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Biomedical subjects

A C Nelson

Publications and source records attributed to A C Nelson.

At least 19 recordsLinked to original sources
PubMed2001

Variables in human liver microsome preparation: impact on the kinetics of l-alpha-acetylmethadol (LAAM) n-demethylation and dextromethorphan O-demethylation.

We examined three primary variables in the preparation of human liver microsomes. In three experiments, each using three livers, we manipulated 1) the force of the first centrifugation (9,000, 10,500, or 12,000g); 2) the presence of sucrose in the homogenization buffer; and 3) the number of homogenizing strokes (6, 8, or 10). Sedimentation plots for the marker enzymes succinate dehydrogenase, NADPH cytochrome P450 reductase (reductase), and glutathione S-transferase in the resulting premicrosomal, microsomal, and cytosolic fractions suggest that enhanced purity of microsomes can be obtained by reducing force of centrifugation, including sucrose, and increasing the number of homogenization strokes. Each microsomal fraction was also assayed for protein content, cytochrome P450, NADH cytochrome b(5) reductase, cytochrome b(5), absorbance at 420, p-nitrophenol hydroxylation, tolbutamide hydroxylation, dextromethorphan N- and O-demethylation, glucuronidation of morphine and 1-naphthol, and ester cleavage of p-nitrophenolacetate. These microsomal indicators were ranked and tested for statistical differences. The use of 9000g statistically increased optimal recovery (per gram of liver) and specific activity (per milligram of protein). The inclusion of sucrose improved activity specific to reductase activity. Ten homogenization strokes improved activity specific to reductase activity. Substrate-dependent activities of dextromethorphan O-demethylation to dextrorphan and the N-demethylation of l-alpha-acetylmethadol (LAAM) to norLAAM and dinorLAAM were compared in microsomes prepared with or without sucrose and microsomes prepared using 9,000 or 12,000g force, respectively. No significant differences were found in the concentration-dependent activities. Variation of the methods used to prepare human liver microsomes can significantly affect the recovery and specific activity of microsomal components; however, they do not appear to affect enzyme kinetics.

Adolescent↗
PubMed2000

DNA repair is activated in early stages of p53-induced apoptosis.

p53 is a complex molecule involved in apoptosis, cell cycle arrest, and DNA repair. Since apoptosis may play an important role in deletion of neoplastic cells, an understanding of the mechanism of p53-induced apoptosis may be critical for possible future therapeutic interventions. Recent evidence suggests that p53-induced apoptosis may involve members of the nucleotide excision repair (NER) family, linking these two cellular events. Our work using a temperature-sensitive p53 construct further analyzes p53-induced apoptosis in cultured murine mammary epithelial cells and also suggests that DNA repair plays a role in that process. Although p21 is induced in our system, apoptosis occurs without a detectable preceding G1 cell cycle arrest and independent of cellular alterations brought on by the temperature shift. In addition, clonogenic assays suggest that early stages of p53-induced apoptosis may be reversible upon removal of the apoptosis stimulus. As a possible explanation for this reversibility, our results show that general DNA repair activity increases early in p53-induced apoptosis. We also show that caspase-3 is activated at a timepoint when colony formation begins to drop, suggesting a possible mechanism for the point of no return in p53-induced apoptosis.

Amino Acid Substitution↗
PubMed1999

Comparison of the color of fecal blood with the anatomical location of gastrointestinal bleeding lesions: potential misdiagnosis using only flexible sigmoidoscopy for bright red blood per rectum.

OBJECTIVE: Flexible sigmoidoscopy has been recommended for diagnosis of patients with bright red rectal bleeding. The purpose of this study was to determine whether lesions associated with bright red hematochezia are located in the distal 60 cm of the colorectum and, therefore, in reach of a flexible sigmoidoscope. METHODS: Three hundred-twelve consecutive patients presenting with hematochezia were shown a card containing three shades of red and asked to choose the color most representative of their fecal blood. Patients then underwent colonoscopy. The colonoscopist noted the length of the scope inserted when bleeding lesions were found. RESULTS: Of 217 patients with bright red hematochezia, 181 bled from the distal 60 cm of the colon, 20 had more proximal lesions (including eight with cancer), and 16 had no lesion found. However, 140 patients with rectosigmoid neoplasms or nonbleeding nonneoplastic lesions (e.g., hemorrhoids, diverticula, vascular anomalies, and fissures) if found by sigmoidoscopy would have subsequently required full colonoscopic surveillance. It was calculated that the average per patient medical charges employing an initial colonoscopic approach would save $12 or $116 over one beginning with sigmoidoscopy (depending on whether sigmoidoscopy is performed in an office setting or endoscopy suite, respectively), and would reduce the probability of perforation slightly. CONCLUSION: A diagnostic approach to hematochezia beginning with colonoscopy should be more effective, safer, and less costly than one beginning with flexible sigmoidoscopy, even when the blood is bright red.

Adolescent↗
PubMed1998

HEp-2 cell-adherent Escherichia coli and intestinal secretory immune response to human immunodeficiency virus (HIV) in outpatients with HIV-associated diarrhea.

HEp-2 cell-adherent Escherichia coli and the human immunodeficiency virus (HIV) itself have recently been incriminated as causes of chronic HIV-associated diarrhea. This study sought to determine the prevalence of these two agents among HIV-infected patients with diarrhea in an outpatient setting in the United States and to compare their prevalence to that of other commonly recognized enteropathogens known to be present in this population. HEp-2 cell-adherent E. coli was found in 20 of 83 (24.1%) patients with diarrhea. A diffuse pattern of adherence was the most common, found in 14 of 20 (70%) patients, followed by a localized adherence pattern (6 of 20; 30%). An intestinal secretory immune response against the p24 antigen of HIV was found in 9 of 34 (27.5%) patients with HIV-associated diarrhea. The following pathogens or products were also detected in lower frequencies: Cryptosporidium spp. (10.8%), Clostridium difficile toxin (8.8%), microsporidia (6%), Isospora belli (3.6%), Blastocystis hominis (2.4%), Giardia spp. (1.2%), Salmonella spp. (1.2%), and Mycobacterium spp. (1.2%). The role of HEp-2 cell-adherent E. coli and HIV enteric infections in patients with HIV-associated diarrhea deserves further study.

Bacterial Adhesion↗
PubMed1997

Gastritis secondary to herpes simplex virus.

Gastric infection with herpes simplex virus is rare, with only two cases previously reported. At the time of the previous reports, the virus could not be cultured, and the diagnosis was based on histological findings. Two cases of culture positive herpes simplex virus gastritis are presented, emphasizing the importance of routine gastric biopsies and viral cultures in immunodeficient patients with dyspeptic symptoms.

Biopsy↗
PubMed1996

Morphological profiles of neutron and X-irradiated small intestine.

This paper describes the response of mouse small intestine, at several time points after treatment with neutron or X-irradiation, using doses expected to give similar effects in terms of crypt/microcolony survival. Using resin histology, the effects of radiation on the numbers of duodenal cell types and measurements of tissue areas were assessed. The results for individual parameters and for an estimate of overall damage are given in a data display, which summarises the morphological profile of the organ after both types of radiation. Damage and recovery were seen for many of the parameters studied but there was no standard response pattern applicable for all parameters. In particular, the response of individual crypt cell types could not be predicted from knowledge of the change in crypt numbers. With regard to the holistic response of the gut, neutron irradiation appeared to have caused more damage and produced more early effects than the X-irradiation. More specifically, neutron treatment led to more damage to the neuromuscular components of the wall, while X-irradiation produced early vascular changes.

Animals↗
PubMed1994

Heavy ion induced changes in small intestinal parameters.

The effects on 17 different structural parameters of mouse small intestine three days after treatment with three types of heavy ion (neon, iron and niobium) are compared, the first two being of particular relevance to space flight. The data for niobium are given in full, showing that changes after niobium ion treatment are not standard and are concentrated in the epithelial compartment, with few of the parameters having a response which is dose dependent. When comparisons are made for the three types of heavy ion, the damage is greatest after neon ion irradiation, implying that the additional non-epithelial damage produced as LET rises from X rays through neutrons to neon ions is not necessarily maintained as LET continues to rise. Further understanding is therefore needed of the balance between changes affecting the vascular and absorptive components of the organ. Variation from group to group is also important, as is variation of strain or gastrointestinal status. All such factors are important in the understanding of changes in multicellular organs after exposure to heavy ion radiation.

Animals↗
PubMed1993

Simulation studies of biomagnetic computed tomography.

The reconstruction of planar and three-dimensional current distributions from measured biomagnetic signals is a new field of research, known as biomagnetic computed tomography. This noninvasive imaging technique promises to provide precise, millimeter-sized resolution images of the electrical currents in tissues or organs. We performed simulation studies on phantom models of electrical sources. As a first step towards the development of an imaging algorithm, we addressed a simplified problem to identify the shape and direction of current flow in a planar surface. The problem was formulated by identifying a space in which the image was to be reconstructed. The space was segmented into a grid. Each grid space represented a current element. The magnetic field at a sampling point due to the current elements was computed using the Biot-Savart law. Since there were many more current elements than sample points, the problem was undetermined and had an uncountable number of solutions. The projection theorem was used to define an analytic solution for the magnitude and orientation of the current elements in the grid space. The solution required the inversion of large matrices in double precision. Such arrays were preprocessed on a mainframe computer, which permitted them to be rendered on any workstation. The accuracy of the image was determined by comparing it with the known location of the sources. Our results show that shape of the filamentary current flow can be imaged with our techniques. The resolution of images based on the sampling of the field, number of voxels in the reconstruction space, and noise is also analyzed.

Computer Simulation↗
PubMed1993

Resolution enhancement of biomagnetic images using the method of alternating protections.

Resolution of biomagnetic images using the technique of the alternating projections is proposed. Our image reconstruction procedure is divided in two steps. First, the biomagnetic inverse problem is solved by use of the projection theorem to reconstruct an initial image of the current distribution from a given magnetic field profile. Although the current distribution thus obtained has poor resolution, it can resemble the original shape of the current distribution. The second step improves the resolution of the reconstructed image by using the method of alternating projections. The procedure assumes that images can be represented by line like elements and involves finding the line like elements based on the initial image and projecting back onto the original solution space. Simulation studies were performed on a set of parallel conductors and a shape of the conductors in the form of letters, UWB@. All conductors were of line like thickness. Restored images closely resemble the original shape of the conductors.

Humans↗
PubMed1992

Renal cell carcinoma and natural killer cells: studies in a novel rat model in vitro and in vivo.

The transplantable rat kidney carcinoma (RKC) provides an excellent experimental model for immunological and therapeutic studies of renal cell carcinoma. In this report, we define the biological characteristics of RKC and explore the interactions between RKC and natural killer (NK) cells. RKC, a transplantable tumor of spontaneous origin, grows progressively over a 12-week period and metastasizes to the lung when implanted orthotopically in the kidneys of female Lewis rats. Rats bearing RKC survived for an average of 10.5 +/- 1.5 (SD) weeks postimplantation. Lung metastases were visible between 7.5 and 8.5 weeks postimplantation, and by 9 to 10 weeks the incidence of metastases reached approximately 67%. Injection of the NK cell-specific monoclonal antibody 3.2.3 depleted Lewis rats of their NK activity for up to 14 days. Adherent lymphokine-activated killer cells generated from the spleens of 3.2.3-injected rats were significantly less lytic than those from control rats and contained a significantly lower percentage of 3.2.3+ cells when analyzed by flow cytometry. Groups of rats were implanted with RKC and received injections of 3.2.3 biweekly to maintain depletion of NK cells or of a control antibody, NK1.1, specific for mouse NK cells. At 10 weeks postimplantation, 3.2.3-injected rats had significantly (P < or = 0.005) larger tumors (104.4 +/- 20.1 g) than NK1.1-injected rats (75.4 +/- 13.9 g). Spleen cells and peripheral blood cells from uninjected, tumor-bearing rats had a slight but nonsignificant decrease in NK activity against 51Cr-labeled YAC-1 targets over the course of RKC progression. The activity of adherent lymphokine-activated killer cells from tumor-bearing rats was lower than that from normal rats, but not significantly. Cultured RKC cells were killed by both splenic NK cells and adherent lymphokine-activated killer cells. These data demonstrate that RKC is NK sensitive and that tumor growth does not abrogate NK activity. The RKC tumor provides a model system for the analysis of immunological factors in renal cell carcinoma growth and presents opportunities for testing therapeutic interventions in a system that closely mimics the human disease.

Animals↗
PubMed1992

Characterization through a data display of the different cellular responses in X-irradiated small intestine.

Previous work on small intestinal radiation injury has reported changes in epithelial and non-epithelial tissues, but with few quantitative comparisons of different responses by individual cell types. The approach used here quantifies the responses of mouse duodenum to X-irradiation with 6 Gy, 10 Gy and 20 Gy, sampled three days after treatment, and 10 Gy sampled 6 hours, 1 day and 3 days after treatment. Tissue area measurements and counts per circumference for 13 different structural elements are subjected to statistical tests. New data reported here for X-irradiation include the fact that cryptal cells do not respond uniformly, indicating that the crypt/microcolony cannot always be used as a standard unit in assessing radiation injury. Non-epithelial structures, such as submucosal arterioles, are also affected. The data display also includes control-referenced ratios, from which are calculated Tissue Indices and a final Morphological Index, which estimates total structural damage. The Indices are useful in drawing attention to unexpected changes in extent or range of data sets. In addition, the Epithelial Index appears to be a sensitive indicator of radiation damage, even at low doses and early time points. The data display includes a graph of the total Indices and summary tables of data, and encourages close study of the constituent data points.

Animals↗
PubMed1992

A processing strategy for automated Papanicolaou smear screening.

A multilayer processing strategy was developed for the automatic screening of conventionally prepared Papanicolaou smears. The processing stages include image segmentation, feature extraction, object classification and slide classification. Mathematical morphology functions were implemented in hardware with custom-built gate array processors for image segmentation. There were 68 features used for classifier training. In object classification we combined the evidential supports of a binary decision tree classifier and a multilayer perceptron classifier to achieve an integrated decision. In this feasibility study, 449 conventionally prepared cervical Papanicolaou smears were tested in a prototype research system between January and May 1991. The 95% confidence interval for the slide false-negative rate was 1-9%, and the 95% confidence interval for the slide sort rate was 45-55%. The estimated sort rate for clearly normal slides is within the range required for a cost-efficient screening system, and the estimated false-negative rate for premalignant and malignant smears is an improvement over published false-negative rates for human performance. Several performance improvement efforts are still under way. We expect that they will result in a vastly reduced slide false-negative rate.

Automation↗
PubMed1992

Relationship between villous shape and mural structure in neutron irradiated small intestine.

Previous work on irradiation of mouse small intestine has assessed the changes produced by counting crypts/microcolonies, scoring villous shape or examining morphological changes in specific parts of the wall. This paper used scanning and transmission electron microscopy to study the effects of whole body irradiation with 5 Gy neutrons on the surface and internal features of the intestinal wall of CFLP mice, 1 day, 3 days and 7 days after treatment. Empirical scores from the ultrastructural findings were inserted into a Morphological Index display calculated from analytical data based on cell counts and area measurements obtained from resin histology sections. The final data display showed that the neutron irradiation produced marked structural changes in different cells and tissues by 1 day. These changes were maximal at 3 days with substantial improvement by 7 days. When this data display was compared with scores taken from scanning electron microscopy of the mucosal surface, the change in villous shape from erect fingerlike projections to lower profiles less suited to absorption was seen to correlate more with changes in the smooth muscle than with the epithelial cryptal compartment.

Animals↗
PubMed1992

Automated prescreening of conventionally prepared cervical smears: a feasibility study.

The feasibility of an automated screening device that will analyze conventionally prepared cervical smears was examined. Consecutive normal and abnormal cervical smears were selected retrospectively and analyzed on a customized microscope imaging workstation system. Specialized image processing, feature extraction, and object classification algorithms were integrated on the imaging workstation to provide an Analysis Score for each slide analyzed. A threshold was set for the Analysis Score, and all slides with a score less than the threshold were classified as normal. Examination of the distribution of the Analysis Score for normal and abnormal cervical smears provided an estimate that 50% of all slides will be sorted as normal, and consequently need no cytologist review. With the Analysis Score threshold set for a 50% sort rate, zero false-negative slides were found in this slide set. This study has shown that a large percentage of slides can be correctly classified as normal while maintaining a high sensitivity to abnormal slides. Given the current workload problems in cytology laboratories, reducing the screening workload by one half will be beneficial. This study has shown that it is now feasible with current technology to provide a clinically useful device to automate screening of conventional cervical smears.

Algorithms↗
PubMed1991

Neutron and X-ray effects on small intestine summarized by using a mathematical model or paradigm.

The responses of intestinal tissues to ionizing radiation can be described by comparing irradiated cell populations qualitatively or quantitatively with corresponding controls. This paper describes quantitative data obtained from resin-embedded sections of neutron-irradiated mouse small intestine at different times after treatment. Information is collected by counting cells or structures present per complete circumference. The data are assessed by using standard statistical tests, which show that early mitotic arrest precedes changes in goblet, absorptive, endocrine and stromal cells and a decrease in crypt numbers. The data can also produce ratios of irradiated: control figures for cells or structural elements. These ratios, along with tissue area measurements, can be used to summarize the structural damage as a composite graph and table, including a total figure, known as the Morphological Index. This is used to quantify the temporal response of the wall as a whole and to compare the effects of different qualities of radiation, here X-ray and cyclotron-produced neutron radiations. It is possible that such analysis can be used predictively along with other reference data to identify the treatment, dose and time required to produce observed tissue damage.

Animals↗
PubMed1991

Intestinal secretory immune response to infection with Aeromonas species and Plesiomonas shigelloides among students from the United States in Mexico.

Intestinal secretory IgA (sIgA) response or lack of response among adults in Mexico with diarrhea was used as an indicator of enteropathogenicity of Aeromonas species and Plesiomonas shigelloides. sIgA was extracted from stool specimens obtained at day of presentation and 5 days later. Total sIgA was standardized, and specific sIgA titer against the organism being shed by each patient was determined. Western blotting was used to determine which microbial antigens elicited an intestinal sIgA response. Of 12 subjects shedding Aeromonas sobria or Aeromonas hydrophila, 11 had a fourfold or greater sIgA titer rise against the infecting strain. Western blotting showed that somatic lipopolysaccharides were the immunodominant antigens. No sIgA titer rises were detected among two patients shedding Aeromonas caviae or in 14 shedding P. shigelloides. This study provides further evidence of the significance of A. sobria and A. hydrophila as pathogens in acute diarrhea but raises additional questions about the role of P. shigelloides, at least in US adults with travelers' diarrhea.

Adult↗