Search PubMed⌕ Search

Biomedical subjects

J Reid

Publications and source records attributed to J Reid.

At least 109 records · Page 6Linked to original sources
PubMed1995

Comparison of in vivo efficacy and mechanism of action of antimurine monoclonal antibodies directed against TCR alpha beta (H57-597) and CD3 (145-2C11).

Monoclonal antibodies (mAbs) directed against the T cell receptor (TCR)-associated CD3 chains and against the TCR-alpha beta heterodimer can inhibit allograft rejection in humans and in experimental animals. Since the effects of stimulation through these cell surface structures may differ, it has been suggested that there could be advantages to targeting one structure versus the other. In order to directly compare two such mAbs for in vivo immunosuppressive properties and mechanisms of action, C57BL/10 mice were treated with mAbs H57-597 (H57, anti-alpha beta) or 145-2C11 (2C11, anti-CD3), either as intact mAb or as F(ab')2 fragments. F(ab')2 fragments of both mAbs had similar effects. Both prolonged skin allograft survival, preferentially depleted CD4+ T cells, downregulated IL-2 secretion, and failed to inhibit CTL. In contrast, the effects of the intact form of the two mAbs differed significantly. Intact H57 was far more effective than 2C11 in prolonging skin allograft survival and in inhibiting cytokine secretion and CTL function. This increased immunosuppressive effect was associated with a significantly more complete and prolonged depletion of both CD4+ and CD8+ T cells and down-modulation of TCR expression on remaining T cells. A markedly greater half-life was observed for H57, associated with reduced immunogenicity. These data suggest that the increased immunosuppressive properties of H57 are due to its reduced immunogenicity, rather than to differences in signal transduction, and support the argument that reducing the immunogenicity of mAbs in the clinical setting by "humanization" may result in improved efficacy.

Animals↗
PubMed1995

Critical re-examination of the distribution of aromatase-immunoreactive cells in the quail forebrain using antibodies raised against human placental aromatase and against the recombinant quail, mouse or human enzyme.

Mouse and quail aromatase cDNAs were isolated from libraries of mouse ovary and quail brain by using a human aromatase cDNA fragment (hA-24) as a probe. These three cDNAs were inserted into plasmid vectors and expressed in Escherichia coli. Antisera against these purified recombinant proteins were raised in rabbit and purified by ammonium sulfate fractionation and affinity chromatography. The three antibodies directed against recombinant human, mouse and quail proteins were used to visualize aromatase-immunoreactive cells in the quail brain. They were compared with the antibody raised against human placental aromatase used in previous experiments and with another antibody recently developed by similar methods. The signal obtained with all antibodies was completely abolished by preadsorption with the homologous recombinant antigens and the signal produced by the two antibodies raised against placental aromatase was similarly abolished by a preadsorption with recombinant quail aromatase. The antibodies raised against recombinant proteins identified the major groups of aromatase cells previously described in the quail brain. The antibodies directed against the mouse and quail antigen identified more positive cells and stained them more densely than the antibodies raised against human recombinant antigen or purified placental aromatase. The new cell groups identified by the antibody raised against quail recombinant aromatase were located in an area ventral to the fasciculus prosencephali lateralis, the nucleus accumbens, the paleostriatum ventrale, the nucleus taeniae, the area around the nucleus ovoidalis, the caudal tuber and the mesencephalic central gray. A critical re-examination of the distribution and nomenclature of the aromatase-positive cells is proposed based on these new findings.

Animals↗
PubMed1995

Characteristics of ulcers of the small bowel induced by non-steroidal anti-inflammatory drugs in the rat: implications for clinical practice.

Small bowel ulcers were created in the rat after the oral administration of non-steroidal anti-inflammatory drugs (NSAIDs). Of the six NSAIDs tested, indomethacin and diclofenac alone were associated with such damage which did not occur in a simple dose-related fashion. Bacteria were observed by electron microscopy in an active state of division in the base of the ulcers. When grown aerobically these were shown to be strains of Escherichia coli and Proteus mirabilis. Anatomically, NSAID-induced ulcers were found throughout the length of the bowel although more abundant in the proximal half. In vivo and in vitro sensitivity to antibiotics suggested that in addition to the bacteria identified, anaerobic beta-lactamase-producing organisms also have an important role in ulcer production in this model. This rat model of NSAID-induced gut toxicity is discussed in relation to the human situation, particularly for patients who take NSAIDs and who have an iron-deficiency anaemia and blood in their faeces, but no lesions in either the upper or lower bowel.

Animals↗
PubMed1995

Comparison of the angiotensin II antagonist UP269-6 with the angiotensin converting enzyme inhibitor enalapril in normotensive volunteers challenged with angiotensin I.

We assessed the inhibitory effect of UP269-6, a new orally active angiotensin II (ANG II) receptor antagonist, on the pressor action of exogenous ANG I in healthy male volunteers maintained on an unrestricted sodium intake and compared it with that of enalapril. Seven different single doses of UP269-6 ranging from 5 to 180 mg, 20 mg enalapril, or placebo were administered to 16 subjects in a double-blind fashion. The order of placebo and enalapril was randomized, and UP269-6 was given in an ascending dose order. The peak systolic blood pressure (SBP) response to a test dose of ANG I was determined serially before and after oral drug administration by monitoring finger BP by a photoplethysmographic method. No drug-related side effect was observed. There was a dose-dependent inhibition of the SBP response to the ANG I challenge. Doses as low as 40 to 80 mg had blocking effects quite similar to that of enalapril 20 mg. Ten hours after the 20- and 40-mg doses of UP269-6, the SBP response was still attenuated when drug levels no longer were measurable in plasma. UP269-6 also produced a dose-related increase in active renin and ANG II levels at 24 h after drug intake. In these volunteers on unrestricted salt intake, no statistically significant effect on 24-h urinary aldosterone excretion was observed. Based on these preliminary data, the pharmacokinetic drug half-life (t 1/2) was estimated at 4.7 h and the EC50 was estimated at 41 ng/ml. UP269-6 appears to be a well-tolerated, potent, orally active, antagonist of ANG II receptors in men. Doses of 40-80 mg might block the ANG I pressor response as does enalapril 20 mg.

Administration, Oral↗
PubMed1995

Failure to influence hypotension during spinal anaesthesia with a limb tourniquet.

Fourty patients undergoing total hip replacement under spinal anaesthesia were allocated randomly to have a thigh tourniquet inflated after exanguination of the leg not being operated on or to act as controls. Significant hypotension (systolic arterial pressure < 70 mm Hg) was treated with i.v. ephedrine in 6 mg boluses. There was no significant difference between the two groups with respect to systolic blood pressure or requirement of ephedrine, during the hour that the tourniquet was applied or the period immediately after the removal of the tourniquet.

Adult↗
PubMed1995

Maternal asthma, premature birth, and the risk of respiratory morbidity in schoolchildren in Merseyside.

BACKGROUND: A study was carried out to analyse the impact of maternal asthma on the risk of preterm delivery and the contribution of preterm delivery to the development of childhood asthma. METHODS: Two cross sectional community studies of 1872 children (5-11 years) in 1991 and 3746 children in 1993 were performed. A respiratory health questionnaire was distributed throughout 15 schools in Merseyside and completed by the parents of the children. RESULTS: Asthmatic mothers were more likely to have a preterm delivery than non-asthmatic mothers (odds ratio (OR) 1.49; 95% CI 1.10 to 2.02). Smoking was a separate risk factor for preterm delivery (OR 1.35; 95% CI 1.10 to 1.65). Asthmatic mothers did not have an increased risk of delivering small, growth retarded babies. Maternal asthma, paternal asthma, and premature birth, in that order, increased the risk of later childhood respiratory morbidity (OR 3.13, 95% CI 2.36 to 4.16; 2.23, 95% CI 1.62 to 3.05; 1.40, 95% CI 1.10 to 1.79). Conversely, babies who were small for gestational age appeared less likely to develop doctor diagnosed asthma or the symptom triad of cough, wheeze, and breathlessness in childhood, although this was not statistically significant (OR 0.63, 95% CI 0.28 to 1.41). CONCLUSIONS: Maternal smoking during pregnancy and maternal asthma are independent risk factors associated with preterm delivery. Asthma in mothers predisposes to preterm delivery but not fetal growth retardation. Preterm birth, but not growth retardation, predisposes the child to the development of subsequent asthma.

Asthma↗
PubMed1995

Inhibition of T lymphocyte activation by a novel p56lck tyrosine kinase inhibitor.

A new p56lck tyrosine kinase inhibitor WIN 61651 [1,4-dihydro-7-(4-methyl-1-piperizinyl)-1-(4-(4-methyl-1-piperi zinyl))phenyl- 4-oxo-3-quinolinecarboxamide) is described. WIN 61651, which is competitive with ATP, demonstrates selectivity for the lymphoid restricted tyrosine kinase p56lck over serine/threonine kinases, such as protein kinase C and protein kinase A, and over some other tyrosine kinases, including erbB2, epidermal growth factor receptor, and insulin receptor; however, it is equipotent for inhibition of p56lck and the platelet derived growth factor receptor tyrosine kinases. WIN 61651 inhibits p56lck activity in cell-free assays, tyrosine kinase activity in a T lymphocytic cell line, and T cell activation, as measured by IL-2 production by purified CD4 positive peripheral blood T lymphocytes and the mixed lymphocyte reaction. WIN 61651 constitutes a new tool for studies on the role for tyrosine kinases in lymphocyte function.

Antibodies↗
PubMed1995

Appetitive as well as consummatory aspects of male sexual behavior in quail are activated by androgens and estrogens.

Appetitive male sexual behavior was measured in male quail with the use of a learned social proximity procedure that quantified the time spent by a male in front of a window providing a view of a female that was subsequently released into the cage, providing an opportunity for copulation. The learned response is not acquired by castrated males but can be acquired when castrates are treated with testosterone (T) or with the synthetic estrogen diethylstilbestrol or with the endogenous estrogen 17 beta-estradiol. Only birds that become sexually active acquire the response. Conversely, birds in which the consummatory copulatory behavior is disrupted by treatment with the antiestrogen tamoxifen lose the anticipatory response. These results demonstrate that appetitive sexual behavior is, like copulation, activated by T and by estrogens. This suggests that intracerebral aromatization of T also plays a critical role in the activation of this behavior.

Androgens↗
PubMed1994

The contribution of AAUAAA and the upstream element UUUGUA to the efficiency of mRNA 3'-end formation in plants.

The requirement for sequence specificity in the AAUAAA motif of the cauliflower mosaic virus (CaMV) polyadenylation signal was examined by saturation mutagenesis. While deletion of AAUAAA almost abolished processing at the CaMV polyadenylation site, none of the 18 possible single base mutations had a dramatic effect on processing efficiency. The effect of replacing all six nucleotides simultaneously varied depending on the sequence used, but some replacements were as detrimental as the deletion mutant. Taken together, these results confirm that AAUAAA is an essential component of the CaMV polyadenylation signal, but indicate that a high degree of sequence variation can be tolerated. A repeated UUUGUA motif was identified as an important upstream accessory element of the CaMV polyadenylation signal. This sequence was able to induce processing at a heterologous polyadenylation site in a sequence-specific and additive manner. The effect of altering the spacing between this upstream element and the AAUAAA was examined; moving these two elements closer together or further apart reduces the processing efficiency. The upstream element does not function to signal processing at the CaMV polyadenylation site if placed downstream of the cleavage site. Analysis of further upstream sequences revealed that almost all of the 200 nt fragment required for maximal processing contributes positively to processing efficiency. Furthermore, isolated far upstream sequences distinct from UUUGUA were also able to induce processing at a heterologous polyadenylation site.

Amino Acid Oxidoreductases↗
PubMed1994

Human endothelial cells are defective in diabetic vascular disease.

Diabetic vascular disease is characterized pathologically by endothelial cell (EC) hyperplasia and basement membrane (BM) thickening. One key question regarding the pathogenesis of diabetic vascular disease is whether the EC or BM or both are primarily defective and responsible for these pathological changes. Previous studies, which took the approach of creating artificial diabetic conditions, have been inconclusive. It is known, however, that the extracellular matrix may be altered by glycosylation as a result of hyperglycemia, thereby altering EC function. To begin to address this question and more closely mimic the situation in vivo, we characterized human diabetic EC harvested from insulin-dependent diabetic mothers (IDDM) at the cellular and molecular levels. Human EC were isolated from both normal and IDDM umbilical cords and cellular functions evaluated using standard assays of attachment (% attached cells), proliferation (cpm/cell), resistance to detachment under shear stress (number of cells remaining attached), and glucose uptake (cpm/2 X 10(4) cells). Gene expression of major BM components (collagen type IV, laminin beta 1, and laminin beta 2) was quantified by Northern analysis. Diabetic EC demonstrated increased proliferation (two- to eightfold compared to normals), were 20-40% less resistant to shear stress and took up glucose 10-15% more slowly than normal EC. Furthermore, Northern analysis showed that the expression of major BM components was increased by an average of 10-18% in diabetic cells compared to normal cells. These results were consistent with in vivo observations and previously published data.(ABSTRACT TRUNCATED AT 250 WORDS)

Basement Membrane↗