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Biomedical subjects

R E Taylor

Publications and source records attributed to R E Taylor.

At least 127 records · Page 7Linked to original sources

Distribution and kinetics of membrane dielectric polarization. 1. Long-term inactivation of gating currents.

Gating currents were measured by subtracting the linear component of the capacitative current recorded at very positive or very negative potentials. When the membrane is depolarized for a few minutes, repolarized to the usual holding potential (HP) of --70 mV for 1 ms, and then pulsed to 0 mV, the charge transferred in 2--4 ms is approximately 50% of that which was transferred during the same pulse holding at --70 mV. This charge decrease, called slow inactivation of the gating current, was found to be consistent with a shift of the charge vs. potential (Q-V) curve to more hyperpolarized potentials. When the HP is 0 mV, the total charge available to move is the same as the total charge available when the HP is --70 mV. The time constants of the fast component of the ON gating current are smaller at depolarized holding potentials than at --70 mV. When the HP is --70 mV and a prepulse of 50 ms duration is given to 0 mV, the Q-V curve is also shifted to more hyperpolarized potentials (charge immobilization), but the effect is not as pronounced as the one obtained by holding at 0 mV. When the HP is 0 mV, a prepulse to --70 mV for 50 ms partially shifts back the Q-V curve, indicating that fast inactivation of the gating charge may be recovered in the presence of slow inactivation. A physical model consisting of a gating particle that interacts with a fast inactivating particle, and a slow inactivating particle, reproduces most of the experimental results.

Animals↗

Distribution and kinetics of membrane dielectric polarization. II. Frequency domain studies of gating currents.

We have studied the admittance of the membrane of squid giant axon under voltage clamp in the absence of ionic conductances in the range of 0-12 kHz for membrane potentials (V) between --130 and 70 mV. The admittance was measured at various holding potentials (HP) or 155 ms after pulsing from a given holding potential. Standard P/4 procedure was used to study gating currents in the same axons. We found that the membrane capacity Cm (omega) is voltage as well as frequency dependent. For any given V, the voltage-dependent part of the membrane capacitance has a maximum as the frequency approaches zero and requires at least a two-time constant equivalent circuit to be described. When the holding potential is varied, the voltage-dependent capacitance follows a bell-shaped curve with a maximum change of 0.15 muF/cm2 at about --60 mV. With the pulse method, the maximum is at --40 mV for HP = --70 and it shifts to --70 mV for HP = 0. The shift in the maximum of the voltage-dependent capacitance is consistent with the shift in the charge (Q) vs. V curve observed in our experiments with regular P/4 procedure when the HP is varied. Our data can be explained qualitatively by a four-state model for the sodium channel gating, where a charged particle can move within the field and interact with another particle not affected by the field.

Animals↗

Cirrhosis, variceal bleeding, and distal splenorenal shunt in hemophilia A.

Chronic liver disease has become a significant complication of the therapy of hemophilia disorders. We describe two patients with hemophilia A and hepatitis B virus hepatitis who progressed to cirrhosis with bleeding esophageal varices. Each underwent distal splenorenal shunt under plasma concentrate therapy without difficulty. One patient died 19 months after operation and unsuspected hepatocellular carcinoma was found at autopsy. These cases illustrate the potential severity of liver disease in hemophilia and the ability to safely perform surgery for portal hypertension if required.

Adult↗

Clinical evaluation of the patient with bruising and bleeding.

Abnormal bleeding or bruising is frequently encountered in the clinical practice of dermatology. A working knowledge of mechanisms of normal hemostasis, a complete history (general, bleeding, familial), a thorough physical examination, and an appropriate laboratory evaluation are the integral steps in the diagnostic process. Cutaneous bruising and/or bleeding may be a manifestation of a previously unrecognized hereditary coagulation deficiency such as mild hemophilia or von Willebrand's disease (vWD), hereditary or acquired qualitative or quantitative platelet disorder, disturbance of the vascular or supporting structure, or it may be due to one of several acquired systemic disorders.

Blood Coagulation↗

In vivo enamel fluoride uptake from and caries inhibition by topical fluoride agents.

Acidulated phosphate fluoride (APF), Duraphat or Fluor Protector, was applied to the molar teeth of rats fed a cariogenic diet. The first maxillary molar teeth were subjected to a microbiopsy procedure for fluoride analysis and the mandibular molars scored for caries. All three topical fluoride agents produced a significant increase in the fluoride content of the outermost 5.0 micron of enamel. Only APF produced a significant reduction in caries incidence at all sites.

Acidulated Phosphate Fluoride↗

Arteriosclerosis in severe hemophilia. A postmortem study.

The clinical histories, risk factors, and autopsy findings were reviewed for five deceased hemophiliacs over the age of 40 years to determine the prevalence and severity of arteriosclerosis. The presence of a severe, congenital, hypocoagulative state did not prevent these five men from displaying typical arteriosclerotic vascular disease. One patient actually died of severe, multivessel, coronary artery disease.

Acute Disease↗

Ionic permeabilities of the frog perineurium.

Ionic permeation was investigated across the perineurium of the frog sciatic nerve, under normal conditions and following treatment by hypertonic Ringer, ouabain or amiloride. A cylindrical segment of perineurium removed from the nerve and mounted in vitro on two cannulae was continuously perfused. Permeation rates of 22Na and 42K across the perineurium were the same in either direction and were unaffected by the drugs. The mean 22Na permeability coefficient at the perineurium equaled 1.68 +/- 0.08 (S.E.M.) X 10(-6) cm/sec. Simultaneous measurement of transperineurial fluxes of 22Na, 42K and 36Cl indicated that the K/Na permeability ratio exceeded the ratio of limiting conductances of these ions in free solution, but that the Cl/K permeability ratio did not differ from the respective limiting conductance ratio. Immersion of the perineurial cylinder in Ringer, made hypertonic by addition of NaCl, increased the absolute permeability coefficients of the three ionic tracers but did not affect their permeability ratios. The flux ratio of 22Na/[14C]sucrose, however, was decreased by hypertonic treatment. It is concluded that there is no evidence of active Na or K transport across the perineurium and that the paracellular path in the perineurium exhibits size-dependent permselectivity properties. In addition, the low rates of transperineurial permeation of ions and water-soluble non-electrolytes (e.g. sucrose) are comparable to those in epithelia with tight junctions. These permeability coefficients provide quantitative estimates of the diffusion barrier properties of the perineurium.

Animals↗

Failure of intensive combination therapy (cyclophosphamide, adriamycin, 5-fluorouracil) to control adenocarcinoma or large-cell anaplastic carcinoma of lung.

Eleven patients with advanced adenocarcinoma of lung and six patients with large cell anaplastic carcinoma of lung were treated with combination chemotherapy using cyclophosphamide 1 g/m2 i.v., adriamycin 30 mg/m2 and 5-FU 500 mg/m2 i.v. on days 1 and 8, of a 28 day cycle. In neither group did any patient achieve a complete remission; 1 patient achieved a partial response in each group, and the rest showed no evidence of response. The duration of survival of the responding patients in each group was not significantly longer than those of the non-responders. Toxicity and side effects were considerable in all patients. This study demonstrates that these tumour types are refractory to this form of intensive combination chemotherapy. A literature review suggests that other forms of combination chemotherapy are usually equally ineffective.

Adenocarcinoma↗

Diffusion models for the squid axon Schwann cell layer.

The Schwann cell, basement membrane, and connective tissue layers that surround the squid giant axon and constitute barriers to diffusion, were modeled in a number of ways to analyze various experimental results. The experiments considered are (a) the time-course of the potassium concentration in the space between the Schwann cell and the axon membrane (from now on referred to as the F-H space) after an initial loading, (b) the time-course of sodium concentration in the F-H space after a sudden change in the sodium concentration in the external fluid; (c) the time-course of the concentration of tetrodotoxin (TTX) or saxitoxin (STX) in the F-H space after a sudden change in external concentration, including (or not) the effects of specific binding of TTX or STX to sites on the axon membrane and nonsaturable binding to sites in the F-H space or in the spaces (clefts) between Schwann cells; (d) the effects of the F-H space, clefts, and diffusion into the clefts from the outside (from now on referred to as convergence into the clefts) on the measured series resistance.The analysis shows that (1) in no case is it necessary to include the effects of the convergence into the clefts from the outside; (2) in case a, the basement membrane, connective tissue layers, and the unstirred layer may be neglected, i.e., the clefts are rate limiting; (3) in case b the clefts may be neglected, i.e., the unstirred layer is rate limiting; (4) in most cases the clefts may be replaced by an equivalent thin diffusion barrier.

Animals↗

In vitro fluoride uptake, distribution and retention by human enamel after 1- and 24-hour application of various topical fluoride agents.

The in vitro fluoride acquisition by human enamel after a 1-hour and 24-hour application of APF, Duraphat (a resin varnish) or Fluor Protector (a polyurethane varnish) and subjection to various procedures was determined. Fluoride acquisition was the greatest in teeth treated with Fluor Protector and the least in APF-treated teeth. Fluoride uptake and distribution were increased by prolonging the contact time between the varnishes and enamel, and fluoride retention was decreased after subsequent exposure to synthetic saliva.

Acidulated Phosphate Fluoride↗

Modification of permeability of frog perineurium to [14C]-sucrose by stretch and hypertonicity.

An in vitro method has been developed to determine quantitatively the permeability of the perineurium to radiotracers at room temperature. The permeability to [14C]sucrose of the isolated perineurium of the sciatic nerve of the frog, Rana pipiens, was measured at rest length, when the perineurium was stretched and after the perineurium had been subjected to hypertonic treatment. Mean permeability at rest length was calculated to be 5.6 +/- 0.27 (S.E.M., n = 45) X 10(-7) cm/sec, and both stretch and hypertonic treatment increased the permeability. A 10% stretch increased permeability reversibly, whereas a 20% stretch or immersion of the perineurium in a hypertonic bath increased permeability irreversibly. Altered permeability under these conditions might be related to changes in the ultrastruct of tight junctions in the perineurium.

Animals↗

Simple and rapid high-pressure liquid chromatographic determination of papaverine in plasma.

A rapid and sensitive high-pressure liquid chromatographic (HPLC) assay is described for the quantification of papaverine in plasma. A paired-ion, reversed-phase system was employed with detection at 254 nm. This procedure yielded reproducible results with a sensitivity of 2 ng/ml. Total extraction and quantification time was less than 1 hr. The suitability of this procedure for plasma sample analysis from a bioavailability study was demonstrated.

Biological Availability↗

Temperature effects on gating currents in the squid giant axon.

The effects of temperature (3 degrees-26 degrees C) on the nonlinear components of the displacement current were measured in internally perfused, voltage clamped squid axons. Steps of potential were applied from a holding potential of -70mV (outside ground) to values from -130 to +70mV and either the current or its integral (charge) was recorded as a function of time. For that component of the charge movement not linearly related to voltage, the total charge moved in a few milliseconds (about 1,500 electronic charges/micron2) between saturation limits (e.g. -100mV to +50mV) showed an apparent increase of 13 +/- 5% for a 10 degrees C rise in temperature. Attempts to fit the falling phase of the gating current (or charge) with the sum of two exponentials showed temperature effects on both components but there was considerable scattering. At short times, records for current or charge made at 16 degrees C, expanded by a factor alpha, superimposed on those made at 6 degrees C for alpha about 1.6. For long times alpha was about 2.3.

Axons↗