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T V Murphy

Publications and source records attributed to T V Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Phorbol esters impair endothelium-dependent and independent relaxation in rat aortic rings.

1. This study examined the ability of various nitro-vasodilators, 8-bromo cyclic guanosine 3':5' monophosphate (8-BrcGMP) and forskolin to relax rings of rat thoracic aorta pre-contracted with either noradrenaline (0.1 microM) or the protein kinase C activators, phorbol 12,13-dibutyrate (PDB, 0.1 microM) or phorbol 12-myristate 13-acetate (PMA, 0.5 microM). 2. In noradrenaline pre-contracted rings, acetylcholine (10 nM-10 microM), sodium nitroprusside (1 nM-0.5 microM), the calcium ionophore A23187 (10 nM-10 microM) and 8-BrcGMP (10 mM) totally reversed the smooth muscle contraction. In PDB-contracted aortic rings acetylcholine, sodium nitroprusside and 8-BrcGMP-induced relaxation was reduced compared to that in noradrenaline-contracted aortic rings, but A23187 and forskolin-induced relaxations were unaffected. Both acetylcholine and A23187-induced relaxations in PDB-contracted rings were abolished in the presence of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine (NOLA, 100 microM). 3. Acetylcholine and sodium nitroprusside were even less potent in their ability to relax PMA-contracted aortic rings compared with noradrenaline and PDB-contracted rings. A23187-induced relaxation was also inhibited in PMA-contracted rings. 4. These results show that protein kinase C activation reduces the ability of agents which liberate nitric oxide to induce smooth muscle relaxation, and also inhibits the biochemical pathways which are subsequently activated by nitric oxide and lead to vascular smooth muscle relaxation.

Acetylcholine↗
PubMed1994

Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery.

1. Small strips from third-order branches of rabbit mesenteric artery (approximately 150-200 microM wide) contracted in response to noradrenaline (10 microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a single, transient contraction in artery strips, while 5-HT (10 microM) failed to induce any response. 2. In strips of mesenteric artery which had been permeabilized with Staphylococcus alpha-toxin and bathed in Ca(2+)-free mock intracellular solution, noradrenaline (10 microM), caffeine (10 mM) and D-myo-inositol (1,4,5)-trisphosphate (IP3, 100 microM), but not 5-HT (10 or 100 microM) induced a transient contraction. In contrast to the non-permeabilized strips, contractions to noradrenaline, caffeine and IP3 were restored by prior incubation (10 min) in solution containing 0.08 microM Ca2+. The contractions to noradrenaline and IP3 in permeabilized muscle strips required the presence of 100 microM guanosine 5'-triphosphate (GTP), although in the absence of Ca2+. GTP alone did not induce contraction. 3. Exposure of permeabilized mesenteric artery strips to IP3 significantly reduced the subsequent contractile responses to caffeine. Contractile responses to caffeine and IP3 were abolished by the Ca(2+)-ATPase inhibitor, thapsigargin (1 microM). 4. Ca2+ (0.1-10 microM) induced concentration-dependent contraction in permeabilized artery strips. In strips which were submaximally contracted with 0.5 microM Ca2+/100 microM GTP, the subsequent addition of 5-HT (10 microM) stimulated further contraction. The protein kinase C inhibitor, H-7 (1 microM) abolished the 5-HT/GTP-induced contraction, but did not alter the contraction to Ca2+. 5. In non-permeabilized, endothelium-denuded segments of rabbit mesenteric artery bathed in Ca2+-replete Krebs solution, noradrenaline (10 microM) stimulated a rapid, transient accumulation of IP3. 5-HT(100 microM) failed to stimulate IP3 accumulation during exposure periods of up to 5 min. 5-HT (100 microM)did stimulate IP3 accumulation if the external K+ concentration was raised (to around 25 mM). This concentration of K+ alone did not stimulate IP3 production and the 5-HT-stimulated IP3 accumulation in the presence of elevated extracellular [K+] was abolished by the alpha l-adrenoceptor antagonist, prazosin(O.1 microM).6. These results suggest that intracellular Ca2+ release does not play an important role in 5-HT-induced smooth muscle contraction in the rabbit mesenteric artery. This is despite the fact that a significant intracellular Ca2+ pool is present in these cells, which can be discharged by either noradrenaline or IP3.However, 5-HT did stimulate smooth muscle contraction in the presence of raised intracellular calcium,suggesting that a component of the contraction to 5-HT will reflect an increase in myofilament Ca2+sensitivity, possibly due to the activation of protein kinase C.

Actin Cytoskeleton↗
PubMed1993

Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination.

OBJECTIVE: To determine the incidence of invasive Haemophilus influenzae type b disease in children living in Minnesota and Dallas County, Texas, before and since introduction of plain polysaccharide vaccine in 1985, and conjugate vaccine in 1988. Initially, use of these vaccines was limited to infants 18 months of age and older. DESIGN: Identification of culture-proven cases of H influenzae type b disease was through systems of active, laboratory-based surveillance. The mean incidence of disease (cases observed/100,000 child-years) for 1983 and 1984 served as a baseline for comparison with subsequent years through 1991. PARTICIPANTS: Children less than 5 years of age in Minnesota and Dallas County, Texas. Overall, there were 2557 confirmed age-eligible cases of invasive H influenzae type b disease from 1983 through 1991. RESULTS: Between the 1983-1984 baseline and 1991, the incidence of H influenzae type b disease decreased 85% in Minnesota and 92% in Dallas. Notably, declines in incidence were observed in children in the age group being vaccinated as well as in infants younger than 18 months of age prior to introduction of vaccination. CONCLUSION: In two widely separated areas of the United States, a profound decrease in the incidence of H influenzae type b disease has occurred. The data suggest that vaccination may be protecting against disease, as well as decreasing the spread of infection to unvaccinated infants.

Bacterial Capsules↗
PubMed1993

Decreased Haemophilus colonization in children vaccinated with Haemophilus influenzae type b conjugate vaccine.

OBJECTIVE: The incidence of invasive Haemophilus disease has unexpectedly decreased in unvaccinated children since the introduction of conjugate vaccine in the United States. The purpose of this study was to determine whether conjugate vaccination decreases colonization with Haemophilus influenzae type b. DESIGN: This study was a prospective, bimonthly survey of pharyngeal colonization with H. influenzae type b in children attending day care from October 1987 through September 1989. Vaccination status was determined from the medical record. SUBJECTS: We obtained 1188 pharyngeal cultures from 283 healthy children, 18 to 59 months of age; 51 children had received unconjugated polysaccharide vaccine (PRP), and 89 had received conjugate vaccine (94% PRP-diphtheria toxoid). MEASUREMENTS AND RESULTS: Multivariate analysis was used to test the possibility of an association between vaccination status and the rate of colonization with H. influenzae type b. Among children known to be exposed to at least one child with a positive culture result, the efficacy of conjugate vaccination to prevent H. influenzae type b colonization in an unmatched analysis was 64% (95% confidence interval: 5%, 86%; p = 0.02) and in a matched analysis 81% (95% confidence interval: 7%, 96%; p = 0.02). No effect on colonization was found with PRP vaccination. CONCLUSIONS: Conjugate vaccination decreases H. influenzae type b pharyngeal colonization and thereby may decrease transmission of this agent among healthy children.

Bacterial Proteins↗
PubMed1993

Induction of immunologic memory in infants primed with Haemophilus influenzae type b conjugate vaccines.

The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease.

Bacterial Outer Membrane Proteins↗
PubMed1992

Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants.

OBJECTIVE: To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas. DESIGN: A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age. SUBJECTS: A convenience sample of 458 infants recruited largely from private pediatric practices. MEASUREMENTS AND RESULTS: At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001). After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine. CONCLUSIONS: In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown.

Age Factors↗
PubMed1992

Invasive Haemophilus influenzae type b disease in children less than 5 years of age in Minnesota and in Dallas County, Texas, 1983-1984.

During 1983 and 1984, 733 cases of invasive Haemophilus influenzae type b disease in children less than 5 years of age were identified in Minnesota and in Dallas County, Texas. The overall incidence of disease was lower in Minnesota than in Dallas County. However, among urban residents, the rates of disease for whites were similar in the two areas. A higher rate of disease among whites in urban Minnesota compared with rural Minnesota resulted from an increased rate of cases for diagnoses other than meningitis. Local practices might have affected the rate of certain diagnoses, since ascertainment of Hib disease other than meningitis is more dependent on diagnostic practices than is diagnosis of meningitis. These data suggest that the incidence of invasive H. influenzae type b disease is influenced by the racial composition of the population, the rates of disease in specific subgroups, and possibly by local medical practices. Understanding the factors that contribute to the incidence of disease is necessary to interpret variations in different populations and changes over time.

Age Factors↗
PubMed1992

Prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are sensitive to N-ethylmaleimide, but not pertussis toxin.

1. The identity of the G-proteins involved in prejunctional alpha 2-adrenoceptor signal transduction in mouse atria was examined by use of the G-protein inactivators N-ethylmaleimide and pertussis toxin. 2. The alpha 2-adrenoceptor partial agonist clonidine (0.03 microM) inhibited the electrical stimulation-induced (S-I) outflow of radioactivity from mouse atria which were incubated with [3H]-noradrenaline and stimulated at 5 Hz. The partial alpha 2-adrenoceptor agonist St 363 (10 microM) inhibited the S-I outflow of radioactivity at the lower stimulation frequency of 2.5 Hz. The inhibitory effects of these compounds were not altered in mice pretreated with pertussis toxin (1.5 micrograms, i.v.). 3. The alpha 2-adrenoceptor antagonist, idazoxan (0.1 microM), increased the S-I outflow of radioactivity from mouse atria stimulated at 5 Hz, and this effect was not altered in atria from mice pretreated with pertussis toxin. 4. The inhibitory effects of clonidine and St 363 and the facilitatory effect of idazoxan on the S-I outflow of radioactivity from mouse atria were significantly less in atria incubated with N-ethylmaleimide (NEM, 3 microM) for 60 min before the [3H]-noradrenaline incubation. 5. The results suggest that prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are NEM-sensitive, but pertussis toxin insensitive.

Adrenergic alpha-Agonists↗
PubMed1991

Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children.

OBJECTIVE: To compare the immunogenicity of four Haemophilus influenzae type b (Hib) conjugate vaccines in different populations of 17- to 19-month-old children in the United States. DESIGN: Four immunogenicity trials with sera were assayed in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and trials 3 and 4 were randomized comparisons of multiple vaccines within a region. SUBJECTS: A convenience sample of 313 healthy children recruited from pediatric practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa. MEASUREMENTS AND RESULTS: Children with prevaccination antibody greater than 0.15 microgram/ml showed higher antibody responses to vaccination than children with less than or equal to 0.15 microgram/ml (p less than 0.001). Among the former, there were no significant differences in antibody response to vaccination with the different conjugates within any of the trials. Among children with less than or equal to 0.15 microgram/ml of antibody before vaccination, there were no significant differences in the geometric mean antibody responses of children in trial 1 vaccinated with polyribosylribitol phosphate-diphtheria toxoid (PRP-D) in Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned to receive Hib oligosaccharide-CRM197 (HbOC) or PRP-D. In contrast, in trial 2, children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly higher geometric mean antibody response than children given PRP-T in Houston (13.5 vs 3.0 micrograms/ml; p = 0.005). In trial 4 in Minneapolis, the geometric mean antibody response was highest in children randomly assigned to receive PRP-outer membrane protein (OMP) (9.3 micrograms/ml), followed by PRP-D (5.0 micrograms/ml) and HbOC (2.3 micrograms/ml) (PRP-OMP vs HbOC; p = 0.005). In all four trials, IgG1 responses predominated compared with IgG2 responses. CONCLUSIONS: All four conjugate vaccines are immunogenic in children 17 to 19 months of age. However, the magnitude of the anticapsular antibody response varied by vaccine type, the level of antibody in prevaccination sera, and geographic location.

Antibodies, Bacterial↗
PubMed1991

Reevaluation of the ambulatory pediatric patient whose blood culture is positive for Haemophilus influenzae type b.

We conducted a retrospective review of 60 patients with Haemophilus influenzae type b bacteremia initially treated as outpatients, to test the hypothesis that a subgroup of these patients is at low risk of continuing invasive infection and thus requires a less comprehensive reevaluation. These patients were 6% of the 975 patients with invasive H. influenzae type b infection identified by active surveillance in Dallas County, Texas, during a 6 1/2-year period. The clinical assessment of "ill" appearance and persistent fever (greater than or equal to 38.0 degrees C) on the return visit were the two most useful variables in identifying patients at risk of continuing infection. Among 25 (42%) patients who were considered "ill" (febrile or afebrile), 20 (80%) had continuing invasive infection and 14 (56%) had a subsequent culture that was positive for H. influenzae type b. Among 8 patients who were considered "well" but who remained febrile, 3 (38%) had continuing infection, including 1 (13%) patient with a second culture that was positive. By contrast, among 27 (45%) patients who were considered "well" and who were afebrile, continuing invasive infection was identified in only 2 (7%) patients, and all repeat cultures were negative. These results suggest that when patients return for reevaluation of H. influenzae type b bacteremia, clinical assessment by an experienced physician, together with the febrile status of the patient, can identify those at high versus low risk of continuing invasive infection and thus guide the extent of diagnostic reevaluation.

Ambulatory Care↗
PubMed1990

Pertussis toxin differentiates between alpha 1- and alpha 2-adrenoceptor-mediated inhibition of noradrenaline release from rat kidney cortex.

In slices of rat kidney cortex incubated in [3H]noradrenaline, the alpha 1-adrenoceptor agonist methoxamine (10 microM), the alpha 2-adrenoceptor agonist clonidine (0.1 microM), as well as adenosine (10 microM), inhibited the electrical stimulation-induced (S-I) outflow of radioactivity, at a stimulation frequency of 1 Hz. Prior treatment of rats with pertussis toxin (25 micrograms/kg i.v.), which abolished the negative inotropic effect of carbachol (10 microM) on isolated atria, prevented the inhibition caused by methoxamine, but not that caused by clonidine or adenosine. At a stimulation frequency of 5 Hz, the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the prostaglandin synthesis inhibitor indomethacin (10 microM) both facilitated the S-I outflow of radioactivity, and neither of these effects were altered by pertussis toxin. These results suggest that a pertussis toxin sensitive G-protein is involved in alpha 1-adrenoceptor inhibition of noradrenaline release, but not in alpha 2-adrenoceptor, adenosine or prostaglandin inhibition.

Animals↗
PubMed1990

Pertussis in hospitalized children.

Before the whole-cell pertussis vaccine was available, Bordetella pertussis infections were an important cause of morbidity and mortality in infants. To determine the extent of continuing morbidity in an era of vaccination, a retrospective review was conducted of the records of neonates and infants hospitalized with pertussis infection at Parkland Memorial Hospital and Children's Medical Center, Dallas, Tex. During the 20 years from 1967 through 1986, 182 patients were younger than 24 months. Among 176 patients whose immunization history was recorded, 89% had received fewer than two doses of pertussis vaccine. The mean hospital stay was 7.4 days (range, 1 to 69 days). A convulsion occurred in 11 patients (6%). Apnea was reported in 45 patients (25%) and observed in the hospital in 26 (14%). Nine patients (5%) received mechanical ventilatory therapy. Intensive care monitoring was required in 18 patients (10%). Three (1.6%) died, all with secondary bacterial pneumonia. This hospital-based population indicates that pertussis continues to be a cause of serious morbidity and mortality in infants.

Bacterial Infections↗
PubMed1990

Prejunctional beta-adrenoceptors, angiotensin II and neuropeptide Y receptors on sympathetic nerves in mouse atria are linked to N-ethylmaleimide-susceptible G-proteins.

We used the alkylating agent N-ethylmaleimide in order to investigate G-proteins linked to release-modulating prejunctional receptors of sympathetic nerves in mouse atria incubated with [3H]-noradrenaline. The receptors tested were facilitatory beta-adrenoceptors and angiotensin II receptors and inhibitory neuropeptide Y receptors. In order to evaluate the specificity of the N-ethylmaleimide treatment, we tested N-ethylmaleimide against the second messenger pathways that are linked to beta-adrenoceptors (adenylate cyclase) and angiotensin II (protein kinase C). The results show that a 60-min preincubation with N-ethylmaleimide (3 microM) abolished the facilitatory effect of isoprenaline (0.1 microM) and angiotensin II (0.1 microM) on the stimulation-induced release of noradrenaline and reduced the inhibitory action of neuropeptide Y (0.3 microM). N-ethylmaleimide had no effect on the stimulatory action of either phorbol dibutyrate (0.01, 0.1 microM), forskolin (10 microM), or a combination of 8-bromo adenosine-3'5'-monophosphate (90 microM) and 3-isobutyl-1-methylxanthine (100 microM). However, at a higher concentration (10 microM), N-ethylmaleimide reduced the facilitatory effect of phorbol dibutyrate (0.1 microM) and the combination of 8-bromo adenosine-3',5'-monophosphate (90 microM) and 3-isobutyl-1-methylxanthine (100 microM). This suggests that N-ethylmaleimide at 3 microM but not 10 microM was selective for receptor-mediated modulation of noradrenaline release without directly affecting the adenylate cyclase (forskolin, 8-bromo adenosine-3',5'-monophosphate + 3-isobutyl-1-methylxanthine) or protein kinase C (phorbol dibutyrate) transduction pathways. In atria from mice pretreated with pertussis toxin (1.5 micrograms/mouse), N-ethylmaleimide preincubation (1 and 3 microM) resulted in a more pronounced reduction of the inhibitory action of neuropeptide Y (0.3 microM). The nature of this interaction is unclear. Since N-ethylmaleimide has been shown in other studies to inactivate G-proteins, the inhibitory effect of N-ethylmaleimide on prejunctional beta-adrenoceptors, angiotensin II receptors and neuropeptide Y receptors of sympathetic nerves may suggest that G-proteins are involved with these receptors, although other effects of N-ethylmaleimide on the receptor coupling processes cannot be ruled out. Moreover, it appears that the concentration of N-ethylmaleimide used is critical since a higher concentration (10 microM) resulted in non-specific effects on signal transduction mechanisms in the present experimental conditions.

Adenylate Cyclase Toxin↗
PubMed1990

Pertussis toxin attenuates angiotensin II but not beta-adrenoceptor facilitation of noradrenaline release from rat kidney cortex.

1. Angiotensin II (AII; 0.01 and 0.1 mumols/L), angiotensin I (AI, 0.1 mumols/L) and the beta-adrenoceptor agonist isoprenaline (0.1 mumols/L) all facilitated the stimulation-induced outflow of radioactivity from slices of rat kidney cortex incubated in [3H]-noradrenaline. 2. Treatment of rats with pertussis toxin (25 and 50 micrograms/kg i.v.) to inactivate G-proteins attenuated the facilitation caused by AII and AI, but not that caused by isoprenaline. 3. The hypothesis that isoprenaline enhances noradrenaline release by generating AII to activate facilitatory prejunctional AII receptors is not supported by the present study. The hypothesis predicts that pertussis toxin, by inactivating the G-proteins associated with AII receptors, should have inhibited the facilitatory effect of isoprenaline. This did not occur.

Angiotensin I↗