Search PubMed⌕ Search

Biomedical subjects

J Powell

Publications and source records attributed to J Powell.

At least 109 records · Page 6Linked to original sources
PubMed1998

Calcium currents and transients of native and heterologously expressed mutant skeletal muscle DHP receptor alpha1 subunits (R528H)

Rabbit cDNA of the alpha1 subunit of the skeletal muscle dihydropyridine (DHP) receptor was functionally expressed in a muscular dysgenesis mouse (mdg) cell line, GLT. L-type calcium currents and transients were recorded for the wild type and a mutant alpha1 subunit carrying an R528H substitution in the supposed voltage sensor of the second channel domain that is linked to a human disease, hypokalemic periodic paralysis. L-type channels expressed in GLT myotubes exhibited currents similar to those described for primary cultured mdg cells injected with rabbit wild type cDNA, indicating this system to be useful for functional studies of heterologous DHP receptors. Voltage dependence and kinetics of activation and inactivation of L-type calcium currents from mutant and wild type channels did not differ significantly. Intracellular calcium release activation measured by fura-2 microfluorimetry was not grossly altered by the mutation either. Analogous measurements on myotubes of three human R528H carriers revealed calcium transients comparable to controls while the voltage dependence of both activation and inactivation of the L-type current showed a shift to more negative potentials of approximately 6 mV. Similar effects on the voltage dependence of the fast T-type current and changes in the expression level of the third-type calcium current point to factors not primarily associated with the mutation perhaps participating in disease pathogenesis.

Animals↗
PubMed1998

Synthesis of a methylenebis(phosphonate) analogue of mycophenolic adenine dinucleotide: a glucuronidation-resistant MAD analogue of NAD.

Mycophenolic alcohol (MPAlc), obtained by reduction of the carboxylic group of mycophenolic acid (MPA), was coupled with 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) (4) in the presence of diisopropylcarbodiimide (DIC) to give P1-(2',3'-O-isopropylideneadenosin-5'-yl)-P2-(mycophenolic alcohol-6'-yl)methylenebis(phosphonate) (8) in 32% yield. Deisopropy-lidenation of 8 with CF3COOH/H2O afforded the methylenebis(phosphonate) analogue 3 of mycophenolic adenine dinucleotide (MAD). Compound 3, beta-methylene-MAD, was found to be a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH) type II (Ki = 0.3 microM) as well as an inhibitor of growth of K562 cells (IC50 = 1.5 microM). In contrast to MPA and mycophenolic alcohol, beta-methylene-MAD was not converted into the glucuronide when incubated with uridine 5'-diphosphoglucuronyltransferase.

Adenine Nucleotides↗
PubMed1998

Resistance of eels (Gymnothorax) to the venom of sea kraits (Laticauda colubrina): a test of coevolution.

Eels of the genus Gymnothorax from the Pacific are selectively preyed upon by banded sea kraits (Laticauda colubrina) and have been reported to sustain massive doses of sea krait venom without ill effect. By contrast, the present study found that Gymnothorax moringa from the Caribbean, where no sea snakes occur, are sensitive to sea krait venom, with doses as low as 0.01 mg dry wt of venom/kg wet wt of eel resulting in signs of envenomation, and doses as small as 0.1 mg/kg proving to be lethal. These observations suggest that the resistance of Pacific Gymnothorax to sea krait venom results from coevolution of predator and prey, rather than from a general hardiness of Gymnothorax. This theory is supported further by literature reports of sensitivity to sea snake venom by other taxa of non-coevolved eels that either are allopatric with sea snakes (Anguilla), or are sympatric with them but occupy different habitats and are not preyed upon by them (Heteroconger).

Animals↗
PubMed1998

Targeted gene knockout mediated by triple helix forming oligonucleotides.

Triple helix forming oligonucleotides (TFOs) recognize and bind sequences in duplex DNA and have received considerable attention because of their potential for targeting specific genomic sites. TFOs can deliver DNA reactive reagents to specific sequences in purified chromosomal DNA (ref. 4) and nuclei. However, chromosome targeting in viable cells has not been demonstrated, and in vitro experiments indicate that chromatin structure is incompatible with triplex formation. We have prepared modified TFOs, linked to the DNA-crosslinking reagent psoralen, directed at a site in the Hprt gene. We show that stable Hprt-deficient clones can be recovered following introduction of the TFOs into viable cells and photoactivation of the psoralen. Analysis of 282 clones indicated that 85% contained mutations in the triplex target region. We observed mainly deletions and some insertions. These data indicate that appropriately constructed TFOs can find chromosomal targets, and suggest that the chromatin structure in the target region is more dynamic than predicted by the in vitro experiments.

Animals↗
PubMed1998

Soft-tissue hemangiomas in infants and children: diagnosis using Doppler sonography.

OBJECTIVE: We describe the sonographic appearance and vascularization of hemangiomas and determine if vessel density and peak systolic Doppler shifts distinguish hemangiomas from other superficial soft-tissue masses. SUBJECTS AND METHODS: Our pilot study included 20 infants and children with hemangiomas who were to undergo biopsy before treatment with interferon alpha-2b. We used Doppler sonography to determine the number of vessels per square centimeter, peak arterial Doppler shift, resistive index, and signs of arteriovenous shunting. All hemangiomas showed high vessel density (more than five per square centimeter) and high Doppler shifts (more than 2 kHz), and these two factors became our diagnostic criteria. A prospective study of 116 patients was then carried out. One hundred sixteen consecutive pediatric patients with superficial soft-tissue masses were examined using Doppler sonography; sonographic findings were compared with the final diagnoses that were established by biopsy, CT, or clinical follow-up. RESULTS: The final diagnoses included 70 hemangiomas, 20 venous malformations, three arteriovenous malformations, three arteriolocapillary malformations, and 20 other masses. Fifty-nine lesions showing high vessel density (more than five per square centimeter) and a peak arterial Doppler shift exceeding 2 kHz were correctly diagnosed as hemangiomas (sensitivity, 84%; specificity, 98%). One arteriovenous malformation showed high vessel density and high Doppler shifts, but none of the other masses that were not hemangiomas did. Eleven patients with hemangiomas who were being treated with interferon at the time of the study fulfilled only one of the two diagnostic criteria. CONCLUSION: High vessel density and high peak arterial Doppler shift can be used to distinguish hemangiomas from other soft-tissue masses.

Arteriovenous Malformations↗
PubMed1998

Steady-state bioavailability of estradiol from two matrix transdermal delivery systems, Alora and Climara.

OBJECTIVE: The relative bioavailability of estradiol from two matrix transdermal delivery systems, Alora (0.05 mg/day when applied for 3-4 days) and Climara (0.05 mg/day when applied for 7 days), was evaluated in this two-period, randomized crossover study. DESIGN: A total of 27 healthy, postmenopausal women completed this study. Each subject received four successive doses of Alora every 84 h (3.5 days) and two doses of Climara every 168 h (7 days) in a randomized sequence without a washout period. Serial serum samples were collected over a 7-day period during the second week of each treatment. Samples were analyzed for estradiol and estrone using a validated radioimmunoassay method. Pharmacokinetic analyses were conducted using baseline-corrected parameters. RESULTS: Fluctuations in serum estradiol levels were 44% higher for Climara, as indicated by the ratio of Cmax/Cmin. Because the Cmin values for the two regimens were similar, the differences in fluctuation reflected the difference in their Cmax values (49.8 pg/ml for Alora, 67.7 pg/ml for Climara.) The estradiol AUC for Climara was 124% (95% CI 115.6-133.7) of the value for Alora. CONCLUSIONS: Serum estradiol concentrations were maintained at a more constant level during twice-weekly application of Alora than during once-weekly application of Climara. Both regimens were generally well tolerated and no serious skin or other adverse effects were reported by the subjects. However, Alora exhibited better skin tolerability as indicated by a lower incidence of moderate skin erythema. In addition, there was less adhesive transfer to skin at the application site with Alora.

Adhesives↗
PubMed1997

Comparison of clinical characteristics and frequency of implantable defibrillator use between randomized patients in the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial and nonrandomized registry patients.

In the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial, all patients who meet the study entry criteria are followed in a registry. During the period between June 1993 and June 1995, of 1,117 patients who were enrolled in the registry and met the study entry criteria, 476 were randomized to receive either implantable cardioverter-defibrillators (ICDs) or drug therapy (amiodarone or sotalol), and 641 patients were not randomized for a variety of reasons including: patient refusal (42%); physician refusal (43%); concerns about ability to maintain follow-up over several years (10%), and others (6%). There were no significant differences between the 476 randomized and 641 nonrandomized patients with regard to clinical characteristics, left ventricular function, history of congestive heart failure, medical history, and previous cardiac procedures performed before the index event, except that randomized patients were slightly older (65 vs 62 years) and had a slightly higher prevalence of coronary artery disease and previous myocardial infarction. The index event and location of the index event were not significantly different between the 2 groups. Although 14% of registry patients received neither ICD nor antiarrhythmic drug therapy, ICDs were no more frequently used in the registry patient than antiarrhythmic drugs (45% for ICD vs 42% for drugs). Thus, randomized AVID patients have very similar clinical characteristics, cardiac history, and presenting arrhythmias as to nonrandomized eligible patients. Therefore, the results of the AVID trial may be generalized for all patients with AVID-eligible arrhythmias.

Adolescent↗
PubMed1997

Classification of Vibrio vulnificus strains by the carbohydrate composition of their capsular polysaccharides.

Pathogenic bacteria are often classified on the basis of the complex polysaccharides found on the surface, usually capsular polysaccharides or lipopolysaccharides. It is common in clinical practice to use reactivity with antisera specific to the various cell surface carbohydrates for this purpose. In this work, we describe a chemotyping method for bacterial capsular polysaccharides which is based on a carbohydrate analysis of an acid hydrolysate of the capsule. High-performance anion-exchange chromatography at high pH (HPAE) with electrochemical detection, which is used for analysis of the hydrolysate, shows preferential sensitivity for sugars. A single acid hydrolysis condition is chosen for screening a large collection of bacterial isolates and a computerized autosampler is used to make possible a large number of rapid analyses. This procedure does not yield a quantitative carbohydrate analysis for the sample but produces a fingerprint which can be used to discriminate among isolates which have different capsular polysaccharide structures. The procedure has been applied to a collection of 120 isolates of Vibrio vulnificus, a water-born species common in shellfish which causes septicemia in immunocompromised individuals, most often from eating of raw oysters. The collection of bacterial isolates includes strains from both clinical cases of septicemia and from such environmental sources such as sea water, sediments, and shellfish. Our results show that a number of unusual sugars including many amino sugars are found in these polysaccharides and that a wide variety of capsular carbotypes in V. vulnificus may be readily distinguished by the HPAE fingerprint.

Anion Exchange Resins↗
PubMed1997

A linkage study of schizophrenia to markers within Xp11 near the MAOB gene.

A sex chromosome locus for psychosis has been considered on the basis of some sex differences in genetic risk and expression of illness, and an association with X-chromosome anomalies. Previous molecular genetic studies produced weak evidence for linkage of schizophrenia to the proximal short arm of the X-chromosome, while some other regions were not ruled out. Here we report an attempt to expand the Xp findings in: (i) a multicenter collaboration focusing on 92 families with a maternal pattern of inheritance (Study I), and (ii) an independent sample of 34 families unselected for parental mode of transmission (Study II). In the multicenter study, a parametric analysis resulted in positive lod scores (highest of 1.97 for dominant and 1.19 for recessive inheritance at a theta of 0.20) for locus DXS7, with scores below 0.50 for other markers in this region (MAOB, DXS228, and ARAF1). Significant allele sharing among affected sibling pairs was present at DXS7. In the second study, positive lod scores were observed at MAOB (highest of 2.16 at a theta of 0.05 for dominant and 1.64 at a theta of 0.00 for recessive models) and ALAS2 (the highest of 1.36 at a theta of 0.05 for a recessive model), with significant allele sharing (P = 0.003 and 0.01, respectively) at these two loci. These five markers are mapped within a small region of Xp11. Thus, although substantial regions of the X-chromosome have been investigated without evidence for linkage being found, a locus predisposing to schizophrenia in the proximal short arm of the X-chromosome is not excluded.

Chromosome Mapping↗
PubMed1997

Allelic variability in D21S11, but not in APP or APOE, is associated with cognitive decline in Down syndrome.

Genetic variation in the APOE gene and variation in chromosome 21 genotypes, including the APP locus, may influence age-associated cognitive decline in adults with Down syndrome. Molecular genetic and longitudinal neuropsychological analysis was performed for 41 unrelated Caucasian individuals (mean age 48.1 +/- 1.1 years (s.c.m.)) with free trisomy 21. Allele frequencies and genotype distributions were compared among subgroups with or without evidence of cognitive decline. Genetic variability at APOE and APP was not significantly associated with evidence of cognitive decline. However, aged individuals with Down syndrome, without evidence of cognitive decline, demonstrated unusual allelic variability at D21S11. These findings are discussed in the context of current hypotheses of Alzheimer-type dementia in Down syndrome and in the general population.

Adult↗
PubMed1997

Allelic functional variation of serotonin transporter expression is a susceptibility factor for late onset Alzheimer's disease.

We examined a deletion/insertion promoter polymorphism of the serotonin transporter gene, which confers an approximately 40% reduction in expression of the protein, in 196 subjects with late onset Alzheimer's disease (AD) and 271 controls. The frequency of the 484 bp low activity allele was elevated in the subjects with AD (p = 0.004), and an excess of the low activity genotype (30%) was also found in comparison with the controls (20%) (chi 2 = 7.16; p = 0.03). This association was unrelated to the age of the subjects or controls, or to epsilon 4 alleles of the ApoE gene. The odds ratio for the effect of the homozygous low activity genotype was 1.7 (95% CI 1.08-2.67), with a population attributable risk of 33% (95% CI 5-54%). These findings indicate that the low activity allele of the serotonin transporter is a risk factor for late onset AD.

Age of Onset↗