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Biomedical subjects

H Wayland

Publications and source records attributed to H Wayland.

At least 19 recordsLinked to original sources
PubMed1994

Pentagastrin enhances gastric mucosal defenses in vivo: luminal acid-dependent and independent effects.

Stimulation of acid secretion is associated with enhanced resistance of the gastric mucosa to damage by luminal acid. We studied the mechanism by which gastric mucosal defenses are modulated in a system in which mucus gel thickness, intracellular pH (pHi), gastric mucosal blood flow, and acid secretion can be measured simultaneously in vivo, using a recently developed microfluorometric technique. Intravenous infusion of pentagastrin in a dose associated with maximal acid secretion increased mucus gel thickness, pHi, and mucosal blood flow during superfusion with a neutral solution. Subsequent superfusion with an acidic buffer (pH 1.7) further increased blood flow to nearly three times basal. During superfusion with luminal acid, pHi fell more slowly and recovered toward baseline more quickly in pentagastrin-infused rats than in controls. Pretreatment with the H2-receptor antagonist cimetidine abolished the increased blood flow associated with pentagastrin, impairing pHi homeostasis, although cimetidine increased mucus gel thickness in the absence of pentagastrin. We conclude that gastric defense mechanisms at the preendothelial and postepithelial levels are enhanced during acid secretion as part of a histamine-dependent homeostatic mechanism that balances gastric protective mechanisms with acid secretion. The net result of these enhanced defenses is the preservation of gastric surface cell pHi despite the presence of a large proton gradient between lumen and blood.

Animals↗
PubMed1990

Intravital observatories. Dream or necessity.

Among the major challenges confronting biomedical studies today two stands out above all others: 1. The need for a better interrelation of the remarkable findings of molecular and cell biology to living systems through careful intravital observation; and 2. The need for a more rapid and skillful application of the findings and methods of intravital observation to clinical applications. Major progress on either or both of these problems will require much greater emphasis on multidisciplinary studies of living animals involving a considerably wider variety of disciplines than has been brought to bear on them to date, plus the availability of the finest and most advanced technology. The cost in both money and manpower to achieve major breakthroughs is such that these goals can only be accomplished by having a few centers of excellence in which both a diversity of skills and of equipment can be made available to as wide a spectrum of the biomedical community as possible. It is the contention of this author that this can best be achieved by establishing a few methods-oriented centers of excellence for Intravital Observation which he has called Intravital Observatories. It is urged that the community of microcirculationists, which has long been a leader in a multidisciplinary approach to physiological studies and has made many of the outstanding advances in intravital microscopy, take the lead in making this major contribution to biomedicine.

Academies and Institutes↗
PubMed1988

Microcirculatory stasis precedes tissue necrosis in ethanol-induced gastric mucosal injury in the rat.

The relation of blood flow stasis to the development of unequivocal histologic necrosis (loss of parietal cells from the column of contiguous cells) in ethanol-induced gastric mucosal injury was studied in anesthetized rats. The most rapid vascular change that occurred when the gastric mucosa was exposed to 100% ethanol was a severe segmental constriction of the large submucosal venules. At 22 sec, the average venular diameter was 52.2 +/- 6.0% of the original one. This was followed by complete superficial mucosal blood flow stasis at 49 +/- 4 sec and appearance of histologic evidence of necrosis in one of seven rats at 2.5 min, four of six rats at 10 min, and seven of seven rats at 60 min. We conclude that in ethanol-induced gastric mucosal injury, submucosal venular constriction occurs first, followed by cessation of mucosal blood flow to be followed later on with histologic evidence of necrosis.

Animals↗
PubMed1988

Role of arachidonic acid metabolites in ethanol vasoaction in rat gastric submucosa.

By use of an in vivo microscopy technique in the anesthetized rat, the effect of 0.5-8.0% ethanol on gastric submucosal blood vessel diameter was studied. The direct application of ethanol onto the exposed submucosal vasculature caused a dose-dependent dilatation of the arterioles (9 +/- 3% by 2% ethanol) but had no effect on venular diameter. In rats pretreated with 5 mg/kg indomethacin subcutaneously to inhibit cyclooxygenase activity, the submucosal application of ethanol caused dose-dependent constriction of both arterioles and venules (2% ethanol decreasing diameters by 21 +/- 3 and 15 +/- 2%, respectively). This constriction by ethanol in indomethacin-pretreated rats was significantly inhibited by BW755C, a lipoxygenase inhibitor. Under these conditions, 2% ethanol had no significant effect on either arterioles or venules. In conclusion, ethanol appears to cause release of vasodilating prostaglandins and vasoconstricting leukotrienes that may mediate or modulate the microvascular response to ethanol.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1984

Permeability characteristics of microvascular walls.

Blood to lymph transport of macromolecules has been modeled by assuming a rather numerous population of small pores and a considerably smaller population of large pores across the microvascular walls. Such "black box" studies, however, are inherently incapable of identifying the precise pathways of movement. Electron microscopy has shown a variety of structures which might be identified as the "pores". These include the intercellular junctions; vesicles which may shuttle across the endothelial cells; chains of vesicles forming open pathways; and, in the case of fenestrated capillaries, the fenestrae. With the exception of the shuttling vesicles, these structures have generally been thought to be relatively static, representing a part of the architecture of the normal cell, albeit varying from organ to organ. Arterioles, capillaries and venules have been shown to have differing transport properties. Three possible barriers to transport are now recognized; a fibrous layer on the surface of the endothelial cells; the endothelial cells themselves; and the basement membrane. Three properties of the macromolecule appear to be important in determining its ease of transmural passage; its size; its charge; and its chemical constitution. The simple "shuttling" model of transport by means of vesicles has recently been seriously questioned, and does not appear to be adequate to explain macromolecular transport. More and more evidence is accumulating to indicate that the chemical nature of the macromolecule is of considerable importance in determining whether or not it will transit the microvascular wall. Evidence will be shown that macromolecular transport is largely, if not entirely, a biochemically stimulated set of dynamic events, rather than being explicable on the basis of passive diffusion processes. The current state of our knowledge of these aspects of the problem of macromolecular transport are discussed, and suggestions made as to how to resolve some of the questions still unanswered.

Animals↗
PubMed1982

Use of telescopic imaging in intravital microscopy: a simple solution for conventional microscopes.

Conventional microscopes can be adapted for telescopic imaging by using a projection eyepiece which focuses the image formed by a standard microscope objective at such a large distance that light emanating from points on the object leaves the eyepiece as parallel bundles. A telescopic transfer lens forms the final image in its focal plane independent of the distance between the eyepiece and the transfer lens. In the system reported in this paper, the distance between the eyepiece and transfer lens can be varied from 0 to 280 mm without appreciable vignetting or image degradation for imaging on 35 mm film or smaller formats. This allows great flexibility in the vertical location of the plane of observation while permitting rigid fixation of the recording system-transfer lens combination. By use of a 45 degrees rotatable mirror between the transfer lens and the recording systems, two or more recording systems can be securely mounted and adjusted in advance and rapid selection among them can be made during the course of an experiment.

Microscopy↗