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Biomedical subjects

R W Gore

Publications and source records attributed to R W Gore.

At least 19 recordsLinked to original sources
PubMed2001

Determinants of cardiac function: simulation of a dynamic cardiac pump for physiology instruction.

A computer model is described that simulates the cardiac cycle of a mammalian heart. The model emphasizes the pressure-volume plot as a teaching tool to explain the behavior of the heart as a pump. It exhibits realistic responses to changes in preload, afterload, contractility, and heart rate while displaying time-dependent changes in pressure and volume in addition to the pressure versus volume plot. It differs from previous models by graphing these parameters on a beat-to-beat basis, allowing visualization of the dynamic adaptation of the pumping heart to various stimuli. A system diagram is also included to further promote student understanding of the physiology of cardiac function. The model is useful for teaching this topic to medical, graduate, or undergraduate students. It may also be used as a self-directed computer laboratory exercise.

Cardiovascular Physiological Phenomena↗
PubMed1997

Use of World Wide Web server and browser software to support a first-year medical physiology course.

We describe the use of a World Wide Web (Web) server to support a team-taught physiology course for first-year medical students. Our objectives were to reduce the number of formal lecture hours and enhance student enthusiasm by using more multimedia materials and creating opportunities for interactive learning. On-line course materials, consisting of administrative documents, lecture notes, animations, digital movies, practice tests, and grade reports, were placed on a departmental computer with an Internet connection. Students used Web browsers to access on-line materials from a variety of computing platforms on campus, at home, and at remote sites. To assess use of the materials and their effectiveness, we analyzed 1) log files from the server, and 2) the results of a written course evaluation completed by all students. Lecture notes and practice tests were the most-used documents. The students' evaluations indicated that computer use in class made the lecture material more interesting, while the on-line documents helped reinforce lecture materials and the textbook. We conclude that the effectiveness of on-line materials depends on several different factors, including 1) the number of instructors that provide materials; 2) the quantity of other materials handed out; 3) the degree to which computer use is demonstrated in class and integrated into lectures; and 4) the ease with which students can access the materials. Finally, we propose that additional implementation of Internet-based resources beyond what we have described would further enhance a physiology course for first-year medical students.

Computer Communication Networks↗
PubMed1995

The mechanics of arteriole-tissue interaction.

Arterioles are embedded in the extensive connective tissue matrix of the interstitium. Mechanical interactions with the interstitium may affect the length-tension characteristics of arterioles, and thus affect their reactivity. However, no studies have adequately characterized the coupling between arterioles and the interstitium or investigated how the interstitium might change the physiological expression of arterioles. Therefore, the goal of this project was to investigate the mechanical interactions between arterioles and the interstitium and then to predict the physiological consequences of these interactions. We measured in situ the mechanical coupling of arterioles to the interstitium, the mechanical properties of the interstitium, and the structure of the interstitium in the hamster cheek pouch. We demonstrated that there are mechanical interactions between arterioles and the interstitium that are mediated both through direct connections and through the movement of extracellular fluid through the connective tissue network. We also found that the elastic modulus of the interstitium increases in the vicinity of the arteriole. Finally, both the mechanical coupling of arterioles to the interstitium and the mechanical properties of the interstitium are explained by the structure of the connective tissue matrix. The arterioles appear to be connected to adjacent fibroblasts and fibrocytes by collagen fibrils. These cells are in turn connected to the fiber matrix of the interstitium. Furthermore, the presence of these cells may explain the mechanical heterogeneity of the interstitium. We propose that the physiological role of the interstitium surrounding arterioles is to protect arterioles from stretching and deformation of the tissue while allowing these vessels to constrict freely.

Animals↗
PubMed1995

Locomotive forces produced by single leukocytes in vivo and in vitro.

We report here the first time-resolved measurements of the forces produced during the migration of single leukocytes in vivo and in vitro. Pulmonary macrophages from hamsters and mice, in vitro, and Nembutal (pentobarbital sodium)-anesthetized hamster neutrophils, in vivo, generated maximum locomotive forces ranging from 1.9 to 10.7 nN or tenths of microdynes. Force production was periodic and correlated with the length of the leading lamellipod but not with generalized cell ruffling. Although the extension of the leading lamella is critical to locomotive force generation, these direct measurements suggest that lamellar extension may not arise from the same contractile processes driving forward motion of the cell mass. Indeed, cell ruffling, lamellar extension, and locomotive force generation may be differentially controlled and have different origins. This technique may be extended to test numerous hypotheses of how these and other nonmuscle cells crawl.

Actins↗
PubMed1995

Alteration of testicular microvascular pressures during venous pressure elevation.

We have addressed the hypothesis that varicocele-related infertility is caused in part by a pressure-induced disturbance of testicular convective transport that upsets the testicular hormonal environment and thus impairs spermatogenesis. The left testis of the hamster [pentobarbital sodium (Nembutal), 70 mg/kg ip] was prepared for microcirculatory observations. Testicular venous pressure was acutely elevated by ligating collateral routes of venous outflow and partially occluding, via a snare, the main venous outflow distal to the pampiniform plexus. Simultaneous direct pressure measurements (servo-null method) were made to monitor venous pressure elevation and quantify resulting pressure and diameter changes in the arterial feed to the testis and in postcapillary venules. The data show that over 90% of the venous pressure elevation (VPE) was transmitted to the postcapillary venules. VPE affected intravascular pressures throughout the testis microvasculature; on average, capsular artery pressure increased by 83% of the VPE, although part of this increase was due to a rise in systemic arterial pressure. Vasoconstriction helped to buffer the pressure rise in the capsular artery, probably at the expense of flow amplitude. Yet the vasoconstriction was ineffective in preventing a rise in exchange vessel pressure. These data suggest that microvascular fluid exchange may be dramatically altered in varicocele, upsetting the hormonal and paracrine environment of the testis, and hence, impairing physiological regulation of gametogenesis.

Animals↗
PubMed1993

Regulation of water balance between blood and lymph in the frog, Rana pipiens.

To determine the relative importance of the lymphatic system and transcapillary reabsorption in maintaining water distribution between blood and lymph in Rana pipiens, the hematocrit (HCT) was measured (12 frogs) when each frog was: 1) under tricaine methanesulfonate (MS222) anesthesia, which inactivates the lymph hearts, 2) conscious at rest (control), and 3) conscious after activity. Arterial pressure (AP), lymph-heart rate (LHR), and plasma and lymph protein concentrations and colloid osmotic pressures (COP) were also measured. The average HCT during control state was 26.0 +/- 5.2% (SD), AP was 21.9 +/- 5.2 mmHg, and LHR was 86 +/- 13 bpm. MS222 increased HCT (42.6 +/- 7.9%), and did not affect AP. Experiments, in which plasma volumes were determined by intra-arterial injection of Evans blue-labeled albumin (EB-BSA) (16 frogs), showed that the increased HCT reflected a reduced plasma volume. Activity did not affect HCT, but increased AP (33.1 +/- 6.4 mmHg, p < 0.01), and LHR (115 +/- 26 bpm, p < 0.01). Thus lymph hearts are largely responsible for maintaining blood volume, and changes in transcapillary filtration rate are rapidly mirrored by changes in lymph heart function. Plasma and lymph COP values after MS222 or activity were not significantly different from control. This observation is consistent with the protein and fluid fluxes resulting from Starling forces if an average reflection coefficient to protein, sigma, of 0.5 is assumed, which is consistent with our EB-BSA data.

Animals↗
PubMed1992

A novel remote-sensing isometric force transducer for micromechanics studies.

We have developed an innovative transducer for measuring force with femtonewton-to-micronewton resolution in biological systems. A magnetic microsphere is attached to the specimen being studied and is positioned between two electromagnets. Video microscopy and edge detection are used to monitor small movements of the microsphere that occur when the specimen generates force. An automatic control system adjusts the current through the electromagnets to keep the microsphere stationary. Measured force is a linear function of this current. This transducer is unique in its combination of sensitivity and isometric properties and its ability to measure force without direct connections to the specimen. That is, the transducer is "remote sensing" and can measure force through intervening membrane or tissue. The transducer is isometric at steady state to the limit at which displacement of the microsphere can be resolved, which can be as low as 19 nm. The completed system is being used to study the mechanics of interstitial connective tissue but may also be used to study molecular generation of force.

Animals↗
PubMed1991

Microvascular pressure distribution in the hamster testis.

Convective transport is a critical element in the regulation of steroidogenesis and spermatogenesis in the testis. Steroid hormones are distributed to their target cells within seminiferous tubules via interstitial fluid. The movement of interstitial fluid and lymph, which transports protein hormones and many of the substrates required for spermatogenesis and steroidogenesis, is driven by capillary filtration. Despite the importance of convective transport in testicular function, however, the mechanisms regulating transvascular exchange in the testis are unknown. As a first step in understanding this process, we measured directly the microvascular hydrostatic pressure distribution in the hamster testis (pentobarbital sodium, 70 mg/kg ip). Using a servo-null transducer, intravascular pressure was measured in all vessel types accessible beneath the surface of the testis of 19 animals. Systemic arterial pressure averaged 89 +/- 2 (SE) mmHg. The most significant observations were that mean capillary pressure was extremely low (10.1 +/- 0.8 mmHg) and remarkably constant (range 8.2-13.3 mmHg), despite a 45 mmHg range in systemic mean arterial pressure among the animals observed. The maintenance of a low hydrostatic pressure in testicular capillaries may serve to sustain fluid filtration at a rate that prevents washout of essential solutes while preserving convective transport. Unfortunately, the anatomical and functional characteristics that determine this unique microvascular environment may also expose the testis to significant pathological risks. For example, the large pre- to postcapillary resistance ratio observed suggests that testicular capillaries must be highly susceptible to increases in venous pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Simultaneous measurement of capillary distensibility and hydraulic conductance.

Capillaries are often assumed to be indistensible. Only recently has the error caused by capillary distensibility in the measurement of hydraulic conductance been considered. An oil-drop method was used to measure simultaneously distensibility and hydraulic conductance (Lp) of mesenteric capillaries of 40 cranially pithed Rana pipiens. All vessels studied were distensible in the range 5-80 mm Hg, with a mean equilibrium time, teq, of 12.4 +/- 0.5 sec (SEM, n = 7). Capillary distensibility decreased with increasing pressure. Mean capillary distensibilities at 10, 30, and 60 mm Hg were 18.9 +/- 4.9 X 10(-4) (mm Hg)-1, 13.5 +/- 1.2 X 10(-4) (mm Hg)-1 (mean +/- SEM, n = 9), and 7.6 +/- 2.7 X 10(-4) (mm Hg)-1 (mean +/- SEM, n = 7), respectively. Mean values of capillary Lp, uncorrected and corrected for distensibility, were 0.0113 +/- 0.0017 microns(sec.mm Hg)-1 and 0.0083 +/- 0.0016 microns(sec.mm Hg)-1 (SEM, n = 8 capillaries), respectively. A paired t test demonstrated that uncorrected and corrected values of Lp were statistically different from one another (P less than 0.005). Both distensibility and Lp varied widely between capillaries indicating the necessity of measuring and correcting for distensibility in each individual capillary when estimating Lp. The finding of a slow component of vessel distensibility demonstrates that previous filtration data taken not only from single vessels, but also from whole organs, should be reinterpreted.

Animals↗
PubMed1989

Length-tension relationship of vascular smooth muscle in single arterioles.

Longitudinal response gradients in the microcirculation may in part be explained in terms of the length-tension relationship of vascular smooth muscle at different points along the vascular tree. To test this hypothesis, four branching orders of arterial vessels (20-80 microns ID) were dissected from the hamster cheek pouch and cannulated with concentric micropipettes. Intraluminal pressure was monitored with a servo-null micropipette, and arteriolar dimensions were measured using a videomicrometer. All arterioles developed spontaneous tone in physiological saline solution. Pressure-diameter curves were recorded for maximally activated vessels and for passive vessels. Maximal active wall tension varied nearly threefold, but maximal active medial wall stress (approximately 4 x 10(6) dyn/cm2) varied only approximately 20% between the different vessel orders. These data support the concept that smooth muscle cells from vessels of different sizes are mechanically similar but do not completely explain the longitudinal response gradients reported in the cheek pouch microcirculation. An analysis of the effect of arteriolar wall buckling suggests that the luminal folds that develop at short vessel radii may broaden the peak of the active stress-length curve and extend the pressure range over which arterioles are most sensitive to physical and chemical stimuli.

Animals↗
PubMed1987

Double-barrel pipette system for microinjection.

A method for constructing double-barrel micropipettes is described. The pipettes are made from theta-tubing, which permits easy beveling of the tips. The two sides of the system operate independently and are suitable for simultaneous microinjection, microperfusion, or servo-null micropressure measurements.

Animals↗
PubMed1986

Vascular anatomy and hydrostatic pressure profile in the hamster cheek pouch.

The purpose of this study was to describe the vascular architecture and blood supply to the hamster cheek pouch and to measure the intravascular pressure distribution in the entire pouch. Previous anatomic descriptions have focused either on the vasculature of the facial region or on the microcirculation of the cheek pouch tip. Micropressures in cheek pouch capillaries, terminal arterioles, and small venules have not previously been measured. Cheek pouches were prepared for examination under an intravital microscope using both everted and noneverted methods. Microvessel diameters were measured through a video system using a video micrometer, and intravascular hydrostatic pressures were measured with a servo null micropressure system. Blood vessels in the face and pouch were traced after injection of Microfil into the external maxillary artery. The results indicate that the pouch is supplied directly or indirectly by six small arteries in the neck and face. Fifty percent of the total pressure drop across the cheek pouch vasculature occurs in the small cheek pouch arteries, suggesting that these vessels are potentially important in controlling cheek pouch blood flow. The measurements of microvascular pressures and diameters in this study help clarify apparent discrepancies in similar measurements from previous studies.

Adenosine↗
PubMed1985

Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum.

In a study of recombinant proteins that might be useful in developing a vaccine against malaria, synthetic peptides from the circumsporozoite (CS) protein of Plasmodium falciparum were found to be immunogenic for mice and rabbits. Antibody to peptides from the repeating region of the CS protein recognized native CS protein and blocked sporozoite invasion of human hepatoma cells in vitro. Antibodies to peptides from regions I and II had no biologic activity, although antibody to region I recognized processed CS protein by Western blot analysis. These data support the feasibility of developing a vaccine against the sporozoite stage of the malaria parasite by using synthetic peptides of the repeating region of the CS protein conjugated to a carrier protein.

Amino Acid Sequence↗
PubMed1985

A new preparation for microcirculatory studies of the hamster cheek pouch.

Existing methods of preparing the hamster cheek pouch for observation under an intravital microscope have several disadvantages. The everted method, described by Duling (Microvasc. Res. 5: 423-429, 1973), appears to restrict blood flow by placing unnatural tension on the retractor muscle and by requiring an incision in the tip of the pouch. The method of Yamaki et al. (Microvasc. Res. 21: 299-301, 1981) requires an incision in the tip of the pouch and complete disconnection of the retractor muscle. The chamber method of Greenblatt et al. (Microvasc. Res. 1: 420-432, 1969) has a limited optical resolution because the tissue cannot easily be transilluminated with properly condensed light. We have devised a less traumatic method of preparing the pouch, which eliminates these disadvantages. The hamster is anesthetized, and a thin, glass support plate is inserted into the left cheek pouch. The plate is constructed and positioned so that it does not restrict flow to any part of the pouch. The free end of the plate is secured to the animal stage. An incision is made in the skin to expose the cheek pouch, and the loose, avascular connective tissue investing the pouch and the retractor muscle is removed. The pouch is positioned at an angle of 20 degrees from the hamster's body in a temperature-controlled chamber over a standard microscope condensor system. Throughout both surgical and experimental procedures, the pouch is superfused with Ringer-bicarbonate solution at 37.5 degrees C. This preparation minimizes surgical trauma and allows the entire vascular supply to the cheek pouch to be studied.

Animals↗
PubMed1985

Capillary pressures in rat intestinal muscle and mucosal villi during venous pressure elevation.

Whole-organ experiments designed to estimate the capillary filtration coefficient require information about the numerical relationship between capillary pressure and venous pressure. Indirect estimates using isogravimetric and isovolumetric methods indicate that 62-85% of a step change in venous pressure reaches the intestinal capillaries, taken as a whole. We have made direct measurements of capillary pressure with a servo-null micropressure system in the microcirculation of both the intestinal muscle and the mucosal villi of rats during local elevation of venous pressure. Consistent regional differences in the relationship between capillary pressure and venous pressure were observed. During increased venous pressure, submucosal arterioles constricted, while muscularis arterioles dilated. The diameter changes of the small arterioles were consistent with blood flow redistribution from mucosa to muscle during venous pressure elevation, but inconsistent with a pure myogenic response. These data raise questions about the exact role for the expression of the myogenic response during venous pressure elevation in the intestine and about previous interpretations of whole-organ experiments concerned with intestinal blood flow and fluid exchange.

Animals↗
PubMed1984

Mechanics of smooth muscle in isolated single microvessels.

In vivo studies on frog mesenteric arterioles (4) indicate that segmental differences in the response of microvessels to physical and chemical stimuli can be explained simply in terms of the length-tension characteristics of vascular smooth muscle at different points along the vascular tree. Studies on single, isolated arterioles in vitro were initiated to examine more closely the validity of this explanation for regional response differences. This paper reports some of the results. First-, second-, and third-order arterioles (18-60 micron i.d.) were dissected from hamster cheek pouches. The vessels were cannulated with a modified Burg microperfusion system, and their mechanical properties studied using the methods described by Duling and Gore. Vessels were activated in four stages with K+ and norepinephrine. During activation, transmural pressures were adjusted to minimize vascular smooth-muscle shortening. Active pressure-diameter curves were recorded while adjusting transmural pressure through the range 5 to 400 cm H20 in 5-25 cm steps. Vessel dimensions were measured with a videomicrometer. Passive curves were obtained after equilibration overnight in Ca2+-free medium. The vessels were then fixed and prepared for histologic sectioning, and measurements of vessel-wall composition were made. The Laplace relationship was used to construct length-tension diagrams, and the histologic data were used to normalize the dimensional data to smooth-muscle lengths. Maximum active tension of second-order arterioles (1,170 dynes/cm) was two times previous values reported by Gore et al. This was due presumably to refinements in techniques and dissection procedures. Maximum active stress averaged 3.9 X 10(+6) dynes/cm2 for second-order arterioles. This number is identical to data obtained from hog carotid strips by Dillon et al.

Animals↗
PubMed1984

Intracellular destruction of Leishmania donovani and Leishmania tropica amastigotes by activated macrophages: dissociation of these microbicidal effector activities in vitro.

Resident peritoneal macrophages were exposed to amastigotes of Leishmania donovani and L. tropica and treated with soluble products of antigen or mitogen-stimulated lymphocytes (lymphokines, LK). Macrophages infected with L. donovani were responsive to lower concentrations of LK for elimination of this parasite than cells infected with L. tropica, and the disappearance of L. donovani amastigotes from activated macrophages preceded that of L. tropica by at least 24 hr. That the differential elimination of amastigotes from LK-treated macrophages may reflect different intracellular killing mechanisms for the two parasites is supported by studies with macrophages activated in vivo; macrophages from BCG-treated C3H/HeJ mice that were incapable of eliminating intracellular L. tropica killed amastigotes of L. donovani. Whether the effector mechanism(s) for intracellular destruction of the two Leishmania are qualitatively or only quantitatively different is as yet unknown.

Animals↗