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G Burke

Publications and source records attributed to G Burke.

At least 163 records · Page 9Linked to original sources
PubMed1981

Role of guanine nucleotides in the stimulation of thyroid adenylate cyclase by prostaglandin E1 and cholera toxin.

Cholera toxin in the presence of GTP increased adenylate cyclase activity in a purified bovine thyroid plasma membrane preparation, whereas, in the presence of guanosine 5'-(beta, gamma-imido)-triphosphate (Gpp(NH)P), cholera toxin had no stimulatory effect. Similarly, prostaglandin E1 enhanced the adenylate cyclase activity induced by GTP but not by Gpp(NH)p. Gpp(NH)p-stimulated adenylate cyclase activity, assayed with hydrolysis-resistant adenosine 5'-(beta, gamma-imido)-[32P]triphosphate as substrate and no ATP-regenerating system was inhibited by GDP in a competitive fashion. Furthermore, prostaglandin E1, but not cholera toxin, influenced the GDP inhibition of Gpp(NH)p-stimulated activity by increasing the concentration of GDP resulting in 50% inhibition approx. 2-fold. Inosyl nucleotides mimicked the effects of guanyl nucleotides on thyroid adenylate cyclase in that ITP could substitute for GTP in enhancing cholera toxin- and prostaglandin #1-induced activities and that inosine 5'(beta, gamma-imido)-triphosphate [Ipp(NH)p] was also a potent stimulator per se. Conclusions. (1) Cholera Toxin and prostaglandin E1 enhance thyroid adenylate cyclase activation by GTP (or ITP), but have no stimulatory effect on the Gpp(NH)p (or Ipp(NH)p) response; (2) the stimulatory effect of prostaglandin E1 on adenylate cyclase may result from decreased affinity for GDP at the guanine nucleotide regulatory site; (3) the date regarding cholera toxin stimulation of thyroid adenylate cyclase are consistent with the hypothesis that cholera toxin exerts its effect by inhibiting an endogenous GTPase.

Adenylyl Cyclases↗
PubMed1981

Arachidonate metabolism in the mouse thyroid implication of the lipoxygenase pathway in thyrotropin action.

The present study of compares the effects of various inhibitors of arachidonate metabolism on mouse thyroid cyclo-oxygenase and lipoxygenase activities and thyrotropin-augmented cyclic-AMP accumulation. Mouse thyroid homogenate converts [1-14C]- arachidonate to several products of the cyclo-oxygenase pathway as well as one major product of the lipoxygenase pathway, 12-L-hydroxyeicosatetraenoic acid (12-Hete). Prostaglandin (PG) formation in thyroid homogenates is inhibited by 1-10 microM indomethacin and etya. 12-HETE accumulation is reduced by 91%, 83% and 20% by 5 microM ETYA, 15-HETE, and indomethacin, respectively. Thyrotropin-stimulated cyclic-AMP accumulation, measured in whole thyroid lobes by radioimmunoassay, is reduced by 45% and 73% by 50 microM and 100 microM ETYA, respectively; indomethacin is without effect at these concentrations. 15-HETE reduces thyrotropin-augmented cyclic-AMP accumulation by 57% and 100 microM. In product inhibition studies, 10 microM 12-HETE reduced the formation of radiolabeled 12-HETE by 20%. 10 microM PGE2, PGF2 alpha or PGD2 had no effect on [1-14C]-PG formation. 12-HETE, however, reduced PG synthesis by 76% at 10 microM. This is the first report implicating the arachidonate lipoxygenase pathway in thyrotropin action at the level of cyclic-AMP regulation. Additionally, our finding that 12-HETE inhibits prostaglandin synthesis suggests that the cyclo-oxygenase and lipoxygenase pathways in the mouse thyroid may be highly integrated.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1981

Nearwork and familial resemblances in ocular refraction: a population study in Newfoundland.

There is considerable epidemiological evidence that the nearwork associated with formal education can cause myopia. The potential for nearwork and education, as aspects of common familial environment, to inflate resemblances among nuclear family members in ocular refraction, was therefore investigated in a sample of 957 persons aged 5 years and over, comprising approximately 80% of the population above that age in three communities on the west coast of Newfoundland. Refraction was evaluated using standard optometric methods, nearwork measured in hours/day as reported by each subject, education measured as last completed school grade in years. The effects of nearwork and education on refraction resemblances were evaluated by adjusting refraction for age and sex, then comparing correlations or regressions among relatives before and after further linear regression adjustment of refraction for nearwork and education. Reductions in sib-sib correlations and offspring-parent regressions were achieved in this way, suggesting that these environmental factors inflate familial resemblances in refraction. Patterns of resemblances among relatives after adjustment suggest that the effects of nearwork and education on refraction resemblances were not completely removed by the linear regression adjustment used.

Adolescent↗
PubMed1980

Chronic regulation of rat thyroid prostaglandin synthetase activity by endogenous thyrotropin.

Prostaglandin (PG) synthetase activity was measured in the rat thyroid after hypophysectomy, T4, and methylthiouracil treatment in order to explore the possibility that PG synthetase is subject to chronic control by endogenous TSH. T4 treatment (5 mg/liter drinking water) lowered PG synthetase activity, as measured in whole homogenates, by 22% and 31% after 2 and 4 days, respectively. Similarly, PG synthetase activity was reduced by 16% and 42% 2 and 4 days after hypophysectomy. Methylthiouracil treatment (100 mg/liter drinking water) effected 51% and 78% increases in synthetase activity by days 2 and 4, respectively. Additionally, differential effects with regards to PGE2 to PGF 2 alpha ratios were observed. The limited prostaglandin-catabolizing capacity of the rat thyroid warrants the conclusion that the observed TSH effects are expressed at the level of the PG synthetase complex.

15-Oxoprostaglandin 13-Reductase↗
PubMed1980

Ethics and medical decision-making.

There is a tendency for physicians to approach ethical problems in a manner similar to that in which they approach medical problems. Instead of disease categories (such as congestive heart failure or diarrhea), the physician substitutes moral quandaries (such as euthanasia or abortion). The goal is to learn what the "right" rules are for this particular problem at this particular moment. Although this method has important practical and instructive value, it can produce an empirical attitude toward ethics akin to that found in students who strive to learn medicine solely by algorithms. Using theoretical models as a center for discussion, this article has attempted to approach medical ethics as a decision-making process derived from the physician-patient relationship model in use. What is the type of physician-patient relationship that forms the soundest base for making ethical decisions? It must be realized that the contractual relationship cannot be ignored, for in our consumer-oriented society it will surely remain as a protection for the patient against the incompetent or immoral physician. It should not become the sole guide of physician behavior, however, lest we be satisfied with mediocre behavior as the maximal standard. Likewise, although technical competence is required for one to make the right and good decision, it is insufficient alone as a guide for moral behavior. Given the medically correct facts, a multitude of responses are available which necessitate a moral choice. Physicians need a guiding principle that goes beyond any aesthetic code of behavior, or protection of self-interest, and which enables them to deal with all the unexpected ethical questions faced in providing care to patients. Moral principles such as truth-telling, promise-keeping, and protecting the patient when he is vulnerable, help the physician to act in a moral manner, but lack the encompassing nature of the covenantal promise. The covenantal model includes a donative element that empowers the physician to go beyond any specific prescriptions of behavior in repayment of his gifted position. It inspires fidelity to the patient and the profession and respect for the patient's rights as an individual without either falling prey to the presumptuous attitude of the parental model or the legalistic tone of the contractual model.

Adult↗
PubMed1979

Effects of cholera toxin on thyroid cyclic AMP-dependent protein kinase and ornithine decarboxylase activities.

Cholera toxin activated beef thyroid cyclic AMP-dependent protein kinase in a dose (0.2 to 8 microgram/ml)-related fashion. Thus, when beef thyroid slices were incubated with toxin (8 microgram/ml) for 90 minutes and then assayed for protein kinase, the activity ratio (i.e. -cyclic AMP/+cyclic AMP) increased from 0.32 +/- 0.02 to 0.77 +/- 0.06. The toxin (5 microgram/ml)-induced increase was abolished by inclusion of ganglioside GM1 in the incubation medium (I50, 0.7 microgram/ml), whereas, gangliosides GD1a and GT1 were without effect. In contrast, TSH-activated protein kinase was unaffected by ganglioside addition. Cholera toxin increased rat thyroid ornithine decarboxylase (ODC) activity in-vitro in a dose (0.1 to 10 microgram/ml)-related fashion [basal, 100 cf cholera toxin (10 microgram/ml), 1500 pmol 14CO2/g tissue/30 min]. The toxin (1 microgram/ml)- (but not TSH-) induced increase in ODC was abolished by inclusion of ganglioside Ga and GT1 were without effect. Cholera toxin stimulation of ODC was inhibited by indomethacin or iodide as are the stimulatory effects of TSH or dibutyryl cyclic AMP. These results demonstrate that although there are differences in the TSH and cholera toxin responses with respect to receptor (ganglioside) interaction, they nevertheless elicit similar intracellular responses in thyroid.

Animals↗
PubMed1978

The role of gastrin in congenital hypertrophic pyloric stenosis.

A study was designed and carried out to determine if the canine model of hypertrophic pyloric stenosis is applicable to other species and to demonstrate the transplacental passage of gastrin. Results of the study show that (1) pentagastrin does not induce hypertrophic pyloric stenosis in the rabbit; (2) human gastrin does not cross the canine placenta, and (3) gastrin has no documented and little inferred role in the etiology of CHPS.

Animals↗
PubMed1978

Inhibition of thyroidal cyclic AMP-dependent protein kinase by thyroid hormone.

Bovine thyroid cyclic AMP-dependent protein kinase was purified by DEAE-Sephadex and Sephadex G-200 chromatography. This preparation showed a 240-fold increase in specific activity over the initial 20,000 x g supernatant with histone as substrate and 1 micronM cyclic AMP in the assay mixture. In the presence of 2.5 X 10(-5)M L-triiodothyronine (T3), protein kinase activity was significantly reduced; 50% inhibition was achieved at 1 X 10(-4) M. Tests of diverse thyroid hormone analogs showed that T3 and its derivatives were more potent inhibitors than T4 and its derivatives which, in turn, were more potent than thyronine or diiodothyronine. Mono- and diiodotyrosine, tyrosine, and iodide were without effect. Triiodothyronine did not inhibit kidney, spleen, or lung protein kinase activity. The magnitude of the inhibition was the same whether or not cyclic AMP (1 micronM) was present in the incubation mixture, suggesting an effect on the catalytic, rather than the regulatory subunit of the enzyme. The inhibition of protein kinase by thyroid hormone was not influenced by Mg++ concentration but was overcome in a competitive manner by increasing ATP concentration. Increasing the histone concentration did not modify the inhibition. Although these studies suggest a novel cellular control mechanism, the high thyroid hormone concentrations required and the lack of concordance between inhibitory effects and biologic activity of the analogs tested precludes assumption of physiologic relevance.

Animals↗
PubMed1978

Semi-automated micro-scale extraction apparatus for assay of free fatty acids in plasma.

We describe the use of a semi-automated micro-scale extraction apparatus as applied to the assay of free fatty acids in plasma. With it, a smaller plasma sample is required, disposable glassware can replace acid-washed glassware, and the number of samples that one technican can assay per day is increased fivefold. Theroretically, this apparatus can be applied to all assay procedures requiring one or more extraction steps.

Autoanalysis↗
PubMed1977

Regulation of thyroid ornithine decarboxylase by the polyamines. Induction of a protein inhibitor of ornithine decarboxylase by the end-products of the reaction.

When spermidine, putrescine or 1,3-diaminopropane was injected (12.5 mumol/100 g body weight) into rats 1 h before thyrotropin, ornithine decarboxylase activity was increased by 75--150% over control levels. However, when greater than or equal to 75 mumol polyamine/100 g body weight was injected, thyrotropin-activated activity was inhibited by 70--95%. Multiple polyamine injections inhibited goitrogen-induced activity and gland weight increase by approx 35%. The polyamines also inhibited thyrotropin-activated rat thyroid ornithine decarboxylase in vitro in a dose-related fashion, with 50% inhibition occurring at 2--5 . 10(-4)M. The inhibition was not due to a direct effect on the enzyme. No stimulation was seen with low concentrations of polyamine. The polyamines had no effect on in vitro thyroid protein/RNA synthesis or glucose oxidation but had a biphasic effect on plasma membrane adenylate cyclase activity. A protein inhibitor to thyroid ornithine decarboxylase was generated in vivo by multiple injections of the polyamines into rats and in vitro by incubating bovine thyroid slices with 2--10 mM polyamine. The inhibitor was non-dialyzable, destroyed by boiling, and its formation was blocked in a dose-related fashion by cycloheximide. We conclude that: (1) thyroid ornithine decarboxylase is subject not only to positive control, but is also negatively regulated by its end-products, the polyamines, which induce a protein inhibitor to ornithine decarboxylase; (2) since gland growth is also inhibited under these conditions, the polyamine effect on thyroid ornithine decarboxylase may be biologically significant.

Animals↗
PubMed1977

Serum gastrin levels in infants and children.

Fasting serum gastrin concentrations were determined by radioimmunoassay for 124 infants and children free of gastrointestinal disease. Values for the entire group ranged from 1.1 to 167.9 pg/ml (mean, 32.3 pg/ml). Mean serum gastrin levels for children who fasted eight or more hours were 22.5+/-23.9 pg/ml while the mean serum gastrin levels for children who fasted four to eight hours ranged from 42.4+/-33.9 pg/ml to 59.2+/-49.6 pg/ml. The mean serum gastrin levels varied inversely with body surface area among children who fasted the same length of time.

Adolescent↗