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Biomedical subjects

M D Olson

Publications and source records attributed to M D Olson.

13 recordsLinked to original sources

Short-term dietary copper deficiency does not inhibit angiogenesis in tumours implanted in striated muscle.

The effect of dietary copper deficiency on tumour growth, neovascularisation and microvascular integrity was studied in the rat cremaster muscle. Male, weanling Sprague-Dawley rats were fed purified diets which were copper deficient (< 0.5 micrograms g-1 of diet) or copper adequate (5 micrograms g-1 of diet). Seven days after initiation of diets, a chondrosarcoma was implanted in the cremaster muscle of each rat. Five, 10 or 20 days after tumour implantation, rats were anesthetised and their cremasters prepared for observation by intravital microscopy. Intraarterial injection of fluorescein isothiocyanate-conjugated albumin and subsequent observation of fluorescence in the perivascular space indicated no difference in microvascular albumin leakage between the tumour vasculature of copper deficient and copper adequate rats. Neither tumour growth (assessed by wet weight), vascular density (assessed by light microscopy), nor any ultrastructural characteristics of the tumour or its vasculature (assessed by electron microscopy) were affected by copper deficiency. In view of findings by others which indicate changes in tumour characteristics with copper deficiency, we conclude that the copper dependency of tumour growth and vascularisation is a function of the type of tumour, the host tissue, or the conditions of copper depletion.

Animals

The effect of TTX-activity blockade and total darkness on the formation of retinotopy in the goldfish retinotectal projection.

In the normal goldfish, neighboring retinal ganglion cells terminate in one small tectal locus to produce the precise retinotopy characteristic of this projection. This can be directly demonstrated by labeling neighboring ganglion cells with small "spot" injections of WGA-HRP, which yield a single small patch of product at the retinotopically appropriate part of the tectum. When the optic nerve is crushed, label from these spot injections was previously found to be widely dispersed during the early phase of regeneration. With time, label subsequently condensed, typically into several discrete patches reminiscent of ocular dominance columns. In this study, we tested whether the formation of these patches required impulse activity by injecting tetrodotoxin (TTX) into the eye during regeneration. We found that impulse blockade completely inhibited the formation of discrete patches while permitting considerable condensation of the label. This implies that these patches are generated by activity but that some map "refinement" utilized cellular processes that are activity independent. This activity-independent condensation progressed at a noticeably slower rate than the equivalent condensation seen with activity, thus suggesting that activity normally participates as a "helper factor," even though it is not strictly required. Since the formation of discrete patches during regeneration provides a sensitive measure of activity-dependent refinement, this was used to further address two controversial questions concerning the role of impulse activity. One is whether there is a chronologically defined critical period for activity-dependent refinement. This was tested by blocking impulse activity for 2 to 4 months, much longer than the activity-dependent refinement is thought to last, and then permitting activity to resume. We found that multiple patches were formed following this period of late activity, thus indicating that synaptic plasticity extends for several months beyond the supposed critical period. The other question was whether spontaneous retinal activity was sufficient for activity-dependent ordering. To test this, fish were kept in constant darkness during optic nerve crush and labelled with retinal spot injections at various times during regeneration. Condensation of label with the final formation of multiple patches formed at about the same time as fish with normal visual experience. This implies that the amount and extent of correlation of spontaneous activity in retina is adequate for driving activity-dependent refinement.

Animals

The common stye.

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Hordeolum

Surface coat material associated with the developing otic placode/vesicle in the chick.

Surface coat material (SCM) has been illustrated in association with the apical surfaces of numerous epithelia during morphogenesis. This study investigates the development of a SCM associated with the invaginating otic placode/vesicle in the chick. Glycoconjugate containing SCM was retained by the inclusion of cetylpyridinium chloride (CPC) in the fixative, histochemically visualized by using ruthenium red (RR) staining, and viewed by scanning (SEM) or transmission (TEM) electron microscopy. Initial characterization of the glycoconjugates present in this material was elucidated by using lectins conjugated to fluorescein isothiocyanate. Lectins utilized included concanavalin A (Con A), wheat germ agglutinin (WGA), and soybean agglutinin (SBA). Invagination of the otic placode was apparent as early as stage 12. By stage 15 the vesicle was beginning to separate from the surface ectoderm as evidenced by its aperture, which was altered in shape and reduced in size. All embryos fixed with glutaraldehyde containing either CPC or RR were shown to possess SCM associated with the surface ectoderm, particularly in the area of the otic placode/vesicle. Additional embryos were processed by cryofixation without prior aldehyde fixation; these also exhibited SCM. All lectins labelled the epithelium of the otic placode/vesicle. However, their binding patterns were not identical. The binding of Con A and WGA remained constant over the stages studied, while SBA increased as the otic vesicle developed. The data clearly indicate that otic placode morphogenesis is accompanied by the synthesis of SCM rich in glycoconjugates.

Animals

A real-time data-logger system using an optical disk WORM for archiving continuous 12-lead ECG data during exercise testing.

An exercise ECG analysis program was developed over 15 years on a number of mainframes, minicomputers and, most recently, microcomputer-based systems. It has been rehosted into both Motorola MC68000 and Intel 80286 microprocessor-based development systems and is currently used with a removable 200 Mbyte optical disk (Write-Once-Read-Many, WORM) based data-logger system that can record and store all 12 leads simultaneously and continuously for an entire exercise test (up to 38 minutes). Data is acquired with 12-bit A/D resolution at 500 samples/sec. All ECG data and patient information are archived on the optical disk for later off-line recall and analysis on a PC or real-time replay through a D/A converter. Recorded ECG signals are at patient levels so they can be replayed through the patient cable box on any commercial system. Current development includes both simultaneous on-line processing and storage of 12-lead ECG data and off-line processing and development performed on the long-term, continuous ECG data being archived on optical disk. Patient medical histories and clinical information are separately entered into an applications database, where ECG measures and test results are later included. This new optical disk based exercise ECG database contains more than 600 complete exercise tests and is projected to increase to nearly 3,000 within 2 years.

Computer Systems

Problems and limitations of ECG baseline estimation and removal using a cubic spline technique during exercise ECG testing: recommendations for proper implementation.

One common variety of exercise-induced artifact is baseline wander resulting from movement, respiration, and poor electrode contact. Although filters can be designed to remove much of this baseline variation, they will distort the low-frequency components of the ECG complex, such as the TP-segment, the PR-segment, and, most problematically, the ST-segment. The ST-segment is the most diagnostically relevant measure of the ECG taken during exercise. While linear baseline interpolation and removal may be adequate at lower heart rates, they also will introduce significant distortions. This is particularly evident when excessive nonlinear wander is present, as seen at higher heart rates and respiration rates. A nonlinear, third-order, polynomial estimator of baseline wander, known as the cubic spline, has been used for nearly 15 years. It is a very robust technique applied to exercise ECG recordings. Since the cubic spline is not a filter and use an a priori knowledge of the shape of the ECG signal, it estimates the true baseline and avoids distortion better. The more common implementations of this technique use relatively short ECG recordings. With the advent of increasing power in computerized ECG systems, the implementation of the cubic spline algorithm for removing baseline wander in continuous, longer-duration ECG records and in real-time processing is being attempted. However, the correct application of the cubic spline to continuous recordings is not straightforward and involves a number of previously unforeseen difficulties. The accuracy and resolution of both floating point and integer operations is critical during long-term application of the cubic spline function.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms

Effect of histamine on cardiac sarcolemmal calcium binding as indicated by use of ionic lanthanum.

To determine whether the inotropic effect of histamine might be associated with enhanced calcium binding to the sarcolemmal-glycocalyx complex, the effect of histamine on lanthanum binding to the cell membrane in the presence of verapamil was assessed. Rabbit hearts were perfused firstly with histamine, secondly with histamine and verapamil, and subsequently with histamine in the presence of lanthanum and verapamil. Subsequent transmission electron microscopy showed the presence of bound lanthanum on both the cellular surface and cytoplasmic vesicles of most cardiac myocytes, which is in contrast to the absence of lanthanum binding that occurs in the presence of verapamil alone. Furthermore, this histamine mediated enhancement of lanthanum binding is not affected by the H1 antagonist diphenhydramine but is reduced by the H2 antagonist cimetidine. This visual evidence of an apparent enhancement of lanthanum binding under histamine and subsequent attenuation with cimetidine supports the hypothesis that histamine may exert its positive inotropic effect by causing increased calcium binding to the sarcolemmal-glycocalyx complex of cardiac muscle and that the effect is mediated at least in part by H2 receptors.

Animals

Histamine induced alteration of calcium binding to microvascular endothelium as indicated by use of ionic lanthanum.

To determine whether histamine's effect on microvascular permeability might be associated with altered calcium binding, the influence of histamine on lanthanum binding to vascular endothelium was assessed in the presence of verapamil. Isolated rabbit hearts were perfused firstly with histamine, secondly with histamine and verapamil, and subsequently with histamine in the presence of lanthanum and verapamil. Examination by transmission electron microscopy showed that 92% of microvessels examined contained bound lanthanum on plasma membranes, plasmalemmal vesicles, or endothelial clefts of vascular endothelium, or all three, in both atria and ventricles, which is in contrast to the low proportion (4%) of microvessels containing bound lanthanum found in the presence of verapamil alone. The enhancement of lanthanum binding was reduced by both H1 and H2 receptor antagonists. This evidence supports the hypothesis that the increase in vascular permeability with histamine may be associated with increased calcium binding to vascular endothelial membranes and that both H1 and H2 receptors play a part in this activity.

Animals

Scanning electron microscopy of developing photoreceptors in the chick retina.

Photoreceptor morphogenesis in the sensory retina of chicks of 2 to 20 days incubation age was studied by scanning electron microscopy (SEM) and correlative transmission electron microscopy (TEM). At 9.5 days spherical inner segments extend into the subretinal space (optic ventricle). They are randomly arranged with chiefly smooth surfaces and contain centrioles, polyribosomes and microtubules. Microvilli project primarily from Müller cells. By the twelfth day immature ellipsoid and myoid regions have formed. Microvilli are abundant on the lateral surfaces of inner segments and extend over the entire spherical surface by the fifteenth day. Occasional cilia with surrounding depressions at their bases were also observed. Inner segments are more symmetrically arranged due to close proximity of photoreceptor cells. Inner segments elongate during the sixteenth day; many display a transitional ovoid form. Microvilli become less numerous but some persist as calycal processes. By the eighteenth day, conical shaped outer segments appear. Thereafter, all photoreceptor cells are comparable to those in the mature retina. Abundant microvilli on the external surface of the sensory retina suggest a supportive role in supplying adequate nutrition to the sensory retina during morphogenesis. The establishment and continual development of the ellipsoid and myoid appear to be primarily responsible for the elongation of photoreceptor cells.

Animals

Morphogenesis of rod cells in the retina of the albino rat: a scanning electron microscopic study.

This study presents scanning electron microscopic (SEM) observations of topographical changes that occur during morphogenesis of rod cells in the albino rat. Correlative transmission electron microscopy (TEM) was also utilized. Albino rats ranging in age from birth to three weeks were used for the study. Tissues were prepared by conventional methods for SEM and TEM. At birth, numerous irregularly arranged inner segments extend from the external surface of the sensory retina. They are spherical, smooth surfaced and possess a randomly oriented cilium. The internal morphology of these immature inner segments is comparable to that observed in other vertebrate species. Statistical analysis reveals a rapid increse in the number of rod cells during the first week. This period is characterized by the elongation of inner segments and their associated cilia. Microvilli project from the apices of Müller cells, but not from adjacent inner segments. By day 5, cilia occasionally display small bulbous outer segments. They are more numerous by day 8 and are usually eccentrically positioned at the tips of cilia. By day 11, outer segments are abundant and frequently obscure from view the underlying inner segments and associated cilia. Elongated cylindrical outer segments are present within the posterior retina at the end of the second week. However, rod cell morphogenesis lags in the peripheral retina. Topographical variations between developing photoreceptor cells in mammalian and non-mammalian retinas are discussed.

Aging

Development of Bruch's membrane in the chick: an electron microscopic study.

The development of fibrous connective tissue in Bruch's membrane within the choroid of chronologically staged chick embryos was observed by means of transmission electron microscopy. The appearance of these connective tissue elements follows an orderly developmental sequence. The first component of Bruch's membrane to appear is a continuous basal lamina at the basal surface of the presumptive retinal pigment epithelium (RPE) at 21/2 days. Microfibrils and associated amorphous material are present in the adjacent connective tissue space. A discontinuous inner collagenous layer is observed at the basal aspect of the RPE during the fourth day. A definitive elastic layer is present during the ninth day and becomes more apparent following subsequent stages of development. An outer collagenous layer begins development during the tenth and twelfth days. Collagenous fibrils average 37 nm in diameter and display axial periodicity measuring 46 nm between major periods. These measurements increase with age as do the number of collagenous fibrils. Only isolated patches of basal lamina are observed in association with the choriocapillary endothelium by the twentieth day.

Animals

Correlated scanning and transmission electron microscopy of developing lens vesicle in the chick.

Cells within the lens placode undergo transient surface modifications during the course of invagination. At stage 13, cellular apices bulge outward and display decreased surface diameters when compared to adjacent surface ectoderm. The lens vesicle is well invaginated by stage 14. An area of modified cells can be recognized ventral to the lens vesicle aperture. These cells present a smaller surface area and increased pleomorphism. Normal surface ectoderm extends to the dorsal and lateral edges of the aperture. The apical surfaces of cells which line the lumen of the lens vesicle display a complex topography such that individual cell boundaries are not easily distinguished. At stage 17, cellular processes which partially occlude the closing aperture of the lens vesicle may assist in reestablishing ectoderm over the newly formed lens. Preliminary results of cytochalasin B exposure on the invaginating lens vesicle suggest that the contractile action of microfilaments influences the complex cellular topography.

Animals

Apical bearing and success with the Bausch and Lomb Soflens (polymacon) contact lens.

Thirty-three patients (63 eyes) were fitted with Bausch and Lomb soflens (polymacon) contact lenses. The initial lenses were selected with the mean posterior apical radius 0.45 mm flatter than the flat keratometer reading of the cornea (S.D. = +/-0.31 MM). Forty-eight eyes (76%) were successfully fitted and 15 eyes (25%) were unsuccessfully fitted. Among the successfully fitted eyes, 31 were fitted with the initial lens, 12 required steeper lenses, and 5 required flatter lenses. The final successfully fitted lenses were on the average 0.40 mm flatter (S.D. = +/-0.32 mm) than the flat keratometer reading of the cornea. The unsuccessfully fitted lenses were not significantly different than the successfully fitted lenses, being 0.47 mm flatter (S.D. = +/-O.32 mm) than the flat keratometer reading of the cornea. Although the central lens-cornea relationship is helpful in fitting the Soflens, the number of successful results are increased significantly by changing to a lens with different parameters when lens performance and patient response are not optimal.

Adolescent