PubMed Health⌕ Search

Biomedical subjects

S M Cooper

Publications and source records attributed to S M Cooper.

At least 91 records · Page 5Linked to original sources

N-methyl-D-aspartate receptors in the cortex and hippocampus of baboon (Papio anubis and Papio papio).

In vitro autoradiography was used to examine the N-methyl-D-aspartate receptor in the brain of a baboon species, Papio anubis, and compared to that of Papio papio which exhibits a photosensitive epilepsy. The epilepsy originates in the frontal cortex and is accompanied by an enhanced sensitivity to N-methyl-D-aspartate. In both Papio anubis and Papio papio, the density of N-methyl-D-aspartate receptors was greatest in the hippocampus, followed by associational areas including frontal cortex, and low in primary sensory areas such as the visual cortex. The receptors were concentrated in the outer cortical layers I-III, very low in layer IV except in primary visual cortex, and of intermediate density in layer V. The density of binding sites was approximately two-fold lower than previously observed in the rodent brain, whereas the affinity of the receptor for [3H]L-glutamate was greater in the primate versus the rodent brain. Glycine potentiated the binding of [3H]L-glutamate in both cortex and hippocampus. No significant differences in the properties of N-methyl-D-aspartate receptors were observed between the two baboon species, suggesting that the photosensitivity of Papio papio is not due to alterations in the binding of L-glutamate to the N-methyl-D-aspartate receptor complex.

Animals↗

A double-blind dose ranging study of BRL 24924 and metoclopramide on lower oesophageal sphincter pressure in healthy volunteers.

1. A double-blind placebo controlled dose ranging study of the effect of single oral doses of 1 and 2 mg BRL 24924 and 10 mg metoclopramide on lower oesophageal sphincter pressure has been performed in 20 healthy volunteers. 2. The 2 mg dose of BRL 24924 caused a statistically significant increase in mean lower oesophageal sphincter pressure (P less than 0.05) at 30-45 min post-dose (20.8 +/- 7.1 cm H2O BRL 24924; 16.4 +/- 5.7 cm H2O placebo). BRL 24924 1 mg and metoclopramide 10 mg failed to increase lower oesophageal sphincter pressure at any time. However, eight volunteers with a hypotensive resting lower oesophageal sphincter pressure (less than 15 cm H2O) showed a statistically significant rise in pressure at 120 min for both 1 mg, 2 mg (P less than 0.01; P less than 0.001) BRL 24924 and 10 mg metoclopramide (P less than 0.01). No other significant effect was detected on oesophageal manometry. 3. BRL 24924 (2 mg) has statistically significant effects on lower oesophageal sphincter pressure. However, further studies in patients with gastro-oesophageal reflux disease and oesophagitis are needed to evaluate its clinical efficacy, especially where a hypotensive lower oesophageal sphincter pressure predominates.

Adult↗

Effect of cromakalim on contractions in rabbit isolated renal artery in the presence and absence of extracellular Ca2+.

1. The inhibitory effects of the K+ channel activator, cromakalim, upon contractions to noradrenaline, histamine and caffeine were examined in rabbit isolated renal artery. For comparison, the effects of pinacidil, dazodipine and sodium nitroprusside were also studied in some experiments. 2. In normal Krebs solution, cromakalim (1 microM) produced a 39.1% reduction in area under the curve (AUC) of the noradrenaline concentration-response, and a 61.8% reduction in the histamine AUC. Ca2+ removal (with EGTA 0.1 mM) gave an 80.0% reduction in the noradrenaline AUC and a 74.5% reduction in the histamine AUC. The combination of Ca2+ removal and cromakalim (1 microM) had no further effect on the noradrenaline responses (a reduction of 78.4% in AUC), but produced a significantly greater reduction in the histamine AUC (86.2%). 3. LaCl3 (1 mM) reduced the noradrenaline AUC by 74.8% and gave an 81.8% reduction in the response to a single (EC90) histamine concentration. LaCl3 (1 mM) plus cromakalim (1 microM) produced no further reduction in the noradrenaline AUC (71.9%) but gave a significant further reduction of the histamine response (94.6%). 4. Pinacidil (3 microM) reduced the noradrenaline AUC by 35.5%. Pinacidil (3 microM) plus LaCl3 (1 mM) produced the same reduction in the noradrenaline AUC (80.9%) as LaCl3 alone (80.9%). 5. In both normal and Ca2+-free Krebs solution, cromakalim (0.1, 1.0 and 10 microM) produced concentration-related inhibition of the contraction to caffeine (10 mM). This inhibition was antagonised by the K+ channel blocker, glibenclamide (3 microM). Similarly, pinacidil (0.3, 3.0 and 30 microM) produced a glibenclamide-sensitive inhibition of the caffeine contraction. At equi-vasorelaxant concentrations, dazodipine (0.01, 0.1 and 1.O microM) and sodium nitroprusside (0.03, 0.3 and 3.0 microM) had no significant effect on caffeine contractions. 6. The data show that the K+ channel activators, cromakalim and pinacidil, unlike the Ca2+ channel blocker, dazodipine, or the guanylate cyclase activator, sodium nitroprusside, can inhibit the contraction which results from caffeine-induced Ca2+ release. Cromakalim and pinacidil, however, inhibit only the component of the noradrenaline response resulting from Ca2+ influx (tonic component) and not that resulting from Ca2 + release (phasic component). Cromakalim may affect both components of the histamine contraction.

Animals↗

Evidence of acute inflammation in the periodontal ligament subsequent to orthodontic tooth movement in rats.

Experimental orthodontic tooth extrusion can result in red cell diapedesis through the PDL vascular wall. Diapedesis is an early sign of acute inflammation. At the ultrastructural level, red cell migration is demonstrated occurring through the endothelial junction of a postcapillary-sized venule. This phenomenon is considered to be indicative of unphysiological tooth loading.

Animals↗

Suppression of murine collagen-induced arthritis with monoclonal anti-Ia antibodies and augmentation with IFN-gamma.

Collagen-induced arthritis (CIA) is an experimental model in which a specific immune response to type II collagen (CII) is associated with the development of inflammatory arthritis. In this study, we evaluated the effects of early and delayed treatments with anti-Ia mAb and IFN-gamma on murine CIA. Administration of anti-Ia mAb at the time of immunization with CII decreased the incidence and delayed the onset of arthritis, whereas anti-Ia treatments begun 2 wk after immunization had no effect upon either arthritis incidence or onset. Neither treatment protocol resulted in a significant decrease in antibody titer or proliferative response to CII. Because IFN-gamma increases Ia expression in a variety of cells, we determined its effect on arthritis incidence and onset. When IFN-gamma treatments were begun at the time of immunization the incidence of arthritis was increased and arthritis onset was more rapid. Treatment with IFN-gamma did not result in an increase in anti-CII antibody levels. These results support the importance of Ia expression in the induction of murine collagen-induced arthritis, and suggest that suppression with anti-Ia antibodies and augmentation with IFN-gamma are not the result of changes in the humoral response to CII, but may be due to local effects within the target organ.

Adjuvants, Immunologic↗

Comparative effects of K+ channel blockade on the vasorelaxant activity of cromakalim, pinacidil and nicorandil.

Three agents with K+ channel blocking activity, procaine, 4-aminopyridine (4-AP) and tetraethylammonium (TEA), were tested for inhibition of vasorelaxation and 86Rb+ efflux induced by cromakalim (BRL 34915), pinacidil and nicorandil in rabbit isolated mesenteric artery. The potency order for inhibition of vasorelaxation was procaine greater than 4-AP greater than TEA and for inhibition of efflux was procaine = 4-AP greater than TEA. The K+ channel blockers did not discriminate between cromakalim, pinacidil or nicorandil on efflux but demonstrated preferential inhibition of vasorelaxation to cromakalim greater than pinacidil greater than nicorandil. In addition, the maximum response to cromakalim was depressed but that to pinacidil and nicorandil was not. The results confirm the role of K+ channel activation in vasorelaxation to cromakalim, pinacidil and nicorandil, but suggest that additional mechanisms may be involved for pinacidil and, in particular, for nicorandil.

4-Aminopyridine↗

Influence of risk area size and location on native collateral resistance and ischemic zone perfusion.

To examine the effect of risk area size on collateral resistance and ischemic region perfusion, we produced different sized risk areas by occluding either the left anterior descending (LAD) or the circumflex (Cx) coronary artery at different sites. The most proximal occlusion of the LAD and Cx produced risk areas of 43 +/- 5 and 36 +/- 2% of left ventricular (LV) mass, respectively, whereas distal LAD and Cx occlusions produced risk areas of 13 +/- 2 and 17 +/- 2% of LV weight, respectively. Although total collateral flow was highest to the largest risk areas, collateral flow per 100 g of ischemic myocardium was 80% higher to the small LAD risk area compared with the large LAD risk area and 43% higher to the small Cx risk area compared with the large Cx risk area. Collateral resistance, calculated from the transcollateral pressure and perfusion per 100 g of myocardium was significantly lower in the small risk areas than in the large ones. We examined the effect of risk area location on collateral perfusion and resistance. Small risk areas (6% LV mass) were created near the base and at the apex of 10 hearts. Collateral flow per 100 g was 60% higher and transcollateral resistance per 100 g 50% lower at the apex than at the base. These experiments show that collateral resistance is influenced both by ischemic region size and location. Small risk areas receive more collateral flow per mass of tissue than large risk areas, and apical risk areas receive greater quantities of collateral flow than those located at the base.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of hypertension and left ventricular hypertrophy on the lower range of coronary autoregulation.

These studies were performed to test the hypothesis that left ventricular hypertrophy arising as a complication of chronic hypertension is associated with impaired coronary autoregulation. Twelve dogs with hypertension and left ventricular hypertrophy (one-kidney, one-clip model) and 11 normal dogs were instrumented and subsequently studied while conscious. Circumflex pressure, measured with an intracoronary catheter, was adjusted to 100, 75, and 40 mm Hg with a hydraulic occluder that was placed proximally. At each circumflex pressure, myocardial perfusion was measured with radioactive microspheres. Reduction of circumflex pressure over this range did not significantly alter heart rate, left atrial pressure, or arterial pressure. In normal dogs, reduction of circumflex pressure did not alter total myocardial perfusion or the transmural distribution of perfusion. In contrast, in dogs with hypertension and left ventricular hypertrophy, circumflex subendocardial perfusion decreased 46% when pressure was decreased from 100 to 40 mm Hg (p less than .05 compared with normal). Autoregulation was quantified for each third of myocardium with the use of autoregulatory gain values (1 = perfect autoregulation; 0 = the absence of autoregulation). For pressure changes of 100 to 75 mmHg, values for autoregulatory gain were near unity for all layers of myocardium in both groups of animals. When pressure was decreased from 75 to 40 mm Hg, values for autoregulatory gain among the normal and hypertensive groups were, respectively: for subepicardium 1 +/- 0.2 (mean +/- SE) vs 0.9 +/- 0.2 (p = NS), for the midwall 0.8 +/- 0.2 vs 0.5 +/- 0.2 (p = NS), and for the subendocardium 0.8 +/- 0.1 vs 0.1 +/- 0.2 (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vivo modulation of murine collagen induced arthritis.

The effects of in vivo modulation of murine collagen induced arthritis with monoclonal anti-CD4 antibodies, monoclonal anti-Ia antibodies, and gamma interferon are reviewed. We detail the mechanism of action of monoclonal anti-CD4 antibody on humoral and cell mediated immune responses and discuss the implications for designing therapeutic strategies. To further explore the induction of collagen induced arthritis, a syngeneic cell transfer system using collagen primed T lymphocytes is described. This cell transfer system provides an opportunity to study the role of CD4 positive T lymphocytes in arthritis induction during a short, defined time period.

Animals↗

In vivo immunomodulation by monoclonal anti-L3T4. 1. Effects on humoral and cell-mediated immune response.

The in vivo administration of monoclonal anti-L3T4 antibody has been shown to be an effective preventative and, in some cases, therapeutic treatment for several murine models of autoimmune disease. This report deals with the effect of such treatments on humoral and cell-mediated responses to T-dependent antigens. Both the primary and secondary IgG responses to tetanus toxoid were inhibited when anti-L3T4 was administered prior to immunization, but it was ineffective in modulating an ongoing IgG response. Cell-mediated immunity, as detected by in vitro antigen-specific proliferative responses, was inhibited only if anti-L3T4 was given prior to immunization. It was not effective if treatment was delayed until 48 hr prior to lymph node harvest even though greater than 90% of L3T4+ lymph node cells were depleted by this treatment. The refractory behavior of the lymph node cells to anti-L3T4 treatment was not exhibited by antigen-primed cells obtained from peripheral blood or spleen. The importance of these findings with regard to antibody therapy for chronic autoimmune disease is discussed.

Animals↗

Increase in OKM1+ granular lymphocytes in patients with rheumatoid arthritis.

Patients with very active rheumatoid arthritis that was being treated only with nonsteroidal antiinflammatory drugs had increased numbers of peripheral blood OKM1+ lymphocytes. In 3 patients, 90 degrees light scatter analysis revealed a double lymphocyte peak. When sorted, the high scatter peak contained a large percentage of granular lymphocytes. Patients with mild-to-moderately active rheumatoid arthritis had normal levels of OKM1+ lymphocytes, but when the drugs were discontinued, the activity of the disease and the numbers of OKM1+ cells increased. Administration of piroxicam was associated with clinical improvement and a decrease in levels of OKM1+ cells. OKM1+ granular lymphocytes are increased in some rheumatoid arthritis patients, and their numbers may correlate with clinical disease activity and/or therapy.

Adult↗

Alpha 1-adrenoceptor-mediated contraction of rabbit mesenteric artery: a role for intra- and extracellular calcium pools.

The alpha-adrenoceptors that mediate contraction to exogenous and endogenous noradrenaline in rabbit isolated mesenteric artery were investigated. Prazosin (10(-9)-10(-7) M) antagonised contractions to noradrenaline, methoxamine, and, in particular, contractions to neuronal noradrenaline released by field stimulation. Only a high concentration (10(-5) M) of idazoxan was able to markedly antagonise the three contractile stimuli. The effects of idazoxan (at high concentrations) and prazosin were studied upon noradrenaline-evoked contractions attributable to intracellular Ca2+ release using Ca2+ -deplete medium, and, on readministration of Ca2+, upon Ca2+ influx. Both components of the response were inhibited by the two antagonists, but the contraction associated with intracellular Ca2+ release was preferentially inhibited in each case. The results demonstrate that only alpha 1-adrenoceptors are involved in the contraction of this tissue to exogenous and endogenous noradrenaline. This receptor type is linked to both extracellular and intracellular Ca2+ sources, although the latter is more sensitive to inhibition by alpha-adrenoceptor blocking drugs.

Animals↗

Antibodies to covalent aggregates of insulin in blood of insulin-using diabetic patients.

A covalent aggregate twice the size of insulin accounts for approximately 28% of total circulating insulin immunoreactivity in type I diabetic patients. These aggregates are probably covalent dimers of insulin and should contain unique epitopes distinct from the parent molecule. Therapeutic insulin contains a similar material and is the source of the circulating aggregate. Anti-aggregate antibodies were detected by binding-inhibition techniques in 9 of 29 long-term diabetic patients. These antibodies were directed against structures distinct from those of the parent molecule insulin monomer. All antibody-positive patients were men whose blood also contained antibodies to insulin monomer. We conclude that the blood of approximately 30% of insulin-using diabetic patients contains antibodies directed against epitopes unique to the insulin aggregates. Because insulin monomer and aggregates probably share a common primary amino acid sequence, the anti-aggregate antibodies are probably directed against conformational determinants. Further work is needed to determine whether such aggregates promote or accentuate the development of anti-insulin antibodies in certain genetically predisposed individuals.

Adult↗

Reiter's syndrome and recurrent peritonitis after appendectomy.

A 15-year-old male adolescent underwent an appendectomy for acute gangrenous appendicitis. One week after surgery, he underwent an exploratory laparotomy that revealed two pericecal abscesses, which were drained. Two weeks later, he had diffuse peritonitis and underwent another laparotomy, which revealed a sterile fibrinous peritonitis. Oligoarticular inflammatory arthritis, urethritis, and recurrent peritonitis subsequently developed. He was found to be positive for HLA-B27 antigens. This case report illustrates that reactive arthritis (Reiter's syndrome) may develop after peritoneal infections. It also raises the possibility that the inflammatory process, which involves other serosal surfaces in Reiter's syndrome, may affect the peritoneum.

Abscess↗

Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease.

We examined the distribution and density of N-methyl-D-aspartate (NMDA) displaceable L-[3H]glutamate binding sites in human hippocampal samples obtained postmortem from Alzheimer's disease (AD) patients and from age-matched controls. Binding to NMDA receptors was stable for at least 72 h postmortem, and the pharmacological profile corresponded to that described using electrophysiology. NMDA receptors were concentrated in the terminal fields of major hippocampal pathways including the perforant path, Schaffer collaterals and the hippocampal output to the subiculum, all of which are proposed to use an excitatory amino acid transmitter. Little if any change in hippocampal receptor density was observed in AD patients compared to age-matched controls except in one case where major hippocampal cell loss occurred. The distribution of NMDA receptors did, however, correspond to the predilection for neuritic plaques and neurofibrillary tangles in hippocampal subfields.

Aged↗

Studies on human blood lymphocytes with iC3b (type 3) complement receptors. I. Granular, Fc-IgG receptor positive and negative subsets in healthy subjects and patients with systemic lupus erythematosus.

By using the OKM1 monoclonal antibody and the fluorescence-activated cell sorter to identify lymphocytes bearing iC3b (type 3) complement receptors, two principal populations of OKM1+ lymphocytes have been identified in human peripheral blood. One subset exhibited azurophilic granules and Fc receptors for IgG stained by Leu-11. The other population did not display FcR, but was enriched in cells reacting with OKT3 and OKT8 (low intensity). In healthy subjects, approximately 60% of CR3+ lymphocytes were granular FcR-bearing cells and only 18% co-expressed OKT3 determinants. In patients with systemic lupus erythematosus (SLE), CR3+ lymphocytes were predominantly FcR negative cells and 71% lacked granules. Only 33% reacted with Leu-11, but 50% co-expressed OKT3, 44% reacted with OKT8+, and 15% were OKT4+. We tested the hypothesis that agranular OKT3+ Leu-11- lymphocytes, such as those found in SLE patients, contained the precursors of natural killer (NK) cells. Leu-11+ cells were removed from normal lymphocytes by complement lysis, and the remaining cells were treated with recombinant IFN-alpha, IFN-gamma, or IL 2. These procedures were ineffective in generating typical NK effector cells. Our studies do not support the hypothesis that CR3+ Leu-11- lymphocytes are the precursors of granular Leu-11+ NK cells.

Antibodies, Monoclonal↗

Reactive arthritis and psittacosis.

A 54-year old man had severe inflammatory polyarthritis 10 days after the onset of an acute febrile illness that was serologically documented to be psittacosis. The pattern and chronicity of the articular symptoms, the response to nonsteroidal anti-inflammatory agents, and the presence of HLA-B7-CREG strongly suggest that this was a reactive arthritis. The association of psittacosis and reactive arthritis has previously been reported in the British literature, but this may be the first reported North American case.

Arthritis, Infectious↗