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Biomedical subjects

C A Wilson

Publications and source records attributed to C A Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Role of thromboxane A2 in the vasoconstrictor response to endothelin-1, angiotensin II and 5-hydroxytryptamine in human placental vessels.

The possibility that the vasoconstrictor agents present in the circulation may mediate their effect on placental blood flow by stimulating local prostanoid production was investigated. Placental cotyledons obtained at term from normal pregnancies were perfused in vitro. The dose-related vasoconstrictor effects of endothelin-1 (ET-1), angiotensin II (A II) and 5-hydroxytryptamine (5 HT) were reduced by graded concentrations of the thromboxane A2 (TXA2) receptor antagonist GR32191 (10(-7)-10(-4)M), aspirin (10(-5)-10(-4)M) and indomethacin (10(-5)M). The effect of the TXA2 receptor agonist U46619 was totally abolished by GR32191 (10(-7)M) but unaffected by the prostanoid synthesis inhibitors, aspirin and indomethacin although they prevented a self-priming effect of U46619. When effluents were collected from perfused placentae, 5-10 min after administration of sub-maximal doses of ET-1 (20 pmol), A II (500 pmol) and 5 HT (15 pmol), there was a significant increase in TXB2, the stable metabolite of TXA2, indicating the vasoconstrictors had induced an increase in local prostanoid production. These findings indicate that the vasoconstrictor effects of ET-1, A II and 5 HT in the placental vascular bed are mediated, at least in part, by vasoconstrictor prostanoids including TXA2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Blood-retinal barrier breakdown following experimental retinal ischemia and reperfusion.

The purpose of this study was to examine the effects of acute ischemia and reperfusion on blood-retinal barrier (BRB) function in the rabbit eye. Hydrostatic pressure (140 mmHg) was used to create total retinal ischemia for intervals of 20, 40, 60, 80 or 100 min in the rabbit eye. The location, size and permeability-surface-area product normalized to the area of retinal leakage (PS') of ischemia-induced BRB lesions were then measured using contrast-enhanced magnetic resonance imaging (MRI) after various intervals of reperfusion. Diffuse outer BRB leakage occurred in most eyes subjected to 80 or 100 min of ischemia. A posterior region of outer BRB sparing was found in eyes that underwent lesser durations of ischemia. On day 1 after retinal ischemia, a linear relationship was found between mean PS' and duration of ischemia for periods of ischemia between 20 and 100 min [slope: 5.65 x 10(-6) to 5.96 x 10(-6) cm min-1 (min ischemia)-1; r2 > or = 0.69]. Lesion size also increased between 20 and 100 min of ischemia. In a longitudinal study, eyes exposed to 60 min of ischemia showed a decrease in PS' and a lesion size over an 8-week period of observation. However, leakage was still present on post-ischemia day 57 in two of three eyes examined. Data obtained in these experiments are expected to prove useful in future studies aimed at understanding how BRB damage relates to neuroretinal damage after ischemia-reperfusion injury.

Animals↗
PubMed1995

Nondestructive measurement of retinal glucose transport and consumption in vivo using NMR spectroscopy.

The cellular events underlying various retinopathies are poorly understood but likely involve perturbation of retinal glucose metabolism. Current methods for assessing this metabolism are destructive, thus limiting longitudinal studies. We hypothesize that following an intravitreous injection, the clearance rate of a glucose analogue will be a nondestructive index of retinal glucose transport and metabolism in vivo. First, radiolabeled glucose analogues were injected into the vitreous. After 40 min, the dominant clearance path was posterior via the retina and was consistent with a facilitated transport mechanism. Next, either [6,6-2H2]glucose or 3-deoxy-3-fluoro-D-glucose was injected into the vitreous of rabbit eyes, and the clearance rate of each analogue was determined over 40 min using, respectively, 2H or 19F NMR. These rates were interpreted as a function of the retinal glucose transport and consumption. From the NMR data, the rate of retinal glucose consumption was approximately 16 times slower than the transport of glucose. These data demonstrate that NMR measurements of glucose analogue clearance rate from the vitreous can provide a nondestructive index of retinal glucose transport and consumption in vivo.

Animals↗
PubMed1995

The dual-function hamster receptor for amphotropic murine leukemia virus (MuLV), 10A1 MuLV, and gibbon ape leukemia virus is a phosphate symporter.

Previously, we showed that the amphotropic receptor homolog in hamster cells functions as a receptor not only for amphotropic murine leukemia viruses and 10A1 murine leukemia virus but also for gibbon ape leukemia virus (C.A. Wilson, K. B. Farrell, and M. V. Eiden, J. Virol. 68:7697-7703, 1994). Here, we demonstrate that this receptor functions as a sodium-dependent Pi transporter and that Na-Pi uptake can be specifically blocked following infection with either amphotropic murine leukemia virus, 10A1 murine leukemia virus, or gibbon ape leukemia virus.

Animals↗
PubMed1995

Occult small bowel adenocarcinoma complicating Crohn's disease: a report of three cases.

Three patients with Crohn's disease are described who were treated by ileal resection for intestinal obstruction. Histological examination of the resected specimen in each case established the diagnosis of adenocarcinoma of the small intestine complicating Crohn's disease. This diagnosis should be considered in patients with longstanding macroscopic Crohn's disease who present with severe or recurrent symptoms. The diagnosis may not be apparent on routine radiological examination or even macroscopically at laparotomy.

Adenocarcinoma↗
PubMed1995

Changes in inhibin-A (alpha-beta A dimer) and total alpha inhibin in the peripheral circulation and ovaries of rats after gonadotrophin-induced follicular development and during the normal oestrous cycle.

Recent modifications to a previously reported two-site IRMA have permitted the measurement of serum/plasma concentrations and ovarian contents of inhibin-A (alpha-beta A dimer) in pregnant mare serum gonadotrophin (PMSG)-treated immature female rats and adult rats throughout the 4-day oestrous cycle. For comparison, total alpha inhibin levels were also measured by alpha subunit-directed inhibin RIA and found to be at least tenfold higher (relative to the same 32 kDa bovine inhibin standard used to calibrate both assays). In immature female rats, serum levels of inhibin-A dimer and total alpha inhibin increased within 3 h of PMSG injection and rose in parallel over the next 48 h to values four- to fivefold higher than pretreatment levels. Ovariectomy led to a rapid and parallel fall in both inhibin-A dimer and total alpha inhibin; initial half-lives (+/- 95% confidence intervals) were 22 +/- 4 and 20 +/- 5 min respectively. In adult rats, marked fluctuations in plasma concentrations and ovarian contents of inhibin-A dimer and total alpha inhibin occurred during the 4-day oestrous cycle, most notably between the morning of pro-oestrus and the morning of oestrus. Plasma levels of inhibin-A dimer and total alpha inhibin peaked on the afternoon of pro-oestrus just before the preovulatory gonadotrophin surge. After ovulation, both inhibin-A dimer and total alpha inhibin fell abruptly (two- to threefold by 0200 h on oestrus; P < 0.001), while FSH showed a secondary rise which peaked at 0700 h on oestrus. Although IRMA- and RIA-derived inhibin values generally followed a similar pattern across the 4-day cycle (plasma: r = 0.52, P < 0.001; ovary: r = 0.41, P < 0.001), a transient rise in plasma and ovarian inhibin-A dimer was detected at 0700 h on oestrus (P < 0.01) which was unaccompanied by a rise in total alpha inhibin. This rise in plasma inhibin-A dimer was probably responsible for terminating the post-ovulatory FSH surge since FSH levels declined steadily over the next 15 h. Overall, plasma inhibin-A dimer and FSH concentrations across the whole cycle were negatively correlated (r = -0.22, P < 0.01) whereas no correlation existed between total alpha inhibin and FSH (r = -0.11, P = 0.12).

Animals↗
PubMed1995

Measurement of blood-retinal barrier breakdown in endotoxin-induced endophthalmitis.

PURPOSE: Endophthalmitis is a severe inflammatory disorder with profound visual consequences. Treatment of this disorder has been limited by the lack of quantitative information regarding retinal responses to severe inflammation. The purpose of this study was to measure the effect of endotoxin-induced endophthalmitis on blood-retinal barrier (BRB) function in vivo using contrast-enhanced magnetic resonance imaging (MRI). METHODS: Endophthalmitis was produced by injecting Escherichia coli endotoxin into the midvitreous of pigmented rabbits. Contrast-enhanced MRI was performed at selected intervals thereafter. In all cases, a clinical grading system was used to assess the severity of inflammation before imaging. In a dose-response experiment, total vitreous protein was measured from vitreous specimens obtained 1 day after endotoxin injection and immediately after the imaging procedure. RESULTS: At 1 day after injection, endotoxin produced a selective breakdown of the inner BRB at all doses evaluated (0.01 microgram to 500 micrograms). Permeability-surface area product normalized to the area of leaky retina (PS') increased from 1.35 +/- 0.78 x 10(-4) cm/minute (mean +/- SEM, n = 4 eyes) at a dose of 0.01 microgram to 8.15 +/- 2.22 x 10(-4) cm/minute n = 4) eyes) at a dose of 10 micrograms. Inner BRB integrity was restored by day 28 after injection. In general, changes in PS', blood-aqueous barrier leakage, mean clinical score, and vitreous protein concentration were found, but the correlation between any two of these parameters was poor. CONCLUSION: Leakage of contrast appears early in the course of endotoxin-induced endophthalmitis and is a self-limited process. In future studies, these quantifiable changes in BRB permeability should prove useful in the assessment of various therapeutic interventions.

Animals↗
PubMed1995

Perfluorinated organic liquid as an intraocular oxygen reservoir for the ischemic retina.

PURPOSE: Liquid perfluorocarbons are used as temporary vitreous substitutes in the surgical management of complicated retinal detachment. The purpose of this study was to determine if physiologic benefits could also be derived from the high oxygen solubility of perfluorochemicals relative to vitreous, especially during retinal ischemia. METHODS: The normal vitreous humor of the rabbit eye was replaced with either perfluorotributylamine (FTBA) or balanced salt solution (BSS). Retinal ischemia was then induced by increasing the intraocular pressure above the peak systolic blood pressure for intervals of 10, 30, or 90 minutes. RESULTS: Over a 10- or 30-minute period of ischemia, during which electroretinographic (ERG) responses were recorded, FTBA-filled eyes and BSS-filled eyes showed decreases in the a- and b-wave amplitudes. However, wave amplitudes were significantly greater in FTBA-filled eyes at most times examined (P < .05). ERG responses were maintained throughout a 30-minute ischemic interval in oxygenated FTBA-filled eyes, but not in oxygenated BSS- or deoxygenated FTBA-filled eyes. When examined 1 day after a 90-minute interval of ischemia, oxygenated FTBA-filled eyes maintained 45% and 57% of the preischemic ERG a- and b-wave amplitudes, respectively, compared to a 5% and 3% retention of wave amplitudes in oxygenated BSS-filled eyes. On light microscopic examination of these eyes, FTBA-exposed retinas showed less ischemic damage than BSS-exposed retinas. CONCLUSIONS: When used as a vitreous substitute, FTBA exerts a neuroprotective effect on the ischemic retina that appears to relate to an increased retinal oxygen supply compared to BSS.

Animals↗
PubMed1994

The cellular receptor for gibbon ape leukemia virus is a novel high affinity sodium-dependent phosphate transporter.

The primate type C retrovirus gibbon ape leukemia virus (GaLV) has been shown to use a widely expressed, multiple membrane-spanning protein of unknown function as its cell surface receptor on human cells (GLVR1) (Johann, S. V., Gibbons, J. J., and O'Hara, B. (1992) J. Virol. 66, 1635-1640; O'Hara, B., Johann, S. V., Klinger, H. P., Blair, D. G., Rubinson, H., Dunni, K.J., Sass, P., Vitek, S. M., and Robins, T. (1990) Cell Growth Diff. 1, 119-127). Here we present evidence that the receptor for GaLV (GLVR1) functions as a sodium-dependent transporter of inorganic phosphate. GLVR1 is shown to have approximately 3-4-fold higher affinity for phosphate than other mammalian phosphate transporters described to date. Productive infection of GLVR1-expressing cells by GaLV, but not other retroviruses, results in the complete blockade of GLVR1-specific uptake of inorganic phosphate. Since productive infection of cells with GaLV is generally not cytotoxic, it is likely that more than one phosphate transporter exists on the cell surface. Our data suggest that GLVR1 represents a sodium-dependent phosphate transporter that differs from other mammalian phosphate transporters in structure, affinity for phosphate, and function.

Amino Acid Sequence↗
PubMed1994

Localization and quantitation of blood-retinal barrier breakdown in experimental proliferative vitreoretinopathy.

OBJECTIVE: To determine the contribution of the breakdown of the blood-retinal barrier (BRB) as measured with magnetic resonance imaging in the development of retinal detachment in an experimental model of proliferative vitreoretinopathy. METHODS: Contrast-enhanced magnetic resonance imaging was used to evaluate BRB breakdown in an intravitreal cell-injection model of proliferative vitreoretinopathy. Intravitreal injection of 2.5 x 10(5) homologous dermal fibroblasts produced specific disruption of the inner, or vascular, BRB. RESULTS: Breakdown of the BRB was greatest in the first 3 days after injection, confirming previous work using fluorescein-based methods. Injection of 1 mg of intravitreal triamcinolone acetonide at the time of cell injection significantly reduced both BRB breakdown and the incidence of eventual traction retinal detachment. Eyes that did develop detachment had significantly greater leakage prior to its development than those that did not, regardless of steroid treatment. CONCLUSIONS: Quantitation and definitive localization of BRB leakage with magnetic resonance imaging provides a better understanding of the relationship between BRB compromise and the development of retinal detachment in this frequently used model.

Animals↗
PubMed1994

Transcorneal oxygenation of the preretinal vitreous.

OBJECTIVE: Transcorneal oxygenation is a promising approach to the treatment of various anterior ocular diseases, but its effect on the vitreous and retina is uncertain. The purpose of this study was to evaluate the ocular conditions necessary to permit transcorneal oxygenation of the preretinal vitreous in the rabbit eye. METHODS: Oxygen at atmospheric pressure was supplied via a goggle to the eye while preretinal oxygen tensions were measured with a minimally invasive technique: fluorine-19 (19F) nuclear magnetic resonance spectroscopy of a small preretinal droplet of perfluorotributylamine. Experiments were performed on lensectomized eyes with intact posterior lens capsules (group 1) or in eyes that had also undergone posterior capsular discission (group 2) and mechanical vitrectomy (group 3). To better understand the results of the oxygenation studies, a water-soluble, freely diffusible contrast agent was applied topically to the cornea, and its penetration into the aqueous and vitreous was studied using T1-weighted magnetic resonance imaging. RESULTS: Preretinal PO2 was significantly increased after 30 minutes of transcorneal oxygenation in group 3 eyes (P = .002). In contrast, no change was observed in the other groups despite 30 minutes (group 1) or 3 hours (group 2) of oxygen exposure. The imaging studies demonstrated that contrast penetration of the vitreous was uniform and rapid in eyes in group 3, consistent with a fluid flow-dominated process. A much slower process of anterior and midvitreous enhancement was observed in groups 1 and 2 that was consistent with contrast diffusion. CONCLUSIONS: Because of bulk fluid movement, transcorneal oxygenation of the retina is feasible in single-compartment (vitrectomized, lensectomized) eyes within a reasonable period (30 minutes). This finding could prove useful in the treatment of retinal diseases in which hypoxia may play a role.

Animals↗
PubMed1994

Effect of vitreous fluidity on the measurement of blood-retinal barrier permeability using contrast-enhanced MRI.

Breakdown of the blood-retinal barrier (BRB), frequently an early clinical sign in retinopathy, can be accurately determined using contrast-enhanced MRI. However, increased vitreous fluidity with age and disease may affect the accuracy of the MRI method. We compared the permeability surface area product per area of leaky retina in eyes with normal vitreous (5.42 +/- 0.48 x 10(-4) cm/min, mean +/- SEM, n = 5) to the contralateral gas-compressed vitrectomized eyes (5.41 +/- 0.54 x 10(-4) cm/min, n = 5). The effect of vitrectomy was not significant (P = 0.325) using a Wilcoxon matched pairs signed rank test on the signed differences of the PS' values.

Animals↗
PubMed1994

Non-invasive measurement of steady-state vitreous lactate concentration.

The cellular events leading to the proliferation of new preretinal blood vessels into the vitreous are unknown. It has been hypothesized that a metabolic trigger, such as increased lactate concentration, induces ambient growth factors to initiate this neovascularization. However, this hypothesis has not been tested in vivo because non-invasive methods for measuring vitreous lactate concentration have not been available. In this study, we identified lactate as the dominant resonance in normal rabbit vitreous using a water-suppressed, localized proton NMR method; negligible spectral contamination from lipid, alanine and threonine was demonstrated. The steady-state vitreous lactate concentration in vivo was 11.3 +/- 4 mM (mean +/- SD, n = 7 eyes) which was not statistically different (p = 0.498) to the enzymatically determined lactate content in vitreous from a parallel group of animals [12.1 +/- 0.6 mM (n = 6 eyes)]. Non-invasive measurement of steady-state vitreous lactate concentration using localized proton NMR represents the necessary first step in understanding the role of lactate in neovascularization.

Animals↗
PubMed1994

Neutrophils plug capillaries in acute experimental retinal ischemia.

Capillary plugging by neutrophils appears to be the mechanism responsible for the no reflow phenomenon following experimental ischemia in many tissues. The purpose of this study was to determine if neutrophils plug capillaries in experimental retinal ischemia. Unilateral retinal ischemia was produced in albino rats by focally exposing three adjacent retinal arterioles to argon blue-green laser light at 100 mW. Total occlusion was achieved in at least two vessels in each eye. The animals were euthanized at 3, 6, 8, or 24 hr following laser treatment. Nonlasered eyes of 17 animals served as controls. Trypsin digests were prepared of the retinal vasculature following formalin fixation. The total number of neutrophils present in the capillaries of each retina was counted using a light microscope and expressed as the number of cells per retina. Other eyes were fixed in glutaraldehyde:paraformaldehyde and the retinal tissue prepared for light and electron microscopy. The mean number of neutrophils in capillaries of retinas subjected to laser treatment was significantly higher than that in untreated control retinas at all time periods studied and increased with time from 3 to 6 hr. Intact as well as degranulated PMNs were present in the capillaries. The presence of large numbers of neutrophils plugging capillaries and their increased number with duration of ischemia supports the hypothesis that they contribute to capillary nonperfusion following acute retinal ischemia.

Acute Disease↗
PubMed1994

Asymmetrical atrophy of the renal medulla: a previously unreported abnormality.

Investigation of the smaller of a pair of unequal kidneys showed a band of atrophy in the inner medulla, sparing the papillary tip, which was viable and contained collecting ducts. The kidney had extensive cortical atrophy with glomerulocystic disease and multiple tiny renal cell neoplasms. These changes were considered secondary to the medullary lesion. Study of 85 other kidneys taken a autopsy and surgery showed 8 other cases with similar band-like atrophy in the medulla to various degrees. All 9 cases had severe vascular disease. This asymmetrical or band-like atrophy of the renal medulla seemed to be fairly common but previously unreported, could be differentiated from renal papillary necrosis, and was most likely due to an episode of severe ischaemia, possibly in kidneys with pre-existing vascular narrowing.

Adult↗
PubMed1994

Interactions between 5-hydroxytryptamine (5-HT) and testosterone in the control of sexual and nonsexual behaviour in male and female rats.

Two 5-hydroxytryptamine2 (5-HT2) agents, ritanserin and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) (both at 0.25 mg/kg IP), were administered to castrated males bearing graded testosterone implants (empty, 2.5-, 5-, and 10-mm length) and to normal and neonatally androgenized ovariectomized females bearing 10-mm testosterone implants. The results indicate that testosterone stimulates male sexual behaviour and appears to have a dose-related anxiolytic effect, but no effect on other nonsexual activities. 5-HT and testosterone had opposite effects on male sexual behavior, with ritanserin (5-HT antagonist) enhancing activity in both sexes and DOI (5-HT agonist) inhibiting behaviour in males, the latter being testosterone-dependent. Independent of testosterone, ritanserin reduced locomotion and exploration and increased anxiety in males, while DOI increased locomotion and exploration in both sexes. Ritanserin had a gender-specific effect on anxiety which was independent of testosterone, since in castrated males it was anxiogenic whether they bore testosterone implants or not, while in females it was anxiolytic whether the female were neonatally androgenized (250 micrograms/pup testosterone proprionate [TP] on day 1) or not. These results show that 5-HT and testosterone have opposite effects on male sexual behaviour and these may be interrelated. In adulthood, their effects on nonsexual activities are not inversely related and are independent of each other in contrast to the relationship seen in the neonatal period.

Amphetamines↗