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Biomedical subjects

R S Nelson

Publications and source records attributed to R S Nelson.

At least 19 recordsLinked to original sources

Local and systemic spread of tobacco mosaic virus in transgenic tobacco.

Expression of a chimeric gene encoding the coat protein (CP) of tobacco mosaic virus (TMV) in transgenic tobacco plants confers resistance to infection by TMV. We investigated the spread of TMV within the inoculated leaf and throughout the plant following inoculation. Plants that expressed the CP gene [CP(+)] and those that did not [CP(-)] accumulated equivalent amounts of virus in the inoculated leaves after inoculation with TMV-RNA, but the CP(+) plants showed a delay in the development of systemic symptoms and reduced virus accumulation in the upper leaves. Tissue printing experiments demonstrated that if TMV infection became systemic, spread of virus occurred in the CP(+) plants essentially as it occurred in the CP(-) plants although at a reduced rate. Through a series of grafting experiments, we showed that stem tissue with a leaf attached taken from CP(+) plants prevented the systemic spread of virus. Stem tissue without a leaf had no effect on TMV spread. All of these findings indicate that protection against systemic spread in CP(+) plants is caused by one or more mechanisms that, in correlation with the protection against initial infection upon inoculation, result in a phenotype of resistance to TMV.

Capsid

Delay of disease development in transgenic plants that express the tobacco mosaic virus coat protein gene.

A chimeric gene containing a cloned cDNA of the coat protein (CP) gene of tobacco mosaic virus (TMV) was introduced into tobacco cells on a Ti plasmid of Agrobacterium tumefaciens from which tumor inducing genes had been removed. Plants regenerated from transformed cells expressed TMV mRNA and CP as a nuclear trait. Seedlings from self-fertilized transgenic plants were inoculated with TMV and observed for development of disease symptoms. The seedlings that expressed the CP gene were delayed in symptom development and 10 to 60 percent of the transgenic plants failed to develop symptoms for the duration of the experiments. Increasing the concentration of TMV in the inoculum shortened the delay in appearance of symptoms. The results of these experiments indicate that plants can be genetically transformed for resistance to virus disease development.

DNA

Effects of flurbiprofen and aspirin on the gastric and duodenal mucosa. An endoscopic comparison.

A single-blind, randomized endoscopic tolerance study was conducted to compare daily doses of flurbiprofen (Ansaid, Upjohn) at 100, 150, and 200 mg per day with 2,600 mg of aspirin per day. Ten normal volunteers were enrolled in each of the flurbiprofen groups, and five were enrolled in the aspirin group. Analysis of the mean gastric mucosal injury scores obtained on day eight revealed statistically significant lower mean scores (p = 0.05) in the 100-mg and 150-mg flurbiprofen treatment groups when compared with the 200-mg flurbiprofen group and the aspirin group. No significant differences were found between any of the treatment groups in duodenal mucosal injury scores. Mean scores for gastric mucosal injury in the three groups receiving flurbiprofen showed a definite dose relationship. The aspirin-treated subjects had significantly decreased uric acid levels (p = 0.006) and a significantly higher incidence of tinnitus (p = 0.04) compared with the flurbiprofen treatment groups. There was a poor correlation between subjective symptomatology and endoscopic pathologic findings.

Adult

Effect of acetaminophen on human gastric mucosal injury caused by ibuprofen.

Acetaminophen has been proposed as an agent which protects the gastric mucosa against damage induced by aspirin and other non-steroidal anti-inflammatory agents. In order to evaluate this proposal further, 45 normal human volunteers were divided into three groups (n = 15); group one received ibuprofen 2400 mg daily (600 mg qid); group two received acetaminophen 3900 mg daily (975 mg qid) and group three received both drugs at the same dosages. There was no significant difference in the mucosal injury scores noted at endoscopy between the ibuprofen and the ibuprofen-acetaminophen group. The acetaminophen group had virtually no observed mucosal injury and this was statistically significant in comparison with the other groups (p less than 0.01). We conclude that contrary to previously reported studies using single doses of aspirin, acetaminophen failed to decrease the mucosal injury seen with ibuprofen when given for a period of seven days in combination with acetaminophen.

Acetaminophen

Mouse peritoneal macrophages plated on mannan- and horseradish peroxidase-coated substrates lose the ability to phagocytose by their Fc receptors.

Ligand-conjugated substrates were used to study mouse macrophage receptor-ligand interactions. Both resident and thioglycollate-elicited macrophages plated on substrates conjugated with mannans and horseradish peroxidase (HRP), ligands for the Man/GlcNAc receptor, lost their ability to phagocytose zymosan. In addition, these macrophages also lost their ability to phagocytose IgG-coated erythrocytes (E(IgG] via their Fc receptors (FcR). The abrogation of Fc receptor-mediated phagocytosis occurred as early as 4 hr after macrophage plating on HRP-coated substrates and was dependent on the amount of HRP conjugated to the substrate. Macrophages plated on those substrates showed a 70% reduction in E(IgG) binding and the same decrease (approximately 35%) in binding of 125I-labeled Fab fragment of monoclonal anti-IgG2b FcR antibody as macrophages plated on dinitrophenyl-anti-dinitrophenyl IgG immune complexes. We interpret these results as showing that modulation of macrophage mannose/GlcNAc receptors induces modulation of FcR.

Animals

Ethanol, aspirin, ibuprofen, and the gastroduodenal mucosa: an endoscopic assessment.

The effect on the gastroduodenal mucosa of alcohol combined either with aspirin or ibuprofen was studied in 60 normal volunteers. The volunteers were divided into six groups comprised of 10 subjects receiving ibuprofen, placebo, or aspirin with or without alcohol. Medications consisted of 1) three 325-mg aspirin tablets, or three identical placebo tablets, 2) one 600-mg ibuprofen tablet, and 3), three ounces of 100 proof vodka diluted in 6 ounces of orange juice, or alcohol placebo made by diluting 3 ounces of water in orange juice. All subjects received 4 doses over a 24-hr period and underwent endoscopic examination the following morning. The gastroduodenal mucosa was graded according to a 0 to 4 + scale. Aspirin caused considerably greater duodenal and gastric damage than did either ibuprofen or placebo. The addition of alcohol to all drugs increased the damage seen in the stomach but not to a significant degree; this effect was slightly more pronounced with ibuprofen than with placebo or aspirin and approached significance (0.1 greater than p greater than 0.05). These results are compatible with alcohol being a mild damaging agent or a potentiating agent for damage from other drugs.

Adult

The effects of ibuprofen, indomethacin, aspirin, naproxen, and placebo on the gastric mucosa of normal volunteers: a gastroscopic and photographic study.

The effects of various nonsteroidal antiinflammatory drugs on the gastric mucosa were endoscopically evaluated in 40 normal volunteers. Eight groups, each containing five subjects were designed: aspirin (3600 mg/d); placebo; ibuprofen (1600 mg/d); ibuprofen (2400 mg/d); indomethacin (100 mg/d); indomethacin (150 mg/d); naproxen (500 mg/d); and naproxen (750 mg/d). All volunteers took medication for seven days and gastroscopy was carried out on day one and day eight. All findings were documented by photography. Severe gastric mucosal injury occurred with aspirin (P less than 0.05), both doses of indomethacin, and the higher dose of naproxen. Lesser changes were seen with the lower dose of naproxen, both doses of ibuprofen and placebo. The higher doses of ibuprofen, indomethacin, and naproxen caused a greater degree of gastric mucosal injury, but statistical significance was achieved only with naproxen (P less than 0.01). Subjective gastrointestinal complaints generally correlated with endoscopic pathology; however, nine volunteers had evidence of severe injury to the gastric mucosa with no symptomatology. This was confined to the patients on indomethacin, naproxen, and ibuprofen. Aspirin patients all had some degree of symptomatology but to a lesser degree than expected in view of the endoscopic findings.

Adult

Distribution of Lyb-4.1 and other membrane antigens on murine lymphoid tumors.

The distribution of membrane antigens on 6 DBA/2-derived tumors (L1210, L5178Y, P815, ABLS 11, ABLS 12, and ABLS 13) was studied by direct cytotoxicity and quantitative absorption assays. Lyb-4.1 antigen was found solely on the L1210 tumor. Iad antigens were absent from all tumors, and H-2Kd and H-2Dd antigens were present on all tumors. Immunoglobulin was adsorbed to the ascites tumors and lost after 3 days or more in tissue culture. These studies were performed to characterize the distribution of DBA/2 membrane antigens on DBA/2-derived tumors as a base line for functional and chemical studies with these tumors and with their solubilized proteins.

Animals

Effects of ibuprofen, tolmetin and placebo on the gastric mucosa of aspirin-sensitive volunteers.

Patients who have demonstrated a gastric mucosal sensitivity to aspirin often react to other nonsteroidal, anti-inflammatory drugs to a similar or lesser degree. In a single-blind crossover study, five healthy volunteers who had previously developed erosive gastritis secondary to one week of aspirin therapy were randomly assigned to seven-day courses of treatment with ibuprofen, tolmetin and placebo. Treatment schedules were separated by washout periods to eliminate residual drug effects. Ibuprofen produced less gastric mucosal injury than tolmetin and, over all, appeared to be better tolerated. It was also noted that clinical symptoms often do not reflect the severity of gastroscopic findings, which may explain silent hemorrhaging in patients treated with agents of this type.

Adult

Treatment of psoriasis with dialysis.

Five patients with psoriasis were treated with haemodialysis. Dialysis therapy was initiated for subsequent development of uraemia in three cases. All of these had successful renal transplants without recurrence of psoriasis while being maintained on post-transplant anti-rejection regimens. Two other cases were haemodialysed, not for uraemia but primarily for psoriasis. One case had moderate improvement of psoriasis after twice-weekly dialysis for two months while the second had no objective improvement up to one month after a single haemodialysis treatment.

Adult

Chemotherapy for metastatic carcinoid tumors: experiences with 32 patients and a review of the literature.

An analysis of results of chemotherapy in 32 patients with metastatic carcinoid tumors was carried out. The most frequently used chemotherapeutic agent was 5-fluorouracil (5-FU) followed by nitrosoureas in combination with 5-FU or with cyclophosphamide. Adriamycin (used as adriamycin-DNA complex) alone or in combination with other drugs was used in seven patients. Seven partial responses were observed, five of them occurring in the patients receiving adriamycin-containing regimens. Based on these findings, adriamycin deserves further evaluation in metastatic carcinoid tumors.

Adult

Evaluation of gastric ulcerations.

All gastric ulcers diagnosed during the period November, 1969-May, 1974, were prospectively evaluated by roentgenography, fiberoptic gastroscopy, directed biopsy, and brush cytology. Gastroscopy was performed routinely in patients with radiologic diagnosis of gastric ulcer or questionable findings, and in symptomatic individuals with negative roentgenograms. A total of 123/142 ulcers, 109 benign, 14 malignant, were available for complete follow-up. Gastroscopy was correct in 106 of 109 benign ulcers visualized. Roentgenoscopy demonstrated 91 of 109, of which 7 were incorrectly called carcinoma. Gross diagnosis was correct by gastroscopy in 11 of 14 malignant ulcers. Radiology visualized 6 of 14; gross diagnosis was correct in 1 of 6 (5 called benign). Directed gastroscopic biopsy was negative for malignant changes in all 109 benign and 3 of 14 malignant ulcers. Total complete gastroscopic diagnostic failures were 4 of 123, for an overall accuracy of 96.7%. Overall roentgenographic accuracy was 70.8%.

Biopsy