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Biomedical subjects

S R Thomas

Publications and source records attributed to S R Thomas.

At least 109 records · Page 6Linked to original sources

Intracellular pH controls cell membrane Na+ and K+ conductances and transport in frog skin epithelium.

We determined the effects of intracellular respiratory and metabolic acid or alkali loads, at constant or variable external pH, on the apical membrane Na+-specific conductance (ga) and basolateral membrane conductance (gb), principally due to K+, in the short-circuited isolated frog skin epithelium. Conductances were determined from the current-voltage relations of the amiloride-inhibitable cellular current pathway, and intracellular pH (pHi) was measured using double barreled H+-sensitive microelectrodes. The experimental set up permitted simultaneous recording of conductances and pHi from the same epithelial cell. We found that due to the asymmetric permeability properties of apical and basolateral cell membranes to HCO3- and NH+4, the direction of the variations in pHi was dependent on the side of addition of the acid or alkali load. Specifically, changing from control Ringer, gassed in air without HCO3- (pHo = 7.4), to one containing 25 mmol/liter HCO3- that was gassed in 5% CO2 (pHo = 7.4) on the apical side caused a rapid intracellular acidification whereas when this maneuver was performed from the basolateral side of the epithelium a slight intracellular alkalinization was produced. The addition of 15 mmol/liter NH4Cl to control Ringer on the apical side caused an immediate intracellular alkalinization that lasted up to 30 min; subsequent removal of NH4Cl resulted in a reversible fall in pHi, whereas basolateral addition of NH4Cl produced a prolonged intracellular acidosis. Using these maneouvres to change pHi we found that the transepithelial Na+ transport rate (Isc), and ga, and gb were increased by an intracellular alkalinization and decreased by an acid shift in pHi. These variations in Isc, ga, and gb with changing pHi occurred simultaneously, instantaneously, and in parallel even upon small perturbations of pHi (range, 7.1-7.4). Taken together these results indicate that pHi may act as an intrinsic regulator of epithelial ion transport.

Animals↗

D-15 performance with short wavelength absorbing filters in normals.

Short wavelength absorbing filters (SWAF's) have become very popular in the prescription and commercial sunglass markets. Like other chromatic filters SWAF's have the potential to alter color vision. Performance on the Farnsworth Panel D-15 (D-15) test was measured to determine whether any of 4 popular SWAF's, in the form of sunglasses, produced color vision changes in 22 color normal adults. Using standard illuminant C, observers were tested under the following conditions: wearing no filter, a 1.0 log unit neutral density filter (NDF), or one of the following SWAF's: Corning CPF 550; NolR Amber 40%; Blu Blocker; and Vuarnet 4006. In addition, the Vuarnets were tested outdoors in shaded daylight to determine the effects of increased illumination. The NDF served as the control and had no effect on D-15 performance. Compared to it, only the Blu Blockers and Vuarnets affected D-15 cap arrangements for these SWAF's significantly. Blu Blocker error patterns had no predominant axis, whereas the predominant axis of errors in both Vuarnet conditions was tritan. Results of quantitative analysis performed on three factors confirmed these findings and indicated the Blu Blockers and Vuarnet SWAF's caused moderate and moderate-to-severe levels of color confusion, respectively. Increasing the illumination level improved performance with the Vuarnets, but it remained significantly outside the normal range.

Adult↗

Re-186(Sn) HEDP for treatment of multiple metastatic foci in bone: human biodistribution and dosimetric studies.

Investigation of the biodistribution of subtherapeutic amounts of a new, chromatographically purified rhenium-186(tin) hydroxyethylidene diphosphonate radiopharmaceutical have been completed in five patients with metastatic carcinoma to bone. The new agent localizes in metastatic foci in bone in the same manner as do standard technetium-99m diphosphonate bone-scanning agents and appears able to deliver therapeutic radiation doses of thousands of rads (tens of grays) to these metastatic foci while limiting the total red marrow dose to less than 75 rad (0.75 Gy). The simultaneous treatment of multiple metastatic foci in bone appears feasible with this new agent.

Adult↗

The Resource-Based Relative Value Scale. Toward the development of an alternative physician payment system.

This article describes the design and methods of a study currently under way to develop a Resource-Based Relative Value Scale (RBRVS); an alternative basis for establishing the payment rate for the services and procedures (S/Ps) of physicians in medical and surgical specialties. Physician resource inputs to be measured include (1) S/P time, (2) pre-S/P and post-S/P times, (3) intensity, (4) practice costs, including malpractice premiums, and (5) the cost of specialty training. These five factors will be combined to produce an RBRVS denominated in nonmonetary units. In the initial phase of the study, data on time and intensity will be obtained through a national survey of physicians who perform these S/Ps. In the second, consensus phase of the project, the investigators will convene a panel of representatives of the medical profession, third-party payers, consumers, and other interested parties to examine areas of agreement and disagreement as to how an RBRVS should be used for policy purposes. The final results of this study are expected by the summer of 1988.

Costs and Cost Analysis↗

Magnetic resonance imaging of congenital hydrocephalus in the rat.

Magnetic resonance imaging (MRI) is an increasingly available technique in clinical medicine for the noninvasive imaging of soft tissues. The purpose of the present study was to demonstrate the potential utility of MRI in experimental toxicology and teratology studies. The progression of severity of prenatally induced hydrocephalus was observed in rat pups from 1 to 4 weeks of age. Pregnant Sprague-Dawley rats were given 0, 15, 30, or 45 mg/kg ethylenethiourea (ETU), po, on Gestation Day 15. The two higher doses have been reported to induce a high incidence of hydrocephalus, which is mild at birth but becomes extensive by 4 weeks of age. The low dose was a no effect level for hydrocephalus. None of the doses of ETU altered birth weight or litter size. Pups from each dose group were imaged serially, on Postnatal Days (PD) 6, 13, 17, and 27, in order to determine the progression in the severity of hydrocephalus. Littermates were also imaged on each of these days, then killed immediately in order to compare the anatomy of the brain with its MR image. Hydrocephalus was detectable in the images from all animals of the 30 and 45 mg/kg dose groups on PD 6, the earliest observation day. At this time, the lateral ventricles were dilated less than 1 mm. Hydrocephalus became increasingly severe, and by 4 weeks of age all of the 45 mg/kg group and approximately half of the 30 mg/kg group had died. The brains of the surviving 30 mg/kg rats were severely hydrocephalic, with little cortex remaining. In all cases, the MR image corresponded precisely with the brain anatomy observed after termination. We have demonstrated that MRI is a useful technique for noninvasively imaging lesions in experimental animals. A number of other potential uses for MRI in toxicology are presented.

Animals↗

Doppler echocardiographic profiles in obstructive right and left atrial myxomas.

Previous reports have suggested that atrioventricular (AV) flow disturbances accompanying atrial myxomas mimic mitral stenosis. Two patients complaining of orthostatic syncope and positional intolerance had a large right and left atrial myxoma, respectively. Doppler flow records showed abrupt early diastolic flow cessation and normal velocity half-times, unlike AV valve stenosis. Large, obstructing atrial myxomas may behave as ball valves.

Adult↗

Photopic spectral sensitivity of the cat.

1. The psychophysical spectral sensitivity of cats was assessed using a two-choice visual discrimination task by determining increment thresholds and critical flicker frequency on white and chromatic backgrounds. 2. For large increments, on 0.0, 0.3 and 3.0 cd/m2 white backgrounds, the cats were most sensitive to 497 nm indicating that these backgrounds are scotopic. On 30 and 300 cd/m2 white backgrounds, the cats were most sensitive to about 454 and 561 nm indicating that these backgrounds are photopic. Sensitivity to intermediate wave-lengths indicated independent action of 'blue' and 'green' cones. 3. For large increments, thresholds on photopic yellow and magenta backgrounds indicated the additive influence of 'blue' and 'green' cones. 4. Spectral sensitivity functions obtained with a critical flicker frequency criterion of 10 Hz on a 30 cd/m2 white background reflected only the activity of the 'green' cone while at 20 Hz the function reflected an additive contribution of both 'blue' and 'green' cones. 5. For small increments, on a 30 cd/m2 white or 96 cd/m2 orange background, sensitivity reflected only the activity of the 'green' cone. 6. The cat's photopic spectral sensitivity is influenced by the psychophysical test upon which it is based in a manner that is similar to what has been found for other vertebrates. No evidence was found for a 500 nm mechanism active at photopic levels.

Adaptation, Ocular↗

Time-dependent apical membrane K+ and Na+ selectivity in cultured kidney cells.

Intracellular microelectrodes were used to study apical membrane selectivity to Na+ and K+ of cultured toad kidney cells (A6) grown on permeable supports. Membrane selectivity was tested by responses of apical membrane potential to replacement of Na+ by K+ or tetraethylammonium and by addition of amiloride to perfusion solutions. The A6 epithelia fell into two groups: those with K+-selective apical membranes, lack of amiloride sensitivity, and near-zero transepithelial potential (group I); and those with Na+-selective apical membranes and a serosa-positive, amiloride-sensitive transepithelial potential (Vm----s; group II). The transition from group I to group II behavior appeared definitive and time dependent, occurring approximately 10 days after plating onto filters. Transepithelial measurements under sterile conditions showed that overnight incubation with aldosterone (10(-7) M), after development of tight junctions (transepithelial resistance elevated) but before development of significant Vm----s, induced the switch from group I to group II behavior. Apical addition of Ba2+, a known blocker of K+ channels, unexpectedly reduced transepithelial resistance (Rm----s) in group I and group II A6, suggesting that it not only blocked K+ channels (when they are present) but may also open a parallel conductive pathway. In summary, after approximately 10 days in culture, apical membranes of A6 epithelia undergo a switch from K+ to Na+ selectivity, overnight incubation with aldosterone can trigger this change, and finally, Ba2+ may open a paracellular conductive pathway.

Animals↗

Exploration of apical sodium transport mechanisms in an epithelial model by network thermodynamic simulation of the effect of mucosal sodium depletion: I. Comparison of three different apical sodium permeability expressions.

A model based on that of Koefoed-Johnsen & Ussing (1958) and elaborated by Hviid Larsen (1978) and Lew et al. (1979), is designed using network thermodynamic theory and used to simulate experiments performed on epithelia. Three different expressions for the apical sodium permeability are tested for their ability to reproduce the saturation of the short-circuit current with increasing mucosal sodium concentration. Using the parameters from the previous models, the sodium entry step is shown to be the rate limiting step. If the apical sodium permeability is constant, there is no saturation of the short-circuit current with increasing mucosal sodium. The saturation of the short-circuit current is simulated with versions of the model which include a variable apical sodium permeability. The phenomenological expressions used for the variable permeabilities are those proposed by Fuchs et al. (1977) and Civan & Bookman (1982). They describe the so-called feedback effect of the mucosal and intracellular sodium concentrations.

Animals↗

Exploration of apical sodium transport mechanisms in an epithelial model by network thermodynamic simulation of the effect of mucosal sodium depletion: II. An apical sodium channel and amiloride blocking.

This paper is the second part of a modeling study on apical sodium transport mechanisms in tight epithelia. In the first part (this issue) we explored three expressions for the apical membrane sodium permeability (PapNa) and showed that only a PapNa which varies as a function of sodium concentration allows simulation of the well known saturation of the short-circuit current with increasing mucosal sodium concentration. However, the ad hoc expressions used have no mechanistic interpretation. We show here that if, instead of an ad hoc expression, one includes a one-site, two-barrier sodium channel in the apical membrane, the model also simulates this saturation. In addition, the equivalent apical sodium permeability computed from the simulations appears to be very similar to the phenomenological equation used by Fuchs et al. (1977) to fit the decrease of the apical sodium permeability with increasing mucosal sodium. The apical sodium channel simulated here is thus a possible mechanism for the feedback effect of the mucosal and intracellular sodium concentrations on the apical sodium permeability. This channel also allows the simulation of the competitive inhibition of the sodium current by amiloride, and the concomitant inhibition of the apical sodium permeability.

Amiloride↗

Ecdysteroid-regulated heat-shock gene expression during Drosophila melanogaster development.

Peaks in hsp 26, 28, and 83 RNA levels are correlated with peaks in ecdysteroid titers during mid-embryogenesis, pupariation, and mid-pupation, and with a peak in the level of RNA from the 74EF ecdysone puff at pupariation. Inhibition of the ecdysteroid peak at pupariation by temperature shift of the conditionally ecdysteroid-deficient strain ecd-1 was followed by a disappearance of hsp 26 RNA and a decline in hsp 83 RNA level; subsequent addition of exogeneous 20-OH-ecdysone to the temperature-shifted strain resulted in a severalfold increase in hsp 83 RNA level, and a dramatic increase in that of hsp 26. These results are consistent with the induction of the hsp 83, 28, and 26 genes by ecdysteroid at several developmental stages.

Animals↗

The reactor accident at Chernobyl: a nuclear medicine practitioner's perspective.

The radiation incident at Chernobyl, USSR, on April 26, 1986 was first detected in Sweden on April 29, when increased radioactivity was observed at a nuclear facility in that country. Subsequently, higher levels of radioactivity were observed in most of Eastern Europe and then in Western Europe. Increased radioactivity was eventually noted in the United States beginning about May 5. The three-day interval between the incident and its discovery outside the USSR caused great apprehension. This chain of events indicates the very important role for the nuclear medicine physician, the medical physicist and their colleagues. It is likely that this medical specialty area is staffed by personnel who are best qualified to interpret these findings and to determine the necessary course of action both for patients and the general public. The nuclear medicine specialist can provide valuable input in estimating the radiation dose impact resulting from such an incident. This estimate may be accomplished either by combining measured activity levels with the physiological and physical factors involved; or by actual in vivo counting and quantitation of radioactivity in individuals exposed to radionuclides. From the measured activities in air, water and food, and assumed intakes for various age groups, doses can be estimated both for inhalation and ingestion of radionuclides. In vivo measurements of radionuclides can be performed with conventional instrumentation used routinely in nuclear medicine laboratories.

Accidents↗

Correlation of [3H]diazepam binding density with anxiolytic locus in the amygdaloid complex of the rat.

Using [3H]diazepam binding, high concentrations of receptors were found in the frontal cortex and lateral amygdala. Infusions of chlordiazepoxide into the lateral amygdala induced a release of responding measured during the component of a conditioned emotional response task previously associated with an aversive stimulus. The lateral amygdala appears to be an important component of the forebrain circuitry involved in the expression of anxiety and sensitive to benzodiazepine drugs.

Amygdala↗

Pulmonary nodules studied by computed tomography.

The authors analyzed 177 pulmonary nodules using thin-section computed tomography (CT), calculating the representative CT number (RCT#) from a computer printout. None of the 96 malignant nodules had an RCT# greater than 151 H. Of the 81 benign nodules, 14 were shown to be calcified by conventional radiography and had an RCT# ranging from 763 and 1,023 H. Thirty had an RCT# greater than 200 H; this included 24 which showed no calcification on conventional tomograms. The remaining 37 benign nodules had an RCT# less than 200 H; 6 of them were hamartomas, including 2 which were diagnosed as such due to their fat content.

Adenocarcinoma↗

Vitamin D metabolite effects on membrane potential and potassium intracellular activity in rabbit cartilage.

In rabbit cartilage growth plates, the membrane potential, Vm, and potassium intracellular activities, alpha iK, were determined in order to study the effects of long-term (48 h) and short-term (1-2 min) exposures to vitamin D metabolites. Results are as follows: (i) in proliferative cells, Vm was -55.6 +/- 0.2 mV, n = 30, and alpha ik = 50.8 +/- 4.2 mM, n = 22; (ii) in hypertrophic cells, Vm was -35.5 +/- 0.8 mV, n = 88, and alpha iK = 85.1 +/- 5.4 mM, n = 20; (iii) Vm (-44.0 +/- 1.0 mV, n = 33) and alpha iK (114.7 +/- 8.7 mM, n = 14) were increased in metatarsal hypertrophic cells incubated with 10(-10)M of 1,25(OH)2D3 but were unaffected by the presence of 24,25(OH)2D3; (iv) an hyperpolarization of Vm was observed after short-term exposure of the hypertrophic cells to 10(-10)M of 1,25(OH)2D3 (-2.2 +/- 0.2 mV, n = 34) and 24,25(OH)2D3 (-2.2 +/- 0.7 mV, n = 17) but not to 25(OH)D3 (+0.3 +/- 0.8 mV, n = 10).

24,25-Dihydroxyvitamin D 3↗

Amygdaloid complex modulates neurotransmission from the entorhinal cortex to the dentate gyrus of the rat.

In urethane-anesthetized rats, single-pulse stimulation of the lateral nucleus of the amygdaloid complex evoked field responses in the dentate gyrus. These responses were similar in many respects to those evoked by stimulation of the monosynaptic perforant path input to the dentate, except for their longer latency. Paired-pulse tests revealed a potent facilitation of perforant path-evoked dentate responses by preceding stimulation of the lateral amygdaloid nucleus. These observations indicate a strong amygdaloid influence on cortico-hippocampal neurotransmission and provide some support for recent anatomical descriptions suggesting that the lateral nucleus of the amygdaloid complex projects to the dentate via a disynaptic pathway relaying in the entorhinal cortex.

Amygdala↗

Perfluorinated organic liquids and emulsions as biocompatible NMR imaging agents for 19F and dissolved oxygen.

Emulsions of fluorocarbons are finding considerable use in physiology for intravascular oxygen transport. Their wide clinical application as blood substitutes, anti-shock, and anti-ischemic agents seems imminent. Whole body NMR imaging is rapidly gaining clinical application and may one day almost completely supplant X-ray imaging. All of the 19F compounds used in biocompatible fluorocarbon emulsions give 19F signals identical to those in the corresponding neat liquid. In concentrations of 10% w/v they are readily imaged. The paramagnetic oxygen molecule reduces T1 in such a way as to make possible whole body imaging of oxygen. T1 typically decreases from 1-4 to 0.3-0.5 seconds and is an inverse linear function of oxygen tension. Spin-lattice relaxation times versus oxygen tensions from 0 to 600 torr have been obtained for F-decalin, F-tributylamine, and F-44E. The usefulness of these 19F effects in clinical NMR imaging depends upon the sensitivity of the method and the tolerable dose. The 19F signal may find use in monitoring 19F compounds as vapors or gases dissolved in plasma or in perfluorocarbons in neat liquid or particle form.

Animals↗