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Biomedical subjects

J M Smith

Publications and source records attributed to J M Smith.

At least 361 records · Page 20Linked to original sources
PubMed1987

Identification and nucleotide sequence of a gene encoding 5'-phosphoribosylglycinamide transformylase in Escherichia coli K12.

5'-Phosphoribosylglycinamide transformylase (EC 2.1.2.2), encoded by the purN gene of Escherichia coli, catalyzes the synthesis of 5'-phosphoribosylformylglycinamide from 5'-phosphoribosylglycinamide (GAR). The mature protein, as deduced from the purN structural gene sequence, contains 212 amino acid residues and has a calculated Mr of 23,241. The purN gene is located adjacent to and immediately downstream from the purM gene encoding 5'-phosphoribosyl-5-aminoimidazole (AIR) synthetase where the initiation codon for GAR transformylase overlaps the termination codon of AIR synthetase. Based on polarity studies, the expression of the purN gene originates from the purM control region and thus forms a purMN operon. The E. coli GAR transformylase shows greater homology to the GAR transformylase domain of the trifunctional Gart polypeptide of Drosophila than to the single GAR transformylase of Saccharomyces. Immediately downstream from the purN gene of the purMN operon is a region of dyad symmetry capable of forming a hairpin stem and loop structure characteristic of a rho-independent terminator.

Acyltransferases↗
PubMed1987

The "battle of the sexes": a genetic model with limit cycle behavior.

A two-locus genetic model, based on Dawkins "sex war" game, with the fitness of the genotypes at each locus depending on the gene frequencies at the other, is shown to give rise to a stable limit cycle. The mathematical analysis involves averaging techniques and elliptic integrals.

Animals↗
PubMed1987

Primary lymphoma of prostate presenting as bladder outflow obstruction.

We report on a patient with prostatic lymphoma who presented with symptoms of bladder neck obstruction. Biopsy specimens from transurethral resection confirmed the diagnosis of prostatic lymphoma. There was no evidence of lymphoma spread. Treatment was by local x-ray therapy to the prostate gland. Since prostatic lymphoma is rare, the clinical literature is briefly reviewed.

Adult↗
PubMed1987

Surgical approach to inferior vena caval extension of renal carcinoma.

Between 1979 and 1985, 10 patients were treated for renal carcinoma with extension into the inferior vena cava but without evidence of disseminated disease. Two of these had tumour thrombus extension up to the level of the hepatic veins and in four the extension was above the level of the diaphragm, two of which entered the atrium. Thrombus was removed en bloc at radical nephrectomy. Six patients are still alive, with a mean survival of 22 months. There was no correlation between the level of tumour thrombus and perinephric extension or indeed any correlation between tumour thrombus level and overall survival. It is suggested that tumour thrombus in the inferior vena cava, in the absence of metastatic disease, should be managed by radical surgery.

Adult↗
PubMed1987

Reduced capacity of peritoneal exudate cells for oxidative killing of Schistosoma mansoni schistosomula.

Peritoneal exudate cells from mice infected with Schistosoma mansoni (S-PEC) can kill schistosomula in vitro in the presence of immune serum. S-PEC produce a low level of respiratory burst, and schistosomula mortality in their presence is not reduced when exogenous antioxidants are added, suggesting that with S-PEC, oxidative killing is not important. Hydrogen peroxide (H2O2) and superoxide production by S-PEC, and cells from BCG and thioglycollate (THGL) injected non-infected mice, non-specifically stimulated with opsonized zymosan, were measured. Levels of H2O2 produced by S-PEC were significantly lower than BCG or THGL PEC, and were below the H2O2 threshold for schistosomula killing. This resulted in lower levels of cell-mediated killing of schistosomula in vitro by S-PEC than by BCG or THGL PEC. Superoxide levels, however, were similar between the three cell populations. The efficiency of PEC to kill schistosomules in vitro correlated with H2O2 rather than superoxide levels. The lower tolerance of schistosomula, compared to adult S. mansoni to GSH depleting agents increases their sensitivity to oxidative attack and resulted in higher levels of cell-mediated killing in vitro.

Animals↗
PubMed1987

Alpha-1 adrenergic receptor binding in aortas from rat and dog: comparison of [3H]prazosin and beta-iodo-[125I]-4-hydroxyphenyl-ethyl-aminomethyl-tetralone.

We have identified and characterized pharmacologically alpha-1 adrenergic receptors in aorta from dog and rat utilizing two alpha-1 antagonists, [3H]prazosin and beta-3-iodo[125I]-4-hydroxyphenyl-ethyl-aminoethyl-tetralone [125I]HEAT, to determine receptor number and affinity. The rat and dog alpha-1 receptors were found to be very similar. In the dog, KD values were 27 and 11 pM for [3H]prazosin and [125I]HEAT, respectively, whereas maximum binding values were 89 and 65 fmol/mg of protein. KD values in rat aorta were 22 and 15 pM for [3H]prazosin and [125I]HEAT, respectively, whereas maximum binding values were 62 and 47 fmol/mg of protein. Both tissues demonstrated a rank order potency of antagonist inhibition of the two radioligands consistent with an alpha-1 adrenergic receptor with prazosin greater than phentolamine greater than yohimbine. A comparison between IC50 values for both the ligands and the tissues shows strong correlations suggesting the two radioligands are identifying a similar receptor population and that the receptor labeled by the ligands has similar pharmacologic characteristics in the two tissues.

Adrenergic alpha-Antagonists↗
PubMed1987

Comparison of the effects of the novel inotropic agent, ibopamine, with epinine, dopamine and fenoldopam on renal vascular dopamine receptors in the anesthetized dog.

The effect of i.v. administration of the novel, p.o. active inotropic prodrug, ibopamine, on canine renal vascular dopamine DA-1 receptors was determined in the anesthetized dog. These effects were compared with those produced by the active form of ibopamine, epinine, and with the standard DA-1 receptor agonists, dopamine and fenoldopam. After pretreatment of pentobarbital-anesthetized dogs with phenoxybenzamine (10 mg/kg i.v.) and propranolol (2 mg/kg i.v.) to block alpha and beta adrenoceptor-mediated effects, respectively, the renal blood flow responses to i.v. administration of ibopamine, epinine, dopamine and fenoldopam were determined before and after selective blockade of DA-1 receptors by i.v. infusion of SK&F R-83566 (0.5 microgram/kg/min). Under control conditions, ibopamine produced a dose-dependent increase in renal blood flow as a result of renal vasodilation (i.e., decrease in renal vascular resistance), and was approximately 10-fold less potent than epinine in this respect. Epinine elicited qualitatively similar renal hemodynamic changes to ibopamine with the exception of potency. Dopamine was approximately equipotent with epinine as a renal vasodilator, and both compounds were 10-fold less potent than fenoldopam. Concurrent with the renal vasodilation produced by all four compounds, there was a reduction in mean arterial blood pressure and total peripheral vascular resistance. After the administration of SK&F R-83566, the renal vasodilator responses to fenoldopam were antagonized markedly with an approximate 30-fold rightward shift in the log dose-response curve, whereas the renal vasodilator responses to dopamine were abolished completely and converted into small vasoconstrictor responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1987

Comparison of the alpha adrenoceptor activity of dopamine, ibopamine and epinine in the pulmonary circulation of the dog.

The ability of dopamine, ibopamine and epinine to elicit alpha adrenoceptor-mediated vasoconstriction was studied in the in situ, autoperfused pulmonary circulation of the open-chest anesthetized dog. Animals were pretreated with propranolol to eliminate beta adrenoceptor-mediated relaxation of the pulmonary vasculature. Heparinized blood was withdrawn from the left femoral artery and transferred via a peristaltic pump to the pulmonary arterial branch supplying the left diaphragmatic lobe of the lung. The flow rate of the pump was adjusted so that mean pulmonary perfusion pressure in the lobe was equal to resting diastolic pulmonary artery pressure (10 +/- 1 mm Hg). Under conditions of constant left atrial pressure and pulmonary blood flow, intralobar administration of dopamine, ibopamine and epinine elicited dose-dependent increases in perfusion pressure of the lobe, reflecting increases in pulmonary vascular resistance. Prazosin (100 micrograms/kg i.v.), a selective alpha-1 adrenoceptor antagonist, inhibited the pulmonary vasopressor responses to dopamine, ibopamine and epinine. Rauwolscine (100 micrograms/kg i.v.), a selective alpha-2 adrenoceptor antagonist, inhibited pulmonary pressor responses to dopamine and epinine without altering significantly the pulmonary vasoconstrictor response to ibopamine. These data indicate that dopamine and epinine stimulate both postjunctional vascular alpha-1 and alpha-2 adrenoceptors to elicit pulmonary vasoconstriction in the dog, whereas ibopamine, when injected directly into the pulmonary circulation, stimulates primarily postjunctional vascular alpha-1 adrenoceptors. However, when ibopamine was administered intraduodenally, both prazosin and rauwolscine were found to inhibit the resulting pulmonary vasopressor response. This finding is consistent with the hypothesis that ibopamine is converted to its active metabolite epinine, which stimulates both pulmonary vascular alpha-1 and alpha-2 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Characterization of the alpha-1 adrenergic receptors in the thoracic aorta of control and aldosterone hypertensive rats: correlation of radioligand binding with potassium efflux and contraction.

Pharmacologic analysis of functional and radioligand binding studies were used to determine whether alterations in adrenergic receptors contribute to the catecholamine supersensitivity observed in the thoracic aorta of aldosterone hypertensive rats (AHR). Adrenergic function was evaluated using receptor-mediated contraction and rate of 42K efflux. The pA2 for phentolamine was the same in AHR (7.9 +/- 0.1 and 8.0 +/- 0.1) and control (7.9 +/- 0.2 and 8.1 +/- 0.1) rats whether measured by contraction or 42K efflux. The pA2 value for the selective alpha-1 antagonist prazosin (9.8 +/- 0.1 to 10.7 +/- 0.2) and the alpha-2 antagonist yohimbine (6.6 +/- 0.2 to 7.4 +/- 0.2) was similar in AHR and control groups using both norepinephrine and phenylephrine as agonists. The rank order of potency was prazosin greater than phentolamine greater than yohimbine in both groups. The KD for [3H]prazosin binding to AHR (26 +/- 3 pM) and control tissue (34 +/- 6 pM) agreed with the prazosin KB obtained by measurements of contraction and 42K efflux. The alpha-1 receptor density was also unaltered: 39 +/- 1 fmol/mg in AHR and 44 +/- 3 fmol/mg in control. Assessment of the NE dissociation constant (Ka) by method of fractional receptor inactivation indicated that the Ka was 4.8 X 10(-7) M in both AHR and control tissues. However, at the same receptor occupancy, the NE-induced increase in 42K efflux was elevated markedly in aorta from AHR. We conclude that alteration in adrenergic receptor density, affinity or type is not the cause of catecholamine supersensitivity in the aorta from AHR and that postreceptor events mediate this phenomenon.

Aldosterone↗
PubMed1987

Enhanced pulmonary alpha-2 adrenoceptor responsiveness under conditions of elevated pulmonary vascular tone.

Alpha-1 and alpha-2 adrenoceptor-mediated vasoconstriction was studied in the in situ, autoperfused pulmonary circulation of the open-chest anesthetized dog under conditions of normal and elevated pulmonary vascular tone. Under conditions of normal pulmonary vascular tone (10 +/- 1 mm Hg), methoxamine, a selective alpha-1 adrenoceptor agonist, and B-HT 933, a selective alpha-2 adrenoceptor agonist, elicited maximal increases in lobar perfusion pressure of 5 and 2 mm Hg above resting pulmonary tone, respectively. When pulmonary vascular tone was elevated progressively with the thromboxane mimetic, U-46619, serotonin or PGF2 alpha, alpha-1 adrenoceptor-mediated pulmonary vasoconstrictor responses to methoxamine were unaffected, whereas alpha-2 adrenoceptor-mediated pulmonary pressor responses to B-HT 933 were enhanced. Overall the response to B-HT 933 was enhanced 4-fold when pulmonary perfusion pressure was elevated to 19.8 +/- 0.8 mm Hg with U-46619 and almost 5-fold when elevated to 27.0 +/- 1.2 mm Hg. Pulmonary vasoconstrictor responses to angiotensin II were unaffected by elevated pulmonary vascular tone. Enhanced responsiveness of B-HT 933 to elevated pulmonary vascular tone was antagonized by the selective alpha-2 adrenoceptor antagonist, rauwolscine (100 micrograms/kg i.v.), and unaffected by the selective alpha-1 adrenoceptor antagonist, prazosin (100 micrograms/kg i.v.). When canine intralobar pulmonary veins were studied in vitro they contracted to B-HT 933 whereas intralobar pulmonary arteries did not respond. These data indicate that alpha-2 adrenoceptor responsiveness is enhanced markedly and selectively under conditions in which pulmonary vascular tone is elevated.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1986

Nucleotide sequence of the purM gene encoding 5'-phosphoribosyl-5-aminoimidazole synthetase of Escherichia coli K12.

5'-Phosphoribosyl-5-aminoimidazole synthetase (EC 6.3.3.1), encoded by the purM gene of Escherichia coli, catalyzes the synthesis of 5'-phosphoribosyl-5-aminoimidazole from 5'-phosphoribosylformylglycinamidine. The purM gene was subcloned from the Clarke and Carbon (Clarke, L., and Carbon, J. (1976) Cell 9, 91-99) plasmid pLC1-41 and the nucleotide sequence determined. The mature protein, as deduced from the purM structural gene sequence, contains 344 amino acid residues and has a calculated Mr of 36,726. The 5' end of the purM mRNA was determined by mung bean nuclease mapping to be 44-45 nucleotides up-stream of the proposed GTG translation initiation codon. A C-G-rich region characteristic of stringently controlled promoters is located immediately in front of the proposed purM promoter region. Comparison of the upstream sequences of the purM and the coregulated purF loci revealed a highly conserved (33 of 39 base pairs are identical) sequence. The presumptive purM promoter is located in this region, thus suggesting that both purine loci share a common mechanism of regulation mediated through this sequence.

Amino Acid Sequence↗
PubMed1986

Purification and characterization of aminoimidazole ribonucleotide synthetase from Escherichia coli.

Aminoimidazole ribonucleotide (AIR) synthetase has been purified 15-fold to apparent homogeneity from Escherichia coli which contains a multicopy plasmid containing the purM, AIR synthetase, gene. The protein is a dimer composed of two identical subunits of Mr 38,500. The N-terminal sequence, amino acid composition, and steady-state kinetics of the protein have been determined. AIR synthetase has been shown to catalyze the transfer of the formyl oxygen of [18O]formylglycinamide ribonucleotide to Pi.

Amino Acids↗