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Biomedical subjects

J M Walker

Publications and source records attributed to J M Walker.

At least 199 records · Page 11Linked to original sources
PubMed1988

Activation of protein kinase C by short chain phosphatidylcholines.

The acidic phospholipid requirement for protein kinase C (Ca2+/phospholipid-dependent enzyme) activation has been well established, although the molecular nature of this lipid-protein interaction is unclear. The additional requirement for Ca2+ has provided the basis for several models involving charge interactions. We now report that short chain neutral phosphatidylcholines also activate the kinase. Examination of a large series of phosphatidylcholines of varying acyl chain length revealed a close correlation between the ability to form micelles and the ability to support kinase activity. Peak activation occurred in the concentration range just before the critical micelle concentration of each phospholipid. Activation was absolutely dependent on the presence of Ca2+ and diacylglycerol. The possible roles of Ca2+ and phospholipid in the activation process are reexamined in light of these unexpected results.

Animals↗
PubMed1988

Correlations between body temperatures, metabolic rate and slow wave sleep in humans.

Amounts of slow wave sleep (SWS) in men exposed to either thermoneutral (29 degrees C) or cool (21 degrees C) ambient temperatures were positively correlated with tympanic and rectal temperatures at SWS onset. Decreases in each temperature measure between sleep onset and the nightly termination of SWS were negatively correlated with oxygen consumption during SWS.

Adult↗
PubMed1988

Dopamine-independent motor behavior following microinjection of rimorphin in the substantia nigra.

The motor-activating effects of rimorphin, an opioid peptide derived from prodynorphin, were examined in the substantia nigra pars reticulata of rats. Unilateral microinjections of rimorphin produced dose-dependent contralateral rotational behavior that was antagonized by naloxone, suggesting that these effects were mediated by opiate receptors. Lesions of midbrain dopamine cells with 6-hydroxydopamine (6-OHDA) produced a 95% or greater depletion of tyrosine hydroxylase in the striatum ipsilateral to the lesion, but failed to reduce the number of circles made by the rats. In addition to an overall preservation of rimorphin-induced circling in animals with 6-OHDA lesions, 50% of these rats exhibited circling that was at least 2 standard deviations above the mean of animals without lesions. The motor activating effects of rimorphin, thus, appear to occur independently of the nigrostriatal dopamine system; these effects may instead be mediated by GABAergic efferents in the pars reticulata.

Animals↗
PubMed1988

Phorbol esters increase adenylate cyclase activity and stability in pituitary membranes.

In this report, we demonstrate that calcium and phorbol esters enhance cAMP production in GH4C1 cell homogenates. The mechanism for this is a reduction in the rate of decay of adenylate cyclase activity over the course of the assay. Purified protein kinase C can reconstitute calcium- and phorbol ester-dependent adenylate cyclase. Phorbol ester-activated protein kinase C increases both the initial rate of cAMP synthesis and reduces the time-dependent decay of adenylate cyclase activity in membrane preparations. The rate of cAMP production is fit to an equation derived from a model which assumes that adenylate cyclase initially exists in a high activity state which decays exponentially into a low activity state. We suggest that protein kinase C can both prevent the decay of the high activity state and convert the low activity state into the high activity state.

Adenylyl Cyclases↗
PubMed1988

Distribution of opiate receptors within visual structures of the cat brain.

The distributions of mu, delta, and kappa opiate receptors within visual regions in the cat cortex, thalamus and midbrain were determined by in vitro autoradiography. The overall distribution of receptors was examined using [3H]-etorphine, a ligand that nonselectively labels all types of opiate receptors. [3H]-[D-Ala2, N-Me-Phe4,Gly(ol)5]-enkephalin (DAGO) was used to selectively label mu receptors, [3H]-[D-Pen2, 5]-enkephalin (DPDPE) for delta receptors, and [3H]-bremazocine for kappa receptors. Each of the areas examined showed clear opiate receptor binding with [3H]-etorphine and a differential distribution of mu, delta, and kappa receptors. Compared to other cortical regions, opiate binding in layers 3 and 4 of areas 17 and 18 was sparse. In the adjacent areas a more uniform distribution across layers was observed. The density of kappa opiate receptors was greater in cortex than in subcortical structures, whereas the reverse was the case for mu receptors. Nevertheless, all three types of opiate receptors were found in the ventral and dorsal subdivisions of the lateral geniculate (LGN), the pulvinar complex, and the suprageniculate nucleus. In the midbrain, the superficial layers of the superior colliculus were heavily labelled with the mu receptor ligand, and modestly with the kappa ligand. Compared with other midbrain and diencephalic areas, delta binding was low in the superior colliculus. These results suggest that the diverse effects of opiates on visual perception are mediated by the unique distributions of opiate receptor types throughout the visual areas in the brain.

Animals↗
PubMed1988

Tissue activities of enzymes of diagnostic interest in the marmoset and rat.

The activities of enzymes of diagnostic interest were investigated in the liver, heart, kidney and muscle of the marmoset (Callithrix jacchus) and the rat. Methods of tissue extraction which gave maximal enzyme activity were used and comparison between the species showed some major differences. AST, LDH and GDH showed a similar distribution in both species but ICDH activity was much higher in the rat heart than in any other rat or marmoset organ. ALP, LAP and GGT were present in much higher activities in the rat kidney than in the marmoset kidney, a finding which was reversed in the liver of these animals. The major ALT-containing organ in the rat was the liver but, in the marmoset, this enzyme was found in relatively large quantities in the heart and muscle also. These differences can be of importance when plasma enzyme activities are measured following tissue damage.

Alanine Transaminase↗
PubMed1988

Epidermal growth factor (urogastrone) in human seminal plasma from fertile and infertile males.

Epidermal growth factor/urogastrone (EGF/URO) was measured in the seminal plasma of 214 untreated patients attending an infertility clinic. Patients were assigned groups according to sperm density and progressive motility and in the case of azoospermia into an obstructive etiology or germinal failure. There was no significant variation in mean EGF/URO levels between groups, suggesting that this peptide plays no role in the density or motility of sperm associated with fertility. Other functions this peptide may fulfill in the female reproductive tract, including that of immunosuppression, are discussed.

Epidermal Growth Factor↗
PubMed1988

Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs.

Haloperidol exhibits a high affinity for a subclass of sigma- "opiate" binding sites which have a unique anatomic distribution and a unique drug selectivity pattern. These binding sites differ from phencyclidine-sensitive sigma-receptors and are found in many brain areas involved in the control of movement. 1,3-Di-o-tolylguanidine (DTG), a highly selective ligand for the haloperidol-sensitive sigma-receptor, produced marked dystonia in rats after microinjection into the red nucleus, a motor area rich in this receptor. Haloperidol and another sigma-ligand [(+)-SKF 10,047] produced similar effects. On the other hand, clozapine, an antipsychotic drug which fails to bind to sigma-receptors and fails to induce movement disorders in humans, failed to induce these dystonic reactions in rats. Phencyclidine was also without effect, as were injections of the active compounds in sites distant to the red nucleus. Microinjections of DTG in the substantia nigra produced vigorous contralateral circling behavior at extremely low doses. These findings suggest that sigma-binding sites represent biologically functional receptors that are active in the neural control of movement. Since haloperidol (and many other antipsychotic drugs) exhibit an affinity for sigma-receptors which is at least equal to its affinity for dopamine receptors, these data raise the further possibility that sigma-receptors are involved in the motor side effects of antipsychotic drugs.

Animals↗
PubMed1988

Rotational behavior mediated by dopaminergic and nondopaminergic mechanisms after intranigral microinjection of specific mu, delta and kappa opioid agonists.

The regulation of motor behavior by mu, delta and kappa opiate receptors in the substantia nigra was examined. Unilateral microinjections of specific mu (DAGO), delta (DPDPE) and kappa (U-50,488H) ligands into the substantia nigra pars reticulata of rats produced dose-dependent contralateral turning. The opiate antagonist naloxone blocked these effects, suggesting that the circling was mediated through opiate receptors. The involvement of midbrain dopaminergic systems in this behavior was tested in two ways. Unilateral 6-hydroxydopamine lesions of the medial forebrain bundle decreased the circling produced by DPDPE and DAGO but increased the circling produced by U-50,488H. In contrast, activating dopaminergic systems with systemic injections of amphetamine increased the circling produced by DAGO and DPDPE but had no effect on the circling produced by U-50,488H. These findings suggest that kappa opioids exert opposite effects on locomotion: motor activation through the SNR and motor inhibition through actions in the SNC. Furthermore, the data suggest that the actions of kappa opioids in the SNC are opposite to those produced by mu and delta opioids.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Selective screening for abdominal aortic aneurysms with physical examination and ultrasound.

Abdominal aortic aneurysm (AAA) is an important cause of preventable death in older persons. Persistently high rupture mortality rates indicate that these deaths can be prevented only by early detection and treatment of AAA. In an effort to develop an effective and efficient program of AAA detection, we selectively screened a high-risk population. Men aged 60 to 75 years with hypertension and/or coronary artery disease were randomly selected from a general medicine clinic and screened with physical examination and ultrasound. Eighteen previously unsuspected aneurysms, 3.6 to 5.9 cm in size (mean, 4.4 cm), were detected in 201 patients, for a prevalence of 9% (95% confidence interval: 4.7% to 13.3%). The specificity and positive predictive value of ultrasound were each 100%. Abdominal palpation detected only half of these aneurysms, but missed none in patients with an abdominal girth less than 100 cm (n = 6). This degree of sensitivity did not occur with "routine" examinations and requires that the examination be directed specifically toward AAA detection. We conclude that undiagnosed AAAs are common in this large subgroup of the clinic population, that ultrasound is an excellent screening test for AAAs, and that physical examination may be adequate for screening thin patients. We recommend that every two or three years persons over the age of 50 years undergo careful abdominal palpation aimed at detecting AAAs, as part of the periodic health examination. We further recommend that obese older men at high risk for AAA have at least one-time screening with abdominal ultrasound, regardless of findings on physical examination.

Abdomen↗
PubMed1987

Opposite effects of mu and kappa opiates on the firing-rate of dopamine cells in the substantia nigra of the rat.

Single unit extracellular recording was carried out in rats to compare the actions of a mu receptor agonist (morphine) to a kappa receptor agonist (U50,488) in the substantia nigra pars compacta (SNC). Intravenously administered morphine and U50,488 exhibited opposite effects: morphine excited SNC dopamine cells, and U50,488 inhibited them. Both effects were blocked by naloxone, although significantly more naloxone was necessary to block the effect of the kappa agonist. Local administration of U50,488 in the caudate also inhibited the firing of SNC dopamine cells. These results are discussed in terms of the natural functions of the prodynorphinergic straiatonigral projection.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Microalgae and cyanobacteria as a source of glycosidase inhibitors.

Culture filtrates and organic solvent extracts of over 500 freshwater and marine eukaryotic microalgae and cyanobacteria were screened for the presence of glycosidase inhibitors. Rapid colorimetric assays were used to detect inhibitors of alpha-glucosidase, alpha-amylase and beta-galactosidase. Inhibitors were found from 38 species. The results suggest that microalgae and cyanobacteria have potential as a source of glycosidase inhibitors which may have clinical applications.

Cyanobacteria↗