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Biomedical subjects

A C Nelson

Publications and source records attributed to A C Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1990

Radiation induced changes in the blood capillaries of rat duodenal villi: a corrosion cast, light and transmission electron microscopical study.

Disturbances of gastrointestinal function are an important limiting factor in radiotherapy of the abdominal and pelvic regions. The pathogenesis of radiation induced intestinal dysfunction is not completely understood, although the intestinal mucosa has been shown to respond to irradiation by a progressive reduction in villous size. Since blood vessels in other organs have been implicated in the initiation of post-irradiation changes, the present study examines the response of villous blood vessels to an X-ray dose of 10 Gy after 3 days. Vascular corrosion casts and light and transmission electron microscopy (TEM) were used to study the post-irradiation vascular response. In control and sham-irradiated animals, the villous plexus was fountain-like: an arteriole entered the villous base and divided apically into two terminal branches. Villous capillaries apparently derived from the terminal branches, and united to form venules. In capillary loops the vertical inter-capillary distance was greater than the horizontal inter-capillary distance. After irradiation, the vessels became tortuous and the plexus was compressed apico-basally, shown by a decrease in the vertical inter-capillary distance. The capillary luminal diameter, as measured on resin semi-thin sections, was significantly increased. TEM showed that the endothelium was irregular and there was evidence of plasma leakage. These results suggest that villous damage seen after irradiation can include changes in the villous vasculature.

Animals↗
PubMed1989

Renal injury and recovery in partial ureteric obstruction.

Partial ureteric obstruction was produced by insertion of an obstructing stent into the left ureter of 21 mongrel dogs and the duration of obstruction was varied as follows: Group A (n = 7) for 60 days; Group B (n = 7) for 28 days; Group C (n = 7) for 14 days. Intrapelvic pressure monitoring confirmed that obstruction had been produced by stent insertion and relieved by reimplantation of the left ureter following the designated obstruction period. The extent of recovery of renal function was assessed by creatinine clearance, with group C maintaining normal function, group B recovering 31% and group A recovering 8% of control function. Methyl-methacrylate extrusion casts of the renal microvasculature were made in group B and C kidneys and studied by scanning electron microscopy. During obstruction there was evidence of arteriolar constriction. These changes provide a morphological basis for the renal functional alterations and support the concept that post-obstructive renal failure is a vascular injury.

Animals↗
PubMed1988

Thrombin: implications for intratumor therapy against metastasis.

The effect of an intratumor injection of thrombin as a potential cancer therapeutic agent was examined in two transplantable solid tumor models: a renal adenocarcinoma implanted beneath the kidney capsule in Wistar-Lewis rats and a rhabdomyosarcoma implanted similarly in Wag-Rij rats. For each tumor type, a group of test animals received a single dose of thrombin injected directly into the central tumor mass 6 weeks following tumor implantation. Corresponding groups of tumor-implanted controls consisted of animals that received an equal volume injection of saline instead of thrombin and animals that were not injected. The tumor-implanted animals receiving thrombin, saline, or no injection were handled identically. The saline-injected and noninjected control animals died of metastasis to the lung within the same well-defined period of time. All animals receiving thrombin showed significantly increased longevity, and the degree of increase was related to variations in tumor size at the time of injection. In every case, animal death was due to pulmonary metastasis verified at autopsy, but animals receiving thrombin therapy lived about 85% longer following tumor implantation than animals not receiving therapy.

Animals↗
PubMed1988

Microtomography from limited projections in conventional TEM for 3D reconstruction of an intact cell.

It is possible to generate three-dimensional reconstructions of whole, non-sectioned biological cells in conventional TEM using an 80 kV tungsten source. A TEM specimen stage was modified to accommodate a precise single-axis tilting mechanism controlled by a digital stepping motor interfaced to a computer. For image collection, a video camera was optically coupled to the TEM phosphorescent screen, and the video image was digitized by a frame buffer interfaced to a computer. Specimen tilt and projection image collection were fully computer-automated. This microtomography system design could be readily adapted for most TEMs. Image reconstruction was achieved through computation on projection images from limited tilts; typically less than thirty projection images were needed for a coarse 3D reconstruction. The iterative reconstruction algorithm used certain statistical assumptions about the distribution of image gray values. Since microtomography was performed on non-sectioned whole mount cells viewed under an 80 kV electron beam, methods of embedment-free specimen preparation with chemical fixation and extraction were employed. These methods were utilized successfully to permit good image formation of the entire cell mitotic nucleus a few micrometers in thickness. The 3D reconstruction of a single kidney cell mitotic nucleus was carried out and shown to produce a reasonable microtomogram of gross features like the condensed chromosomes.

Algorithms↗
PubMed1988

Characterization of solid tumor microvasculature: a three-dimensional analysis using the polymer casting technique.

Using a polymer casting technique in conjunction with scanning electron microscopy, the three-dimensional characterization of tumor microvasculature as a function of age of renal adenocarcinoma in the rat kidney is undertaken. The microvasculature of the rat tumor model is compared with VX2 carcinoma in the rabbit leg muscle. Light microscopy and transmission electron microscopy on the rat tumor model are performed to correlate the features seen under scanning electron microscopy of vascular casts. The casts show marked differences between tumor and normal microvasculature. The tumor vascular architecture appears disarrayed with prevalent atypical features such as coils, ribbons, sheets, dense capillary networks, saccular dilatations, leaky and otherwise highly irregular vessels. Sprouts of new growth capillaries are seen throughout the tumor casts. Compressed vessels are present and become more pronounced in older tumors. These features are not observed in normal controls treated under identical conditions. The application of this high resolution three-dimensional casting technique to tumor studies is promising for research in basic tumor mechanics as well as in the effects of tumor vasculature on mediating radiation and chemotherapy and the fundamental mechanisms of metastasis.

Adenocarcinoma↗
PubMed1987

Study of rat lung alveoli using corrosion casting and freeze fracture methods coupled with digital image analysis.

Relative areas and volumes can be estimated from vascular corrosion casts of rat lung alveoli using a calibration obtained from bulk frozen hydrated tissue. These morphometric measurements are roughly independent of the shrinkage and distortion artifacts known to arise in the corrosion casting procedure. Digital image processing of the SEM micrographs is employed to facilitate the measurement of casts and frozen tissue. The vascular corrosion casting technique is modified also to permit successful casting of alveolar air passages. The modified technique produces faithful casts of dead-ended luminal structures where continuous perfusion of casting medium into the tissue is not possible. The casts of alveolar air passages and their corresponding vasculature are compared to determine the volume of a single alveolus. By utilizing the calibrated measurements of lung areas and volumes, an estimate of lung vascular surface area per unit volume is obtained. This number, when multiplied by the respiratory tidal volume of the rat, may represent the total lung vascular surface are available for physiological gas exchange during normal respiration.

Animals↗
PubMed1987

A lesson from Tony.

Explore the source record for details and available documents.

Child, Hospitalized↗
PubMed1986

Computer-aided microtomography with true 3-D display in electron microscopy.

A novel research system has been designed to permit three-dimensional (3-D) viewing of high resolution image data from transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The system consists of front-end primary data acquisition devices, such as TEM and SEM machines, which are equipped with computer-controlled specimen tilt stages. The output from these machines is in analogue form, where a video camera attached to the TEM provides the sequential analogue image output while the SEM direct video output is utilized. A 10 MHz digitizer transforms the video image to a digital array of 512 X 512 pixel units of 8 bits deep-stored in a frame buffer. Digital images from multiple projections are reconstructed into 3-D image boxes in a dedicated computer. Attached to the computer is a powerful true 3-D display device which has hardware for graphic manipulations including tilt and rotate on any axis and for probing the image with a 3-D cursor. Data editing and automatic contouring functions are used to enhance areas of interest, and specialized software is available for measurement of numbers, distances, areas, and volumes. With proper archiving of reconstructed image sequences, a dynamic 3-D presentation is possible. The microtomography system is highly versatile and can process image data on-line or from remote sites from which data records would typically be transported on computer tape, video tape, or floppy disk.

Computers↗
PubMed1986

Theory for calcium-phosphate crystal formation in tissue from scanning electron microscope data.

Scanning electron microscope (SEM) morphological analysis combined with energy dispersive characteristic x-ray analysis provides insight into the mechanism of biological mineralization. A time series of tissue micrographs and mineralization measurements can permit the determination of the mineralization kinetic behavior and is the basis upon which a computer model has been devised. The computer model is constructed from fundamental principles of crystal nucleation and precipitation theory. Various general forms of the model are tested against the laboratory data for goodness-of-fit using the least squares method, and two models are found to be acceptable. Both of the acceptable models involve inhibition of the mineralization process which has a reaction order ranging from one to two. A third model involving constant nucleation rate must be rejected. Having established working first principle models for the mineralization process, one can compute a constant number of nucleation sites and a supersaturation value for calcium in various mineralized tissues such as the spongiosa and fibrosa of heart valve leaflet implants. These quantities are determined and used in discussing a general theory for biomineralization which emphasizes therapeutic considerations.

Animals↗
PubMed1985

Onset and progression of experimental bioprosthetic heart valve calcification.

Calcification, the major cause of bioprosthetic heart valve failures, is a serious clinical problem with uncertain pathogenesis. The objectives of the present study were to define the progressive chemical and morphologic sequence of mineralization in glutaraldehyde-treated porcine aortic valve cusps implanted subcutaneously in rats and to compare the pathology and pathophysiology of calcification in subcutaneous implants with that of orthotopic valve replacements in calves. Cusps were implanted subcutaneously in 3-week-old rats for 24 hours to 18 weeks. Cuspal calcium was 114 +/- 18 micrograms/mg of dry weight (mean +/- SEM) at day 21 and 218 +/- 6 at day 56 of implantation and unchanged thereafter. The earliest mineral deposits, noted at 48 hours, were associated with devitalized porcine connective tissue cells, but by 7 days, mineral deposits also involved collagen bundles. Scanning electron microscopy with energy-dispersive x-ray analysis demonstrated predominant accumulation in the spongiosa with a spongiosa to fibrosa energy-dispersive x-ray analysis count ratio of calcium of 15 at 21 days. In stent-mounted glutaraldehyde-preserved porcine valves implanted in five calves as mitral replacements for 69 to 142 days, cuspal calcium was 86 micrograms/mg (mean) (range 47 to 128). Calf implants also had cell oriented and collagen calcification predominating in the valvar spongiosa. In both rat subcutaneous and calf mitral valve models, early diffuse calcific microcrystals evolved into confluent nodules that disrupted tissue architecture. It is concluded that calcification of glutaraldehyde-preserved porcine aortic valves implanted subcutaneously in rats begins within 48 hours, earliest deposits are localized to residual porcine connective tissue cells, but latter deposits also involve collagen fibrils, mineralization is most prominent in the spongiosa, the pathology of calcification in rat subcutaneous implants and calf mitral replacements is comparable, suggesting a common pathophysiology, and calcific nodule formation most likely initiates clinical features.

Animals↗
PubMed1985

Scanning electron microscopy methodology for study of the pathophysiology of calcification in bioprosthetic heart valves.

Scanning electron microscope (SEM) morphologic analysis combined with energy dispersive characteristic X-ray (EDX) microprobe analysis provides insight into the mechanisms associated with disease-related crystal formation in biological materials. SEM and EDX were employed in analyzing specimens which were embedded in standard fashion in glycolmethacrylate. The specimen surfaces under electron microscope investigation resulted from microtomy used in the preparation of reference light microscope histological sections; thus histology served as a direct reference for the SEM and EDX analyses. The particular application of these methods was in the study of bioprosthetic heart valve calcification, largely responsible for clinical failure of these heart valve substitutes. To simulate the clinically observed mineralization processes, glutaraldehyde-pretreated porcine heart valve leaflets were implanted subcutaneously in rats and subsequently removed at various time intervals from 1 to 56 days. Also, to address the hypothesis that the calcification process generates crystalline materials analogous to those in bone, EDX data obtained from pure hydroxyapatite were compared with the embedded tissue results. Further, EDX results were compared with data obtained by chemical analysis of the bulk specimens to assess the validity of the electron microscope technique.

Animals↗
PubMed1985

Morphological changes in neutron irradiated red blood cells.

Living human red blood cells (erythrocytes) were irradiated with a beam of thermal neutrons having a thermal neutron flux of 9.4 X 10(9) neutrons/cm2 per sec corresponding to a dose rate of 5 Gray per hour. The neutron beam was obtained from the thermal neutron facility at the MIT Nuclear Reactor and contained some gamma-ray contamination which contributes approximately 8% of the dose effect. Approximately 92% of the dose effect is due to the neutron radiation. Populations of neutron irradiated red blood cells were examined under scanning electron microscopy to observe morphological changes due to the radiation dose. The thermal neutron doses ranged from zero for controls to 75 Gray, and cell populations were examined at various post-irradiation time periods of 10, 48, and 96 h. A four-stage discoid to spheroid shape transformation of the damaged red blood cells was characterized, and the time dependence of each transformation stage was determined for both unirradiated and irradiated cells. The radiation dose caused an initial dose-dependent shift from Stage 1 to Stage 2 with an associated increase in the transformation rate constants. The thermal neutron doses delivered are considered to be in the low dose range for radiation effects on red blood cells, yet the pronounced effects indicate a high relative biological effectiveness (RBE) for thermal neutrons.

Dose-Response Relationship, Radiation↗
PubMed1984

Radiation damage in rat kidney microvasculature.

Scanning electron microscopy (SEM) combined with a specialized polymer injection casting technique permits the analysis of radiation induced damage in rat kidney glomeruli. A lead shielding device is constructed to enable the irradiation of the living rat left kidney, while the remainder of the animal is shielded from the dose, the right kidney serves as a control. The source of radiation is 137Cs which produces 0.66 MeV gamma-rays to achieve a kidney dose of 100 rad and 5000 rad in these experiments. Radiation damage to kidney glomeruli is assessed at intervals of 0, 1, 3 and 7 days post-irradiation at the two dose levels. It is found that radiation damage to kidney glomeruli is expressed morphologically at 7 days post-irradiation at the 100 rad dose level, while glomerular damage is apparent as early as 3 days post-irradiation at the 5000 rad dose level. Moreover, by 7 days post-irradiation with a 5000 rad dose, the kidney glomerulus thoroughly degenerates to a leaky fused mass of vessels. From a morphological viewpoint, kidney glomeruli are significantly more sensitive to radiation than surrounding vasculature. The methods developed here for assessment of radiation damage are highly repeatable and could serve as a standard technique in radiobiology.

Animals↗
PubMed1983

Rapid development of corneal lesions in rats produced by heavy ions.

Scanning electron micrographs of heavy ion irradiated corneas demonstrate a significant correlation with the heavy ion beam: The average number of plasma membrane lesions per unit area of corneal surface is correlated with the particle fluence of the beam. This observation corroborates what has already been suggested theoretically about heavy ion tracks and what has been shown experimentally through etched plastics, developed emulsions, and bubble chambers. But the new data indicate that particle tracks occur in biological tissues as well, and that a single heavy ion is responsible for each membrane lesion.

Animals↗
PubMed1983

Biologic determinants of dystrophic calcification and osteocalcin deposition in glutaraldehyde-preserved porcine aortic valve leaflets implanted subcutaneously in rats.

Bioprosthetic cardiac valve calcification is a frequent complication after long-term valve replacement. In this study the authors sought to examine the biologic determinants of this type of dystrophic calcification using subcutaneous implants of glutaraldehyde-preserved porcine aortic valve leaflets (GPVs) in rats. GPVs and clinical valvular bioprostheses were prepared identically. Retrieved implants were examined for calcification and the deposition of osteocalcin (OC), a vitamin K-dependent, bone-derived protein, that is found in other dystrophic and ectopic calcifications. GPVs implanted in 3-week-old rats calcified progressively (GPV Ca2+, 122.9 +/- 6.0 micrograms/mg) after 21 days, with mineral deposition occurring in a morphologic pattern comparable to that noted in clinical retrievals. Calcified GPVs accumulated osteocalcin (OC, 183.4 +/- 19.4 ng/mg); Nonpreserved porcine aortic leaflet implants did not calcify (Ca2+ + 5.6 +/- 1.0 micrograms/mg). Millipore diffusion chamber (0.45-mu pore size enclosed GPV implants accumulated calcium and adsorbed osteocalcin despite the absence of attached host cells. GPVs implanted for 21 days in 8-month-old rats calcified less (GPV Ca2+, 22.4 +/- 5.0 micrograms/mg) than did GPVs implanted in 3-week-old rats (see above). High-dose warfarin therapy (80 mg/kg) did not alter GPV calcification (GPV Ca2+, 39.6 +/- 2.9 micrograms/mg) in 72-hour subcutaneous implants in 3-week-old male rats, compared with control rats (GPV Ca2+, 40.8 +/- 4.8 micrograms/mg).

Age Factors↗
PubMed1981

Some indications of structural damage in retina by heavy ion radiation.

At the Lawrence Berkeley Laboratory Bevalac Facility, iron nuclei were accelerated to an energy of 600 MeV/amu. The beam of iron thus obtained was used to irradiate living biological specimens in order to study possible microscopic tissue damage with the aid of SEM. The experiments involved total head irradiation of live rats which were subsequently returned to their cages to remain for 1 day and 30 days before further examination. After the 1 day and 30 day waits, both eyes were enucleated and placed in chemical fixative followed by ethanol dehydration and critical point drying. Retinas were carefully removed from the eye cups and loaded separately on aluminum stubs which were sputter coated. SEM of the 1 day and 30 day retinas revealed lesions which were not found at all in control retinas. The 1 day and 30 day retinas manifest regions where outer rod segments were missing or rearranged. A single energetic iron nucleus may be capable of generating a retinal lesion which becomes enlarged as biological processes intervene during the 1 day and 30 day waits. Being composed of highly specialized nerve cells, retinas cannot regenerate following irradiation which severely damages the rod cells. Thus one would expect the observed radiation induced retinal lesions to correspond to permanent tissue damage and possible loss of visual acuity in the intact animal.

Animals↗