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Biomedical subjects

C A Wilson

Publications and source records attributed to C A Wilson.

At least 127 records · Page 7Linked to original sources

Blood-retinal barrier breakdown caused by diode vs argon laser endophotocoagulation.

We compared the effects of argon and diode laser endophotocoagulation on blood-retinal barrier breakdown using real-time magnetic resonance imaging following intravenous gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) injection. Endophotocoagulation was performed on eyes of pigmented rabbits with either the argon or the diode laser to produce ophthalmoscopically similar lesions. Magnetic resonance imaging studies were performed either 2 or 7 days after laser treatment, and coronal T1-weighted proton images were obtained in the first 20 minutes following Gd-DTPA injection. The mean signal intensity over a region of interest in the vitreous cavity was analyzed, and an initial rate analysis was performed on each time-course curve. Two days after treatment, argon laser-treated eyes showed significantly greater leakage of Gd-DTPA than diode laser-treated eyes. The leakage in both groups was substantially reduced by posttreatment day 7. Histopathologic examination performed 2 days following photocoagulation showed less damage of the retinal pigment epithelium and more severe occlusion of the choriocapillaris and deep choroidal vessels in diode laser-treated eyes. These changes may serve to explain the observed differences in Gd-DTPA leakage.

Animals↗

Measurement of preretinal oxygen tension in the vitrectomized human eye using fluorine-19 magnetic resonance spectroscopy.

We obtained oxygen measurements from a human eye that contained small preretinal droplets of perfluorotributylamine (FTBA) by using fluorine-19 magnetic resonance spectroscopy. These droplets were the remainder of a larger volume of FTBA that was used as an intraoperative retinal tamponade during retinal detachment repair. The spin-lattice relaxation rate ([T1]-1) of the FTBA fluorine nuclide was obtained that could then be related, by direct proportionality, to droplet PO2. With the patient in a supine position, the droplets could be positioned over the macula in the preretinal vitreous space, whereon the FTBA PO2 could be influenced by the preretinal oxygen concentration. Preretinal PO2 values, derived from magnetic resonance spectroscopy, were in the range of 6 to 9 mm Hg, although multiple components were identified that were suggestive of a heterogeneous distribution of PO2 values in the population of droplets. To our knowledge, this investigation is the first to demonstrate the feasibility of this approach to performing long-term, noninvasive preretinal oxygen measurements in the vitrectomized human eye by using small droplets of a liquid perfluorochemical.

Adult↗

Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due to retinal photocoagulation.

The effect of corticosteroid treatment on blood-retinal barrier breakdown caused by argon-laser panretinal photocoagulation was evaluated in the rabbit eye. One day before photocoagulation, eyes were given either a sub-Tenon (20-mg) or intravitreal (2-mg) injection of triamcinolone acetonide. The severity of blood-retinal barrier breakdown was measured after photocoagulation using rapid sequential magnetic resonance imaging following intravenous administration of gadolinium diethylenetriaminepentaacetic acid. Leakage of gadolinium diethylenetriaminepentaacetic acid into the vitreous space was significantly lower in eyes that received intravitreal triamcinolone acetonide than in control eyes (P = .007); however, sub-Tenon triamcinolone acetonide produced no significant reduction in leakage (P = .65) compared with controls. Fluorescein angiography supported the magnetic resonance imaging findings. We conclude that retinal photocoagulation in the rabbit eye produces blood-retinal barrier breakdown that is partially amenable to corticosteroid treatment.

Animals↗

Oxygen kinetics in preretinal perfluorotributylamine.

Previous studies have relied on various electrodes or probes to monitor preretinal oxygen tension in an effort to gain insight into retinal oxygenation. In order to corroborate and extend the results of such studies, we developed a relatively non-invasive method of determining preretinal oxygen tension using 19F nuclear magnetic resonance (NMR) spectroscopy. Small liquid perfluorocarbon (LPFC) droplets were injected into the preretinal vitreous space of the rabbit eye. The T1 value obtained from the fluorine nuclide could then be used to determine preretinal oxygen tension (PO2) with a high degree of sensitivity, since the fluorine spin-lattice relaxation rate (T1)-1 in LPFCs is directly proportional to PO2 under conditions of no flow and known temperature. In the present study, we investigated the oxygen uptake and clearance rates from small preretinal droplets of the LPFC perfluorotributylamine (FTBA) in response to step changes in arterial PO2. At all FTBA volumes examined (2, 10 and 100 microliters), the oxygen uptake and clearance curves were well approximated by a simple exponential equation with mean time constants 9.8/15.3, 21.4/19.4 and 77.7/45.3 min (uptake/clearance), respectively. Following return to normoxemic (baseline) conditions, FTBA droplets provided a preretinal PO2 of 39.4 +/- 9.2 mmHg (mean +/- S.D., n = 12). The 19F NMR method provides a measure of steady-state preretinal PO2 that independently verifies and complements information obtained using oxygen-sensitive microelectrodes or probes. However, the long time constants for oxygen uptake and clearance, particularly in FTBA volumes on the order of 10 microliters and greater, may represent a practical limitation of this method for determining rapid oxygen flux in the preretinal vitreous space.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Behavioural effects in adulthood of neonatal manipulation of brain serotonin levels in normal and androgenized females.

5HT concentrations in the hypothalamus are higher in females than males over the second week of life and this differentiation is testosterone-dependent. We have investigated the possible influence of 5HT over this period on the development of systems that control adult behaviour, in particular those influenced by neonatal testosterone. Neonatal androgenization (250 micrograms/pup testosterone propionate; TP; on day 1 postpartum) induced a masculine pattern of behaviour in females ovariectomised in adulthood and bearing a TP implant. The neonatal treatment reduced exploration, motor activity and female sexual behaviour and increased anxiety, orientation toward the incentive female and male sexual behaviour. Depletion of 5HT by pCPA (100 mg/kg days 8-16 postpartum) enhanced the TP-induced increment in locomotion and female sexual behaviour and increased sexual orientation toward the incentive female, while 5HTP (20 mg/kg days 8-16 postpartum) antagonised the reduction in exploration by TP. Thus 5HT may normally exert an inhibitory control on the action of neonatal testosterone on exploration, motor activity and sexual behaviour. Neonatal PCPA treatment also had a marked anxiolytic effect which was independent of the presence of T as it was noted in normal and androgenized females and previously has been observed in intact males. This might indicate a primary control by a serotonergic system on the development of the systems controlling anxiety.

5-Hydroxytryptophan↗

The requirements for viral entry differ from those for virally induced syncytium formation in NIH 3T3/DTras cells exposed to Moloney murine leukemia virus.

Moloney murine leukemia virus (Mo-MuLV) has the unique ability to infect different cells via either a low-pH-dependent or a pH-independent entry pathway. Only the pH-independent mechanism of Mo-MuLV entry has been associated with Mo-MuLV-induced syncytium formation. We have now identified a transformed cell line (NIH 3T3/DTras) which efficiently forms syncytia when exposed to Mo-MuLV, yet is low pH dependent for Mo-MuLV entry. Treatment of NIH 3T3/DTras cells with chloroquine, an agent which raises endosomal pH, blocks Mo-MuLV entry, but not Mo-MuLV-induced syncytium formation. This demonstrates that fusion which accompanies viral entry and fusion which is responsible for syncytium formation occur as independent processes in these cells. In addition, we determined that neither inherent differences in the Mo-MuLV receptor nor reduced affinity for Mo-MuLV gp70 can account for resistance of NIH 3T3 cells to Mo-MuLV-induced syncytium formation.

3T3 Cells↗

In vivo effects of interleukin-1 beta on blood leukocytes in BB rats prone or resistant to diabetes.

Previous studies have determined that daily low dose injections of the potent cytokine interleukin-1 beta (IL-1 beta) decreased the frequency of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone (DP) BB rats. In contrast, high dose injections induced an earlier than normal onset. In this study we tested whether the effects of daily human recombinant IL-1 beta injections on leukocyte subsets were associated with its modulation of IDDM onset in BB rats. Prior to the onset of IDDM in DP BB rats, high dose IL-1 beta induced leukocytosis (P less than 0.05), neutrophilia (P less than 0.01), and monocytosis (P less than 0.001). At the onset of IDDM, lymphocyte (P less than 0.01) and neutrophil (P less than 0.001) numbers were increased in high dose treated DP rats but not in rats given saline or low dose IL-1 beta. In 60-day-old diabetes-resistant (DR) BB rats, neurophilia was induced by both low (P less than 0.05) and high (P less than 0.001) dose IL-1 beta without the development of IDDM. At 130 days of age, when the rats were killed, it was discovered that 14/22 (64%) IL-1 beta injected DR rats developed neutralizing IL-1 beta antibodies. Significantly lower neutrophil numbers were observed in high dose DR rats which developed IL-1 beta antibodies compared with those which did not (P = 0.032). Thus, neutrophilia was dissociated from high IL-1 beta acceleration of IDDM onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effectiveness of strategic anthelmintic dosing in controlling Haemonchus contortus infections in sheep in the United Kingdom.

The strategic use of anthelmintics in the control of infections of Haemonchus contortus in ewes and lambs, was investigated in a series of paddock trials. The levels of infection and clinical signs associated with the presence of either benzimidazole-resistant or benzimidazole-susceptible strains of H contortus in lambs were controlled by regular drenching with levamisole or mebendazole, respectively, or by the strategic use of closantel in combination with mebendazole. In the latter case, control was achieved by dosing either the ewes in the early part of the grazing season, or the lambs from June onwards. It was concluded that worm control strategies based on closantel could provide effective control of both benzimidazole-susceptible and benzimidazole-resistant strains of H contortus on farms in the United Kingdom.

Animals↗

Effectiveness of clean grazing strategies in controlling Haemonchus contortus infections in sheep in the United Kingdom.

The effectiveness of clean grazing systems for controlling the sheep abomasal parasite Haemonchus contortus under experimental conditions was monitored for a grazing season in ewes and lambs carrying either benzimidazole-susceptible or resistant populations of the parasite. Both preventive and evasive strategies failed to give effective control of H contortus. Lambs grazing with ewes that had received no anthelmintic showed clinical signs of haemonchosis by early July. Lambs from ewes dosed with a benzimidazole (mebendazole) before turn out, developed clinical signs of haemonchosis later in the season. The presence of anthelmintic resistant genotypes had a significant effect on the appearance of clinical signs, and on the epidemiology and control of disease. It was concluded that alternative worm control strategies will be required for the effective control of H contortus in the United Kingdom.

Abomasum↗

Exudative retinal detachment after photodynamic injury.

Exudative retinal detachments occur in a variety of retinal and choroidal diseases. We created serous retinal detachment in the cat eye by means of photodynamic injury produced by activation of intravascular rose bengal using filtered, focused light (550 nm). Fluorescein angiography later revealed focal retinal and choroidal vascular occlusion surrounded by a larger area of leakage through the pigment epithelium. Serous retinal detachments occurred rapidly, gradually enlarged over the next 3 days, and resolved in all eyes after 14 to 21 days. Histopathologic and ultrastructural features of early lesions included the accumulation of proteinaceous fluid in the subretinal space, pigment epithelial cell damage, and localized occlusion of retinal vessels and the choriocapillaris. Later changes consisted of limited regeneration of the retina and portions of the tapetum. In several respects, these experimental detachments resemble the serous retinal detachments associated with choroidal ischemia in humans, and may serve as a useful model in the study of choroidal microvascular hypoperfusion.

Animals↗

Quantitative determination of the partial oxygen pressure in the vitrectomized rabbit eye in vivo using 19F NMR.

We have quantitatively determined the PO2 within the vitreous space of the vitrectomized rabbit eye in vivo using 19F NMR and perfluorotributylamine (FTBA). The results of the present work are in good agreement with previous measurements of PO2 within the nonvitrectimized rabbit eye obtained using oxygen microelectrodes. In this study, good precision and accuracy were achieved by: (1) having minimal flow effects present, (2) optimizing the signal-to-noise through the use of neat FTBA and surface coil transmission and detection, and (3) performing an inversion-recovery pulse sequence, with adiabatic pulses, to optimize the dynamic range of the T1 experiment. Possible deleterious effects on the measured T1 due to the vitreal temperature gradient are discussed. To the best of our knowledge the results of this study demonstrate, for the first time, a quantitative determination of intraocular PO2 in vivo using 19F NMR and FTBA.

Animals↗

Experimental traction retinal detachment in the cat.

We developed a reproducible model of traction retinal detachment (TRD) in the cat eye by creating a serous retinal detachment and then injecting 2.5 x 10(5) kitten dermal fibroblasts into the vitreous cavity at the site of a retinal wound. Serous detachments were produced by exposing an area of retina to focused light after intravenous injection of rose bengal (a photosensitizing dye). TRD developed rapidly within the first 2 weeks after fibroblast injection, accompanied by the formation of vitreoretinal strands and, to a lesser degree, epiretinal and/or subretinal proliferation. Histopathology demonstrated fibroblasts within the vitreous or along the posterior hyaloid face. Focal deposits of fibroblasts were occasionally found on the inner surface of the retina and/or in the subretinal space. Fibroblast proliferation was confirmed by uptake of radiolabeled thymidine. Deposition of collagen was noted at as early as 3 days after fibroblast injection. Neovascularization was not observed. Control eyes that did not receive fibroblasts showed resolution of serous detachment without retinal traction. In all eyes, retinal degeneration and thinning were seen in the area of previous photodynamic treatment. In this model of TRD, anteroposterior traction (due to vitreous strands) predominates, as is observed in experimental posterior penetrating ocular injury induced by intravitreal blood injection, which also results in vitreous strand formation. Our model, however, enables clinical assessment of TRD in the cat without the media opacification produced by vitreous blood.

Animals↗

Firstborn adolescent daughters and mothers with and without premenstrual syndrome: a comparison.

Firstborn adolescent daughters and their mothers with and without premenstrual syndrome (PMS) were evaluated for two menstrual cycles in order to compare menstrual, postmenstrual (follicular), and premenstrual (luteal) symptomatology. Physical and psychological symptoms were evaluated according to the Premenstrual Assessment Form (PAF) and the Utah PMS Calendar II. The onset of the luteal phase was defined as the day of the midcycle surge of luteinizing hormone (LH), determined by utilizing the CUE Ovulation Predictor. The PAF showed that 1) irrespective of diagnosis, severity of symptoms was not significantly different between adolescents and adults; however, 2) when daughters and mothers were grouped according to mother's diagnosis, the PMS mother/daughter dyads experienced significantly more premenstrual symptoms when compared to the non-PMS mother/daughter dyads. Furthermore, the PMS Calendar revealed menstrual cycle phase delineation. There were no significant differences in severity of symptoms between adults and adolescents during the postmenstrual (follicular) phase and the premenstrual (luteal) phase. However, the adolescents experienced significantly more symptoms during the menstrual phase than the adults. 1) There were no significant differences in severity of adolescents' menstrual symptoms and their premenstrual (luteal) symptoms; 2) the number and severity of luteal phase symptoms were significantly greater for the women with PMS and their daughters than women without PMS and their daughters.

Adolescent↗

Interleukin-1 beta regulation of islet and thyroid autoimmunity in the BB rat.

Daily injections of high dose human recombinant interleukin-1 beta (IL-1 beta) accelerated the onset of both insulin-dependent diabetes mellitus and lymphocytic thyroiditis in genetically prone BB rats. In diabetes-resistant BB rats, high dose IL-1 beta failed to induce diabetes. Additionally, the presence of neutralizing IL-1 beta antibodies in these rats strongly correlated with inhibition of lymphocytic thyroiditis. Since low dose IL-1 beta protects diabetes-prone rats from IDDM, we conclude that IL-1 beta is a potent modulator of autoimmune diabetes and thyroid disease in genetically susceptible rats.

Adrenal Glands↗

Experimental retinal tolerance to emulsified silicone oil.

Vitreous replacement by silicone oil has become increasingly popular in the treatment of severe and complicated retinal detachment. Several studies have suggested that silicone oil may be toxic to the retina or may stimulate periretinal proliferation. To better understand its effects, emulsified or nonemulsified silicone oil was injected into rabbit eyes that had undergone mechanical vitrectomy. Silicone oil was labeled with phthalocyanine blue to aid in histologic localization. Retinal changes were compared by light microscopy at 1, 4, and 12 weeks after intraocular injection. Emulsified silicone oil was found to penetrate the inner retina at 1 week and cause epiretinal membrane formation as early as 4 weeks after injection. Nonemulsified oil produced no histologic changes in the retina. No cytotoxic effects were observed in eyes treated with ether emulsified or nonemulsified silicone oil. It is concluded that emulsified silicone oil can both penetrate the retina and stimulate epiretinal membrane formation in the vitrectomized rabbit eye.

Animals↗

Viral and cellular factors governing hamster cell infection by murine and gibbon ape leukemia viruses.

Hamster cells are resistant to infection by most retroviruses, including Moloney murine leukemia virus (MoMLV) and gibbon ape leukemia viruses (GaLVs). We have constructed MoMLV-GaLV hybrid virions to identify viral and cellular determinants responsible for the inability of GaLV and MoMLV to infect hamster cells. The substitution of MoMLV core components for GaLV core components circumvents the resistance of hamster cells to infection by GaLV, demonstrating that hamster cells have receptors for GaLV but are not efficiently infected by this primate retrovirus because of a postpenetration block. In contrast, hamster cells are apparently resistant to MoMLV infection because although they bear a receptor for MoMLV, the receptor is nonfunctional. Treatment of CHO K1 or BHK 21 hamster cells with the glycosylation inhibitor tunicamycin allows the cells to be infected by MoMLV. The construction of MoMLV-GaLV hybrid virions that can efficiently infect resistant cells has allowed the identification of viral and cellular factors responsible for restricting infection of hamster cells by MoMLV and GaLV.

3T3 Cells↗