstrated between the two groups although the trends for new lesion formation outside the dermatome, full crusting, involution and diminution of acute pain all favoured acyclovir.

Acyclovir↗
PubMed1984

A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man.

The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Subacute sclerosing panencephalitis (SSPE): a report of 16 cases.

Sixteen cases of subacute sclerosing panencephalitis (SSPE) were diagnosed at the Royal Children's and Mater Misericordiae Children's Hospitals in Brisbane from September 1974 to June 1983. Although the incidence of the disease with regard to age at onset, previous exposure to measles virus, and longevity was similar to that reported in the United States and Europe, the frequency of the illness was substantially higher in the present study. The high frequency of the disease in Queensland appears to reflect a relatively low level of immunity to measles virus in the population at risk.

Antibodies, Viral↗
PubMed1983

Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial.

Twenty patients undergoing allogeneic bone marrow transplantation and 39 patients receiving remission induction chemotherapy for acute leukaemia were entered into a double blind, placebo controlled stratified trial of acyclovir prophylaxis against herpes group virus infections. Within the transplant group intravenous acyclovir 5 mg/kg twice daily given throughout the period of granulocytopenia completely prevented oropharyngeal herpes simplex virus infection compared with a 50% incidence in the placebo arm (p = 0.033). The acyclovir group also had fewer days of fever during the trial and a shorter duration of leukopenia, possibly because of the prevention of herpes simplex virus infections. There was a high incidence of herpes infections after the trial in patients who received either acyclovir or placebo. In the non-transplant group there was also a significant reduction of herpes simplex virus infection in the oropharynx and oesophagus (two out of 19 patients as compared with 10 out of 20; p = 0.018). Herpes simplex virus was isolated in the acyclovir arm within a day after starting the trial in one patient, and the other failure was due to a virus with reduced sensitivity to acyclovir in a patient who had had several previous courses of the drug. The incidence of herpes infections after stopping treatment was low. The influence of acyclovir on excretion of Epstein-Barr virus in saliva in either group was inconclusive. One patient (transplant group) developed a cytomegalovirus infection while receiving acyclovir. Acyclovir provides effective prophylaxis against oropharyngeal and oesophageal herpes simplex virus infection in severely immunocompromised seropositive (greater than or equal to 1/8) patients. In patients given bone marrow transplants this may have the additional benefit of reducing the time to recovery of an adequate blood count and the number of days of fever.

Acyclovir↗
PubMed1983

Pituitary adenomas: immunohistology and ultrastructural analysis of 118 tumors.

An analysis is presented of the immunohistological and ultrastructural features in a series of 118 surgically removed pituitary adenomas all of which were studied immunohistologically using antisera to growth hormone (GH), prolactin (PRL) ACTH, beta FSH, beta LH and beta TSH, and 75 of which were studied ultrastructurally. Results were analysed according to the mode of presentation of patients. Forty-one (35%) of the tumours were from patients with acromegaly or gigantism, ten (9%) from patients with Cushing's syndrome or Nelson's syndrome, 19 (16%) from patients with clinical features associated with hyperprolactinaemia and 48 (40%) from patients with space occupying lesions which appeared clinically to be overtly endocrinologically functionless. By light microscopy, using the immunoperoxidase (PAP) technique, immunoreactive GH was demonstrated in all the tumours from patients with acromegaly or gigantism, immunoreactive ACTH in all tumours from patients with Cushing's syndrome or Nelson's syndrome and immunoreactive PRL in 95% of tumours associated with effects of hyperprolactinaemia. Forty-five percent of the tumours from acromegalic patients contained some PRL-positive cells as well as GH-positive cells. Among the tumours which appeared clinically to be endocrinologically functionless were three tumours (from males) uniformly stained for immunoreactive PRL. Of the remainder, 60% were negative for immunoreactive hormones and 40% contained small numbers of cells which were positive for a variety of immunoreactive hormones. ACTH-cell and PRL-cell tumours had ultrastructural features as described in previous studies. Fifty percent of GH-cell tumours examined at the EM level contained fibrous bodies, while in the remainder these structures were not identified. Tumours with fibrous bodies were more likely to contain PRL as well as GH with immunoperoxidase. All tumours that were endocrinologically functionless and which were examined at the EM level contained secretory granules. Oncocytic change was common in these tumours. No ultrastructural differences were observed between those which contained immunoreactive hormones by light microscopy and those which did not.

Acromegaly↗
PubMed1983

Effects of intravenous epoprostenol on platelets and the cardiovascular system are not potentiated by dipyridamole.

Normal subjects received infusions of epoprostenol (prostacyclin, PGI2) at doses of 2, 4, 6, and 8 ng/kg/min on each of two occasions after pretreatment with dipyridamole (400 mg/day for 3 days) or placebo. Baseline headache and bleeding time were increased and preejection period (PEP) shortened after dipyridamole. The baseline heart rate was increased on dipyridamole by an amount that correlated to the blood dipyridamole level. PGI2 infusion increased heart rate, systolic blood pressure (BP), pulse pressure, left ventricular ejection time index, and degree of flushing and severity of headache, and reduced diastolic BP, PEP, and T wave height. There was no apparent interaction between PGI2 and dipyridamole on these variables. PGI2 inhibited adenosine diphosphate-induced platelet aggregation and increased bleeding time. We conclude that, despite the synergism between dipyridamole and PGI2 that might be predicted and has been demonstrated in some animal experiments, no such interaction is apparent in normal humans after standard doses.

Adult↗
PubMed1982

The cardiovascular and platelet effects of epoprostenol (prostacyclin, PGI2) are unaffected by beta-adrenoceptor blockade in man.

1 Atenolol 0.2 mg/kg i.v., propranolol 0.2 mg/kg i.v. or placebo were given in a double-blind crossover study to six healthy male subjects, and the effects of a subsequent infusion of epoprostenol (prostacyclin, PGI2) 0-6 ng kg-1 min-1 monitored. 2 PGI2 caused a tachycardia, a fall in diastolic blood pressure, a rise in pulse pressure, reduction in pre-ejection period (PEP) and rise in left ventricular ejection time index (LVETI), headache and facial flushing at doses of PGI2 greater than 2 ng kg-1 min-1,, (P less than 0.05). 3 Beta-adrenoceptor blockade did not prevent the tachycardia in response to PGI2, and did not interact with any of the other dynamic effects of PGI2. 4 In vitro, PGI2 at 1 and 2 ng/ml inhibited platelet aggregation to ADP (P less than 0.01), although no significant effect on platelet aggregation was seen in the in vivo study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect this in vitro study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect in vitro effect of PGI2 on platelet aggregation. 5 Pretreatment with atropine 0.04 mg/kg i.v. in three subjects did not attenuate the tachycardia caused by PGI2 infusion, even though the baseline heart rate was increased. 6 Adverse effects to PGI2 infusion included sudden bradycardia, pallor and sweating, suggesting that the Bezold-Jarisch reflex seen in animals in response to PGI2 may also occur in humans. 7 Neither increased sympathetic drive nor vagal withdrawal are likely causes of the tachycardia following PGI2 infusion.

Adrenergic beta-Antagonists↗