Biomedical subjects

A J Lewis

Publications and source records attributed to A J Lewis.

At least 163 records · Page 9Linked to original sources

PubMed1984

Effect of gold salts, D-penicillamine and benoxaprofen on type II collagen-induced arthritis in rats.

We investigated the therapeutic effect of two gold salts, gold sodium thiomalate (GST, i.m.) and auranofin (p.o.), D-penicillamine (p.o.) and benoxaprofen (p.o.) in rat collagen-induced arthritis using type II collagen from fetal bovine articular cartilage. GST, but not auranofin, reduced hind paw edema and bone pathology. However, auranofin reduced serum copper and zymosan-induced prostaglandin production from peritoneal macrophages. In contrast, GST increased both serum copper and macrophage prostaglandin production by zymosan. Benoxaprofen reduced both hind paw edema and pathology, whereas D-penicillamine was without effect. None of these treatments influenced the circulating level of antibody to type II collagen.

Animals↗

PubMed1984

Simian virus 40 specific cytotoxic lymphocyte clones localize two distinct TSTA sites on cells synthesizing a 48 kD SV40 T antigen.

Simian virus 40 specific antigenic sites (TSTA) which react with SV40 specific cytotoxic lymphocytes (CTL) were localized on the surface of mouse embryo fibroblasts (H-2b) transformed with a recombinant plasmid which contain SV40 large T antigen coding DNA sequences (0.65-0.37 map units). These cells (B6/pSV-20-GV) synthesize a large T antigen polypeptide of 48 kD and could be lysed with two independently isolated CTL clones which recognize distinct antigenic sites on SV40 transformed cell surface. These results suggest that at least two distinct TSTA sites are present in cells synthesizing only the amino terminal half of SV40 T antigen.

Animals↗

PubMed1984

Lymphoid abnormalities in rats with adjuvant-induced arthritis. I. Mitogen responsiveness and lymphokine synthesis.

Lewis rats injected in the hind paw with Mycobacterium butyricum develop a severe polyarthritis which shares certain features in common with rheumatoid arthritis in man. Spleen and peripheral blood mononuclear cells from rats with this form of arthritic disease proliferate poorly in vitro in response to concanavalin A (con A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM). The splenic hyporesponsiveness appears within four days of M. butyricum injection (three to five days prior to the development of detectable arthritis), reaches a peak 16-22 days following injection, and persists for at least 40 days. Buffalo strain rats injected with M. butyricum do not develop arthritis, and their spleen cells respond normally to con A, PHA, and PWM. In response to lipopolysaccharide (LPS) the synthesis of interleukin 1 (IL-1) by spleen or peritoneal macrophages from arthritic Lewis rats equalled or exceeded that of macrophages from normal rats. In contrast splenic T cells from arthritic rats produced reduced amounts of interleukin 2 (IL-2; T cell growth factor) in response to stimulation with PHA or con A. Moreover, con-A-activated spleen cells from arthritic rats failed to bind IL-2 and to respond to this growth factor with increased 3H-TdR uptake as did normal spleen cells. In-vitro treatment of 'arthritic' cells with 10(-5) M indomethacin did not restore to normal their reduced mitogen responsiveness, and spleen cells from normal and arthritic rats were equally sensitive to the inhibitory effects of prostaglandin E2 on con-A-induced proliferative responses. These results indicate that peripheral lymphoid function is compromised in rats with adjuvant-induced arthritis and that this functional deficit is mediated by aberrant synthesis of and response to IL-2 by T cells of arthritic animals.

Animals↗

PubMed1984

Modulation of sulfur dioxide-induced airways hyperresponsiveness in the conscious dog.

Brief exposure of conscious dogs to 30 ppm SO2 directly into the lungs resulted in a transient bronchoconstriction followed by a period of hypersensitivity to aerosolized methacholine and 5-hydroxytryptamine. The hypersensitivity was maximal 4 h after exposure to SO2. Both Wy-41,195 and disodium cromoglycate, two antiallergic drugs, inhibited the hypersensitivity to methacholine when administered just prior to methacholine challenge. Neither drug significantly influenced SO2-induced bronchospasm nor influenced methacholine hypersensitivity when administered just prior to SO2 exposure. Furthermore, Wy-41,195 was ineffective against methacholine hypersensitivity when administered orally for 4 days. SO2-induced airway hypersensitivity in the dog may thus provide a useful model for exploring mechanisms and pharmacologic modulation of bronchial hyperreactivity, a common feature of asthma.

Administration, Oral↗

PubMed1984

The comparative bronchodilator properties of alkyl quaternary salts of promethazine.

Several salts of thiazinamium, a quaternary analogue of promethazine, administered by aerosol, possessed equipotent anticholinergic activity in anesthetized guinea pigs but the duration of this effect differed somewhat. N-Butyl substitution in the side chain, but not the corresponding ethyl or n-propyl substitutions, reduced the aerosol anticholinergic potency and duration. There was also a tendency for a corresponding reduction in antihistaminic activity with different alkyl substitutions and for a greatly reduced duration of this effect.

Aerosols↗

PubMed1984

Effect of various dietary arginine: lysine ratios on performance, carcass composition and plasma amino acid concentrations of growing-finishing swine.

Crossbred growing-finishing pigs (112 barrows, 48 gilts) were used to determine the effect of reducing excess dietary arginine, through feedstuff variation, on performance, carcass composition and plasma amino acid concentrations. Diets contained five, four, three or two times the NRC requirement for arginine. Lysine in all diets was formulated to be equal to NRC requirements, and all diets contained at least 100% of the NRC recommendations for all other essential amino acids. Initial weight, final weight and days on test for the grower phase were 26.7 kg, 44.2 kg and 28 d, respectively. Weight gain and gain/feed were not different among treatments but feed intake showed a quadratic response during the grower phase, being highest at four times the NRC requirement for arginine. Initial weight, final weight and days on test for the finisher phase were 44.2 kg, 96.9 kg and 67 d, respectively. Weight gain during the finisher phase and for the total experiment exhibited a quadratic response, being highest for the pigs fed the intermediate arginine levels. Gain/feed for the finisher phase followed the same trend as weight gain. Feed intakes for the finisher phase and total experiment were not different among treatments. Carcass data were collected on all barrows. There were no differences in hot carcass weight or adjusted average backfat among treatments. Loin eye area and percentage of lean decreased linearly as arginine level decreased in the diet. Plasma urea, arginine and orthinine concentrations decreased linearly with decreasing dietary arginine. Plasma lysine exhibited both a quadratic and a cubic response. The data indicate that reducing excess dietary arginine had little effect on performance or carcass composition and no consistent effect on plasma lysine of growing-finishing swine.

Amino Acids↗

PubMed1984

Effects of excess arginine with and without supplemental lysine on performance, plasma amino acid concentrations and nitrogen balance of young swine.

Three experiments were conducted to determine the effects of excess arginine on performance, plasma amino acid levels and N balance of young pigs (initial weights 6.9, 7.0 and 10.3 kg, respectively). In a 28-d growth trial, various amounts of arginine (0 to 1.6%) were added to a conventional starter diet. Addition of arginine decreased (P less than .01) average daily feed intake (ADFI) and gain (ADG), but had no effect on feed efficiency (G/F). Plasma urea, arginine and ornithine concentrations were elevated (P less than .001) by the increasing dietary arginine levels at d 14 and 28. Plasma histidine levels were reduced (P less than .01) at d 28. Plasma lysine levels exhibited a cubic response (P less than .05) at d 14, but were not affected by excess arginine at d 28. In a second growth trial ADFI and ADG were decreased (P less than .05), but G/F was not affected by the addition of 1.6% dietary arginine. Lysine supplementation (0, .15 or .30%) increased performance in the absence of excess arginine, but the main effect of lysine was not significant for any performance criteria. As in the first experiment, plasma concentrations of urea, arginine and ornithine were increased (P less than .001) by the addition of arginine. Plasma histidine was not affected by either arginine or lysine. Plasma lysine levels were reduced (P less than .001) by dietary arginine and increased (P less than .001) by lysine. In a N balance experiment, addition of 1.6% dietary arginine increased N digestibility, but decreased apparent biological value. Nitrogen balance was not affected by added arginine. Lysine addition did not improve any of these three indices of N utilization. The inability of lysine supplementation to alleviate any of the adverse effects of excess arginine in young swine indicates that the reduced performance is caused by a generalized amino acid imbalance, and not by a specific interference with lysine utilization in the manner of a classical arginine-lysine antagonism.

Amino Acids↗

PubMed1984

Relationship of lactation energy intake and occurrence of postweaning estrus to body and backfat composition in sows.

Forty-five crossbred primiparous sows were used to determine the relationship of lactation energy intake and the occurrence of postweaning estrus to (1) body fat (percentage), (2) lean body mass (LBM) and (3) qualitative and quantitative characteristics of adipose tissue. Sows received 8 (Lo) or 16 (Hi) Mcal of metabolizable energy (ME)/d during lactation and 5.4 Mcal of ME/d postweaning. Serum samples were obtained 1 d before weaning (d 0) and analyzed for creatinine and urea-N (indices of muscle and amino acid catabolism, respectively). Subcutaneous adipose tissue samples were obtained and analyzed for total lipid and myristic, palmitic, palmitoleic, stearic, oleic and linoleic acids. Last rib backfat thickness determined at weaning was used to estimate body fat (percentage). Lean body mass was estimated from 48-h creatinine excretion rates determined on d 15 and 16 postweaning. Sows fed the Lo diet that returned (Lo-R) and did not return (Lo-NR) to estrus by d 14 postweaning lost more (P less than .01) weight during lactation, gained more (P less than .01) weight postweaning, had higher (P less than .07) body fat (percentage) and a slight trend toward lower creatinine excretion rate than sows fed the Hi diet that returned to estrus (Hi-R). Adipose tissue from sows in the Lo-R and Lo-NR groups had less (P less than .05) lipid than that from sows in the Hi-R group. Concentrations of oleic and stearic acids were lower and higher (P less than .01), respectively, in adipose tissue from sows in the Lo-R and Lo-NR vs Hi-R groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1984

Effects of oral aspirin and oxaprozin on the development of lupus-like disease in MRL/1 mice.

We examined the effects of two prostaglandin synthetase inhibitors, aspirin and oxaprozin, on the development of lupus-like disease in MRL/1 mice. Daily oral administration of 100 mg/kg of these compounds over a period of 3 months significantly reduced thymic lymphoid hyperplasia. In addition, aspirin but not oxaprozin significantly lowered total lymphocyte counts in the peripheral blood. Other drug-related changes, including reduced hyperplasia in the spleen and lymph nodes and an improvement in kidney vasculitis by aspirin, did not reach statistical significance. Neither aspirin nor oxaprozin influenced the circulating levels of anti-ds DNA antibodies or the severity of kidney glomerulonephritis. While the overall effects of these cyclooxygenase inhibitors were not dramatic, the results do indicate that further studies are warranted to determine the precise therapeutic role, if any, for PG-synthetase inhibitors in lupus-like disease.

Administration, Oral↗

PubMed1984

Humoral and cellular immunologic responses in collagen-induced arthritis in rats: their correlation with severity of arthritis.

Collagen arthritis in rats has a well defined humoral and cellular immunologic response to type II collagen, the inciting antigen. Like other chronic models of inflammation, considerable variation exists in terms of severity and incidence. We have attempted to correlate the inflammatory response as measured by paw volume, with serum type II collagen antibody and skin delayed hypersensitivity (DH) to type II collagen. Surprisingly, the incidence and severity of collagen arthritis, induced in the presence of MDP to increase incidence of the disease, are neither correlated with type II collagen antibody nor DH to type II collagen. However, tarsometatarsal bone erosion is significantly correlated with paw edema. Further studies will be necessary to elucidate the role of both humoral and cellular immune responses in the development of type II collagen arthritis in the rat.

Animals↗

PubMed1984

Effect of acute spinal cord injury on axonal counts in the pyramidal tract of rats.

The concentration of axons in the pyramidal tract of normal and spinal cord-injured rats was determined by counting axons in sections of spinal cord stained by the Holmes technique. In the normal rat the axon concentration was uniform in the cervical, thoracic, and lumbar regions, although the size of the tract diminished progressively with its descent in the cord. After acute cord transection or compression injury, the axon concentration distal to the injury site diminished markedly. However, an appreciable number of distal axons persisted after injury, due to either delayed degeneration or to the presence of an admixture of afferent fibers. The axonal counting technique developed in this study should be helpful in experiments on spinal cord injury and regeneration.

Animals↗

PubMed1984

Neurologic complications associated with gold therapy for rheumatoid arthritis.

Neurologic complications of gold are rare and include peripheral neuropathy, a Guillain-Barré-type syndrome, cranial nerve palsies and encephalopathy. Three cases of cranial neuropathy complicating chrysotherapy for rheumatoid arthritis are described. One also had a sensorimotor neuropathy associated with segmental demyelination and axonal degeneration, and another developed an encephalopathy which, on contrast enhanced computed tomographic scanning, showed reversible cerebral and cerebellar white matter lesions. Early recognition and prompt withdrawal of chrysotherapy are the mainstay of management of this lesser known complication.

Adult↗

PubMed1984

Serum chemical values of gestating and lactating swine: reference values.

Reference values of 18 serum constituents were determined in gestating (n = 33) and lactating (n = 13) swine. Serum concentrations of calcium, glucose, urea nitrogen, cholesterol, total protein, and globulin were lower (P less than 0.10) during gestation than during lactation. Concentrations of creatinine, triglycerides, and creatine phosphokinase were higher (P less than 0.10) during gestation than during lactation. Creatinine concentration increased (P less than 0.05) from lactation days 14 to 26.

Animals↗

PubMed1983

Effects of thiazinamium chloride, promethazine and chlorpromazine on thromboxane B2 synthesis, phagocytosis and respiratory burst by rat alveolar macrophages.

The effects of three phenothiazines, promethazine, thiazinamium chloride and chlorpromazine, on macrophage function were investigated in rat alveolar macrophages. The study focused on thromboxane B2 (TxB2) synthesis, zymosan phagocytosis, and hexosemonophosphate (HMP) shunt activity in these phagocytes. TxB2 synthesis by resting macrophages was inhibited by thiazinamium chloride and promethazine in a dose-dependent manner. However, chlorpromazine was inhibitory only at 10(-3) M. Promethazine treatment of zymosan-activated macrophages led to a concomitant reduction in both phagocytosis and TxB2 synthesis. Thiazinamium chloride inhibited TxB2 synthesis but had no effect on the ingestion of zymosan particles. In contrast, chlorpromazine inhibited phagocytosis but not TxB2 synthesis except at 10(-3) M. The effects of these agents on the formation of TxB2 synthesis from exogenous arachidonic acid were also investigated. Under these conditions where indomethacin, a known cyclooxygenase inhibitor, was inhibitory, promethazine but not thiazinamium chloride inhibited TxB2 synthesis from exogenous arachidonic acid. Treatment of macrophages with promethazine and chlorpromazine but not thiazinamium chloride results in a reduction in the oxidative burst during phagocytosis. The results suggest that the phenothiazines used in this study differ from one another in their actions on macrophage function. Furthermore, the ability of thiazinamium chloride to selectively inhibit arachidonic acid metabolism may contribute to its bronchodilator/antiallergic activity.

Animals↗

PubMed1983

Biology of simian virus 40 (SV40) transplantation antigen (TrAg). IX. Analysis of TrAg in mouse cells synthesizing truncated SV40 large T antigen.

Mouse LTK- cells (H-2k) were transfected with a series of recombinant plasmids consisting of the herpes simplex virus type 1 thymidine kinase (TK) gene linked to fragments of SV40 DNA coding for portions of SV40 T antigen in pBR322, and TK+ transformants (LTK+) were selected in HAT medium. The TK+ transformants were analyzed for SV40 transplantation rejection antigen (TrAg) at the cell surface by reacting them with cytotoxic lymphocytes (CTL) generated to SV40 TrAg in C3H/HeJ (H-2k) mice. The results indicated that the cells transformed by pVBETK-1 and synthesizing full size SV40 large T antigen were efficiently lysed by SV40 CTL. In addition, cells transformed by the plasmid pVBt1TK-1 and synthesizing a truncated 33 K T antigen were also found to be susceptible to lysis by the CTL. However, LTK+ cells that were transformed with the plasmid pVBt2TK-1 and which synthesized a truncated T antigen of 12.3 K did not provide a target for SV40 CTL nor did pVBETK-1-transformed cells that did not express any of the SV40 tumor antigens. Only the pVBETK-1-transformed cells that express 94 K T antigen were able to immunize mice against a challenge of syngeneic SV40-transformed cells. These results suggest that the TrAg expression at the cell membranes of transformed cells may be associated with the proximal half of SV40 T antigen.

Animals↗

PubMed1983

Alteration of drug responsiveness in guinea-pig lung anaphylaxis using different antigen challenge concentrations.

Antihistamine-resistant anaphylactic bronchospasm in guinea pigs is increased with increasing doses of antigen (ovalbumin, OA) challenge. This was observed in passively and actively sensitized animals, and by both i.v. and aerosol routes of antigen challenge. At a challenge concentration of 100 mg/kg OA, antihistamines were virtually inactive. Indeed, the resulting bronchospasm was inhibited by isoproterenol, theophylline and ketotifen but not any anticholinergics, anti-5HT, SRS-A antagonists, arachidonic acid lipoxygenase inhibitors or antiallergic drugs. However, in the presence of chlorpheniramine, the response was antagonized by SRS-A antagonists (FPL 55712 and isamoxole), but not the lipoxygenase inhibitors (BW 755C, ETYA, NDGA and phenidone). This suggests that the antihistamine-resistant bronchospasm produced in guinea pigs challenged with high antigen concentrations might be the result of SRS-A release. This is by no means certain since the currently available SRS-A antagonists possess other mechanisms of action; furthermore, the failure of lipoxygenase inhibitors to influence this response is not consistent with a role for SRS-A. Elucidation of the mechanism of the antihistamine-resistant bronchospasm awaits development of more specific SRS-A antagonists.

Aerosols↗

PubMed1983

Functional basis of poliovirus neutralization determined with monospecific neutralizing antibodies.

Antibody-mediated poliovirus neutralization was studied by using a series of 13 monospecific neutralizing antibodies. These antibodies were found to recognize seven individual viral epitopes, several of which functionally overlap one another. Each epitope was capable of undergoing variation so that the variant virus was no longer capable of being neutralized by antibody directed against that epitope. The measured degree of variation for each site varied from -3.1 to -4.2 log10 variant PFU per wild-type PFU. Under nonsaturating but neutralizing conditions, the antibodies, with the exception of those directed to one specific epitope, failed to completely inhibit the virion's binding to the cell. Similarly, none of the neutralizing antibodies completely inhibited viral penetration, but all prevented virus-specific transcription. A strong correlation was established between the binding of each of the neutralizing antibodies, with one exception, to the virion and a significant shift in the virion's pI from 7.0 to ca. 4.0.

Antibodies, Monoclonal↗

PubMed1983

Isolation of monoclonal antibodies that recognize the transforming proteins of avian sarcoma viruses.

Thirteen clones of hybrid cells which synthesize antibodies directed against the Rous sarcoma virus (RSV) transforming protein, pp60src, were isolated. Mouse myeloma cells were fused with spleen cells from mice that had been immunized with purified pp60src from bacterial recombinants which direct the synthesis of the RSV src gene. The hybridomas which survived the selection medium were screened by immunoprecipitation of pp60src from 32P-labeled lysates of RSV-transformed cells. Monoclonal antibodies produced by subclones derived from 13 hybridomas recognized pp60src encoded by the Schmidt-Ruppin and Prague strains of RSV and the cellular homolog of pp60src. Antibody from clone 261 had a high affinity for the viral yes gene product, and antibodies from clones 443 and 463 recognized the transforming proteins encoded by viruses containing the related transforming genes fps and ros. Several other clones had a low affinity for the viral yes, fps, and ros gene products which could be detected by in vitro phosphorylation of the transforming proteins after immunoprecipitation with the monoclonal antibody. All of the monoclonal antibodies allowed phosphorylation of pp60src and casein in an immune complex-bound reaction.

Animals↗