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Biomedical subjects

G C Brown

Publications and source records attributed to G C Brown.

At least 163 records · Page 9Linked to original sources
PubMed1991

Total cell protein concentration as an evolutionary constraint on the metabolic control distribution in cells.

Cell protein occupies 15-35% of cell volume. This level is argued to be the maximum compatible with cell function. Because of this constraint, selection pressure during evolution is likely to have maximized pathway fluxes for minimum total protein level. Pathways optimized in this way are shown to have the following characteristics: (1) the "simple" flux control coefficients of all enzymes are equal, (2) the normal flux control coefficients depend on the relative kinetic constants of the enzymes, such that enzymes with low specific activity are present at relatively high levels and have high flux control, (3) the normal flux control coefficients are proportional to enzyme levels. A single rate limiting step located at the first step in a pathway is likely to be inefficient in terms of protein levels, and the major metabolic pathways are therefore expected to have control distributed throughout the pathway. This has important implications for metabolic control.

Animals↗
PubMed1991

On the nature of the mitochondrial proton leak.

Respiring mitochondria have a significant passive permeability to protons; the mechanism of this proton leak is unknown. Several putative mechanisms were tested. Mitochondrial permeability to small sugars was unaffected by energization, suggesting that there is no significant dielectric breakdown at high membrane potential. Mitochondria are argued to have a proton permeability that is 6 to 8 orders of magnitude higher than the permeability to other cations, suggesting that the proton leak is probably not via a simple pore or membrane defect. 15-30% of the proton leak of freshly prepared mitochondria was extractable with bovine serum albumin and is probably due to fatty acids. Little if any of the proton leak appears to be due to cycling of ions other than protons, or to be associated with the functional activity of the proton pumps. The mitochondrial proton leak shares several properties with the proton permeability of pure phospholipid bilayers, suggesting that they share the same mechanism, although the leak through the bilayer in mitochondria may be modified by the presence of proteins.

Animals↗
PubMed1991

Cytochrome oxidase content of rat brain during development.

The cytochrome oxidase concentration and content of rat brain during development was measured using a simple new assay for cytochrome a. The cytochrome oxidase concentration increased from 1.2 nmol/g wet wt. of brain at birth to about 5.5 nmol/g in the adult, most of the change occurring between 5 and 25 days after birth.

Animals↗
PubMed1991

Prevalence and association of asteroid hyalosis with systemic diseases.

We performed a cross-sectional study of 12,205 patients, which identified 101 patients (0.83%) with asteroid hyalosis. These patients were examined for associated systemic and ocular conditions. Diabetes mellitus was found in 29 of the patients with asteroid hyalosis (29%), as compared to ten of 101 (10%) control subjects (P = .0007). An increased prevalence of systemic arterial hypertension (61 of 101 [60%] patients with asteroid hyalosis compared with 29 of 101 [29%] control subjects; P = .0001) and atherosclerotic vascular disease (30 of 101 [30%] patients with asteroid hyalosis compared with 13 of 101 [13%] control subjects; P = .006) was also discovered in the asteroid hyalosis group. Additionally, patients with asteroid hyalosis were found to be more hyperopic than control subjects (P = .009).

Adult↗
PubMed1991

A prospective study of acute central retinal artery obstruction. The incidence of secondary ocular neovascularization.

We conducted a prospective study to determine the incidence of ocular neo-vascularization following acute central retinal artery obstruction. Only patients initially evaluated within 7 days of visual loss were eligible. Any patient with pre-existing ocular neovascularization or clinical evidence of the ocular ischemic syndrome noted at the initial evaluation was excluded. During the 18-month study, 33 consecutive patients were enrolled. Six patients subsequently developed neovascularization of the iris, an incidence of 18.2%. In these six patients, neovascularization of the iris appeared as early as 12 days to as late as 15 weeks following the artery obstructions. Five of the six patients (15.2% of the total) later developed neovascular glaucoma. Another patient in this series developed neovascularization of the optic disc without neovascularization of the iris, an incidence of 3.0%. Only two of the seven patients with ocular neovascularization had ipsilateral hemodynamically significant carotid artery disease as determined by noninvasive carotid artery testing. This study confirms results of previous retrospective studies that the incidence of ocular neovascularization after central retinal artery obstruction is higher than commonly thought. It also shows that, in the majority of cases, carotid artery disease is not responsible for the neovascularization seen after central retinal artery obstruction.

Acute Disease↗
PubMed1991

Foveal avascular zone diameter and sickle cell disease.

Patients with sickle cell disease can have a distinct retinopathy in which the posterior pole shows abnormalities, including perifoveolar vascular abnormalities. The foveal avascular zone (FAZ) was examined using fluorescein angiography in patients with sickle cell disease and in healthy normal controls. The longest FAZ diameters of 38 patients (51 eyes) with sickle cell disease were compared with those of the 48 patients (60 eyes) in the control group. The average of the longest FAZ diameter in the patients with sickle cell disease was 1.00 mm compared with 0.61 mm for the controls. This difference was statistically significant (P less than .00001). Within the sickle cell group, there were no significant differences in the FAZ diameters with respect to degree of retinopathy, type of sickle hemoglobinopathy, or visual acuity. Thus, an enlarged FAZ diameter in patients with sickle cell disease is confirmed.

Adult↗
PubMed1991

The ocular ischemic syndrome. III. Visual prognosis and the effect of treatment.

The records of fifty-two consecutive patients with the ocular ischemic syndrome seen between 1978 and 1985 were reviewed with the purpose of investigating the visual prognosis and effects of treatment. On initial presentation, 43% of affected eyes had a visual acuity of 20/20-20/50, whereas 37% were counting fingers or worse. By the end of one year, only 24% remained in the 20/20-20/50 group, while 58% were counting fingers or worse. The presence of rubeosis iridis was an indicator of poor visual prognosis. Ninety-seven percent of eyes with rubeosis had vision of counting fingers or worse at the end of one year. We were unable to demonstrate convincingly that carotid endarterectomy and superficial temporal artery to middle cerebral artery bypass were of benefit in stabilizing or improving vision in persons with the ocular ischemic syndrome.

Aged↗
PubMed1991

Behavioral toxicity of anticholinesterases in primates: chronic pyridostigmine and soman interactions.

Dose rates for continuous infusion of pyridostigmine bromide required to inhibit 30% and 60% of normal serum cholinesterase activity in rhesus monkeys were determined. The effects of continuous pyridostigmine infusion at these dose-rates on the behavioral toxicity of 5 daily repeated low-dose exposures to a toxic organophosphate (soman) were determined not be deleterious; in fact, they were slightly (and variably) protective. Relative to controls (5-day soman ED50 = 0.89 micrograms/kg/day), pyridostigmine infusions producing 30% and 60% inhibition produced 5-day ED50s of 1.25 and 1.11 micrograms/kg/day, respectively. Variability in response to the pyridostigmine-soman combinations appeared to be greater than in response to daily soman exposure without pyridostigmine infusion.

Animals↗
PubMed1991

Long-term stability and visual outcome after favorable initial response of proliferative diabetic retinopathy to panretinal photocoagulation.

The authors assessed the relationship between early objective response to panretinal photocoagulation (PRP) and the subsequent long-term visual outcome in 59 eyes of 59 consecutive patients who developed proliferative diabetic retinopathy while under the care of a retinal specialist. Thirty five eyes (59%) had regression of high-risk retinopathy characteristics within 3 months of treatment. Eighteen of these eyes (52%) had a final visual acuity of 20/20 or better with a mean follow-up of more than 4 years. Only 2 of the 24 nonresponder eyes (8%) had visual acuity of 20/20 or better. Thirteen of the responder eyes (37%) sustained a delayed vitreous hemorrhage, which was usually self-limited. Three responders underwent vitrectomy with excellent visual results. The authors conclude that the beneficial effect of PRP on visual outcome is directly related to the regression of retinopathy risk factors and that the long-term visual prognosis in high-risk eyes manifesting a favorable initial response to PRP is excellent.

Adult↗
PubMed1991

Laser photocoagulation for stage 3+ retinopathy of prematurity.

Twenty-two infants with "threshold" stage 3+ retinopathy of prematurity (ROP) were entered into a prospective, randomized clinical trial to compare the efficacy of transscleral cryotherapy versus laser photocoagulation delivered by the indirect ophthalmoscope. Eighteen infants have been followed for at least 3 months. Fifteen of 16 eyes randomized to laser and 9 of 12 eyes randomized to cryotherapy showed regression. The results suggest that laser therapy is as effective as cryotherapy in the treatment of ROP (P = 0.285).

Cryosurgery↗
PubMed1991

Color Doppler imaging provides accurate assessment of orbital blood flow in occlusive carotid artery disease.

Color Doppler imaging was used to evaluate the hemodynamics of the ophthalmic vasculature in a case of complete internal carotid artery occlusion. This procedure, which allows rapid, noninvasive imaging, showed a partial ophthalmic artery obstruction with absent flow in the central retinal artery, central retinal vein, and nasal posterior ciliary arteries. Although altered perfusion of the retinal vessels may be evaluated clinically, assessment of blood flow in the ophthalmic and ciliary arteries previously could be evaluated only indirectly by intravenous fluorescein angiography. The color Doppler imaging findings were confirmed by intravenous fluorescein angiography and carotid arteriography. Color Doppler imaging represents a noninvasive method to diagnose abnormal blood flow of the ophthalmic artery and its branches and to evaluate serial changes of the circulation in a noninvasive manner.

Adult↗
PubMed1991

Inadvertent globe perforation during retrobulbar and peribulbar anesthesia. Patient characteristics, surgical management, and visual outcome.

The authors report a series of 20 eyes from 20 patients in whom inadvertent perforation of the globe occurred during local anesthesia for ocular surgery. Perforation resulted from retrobulbar anesthesia in 18 eyes and from peribulbar anesthesia in 2 eyes. Nine (45%) of 20 eyes had an axial length greater than or equal to 26.00 mm. Combining this figure with axial length data for the general population and estimates for the risk of globe perforation during local anesthesia yields an approximate incidence of perforation in eyes with axial length greater than or equal to 26.00 mm of 1 in 140 injections. Proliferative vitreoretinopathy (PVR) developed in 8 of the 20 eyes (40%) in this series. Overall, 15 (75%) of the 20 eyes were successfully repaired, and, in five eyes (25%), the final visual acuity was 20/70 or better.

Adult↗
PubMed1991

Quantification of concentration changes in neonatal human cerebral oxidized cytochrome oxidase.

The oxygenation of cerebral cytochrome oxidase in vivo was investigated in eight newborn preterm infants. Near-infrared spectroscopy was used to quantify changes in the concentration of oxidized cytochrome oxidase ([CytO2]) observed during alterations in arterial oxygen saturation (SaO2) in the range of 85-99% and of carbon dioxide tension (PaCO2) in the range of 4.3-9.6 kPa. No relation was found between changes in SaO2 and [CytO2]. Alterations in PaCO2 were positively related both to changes in [CytO2] and total cerebral hemoglobin concentration [( Hb]t). The changes in [CytO2] ranged from 0.09 to 0.33 (median 0.21) mumol.l-1.kPa-1. The ratio [CytO2]/[Hb]t ranged from 0.06 to 0.12 (median 0.08). The relation of delta [CytO2] to the change in cerebral blood volume (delta CBV) was calculated: delta [CytO2]/delta CBV ranged from 0.09 to 0.18 (median 0.11) mumol/ml. These results define a fraction of cerebral cytochrome oxidase in the newborn infant that is oxidized after an increase in PaCO2 but demonstrate that a change in SaO2 in the range studied was not sufficient by itself to change [CytO2]. They differ from results of studies in adults; this may reflect significant differences between adult and neonatal brain.

Brain↗
PubMed1991

Retinal tolerance of an implantable light source for use during vitrectomy surgery.

To assess for the possible development of a phototoxic lesion, we exposed five Dutch belted rabbit retinas to constant illumination with an implantable "chandelier" light source at maximal intensity for 1 hour. No clinically apparent lesion developed in any of the experimentally treated eyes by 48 to 72 hours posttreatment. Light and electron microscopic examination failed to reveal any of the characteristic changes of retinal phototoxicity. A control eye treated with a 20-minute exposure to a standard endoiluminator probe at maximal intensity held 2 mm from the retinal surface demonstrated typical light and electron microscopic phototoxic abnormalities, whereas a retina similarly treated with a 5-minute exposure was normal. We have confirmed that a standard endoilluminator probe can create a phototoxic lesion in the experimental setting. Furthermore, no phototoxicity from the sustained retinal exposure to a fixed, implantable light source for a clinically relevant duration could be demonstrated.

Animals↗
PubMed1990

Control of respiration and oxidative phosphorylation in isolated rat liver cells.

NAD(P)H fluorescence, mitochondrial membrane potential and respiration rate were measured and manipulated in isolated liver cells from fed and starved rats in order to characterize control of mitochondrial respiration and phosphorylation. Increased mitochondrial NADH supply stimulated respiration and this accounted for most of the stimulation of respiration by vasopressin and extracellular ATP. From the response of respiration to NADH it was estimated that the control coefficient over respiration of the processes that supply mitochondrial NADH was about 0.15-0.3 in cells from fed rats. Inhibition of the ATP synthase with oligomycin increased the mitochondrial membrane potential and decreased respiration in cells from fed rats, while the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone had the opposite effect. There was a unique relationship between respiration and membrane potential irrespective of the ATP content of the cells indicating that phosphorylation potential controls respiration solely via phosphorylation (rather than by controlling NADH supply). From the response of respiration to the mitochondrial membrane potential (delta psi M) it was estimated that the control coefficients over respiration rate in cells from fed rats were: 0.29 by the processes that generate delta psi M, 0.49 by the process of ATP synthesis, transport and consumption, and 0.22 by the processes that cycle protons across the inner mitochondrial membrane other than via ATP synthesis (e.g. the passive proton leak). Control coefficients over the rate of mitochondrial ATP synthesis were 0.23, 0.84 and -0.07, respectively, by the same processes. The control distribution in cells from starved rats was similar.

Animals↗
PubMed1990

Non-ohmic proton conductance of the mitochondrial inner membrane in hepatocytes.

The mitochondrial membrane potential in isolated hepatocytes was measured using the distribution of the lipophilic cation triphenylmethylphosphonium (TPMP+) with appropriate corrections for plasma membrane potential, cytoplasmic and mitochondrial binding of TPMP+, and other factors. The relationship between mitochondrial membrane potential and respiration rate in hepatocytes was examined as the respiratory chain was titrated with myxothiazol in the presence of oligomycin. This relationship was nonproportional and similar to results with isolated mitochondria respiring on succinate. This shows that there is an increased proton conductance of the mitochondrial inner membrane in situ at high values of membrane potential. From the respiration rate and mitochondrial membrane potential of hepatocytes in the absence of oligomycin, we estimate that the passive proton permeability of the mitochondrial inner membrane accounts for 20-40% of the basal respiration rate of hepatocytes. The relationship between log[TPMP+]tot/[TPMP+]e and respiration rate in thymocytes was also nonproportional suggesting that the phenomenon is not peculiar to hepatocytes. There is less mitochondrial proton leak in hepatocytes from hypothyroid rats. A large proportion of the difference in basal respiration rate between hepatocytes from normal and hypothyroid rats can be accounted for by differences in the proton permeability characteristics of the mitochondrial inner membrane.

Animals↗
PubMed1990

Treatment of foveal pigment epithelial detachments with contiguous extrafoveal choroidal neovascular membranes.

Fourteen eyes of 14 patients who had subfoveal retinal pigment epithelial detachments and extrafoveal contiguous choroidal neovascular membranes associated with age-related macular degeneration underwent laser photo-coagulation treatment directed solely to their choroidal neovascular membrane. In eight of 14 eyes (57%), photocoagulation treatment resulted in closure of the choroidal neovascular membrane with subsequent collapse of the pigment epithelial detachment. Six of the eight eyes also had visual improvement. In six of 14 eyes (43%), the neovascular membrane eventually progressed into the fovea with resultant visual loss. The results of our study suggest that photocoagulation of extrafoveal choroidal neovascular membranes associated with foveal detachments of the retinal pigment epithelium may preserve and even improve visual function in affected patients.

Aged↗