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Biomedical subjects

R E Taylor

Publications and source records attributed to R E Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1985

Cisplatin combination chemotherapy for advanced germ-cell testicular tumours.

Thirty-six patients with advanced non-seminomatous germ-cell testicular tumours and two patients with advanced seminomas were treated with cisplatin-containing combination chemotherapy. Thirty-four patients received cisplatin 100 mg/m2 iv, vinblastine 0.3 mg/kg iv and bleomycin 30 mg iv (PVB) and three patients received this combination with etoposide (VP16-213) 120 mg/m2 iv on 3 consecutive days substituted for vinblastine (BEP). One patient received cisplatin and bleomycin only. All 35 evaluable patients with non-seminomatous tumours responded; 22 patients (61%) achieved a complete response (CR); 16 of these (73%) are alive with no evidence of disease at follow-up ranging from 18 to 55 months (median 36). Of 13 patients achieving a partial response (PR), 11 have died of progressive disease at 7 to 30 months (median 11) and two are alive with disease which has continued to regress following chemotherapy. Of 32 patients who received adequate chemotherapy, 16 (50%) are alive and disease-free and three (9%) are alive with evidence of disease. The chances of achieving a CR were reduced in those patients with bulky disease or high levels of AFP or beta hCG at presentation but not in those who had received prior radiotherapy. Toxicity was considerable, including alopecia and nausea or vomiting in all patients, and haematological toxicity, neurotoxicity, hearing loss and dyspnoea in a substantial number of patients.

Adult↗
PubMed1985

Effect of osmolality on aldosterone secretion.

The purpose of these experiments was to determine if the powerful effect of sodium chloride concentration on angiotensin II- and potassium-stimulated aldosterone secretion by isolated perfused adrenal glands is mediated by the sodium or chloride ion or by the obligatory change in osmolality. We used isolated Ringer's bicarbonate perfused canine adrenal gland preparations to determine the effects of a variety of isosmotic, hyperosmotic, and hyposmotic solutions on angiotensin II- and potassium-stimulated aldosterone secretion. When we increased the osmolality of the perfusion medium (8-10 mosmol) by the addition of NaCl, sucrose, mannitol, or glucose, angiotensin II-stimulated aldosterone secretion was inhibited to a similar extent, whereas urea addition had no effect. Similarly, when we increased the osmolality of the perfusion medium (8-10 mosmol) by the addition of NaCl, sucrose, or mannitol, potassium-stimulated aldosterone secretion was also inhibited to a similar extent. In contrast to the increase in angiotensin II- and potassium-stimulated aldosterone secretion observed during hyposmotic reductions in NaCl concentration, (addition of sucrose) did not increase angiotensin II- or potassium-stimulated aldosterone secretion. Even the marked increase in aldosterone secretion caused by large hyposmotic reduction in NaCl concentration did not occur with an equivalent isosmotic reduction in NaCl concentration. These results clearly demonstrate that changes in NaCl concentration affect aldosterone secretion by a mechanism sensitive to the osmolality. Moreover, since hyperosmolality caused by urea addition had no effect on angiotensin II-stimulated aldosterone secretion, changes in intracellular volume or composition appear to be an important modulator of aldosterone secretion.

Adrenal Glands↗
PubMed1985

Clinical pharmacokinetics: a simplified approach, Part 1.

Clinicians often find that the application of pharmacokinetic principles for the calculation of a drug regimen is bewildering and difficult. In this article it is shown that clinically useful calculations can be simply done at the bedside using a handheld calculator. The only requirement is an understanding of the terms that define the pharmacokinetic behavior of a drug. Appropriate manipulation of these terms will allow calculation of loading and maintenance doses, peak and average plasma concentrations, and other useful pharmacological data. The result will be improvement in drug therapy.

Adult↗
PubMed1984

Evidence for an extracellular plasmin-dependent proteolytic system in mineralizing matrices.

Plasminogen activator, which specifically catalyzes the extracellular conversion of plasminogen to plasmin, was identified in the cell-free mineralizing matrices of enamel, dentin, cementum, and bone by a fibrinolytic overlay technique. The spatial separation in developing teeth of successive stages of dentinogenesis allowed us to identify predentin as a major site of plasminogen activator activity. In addition, plasminogen, the natural substrate for the activator, was demonstrated in predentin by immunohistochemical techniques. Extraction of human dentin/predentin with neutral demineralizing buffers solubilized the activator along with inhibitory components capable of blocking the activation of plasminogen. When resolved by polyacrylamide electrophoresis under dissociative conditions, however, the activator emerged in active form as two closely spaced bands at Mr 66,000 and 62,000. In the mineralizing enamel matrix of continuously forming rodent incisors, activator activity was limited to a 3-5 mm wide segment which marks the transition between "soft" and "chalky" enamel, whereas the entire overlying enamel organ was rich in activator activity at all developmental stages. This suggests that the activator is transported to the enamel matrix only in a narrow zone which coincides with the most rapidly mineralizing site. The coincident expression of plasminogen activator activity and mineral accretion suggests that plasmin-dependent proteolysis may play a role in the extracellular regulation of matrix mineralization.

Animals↗
PubMed1984

AC impedance of the perineurium of the frog sciatic nerve.

The AC impedance of the isolated perineurium of the frog sciatic nerve was examined at frequencies from 2 Hz to 100 kHz. A Nyquist plot of the imaginary and real components of the impedance demonstrated more than 1 capacitative element, and a DC resistance of 478 +/- 34 (SEM, n = 27) omega cm2. Transperineurial potential in the absence of externally applied current was 0.0 +/- 0.5 mV. The impedance data were fitted by nonlinear least squares to an equation representing the generalized impedance of four equivalent circuits each with two resistive and two capacitative elements. Only two of these circuits were consistent with perineurial morphology, however. In both, the perineurial cells were represented by a resistive and capacitative element in parallel, where capacitance was less than 0.1 microF/cm2. The extracellular matrix and intercellular junctions of the perineurium were represented as single resistive and capacitative elements in parallel or in series, where capacitance exceeded 2 microF/cm2. Immersion of the perineurium in low conductance Ringer's solution increased DC resistive elements as compared with their values in isotonic Ringer's solution, whereas treatment for 10 min with a hypertonic Ringer's solution (containing an additional 1.0 or 2.0 mol NaCl/liter of solution) reduced DC resistive elements, consistent with changes in perineurial permeability. The results indicate that (a) perineurial impedance contains two time constants and can be analyzed in terms of contributions from cellular and extracellular elements, and (b) transperineurial DC resistance, which is intermediate between DC resistance for leaky and nonleaky epithelia, represents intercellular resistance and can be experimentally modified by hypertonicity.

Animals↗
PubMed1984

Effect of sodium concentration on aldosterone secretion by isolated perfused canine adrenal glands.

Small changes in sodium concentration [( Na]) are not generally considered to have a major direct effect on aldosterone secretion. However, a marked disruption in the renin-aldosterone relationship has been observed in a variety of hypernatremic and hyponatremic states. Therefore, we evaluated the hypothesis that small changes in [Na] have a potent direct effect on angiotensin II- and potassium-stimulated aldosterone secretion. The left adrenal gland, abdominal aorta, and surrounding periadrenal tissue were surgically isolated from mongrel dogs and perfused with Ringers bicarbonate solution at a pressure of approximately 57 mm Hg. Infusion of a KCl test solution at the beginning and end of most experiments produced similar increases in aldosterone secretion, thus documenting the stability of these preparations. After a stable response was established to either a low dose of angiotensin II or a small increase in perfusate [K], the [Na] was changed by adding or removing NaCl. Changing perfusate [Na] from 152 to 139 mM during the infusion of either angiotensin II or potassium caused 20- to 25-fold increases in aldosterone secretion. Increasing perfusate [Na] from 145 to 152 mM inhibited aldosterone secretion to a greater extent during stimulation by lower doses (40-50 pg/ml) than by higher doses (80-100 pg/ml) of angiotensin II. These data demonstrate that during moderate stimulation by angiotensin II or potassium, small changes in [Na] have a powerful inverse effect on aldosterone secretion by a direct action on the canine adrenal gland.

Adrenal Glands↗
PubMed1983

Production of three plasminogen activators and an inhibitor in keratinocyte cultures.

Keratinocyte function in extracellular proteolysis was investigated. Keratinocytes derived from rat tongue ventral epithelium were maintained and serially propagated under conditions which support continuous expansion of epithelial colonies but are restrictive to fibroblast proliferation (30-32 degrees C and pH 6.8-7.0). These cultures, and cultures of an established, terminally differentiating keratinocyte line, also derived from the ventral epithelium of the rat tongue, released substantial plasminogen activator activity as visualized by the fibrin-agar overlay technique. In addition, keratinocytes grown directly on 3H-labeled fibrin lysed this substrate in a plasmin-assisted process. The presence of serum modulated the kinetics of the reaction in a manner which suggests that a constant inhibitor tonus serves to contain the proteolytic reaction in the tissues and to prevent a chain reaction. Electrophoretic resolution of keratinocyte secretory proteins and of cell lysates revealed three distinct activators migrating at molecular weights of 48 000, 66 000 and 95 000. The keratinocytes also manufactured inhibitor(s) of the fibrinolytic reaction mainly directed against the activation step. The inhibitory activity was present in serum-free culture harvest media in quantities sufficient to completely annihilate the endogenous activators.

Animals↗
PubMed1983

Sodium and gating current time shifts resulting from changes in initial conditions.

The sodium and gating currents of the squid giant axon elicited by a depolarizing pulse are delayed, with little change in shape, as a result of a hyperpolarizing prepulse. The delays are almost completely saturated, at approximately 45 microseconds, for prepulses to -140 mV. At 8 degrees C they develop with time constants of between 60 and 180 microseconds for prepulses in the -130- to -150-mV range. There is a correlation between the extra charge moved during the gating current and the increase in the time delay of the sodium current as the magnitude of the hyperpolarizing prepulse is increased. These results strengthen the conclusion that the gating current is indeed closely associated with the process of sodium channel opening and provide information concerning the kinetics of the early steps, which are hidden in ionic current measurements. The main features of the gating and sodium current time shifts and the correlation between charge movement and time shifts are duplicated by a sequential six-state model for sodium activation.

Animals↗
PubMed1983

Induced capacitance in the squid giant axon. Lipophilic ion displacement currents.

Voltage-clamped squid giant axons, perfused internally and externally with solutions containing 10(-5) M dipicrylamine (DpA-), show very large polarization currents (greater than or equal to 1 mA/cm2) in response to voltage steps. The induced polarization currents are shown in the frequency domain as a very large voltage-and frequency-dependent capacitance that can be fit by single Debye-type relaxations. In the time domain, the decay phase of the induced currents can be fit by single exponentials. The induced polarization currents can also be observed in the presence of large sodium and potassium currents. The presence of the DpA- molecules does not affect the resting potential of the axons, but the action potentials appear graded, with a much-reduced rate of rise. The data in the time domain as well as the frequency domain can be explained by a single-barrier model where the DpA- molecules translocate for an equivalent fraction of the electric field of 0.63, and the forward and backward rate constants are equal at -15 mV. When the induced polarization currents described here are added to the total ionic current expression given by Hodgkin and Huxley (1952), numerical solutions of the membrane action potential reproduce qualitatively our experimental data. Numerical solutions of the propagated action potential predict that large changes in the speed of conduction are possible when polarization currents are induced in the axonal membrane. We speculate that either naturally occurring substances or drugs could alter the cable properties of cells in a similar manner.

Animals↗
PubMed1983

Treatment of a high titer anti-factor-VIII antibody by continuous factor VIII administration: report of a case.

Daily administration of large doses of factor VIII concentrate in a hemophiliac with a high titer factor VIII inhibitor resulted in marked reduction in the titer and response of the inhibitor to factor VIII administration and made possible elbow and bilateral knee replacements under conventional factor VIII coverage. Studies performed during the course of treatment indicated that the reduction in the inhibitor was the result of specific tolerance to factor VIII.

Adult↗
PubMed1982

Isolation of infectious bovine rhinotracheitis virus from the soft-shelled tick, Ornithodoros coriaceus.

Infectious bovine rhinotracheitis virus was isolated from the soft-shelled tick (Ornithodoros coriaceus). Serological identification of the isolated viruses was confirmed by restriction endonuclease digestion of purified virus DNA. These isolations indicate that the soft-shelled tick may be a vector for infectious bovine rhinotracheitis virus. This may be the first reported isolation of mammalian herpesvirus from an arthropod vector.

Animals↗
PubMed1982

Etoposide as a single agent in relapsed advanced lymphomas. A phase II study.

Twenty-three patients with relapsed lymphomas resistant to standard chemotherapy, 13 with Hodgkin's disease and 10 with non-Hodgkin's lymphomas, were treated with etoposide 120 mg/m2 i.v. daily for 5 days or orally for 7-10 days, repeated 3-weekly. This is a higher dose than has been used previously to treat these tumours. Objective responses were seen in eight of 13 (61%) patients with Hodgkin's disease (three CR, five PR) and in three of 10 (30%) patients with non-Hodgkin's lymphomas (three PR). The response rates for Hodgkin's disease are higher than those previously reported and are probably due to the greater dose of drug than has been previously employed. The dose-limiting toxicity was haematological, with gastro-intestinal toxicity occurring in the minority of patients only. It is concluded that etoposide has significant activity particularly in Hodgkin's disease. Its use in drug combinations should now be assessed.

Adult↗
PubMed1982

Effects of endocrine therapy on steroid-receptor content of breast cancer.

In order to determine the mechanisms of relapse following response to endocrine therapy, we have measured the oestrogen receptor (RE) content of biopsies of breast cancer in patients receiving various types of endocrine treatment. RE content fell in responding (means of 260.2 to 12 fmol/mg protein) and in nonresponding (means of 155.1 to 31.8 fmol/mg protein) patients who had measurable receptor at the start of treatment. Some of these patients, and a further group of responders to endocrine therapy, were monitored until relapse. Tumour biopsies at the time of relapse showed that 10/14 tumour samples contained significant RE (mean of 86.7 fmol/mg protein; range less than 10-271 fmol/mg protein) after successful endocrine therapy. No relationship could be found between RE content and plasma gonadotrophin or steroid-hormone concentration, but the fall in RE content correlated with reduced numbers of tumour cells in the biopsy. These results indicate that relapse following successful endocrine therapy in breast cancer does not appear to be due to the emergence of RE-negative tumour cells. The fall in RE content during response to endocrine therapy may be due to reduced tumour-cell content of the biopsy.

Adult↗