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J R Ward

Publications and source records attributed to J R Ward.

At least 19 recordsLinked to original sources
PubMed1992

Yeast artificial chromosomes for the molecular analysis of the familial polyposis APC gene region.

Two yeast artificial chromosomes (YACs) spanning a total distance of 1.1 megabase pairs of DNA around the MCC (for mutated in colorectal carcinoma) and APC (for adenomatous polyposis coli) genes at 5q21 have been isolated and characterized. Starting from the MCC gene, a strategy was undertaken to identify constitutional submicroscopic deletions in familial adenomatous polyposis patients that might considerably narrow down the position of the APC gene. To this end, YACs identified by the MCC gene were screened across a chromosome 5-specific cosmid library to provide a source of DNA probes for genomic scanning. The cosmids isolated from these experiments were used to screen a panel of somatic cell hybrids containing chromosome 5 segregated from patients suspected to carry putative interstitial deletions. This screening approach led to the confirmation of a small heterozygous deletion in a polyposis patient that overlaps one of the two isolated YACs. This YAC has been shown to contain the entire APC gene, in addition to a significant portion of DNA flanking the 5' end of the gene, and should therefore prove a valuable resource for functional studies by transfer to colorectal tumor-derived cell lines.

Adenomatous Polyposis Coli↗
PubMed1992

Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial.

OBJECTIVE: To compare the relative safety and efficacy of auranofin (AUR), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Three hundred thirty-five patients with active RA were entered into a 48-week, prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: Two hundred eleven patients completed the trial. No remissions were seen, and there were no statistically significant differences among the treatment groups in the clinical or laboratory variables measured. Patients taking AUR alone had a slower onset of response than did patients taking MTX alone or in combination. Withdrawals because of adverse drug reactions were slightly more common for those taking combination therapy, but the differences were not statistically significant. Withdrawals because of lack of response were more common for single-drug therapy, with the difference between AUR and the combination reaching statistical significance. No unexpected adverse drug effects were identified, and all reactions resolved without sequelae. CONCLUSION: Except for fewer withdrawals because of lack of response, combination therapy did not demonstrate any advantage in efficacy over single-drug treatment within the time frame of the study.

Adolescent↗
PubMed1992

Serum hormone and metabolite concentrations in fasted young bulls and steers.

The effect of dietary energy restriction on serum insulin, insulin-like growth factor I (IGF-I), growth hormone, (GH), cortisol, plasma urea nitrogen (PUN) and nonesterified fatty acid (NEFA) concentrations was examined. Angus bulls and steers (10 mo) were allotted to two groups of 12 animals and assigned a treatment order. In a switchback design, animals in order 1 were fed a high grain diet, then fasted, while order 2 animals were fasted, and then fed. Animals were allowed 60 hr to acclimate between treatments. Serum and plasma were obtained at 20 min intervals and 60 min, respectively, for 6 hr after feeding and for the last 6 hr of a 30 hr fast. Serum was assayed for insulin, IGF-I, GH, and cortisol (total and free). Plasma was assayed for PUN and NEFA. Mean insulin (ng/ml) differed between fed (.95 +/- .08) and fasted (.26 +/- .08) animals (P less than 01). Both mean total and free cortisol (ng/ml) were lower in fed (11.48 +/- .99) (1.06 +/- .12) than in fasted (17.10 +/- .93) (1.62 +/- .12) animals, respectively (P less than .01). Animals in order 1 differed in mean IGF-I (ng/ml) between fed (199.0 +/- 8.0) and fasted (116.5 +/- 7.2) treatments (P less than .01). Mean IGF-I for animals in order 2 was 146.7 +/- 7.2 in fed and 213.9 +/- 7.2 in fasted animals (P less than .01). Mean GH did not differ between treatments. Mean PUN and NEFA were higher in fasted than in fed animals (P less than .01). Except for % free cortisol (P less than .05), the hormones did not differ between bulls and steers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Septic arthritis mimicking cellulitis: distinction using radionuclide bone imaging.

Two patients originally diagnosed as having cellulitis involving the dorsum of the foot actually had bacterial arthritis of an underlying joint. In both patients, even after pyarthrosis was suspected, the wrong joint was aspirated. The arthropathies were located by subsequent 99mTc-phosphate bone imaging at a time when roentgenograms were normal. Early diagnosis and aggressive therapy of septic arthritis are essential to prevent joint destruction and osteomyelitis. Radionuclide bone imaging can identify inflammatory joint disease but it cannot specify etiology. In our patients, however, the differential diagnosis was between skin and joint infection. Radionuclide imaging was of great help in making this distinction.

Adult↗
PubMed1979

Endotoxin toxicity in rats with 6-sulfanilamidoindazole arthritis.

Seven oral administrations of 6-sulfanilamidoindazole (6-SAI) to 10- to 12-month-old rats sensitized the animals to endotoxin, with dosages as small as 2.5 microgram causing death in 80% of animals. Endotoxin in a dosage of 3,000 microgram was not lethal for nonmedicated control animals. 6-SAI-treated 1-month-old rats were not as sensitive to endotoxin as aged animals. The sulfonamide-induced sensitivity to endotoxin could not be passively transferred and could not be explained by blockade of the reticuloendothelial system or impairment of endotoxin detoxification. 6-SAI administration was associated with both depletion of liver glycogen and lowering of blood glucose concentration without changes in blood lactic acid concentration. Disseminated intravascular coagulation is believed to be involved in the pathogenesis of shock and death as evidenced by: (i) concomitant decreases in plasma fibrinogen concentration and elevations in fibrin degradation products after endotoxin challenge; (ii) protection against lethal actions of endotoxin by pretreatment with heparin. Treatment of 6-SAI-medicated rats with glucocorticoids before endotoxin challenge protected the animals against lethal doses of endotoxin and prevented deposition of fibrin thrombi in the glomerular capillaries.

Aging↗
PubMed1978

Naproxen vs. aspirin in osteoarthritis of the hip and knee.

This 12-week double-blind trial compared the efficacy and tolerance of naproxen (750 mg/day) with that of aspirin (3.6 gm/day). There was no statistical difference in efficacy between the two trial drugs for any of the objective (e.g., 25-foot walking time) or subjective (e.g., overall severity of symptoms) variables measured. No side effects were experienced by 69% of the naproxen patients and 37.5% of the aspirin patients. There were a statistically greater number and more severe side effects during aspirin therapy than during naproxen therapy (p = 0.002). The results show naproxen to be a potentially useful drug for the treatment of osteoarthritis.

Adult↗
PubMed1977

Chronic arthropathy associated with rubella vaccination.

Eleven children suffered recurrent ipisodes of knee stiffness ("catcher's crouch syndrome") after receiving HPV-77DK12 rubella vaccine. One was evaluated by arthroscopy and the synovium was found to be hypertrophied posteriorly and to protude in folds into the intercondylar notch and lateral joint space. Culture for rubella virus was unsuccessful. The author's observations provide evidence that "catcher's crouch syndrome" is a synovial disease and that chronic joint disease can be a sequela of rubella immunization.

Child↗
PubMed1977

A multicenter trial of sulindac in osteoarthritis of the hip.

Sulindac (cis-5-fluoro-2-methyl-l-[(p-methyl sulfinyl)-benzylidene]-indene-3-acetic acid) is a new nonsteroidal antirheumatic drug recently evaluated in a double-blind trial of 91 patients with hip osteoarthritis. Consecutive patients with documented flare following previous drug withdrawal were randomly assigned to one of 3 treatment groups: (1) sulindac given twice daily, (2) sulindac given 4 times daily, and (3) placebo. The dosage of sulindac, 100 to 300 mg daily, was adjusted according to patient global response and tolerance at 3- to 7-day intervals over 3 wk. Of 15 efficacy measurements evalulated, there was no difference between sulindac given 2 or 4 times daily, but differences were disclosed between one or both sulindac treatment groups and placebo in 11 of the 15 efficacy measurements (p less than 0.05, less than 0.01). The frequency of adverse reactions was of the same order for each treatment group. These included gastrointestinal upset, rash, and dizziness, usually transient and mild to moderate in severity. Serial laboratory studies revealed no evidence of renal, hepatic, or hematopoietic toxicity.

Adult↗
PubMed1977

Treatment of rheumatoid arthritis with flurbiprofen or ibuprofen.

Flurbiprofen and ibuprofen were compared in a six-week double-blind randomized study in 208 patients with rheumatoid arthritis. Daily dosages were 120 mg flurbiprofen and 2400 mg ibuprofen for six weeks. Both drugs were effective in providing partial control of RA symptoms. Either or both drugs produced statistically significant improvement in mean values of time of onset of fatigue, grip strength and tender and swollen joint counts. All other standard endpoints of efficacy (except ESR) were improved but not at a statistically significant level. Slightly more than half of the patients improved during the trial. There was no statistically significant difference in the efficacy of the drugs. The incidence of side effects was low with both drugs. Most side effects were related to gastrointestinal tract irritation.

Arthritis, Rheumatoid↗
PubMed1977

New models of chronic synovitis in rabbits induced by mycoplasmas: microbiological, histopathological, and immunological observations on rabbits injected with Mycoplasma arthritidis and Mycoplasma pulmonis.

A dose-dependent chronic synovitis was induced in rabbit knees after the intra-articular injection of both Mycoplasma arthritidis and Mycoplasma pulmonis. The inflammation progressed from an initial acute phase at 1 week characterized by edema, infiltration of the synovium with monocytes and heterophils, and desquamation of lining cells, to a more chronic phase at 1 and 3 months, in which villus hyperplasia, lymph "nodules," mononuclear cell infiltration, fibroplasia, and collagen deposition were prominent. With one exception, mycoplasmas could no longer be cultivated from the joints 1 month postinoculation. Both mycoplasma species evoked a humoral antibody response that was more marked in synovial fluids than in peripheral blood. A cell-mediated immune reaction, as evidence by enhanced uptake by [3H]thymidine by sensitized blood, spleen, or node lymphocytes in the presence of homologous antigen, was detected only in rabbits injected with M. pulmonis. Lymphocytes taken from arthritic rabbits were no more cytotoxic toward synovial cells derived from normal or arthritic rabbits than were normal lymphocytes. The models of synovitis described in this study offer a convenient probe for determining the mechanisms of mycoplasma-induced inflammation, since they require only a single injection of the initiating agent and, in addition, utilize an animal host large enough for detailed investigation into the nature of mycoplasma/synovium interactions.

Animals↗
PubMed1977

Mycoplasma-dependent activation of normal lymphocytes: induction of a lymphocyte-mediated cytotoxicity for allogeneic and syngeneic mouse target cells.

Mycoplasma arthritidis, M. hominis, and M. arginini were tested for their ability to induce a cytotoxic response from normal CBA mouse lymphocytes against 51Cr-labeled allogeneic target cells. In most cases, the mycoplasmas alone were not toxic for the target cells. Furthermore, the mycoplasmas did not result in decreased lymphocyte viability but, in fact, contributed to enhanced lymphocyte survival. In the absence of normal CBA lymphocytes, mycoplasmas alone did not induce a significant amount of cell damage in either the allogeneic or the syngeneic target cells. Strains of M. arthritidis and M. hominis, when added to the lymphocyte-target cell mixtures, induced statistically significant increases in 51Cr release from both target cell types at each assay period after 6 h. The release of 51Cr was taken as a measure of cell death. M. arginini induced only low levels of cytotoxicity or none at all. Both arthritogenic and non-arthritogenic strains of M. arthritidis induced the cytotoxic response. The degree of cytotoxicity produced was directly related to the size of the initial inoculum. The presence or absence of serum in the culture medium did not contribute significantly to the cytotoxicity response.

Animals↗
PubMed1977

Mycoplasma-dependent activation of normal lymphocytes: role of arginine and nonviable mycoplasma antigen in the induction of lymphocyte-mediated cytotoxicity for syngeneic mouse target cells.

The ability of arginine supplementation to abrogate or potentiate Mycoplasma arthritidis-mediated cytotoxicity induction by normal CBA mouse lymphocytes was investigated. Also, nonviable antigens of M. arthritidis were assayed for their ability to induce a cytotoxic response. The presence of additional arginine in the culture medium had no significant effect on the amount of cytotoxicity produced. In some cases, an increase in cytotoxicity was seen in the presence of additional arginine. Amino acid analysis of the culture supernatants showed that the arginine in the nonsupplemented medium was exhausted during the assay, whereas ample amounts of arginine were present in the supplemented medium. However in both cases the amount of cytotoxicity was comparable. Nonviable antigens of M. arthritidis were unable to induce a significant cytotoxic response in the presence of normal lymphocytes. The same antigens exhibited a suppressive response when tested for blastogenesis in the presence of normal lymphocytes. A discussion of lymphocyte involvement is presented.

Animals↗
PubMed1977

Mycoplasma-dependent activation of normal lymphocytes: mitogenic potential of mycoplasmas for mouse lymphocytes.

Nonviable preparations of a wide variety of glucose-utilizing mycoplasma species, including Acholeplasma laidlawii and Spiroplasma citri, were found to be mitogenic for mouse lymphocytes. Particularly strong reactions were obtained with Mycoplasma synoviae, M. gallisepticum, M. pneumoniae, S. citri, and a strain of M. fermentans that was previously isolated from a leukemic patient. Nonviable preparations of arginine-utilizing mycoplasmas inhibited the uptake of [3H]thymidine by lymphocytes, but this effect could be reversed by heat treatment or arginine supplementation, and a stimulatory effect was then observed. Viable M. arthritidis was also found to have a mitogenic effect, as detected by an increased uptake of [3H]thymidine by normal lymphocytes and by autoradiographic techniques in which an increase in the numbers of transformed cells was seen. These observations provide the potential for enhanced immunological responsiveness or lymphokine-mediated inflammation in mycoplasma-infected hosts.

Acholeplasma laidlawii↗
PubMed1977

Septic arthritis: a complication of rheumatoid arthritis.

Eighteen cases of long-standing rheumatoid arthritis and superimposed pyarthrosis were reviewed to determine the most distinguishing radiographic features. Soft-tissue changes allowed earlier diagnosis in the knee and ankle joints and consisted of large asymmetrical joint effusion and fat-pad edema. Bony articular changes were more helpful than soft-tissue changes in the wrist and hip because of the paucity of adjacent extracapsular fat and were associated with delayed radiographic recognition of superimposed pyarthrosis. These changes are presumptive evidence of complicating septic arthritis and their presence necessitates needle aspiration and culture of the joint for proper definitive treatment.

Adult↗