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Biomedical subjects

T Yeh

Publications and source records attributed to T Yeh.

At least 37 records · Page 2Linked to original sources

Temporal response of ganglion cells of the macaque retina to cone-specific modulation.

The temporal response of cone inputs to macaque retinal ganglion cells were compared with cone-specific sinusoidal modulation used to isolate each cone type. For all cell types of the parvocellular (PC) pathway, temporal responsivity was similar for short (S)-, middle (M)-, and long (L)-wavelength-sensitive cone inputs, apart from small latency differences between inputs to center and surround. The temporal response resembled that expected from receptor physiology. Responses of cells of the magnocellular pathway to M- or L-cone modulation showed more complex properties indicative of postreceptoral processing. Human psychophysical temporal-sensitivity functions were acquired with S-cone modulation under conditions similar to those for the physiological measurements. Ratios of psychophysical to physiological data from S-cone cells (the only cells that respond to this stimulus) yielded an estimate of the central filter acting upon PC-pathway signals. The filter characteristic could be described by a four-stage low-pass filter with corner frequency 3-5 Hz.

Animals↗

Visual responses in the lateral geniculate nucleus of dichromatic and trichromatic marmosets (Callithrix jacchus).

New-world primates such as the marmoset (Callithrix jacchus) show polymorphism for the middle- to long-wavelength sensitive cone pigments. Each X-chromosome carries a gene for only one of three possible pigments. All males are thus dichromats, but some females will be trichromats. We have investigated the responses of cells of the parvocellular (PC) and magnocellular (MC) systems within animals from a single marmoset family. The middle- to long-wavelength pigment of dichromats was identified physiologically. Trichromats could readily be distinguished from dichromats by the presence of a high proportion of red-green opponent PC-cells. The physiological classification of phenotypes was confirmed with genetic analysis. The pattern of inheritance was consistent with current genetic models. In trichromatic females, the properties of cells resembled in detail those of cells from the PC- and MC-pathways of the macaque. In dichromats, cell responses resembled those of trichromats (except for the lack of opponency in PC-cells); PC-cells showed sustained and MC-cells transient responses, with a lower contrast gain for the former type. One difference was that a proportion of PC-cells in dichromats showed strong rod input even at high levels of retinal illuminance. Thus, in trichromatic marmosets the presence of two middle- to long-wave pigments appears to permit the elaboration of all the physiological properties associated with trichromacy.

Animals↗

Early gene changes in myocardial ischemia.

After certain periods of myocardial ischemia and reperfusion, cardiac dysfunction exists in the absence of myonecrosis. In a blood-perfused isolated rat heart model, we have demonstrated early gene changes that are associated with global myocardial "stunning." Early gene changes included elevations in the expression of messenger RNAs for HSP70, c-myc and c-fos. Increased expression of messenger RNAs for protooncogenes is an important observation because of the role of protooncogenes as nuclear transcription factors. From these study findings, it would appear that the stunning state is associated with early gene changes that may signal the induction of a hypertrophic process. Subsequent studies are required to demonstrate the exact events which take place in the course of stunning that directly initiate an alteration in gene expression.

Animals↗

Orotic acid improves left ventricular recovery four days after heterotopic transplantation.

Orotic acid accelerates compensatory myocardial hypertrophy after regional ischemia and improves left ventricular function acutely after global ischemia. In this study, the effect of orotic acid on left ventricular function was investigated 4 days after global ischemia (75 minutes, 21 degrees C) using heterotopically transplanted rabbit hearts (n = 18). Experimental animals received daily 100-mg/kg doses of intraperitoneally administered orotic acid, starting 1 day before transplantation, and showed a threefold increase in the serum level of orotic acid by 4 days. After 1 hour of reperfusion, the developed pressure was equally depressed in both the control and experimental groups; however, 4 days later, the developed pressure in control animals was decreased by 3 +/- 3 mm Hg (versus the developed pressure measured at 1 hour) while the developed pressure in experimental animals was significantly increased by 25 +/- 8 mm Hg. Heterotopically transplanted hearts manifested diminished systolic function (stemming from ischemia and unloading) as well as decreased expression of adult myosin. Because orotic acid has been observed to produce an increase in protein synthesis in other models, we investigated whether this improvement in systolic function resulted from an orotic acid-mediated augmentation (or preservation) or normal adult myosin expression. Both orotic acid-treated and untreated hearts manifested decreased expression of the beta-myosin heavy chain protein and steady-state messenger RNA levels. Because function improved with decreased beta-myosin heavy chain expression, an alternate mechanism underlying orotic acid-mediated improvement in function is implicated. Nevertheless, orotic acid may be a therapeutic agent facilitating long-term recovery from global ischemia.

Animals↗

Intractable bleeding from anorectal varices relieved by inferior mesenteric vein ligation.

Intractable anorectal variceal bleeding is an uncommon manifestation of portal hypertension, distinct from simple hemorrhoids, that is managed with therapies as conservative as bedrest, stool softeners, and correction of coagulopathy and those as invasive as portosystemic shunt. In this case report, instant variceal decompression and cessation of bleeding followed a novel treatment: inferior mesenteric vein ligation.

Anus Diseases↗

The response of macaque ganglion cells and human observers to heterochromatically modulated lights: the effect of stimulus size.

Psychophysical sensitivity of human observers closely resembles responsivity of retinal ganglion cells of the magnocellular (MC-) pathway as a function of the relative phase of heterochromatically modulated lights. The MC-pathway phase effect is absent if the receptive field centre alone is stimulated. Here we confirm this physiological result, and show that the psychophysical phase shift is also abolished with small stimuli. The space constant of the psychophysical effect is consistent with a surround diameter for MC-pathway cells in the fovea of about 50 min arc, about 10 times estimated centre diameter. On changing retinal illuminance, the amplitude of the physiological and psychophysical phase shifts also changed in a parallel manner. These experiments support the hypothesis that the physiological origin of psychophysical phase shifts is in the MC-pathway, and indicate the spatial frequency (c. 2c/deg) below which the psychophysical phase shift should become apparent.

Animals↗

Myocardial stunning: association with altered gene expression.

Regional and global myocardial ischemia and reperfusion have been demonstrated to induce expression of the stress response protein heat shock 70 (HSP70) and of immediate early genes, c-jun, c-fos, and c-myc. Because of the models that have been utilized, it has not been possible to discriminate whether this response is the consequence of ischemia, reperfusion, or abnormal hemodynamic stress superimposed on stunned myocardium. In a nonworking isolated and blood-perfused rat heart model, we evaluated the mRNAs for c-fos, c-myc, and hsp70. The heart was subjected to varying periods of ischemia and reperfusion. Significant increases in hsp70 and c-fos were observed, which increased with longer periods of ischemia. No significant increase in c-myc was measured. In addition, mRNA encoding the Ca2+/glucose responsive stress protein GRP78 was evaluated. No increase in this early response gene was noted despite the use of a model associated with cellular calcium loading. Based on these observations, we suggest that the induction of hsp70 and c-fos is the consequence of ischemia and reperfusion and not dependent upon an early hypertrophy response such as would be observed in afterload mismatching or on calcium loading. Further investigations are necessary to isolate the effects of ischemia from those of reperfusion.

Animals↗

Chromatic discrimination with variation in chromaticity and luminance: data and theory.

Boynton and Kambe developed a model of chromatic discrimination in which thresholds are mediated by two independent mechanisms: the short-wavelength sensitive (S-) cones (S-cone axis), and the middle-wavelength sensitive (M-) and long-wavelength sensitive (L-) cones (M/L-cone axis). In this study, we used a Maxwellian view optical system to investigate fundamental properties of the model as a function of chromaticity and luminance. We confirmed that discriminations along the S-cone axis were dependent on S-cone excitation level. However, changes in chromaticity and changes in mean luminance were not described by a single threshold-vs-radiance (TVR) template. We developed a model to account for the different effects of changing S-cone excitation by varying mean chromaticity and by varying mean luminance. M/L-cone discriminations showed a minimum at the L-cone excitation to white, indicating strong opponency. The thresholds increased with luminance approaching a Weber region and showing parallel functions for differing chromaticities. These data are fit by a model allowing retinal gain controls and spectral opponency.

Adult↗

Colorimetric purity discrimination: data and theory.

Colorimetric purity, measured as the first step from white toward the spectrum has a V-shaped function. Purity discrimination is best near 400 nm, least at 570 nm and intermediate at mid-spectrum and long wavelengths. A much flatter function occurs when colorimetric purity is measured as the first step from the spectrum toward white. In this study, we applied the formulation of chromatic discrimination thresholds measured along the S-cone and M/L-cone axis to account for chromatic discrimination in the equiluminant plane. The modeling results show that the purity step from white has a 1.6 log unit calculated range, similar to the classical data. The purity step from the spectrum is much flatter. The predicted range is dependent on the individual variance in chromatic discrimination thresholds and the luminance level. We then used psychophysical procedures to test the model's predictions. The resulting purity discrimination functions were generally in agreement with the model. Our modeling indicates that discrepant data of colorimetric purity can be explained with the context of discrimination models.

Adult↗

Pigment tests evaluated by a model of chromatic discrimination.

Clinical color-vision tests are evaluated within the framework of a model of chromatic discrimination in terms of cone excitation. The motivation for this study was to derive a method for evaluation of test design, test sensitivity, and observer performance. The discrimination model is based on the assumption that chromatic discrimination is mediated in two independent channels, one for short-wavelength cones and one for long- and middle-wavelength cones. Luminance-dependent templates are derived for each channel, and they describe chromatic-discrimination behavior of the young color-normal observer. The templates incorporate receptor- and opponent-level gain controls. We show how the chromaticities of clinical tests can be calculated in cone-excitation units and how discrimination behavior on the tests can be plotted on the templates. The tests include the Farnsworth-Munsell 100-hue, the Farnsworth Panel D-15, the Farnsworth Panel D-15 desaturated, the American Optical Hardy-Rand-Rittler, the Farnsworth F2 plate, the Standard Pseudoisochromatic Plates, Part II, the Ishihara, and the Minimalist tests. Clinical-test data collected on young color-normal observers at different illumination levels show the validity of the techniques.

Color Perception↗

Coronary artery endothelial cell and smooth muscle dysfunction after global myocardial ischemia.

We hypothesized that coronary artery endothelial cell function and smooth muscle function are modified by global myocardial ischemia and used bradykinin-induced secretion of endothelium-derived relaxing factor as a marker of endothelial cell function. Bradykinin and sodium nitroprusside together determined maximum smooth muscle relaxation. Potassium chloride-induced contraction determined smooth muscle contractility. Endothelium-mediated smooth muscle relaxation expressed as a ratio of total coronary smooth muscle relaxation before and after ischemia quantified endothelial cell function. The effect of global normothermic ischemia on in situ coronary arteries from 7 swine hearts was studied. Coronary arterial rings taken from 0 to 220 minutes of ischemia at 20-minute intervals were studied in vitro. The data revealed unexpected tolerance of endothelium-mediated relaxation to ischemia. Endothelium-derived relaxing factor function was maintained to 160 minutes and smooth muscle function, to 120 minutes of ischemia. Coronary artery dysfunction seen in other studies after less ischemia may be the result of injury introduced during reperfusion, may be the consequence of myocardial injury, or may be due to events operative at the level of small arterioles.

Animals↗

The influence of age and sex on human internal mammary artery size and reactivity.

Internal mammary arteries (IMAs) from women and the elderly have been postulated to be smaller and more reactive than IMAs from men and younger patients and, therefore, not as reliable for coronary artery bypass grafting in the short term. This study tests the physiologic basis for that hypothesis. Trimmed IMA segments were obtained from patients aged 50 to 76 years at coronary artery bypass grafting. Eighteen ring segments from 12 women and 35 ring segments from 17 men were mounted on a strain-gauge apparatus, and internal diameter at a transmural pressure of 100 mm Hg was determined from length-tension curves. Contractions to potassium chloride and a dose-response curve to norepinephrine or serotonin were obtained to simulate physiologic vasospasm. Sodium nitroprusside determined arterial relaxation. Linear regression was used to determine correlation of these parameters with age. Internal mammary arteries from women and men were of equal size. They had equal strength of contraction to potassium chloride and norepinephrine, but female IMAs had greater strength of contraction to serotonin. Female IMAs had weaker contraction to norepinephrine as a percent of maximum contraction to potassium chloride than IMAs from men. Internal mammary arteries from women had equal relaxation to sodium nitroprusside compared with IMAs from men. There was no correlation between age and arterial reactivity to vasoconstrictors, relaxation to sodium nitroprusside, or size. These data suggest that IMAs from women and the elderly are not more susceptible to reduction in flow due to smaller size. Postoperatively, it may be important that women be kept on platelet inhibitors because of their greater absolute contraction to serotonin and men on nitrovasodilators because of their greater relative contraction to norepinephrine.

Age Factors↗

Limiting edema in neonatal cardiopulmonary bypass with narrow-range molecular weight hydroxyethyl starch.

The marked edema observed in neonatal cardiopulmonary bypass is thought to result from pathologic increases in capillary permeability. Pentafraction is a subfraction of hydroxyethyl starch that is thought to be of appropriate size and shape to be retained by leaking capillaries and seal endothelial gaps in capillary basement membranes. To test the hypothesis that pentafraction would reduce edema in neonatal cardiopulmonary bypass, we established a model of edema formation in neonatal bypass in which neonatal piglets underwent 2 hours of normothermic cardiopulmonary bypass with crystalloid prime and no myocardial ischemia. Before initiation of bypass, experimental animals (n = 11) received intravenous pentafraction, 3 gm/kg. Control animals (n = 10) received an equivalent volume of saline. Hemodynamic parameters, animal weight, fluid redistribution, and percent tissue water of individual organs were assessed during and after bypass. Pentafraction treatment resulted in significant differences in (1) lowered percent body weight gain from baseline (11% versus 48%), (2) lowered volume requirement to maintain venous reservoir during cardiopulmonary bypass (148 ml/kg versus 581 ml/kg), (3) less fluid loss from the peritoneum (11 ml/kg versus 115 ml/kg), and (4) lowered percent tissue water of kidney, pancreas, stomach, jejunum, colon, and skeletal muscle (p less than 0.05 by unpaired t test). Pentafraction had no effect on hemodynamic parameters during bypass nor in percent tissue water of heart, lung, liver, spleen, skin, or brain. In summary, pentafraction lessened weight gain and fluid requirements during cardiopulmonary bypass, favorably influencing the percent tissue water of certain organs. If pentafraction functions as proposed, it may have wide applicability not only in cardiopulmonary bypass (or extracorporeal membrane oxygenation) but also in other clinical scenarios with altered capillary permeability.

Animals↗

Polyethylene glycol-conjugated superoxide dismutase attenuates reperfusion injury when administered twenty-four hours before ischemia.

Covalent linkage of polyethylene glycol to superoxide dismutase prolongs the serum half-life of the enzyme and may facilitate intracellular access. We tested the myocardial protective effect of polyethylene glycol superoxide dismutase administered once, 24 hours before ischemia. Because hearts were studied ex vivo in a crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of polyethylene glycol alone, without conjugation to superoxide dismutase (n = 8); (3) PEG-SOD 10,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4) PEG-SOD 30,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG-control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of polyethylene glycol superoxide dismutase significantly reduce reperfusion injury when administered 24 hours before initiation of global ischemia. Moreover, since the perfusate was superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating superoxide dismutase.

Animals↗

Reactivity of gastroepiploic and internal mammary arteries. Relevance to coronary artery bypass grafting.

The gastroepiploic artery is an alternate conduit for coronary artery bypass grafting. To test the hypothesis that its vasoreactive properties are different from those of the internal mammary artery, we obtained gastroepiploic artery segments from human gastrectomy specimens. Trimmed internal mammary artery segments were obtained during coronary artery bypass. Ring segments were mounted on a strain gauge and stretched to optimum resting length (90% of the internal circumference at 100 mm Hg). Potassium chloride, serotonin, and norepinephrine were chosen to simulate physiologic vasospasm induced by depolarization, platelet aggregation, or adrenergic stimulation, respectively. Contractions to potassium and a concentration-response curve to serotonin or norepinephrine were obtained. Sodium nitroprusside was used to assess relaxation. Gastroepiploic artery segments had stronger contractions to the depolarizing agent (potassium chloride), adrenergic stimulation (norepinephrine), and product of platelet aggregation (serotonin). The gastroepiploic and internal mammary arteries showed equal sensitivity, measured by concentration causing half-maximal contraction to norepinephrine and serotonin. There was no difference in relaxation to sodium nitroprusside. These data suggest that prevention of platelet-, adrenergic-, or potassium-induced contraction may be more important when the gastroepiploic artery is used as an alternate conduit for coronary artery bypass, reinforcing consideration of nitrovasodilators and platelet inhibitors in the perioperative interval.

Arteries↗

Inotropic stimulation and oxygen consumption in a canine model of dilated cardiomyopathy.

Inotropic support for the dilated, failing ventricle results in complex hemodynamic changes affecting preload, afterload, contractility, and heart rate, each of which affects myocardial oxygen consumption. Appreciation of a hierarchy of hemodynamic determinants of myocardial oxygen consumption may be helpful to the clinician trying to balance oxygen demands and hemodynamic performance. We tested the hypothesis that epinephrine alters the hierarchy of hemodynamic determinants of myocardial oxygen consumption in a canine model of dilated cardiomyopathy created by rapid ventricular pacing. Dogs (n = 10) were instrumented to record left ventricular pressure and dimension, and a modified right heart bypass preparation was used to control left ventricular workload. Coronary sinus effluent was quantitatively collected and analyzed for oxygen content and used to calculate myocardial oxygen consumption. Epinephrine administration significantly increased myocardial oxygen consumption in the empty, beating heart; however, when the relationships of multiple determinants of left ventricular work and load were compared before and after epinephrine administration, no oxygen wasting effect was observed. Using multivariate linear regression analysis, a hierarchy of hemodynamic determinants of myocardial oxygen consumption was created. In the untreated heart, stroke work and cardiac output were the primary hemodynamic determinants of oxygen consumption; epinephrine significantly altered the determinants such that wall stress became the dominant hemodynamic determinant of myocardial oxygen consumption. Focused manipulation of wall stress in the treated, failing heart may limit the potentially deleterious effects of inotropic stimulation in this setting.

Adenine Nucleotides↗

Triiodothyronine-enhanced left ventricular function after ischemic injury.

Hypothyroidism is associated with profound left ventricular dysfunction. Brain-dead organ donors and patients undergoing cardiopulmonary bypass are chemically hypothyroid with significantly reduced circulating free triiodothyronine (T3). To test the hypothesis that T3 enhances left ventricular function in a hormonally deficient environment, a total of 36 healthy New Zealand White rabbit hearts were studied using a modified Langendorff preparation with Krebs-Henseleit perfusate and intra-ventricular balloon. In 9 normal rabbit hearts a cumulative dose-response curve with logarithmically increasing doses of T3 was obtained. The vehicle solution for T3 dissolution served as control (n = 9). Left ventricular function was assessed from peak developed pressure at baseline and after T3 administration. Triiodothyronine had no effect in normal hearts on peak developed pressure or end-diastolic pressure. In 18 rabbits, the acute effect of T3 administration after ischemia was investigated. Preischemic left ventricular function was measured to serve as baseline, and hearts were subjected to 37 degrees C global ischemia. Triiodothyronine (n = 9) or vehicle (n = 9) was infused during reperfusion, and left ventricular peak developed pressure was measured at 30 and 60 minutes of reperfusion. Recovery of function (expressed as percent return of left ventricular peak developed pressure) was significantly improved within 15 minutes of reperfusion (65.0% +/- 2.1% versus 80.2% +/- 4.1%) and remained significantly improved throughout the reperfusion period (p less than 0.05 by analysis of variance). These data suggest that although T3 possesses no inotropic properties, it significantly improves postischemic left ventricular function. The rapidity of the functional improvement suggests that these effects may be due to plasma membrane-mediated mechanisms.

Animals↗