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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 577 records · Page 32Linked to original sources
PubMed1987

Sodium-potassium pump, ion fluxes, and cellular dehydration in sickle cell anemia.

We studied the role of the sodium-potassium pump in erythrocytes of 12 patients with sickle cell anemia (SS). Ouabain-binding sites per cell and pump-mediated Rb/K uptake were significantly higher in SS patients than in white or black controls. Ouabain-resistant Rb/K influx was also greater than in normal controls or patients with sickle cell trait. Deoxygenation of SS erythrocytes increased ouabain-sensitive Rb/K influx without altering ouabain binding, presumably as the consequence of an increase in the passive influx of sodium. Deoxygenation increased mean corpuscular hemoglobin concentration (MCHC) by 5.5%, and studies of the density distribution of SS cells indicated an increase in highly dense fractions known to contain sickled erythrocytes. Ouabain prevented the rise in MCHC and reduced the percentage of dense cells. These findings indicate a magnified role for the sodium-potassium pump in the pathophysiology of SS erythrocytes and suggest that its inhibition might prove useful in therapy.

Adolescent↗
PubMed1987

Reconstruction of an early seduction and its aftereffects.

This clinical presentation deals with the aftereffects, in a male patient, of a severely disturbed rapprochement phase, marked by many separations and a molestation before the age of three. The patient dreamed repeatedly of violence, often directed against himself, but the actual molestation was sealed off by formidable repression. A first analysis, with a male analyst, produced no relief from the patient's depression, crippling insomnia, and inability to form an intimate relationship. The second analysis progressed only when the repetitive dreams were understood to be repressed experiences of seduction and molestation.

Child Abuse, Sexual↗
PubMed1987

Biochemical characterization of the triazoloquinazoline, CGS 15943, a novel, non-xanthine adenosine antagonist.

CGS 15943A, a triazoloquinazoline, is a potent and selective adenosine receptor antagonist as assessed by its effects on radioligand binding and adenosine-stimulated adenylate cyclase activity in guinea pig synaptoneurosomes. At the adenosine A-1 receptor labeled with [3H]cyclohexyladenosine, CGS 15943A had an IC50 value of 20 nM. At the striatal A-2 receptor labeled with [3H]5'-N-ethylcarboxamidoadenosine in the presence of a low concentration of cyclopentyladenosine to block A-1 receptors labeled by this nonselective adenosine agonist, CGS 15943A had an IC50 value of 3 nM, indicating that the compound had some degree of selectivity for the A-2 receptor. Analysis of the effect of the compound on the saturation isotherms for each of the receptors indicated that it was a competitive antagonist at the brain A-1 receptor but that it was noncompetitive at the striatal A-2 receptor. CGS 15943A was a potent adenosine antagonist in the adenosine-stimulated adenylate cyclase system in guinea pig synaptoneurosomes, where the compound was found to have an IC50 value of 30 to 70 nM against the increase in cyclic AMP evoked by 5 microM adenosine. CGS 15943A had no effect on the binding of [3H]nitrobenzylthioinosine, a ligand thought to bind to adenosine uptake sites, and, at a concentration of 10 microM, had no effect on beef heart type III phosphodiesterase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1987

Interaction of L-glutamate and magnesium with phencyclidine recognition sites in rat brain: evidence for multiple affinity states of the phencyclidine/N-methyl-D-aspartate receptor complex.

Biochemical and electrophysiological studies have provided evidence that a complex comprising the N-methyl-D-aspartate (NMDA)-type excitatory amino acid (EAA) receptor and the phencyclidine (PCP) recognition site exists in mammalian brain. This complex, which has been compared to that established for the inhibitory amino acid, gamma-aminobutyric acid, and the benzodiazepine anxiolytic, diazepam, is sensitive to the effects of the divalent cation Mg2+, which has suggested the presence of a third, ion channel component. Using a radioreceptor assay for the PCP receptor, L-glutamate (L-Glu) produced a concentration-dependent increase in the binding of [3H]thienyl cyclohexylpiperazine ([3H]TCP) in well washed membranes from rat forebrain. The EAA produced a maximal increase in specific binding of 400%, with an EC50 value of 340 nM. The ability of L-Glu to enhance [3H]TCP binding was 10-fold more potent in the presence of 30 microM Mg2+, which inhibits NMDA-evoked responses in intact tissue preparations and produces a 50% increase in [3H]TCP binding on its own. Analysis of saturation curves indicated that the effect of both L-Glu and Mg2+ could be attributed to an increase in receptor affinity as well as increases in the proportion of a high affinity state of the PCP-binding site. Assessment of the effect of a number of EAAs on basal [3H]TCP binding (well washed membranes in the absence of either L-Glu or Mg2+) showed that the EAA recognition site involved in the effects of L-Glu was the NMDA subtype. Further studies examined a series of compounds thought to interact with either the NMDA or PCP components of the receptor complex under four binding conditions: basal, +Mg2+; +L-Glu; and +Mg2+/L-Glu. These results showed that dissociative anesthetics, such as dexoxadrol and PCP, as well as the novel anticonvulsant MK-801, selectively interact with the high affinity state of the PCP receptor. NMDA antagonists, such as CPP, were also found to inhibit binding to the high affinity state of the PCP receptor, although not as potently as the dissociative anesthetics. Interestingly, the NMDA antagonists did not inhibit any of the binding to the low affinity state of the receptor. The sigma ligands (+/-)-SKF 10,047 and haloperidol recognized two components of [3H]TCP binding only in the presence of L-Glu. The results of the present study are consistent with the finding that agonists of the NMDA receptor induce a high affinity state of the PCP receptor.

Animals↗
PubMed1987

Binding of [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to rat brain membranes: a selective, high-affinity ligand for N-methyl-D-aspartate receptors.

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a rigid analog of 2-amino-7-phosphonoheptanoic acid, has been reported as a selective N-methyl-D-aspartate (NMDA) antagonist. [3H]CPP bound with relatively high affinity (Kd = 201 nM) to Triton-treated rat brain crude synaptic membranes using a centrifugation assay. Binding was saturable, reversible, heat sensitive and dependent on protein concentration. Specific binding, which represented 75 to 85% of the total counts bound, was enriched in synaptosomal and microsomal fractions of rat brain, suggesting an involvement in events related to synaptic transmission. On a regional basis, binding was highest in hippocampus, followed by cortex greater than striatum greater than cerebellum = thalamus. No specific binding could be detected in pons medulla or in liver, kidney, heart, lung and adrenal tissue. [3H]CPP binding was stereoselective for the isomers of glutamate, 2-amino-5-phosphonopentanoic acid, homocysteic acid, alpha-aminoadipic acid and N-methyl-aspartate. The most potent compounds tested were L-glutamate and CPP, which were equiactive in displacing [3H]CPP. The order of activity of other excitatory amino acid receptor ligands was D-2-amino-5-phosphonopentanoic acid greater than L-homocysteic acid greater than or equal to DL-2-amino-7-phosphonoheptanoic acid = D-aspartate = L-aspartate greater than L-serine-O-sulfate = D-alpha-aminoadipic acid = ibotenate greater than NMDA greater than DL-2-amino-6-phosphonohexanoic acid greater than quisqualate greater than N-methyl-L-aspartate. The quisqualate- and kainate-type receptor agonists DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and kainic acid, respectively, had negligible activity at 100 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Ineffective breathing pattern related to decreased lung expansion.

This article reviews the general pathophysiology of restrictive processes that cause decreased lung expansion. It describes their clinical features and illustrates how these restrictive disorders lead to an altered breathing pattern related to decreased lung expansion. It also shows how nurses intervene and manage the manifestations of the decreased lung expansion.

Humans↗
PubMed1987

Pharmacological characterization of CGS 15943A: a novel nonxanthine adenosine antagonist.

CGS 15943A is a potent adenosine receptor antagonist with a novel nonxanthine heterocyclic ring structure. In vitro, CGS 15943A competitively inhibited the 2-chloroadenosine-induced A2 receptor-mediated relaxation of dog coronary artery strips contracted with KCl (25 mM). Similarly, CGS 15943A blocked 2-chloroadenosine- and N-ethylcarboxamideadenosine-induced A2 receptor-mediated relaxation of histamine-contracted guinea pig tracheal strips. Schild analysis of these results yielded pA2 values of 10.8 and 10.1 for the coronary arteries and the tracheal smooth muscle strips, respectively. In comparison, 8-phenyltheophylline blocked 2-chloroadenosine-induced tracheal response with a pA2 value of 7.0. CGS 15943A was devoid of intrinsic activity, and did not affect either histamine- or KCl-induced contractions of the smooth muscle strips. In the electrically stimulated guinea pig left atrial preparation, CGS 15943A antagonized the A1 receptor-mediated negative inotropic effects of R-phenylisopropyladenosine with a pA2 value of 7.4. In vivo, i.v. administration of CGS 15943A blocked the vasodepressor response to 2-chloradenosine in anesthetized normotensive rats with an ID50 of 0.024 mg/kg. In addition, p.o. administration of CGS 15943A (4.0 mg/kg) to conscious rats inhibited 2-chloroadenosine-induced decreases in diastolic blood pressure; maximal effects were observed 30 min after dosing, with a T1/2 of approximately 103 min. Therefore suggesting that CGS 15943A is an orally active antagonist of adenosine receptors. These results indicate that CGS 15943A antagonized both A1 and A2 receptor-mediated responses with a greater affinity toward the A2 than the A1 receptor subtype.

2-Chloroadenosine↗
PubMed1986

[3H]cyclohexyladenosine binding in rat brain: a pharmacological analysis using quantitative autoradiography.

Quantitative autoradiography was used to characterize the regional binding parameters of [3H]cyclohexyladenosine (CHA) and the regional inhibition of specific [3H]CHA binding observed with a series of adenosine agonists and antagonists. Under the conditions described [3H]CHA binding was best fit by a single, high affinity site model in all areas examined. No major regional differences were observed in the inhibition of [3H]CHA binding by the adenosine and xanthine analogs examined. Overall, the rank order of activity throughout all regions was CPA greater than R-PIA greater than NECA much greater than PACPX greater than or equal to 2-CADO greater than or equal to S-PIA much greater than DPX.

Adenosine↗
PubMed1986

Functional morphology of insect neuronal cell-surface/glial contacts: the trophospongium.

Ultrastructural studies were carried out on the surfaces of insect nerve cell bodies. Some of the neurons were identified, by using physiological criteria, before filling with dye. Their surface patterns were compared, to provide data needed for understanding dynamic relationships with glial cells, in the trophospongium. The data are also needed in connection with interpretation of electrical signals recorded from the somata and of their roles in integration and in learning and memory. The surfaces were found to be extremely complex and also varied, even for neurons of comparable size and function, as well as for different regions of the same neuron, suggesting that the surface is constantly changing as the neuron receives food and loses waste. There is a variety of cytoplasmic types of invagination of neuron somata by glial processes. The invaginations were classified into four easily recognized types: regular, chunky, filigree, and ridge (present only in axon hillock regions). Motor neurons also make reciprocal invaginations into the glial cells that surround them. Some of these extend for distances up to 40 microns from the surface. The effective surface area is increased, compared with that calculated for a smooth surface, as a result of the invaginations, by from as little as 5% for a small interneuron to as much as 12-fold for a large motor neuron. The axon hillock region of all types of neurons is heavily invaginated.

Animals↗
PubMed1986

Evaluation of the binding of the A-1 selective adenosine radioligand, cyclopentyladenosine (CPA), to rat brain tissue.

The binding of [3H]-Cyclopentyladenosine (CPA), an N6-substituted analog of adenosine, was examined in vitro. CPA bound with high affinity (Kd = 0.48 nmol/l) to rat brain membranes. Specific binding, which represented 90-97% of the total counts bound at a ligand concentration of 1 nmol/l, was saturable, reversible and sensitive to protein denaturation. The pharmacology of binding was consistent with the labeling of an A-1 receptor, the R- and S-diasteromers of N6-phenylisopropyladenosine (PIA) showing a sixteenfold difference in their ability to displace CPA. The prototypic A-1 selective adenosine agonist, N6-cyclohexyladenosine (CHA) was twofold less active than CPA in displacing radiolabeled CPA. Comparison of the ability of cold CHA and CPA to displace [3H]-CPA gave rate dissociation constants of 1.88 and 1.80 X 10(4) s-1, respectively suggesting that both CHA and CPA bound to the same recognition site. In contrast however, comparison of the binding of [3H]-CPA with that of [3H]-CHA showed distinct differences. The Kd for CHA was approximately twice that of CPA while the apparent Bmax was 60% greater. In comparing the pharmacology of CPA binding with that of CHA, it was found that CHA, S-PIA and the antagonist, PACPX were more active in displacing CHA than CPA. In general however, CPA has a binding profile very similar to that observed with CHA.

Adenosine↗
PubMed1986

A bone marrow transplant with an acquired anti-Le(a): a case study.

A patient with aplastic anemia received an ABO incompatible bone marrow transplant (BMT) from an HLA identical sibling. Weekly HLA antibody screens were performed as part of the BMT protocol. At the time of transplant, a hemolytic anti-Le(a) was detected in the Le (a-b-) donor. The Le (a-b+) recipient had no red cell or LCT antibody. A hemolytic anti-Le(a) was detected in the recipient on day 8, but no LCT reactivity was noted at this time. On day 15, the LCT panel demonstrated reactivity with 9 of 50 panel cells without apparent HLA specificity. Graft vs. host disease (GVHD) was present on the skin at this time. The dose of cyclosporin A was increased, but by day 20 the GVHD worsened and the LCT titers increased to 8. This strong reactivity was noted only in the Le (a+) panel members (12/50) and was neutralized with commercial Lewis substance. On day 34 there was no evidence of GVHD, but the lymphocytotoxic anti-Lea continued to be present. The patient began experiencing renal and gastrointestinal difficulties by day 48, and expired on day 60. In renal transplants the kidneys retain their Lewis type and secrete Lewis substance in the urine. In our experience BMT patients retain their Lewis type regardless of the type of the donor. The Lewis system has been linked to renal allograft rejection, and Lewis antigens may function as transplantation antigens in BMT patients as well. In addition, lymphocytotoxic Lewis antibodies can mask other significant HLA antibodies and must be identified when screening patients in need of plateletpheresis products.

Anemia, Aplastic↗
PubMed1986

Cancer of the floor of the mouth and buccal cavity.

The ability of the surgeon to use the entire armamentarium of reconstructive techniques is essential in head and neck reconstruction. Each modality has its advantages and disadvantages. The decision of which technique to use is, of course, left to the individual surgeon's best judgment. Many new ideas will be explored in the future as the challenge of reconstruction awaits the perfect answer.

Adult↗
PubMed1986

Experimental pancreatic allotransplantation in large animals. The role of donor kidney and cyclosporine in modifying rejection.

Experiments were carried out in outbred dogs and pigs to evaluate the relative immunogenicity of pancreatic islets and segmental pancreas grafts, and whether these could be ameliorated by transplanting a kidney simultaneously from the same donor animal. Various immunosuppressive regimens were also studied. Pancreatic islet allografts never normalized blood glucose in totally pancreatectomized recipients despite the use of cyclosporine (CsA) in high doses (40 mg/kg/day) and the simultaneous transplantation of a kidney from the same donor. These grafts which never "took" contrast sharply with the experience of pancreatic islet autografts prepared in the same way and inoculated into the spleen, which in all nine instances normalized blood glucose in pancreatectomized recipients. Segmental transplants were performed in swine with duct drainage into the jejunum. Totally pancreatectomized pigs died at 7.8 +/- 1.0 days. In recipients suppressed with low-dose azathioprine (Az) and prednisone (Pred) pancreas grafts alone were rejected in 12.9 +/- 10 days. Synchronous pancreas and kidney transplants treated similarly extended the mean survival of pancreatic grafts to 20 +/- 10 days--which, however, was not significant (P less than 0.1 greater than 0.05). Mean survival time of pancreatic grafts in recipients receiving CsA at 20 mg/kg/day and prednisone 1 mg/kg/day was 14 +/- 6.3 days. The combination of CsA 20 mg/kg/day, Az 2 mg/kg/day, and Pred 1 mg/kg/day prolonged the mean survival time to 39.8 +/- 22 days. These results allow us to conclude that: crude preparations of islet tissue invariably capable of normalizing blood sugar at day 4 when used as autografts failed to "take" despite the existence of alternative sources of antigen present in a well vascularized kidney from the same donor, and despite very high dosages of CsA; triple immunosuppressive therapy had synergistic effects on pancreatic allograft survival; and simultaneous transplantation of kidney and pancreas had little effect on survival times of the pancreas or the kidney.

Animals↗
PubMed1986

Effects of purine nucleotides on the binding of [3H]cyclopentyladenosine to adenosine A-1 receptors in rat brain membranes.

Adenine nucleotides displace the binding of the selective adenosine A-1 receptor ligand [3H]cyclopentyladenosine (CPA) to rat brain membranes in a concentration-dependent manner, with the rank order of activity being ATP greater than ADP greater than AMP. Binding was also displaced by GTP, ITP, adenylylimidodiphosphate (AppNHp), 2-methylthioATP, and the beta-gamma-methylene isostere of ATP, but was unaffected by the alpha-beta-methylene isosteres of ADP and ATP, and UTP. At ATP concentrations greater than 100 microM, the inhibitory effects on CPA binding were reversed, until at 2 mM ATP, specific binding of CPA was identical to that seen in controls. Concentrations of ATP greater than 10 mM totally inhibited specific binding. Inclusion of the catabolic enzyme adenosine deaminase in the incubation medium abolished the inhibitory effects of ATP, indicating that these were due to adenosine formation, presumably due to ectonucleotidase activity. The inhibitory effects were also attenuated by the alpha-beta-methylene isostere of ATP, an ectonucleotidase inhibitor. Adenosine deaminase, alpha-beta-methylene ATP (100 microM), and beta-gamma-methylene ATP (100 microM) had no effect on the "stimulatory" phase of binding, although GTP (100 microM) slightly attenuated it. Comparison of the binding of [3H]CPA in the absence and presence of 2 mM ATP by saturation analysis showed that the KD and apparent Bmax values were identical. Examination of the pharmacology of the control and "ATP-dependent" CPA binding sites showed slight changes in binding of adenosine agonists and antagonists. The responses observed with high concentrations of ATP were not observed with GTP, AppNHp, the chelating agents EDTA and EGTA, or inorganic phosphate. The divalent cations Mg2+ and Ca2+ at 10 mM attenuated the stimulatory actions of high (2 mM) concentrations of ATP, whereas EGTA and EDTA (10 mM) enhanced the "stimulatory" actions of ATP. EDTA (10 mM) abolished the inhibitory effects of ATP, indicating a specific dependence on Mg2+ for the inhibitory response. The effects of ATP on [3H]CPA binding were reversible for antagonists but not agonists. The mechanism by which ATP reverses its own inhibitory action on adenosine A-1 radioligand binding is unclear, and from the observed actions of the divalent cations and chelating agents probably does not involve a phosphorylation-dependent process.

Adenine Nucleotides↗