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Biomedical subjects

J M Walker

Publications and source records attributed to J M Walker.

At least 181 records · Page 10Linked to original sources
PubMed1989

Age-related differences in the sensitivity of rats to a selective sigma ligand.

Differences in sigma binding parameters and behavioral responses to injections of a selective sigma ligand were found in adult rats of different ages. Middle-aged rats (5-6 months old) had fewer sigma binding sites and sites with lower affinity for [3H]di-o-tolylguanidine than young adult animals (2-3 months old). The older animals also exhibited a decreased behavioral response to the selective sigma ligand, di-o-tolylguanidine (DTG). Unilateral microinjection of DTG into the substantia nigra of rats produced fewer net contralateral turns in middle-aged animals, compared to younger rats. Likewise, the postural changes produced by unilateral microinjection of DTG into the red nucleus were less pronounced in the older animals. These data suggest that changes in the number and affinity of sigma binding sites may affect movement and posture as an organism ages.

Aging↗
PubMed1989

Phosphorylation of protein kinase C by casein kinase-1.

Because phosphorylation of protein kinase C (PKC) may provide a mechanism for regulation of this enzyme, we have examined the ability of two other kinases to phosphorylate PKC. Our results show that casein kinase 1 (CK-1), but not casein kinase 2 (CK-2), can phosphorylate PKC in the absence of Ca2+ and phospholipids. The 32P incorporation into PKC in the presence of Ca2+ and phospholipids is also enhanced by CK-1.

Calcium↗
PubMed1989

Synthesis and evaluation of optically pure [3H]-(+)-pentazocine, a highly potent and selective radioligand for sigma receptors.

Tritium-labeled (+)-pentazocine ([3H]-1b) of specific activity 26.6 Ci/mmol was synthesized in 3 steps starting with (+)-normetazocine (2) of defined optical purity. [3H]-1b has been characterized as a highly selective ligand for labeling of sigma receptors. Competition data revealed that [3H]-1b could be displaced from guinea pig brain membrane preparations with a number of commonly used sigma receptor ligands. [3H]-1b exhibited saturable, enantioselective binding with a Kd of 5.13 +/- 0.97 nM and a Bmax of 1146 +/- 122 fmol/mg protein. Phencyclidine (PCP) displaced [3H]-1b with low affinity while MK-801 was inactive, thus indicating insignificant activity at the PCP-binding site; apomorphine failed to displace [3H]-1b indicating lack of dopamine receptor cross-reactivity. Since the affinity of [3H]-1b is about 6 times that of the two commonly employed sigma ligands ((+)-3-[3H]PPP and [3H]DTG) and since it is more selective for sigma receptors than the benzomorphan [3H]SKF-10,047, it represents the first example of a highly selective benzomorphan based sigma receptor ligand. [3H]-1b should prove useful for further study of the structure and function of sigma receptors.

Animals↗
PubMed1989

The diagnostic usefulness of isocitrate dehydrogenase (ICDH) in the marmoset (Callithrix jacchus).

Marmosets were given either a hepatotoxin, carbon tetrachloride, orally or an i.m. injection of a mytoxin, chlorpromazine. Although muscle damage alone caused small increases in the plasma levels of lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and isocitrate dehydrogenase (ICDH), only the isoenzyme analysis of ICDH can differentiate definitely between liver and muscle damage. Only very severe muscle damage can increase the plasma concentration of this enzyme but, in this case, the elevation of plasma creatinine kinase levels helps differentiation. It is recommended that the elevation of ICDH is the most specific indicator of hepatic damage in the marmoset.

Alanine Transaminase↗
PubMed1989

The histochemical location of three diagnostic enzymes in the marmoset liver.

The histochemical locations of alkaline phosphate (ALP), leucine aminopeptidase (LAP) and gamma glutamyltransferase (GGT) were demonstrated in the liver of the marmoset (Callithrix jacchus). Although all three enzymes were located in cell membranes, the location of LAP was demonstrated by a chromogenic substrate, in the canalicular membrane. GGT was seen in a vascular network, provisionally identified as the peribiliary arterial plexus. Possible diagnostic applications in toxicology are discussed.

Alkaline Phosphatase↗
PubMed1989

Motor effects of two sigma ligands mediated by nigrostriatal dopamine neurons.

(+)-Pentazocine, a potent sigma ligand that lacks affinity for PCP receptors, produced dose-dependent contralateral circling behavior following microinjections in the substantia nigra of rats. This effect was attenuated by 6-hydroxydopamine (6-OHDA) lesions of ascending dopamine neurons and enhanced by systemic injections of amphetamine, 6-OHDA lesions also attenuated the circling produced by another selective sigma ligand, 1,3-di-o-tolylguanidine (DTG). These findings suggest that sigma receptors are involved in the neural control of movement and the regulation of the ascending dopamine system. Since all typical antipsychotic drugs tested bind to sigma receptors with Ki values less than 1 microM, these findings further suggest that sigma receptors may mediate some of the motor side effects of antipsychotic drug therapy.

Amphetamines↗
PubMed1989

Activation of protein kinase C by short chain phospholipid micelles.

PKC (80 kDa) can be cleaved by limited proteolysis into distinct catalytic (50 kDa) and regulatory (32-35 kDa) fragments. After cleavage, the catalytic fragment is active in the absence of Ca2+, phospholipid, or DAG while the regulatory fragment is found associated with phospholipid and continues to bind phorbol esters in a Ca2(+)- and PS-dependent manner (28, 29). In the holoenzyme, the association of the regulatory domain with the membrane may be important to release the catalytic domain from inhibition by the regulatory domain. We have presented evidence indicating that effective membrane binding occurs through interaction with the hydrophobic and/or interfacial regions of the bilayer, and does not result from binding to individual phospholipids. In vivo and in vitro studies suggest that the binding event is carefully regulated. An important function of Ca2+ may be to modify the local structure of the membrane, and thus affect the ability of PKC to associate with it. For at least one of the isozymes, however, Ca2+ may also play an additional role at a site distant from the membrane, suggesting the possibility that the isozymes may be differentially regulated.

Animals↗
PubMed1989

Alterations in the stereochemistry of the kappa-selective opioid agonist U50,488 result in high-affinity sigma ligands.

The synthesis and in vitro sigma receptor activity of the two diastereomers of U50,488 [(+/-)-2], namely, (1R,2S)-(+)- cis-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacet ami de [(+)-1] and (1S,2R)-(-)-cis-3,4-dichloro- N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide [(-)-1], are described. (+)-1 and (-)-1 were synthesized from (+/-)-trans-N-methyl-2-aminocyclohexanol [(+/-)-3]. Pyridinium chlorochromate (PCC) oxidation of the N-t-Boc-protected derivative of (+/-)-3 afforded (+/-)-2-[N- [(tert-butyloxy)carbonyl]-N-methylamino]cyclohexanone [(+/-)-5]. The sequence of enamine formation with pyrrolidine, catalytic reduction, N-deprotection, and optical resolution afforded (1R,2S)-(-)-cis-2-pyrrolidinyl-N-methylcyclohexylamine [(-)-10] and (1S,2R)-(+)-cis-2-pyrrolidinyl-N-methylcyclohexylamine [(+)-10]. The optical purity (greater than 99.5%) of (-)-10 and (+)-10 was determined by HPLC analysis of the diastereomeric ureas formed by reaction with optically pure (R)-alpha-methylbenzyl isocyanate. The absolute configuration of (-)-10 and (+)-10 was determined by single-crystal X-ray diffractometry of the bis-(R)-mandelate salt. Condensation of optically pure (-)-10 and (+)-10 with 3,4-dichlorophenylacetic acid furnished (+)-1 and (-)-1, respectively. Compounds (+)-1, (-)-1, (-)-2, and (+)-2 were compared for their binding affinities at kappa opioid, sigma, D2-dopamine, and phencyclidine (PCP) receptors in competitive binding assays using [3H]bremazocine ([3H]BREM) or [3H]U69,593, [3H]-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [[3H]-(+)-3-PPP], or [3H]-1,3-di(o-tolyl)guanidine ([3H]DTG), [3H]-(-)-sulpiride [[3H]-(-)SULP], and [3H]-1- [1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP), respectively. In the systems examined, (-)-2 exhibited the highest affinity for kappa receptors, with a Ki of 44 +/- 8 nM. However, (-)-2 also showed moderate affinity for sigma receptors, with a Ki of 594 +/- 3 nM [[3H]-(+)-3-PPP]. The (1R,2R)-(+)-enantiomer, (+)-2, had low affinity for both kappa and sigma receptors, exhibiting Ki values of 1298 +/- 49 nM at kappa ([3H]BREM) and 1270 +/- 168 nM at sigma [[3H]-(+)-3-PPP]. In contrast, the chiral cis compounds (+)-1 and (-)-1 showed high affinity for sigma receptors and negligible affinity for kappa opioid receptors in the [3H]BREM assay. Compound (-)-1 exhibited a Ki of 81 +/- 13 nM at sigma receptors [[3H]-(+)-3-PPP] and 250 +/- 8 nM ([3H]DTG).(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Pelvic exercise and gait in hemiplegia.

The purpose of this study was to describe and compare the gait of 20 patients with hemiplegia secondary to cerebrovascular accident (CVA) before and after a treatment regimen of resisted pelvic motions. Ten women and 10 men were studied, with a mean age of 48 years and a mean duration post-CVA of two months. Nine subjects (45%) were right hemiplegic, and 11 subjects (55%) were left hemiplegic. Treatment consisted of four sets of five repetitions each of manually resisted pelvic anterior-elevation and posterior-depression movements on the involved side. An insole footswitch system, knee electrogoniometer, and force walking aid were used in gait analysis performed before treatment, immediately after treatment (posttest 1), and 30 minutes after treatment (posttest 2). Results showed significant overall improvement in gait in posttest 1 (p less than .005) compared with the pretest. This improvement, however, was not maintained in posttest 2. Ten patients improved overall in posttest 1; only 4 patients also showed improvement in posttest 2. The major improvements seen immediately after treatment were observed in stance stability and limb advancement in the involved limb. More research is needed to identify an optimum treatment with carry-over using this technique.

Adult↗
PubMed1989

The nursing management of pain in the community: a theoretical framework.

This paper is based upon a research project designed to investigate the nursing management of pain in the community. A theoretical framework is described which has been designed to encompass the complexities of different types of pain, individual differences in reaction to pain, and to identify key differences between patients who cope with pain and those who do not. The framework is based on a model of stress, the concept of controllability, and contemporary learning theory. It identifies a unique role for the nurse in pain management and will be used to direct a study into strategies which nurses can use to enhance the coping abilities and resources of elderly patients in the community with pain.

Adaptation, Psychological↗
PubMed1989

Permanent transvenous pacing after a Mustard procedure.

We report the case of a 20-year-old man born with transposition of the great vessels who underwent emergency balloon septostomy and subsequently a Mustard procedure. When aged 20 years, he had several syncopal attacks due to sinoatrial disease for which he was simply and successfully paced transvenously in VVI mode.

Adult↗
PubMed1988

Inhibition of rubral neurons by a specific ligand for sigma receptors.

1,3-Di-ortho-tolylguanidine (DTG), a compound with marked selectivity for sigma receptors was iontophoretically applied to neurons in the red nucleus and nearby mesencephalic reticular formation. Spontaneous firing of rubral neurons was reduced by DTG in most cases. However, in the reticular formation, less than half of the cells tested showed inhibition; the remaining cells showed either an increase in rate or no consistent response to DTG. This corresponds to the greater density of sigma receptors in the red nucleus and supports previous work which suggests that sigma receptors play a role in the regulation of movement and posture.

Action Potentials↗