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Biomedical subjects

J M Wright

Publications and source records attributed to J M Wright.

At least 127 records · Page 7Linked to original sources

Conservation of a satellite DNA sequence (SATB) in the tilapiine and haplochromine genome (Pisces: Cichlidae).

We have cloned and sequenced a 1900-bp EcoRI fragment (SATB) from the tilapiine fish Oreochromis niloticus. The SATB sequence is highly reiterated in the tilapiine genome and organized in long tandem arrays. A 760-bp HindIII fragment, an internal component of SATB, has also been cloned and sequenced from the related tilapiine species Oreochromis hornorum. Hybridization of the radiolabelled 760-bp HindIII repeat detected the presence of the SATB repeat in the genomes of several tilapiine species as well as the haplochromine species Haplochromis (Protomelas) similis. The 760-bp HindIII fragment did not hybridize to genomic DNA of Etroplus maculatus (an Asian cichlid) or to that of Cichlasoma meeki (a South American cichlid). The SATB repeat sequence is 56% AT and constitutes 0.2-5% of the tilapiine genome depending on the species examined. Four imperfect 21-bp direct repeat sequences are present within the cloned 1900-bp EcoRI repeat. Alignment of the four direct repeats from the O. niloticus cloned 1900-bp DNA and the two homologous direct repeats from the O. hornorum 760-bp HindIII repeat revealed a core motif of 11 bp that exhibits 100% sequence identity between all of the direct repeats. The conservation of this motif in the SATB repeat suggests that this sequence may be under selective constraint.

Animals↗

Nucleotide sequence and evolutionary conservation of a minisatellite variable number tandem repeat cloned from Atlantic salmon, Salmo salar.

We describe the nucleotide sequence, extent of polymorphism, and evolutionary conservation of a minisatellite cloned from a fish, Atlantic salmon (Salmo salar). The Ssal minisatellite contains a 16-bp repeat exhibiting partial sequence identity to bird and mammal minisatellites but most closely resembling an insect minisatellite (81% sequence identity). The Ssal locus exhibits a minimum of three to seven alleles per population in three eastern North American salmon populations. A probe based on the nonrepetitive 5' flank of Ssal detected a polymorphic locus in a variety of salmoid species, suggesting that this locus has persisted in its polymorphic state for > 25 million years. Multiple polymorphic bands detected by the same probe suggest the presence in salmonid genomes of additional minisatellite loci that are related to Ssal either through the tetraploidization of the salmonid genome or some other mechanism of gene duplication.

Alleles↗

Pregnancy-specific protein B in serum of postpartum beef cows.

To determine whether the uterus was the source of serum pregnancy-specific protein B (PSPB) after calving, five beef cows were hysterectomized at 21 d postpartum and five served as intact controls. A single blood sample was taken from all cows immediately after calving and then twice weekly until 21 d postpartum. Beginning on d 22, blood samples were taken from all cows at 3-h intervals for 4 d and then twice weekly until 53 d postpartum. When the half-life calculated for the interval from d 1 to 21 was used as a covariate, the adjusted d-22 to -53 half-lives were 8.4 d for control cows vs 7.3 d for hysterectomized cows (P = .044). Data show that PSPB has a long half-life in the circulation and that the uterus is a minimal, if any, source of postpartum circulating PSPB. In another experiment, PSPB was measured weekly after calving in serum of 58 Polled Hereford and Simmental cows. Cows were exposed to fertile bulls and allowed to mate at every estrus. Observations were made for estrus, and progesterone concentrations in serum were measured to estimate the time of ovulations. Levels of PSPB were highest at approximately the time of calving, then decreased rapidly. Concentrations of PSPB were < 1 ng/mL by 80 d in eight cows that had not conceived since calving. Two cows eventually had nondetectable PSPB levels, one by 86 d and the other by 96 d after calving.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ethanol action on excitatory amino acid activated ion channels.

The effects of ethanol on excitatory amino acid activated ion channels were investigated using patch-clamp recording methods. Intoxicating concentrations of ethanol (5-50 mM) inhibited ion current activated by the glutamate receptor agonist N-methyl-D-aspartate (NMDA) in a concentration-dependent manner (IC50 = 30 mM). The intoxicating potency of different alcohols was correlated with their potency for inhibiting NMDA-activated current, suggesting that alcohol-induced inhibition of NMDA channel function may contribute to the neural and cognitive impairments associated with intoxication. Analysis of mechanism suggests that ethanol inhibits NMDA-activated current by altering gating of the channel, rather than by affecting channel conductance, ion permeance or regulatory sites on the channel. Anesthetic concentrations of ethanol (> 50 mM) produced a concentration-dependent inhibition of kainate- and quisqualate-activated currents (IC50 = 220 mM), suggesting that this inhibition may contribute to the general anesthetic effects of ethanol. This hypothesis is supported by the observations that the general anesthetic agents, trichloroethanol (the active metabolite of chloral hydrate), pentobarbital and halothane, all inhibit kainate- and quisqualate-activated currents.

Animals↗

Chromosomal proteins of Physarum polycephalum with preferential affinity for the sequence, poly d(A-T).poly d(A-T).

We have identified two novel chromosomal proteins from Physarum polycephalum using a protein blotting DNA-binding assay. A fraction of these proteins was readily released from nuclei by solutions of moderate ionic strength (0.15 N-0.35 M NaCl) or mild nuclease treatment and appear associated with chromatin that is nucleosome-free. A significant proportion of these proteins, however, was not released from nuclei by solutions of high ionic strength (1.6 M NaCl) or treatment with excess nuclease. These results suggest that these chromosomal proteins are distributed between transcriptionally-competent and inert domains of chromatin. Both proteins preferentially and tenaciously bound duplex DNA, especially to the alternating B-DNA conformation displayed by the synthetic sequence, poly d(A-T).poly d(A-T).

Animals↗

A review and critical analysis of treatment research related to articulation and phonological disorders.

This article contains a summary of aspects of research designs and strategies found in 63 published reports in which the effectiveness of treatment of articulation or phonological disorders was evaluated. These research reports were published in four nationally refereed journals that contained most of the literature published in the decades of the 1970s and 1980s. A total of 91 items were evaluated in each report by two reviewers working independently, including types of research designs, details about subjects, sampling, and types of independent and dependent variables used by researchers. Comparisons were made within each decade and across both decades to identify strengths and limitations. Some significant differences in research designs and variables under investigation occurred between the decades. A critical analysis was performed, and suggestions for changes are discussed.

Articulation Disorders↗

Oral presentation of pemphigus vulgaris and its response to systemic steroid therapy.

This article reviews our experience during a 20-year period with patients with oral lesions of pemphigus vulgaris. Of the 30 patients, 20 were women and 10 were men, with an age range of 24 to 68 years. The soft palate was involved in 80% of cases at initial presentation. Direct immunofluorescence studies were positive for IgG in the intercellular region in all cases where lesional tissue was histologically studied. Systemic steroid therapy alone controlled the disease in 24 patients, one patient was given no treatment, and the remaining five required additional treatment with either azathioprine, cyclophosphamide, or gold. Steroid therapy was continued in the long-term at a reduced dose, but side effects such as diabetes mellitus, hypertension, and duodenal ulcers were observed. Long-term steroid therapy is therefore the treatment of choice for the oral lesions of pemphigus vulgaris, but in some cases alternative treatment options may be required.

Adult↗

Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg(2+)-free solutions.

Many single-channel studies rely on the assumption that the channels are functioning under steady-state conditions. In examining the basis for nonlinear whole-cell current-voltage curves in Mg(2+)-free solutions we discovered that N-methyl-D-aspartate (NMDA) channels in excised patches reversibly shifted their open-state probability (Po) in a voltage-dependent way, exhibiting approximately 3- to 4-fold greater Po at positive potentials than at rest. Changes in Po were mainly attributable to shifts in frequency of channel opening. Po changed remarkably slowly (2-15 min), explaining the hysteresis of whole-cell current-voltage curves obtained in nonequilibrium conditions. The slow increase in Po provides a mechanism by which NMDA channels can substantially increase Ca2+ influx in cells depolarized for prolonged periods of time and may play a role in excitotoxicity.

Animals↗

Inhibition of hamster buccal pouch carcinogenesis by limonin 17-beta-D-glucopyranoside.

Limonin 17-beta-D-glucopyranoside, nomilin 17-beta-D-glucopyranoside, and nomilinic acid 17-beta-D-glucopyranoside, three limonoid glucosides isolated from oranges, were tested for cancer chemopreventive activity. Eighty female Syrian hamsters were divided into four equal groups. The left buccal pouches of the animals in each group were pretreated topically with two applications of water (Group I) or a 3.5% solution of limonin 17-beta-D-glucopyranoside (Group II), nomilin 17-beta-D-glucopyranoside (Group III), or nomilinic acid 17-beta-D-glucopyranoside (Group IV). After this initial treatment, the left buccal pouches of 16 hamsters from each group were painted five times per week. Two or three times per week the pouches were treated with a 0.5% solution of the carcinogen 7,12-di-methylbenz[a]anthracene (DMBA) dissolved in mineral oil. On alternate days, the pouches were treated with water (Group I) or a 3.5% solution of limonin 17-beta-D-glucopyranoside (Group II), nomilin 17-beta-D-glucopyranoside, or nomilinic acid 17-beta-D-glucopyranoside. The 16 remaining animals were used as controls. These hamsters were treated five times per week, one day with mineral oil and the next with either water (Group I) or one of the 3.5% solutions of the limonoid glucosides (Groups II-IV). After 15 weeks (71 applications), the hamsters were killed. Multiple tumors were common in the animals treated with DMBA; however, the animals treated with limonin 17-beta-D-glucopyranoside exhibited a 55% decrease in average tumor burden. Further comparisons between Groups I and II showed that this reduction in tumor burden was mainly due to a decrease in tumor mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Genetic variability in a family of satellite DNAs from tilapia (Pisces: Cichlidae).

We have cloned and sequenced members of a family of satellite DNAs from three genera of the tilapiine tribe of fishes: Oreochromis, Sarotherodon, and Tilapia. The satellite DNAs, visualized as intensely staining bands following electrophoretic separation of EcoRI-digested genomic DNA, consist of three size variants differentially distributed in the various tilapiine species. The sizes of the monomers are approximately 237 bp (type I), 230 bp (type II), and 209 bp (type III). Several cloned monomers were sequenced from Oreochromis niloticus (type III), Oreochromis placidus (types I and II), Sarotherodon galilaeus (type I), Tilapia zillii (type I), and Tilapia rendalli (type I). Comparison of derived consensus sequences for the monomer units of the satellite DNAs revealed sequence identities within and between species that ranged from 89 to 96%. The type II and type III size variants appear to have arisen by deletions of 9 and 29 bp, respectively, within different regions of the type I satellite. Hybridization of a cloned monomer satellite from O. niloticus (type III) to PalI digests of genomic DNA from all three genera detected polymorphic, high molecular weight restriction fragments that produced fingerprint-like patterns. The complexity of these DNA fingerprints varied from one species to another, suggesting a markedly different genomic organization for these polymorphic satellite DNAs.

Animals↗

Effects of low doses of bicuculline on N-methyl-D-aspartate single-channel kinetics are not evident in whole-cell currents.

Bicuculline methiodide (BIC-Mel) (10-100 microM) altered the kinetics of N-methyl-D-aspartate (NMDA) responses in single-channel and whole-cell recordings. The principal effect of BIC-Mel (10-100 microM) on NMDA channels was a dose-dependent decrease in mean channel open time (tau o), accompanied by the introduction of a new closed time (tau B) of 14.0 +/- 3.5 msec (mean +/- standard deviation; n = 14) in closed time distributions, which was independent of BIC-Mel concentration. BIC-Mel (10-100 microM) increased the frequency of NMDA channel opening in a dose-dependent manner, offsetting the decrease in tau o, such that the total time spent in the open state per minute was unchanged, and thus the total charge/min through NMDA channels was unchanged. Similarly, the amplitudes of NMDA whole-cell current responses were not noticeably affected by 10-80 microM BIC-Mel, even though power spectra density analysis of the whole-cell NMDA-stimulated noise revealed changes in the underlying channel kinetics in the presence of BIC-Mel. Taken together, the effects of 10-80 microM BIC-Mel on NMDA responses were consistent with the predictions of the sequential block model; however, the effects of BIC-Mel exhibited no obvious voltage dependence. In addition to the low-dose effects of BIC-Mel, 100 and 200 microM BIC-Mel inhibited whole-cell NMDA responses. The inhibition by 100 microM BIC-Mel was not large, but it was augmented from 15% to 30% by increasing the NMDA concentration from 10 microM NMDA to 20 microM NMDA, indicating that channel activation was necessary for BIC-Mel-mediated inhibition. Preliminary single-channel experiments performed under conditions conducive to trapping of an open channel blocker at its binding site indicated that the effect of BIC-Mel on tau o persisted after the removal of the blocker, consistent with use dependence of the dissociation of BIC-Mel from the NMDA receptor-channel complex.

Animals↗

Immunologically-related nucleic acid-binding proteins associated with the nuclear matrix of Physarum polycephalum.

The nuclear matrix of Physarum polycephalum is composed of two abundant polypeptides of 27 and 38 kDa as well as numerous minor polypeptides of various molecular weight. By contrast, the nuclear matrix of vertebrates consists of three major (the lamins) and many minor polypeptides mainly in the 60-70 kDa molecular weight range. In order to better characterize the major nuclear matrix proteins of P. polycephalum and, perhaps, define their relationship with the major nuclear matrix proteins of vertebrates, we have purified the abundant nuclear matrix proteins of P. polycephalum. In Western blot analyses, polyclonal antibodies raised against the purified 27 kDa polypeptide recognised polypeptides of 50 kDa, 45 kDa and several low molecular weight species (14-21 kDa) in the P. polycephalum nuclear matrix. The polyclonal antibodies did not react with the other abundant nuclear matrix protein of 38 kDa from P. polycephalum nor with polypeptides of the mouse nuclear matrix. Two-dimensional gel electrophoresis showed that the major nuclear matrix proteins of P. polycephalum were more basic than the major nuclear matrix proteins of vertebrates, the lamins. Moreover, both the 27 and 38 kDa polypeptides are post-translationally modified by either D-mannosyl or D-glycosyl moieties, and not by phosphorylation as has been demonstrated for the vertebrate lamins. DNA-binding assays further revealed that the immunologically related polypeptides of 50 kDa, 45 kDa, 27 kDa and low molecular weight species of 14-21 kDa preferentially bound single-stranded DNA, but the 38 kDa polypeptide of Physarum matrix did not. Based on these findings, we conclude that the abundant nuclear matrix protein of 27 kDa belongs to a group of immunologically-related nucleic acid-binding proteins, and is immunologically and functionally distinct from the other major nuclear matrix protein of 38 kDa from P. polycephalum and the vertebrate lamins.

Autoradiography↗

Kahweol and cafestol: inhibitors of hamster buccal pouch carcinogenesis.

Kahweol and cafestol, two compounds extracted from green coffee beans, were tested for cancer chemopreventive activity. For the experiment, 60 hamsters were divided into three equal groups and placed on one of three diets. The animals in Group I received a normal diet, whereas the animals in Groups II and III received the same diet supplemented with a 50:50 mixture of kahweol and cafestol. The content of the kahweol and cafestol mixture in these two diets was 0.2 g/kg of food (Group II) and 2.0 g/kg of food (Group III). After the hamsters adjusted to their respective diets, 16 hamsters from each group were selected. The left buccal pouches of these animals were painted three times weekly with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil. The 12 remaining hamsters were used as controls. The left buccal pouches of these animals were painted three times weekly with mineral oil. After 13 weeks (39 applications) the hamsters were killed. Multiple tumors were common in animals treated with DMBA; however, the animals receiving kahweol and cafestol in the diet (2 g/kg of food) exhibited a 35% reduction in tumor burden. Further comparisons between Groups I and III showed that this reduction in tumor burden was due to a decrease in tumor number. The results for Group II were inconclusive. Some reduction in tumor number was found, but this was offset by an increase in the size of the tumors.

Animals↗

Once- vs. twice-daily nitrendipine in the treatment of mild to moderate hypertension, Canadian Nitrendipine Study Group.

Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life of 17-21 h, allowing once-daily (o.d.) instead of currently twice-daily (b.i.d.) dosing. To determine the effectiveness of nitrendipine given o.d. vs. b.i.d., 78 hypertensive patients, [supine diastolic blood pressure (DBP) of 95-114 mm Hg] were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 10 mg b.i.d. (n = 39) or nitrendipine 20 mg o.d. (n = 39) after a 2-week placebo baseline period. Blood pressures (BPs) were measured in the morning at the end of the dosing interval. Mean +/- SD reduction in supine systolic BP (SBP) and DBP in patients evaluable for efficacy (greater than or equal to 14 days treatment) were 7.2 +/- 16.5 and 7.7 +/- 10.3 mm Hg, respectively, after nitrendipine b.i.d. (n = 38) and 9.4 +/- 15.1 and 9.5 +/- 7.0 mm Hg, respectively, after nitrendipine o.d. (n = 36). Similar falls in BP were found for both regimens in patients completing the full 12 weeks of treatment period (n: o.d. = 28, b.i.d. = 32). Discontinuation due to adverse experiences (AEs) occurred in three patients on b.i.d. and eight patients on o.d., the latter mostly in the first 2 weeks of therapy. Overall, AEs were higher in the o.d. group (% AEs at least possibly related to study medication: o.d. = 44%, b.i.d. = 33%). Most frequent AEs were headache and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Inhibition of the metabolism of paracetamol by isoniazid.

1. The effect of isoniazid given daily for 7 days on paracetamol (acetaminophen) kinetics and metabolism was studied in 10 healthy volunteers. Paracetamol, 500 mg, was given before isoniazid, on day 7 of isoniazid administration, and 2 days after the last dose of isoniazid. 2. On day 7, isoniazid markedly inhibited the formation clearance of the glutathione and catechol metabolites by 69.7% and 62.2%, respectively. Total paracetamol clearance was lowered by 15.2%. There was no effect of isoniazid on the non-oxidative pathways of paracetamol elimination. 3. Two days after isoniazid was discontinued, paracetamol metabolism had returned to pre-isoniazid values.

Acetaminophen↗