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Biomedical subjects

R Murphy

Publications and source records attributed to R Murphy.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial.

CONTEXT: Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration. OBJECTIVE: To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy. DESIGN: Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING: Thirty-three US HIV treatment centers. PARTICIPANTS: Of 1171 patients screened, 442 patients infected with HIV receiving stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater than 2500 copies/mL and CD4+ cell count above 0.20 x 10(9)/L were randomized. INTERVENTION: Patients were randomized to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after 24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES: Changes in HIV RNA from baseline, based on area under the curve and CD4+ cell levels, adverse events, and effect of baseline genotypic resistance on response to adefovir. RESULTS: Patients assigned to adefovir demonstrated a 0.4-log10 decline from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated hepatic enzyme levels (P<.001), gastrointestinal tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between 24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients, usually returning to baseline after discontinuation of adefovir. Patients with lamivudine or lamivudine and zidovudine resistance mutations demonstrated anti-HIV effects with adefovir (P< or =.01 vs placebo group). CONCLUSIONS: This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine. Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.

Adenine↗
PubMedDate not supplied

Effectiveness of nantradol in blocking narcotic withdrawal signs through nonnarcotic mechanisms.

Male rats were made narcotic dependent through continuous intravenous infusion of morphine. During withdrawal, nantradol, clonidine, and morphine were found to block withdrawal signs in a dose-dependent manner. Almost complete alleviation of withdrawal occurred with nantradol or clonidine at 0.16 mg/kg and with morphine at 40 mg/kg. The effectiveness of morphine, but not of nantradol or clonidine, was reversed by naloxone. Likewise, in naive rats given castor oil, naloxone did not block the antidiarrheal effect of nantradol or clonidine. In order to compare possible subjective effects of nantradol with other antiwithdrawal drugs, naive rats were trained to discriminate either morphine, cyclazocine, or clonidine from vehicle by selecting different levers for reinforcement. Nantradol failed to produce any generalization to morphine, cycloazocine, or clonidine, suggesting that this drug does not produce central subjective effects like those of the training drugs. In additional testing in behavioral experiments, nantradol failed to produce any sign of anxiogenic activity.

Animals↗
PubMedDate not supplied

Synthesis and biological characterization of a series of analogues of omega-conotoxin GVIA.

The 27-residue polypeptide omega-conotoxin GVIA (omega-CgTx), from the venom of the cone shell Conus geographus, blocks N-type neuronal calcium channels. It contains three disulphide bridges. We report here the synthesis and biological characterization of a series of analogues in which one disulphide has been replaced by substitution of appropriate Cys residues with Ser, viz. [Ser1,16]-omega -CgTx, [Ser8,19]-omega-CgTx, [Ser15,26)-omega-CgTx, [Ser16]-omega-CgTx8-27 and [Ser15]-omega-CgTx1-19. All syntheses were conducted manually using either Boc or Fmoc methodology. Deprotected peptides were oxidized to their bridged forms using either aerial oxidation or aqueous dimethyl sulphoxide. Peptides were purified using RP-HPLC, and their purity and identity were checked by RP-HPLC, capillary electrophoresis and mass spectrometry. Inhibition of neuronal N-type calcium channels was assessed as the inhibition of the twitch responses of rat vas deferens stimulated with single electrical pulses at 20 second intervals. None of these analogues was biologically active, suggesting that the disulphides play an important role in maintaining biological activity.

Amino Acid Sequence↗
PubMedDate not supplied

Superficial siderosis of the central nervous system.

Two patients with superficial siderosis of the central nervous system are reported. Both developed progressive deafness over many years; one with associated anosmia and partial seizures; the other with progressive ataxia and diplopia. The cerebrospinal fluid was xanthochromic in one and the protein was raised in both. Magnetic resonance imaging revealed a hypodense rim around the eighth cranial nerve, cerebellum, brain stem and spinal cord. Despite extensive investigations the cause of the superficial siderosis in both patients remains undetermined.

Adult↗
PubMedDate not supplied

Effect of chronic morphine administration on measured levels and chromatographic characterization of six neuropeptides in guinea-pig ileum.

Guinea-pigs were chronically treated with morphine by subcutaneous implantation of a compounded morphine pellet. After 7 days, the animals were sacrificed, and the small intestine was removed and extracted for the assay of 6 neuropeptides (substance P, vasoactive intestinal peptide, galanin, dynorphin A (1-8), dynorphin A (1-17) and alpha-neo-endorphin). The neuropeptide content of the extracts was measured by radioimmunoassay, and the extracts were subjected to analysis by reversed-phase high pressure liquid chromatography. The measured level of each neuropeptide was not significantly different from that in a control group of animals, and the chromatographic elution pattern obtained for each peptide was also similar in control and morphine-treated animals. Furthermore, the major peak of immunoreactivity for each peptide occurred with approximately the same retention time as synthetic standards having the porcine sequence for that peptide. It is concluded that chronic morphine treatment does not alter the tissue concentration or molecular form of at least 5 of the 6 neuropeptides studied. In the case of a alpha-neo-endorphin, a peak of immunoreactivity was discovered that did not correspond to the synthetic peptide. The amount of immunoreactive material present in this peak varied with oxidation and so its contribution to the assay results could not be calculated.

Animals↗
PubMedDate not supplied

Primary amino acid sequence of guinea-pig substance P.

The neuropeptide, substance P, has been isolated from guinea-pig small intestine by use of a multi-dimensional chromatographic strategy, and its primary amino acid sequence determined. The sequence is the same as that for all other species in which it has been determined, viz.: H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-(NH2).

Amino Acid Sequence↗
PubMedDate not supplied

Porcine VIP is more potent than guinea pig VIP in relaxing the guinea pig uterine artery.

The vasodilator potency of guinea pig VIP (gp VIP) on the guinea pig uterine artery was compared with the potency of porcine VIP (p VIP), which differs in amino acid sequence at four locations. When antioxidants were not used, the two peptides were approximately equipotent in causing relaxation of precontracted vessel segments. Use of the antioxidants ascorbic acid and dithiothreitol resulted in significantly increased potency of both peptides. Porcine VIP was 15 times more potent than gp VIP synthesized by the same method (tBoc), and gp VIP synthesized by tBoc methodology was 2 times more potent than gp VIP synthesized by Fmoc methodology. Therefore, care should be taken in the choice and handling of synthetic peptides when aiming to mimic actions of endogenous peptides.

Animals↗
PubMedDate not supplied

Isolation and microsequence analysis of a novel form of neuromedin U from guinea pig small intestine.

A multidimensional chromatographic regimen has been used to isolate and purify a peptide showing immunoreactivity for neuromedin U from guinea pig small intestine. Microsequence Edman N-terminal analysis and C-terminal analysis by enzymatic digestion showed this peptide to be a nonapeptide with the following sequence: H-Gly-Tyr-Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH2. The C-terminal octapeptide of this sequence is the same as porcine NMU-8, and the C-terminal heptapeptide is identical to rat NMU(17-23).

Amino Acid Sequence↗
PubMedDate not supplied

Isolation and microsequence analysis of guinea pig alpha-neo-endorphin.

A multidimensional chromatographic regimen was used to isolate and purify alpha-neo-endorphin-like immunoreactive material from guinea pig small intestine. Microsequence analysis of the material obtained showed that the sequence of this peptide in guinea pig is the same as that previously reported for pig and rat, namely: H-Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro-Lys(OH). Thus, the sequence of alpha-neo-endorphin is conserved in all species thus far examined.

Amino Acid Sequence↗
PubMedDate not supplied

The self-management of skills by persons with mental retardation.

The transition of persons with mental retardation to less restrictive environments is often hindered by difficulties in managing their own behavior in the absence of external controls. This observation has led to an upsurge of interest in the advantages of teaching self-management skills to persons with mental retardation. This article reviews evidence about the effects of self-management training on the acquisition, maintenance, and generalization of skills. The analyses show that self-management training has been useful in promoting the maintenance of behavior change first effected by external control procedures, but that a dearth of evidence and a number of methodological problems preclude convincing conclusions about its value in promoting generalization. The empirical evidence also suggests that the effectiveness of these procedures may depend upon the cognitive and linguistic abilities of the persons receiving self-management training. Finally, the design of much of the empirical research does not enable the disentanglement of the specific effects of self-management training from those arising from the concurrent application of external control procedures. Carefully controlled componential studies of the effects of self-management training and external control procedures are sorely needed.

Activities of Daily Living↗
PubMedDate not supplied

Inhibitors of neovascularization.

The use of neovascular inhibitors in the treatment of CNV will no doubt have a profound impact in the future. However, complex issues surround the use of these agents. Careful clinical trials will be necessary to determine the optimal parameters for their use. Furthermore, it must be determined whether these inhibitors will be most efficacious as primary agents or as agents used to augment the efficacy of photoreactive laser treatment or feeder vessel treatment.

Angiogenesis Inhibitors↗