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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 559 records · Page 31Linked to original sources
PubMed1987

Autoradiographic localization of adenosine A1 receptors in rat brain using [3H]XCC, a functionalized congener of 1,3-dipropylxanthine.

Quantitative autoradiography was used to visualize the anatomical distribution of adenosine receptors labeled by the carboxylic acid congener of 1,3-dipropylxanthine, [3H](8-(p-carboxymethyloxy)phenyl-1,3-dipropylxanthine)([3H]XCC ) in the rat brain. [3H]XCC was observed to specifically bind to rat brain sagittal sections in a heterogeneous pattern. Saturation experiments revealed that [3H]XCC binds with nanomolar affinity to 20-microns frozen tissue sections with the highest binding densities occurring in the hippocampus and cerebellum. Both the binding characteristics and regional receptor distribution obtained with [3H]XCC demonstrate the potential usefulness of this new ligand in the study of adenosine A1 receptors.

Animals↗
PubMed1987

Barriers and incentives for primary-care physicians in cancer prevention and detection.

The American Cancer Society (ACS) estimates that nearly a million new cases of cancer will occur and that approximately 500,000 lives will be lost in 1987. These figures may double by the year 2000 primarily because of our aging population, with age being the leading risk factor for cancer. It is believed that most cancers can either be prevented or treated successfully if they are diagnosed early. Primary-care physicians and other health professionals delivering information on prevention and performing early diagnostic studies in various ambulatory settings represent the key to the reduced complications and mortality of cancer by virtue of their position in the health care delivery system within communities. Barriers and incentives for delivering these all important health measures are examined and suggestions are made for their accomplishment. It is recommended that the primary thrust should be toward the development of methodology which will allow the primary care physician to institute these measures in his regular medical practice and to coordinate them with other health maintenance and early diagnostic activities in the ambulatory setting.

Attitude of Health Personnel↗
PubMed1987

Quantitative autoradiographic localization of NMDA receptors in rat brain using [3H]CPP: comparison with [3H]TCP binding sites.

The regional distribution of N-methyl-D-aspartate (NMDA) receptors in rat brain using the selective NMDA receptor ligand [3H]3-[+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) has been quantitated by in vitro autoradiography. [3H]CCP binding was highest in the CA1 region of the hippocampus. Relatively high levels of binding were also observed in the cerebral cortex, while moderate binding was obtained in the thalamus, striatum and granule cell layer of the cerebellum. Concurrent studies examining the phencyclidine receptor ligand [3H]1-[1-(2-thienyl)cyclohexyl]-piperidine (TCP), revealed a similar pattern of binding that correlated well with the localization of [3H]CPP-labeled NMDA receptors (r = 0.88, P less than 0.01).

Animals↗
PubMed1987

Biochemical and pharmacological characterization of CGS 12066B, a selective serotonin-1B agonist.

CGS 12066B is a novel pyrroloquinoxaline with selectivity for the serotonin-1B (5HT1B) recognition site as assessed by binding, biochemical and electrophysiological studies. The compound had an IC50 value of 51 nM at the 5HT1B recognition site as determined using the binding of [3H]5HT in the presence of 1 microM spiperone. At the 5HT1A receptor the compound had an IC50 value of 876 nM, providing a 5HT1A/5HT1B ratio of 17 in contrast to the putative 5HT1B selective agent trifluoromethylphenylpiperazine (TFMPP) which had a corresponding ratio of 3.6. The compound had minimal affinity for alpha 1-, alpha 2- and beta-adrenoceptors and for dopamine D-1 and D-2 receptors. CGS 12066B, in contrast to TFMPP, which was inactive, was found to inhibit dorsal raphe cell firing with an ED50 value of 358 nmol/kg i.v. The corresponding values for the 5HT1A selective agonists 8-OH-DPAT and ipsapirone were 1.3 and 33 nmol/kg. CGS 12066B was also effective in decreasing rat brain 5-HTP concentrations and inhibiting in vitro 5HT release. The data obtained indicate that CGS 12066B is a reasonably active 5HT1B site agonist, which due to its selectivity as compared to compounds such as TFMPP, will be a useful tool for evaluating the physiological role of such receptors in the mammalian CNS.

5-Hydroxytryptophan↗
PubMed1987

Characterization of quisqualate recognition sites in rat brain tissue using DL-[3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and a filtration assay.

The binding of [3H]AMPA (DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), a ligand for the putative quisqualate excitatory amino acid receptor subtype, was evaluated using centrifugation and filtration receptor binding techniques in rat brain crude synaptosomal membrane preparations. Maximal specific binding of [3H]AMPA occurred in Triton X-100 treated membranes in the presence of the chaotropic agent potassium thiocyanate (KSCN). The effects of KSCN on binding were reversible and optimal at 100 mM. Supernatant obtained from detergent-treated membranes inhibited specific [3H]AMPA and [3H]kainic acid binding, suggesting the presence of an inhibitory agent which was tentatively identified as glutamate. Using centrifugation, saturation analysis revealed two distinct binding sites in both the absence and presence of KSCN. The chaotrope was most effective in increasing binding at the low affinity binding site, enhancing the affinity (Kd) without a concommitant change in the total number of binding sites. Using filtration, a single binding site was detected in Triton-treated membranes. Like the data obtained by centrifugation, KSCN enhanced the affinity of the receptor (Kd value = 10 nM) without altering the number of binding sites (Bmax = 1.2 pmol/mg protein). The rank order of potency of various glutamate analogs in the [3H]AMPA binding assay was quisqualate greater than AMPA greater than L-glutamate greater than kainate greater than D-glutamate, consistent with the labeling of a quisqualate-type excitatory amino acid receptor subtype. L-glutamic acid diethylester, and 2-amino-7-phosphonoheptanoic acid (AP7) were inactive. The present technique provides a rapid, reliable assay for the evaluation of quisqualate-type excitatory amino acid agonists and/or antagonists that may be used to discover more potent and selective agents.

Animals↗
PubMed1987

Medical nomenclature and common conventions for trauma registries.

A trauma registry has been created containing lexicons of terms arranged to foster the adoption of standardized and extensible terminology for the nature and mode of injury. Identification of attribute sets for the nature-of-injury (body region:detailed part:type of injury) and for the mode-of-injury (mechanism:agent:activity:intent:setting) allows the assembly of a clear, concise, easily usable, nad extensible format for representing the appropriate level of detail for nomenclature or classification. This ability allows the use of a common list of terms that is adaptable for case records used in patient care as well as in trauma registry statistics. Several examples of reports using these attributes are shown.

Humans↗
PubMed1987

Characterization of feline omentum lipids.

Feline omental lipid extracts, previously reported to be angiogenic in the cornea of rabbits, were fractionated and the major lipid components characterized. Approximately 97% of the chloroform/methanol extract consisted of triglycerides containing primarily 16:0, 18:0, 18:1 and 18:2 fatty acids. Trace quantities of free fatty acids, cholesterol, di- and monoglycerides were also detected. The phospholipid fraction, obtained by solvent partition and Unisil column chromatography and characterized by high performance liquid chromatography (HPLC)-mass spectrometry, was found to consist of phosphatidylcholine, sphingomyelin, phosphatidylethanolamine and phosphatidylserine. The neutral glycolipids, isolated by solvent partition and Unisil column chromatography and identified by high performance thin layer chromatography and HPLC of their perbenzoylated derivatives, were found to consist of glucosyl- and galactosylceramides, galabiosylceramide, lactosylceramide, globotriaosylceramide and globotetraosylceramide. The complex glycolipid fraction, obtained from Folch upper phase solvent partition, was found to consist primarily of Forssman glycolipid and gangliosides GM3 and GD3. Smaller amounts of GM1 and other unidentified gangliosides were also present.

Animals↗
PubMed1987

Identification of a monoclonal antibody-defined breast carcinoma antigen in body fluids.

The monoclonal antibody NCRC-11 defines antigens associated with secretory glandular epithelia as well as most epithelial malignancies. These components have been identified in, and isolated from, normal body fluids including urine and skim milk. The immunoadsorbent purified antigens from urine and milk were very similar to those purified from breast and ovarian carcinomas; by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) and immunoblotting, NCRC-11 antibody-binding antigens from all sources were of high apparent molecular weight (greater than 400 kD) with the major component(s) present as a single band or a doublet. Also, by analysing epitope profiles, all purified antigen preparations were shown to react in a characteristic manner with a panel of monoclonal antibodies which were originally produced against human milk products or materials from tumours. Since it was shown that NCRC-11 antigens were released from tissues in a soluble form, the possibility that these antigens might represent a diagnostic marker for breast cancer was evaluated. The findings obtained indicated that NCRC-11 antigens were elevated in the serum of advanced breast cancer patients in comparison to healthy control females, so that access to the circulation was available to these products released from the tumour but not to those released from normal epithelia.

Aged↗
PubMed1987

Muscarinic, benzodiazepine, GABA, chloride channel and other binding sites in frontal cortex in hepatic coma in man.

Alterations in several neurotransmitter systems in brain have been implicated in the pathophysiology of hepatic coma (HC). Studies on human autopsy material are few. We investigated 3H-quinuclidinylbenzilate (QNB), 3H-spiperone, 3H-imipramine, 3H-PN-200-110, 3naloxone, 3H-flunitrazepam, 3H-muscimol, 35S-t-butylbicyclophosphothionate and 3H-cyclohexyladenosine binding sites in frontal cortex from seven patients with HC and five controls. The density of 3H-QNB binding sites was significantly decreased and the affinity slightly increased in HC. The functional significance of these selective changes in muscarinic receptor binding sites is unclear. Further studies evaluating cholinergic function in HC are indicated. Acute studies in animals point to an increase in GABA and BZ binding sites in HC. The present results show that the BZ/GABA-receptor-chloride-ionophore complex is unchanged in HC in man. Serotonergic (5HT-2), adenosine (A-1), imipramine (5HT uptake sites), opiate (naloxone) and calcium channel antagonist binding sites are unchanged in HC.

Adenosine↗
PubMed1987

Speech and language development in preschool twins.

While language, articulation and reading problems have been well documented in young twins, it is not clear how extensive such problems can be or how early in childhood they become evident. At the age of 30 months, twin boys in the La Trobe Twin Study were 8 months behind matched singletons and twin girls on expressive language and 6 months behind on verbal comprehension. They were also 5 months behind on symbolic play and this delay was closely related to language. "Secret" language characterised most of the twin boys but not the girls and the relation of this to articulation delays is discussed. To examine if exposure to other children helps the twin boys, 38-53 month old twins and singletons were matched on the Columbia Mental Maturity Scale at the time of starting preschool. The twin boys had more articulation problems and all twins scored much lower on a Sociability questionnaire completed by the teacher. After 8 months at preschool, all children had advanced in Sociability, but the twins remained just as far behind with poor Sociability relating to poor articulation. The role of intervention programs is discussed.

Articulation Disorders↗
PubMed1987

Evaluation of immunoreactivity with monoclonal antibody NCRC 11 in breast carcinoma.

Immunocytochemical staining with monoclonal antibody NCRC 11 of formalin fixed paraffin embedded tumour tissue has been studied in 444 cases of primary breast cancer with a minimum follow period of 6 years. The relationship between extent of staining, assessed on a four point scale, and patient survival has been confirmed. There are significant relationships between staining and both histological grade and oestrogen receptor status. No association has been shown between staining and lymph node stage or tumour size. Simplification of staining assessment by modification to two staining groups still allows significant separation of patients into prognostic groups and incorporation into an existing prognostic index.

Adenocarcinoma↗
PubMed1987

Characterization of adenosine receptors in the PC12 pheochromocytoma cell line using radioligand binding: evidence for A-2 selectivity.

Examination of the binding characteristics of the adenosine agonist radioligands [3H]N6-cyclohexyladenosine [( 3H]CHA), [3H]cyclopentyladenosine [( 3H]CPA), and [3H]5'-N-ethylcarboxamido adenosine [( 3H]NECA) to membranes prepared from PC12 cells showed that the A-1-selective ligands (CHA and CPA) had minimal binding, which was not amenable to analysis using curve-fitting programs. However, [3H]NECA, a nonselective A-1/A-2 agonist, gave reproducible binding, which was enhanced by removal of endogenous adenosine, using the catabolic enzyme adenosine deaminase. This binding was of high affinity (KD = 4.7 nM) with limited capacity (263 fmol/mg of protein). Specific binding of [3H]NECA was unaffected by the presence of either CPA (50 nM) or MgCl2 (10 mM) but was sensitive to guanylylimidodiphosphate (100 microM), a finding suggesting involvement of an N-protein mechanism in the coupling of the adenosine receptor labeled by [3H]NECA to other components of the receptor complex. Binding of [3H]NECA to PC12 cell membranes was stereo-selective, with the R isomer of N6-phenylisopropyladenosine (PIA) being approximately 12 times more active than S-PIA. The A-1-selective agonist CPA was a weak inhibitor of [3H]NECA binding (Ki = 251 nM). The rank order of activity of adenosine agonists in displacing specific [3H]NECA binding was NECA greater than or equal to 2-chloroadenosine greater than CHA greater than or equal to 5'-N-methylcarboxamido adenosine greater than or equal to R-PIA greater than CPA greater than S-PIA. Binding was also displaced by the marine adenosine agonist 1-methylisoguanosine and by a series of xanthine antagonists with the activity order being 1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine greater than 8-phenyltheophylline greater than 8-p-sulfophenyltheophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗