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Biomedical subjects

A Beasley

Publications and source records attributed to A Beasley.

18 recordsLinked to original sources
PubMed2006

Severe persistent sciatic pain and weakness due to a gluteal artery pseudoaneurysm as a complication of bone marrow biopsy.

Complications of bone marrow trephine are thought to be uncommon. Herein, we present a case of severe debilitating sciatic nerve palsy secondary to a gluteal artery pseudoaneurysm following bone marrow biopsy. The pseudoaneurysm was treated successfully by percutaneous embolization; however, the patient remains significantly impaired with persistent painless foot drop.

Aneurysm, False↗
PubMed2002

Structure and function of the gnathosoma of the mange mite, Psoroptes ovis.

Mites of the genus Psoroptes (Acari: Psoroptidae) are obligate, non-burrowing, astigmatid ectoparasites of mammals. A detailed understanding of the morphology of the gnathosoma is an important step towards elucidation of the feeding behaviour of this mite and, hence, the pathology of psoroptic mange. Scanning and transmission electron microscopy were used to examine Psoroptes ovis (Hering) (syn. P. cuniculi). The gnathosoma is composed of an infracapitulum (hypostome), which forms the floor of an extended U-shaped pre-oral trough, bounded by laterally compressed palps and enclosing paired chelicerae. Distally, each palp terminates in a flap-like process and four tapered terminal sensillae. The floor of the infracapitulum is interrupted along its length by a dorsally projecting ridge. At the distal end of the infracapitulum are paired, grooved pseudorutellae and, between them, paired, ungrooved lateral lips. Between the lateral lips is a grooved, elongate labium. Medially, a pair of finger-like projections emanates from the paraxial walls of the palps and project anteriorly. Each chelicera is made up of fixed and mobile digits, with a cheliceral membranous fold articulating the two. The distal ends of both digits are chelated. For much of its length, the mobile cheliceral digit appears to lie within a fold formed by the infracapitular ridge, thereby creating a central channel between the chelicerae. It is suggested that this arrangement of elements may facilitate a two-way flow of liquid, where saliva flows down a central salivary canal and spills out onto the host's skin over the labium at the point where the chelated tips of the chelicerae meet and abrade the skin. Liquid food may move along the grooves of the pseudorutellae and then be sucked up a food canal formed by the paraxial walls of the palps and the outer wall of the chelicerae.

Animals↗
PubMed2002

Non-neoplastic demyelinating process mimicking a disseminated malignant brain tumour.

Non-neoplastic demyelinating processes of the brain with ring enhancing lesions and mass effect on MRI imaging, mimicking malignant brain tumours, are rare phenomena. We document the case of a 32 year old male with clinical, radiological and initial histological findings, suggestive of a malignant brain tumour. Additional investigations confirmed the diagnosis of multiple sclerosis. This case is significant as the lesion could not be easily distinguished from a malignant brain tumour on imaging alone. Cases such as this illustrate the importance of considering a demyelinating process in the differential diagnosis of tumour-like brain lesions.

Astrocytoma↗
PubMed2001

Methylphenidate sensitization is modulated by valproate.

Repeated administration of the stimulant methylphenidate (MPD) produces sensitization to its own effects. Glutamate, dopamine, and GABA have been implicated in the underlying mechanism of sensitization to stimulants such as amphetamine and cocaine. We have investigated effects of the GABAergic agent sodium valproate (VAL) on the locomotor response to MPD. Activities of male Sprague-Dawley rats were continuously recorded by a computerized activity monitoring system for 15 days. We studied the dose effect of valproate 1) at 50, 100, and 200 mg/kg (i.p.) on motor activities, 2) on the acute response of motor activities to 2.5 mg/kg MPD, and 3) on behavioral sensitization to subsequent repeated injections of MPD. Valproate alone did not significantly affect motor activities. All three doses of valproate attenuated the acute locomotor effects of MPD, while only the 50 mg/kg dose blocked the development of sensitization to subsequent administration. Possible mechanisms involving substrates for the effect of GABA agonists on sensitization are discussed.

Animals↗
PubMed2000

Valproate prevents the induction of sensitization to methylphenidate (ritalin) in rats.

Repetitive exposure to methylphenidate (MPD) elicits sensitization to its locomotor effects. Drugs that affect the GABA system may modify adaptations to drug exposure. Therefore, we have examined the effect of sodium valproate, which enhances GABA function, on the development of sensitization to MPD using an automated, computerized animal activity monitoring system to record each rat's motor activities for 15 consecutive days. Rats were recorded before and after saline injection (Days 1-2) to provide baseline activity. Animals were then randomly assigned to the following three groups that received: (1) 2.5 mg/kg MPD (s.c.) for six consecutive days (Days 3-8), (2) a single dose of valproate (50 mg/kg; i.p.) 1 h prior to the first (Day 3) of six daily doses of MPD (2.5 mg/kg; s.c. ), or (3) five daily doses of valproate (50 mg/kg, i.p.) 1 h prior to MPD (2.5 mg/kg, s.c.) on Days 4-8. There was no drug treatment during the next 5 days (Days 9-13). All rats were then re-challenged with MPD (2.5 mg/kg, s.c.) on Day 14. Group 2 rats were also re-challenged with 50 mg/kg valproate followed by 2.5 mg/kg MPD 1 h later on Day 15. Administration of MPD alone produced a sensitized response. Multiple valproate injections prevented the induction of MPD-elicited sensitization in all four motor indices, while a single valproate injection prevented the induction of MPD-elicited sensitization in two of four motor indices studied. In conclusion, a single injection 50 mg/kg valproate given prior to any MPD treatment partially blocked the induction of MPD sensitization while repeated injections of valproate co-administered with MPD treatment completely prevented this effect.

Animals↗
PubMed2000

Valproate modulates the expression of methylphenidate (ritalin) sensitization.

Repeated administration of amphetamine, cocaine, and methylphenidate (MPD) has been reported to elicit behavioral sensitization to their locomotor and stereotypic effects in rodents. GABAergic drugs have been shown to inhibit behavioral effects of stimulants. The objective of the present study was to determine whether single or multiple administration of sodium valproate, a GABA agonist, would prevent the expression of sensitization to the locomotor effect of MPD once it has developed. Twenty-eight male Sprague-Dawley rats were randomized into three treatment groups: a control group received only 2.5 mg/kg MPD during the 14-day cycle, a group received a single 50 mg/kg valproate injection on Day 9, and a group received multiple 50 mg/kg valproate injection on Days 9-13. Rats were housed in test cages and behavioral activities were recorded for 14 consecutive days. All injections were given between 12:00 h and 14:00 h. Multiple injection of MPD elicited sensitization to its locomotor and stereotypic effects. Single administration of valproate did not block the expression of sensitization in the four locomotor indices measured. However, multiple administration of valproate prevented MPD sensitization to horizontal activity, total distance and number of stereotypic movements.

Animals↗
PubMed2000

Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities.

In addition to its cGMP-selective catalytic site, cGMP-binding cGMP-specific phosphodiesterase (PDE5) contains two allosteric cGMP-binding sites and at least one phosphorylation site (Ser92) on each subunit [Thomas, M.K., Francis, S.H. & Corbin, J.D. (1990) J. Biol. Chem. 265, 14971-14978]. In the present study, prior incubation of recombinant bovine PDE5 with a phosphorylation reaction mixture [cGMP-dependent protein kinase (PKG) or catalytic subunit of cAMP-dependent protein kinase (PKA), MgATP, cGMP, 3-isobutyl-1-methylxanthine], shown earlier to produce Ser92 phosphorylation, caused a 50-70% increase in enzyme activity and also increased the affinity of cGMP binding to the allosteric cGMP-binding sites. Both effects were associated with increases in its phosphate content up to 0.6 mol per PDE5 subunit. Omission of any one of the preincubation components caused loss of stimulation of catalytic activity. Addition of the phosphorylation reaction mixture to a crude bovine lung extract, which contains PDE5, also produced a significant increase in cGMP PDE catalytic activity. The increase in recombinant PDE5 catalytic activity brought about by phosphorylation was time-dependent and was obtained with 0.2-0.5 microM PKG subunit, which is approximately the cellular level of this enzyme in vascular smooth muscle. Significantly greater stimulation was observed using cGMP substrate concentrations below the Km value for PDE5, although stimulation was also seen at high cGMP concentrations. Considerably higher concentration of the catalytic subunit of PKA than of PKG was required for activation. There was no detectable difference between phosphorylated and unphosphorylated PDE5 in median inhibitory concentration for the PDE5 inhibitors, sildenafil, or zaprinast 3-isobutyl-1-methylxanthine. Phosphorylation reduced the cGMP concentration required for half-maximum binding to the allosteric cGMP-binding sites from 0.13 to 0.03 microM. The mechanism by which phosphorylation of PDE5 by PKG could be involved in physiological negative-feedback regulation of cGMP levels is discussed.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

Expression of an active, monomeric catalytic domain of the cGMP-binding cGMP-specific phosphodiesterase (PDE5).

Phosphodiesterases (PDEs) comprise a superfamily of phosphohydrolases that degrade 3',5'-cyclic nucleotides. All known mammalian PDEs are dimeric, but the functional significance of dimerization is unknown. A deletion mutant of cGMP-binding cGMP-specific PDE (PDE5), encoding the 357 carboxyl-terminal amino acids including the catalytic domain, has been generated, expressed, and purified. The K(m) of the catalytic fragment for cGMP (5.5 +/- 0. 51 microM) compares well with those of the native bovine lung PDE5 (5.6 microM) and full-length wild type recombinant PDE5 (2 +/- 0.4 microM). The catalytic fragment and full-length PDE5 have similar IC(50) values for the inhibitors 3-isobutyl-1-methylxanthine (20 microM) and sildenafil (Viagra(TM))(4 nM). Based on measured values for Stokes radius (29 A) and sedimentation coefficient (2.9 S), the PDE5 catalytic fragment has a calculated molecular mass of 35 kDa, which agrees well with that predicted by amino acid content (43.3 kDa) and with that estimated using SDS-polyacrylamide gel electrophoresis (39 kDa). The combined data indicate that the recombinant PDE5 catalytic fragment is monomeric, and retains the essential catalytic features of the dimeric, full-length enzyme. Therefore, the catalytic activity of PDE5 holoenzyme requires neither interaction between the catalytic and regulatory domains nor interactions between subunits of the dimer.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Ligand-induced conformational changes in cyclic nucleotide phosphodiesterases and cyclic nucleotide-dependent protein kinases.

Three methods have been used to assess the conformational effects associated with ligand binding to two unrelated cyclic nucleotide receptor proteins: the cGMP-binding, cGMP-specific phosphodiesterase (cGB-PDE or PDE5A) and the cGMP-dependent protein kinase (PKG). The methods should be applicable to other proteins and to other types of modification such as phosphorylation. The procedures use either ion-exchange chromatography, size-exclusion chromatography, or native gel electrophoresis of these proteins in the absence and presence of regulatory ligands. Measurements from these respective approaches allow documentation of changes in the quaternary structure, surface electronegativity, and relative compactness (Stokes radius) of the protein molecule. The combined data allow the changes in protein conformation to be quantitated in terms of alterations in the axial ratio or length/width dimension of the molecule. The methods can be applied to partially purified proteins and to proteins that are available in limited quantities. Conformational changes due to stable modifications of proteins can be potentially examined in crude extracts of intact cells. Each of the methods can be tailored to optimize resolution of a particular protein under a variety of conditions. Activity measurements, Coomassie brilliant blue or silver staining of gels, radioautography, or Western blot analysis can be used for detection of the protein.

1-Methyl-3-isobutylxanthine↗
PubMed1998

A photoaffinity probe covalently modifies the catalytic site of the cGMP-binding cGMP-specific phosphodiesterase (PDE-5).

The cGMP-binding cGMP-specific phosphodiesterase (PDE-5) contains distinct catalytic and allosteric binding sites, and each is cGMP-specific. Cyclic nucleotide phosphodiesterase inhibitors, such as 3-isobutyl-1-methylxanthine (IBMX), are believed to compete with cyclic nucleotides at the catalytic sites of these enzymes, but the portion of PDE-5 that accounts for interaction of either of these inhibitors of the substrates themselves with the catalytic domain of the enzymes has not been identified. IBMX was derivatized to yield the photoaffinity probe 8([3-125I,-4-azido]-benzyl)-IBMX, which is referred to as 8(125IAB)-IBMX. This probe was incubated with partially purified recombinant bovine PDE-5. After UV irradiation and SDS-PAGE, a single radiolabeled band that coincided with the position of PDE-5 was visualized on the gel, and the photoaffinity labeling of PDE-5 was linear with increasing concentration of the 8(125IAB)-IBMX. Prominent Coomassie blue-stained bands other than PDE-5 were not labeled significantly. The photoaffinity labeling was progressively blocked by cGMP at concentrations higher than 10 microM, whereas cAMP or 5'-GMP exhibited only weak inhibitory effects. Other compounds that are believed to interact with the PDE-5 catalytic site, including IBMX, cIMP, and beta-phenyl-1,N2-etheno-cGMP (PET-cGMP), also inhibited the photoaffinity labeling in a concentration-dependent manner. The IC50 of PET-cGMP for inhibition of photoaffinity labeling was 10 microM, which compared favorably with an IC50 of 5 microM for inhibition of PDE-5 catalytic activity by this compound. It is concluded that the interaction of this photoaffinity probe with PDE-5 is highly specific for the catalytic site over the allosteric binding sites of PDE-5 and could prove useful in studies to map the catalytic site of PDE-5.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Breastfeeding studies: culture, biomedicine, and methodology.

The research and literature focusing on aspects of human lactation and infant feeding are dominated by a biomedical orientation. This paper posits that such a manner of delimiting the data to be acquired and analysed represents a peculiarly Western mode of thought. An overview and classification of the types of cultural studies on human lactation and infant feeding confirms the domination of a biomedical approach to the subject and allows the identification of areas which have received little attention. Thus many English language cultural studies of breastfeeding by employing this same methodology against different cultural backdrops offer little or no fresh knowledge or insight into that culture's view of breastfeeding.

Attitude to Health↗
PubMed1977

Altering student responses through changes in teacher verbal behavior.

Two experiments were conducted in a junior-high special-education class of eight pupils in an inner-city school. In the first experiment, the teacher doubled the number of words used by the pupils in answering questions by altering the type of questions asked. In the second experiment, the number of words used by students and the percentage of answers given in complete sentences, increased from less than 5% to approximately 90% when the teacher instructed the pupils to answer in complete sentences and asked another pupil to answer using a sentence if the first one did not do so. In both experiments, a brief return to baseline conditions brought a return to low levels of verbal responding. An analysis of which pupils were called on by the teacher, teacher praise, and in the second experiment the types of questions asked, indicated that these variables were not responsible for the increases in verbal responding.

Journal Article↗
PubMedDate not supplied

High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients.

The physiological role of phosphodiesterase (PDE)11 is unknown and its biochemical characteristics are poorly understood. We have expressed human His-tagged PDE11A4 and purified the enzyme to apparent homogeneity. PDE11A4 displays K(m) values of 0.97 microM for cGMP and 2.4 microM for cAMP, and maximal velocities were 4- to 10-fold higher for cAMP than for cGMP. Given the homology between PDE11 and PDE5, we have compared the biochemical potencies of tadalafil (Cialis, Lilly-ICOS), vardenafil (Levitra, Bayer-GSK), and sildenafil (Viagra, Pfizer Inc.) for PDE11A4 and PDE5A1. PDE5A1/PDE11A4 selectivities are 40-, 9300-, and 1000-fold for tadalafil, vardenafil, and sildenafil, respectively. This suggests that none of these three compounds is likely to crossreact with PDE11A4 in patients.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

A comparison of injectable anesthetic combinations in horses.

Six combinations of injectable anesthetic agents were administered to six adult horses in a Latin square design. The drug combinations were xylazine-ketamine, xylazine-butorphanol-ketamine, xylazine-tiletamine-zolazepam, xylazine-butorphanol-tiletamine-zolazepam, detomidine-ketamine, and detomidine-butorphanol-ketamine. Measured variables were heart rate, respiratory rate, systolic blood pressure, arterial pH (pHa), PaCO2, PaO2, recumbency time, and number of attempts necessary to stand. Quality of induction and recovery, muscle relaxation, and response to stimulus were evaluated subjectively. The horses required significantly more attempts to stand after administration of xylazine-tiletamine-zolazepam, xylazine-butorphanol-tiletamine-zolazepam, and detomidine-ketamine than after xylazine-ketamine, xylazine-butorphanol-ketamine, or detomidine-butorphanol-ketamine. Mean recumbency times varied from 23.0 minutes with xylazine-ketamine to 41.3 minutes with xylazine-butorphanol-tiletamine-zolazepam. There were significant differences in mean heart rates at minute 15, mean respiratory rates at minutes 5, 10 and 15, and mean systolic blood pressures at minute 10 of anesthesia. There were no significant differences in pHa, PaCO2 or PaO2.

Acid-Base Equilibrium↗