Biomedical subjects

G O Sperber

Publications and source records attributed to G O Sperber.

At least 19 recordsLinked to original sources

PubMed1990

Aspects of oxygen and glucose consumption in the retina: effects of high intraocular pressure and light.

Studies on retinal oxygen and glucose consumption in cats and pigs are reviewed and recent experiments with the deoxyglucose method in monkeys are described. In all three species, the retina is supplied with nutrients by both the retinal and the choroidal blood vessels. Studies on regional blood flow and differences in arteriovenous concentration in cats have indicated that under conditions of general anesthesia and exposure to laboratory light, the oxygen supply from the choroid is about 5.6 microliters/min and that from the retinal vessels, 1.3 microliters/min. In pigs the corresponding figures were about 4 and 2.9 microliters/min, respectively. Moderate reductions in perfusion pressure caused by increments in intraocular pressure or reductions in arterial blood pressure resulted in little change in oxygen tension in the inner retina, due to efficient autoregulation of retinal blood flow. Reduced choroidal blood flow was to a large extent compensated by increased differences in arteriovenous concentration. Studies using the deoxyglucose method in monkeys indicated that pentobarbital anesthesia and constant illumination tend to reduce the metabolism of the retina. In darkness, glucose consumption in the photoreceptors was higher than that recorded under conditions of constant illumination with white light. Flickering light at 4 Hz enhanced glucose consumption in the inner retina. At very high intraocular pressures glucose consumption in the retina was enhanced, probably as a result of partial ischemia, with a shift to more anaerobic glucose metabolism.

Animals↗

PubMed1990

Computer-assisted quantification and image processing of whole-body autoradiograms.

A computerized image-processing system especially adapted for analysis of whole-body autoradiograms has been developed. It consists of commercially available standard components, including a black-and-white video camera, a microcomputer, and graphics equipment. The lower performance of the hardware has been compensated for by more flexible software. When the system was calibrated, special attention was paid to local variations in the measuring system in different parts of the picture. Utility programs for the manipulation of contrast, pseudocoloring, and image enhancement, etc., are available. Some programs have been especially designed to comply with specific problems and demands related to different autoradiographic applications. A program displaying the density histogram for an area of interest is particularly useful for the quantitation of whole-body autoradiograms. It allows the operator to select interactively a range of densities. Image elements (pixels) corresponding to the densities in this range are shown in red on the monitor, and their average true density is calculated. This procedure permits the marking and analysis of delicate structures on autoradiograms. Other programs allow a picture, stored in memory, to be rotated or translated, and two pictures to be superimposed for comparison. Various applications of using image analyses in whole-body autoradiography are presented and illustrated.

Animals↗

PubMed1990

Control of retinal and choroidal blood flow.

Earlier studies on the control of retinal and choroidal blood flow are reviewed and some recent observations on the effects of light on retinal metabolism and retinal and choroidal blood flow in monkeys (Macaca fascicularis) are reported in preliminary form. The retina is nourished by the retinal blood vessels, where blood flow is autoregulated and the choroidal blood vessels where autoregulation is absent. Studies with the deoxyglucose method of Sokoloff indicate that flickering light tends to increase the metabolism of the inner retina, while constant light reduces the metabolism in the outer retina. Retinal blood flow in flickering light, 8 Hz, is higher than in constant light. The sympathetic nerves of the choroid are probably involved in a protective mechanism, preventing overperfusion in fight and flight situations with acute increments in blood pressure. The facial nerve contains parasympathetic vasodilator fibres to the choroid; the physiological significance of these fibres is unknown. The neuropeptides NPY, VIP and PHI are likely to be involved in autonomic reflexes in the eye.

Animals↗

PubMed1989

A fast method for T1 fitting.

When NMR signal amplitudes achieved from spin-echo sequences with several different repetition times are used to calculate T1, this can be done rapidly by calculating the time coordinate of the center of gravity of the data and determining which T1 should theoretically give this value. In particular, when a large number of similar calculations are made, the time gain may be massive. Simulations suggested that this procedure is only slightly less accurate than least-squares fitting, and far more rapid. The procedure may also be useful in other types of T1 determination.

Humans↗

PubMed1989

An alternative procedure for calculating glucose consumption from 2-deoxyglucose uptake.

In the commonly used model (Sokoloff) for the transport and metabolism of glucose and 2-deoxyglucose in brain tissue a novel choice of constant parameters is proposed. In particular the maximal transport capacity for glucose is assumed proportional to the rate of glucose consumption. The proportionality factor, the "transport factor", may be calculated from the lumped constant and is more likely than the latter to remain constant under varying conditions. Calculations founded on these considerations should yield results similar to the Sokoloff procedure in many situations, but differences appear when the arterial glucose concentration changes. The model is flexible and allows changes.

Animals↗

PubMed1989

The effect of prostaglandin F2 alpha-1-isopropylester (PGF2 alpha-IE) on uveoscleral outflow.

These studies assessed the acute effects of a single dose of prostaglandin F2 alpha-1-isopropylester (PGF2 alpha-IE) on the IOP and AHF, as well as on conventional and uveoscleral outflow, in cynomolgus monkeys. The AHF was determined by a dilution method, using radioactive albumin as a marker. Arterial blood samples were collected and analyzed for radioactivity to determine the flow of aqueous humor to blood, corresponding to the conventional outflow. The uveoscleral outflow was calculated as the difference between the measured AHF and the conventional outflow. Topical application of PGF2 alpha-IE (1 microgram free acid equivalents) to eyes of cynomolgus monkeys caused a small initial increase in IOP followed by a gradual decrease, which was greatest (2.9 +/- 0.6 mmHg below the control eye) at about three hours after the PG application. The mean AHF during 4 hours was slightly higher in the experimental eyes than in the control eyes. The mean uveoscleral outflow during 4 hours was significantly higher in the experimental eyes (0.98 +/- 0.12 microliters.min-1) than in the control eyes (0.61 +/- 0.10 microliters.min-1), while the conventional outflow was significantly lower. The ability of PGF2 alpha-IE to increase the uveoscleral outflow was also demonstrated by autoradiography. These results suggest that PGs exert at least part of their ocular hypotensive effect by increasing the uveoscleral outflow. It remains to be established whether this effect is caused by relaxation of the ciliary muscle or whether other mechanisms, such as structural and metabolic changes, are involved.

Administration, Topical↗

PubMed1987

The microsphere method for measuring low blood flows: theory and computer simulations applied to findings in the rat cochlea.

When the microsphere method of blood flow measurement is used in small organs, the number of spheres actually recovered may be small. This introduces errors which, however, are not necessarily important as compared with the biological variation. A mathematical model was constructed which allowed estimation of the extra uncertainty caused by the low number of spheres. It was applied to an experimental material of over 100 measurements of cochlear blood flow in the rat, where only about 60 spheres were recovered per cochlea. It was concluded that this paucity of spheres introduced only a small to moderate extra error. Simple approximate formulae were derived allowing easy estimation of the uncertainty caused by low number of spheres under different conditions. In general, there appear to be many situations where fewer microspheres than are commonly used would suffice.

Age Factors↗

PubMed1987

Saturable accumulation of retinoic acid in neural and neural crest derived cells in early embryonic development.

Retinoic acid (RA) binds to a cytosolic protein distinguishable from the cellular retinol (R) binding protein. Recent studies, showing an influence by R and RA on genomic expression, suggest an interaction with the cell nucleus mediated by the specific binding proteins in a manner resembling that of steroid hormones. RA can irreversibly stimulate in vitro differentiation of teratocarcinoma cells and support early embryonic development in vitamin A depleted animals. This study demonstrates a saturable, highly specific and regional accumulation of RA in the neuroepithelium and developing CNS that occurs in early but not in late fetal development in the mouse. The results suggest that a binding protein, or some other cellular mechanism for accumulation of RA is expressed in the neural cells only during restricted periods of development. High levels are recorded also in regions where cranial neural crest cells are known to migrate, and later in the visceral arches and maxillary areas, the mesenchyme of which is known to be partly derived from migrating cranial neural crest cells. The specific accumulation of RA in embryonic neural and cranial neural crest cells is in line with animal experiments and human clinical data, showing that retinoids specifically impair CNS, eye, ear, and facial development.

Animals↗

PubMed1986

Improved formulae for signal amplitudes in repeated NMR sequences: applications in NMR imaging.

An improved formalism describing the dependence of the signal strength on relaxation times and spin densities in pulsed nuclear magnetic resonance experiments is presented. It is especially applicable to repetitive experiments such as occur in imaging applications. Essentially, it includes long-time spin coherence effects not considered in the algorithms usually adopted. Also, some generalizations of classical concepts are made. Validity criteria are studied using numerical simulations. The algorithm assumes a relatively inhomogeneous main magnetic field, but the computer simulations indicate that the inhomogeneity normally present in magnetic resonance imagers is sufficient. The simulations also indicate that the field gradient pulses applied in the spatial encoding procedure do not necessarily interfere seriously with the validity of the formulae, but complicate the choice of optimal formula and may in some circumstances prevent the spin system from reaching a steady state.

Algorithms↗

PubMed1986

Effects of vasoactive intestinal polypeptide (VIP) on intraocular pressure, facility of outflow and formation of aqueous humor in the monkey.

Stimulation of the facial nerve causes a non-cholinergic vasodilation in the uvea and a rise in the intraocular pressure in rabbits, cats and monkeys. Vasoactive intestinal polypeptide (VIP) has been suggested as the neurotransmitter mediating these effects. In the present investigation, the effects of VIP on aqueous humor dynamics were studied in cynomolgus monkeys. After intracameral injection of 1 microgram VIP, the outflow facility was higher in the experimental eye than in the control; 0.42 +/- 0.46 compared with 0.33 +/- 0.03 microliter cm H20-1 min-1, difference 0.09 +/- 0.04 microliter cm H2O-1 min-1. Intravenous infusion of VIP, 160 ng min-1, increased aqueous humor flow from 1.12 +/- 0.07 to 1.65 +/- 0.09 microliter min-1. Almost the same effect, a 50% increase in aqueous humor flow, was found after intracameral administration of 90 micrograms VIP. This dose of VIP caused a significant increase in intraocular pressure (IOP) in the experimental eye. The maximal difference in IOP between the experimental eye and the control eye was 7.5 +/- 0.4 cm H2O. A lower dose of VIP, 30 micrograms intracamerally, increased aqueous humor flow by about 20%, but had no consistent effect on IOP. The effect of VIP on aqueous humor flow was not affected by pretreatment with indomethacin. The results suggest that most of the rise in IOP caused by intracameral VIP administration is due to a rise in the pressure in the veins into which the aqueous humor is drained. Enhanced formation of aqueous humor plays a smaller role. The effects of VIP on aqueous humor formation and outflow facility suggest that the facial nerve may be involved in nervous control of aqueous humor dynamics, as VIP is most probably released in the eye by stimulation of the facial nerve.

Animals↗

PubMed1986

Fetal epithelial binding of 1,2-dibromoethane in mice.

Whole-body autoradiography and computer-assisted image analysis were used to study the tissue binding of the volatile carcinogenic pesticide 1,2-dibromo[14C]ethane (DBE) in C57BL mouse fetuses. Autoradiograms obtained from pregnant mice in late gestation (day 16-17), showed a high level of non-volatile metabolites in the epithelia of the fetal upper alimentary tract and respiratory tract. As determined by image analysis, the concentration of non-extractable (presumably covalently bound) metabolites in the oral epithelium was three times higher than in the maternal liver (day 17). The concentrations in the junction region of the forestomach and the mucosa of the nasal cavity were equal to that in the maternal liver, whereas the bronchi contained lower levels of non-extractable metabolites than the maternal liver. Autoradiography of excised fetal tissues incubated with DBE showed that high levels of non-extractable metabolites were present in the epithelia of the oral cavity, oesophagus and forestomach also in vitro. The results indicate that the fetal epithelia can activate DBE to products that bind to the tissue; they also raise the possibility that DBE is a transplacental carcinogen in mice.

Animals↗

PubMed1986

Regional glucose metabolism in the rabbit brain in control and TRH-treated animals.

The local cerebral metabolism in urethane anaesthetized control and TRH-treated rabbits was studied with the [14C]2-deoxyglucose method. In the controls, the glucose use was found to be highest in regions known to have a high blood flow and low in regions with low flow. The glucose consumption was, calculated using the constants found by Kennedy et al. in monkeys, 23.5 +/- 6.0 mumol 100 g-1 min-1 in parietal cortex. The TRH was infused at a dose of 0.06 mg kg-1 min-1 which is known to cause vasodilation in the brain. No marked influence of the peptide on the glucose use was detected. It was concluded that the previously reported cerebral vasodilation caused by TRH is not due to an increase in cerebral metabolism.

Acid-Base Equilibrium↗

PubMed1986

3,3',4,4'-tetrachloro[14C]biphenyl in pregnant mice: enrichment of phenol and methyl sulphone metabolites in late gestational fetuses.

The distribution of radioactivity after injection of 3,3',4,4'-tetrachloro[14C]biphenyl (14C-TCB) in pregnant mice was determined by autoradiography and computer-assisted densitometric analysis. TCB metabolites in fetal tissue were analysed by g.l.c. and g.l.c.-mass spectrometry and compared to the synthesized reference compounds 2-, 5- and 6-methoxy-3,3',4,4'-tetrachlorobiphenyl. The concentration of radioactivity was high in the uterine fluid, and in the fetuses in late gestation. Fetal radioactivity decreased after pretreatment with a high dose of unlabelled TCB. Radioactivity was reversibly bound to fetal tissues. A phenolic metabolite, 3,3',4,4'-tetrachloro-2-biphenylol, and a methylsulphonyl-tetrachlorobiphenyl were found in fetuses in late gestation. No unmetabolized TCB was detected in the fetuses.

Animals↗

PubMed1985

Blood flow and glucose consumption in the optic nerve, retina and brain: effects of high intraocular pressure.

Glucose consumption and regional blood flow were determined using the [14C]-2-deoxyglucose (2-DG) method and microspheres in the optic nerve, the retina and different parts of the brain in monkeys. The relationship between the 2-DG accumulation and blood flow in the optic nerve head region was similar to that in grey matter of the brain under pentobarbital anaesthesia as well as under urethan anaesthesia. Pentobarbital anaesthesia resulted in lower values for blood flow and glucose metabolism in most regions. In the optic nerve the highest values were observed in the distal part; there was a fall in blood flow and metabolism along the nerve. There was a corresponding increase in myelin content. Artificial increments in intraocular pressure resulting in a perfusion pressure (mean arterial pressure minus intraocular pressure) of 40 cm H2O had no appreciable effect on the 2-DG accumulation. At a perfusion pressure of 20 cm H2O 2-DG accumulation in the retina and prelaminar part of the optic nerve was markedly increased indicating partial ischemia resulting in anaerobic glycolysis. At intraocular pressures higher than the systolic arterial blood pressure there was still some accumulation of 2-DG in the intraocular tissues, but no blood flow, which indicates that glucose could diffuse into the eye through the sclera. Behind the lamina cribrosa there was no indication of a reduction in blood flow or a metabolic disturbance. The results indicate that the blood flow and metabolism of the retina and prelaminar part of the optic nerve is disturbed only at very high intraocular pressures, and that even at extreme pressures there is no disturbance behind the lamina cribrosa in acute experiments. The 2-DG method will be useful in further studies on the nutritional status of the optic nerve head since it can detect abnormal glycolysis even in very discrete regions due to its high spatial resolution.

Animals↗

PubMed1984

A method for near-continuous determination of aqueous humor flow; effects of anaesthetics, temperature and indomethacin.

A method is described for near-continuous determination of aqueous humor flow. The anterior chamber is perfused with push-pull coupled syringes at a low rate with a fluid containing labelled albumin. An external circuit is used to determine continuously the anterior chamber concentration of the labelled protein. The dilution data are analysed on-line by a minicomputer which permits rapid calculation of the anterior chamber volume and the rate of flow of aqueous humor. The technique and some experiments of technical interest are reported. Experiments in monkeys with different anaesthetics resulted in flow values of 0.99 +/- 0.02, 1.47 +/- 0.09 and 0.99 +/- 0.04 microliter min-1 for pentobarbital, urethane and ketamine anaesthesia, respectively. By using 125I-labelled albumin in one eye and 131I-labelled albumin in the other, it was possible to determine flow in both eyes. Highly significant correlation coefficients between the two sides were found for the rate of aqueous flow, intraocular pressure and anterior chamber volume. Rapid changes in inflow into the anterior chamber from the posterior chamber were produced by elevating and then lowering the intraocular pressure; the delay inherent in the method was about 6 min. Indomethacin, 3 mg kg-1 body wt., had no effect on aqueous humor flow in eyes cannulated with a minimum of trauma. In eyes with problematic cannulation indomethacin at this dose tended to delay an irritation response. Changes in temperature of the fluid perfused through the anterior chamber had no clear effect on the rate of aqueous flow. Warming the animals about 3-4 degrees C above the normal temperature tended to increase the rate of aqueous flow. Cooling by 3-4 degrees C had no clear effect. Cooling after an initial warming also had no clear effect. The rate of flow of aqueous humor from the anterior chamber to the general circulation was calculated from data for the accumulation of labelled albumin in the general circulation. The difference between the rate of aqueous flow determined from the dilution data and the flow into blood was assumed to represent uveoscleral flow. In 14 animals with an aqueous flow of 1.19 +/- 0.08 microliters min-1 the flow to the general circulation was 0.57 +/- 0.055 and uveoscleral flow 0.61 +/- 0.09 microliters min-1. The procedure and mathematical treatment will be applicable to flow determinations with other large molecules and in other systems.

Anesthetics↗

PubMed1978

The inherent mathematical error factors in the radiological determination of heart volume.

When heart volume is calculated from two X-ray projections, part of the error is due to the fact that the formulas employed are not mathematically exact. This error was calculated for a variety of shapes and positions of the heart. The results indicate that this error may reach about 30% for hearts of fairly ordinary shape. When the standard projections are used, horizontally positioned hearts are particularly liable to give rise to large errors of this kind.

Cardiac Volume↗

PubMed1977

Coacervate-like membrane structures and olfactory transduction.

Current theories concerning the olfactory transduction process are discussed. A hypothesis is formulated, according to which the olfactory receptor membrane contains regions where it has the structure of a lipid-protein coacervate. Such structures may well occur in living cells. Such a membrane would have the ability to change its permeability in response to adorants and a sensitivity comparable to that of the sense of smell. The model also explains the fact that different receptor cells have different sensitivity patterns towards odorants. The model is consistent with the results of experiments that seek to establish the locus of odorant action.

Cell Membrane Permeability↗

PubMedDate not supplied

Relaxation enhancement of the dog liver and spleen by biodegradable superparamagnetic particles in proton magnetic resonance imaging.

Bio-degradable superparamagnetic particles of about 0.5 micron diameter were investigated in 2 dogs as potential intravenous contrast enhancing agents for the reticuloendothelial system. The particles lowered the MRI signal of the liver for all investigated sequences, while the signal of the spleen was lowered only in T2 weighted sequences. No clear effect was seen on signals of fat and muscle. There was a pronounced effect on T2 in both liver and spleen but relatively little effect on T1. Diminishing contrast effect with time indicates that the particles degrade. The particles did not have any adverse effects on the general state of the dogs or on routine liver and kidney function tests.

Animals↗