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Biomedical subjects

M Riggs

Publications and source records attributed to M Riggs.

34 records · Page 2Linked to original sources

Colorectal cancer: current trends in initial clinical manifestations.

Colorectal carcinoma (CRC) is a common cause of cancer morbidity and mortality in the United States. There continues to be controversy regarding the effectiveness and feasibility of various screening programs for CRC. To determine how cases of CRC are currently detected, we reviewed a series of 246 consecutive patients with well-documented pathologic staging and clinical presentation. Patients with low stage CRC (0 or A) had smaller tumors, were less likely to be anemic at presentation, and were more likely to have tumors located in the left side of the colon than patients with tumors at stage B or higher. Thirty-two of the 246 tumors were detected in asymptomatic patients through screening. These tumors were more likely to be of a lower stage than those in patients with active gastrointestinal symptoms. In our experience active screening programs detect a relatively small number of CRCs. A majority (66%) of CRCs are still detected from symptoms referable to the gastrointestinal tract.

Aged↗

Mast cell tumors in three ferrets.

Pruritic open skin lesions (5 mm diameter) on the thorax, neck, or head of 3 ferrets were diagnosed as mast cell tumors. Diagnosis of the tumors was based on histologic examination of biopsy specimens. Histologic diagnosis was necessary because the lesions had been treated as mycotic or bacterial ulcers and did not respond to conventional treatment. Excised mast cell tumors did not recur, and malignant behavior of the tumors was not observed.

Animals↗

Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients. Pediatric Zidovudine Phase I Study Group.

Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.

AIDS-Related Complex↗

Characterization of ROS1 cDNA from a human glioblastoma cell line.

We have isolated and characterized a human ROS1 cDNA from the glioblastoma cell line SW-1088. The cDNA, 8.3 kilobases long, has the potential to encode a transmembrane tyrosine-specific protein kinase with a predicted molecular mass of 259 kDa. The putative extracellular domain of ROS1 is homologous to the extracellular domain of the sevenless gene product from Drosophila. No comparable similarities in the extracellular domains were found between ROS1 and other receptor-type tyrosine kinases. Together, ROS1 and sevenless gene products define a distinct subclass of transmembrane tyrosine kinases.

Amino Acid Sequence↗

Biological activity of the mammalian RAP genes in yeast.

We have screened expression libraries for mammalian cDNAs capable of suppressing defects in ras1- Schizosaccharomyces pombe. Both the RAP1A and RAP1B genes were identified in this manner. They suppress defects in cell morphology and sporulation, although not conjugation. In contrast, RAP genes do not suppress phenotypes in the yeast Saccharomyces cerevisiae that are deficient in RAS. Indeed, expression of RAP1A appears to antagonize the activated S. cerevisiae RAS2val19 gene. These results indicate that RAP proteins can interact with RAS targets, sometimes productively, sometimes nonproductively.

Cell Line↗

Isolation and characterization of a mammalian gene encoding a high-affinity cAMP phosphodiesterase.

A rat brain cDNA library has been constructed in a Saccharomyces cerevisiae expression vector and used to isolate genes that can function in yeast to suppress the phenotypic effects of RAS2val19, a mutant form of the RAS2 gene analogous to an oncogenic mutant of the human HRAS gene. One cDNA, DPD, was cloned and its genetic and biochemical properties were characterized. A DPD product would share 80% amino acid sequence identity with the Drosophila melanogaster dunce-encoded protein over an extended region. We have shown that the DPD protein is a high-affinity cAMP-specific phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗

The adenylyl cyclase gene from Schizosaccharomyces pombe.

We cloned the adenylyl cyclase gene from the fission yeast Schizosaccharomyces pombe using low-stringency hybridization to the Saccharomyces cerevisiae adenylyl cyclase gene. The Sc. pombe gene encodes a 1692-amino acid-residue protein. The identity of this gene was confirmed by studies of its expression in Sa. cerevisiae. Expression of the carboxyl-terminal region of the Sc. pombe adenylyl cyclase protein will suppress a temperature-sensitive mutation in the Sa. cerevisiae adenylyl cyclase gene. Furthermore, Sa. cerevisiae that lack their endogenous adenylyl cyclase gene and express the carboxyl-terminal region of the Sc. pombe adenylyl cyclase protein have measurable adenylyl cyclase activity. The carboxyl-terminal region of this protein has strong homology with the catalytic domain of the Sa. cerevisiae adenylyl cyclase. Also, Sc. pombe adenylyl cyclase, like Sa. cerevisiae adenylyl cyclase, contains a tandemly repeated motif rich in leucine. Neither yeast protein is particularly homologous to the recently cloned Gs-responsive mammalian adenylyl cyclase [Krupinski, J., Coussen, F., Bakalyar, H. A., Tang, W.-J., Feinstein, P. G., Orth, K., Slaughter, C., Reed, R. R. & Gilman, A. G. (1989) Science 244, 1558-1564].

Adenylyl Cyclases↗

Expression of hepatitis B virus large envelope polypeptide inhibits hepatitis B surface antigen secretion in transgenic mice.

The outer membrane of the hepatitis B virus consists of host lipid and the hepatitis B virus major (p25, gp28), middle (gp33, gp36), and large (p39, gp42) envelope polypeptides. These polypeptides are encoded by a large open reading frame that contains three in-phase translation start codons and a shared termination signal. The influence of the large envelope polypeptide on the secretion of hepatitis B surface antigen (HBsAg) subviral particles in transgenic mice was examined. The major polypeptide is the dominant structural component of the HBsAg particles, which are readily secreted into the blood. A relative increase in production of the large envelope polypeptide compared with that of the major envelope polypeptide led to profound reduction of the HBsAg concentration in serum as a result of accumulation of both envelope polypeptides in a relatively insoluble compartment within the cell. We conclude that inhibition of HBsAg secretion is related to a hitherto unknown property of the pre-S-containing domain of the large envelope polypeptide.

Animals↗

Exsanguination due to gastric ulceration in a foal.

An Arabian foal with a congenital heart disease died due to hemorrhage secondary to a large gastric ulcer. Previously, death of foals with gastric ulcers has been due to diffuse peritonitis resulting from gastric ulcer perforation. The foal in this case report died due to hemorrhage secondary to a large gastric ulcer.

Animals↗

Dietary effect on urinary thioethers.

Urinary thioethers are a biomarker for reactive metabolites, which are detoxified via glutathione. We conducted this study to establish the effect of diet on a sample of persons we screened to exclude exposure from such substances. Our second objective was to develop a distribution curve to be used for comparison to exposed populations. Volunteers were sought who did not work or live in locations where known toxic exposures were likely to occur. We mainly recruited office personnel and secretarial staff. We screened subjects for environmental exposures via a written questionnaire. Subjects gave us an initial random urine specimen before they were placed on a diet low in thioethers. We then measured urinary thioethers on these specimens with a modified Ellman technique. We compared 126 paired results. Results demonstrated that diet decreased urine thioether excretion in most cases (i.e., 75 of 126 had a decrease in thioethers). Initially, the difference in mean excretion at the time of prediet and postdiet, however, was not significant (p = .22). We removed 2 extreme outliers, the result of which was a significant difference in means (paired t test, p < .01). The standard deviation within each of the two groups did not differ significantly (p = .82).

Diet↗

A comparison of three educational techniques used in a venereal disease clinic.

The communications methods that could be used in educational programs for venereal disease patients were examined as to their relative effectiveness: a programed learning guide, an audiovisual (cinematographic) technique, and an interview method. An experimental design was used to study three groups of patients at a venereal disease clinic; (a) persons who were pretested, exposed to an educational method, and tested again, (b) a control group whose members were pretested and post-tested but not exposed to an educational method, and (c) another control group whose members were exposed to an educational method and then took a post-test. Each of those groups exposed to the educational techniques was further subdivided according to the technique applied. Analysis of the data collected from 443 subjects led to the following tentative conclusions: 1. Representation in the nine groups was demographically uniform as measured by age, sex, marital status, and ethnic origin. 2. All three educational techniques significantly raised the subjects' level of knowledge about venereal disease, as measured by their test scores. 3. All three techniques were favorably received by the subjects. The majority reported that the techniques were the right length (10 to 15 minutes), interesting, informative, useful, and anxiety-reducing. The three techniques apparently accounted for an increase of more than 20 percent in subjects' scores on tests about venereal disease, and the subjects perceived all three techniques as interesting and beneficial. The interview method proved significantly more effective than the other two techniques in raising the knowledge level. It was also the technique most favorably received by the subjects. As expected, those persons who entered the clinic with a low level of knowledge learned much more when exposed to an educational techniques than persons entering the clinic with a high level of knowledge. Reaction to the three methods did not differ significantly by the subjects' age or sex.

Achievement↗