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Biomedical subjects

E Jackson

Publications and source records attributed to E Jackson.

At least 91 records · Page 5Linked to original sources

Nematodirus infection in lambs on an alternate grazing system of husbandry.

The epidemiology of Nematodirus battus infection under a husbandry system based on an annual alternation of sheep and cattle was studied from 1983 to 1985. Pasture larval levels and sheep and cattle worm egg outputs were monitored from April to September each year. The level of N battus contamination on the sheep pasture and the number of clinically affected lambs increased over the three years despite grazing with cattle in the intervening year. Examination of cattle faeces demonstrated that six-month-old calves excreted moderate numbers of N battus eggs in June and July, thus contaminating next season's sheep grazing.

Animal Husbandry↗

Genetically determined hypercholesterolemia in a rhesus monkey family due to a deficiency of the LDL receptor.

A family of rhesus monkeys comprising a sire, a dam, and four male offspring were fed a cholesterol-free Purina Chow diet for several months. The sire, 431-J, and two of the offspring, B-8204 and B-8806, had persistent plasma cholesterol levels in the range of 100-130 mg/dl, whereas the dam, 766-I, and the two other offspring, B-1000 and B-7643, exhibited a marked hypercholesterolemia in the 250-300 mg/dl range associated with an elevation of plasma LDL and apoB. When fed for 12 weeks a diet containing 12.5% lard and 0.25% cholesterol, sire, dam, B-1000 and B-7643 exhibited a marked hypercholesterolemia (500-800 mg/dl range), whereas B-8204 and B-8806 developed only a modest hypercholesterolemia (200-250 mg/dl). All animals were Lp[a]+. Skin fibroblasts from each animal and from control cells were grown in 10% fetal calf serum, transferred to 10% lipoprotein-deficient serum for 48 hr, and then incubated at 4 degrees C or 37 degrees C with 125I-labeled Lp[a]-free LDL. The fibroblasts from dam and offspring B-1000 and B-7643 bound and internalized 125I-labeled LDL less efficiently than control cells. Mathematical analyses of the 4 degrees C binding data indicated that there were no significant differences in LDL binding affinity between test and control cells suggesting that cells from the animals with a spontaneous hypercholesterolemia had a decreased number of LDL receptors. This conclusion was supported by the results of ligand and immunoblot analyses carried out on cell lysates separated by gradient gel electrophoresis. We conclude that a genetically determined LDL receptor deficiency was responsible, in part, for the spontaneous hypercholesterolemia observed in three out of the six family members and that this deficiency accounted for the hyperresponsiveness to a dietary fat and cholesterol challenge by the dam and the two offspring, B-1000 and B-7643. The hyperresponsiveness noted in the sire that had no evidence for LDL-receptor deficiency illustrates that factors other than the LDL receptor were responsible for the hypercholesterolemia attending the fat challenge.

Animals↗

Lymphotoxic activity of methyl prednisolone in vitro--I. Comparative toxicity of methyl prednisolone in human cell lines of B and T origin.

The cytotoxic activity of methyl prednisolone was compared in EB-3(B), NALM-6(B), CCRF-CEM(T) and RPMI-8226 (plasma cell) cell lines derived from human lymphoid malignancies. Whereas EB-3 cells were steroid-sensitive, NALM-6 cells were partially sensitive and CCRF-CEM and RPMI-8226 were steroid resistant at concentrations of methyl prednisolone up to 10(-4) M. A high concentration of methyl prednisolone, 2.5 X 10(-3) M was toxic to all cell lines. Steroid-sensitivity did not correlate with the incorporation of [3H] dexamethasone and could not be mimicked by flurbiprofen, a non-steroidal anti-inflammatory agent. Both theophylline and di-butyryl cAMP were toxic towards NALM-6, EB-3 and CCRF-CEM cells; however, this toxicity was reversible and did not reflect the cells' sensitivities towards methyl prednisolone. Furthermore, elevated levels of cAMP in theophylline-treated cells, were not demonstrable in cells treated with methyl prednisolone at toxic or non-toxic concentrations of the steroid. Steroid-sensitive EB-3 cells exposed to 10(-5) M methyl prednisolone, produced a soluble factor which was toxic CCRF-CEM cells.

B-Lymphocytes↗

Tumour necrosis factor in man: clinical and biological observations.

Eighteen patients with advanced cancer have been treated intravenously with human recombinant tumour necrosis factor (rhTNF). The drug produced febrile reactions at all doses although these were preventable by steroids and indomethacin. Doses at or above 9 x 10(5) units (400 micrograms)m-2 were associated with hypotension, abnormal liver enzymes, leucopenia and mild renal impairment in a substantial proportion of patients. RhTNF was cleared from plasma with a half life of approximately 20 minutes but non-linear pharmacokinetics lymphoma, improvements in their tumours were recorded. RhTNF was noted to produce rapid increases in serum C-reactive protein concentrations. Endogenous TNF levels were not found to be elevated in 72 cancer patients. TNF deserves further therapeutic evaluation and these observations support its biological importance as an endogenous pyrogen, mediator of acute phase protein responses, and a mediator of endotoxic shock.

Adolescent↗

A receptor for monomeric IgG2b on rat macrophages.

The binding to rat splenic and peritoneal macrophages of affinity-purified monoclonal rat IgGs, representing all IgG subclasses, was measured by the direct binding of 125I-labelled proteins using an assay that did not require the removal of unbound Ig by washing. Only rat monomeric IgGs of the subclass IgG2b bound specifically and in large amounts to rat macrophages. The binding was temperature dependent and more IgG2b bound to the cells at 4 degrees than at 37 degrees. Spleen macrophages bound approximately 10 times more IgG2b than the same number of peritoneal macrophages, although the association constants (Kas) for the binding were similar for both types of macrophage. The calculated values for the Kas, which varied slightly with each experiment and increased with decrease in temperature, fell within the range 1.3-5.3 X 10(8) M-1; the number of binding sites was estimated as about 10(5)/splenic macrophage and 10(4)/peritoneal macrophage. The binding of 125I-IgG2b to splenic macrophages was inhibited only by unlabelled proteins of the IgG2b isotype and not by IgG1, IgG2a and IgG2c proteins. Soluble IgG2b-antigen complexes also bound to the FcR for monomer but a soluble IgG2a-antigen complex did not inhibit the binding of monomeric IgG2b.

Animals↗

Mucosal IgA production and lymph cell traffic following prolonged low level infections of Ostertagia circumcincta in sheep.

Some aspects of the local immune response to daily challenge with 2000 Ostertagia circumcincta larvae were studied by monitoring changes in the composition of gastric lymph of naive and previously infected sheep. The main changes in the naive group were increases in lymphoblast output and concentrations of pepsinogen whereas lymph albumin values decreased markedly and IgA concentrations were usually unchanged. In contrast, in the previously infected sheep, the continuous challenge stimulated only transient increases in lymphoblast and IgA containing cell traffic whereas lymph IgA and pepsinogen concentrations remained elevated throughout the experiment. By temporarily interrupting the challenge in a second group of previously infected sheep it was shown that elevated IgA and pepsinogen values were maintained only if larval intake was continuous.

Abomasum↗

Management of posttreatment endodontic pain with oral dexamethasone: a double-blind study.

In a double-blind study, twenty-five subjects who received oral dexamethasone and twenty-five placebo subjects rated their postoperative pain 8 and 24 hours following initial endodontic treatment. The subjects who received dexamethasone reported statistically significantly less postoperative pain than the subjects who received the placebos. The question is raised as to whether oral corticosteroids are appropriate for routine management of posttreatment endodontic pain.

Administration, Oral↗

Coronary vascular occlusion mediated via thromboxane A2-prostaglandin endoperoxide receptor activation in vivo.

The use of enzyme inhibitors to clarify the role of thromboxane A2 in vasoocclusive disease has been complicated by their non-specific action. To address this problem we have examined the effects of thromboxane A2/prostaglandin endoperoxide receptor antagonism in a canine model of platelet-dependent coronary occlusion. Two structurally distinct thromboxane A2/prostaglandin endoperoxide receptor antagonists, 3-carboxyl-dibenzo (b, f) thiepin-5,5-dioxide (L636,499) and (IS-(1 alpha,2 beta(5Z),3 beta,4 alpha))-7-(3-((2-((phenylamino)-carbonyl)hydrazino)methyl)-7- oxabicy-clo(2.2.1)-hept-2-yl)-5-heptenoic acid (SQ 29,548), were studied to ensure that the effects seen in vivo were mediated by receptor antagonism and did not reflect a nonspecific drug effect. Both compounds specifically inhibited platelet aggregation induced by arachidonic acid and by the prostaglandin endoperoxide analogue, U46619, in vitro and ex vivo, and increased the time to thrombotic vascular occlusion in vivo. When an antagonist (L636,499) was administered at the time of occlusion in vehicle-treated dogs, coronary blood flow was restored. In vitro L636,499 and a third antagonist, 13-azaprostanoic acid, specifically reversed endoperoxide-induced platelet aggregation and vascular smooth muscle contraction. Neither compound altered cyclic AMP in platelet-rich plasma before or during disaggregation. Therefore, reversal of coronary occlusion may reflect disaggregation of platelets and/or relaxation of vascular smooth muscle at the site of thrombus formation through specific antagonism of the thromboxane A2/prostaglandin endoperoxide receptor. Thromboxane A2/prostaglandin endoperoxide receptor antagonists are compounds with therapeutic potential which represent a novel approach to defining the importance of thromboxane A2 and/or endoperoxide formation in vivo.

Animals↗

Transfer of immunity to Ostertagia circumcincta and IgA memory between identical sheep by lymphocytes collected from gastric lymph.

Sheep rendered immune to Ostertagia circumcincta were challenged with 50,000 larvae and lymphocytes were collected from the gastric lymph up to eight days after challenge. The cells were transferred intravenously to genetically identical worm-free sheep which, together with controls, were challenged with 50,000 larvae and killed nine days later. Cells obtained during the donors lymphoblast response to challenge transferred partial immunity, measured either as stunting or loss of worms. Significantly less immunity was transferred by cells collected either before or after this response. Thus the responding cells can mediate protective immunity to O circumcincta. On the other hand the donor sheep remained immune to their challenge infection despite being depleted of these functional cells, showing that their presence was not essential for immunity to be maintained. Comparison of the immunoglobulin A (IgA) concentrations in the gastric lymph of recipient and control sheep showed that a local IgA response had also been transferred. Enumeration of mucosal mast cells suggested that a mastocytosis had been transferred to the two recipients which were most immune to challenge.

Animals↗

Age immunity to Ostertagia circumcincta: comparison of the local immune responses of 4 1/2- and 10-month-old lambs.

In 2 experiments, the local immune response to infection with 50,000 O. circumcincta was monitored in 4 1/2-month-old previously infected lambs by following changes in the composition of gastric lymph. The previously infected lambs were partially resistant to the challenge in that they harboured a greater proportion of early fourth stage parasites and that the developing larvae recovered from them were distinctly shorter than those present in controls. They also exhibited a secondary local immune response in the gastric lymph consisting of increases in the output of lymphoblasts and IgA cells which peaked 3 to 5 days after challenge, followed by increases in lymph IgA and IgA anti-larval antibody on days 6 and 7. The size of the total IgA response in a sheep was highly correlated with the degree of stunting of its larvae, suggesting that IgA antibody can reduce the growth of developing Ostertagia. When compared with the results of 2 identically designed experiments carried out previously in 10-month-old sheep, the younger lambs were measurably less resistant to challenge and most aspects of the magnitude of the local immune response were significantly depressed, although the timing of the response was similar. It is suggested that this poorly developed ability to mount a secondary mucosal immune response may explain the relative failure of the younger lamb to develop resistance to gastro-intestinal nematodes.

Aging↗

Cholinergic REM sleep induction response correlation with endogenous major depressive subtype.

We compared central cholinergic responsiveness (using the latency to induction of rapid eye movement sleep after arecoline challenge as a response marker) in 90 subjects: patients with major depressive disorder (MDD) (n = 53), nonaffective psychiatric controls (n = 17), and normal controls (n = 20). MDD patients as a whole showed a supersensitive cholinergic response compared to nonaffective patients and normal subjects. Further analysis indicated a strong association between cholinergic supersensitivity and endogenous subtype of MDD, including a significant correlation with specific endogenous features such as distinct quality of mood, anhedonia, lack of reactivity, and agitation. Unlike rapid eye movement (REM) latency (a more conventional physiological marker), cholinergic sensitivity did not correlate with age or severity of illness but only with the presence of endogenous features. Previously described sleep physiological correlates such as REM latency and REM density of the first REM period also distinguished between endogenous and nonendogenous MDD. There was a statistically significant correlation between REM latency and arecoline REM induction response.

Adult↗

Manifestations of resistance to ovine ostertagiasis associated with immunological responses in the gastric lymph.

Groups of previously infected and worm-free sheep were serially killed up to 10 days after challenge with 50 000 Ostertagia circumcincta larvae. Two similar groups of sheep were killed 10 days after challenge with 1000 larvae. The previously infected sheep were resistant to the smaller challenge dose in that fewer, stunted worms were recovered from them than from controls. However, this resistance was not as marked as that observed in the previously infected sheep which received the large challenge, because proportionally fewer worms were recovered after the 50000 dose and the great majority of these were arrested at the early fourth stage. The gastric lymph ducts of 6 previously infected sheep were cannulated successfully and a marked local immune response was detected in 3 sheep which were challenged with 50 000 larvae. No response was detected in 3 cannulated sheep challenged with 1000 larvae. In the lymph of the 50 000 dose group, a temporary increase in pepsinogen activity suggested that a hypersensitivity reaction related to the presence of large numbers of mucosal mast cells began between 24 and 48 h after challenge. This was followed by marked increases in the cellular and IgA content of lymph, which reached peaks on days 3 and 6, respectively. It is suggested that the response detected in the gastric lymph reflected aspects of a local immune reaction in the abomasal mucosa and that this reaction accounted for the enhanced degree of resistance to the larger challenge dose.

Animals↗

Measurement of levels of aminoglycosides and vancomycin in serum in the presence of new beta-lactam antibiotics.

We evaluated the effect of new beta-lactam antibiotics (azlocillin, mezlocillin, piperacillin, cefotaxime, moxalactam, and cefoperazone) on assays for aminoglycosides and vancomycin. These antibiotics produced no interference in an immunoassay for gentamicin and tobramycin. The new penicillins produced no interference in a bioassay of amikacin and vancomycin with penicillinase incorporated into the assay agar. Bioassay in the presence of the cephalosporins required predigestion with cephalosporinase. We describe a method for accurate bioassay in the presence of the available cephalosporins, with the exception of moxalactam.

Aminoglycosides↗

The production of hybridomas from the gut associated lymphoid tissue of tumour bearing rats. I. Mesenteric nodes as a source of IgG producing cells.

Rat X rat hybridomas secreting antibodies with tumour specificity have been prepared using cells from the mesenteric nodes of rats bearing syngeneic sarcomata in their Peyer's patches. The antibodies obtained, which embraced all of the major immunoglobulin classes, varied in cellular reactivity from the individually tumour specific to cross-reactive with both normal and tumour cells. Several IgA producing hybridomas were prepared using this protocol but IgG secretors were obtained more frequently and they accounted for about half of the specific hybridomas. Specific IgG producers were found to predominate also when hybridomas were prepared from the mesenteric nodes of a rat immunized by injection of horseradish peroxidase into the Peyer's patches. Comparison of these data with our earlier results using spleen cells taken from rats that were either hyperimmunized with, or were bearing the same tumours in the leg, show that mesenteric nodes draining a tumour growing in the Peyer's patches are a much better source specific IgG producing B cells.

Animals↗

Comparison of saline incubation and pepsin digestion as methods for recovering Ostertagia circumcincta larvae from the abomasum of sheep.

Incubation in saline at 37 degrees C was compared with pepsin digestion as a quantitative method for recovering larval stages of Ostertagia circumcincta from the abomasal mucosa of sheep. Experiments showed that the techniques were of roughly similar efficiency even when the larvae were arrested but that the saline method was preferable because worm searching was easier and quicker.

Abomasum↗