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Biomedical subjects

J R Peterson

Publications and source records attributed to J R Peterson.

At least 19 recordsLinked to original sources
PubMed2003

Effect of tumour necrosis factor alpha antagonists on serum transaminases and viraemia in patients with rheumatoid arthritis and chronic hepatitis C infection.

BACKGROUND: Tumour necrosis factor alpha (TNF alpha) antagonists are effective for the treatment of rheumatoid arthritis (RA), but concerns remain about the safety of these agents in the presence of chronic infections, including hepatitis C virus (HCV) infection. OBJECTIVE: To examine the influence of treatment with TNF alpha antagonists on levels of HCV viraemia and serum transaminases in patients with RA and HCV. METHODS: In a retrospective survey the course of 16 HCV infected patients with RA who had received the TNF alpha antagonists etanercept or infliximab was analysed. Eight additional patients with RA and HCV were also enrolled into a three month prospective trial of etanercept. Serum concentrations of albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and HCV were followed. RESULTS: Viraemia was measured in 22 patients receiving a TNF alpha antagonist at the start of treatment and after 1-34 months (median 9 months follow up). Twenty four patients had serial tests of liver related enzymes and albumin. None of the differences between liver related tests at baseline and at follow up achieved significance (p>0.05). Similarly, the mean HCV measurement at 1-3, 4-6, 7-12, and 13-34 months did not differ significantly from baseline (p>0.05). CONCLUSION: In this study, liver related blood tests and HCV viral load measurements did not change substantially. These findings suggest that TNF alpha antagonists merit further study for the treatment of RA in HCV infected patients. Larger and longer term studies are still needed.

Adult↗
PubMed2001

A chemical inhibitor of N-WASP reveals a new mechanism for targeting protein interactions.

Cell morphology and motility are governed largely by complex signaling networks that ultimately engage the actin cytoskeleton. Understanding how individual circuits contribute to the process of forming cellular structures would be aided greatly by the availability of specific chemical inhibitors. We have used a novel chemical screen in Xenopus cell-free extracts to identify compounds that inhibit signaling pathways regulating actin polymerization. Here we report the results of a high-throughput screen for compounds that inhibit phosphatidylinositol 4,5-bisphosphate (PIP(2))-induced actin assembly and the identification of the first compound, a cyclic peptide, known to block actin assembly by inhibiting an upstream signaling component. We identify the target of this compound as N-WASP, a protein that has been investigated for its role as a node interconnecting various actin signaling networks. We show that this compound prevents activation of the Arp2/3 complex by N-WASP by allosterically stabilizing the autoinhibited conformation of N-WASP.

Actin-Related Protein 2↗
PubMed1999

Time-intensity trading in the late auditory evoked potential.

The present study investigated physiological correlates of the time-intensity trading relationship in late components (N1, P2) of the auditory evoked potential. Late-potential and behavioral thresholds were estimated in five normal-hearing, young adult participants for 1000- and 4000-Hz tone bursts having durations of 8, 16, 32, 64, and 128 ms. The results showed that late-potential thresholds decreased by an average of 24 dB for 1000-Hz conditions and 18 dB for 4000-Hz conditions. Behavioral thresholds also improved by about 22 dB and 18 dB for 1000-Hz and 4000-Hz conditions, respectively. The slope of improvement for both late-potential and behavioral thresholds was on the order of -4 to -6 dB per doubling of stimulus duration, depending on stimulus frequency. Stimulus duration also influenced latency and amplitude measures of the N1 and P2 components such that response latency decreased and amplitude increased as stimulus duration increased. The present results demonstrate a time-intensity trading relationship in components of the late potentials that is consistent with previous psychophysical and physiological data.

Acoustic Impedance Tests↗
PubMed1999

In vitro reconstitution of calreticulin-substrate interactions.

Calreticulin is a soluble, endoplasmic reticulum-resident protein and a molecular chaperone for glycoproteins. We have reconstituted the binding of recombinant calreticulin to two glycoprotein substrates, vesicular stomatitis virus G protein and influenza hemagglutinin, in vitro. The binding was found to be direct and to require monoglucosylated, asparagine-linked oligosaccharides on the substrate glycoprotein but no other cellular factors. The binding could be modulated in vitro by incubation of substrate with purified preparations of the glycan modifying enzymes glucosidase II and the UDP-glucose:glycoprotein glucosyltransferase, thus recapitulating the regulation of calreticulin-binding by glycan modification that occurs in vivo. Using the purified ER enzymes and the recombinant calreticulin, an assay was established for reconstituting a complex, multicomponent chaperone binding cycle in vitro. We demonstrated, moreover, that the acidic C-terminal 62 residues of calreticulin are dispensable for substrate binding whereas further deletions inhibit substrate binding.

Animals↗
PubMed1996

Acupuncture in the 1990s. A review for the primary care physician.

The purpose of this article is to educate primary care providers regarding the theory and basic principles of acupuncture. Various indications for acupuncture are discussed. It is hoped that this article will allow the primary care practitioner to correctly identify patients in his or her practice who might benefit from acupuncture treatment.

Acupuncture Therapy↗
PubMed1995

Transient, lectin-like association of calreticulin with folding intermediates of cellular and viral glycoproteins.

The soluble, calcium-binding protein calreticulin shares high sequence homology with calnexin, a transmembrane chaperone of glycoprotein folding. Our experiments demonstrated that calreticulin, like calnexin, associated transiently with numerous newly synthesized proteins in the endoplasmic reticulum. The population of proteins that bound to calreticulin was partially overlapping with those that bound to calnexin. Hemagglutinin (HA) of influenza virus was shown to associate with both calreticulin and calnexin. Using HA as a model substrate, it was found that both calreticulin- and calnexin-bound HA corresponded primarily to incompletely disulfide-bonded folding intermediates and conformationally trapped forms. Binding of all substrates was oligosaccharide-dependent and required the trimming of glucose residues from asparagine-linked core glycans by glucosidases I and II. In vitro, alpha-mannosidase digestion of calreticulin-bound HA indicated that calreticulin was specific for monoglucosylated glycans. Thus, calreticulin appeared to be a lectin with similar oligosaccharide specificity as its membrane-bound homologue, calnexin. Both are therefore likely to play an important role in glycoprotein maturation and quality control in the endoplasmic reticulum.

Animals↗
PubMed1994

Isolation of a mouse cDNA encoding Rab23, a small novel GTPase expressed predominantly in the brain.

The full-length cDNA encoding Rab23, a novel Ras-related small GTPase, was isolated using the sequence of a previously described [Chavrier et al., Gene 112 (1992) 261-264] short cDNA fragment and the rapid amplification of cDNA ends (RACE) PCR techniques. The deduced amino acid sequence was not very closely related to any previously described small GTPase, but was within the Rab subfamily. A Northern analysis revealed that the rab23 mRNA is predominantly expressed in the brain, which places the protein, together with Rab3a and Rab15, in the group of small GTPases characteristic of the nervous system.

Amino Acid Sequence↗
PubMed1994

Antimicrobial properties of alkaloids from Xanthorhiza simplicissima.

The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae. Bioassay-directed fractionation of the extract led to the isolation of the known alkaloid berberine as the major active component. A second alkaloid of the isohomoprotoberberine family, puntarenine, was isolated from this plant family for the first time. Puntarenine also showed marginal activity against the dermatophytic fungus Trichophyton mentagrophytes and the yeast Saccharomyces cerevisiae.

Alkaloids↗
PubMed1992

Copyrine alkaloids: synthesis, spectroscopic characterization, and antimycotic/antimycobacterial activity of A- and B-ring-functionalized sampangines.

Several A- and B-ring-substituted sampangines were synthesized and evaluated for antifungal and antimycobacterial activity against AIDS-related opportunistic infection pathogens. Electrophilic halogenation provided a channel for structural elaboration of the sampangine B-ring at position 4, while the synthesis of A-ring 3-substituted sampangines and benzo[4,5]sampangine (24) were achieved from the corresponding functionalized cleistopholines. Two-dimensional NMR spectroscopy was used to rigorously characterize the A- and B-ring substituent patterns. Structure-activity relationship studies revealed the activity of the sampangines was enhanced by the presence of a substituent at position 3 or by a 4,5-benzo group.

AIDS-Related Opportunistic Infections↗
PubMed1991

X-ray structure and crystal lattice interactions of the taxol side-chain methyl ester.

A colorless, parallelepiped crystal of methyl (2R,3S)-N-benzoyl-3-phenylisoserinate belonging to the space group P2(1) with a = 5.414(4), b = 7.813(1), c = 17.802(7) A, beta = 90.87(4) degrees, Z = 2, V = 752.9 A3, Dcalc = 1.32 g cm-3, and mu calc = 1.02 cm-1 was selected and the structure solved using direct methods. Refinement led to a final R = 0.079 for 819 [Fo greater than or equal to 5 sigma (Fo)] reflections. Intermolecular hydrogen-bonding interactions are prevalent in the crystal lattice of this compound.

Alkaloids↗
PubMed1989

Platelet activating factor antagonist design. 3. X-ray crystal structure and intermolecular crystal lattice interactions of methyl trans-4-acetoxymethyl-4,5-dihydro-2,5-bis(3,4-methylenedioxyphenyl)- 3-furancarboxylate.

C23H20O9, Mr = 440.41, monoclinic, P21/c, a = 11.433 (1), b = 7.808 (2), c = 23.313 (3) A, beta = 99.67 (1) degree, V = 2052 A3, Z = 4, Dx = 1.43 g cm-3, lambda(MoK alpha) = 0.71073 A, mu = 0.69 cm-1, F(000) = 920, T = 293 K, final R = 0.048 for 1645 observed [Fo greater than or equal to 5 sigma(Fo)] reflections. The observed structure reveals a trans relationship for the 4-acetoxymethyl and 5-aryl substituents. The 4,5-dihydrofuran ring system adopts an envelope conformation. There is no crystallographically imposed symmetry. Several intermolecular van der Waals interactions occur in the cell lattice of this compound.

Chemical Phenomena↗
PubMed1989

Platelet activating factor antagonist design. 2. X-ray structure of dimethyl 2,3,4,5-tetrahydro-5 beta-(3,4-methylenedioxyphenyl)-2-oxo-3 beta-(3,4,5-trimethoxybenzoyl)-3 alpha,4 alpha-furandicarboxylate.

C25H24O12, Mr = 516.46, triclinic, P-1, a = 8.780 (3), b = 11.298 (4), c = 13.271 (6) A, alpha = 71.77 (4), beta = 70.31 (3), gamma = 72.66 (3) degrees, V = 1189 A3, Z = 2, Dx = 1.44 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.74 cm-1, F(000) = 540, T = 293 K, final R = 0.046 for 2495 observed [Fo greater than or equal to 5 sigma (Fo)] reflections. The observed structure reveals a trans disposition for the methoxycarbonyl and aryl substituents at positions 4 and 5 of the heterocycle and a cis-3,4-bis(methoxycarbonyl) relationship. There is no crystallographically imposed symmetry. Several intermolecular van der Waals interactions occur in the cell lattice of this compound.

Chemical Phenomena↗
PubMed1989

Platelet activating factor antagonist design: structure of methyl trans-5-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydro-2-oxo-4- furancarboxylate.

C14H16O6, Mr = 280.28, monoclinic, P2(1)/c, a = 6.070 (2), b = 9.526 (5), c = 22.418 (5) A, beta = 94.32 (2) degrees, V = 1293 A3, Z = 4, Dx = 1.44 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 0.71 cm-1, F(000) = 592, T = 293 K, final R = 0.043 for 1400 observed [F0 greater than or equal to 5 sigma(F0)] reflections. The observed structure confirms a trans stereorelationship for the two substituents and an envelope conformation for the lactone ring. There is no crystallographically imposed symmetry. An analysis of the closest contacts in the cell lattice reveals two types of intermolecular interactions for this compound.

Chemical Phenomena↗
PubMed1989

Fever, bacteriuria, and pyuria in spinal cord injured patients with indwelling urethral catheters.

Little is known about the significance of pyuria in spinal cord injury patients with indwelling urethral catheters (IUCs). The hospital courses of 32 such patients admitted to a rehabilitation hospital from January 1986 to December 1987 were reviewed to determine the incidence of unexplained febrile episodes, ie, no obvious nonurinary source of infection. All patients had positive admission urine cultures (greater than 100,000 colony-forming units/mL). Patients were divided into two groups based on the level of pyuria in admission urinalyses. Group A (the low pyuria group) was composed of 22 patients with less than or equal to 50 white blood cells per high-power field (WBC/HPF). Group B (the high pyuria group) was composed of ten patients with less than 50 WBC/HPF. None were admitted to the rehabilitation program taking antibiotics; none were prophylactically treated for urinary tract infection. The difference in incidence of fever between febrile episodes. Group B had an incidence of 6/10 (60%) febrile episodes. The difference in incidence of fever between the groups was statistically significant (chi2 = 7.31, p less than .01). These results suggest that SCI patients with IUCs and gross pyuria may be at risk for increased morbidity secondary untreated urinary tract infection.

Adolescent↗
PubMed1987

Prolonged electrocardiographic monitoring in patients with syncope. Importance of frequent or repetitive ventricular ectopy.

The purposes of this study were to document the findings on prolonged electrocardiographic monitoring in patients with syncope, correlate these findings with symptoms during monitoring, and define the prognostic importance of these findings. A total of 235 patients with syncope in whom a cause was not assigned or suggested by the initial history, physical examination, and electrocardiography were studied. Although a variety of arrhythmias were documented during monitoring, the vast majority of arrhythmias were of short duration and did not produce symptoms. At two years, the patients with frequent or paired premature ventricular contractions (PVCs) when compared with patients with rare PVCs, had a higher incidence of sudden death (18.2 percent versus 4.0 percent; p less than 0.001) and higher overall mortality (28.3 percent versus 10.8 percent; p less than 0.003). Similarly, patients with ventricular tachycardia, when compared with patients with rare PVCs, had a higher incidence of sudden death (18.7 percent versus 4.0 percent; p less than 0.0001) and higher overall mortality (36.5 percent versus 10.8 percent; p less than 0.00001). Cox regression analyses revealed that frequent or repetitive PVCs and sinus pauses were independent electrocardiographic predictors of sudden death and mortality in patients presenting with syncope. Therefore, patients with syncope and frequent or repetitive ventricular ectopy or sinus pauses constitute a high-risk subgroup and may be candidates for more extensive diagnostic evaluation.

Adolescent↗