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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
PubMed1990

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

Stages IE and IIE non-Hodgkin's lymphomas of the stomach. Comparison of treatment modalities.

Seventy-nine patients with Stages IE and IIE non-Hodgkin's lymphomas of the stomach were treated between 1953 and 1980. The histopathologic classification was as follows: diffuse large cell, 61 (of which 23 were immunoblastic sarcomas [plasmacytoid]); diffuse well-differentiated lymphocytic, 6; diffuse mixed, 1; undifferentiated non-Burkitt's, 1; nodular, 9; and unclassifiable, 1. Thirty-five patients had Stage IE disease and 44 had Stage IIE. Treatment modalities included surgery, radiotherapy, chemotherapy, and combinations thereof. Sixty-six patients had a laparotomy for diagnosis and/or management. Of these, only 42 had a gastrectomy. The stomach was considered to be unresectable in the other 24 patients. There were 5 postoperative deaths among 31 patients who had a laparotomy or gastrectomy at our institution. The overall 5-year actuarial survival was 56%; the disease-free survival was 54%. For patients with Stage IE disease the survival was 76%, and for those with Stage IIE, 42%. Promising results were obtained in 13 patients who were treated on a multimodality program consisting of four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus bleomycin (Bleo), which was alternated with involved field radiotherapy. All 13 patients had no evidence of disease as of this report. Only one patient had a relapse (Waldeyer's ring), and he was salvaged with radiotherapy. Six of these 13 were diagnosed by endoscopic biopsy and did not have a laparotomy, 3 were found to have unresectable disease at laparotomy, and 4 had a resection. Biopsy with the flexible fiberscope and treatment with CHOP-Bleo and radiotherapy can avoid the morbidity and mortality of gastrectomy.

Adult↗
PubMed1984

Digital subtraction angiography with an Isocon camera system: clinical applications.

A new imaging system for digital subtraction angiography (DSA) was evaluated in 30 clinical studies. The image receptor is a 25 X 25 cm, 12 par gadolinium oxysulfate rare-earth screen whose light output is focused to a low-light-level Isocon camera. The video signal is digitized and processed by an image-array processor containing 31 512 X 512 memories 8 bits deep. In most patients, intraarterial DSA studies were done in conjunction with conventional arteriography. In these arterial studies, images adequate to make a specific diagnosis were obtained using half the radiation dose and half the amount of contrast material needed for conventional angiography. In eight intravenous studies performed either to identify renal artery stenosis or for evaluation of congenital heart anomalies, the images were diagnostic but objectionably noisy.

Angiography↗
PubMed1983

Effects of fenbufen, indomethacin, naproxen, and placebo on gastric mucosa of normal volunteers. A comparative endoscopic and photographic evaluation.

The effects of fenbufen (1,000 mg a day), indomethacin (150 mg a day), naproxen (750 mg a day), and placebo on gastric mucosa were determined by endoscopy and recorded photographically. One hundred normal subjects, randomly divided into equal, parallel-treatment groups, were given the drugs in divided daily doses for seven consecutive days. The results revealed that the effects of fenbufen on gastric mucosa were significantly (p less than or equal to 0.05) less than those of either naproxen or indomethacin and not statistically different from those observed with placebo.

Adult↗
PubMed1983

The role of the mannose/N-acetylglucosamine receptor in the pinocytosis of horseradish peroxidase by mouse peritoneal macrophages.

Saccharomyces cerevisiae mannan inhibits the pinocytosis of horseradish peroxidase (HRP) by resident, thioglycollate-,proteose peptone-, and Corynebacterium parvum-elicited macrophages from 30 to 70% when 1 mg/ml HRP is used, and 65 to 87% when 250 micrograms/ml HRP is used. In contrast, HRP uptake by J774 cells, a macrophage cell line reported to have little mannose receptor activity, is inhibited only about 25% by mannan. HRP uptake by resident and thioglycollate-elicited (thio) macrophages is also inhibited 34 and 66% by addition of EGTA to the medium and 55 and 79% by trypsin treatment of the macrophages, respectively. The inhibitory effect of EGTA can be reversed by 1 mM excess Ca2+. High extracellular concentrations of Ca2+, in the range of 10-20 mM, however, inhibit pinocytosis in resident macrophages by about 50%. Sucrose uptake by resident macrophages is not appreciably affected by mannan. These results support the hypothesis that HRP uptake is mediated by the macrophage mannose/N-acetylglucosamine receptor. PMA stimulates fluid-phase pinocytosis of HRP by thio macrophages but does not affect receptor-mediated uptake of HRP, while the combination of adenosine, homocysteine, and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) selectively inhibits bulk-phase uptake by thio macrophages.

Animals↗
PubMed1983

Thrombocytopenia and gastrointestinal hemorrhage in the cancer patient: prevalence of unmasked lesions.

Some coagulation deficiencies are known to cause bleeding by unmasking existing gastrointestinal pathology, as opposed to directly causing mucosal blood loss. Characteristics and etiology of gastrointestinal hemorrhage associated with thrombocytopenia have not been analyzed. Our objectives were to correlate the distribution and cause of gastrointestinal bleeding, as diagnosed by fiberoptic endoscopy, with the severity of thrombocytopenia. One hundred thirty-three patients were divided into three groups, determined by platelet count at the time of bleeding (group A: less than 20,000/mm3; group B: 20,000 to 40,000/mm3; group C greater than 40,000/mm3). Results of 187 endoscopies revealed unifocal sources of blood loss in over 50% of each group, and diffuse mucosal oozing independent of gastrointestinal pathology was seen in only 1% of group C. The only significant difference (p = 0.04) comparing unifocal, multifocal, and diffuse sources of bleeding was observed between groups A and C, where in the distribution of multifocal or diffuse sources of bleeding was more common in group A. Esophagitis was more common and gastric ulceration less common in group A. No endoscopic complications occurred. Gastrointestinal bleeding associated with thrombocytopenia is most commonly due to co-existent gastrointestinal pathology as opposed to diffuse mucosal bleeding. Even when an inflammatory process, such as esophagitis or gastritis, affects a particular organ, bleeding is usually unifocal or multifocal as opposed to diffuse even in the presence of moderately severe thrombocytopenia.

Endoscopy↗
PubMed1983

Gastrointestinal hemorrhage in the cancer patient.

The usefulness of fiberoptic endoscopy, performed to identify the cause(s) of gastrointestinal bleeding in cancer patients was assessed by (1) identifying the clinical presentation of bleeding, (2) evaluating the safety and diagnostic yield of fiberoptic endoscopy, (3) determining the frequency distribution of causes of bleeding, and (4) evaluating the clinical course following acute gastrointestinal bleeding in a cancer patient population. Hematemesis, melena, and hematochezia were observed in decreasing order of frequency as manifestations of bleeding. Of 187 endoscopic procedures performed on 133 patients, 75% were bleeding from benign lesions with the majority due to gastric ulceration, gastritis, or duodenal ulceration. One third of patients with tumors involving the gastrointestinal tract were bleeding from another source. Mortality from major hemorrhage was 8%; 55% of patients were alive at the end of 2 years. Endoscopy was performed without complications and contributed to medical management, angiographic therapy, and surgical planning.

Endoscopy↗
PubMed1983

Yeast mannans inhibit binding and phagocytosis of zymosan by mouse peritoneal macrophages.

We have examined the effects of various mannans, glycoproteins, oligosaccharides, monosaccharides, and sugar phosphates on the binding and phagocytosis of yeast cell walls (zymosan) by mouse peritoneal macrophages. A phosphonomannan (PO(4):mannose ratio = 1:8:6) from kloeckera brevis was the most potent inhibitor tested; it inhibited binding and phagocytosis by 50 percent at concentrations of approximately 3-5 mug/ml and 10 mug/ml, respectively. Removal of the phosphate from this mannan by mild acid and alkaline phosphatase treatment did not appreciably reduce its capacity to inhibit zymosan phagocytosis. The mannan from saccharomyces cerevisiae mutant LB301 inhibits phagocytosis by 50 percent at 0.3 mg/ml, and a neutral exocellular glucomannan from pichia pinus inhibited phagocytosis by 50 percent at 1 mg/ml. Cell wall mannans from wild type S. cervisiae X2180, its mnn2 mutant which contains mannan with predominantly 1(arrow)6- linked mannose residues, yeast exocellular mannans and O-phosphonomannans were less efficient inhibitors requiring concentrations of 1-5 mg/ml to achieve 50 percent reduction in phagocytosis. Horseradish peroxidase, which contains high-mannose type oligosaccharides, was also inhibitory. Mannan is a specific inhibitor of zymosan binding and phagocytosis. The binding and ingestion of zymosan but not of IgG- or complement-coated erythrocytes can be obliterated by plating macrophages on substrates coated with poly-L-lysin (PLL)-mannan. Zymosan uptake was completely abolished by trypsin treatment of the macrophages and reduced by 50-60 percent in the presence of 10 mM EGTA. Pretreatment of the macrophages with chloroquine inhibited zymosan binding and ingestion. These results support the proposal that the macrophage mannose/N-acetylglucosamine receptor (P. Stahl, J.S. Rodman, M.J. Miller, and P.H. Schlesinger, 1978, Proc. Natl. Acad. Sci. U.S.A. 75:1399-1403, mediates the phagocytosis of zymosan particles.

Animals↗
PubMed1983

Collagenous colitis.

Collagenous colitis is a newly described entity that clinically manifests itself as watery diarrhea of long-standing duration. The main histopathologic characteristic is the presence of a collagen band immediately beneath the colonic surface epithelium. Ultrastructurally, the collagen is deposited beneath the basement membrane, which is intact. Pathogenetically, an aberrant function of the pericryptal fibroblastic sheath may be involved.

Cathartics↗
PubMed1982

The Isocon camera system in digital subtraction imaging.

A new system for digital vascular subtraction imaging is presented. The image receptor consists of a rare-earth screen with light output optically focused onto the photocathode of a low-light-level image Isocon camera. This system represents a departure from the conventional use of the image intensifier for digital subtraction imaging. Our initial results suggest that this system could be competitive with traditional image intensifier systems and that it deserves clinical trial.

Angiography↗
PubMed1981

Colorectal cancer in young adults.

The clinical and pathologic characteristics of colorectal cancer in patients younger than 30 years are compared with those in patients 30 to 39 years of age. Patients in the two age groups had similar symptoms, predominantly undifferentiated neoplasms, and poor prognoses. However, when the characteristics of these patients were compared with those described for a general patient population with colorectal cancer there was a gradual decrease in the incidence of mucin-producing tumors, poorly differentiated carcinomas, and primary lesions in the right colon, with increasing age at diagnosis. The highest incidences were found in patients less than 30 years old. The degree of tumor anaplasia and stage of tumor at diagnosis significantly influenced the duration of disease-free interval after curative resection of the primary and the duration of survival. Ninety-six percent of patients younger than 40 years had carcinomas extending beyond the colonic wall at diagnosis, adversely affecting long-term survival. The five-year survival of only 25% to 30% in these patients emphasizes the need for early diagnosis and aggressive treatment.

Adolescent↗