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Biomedical subjects

W G Simpson

Publications and source records attributed to W G Simpson.

36 records · Page 2Linked to original sources
PubMed1989

Career change: in quest of a controllable lifestyle.

Over the past decade, top medical students are selecting "controllable lifestyle" (CL) specialties at an increasing rate. CL specialties include anesthesiology, dermatology, emergency medicine, neurology, ophthalmology, pathology, psychiatry, and radiology. The choice of "noncontrollable lifestyle" (NCL) specialties such as family practice, internal medicine, obstetrics/gynecology, and pediatrics was negatively affected by this trend. The effect of CL on the selection of surgical training by top medical students was variable. The purpose of this study was to determine if CL is a factor in career change by young surgeons during and after residency. Graduates of the University of Kentucky College of Medicine from 1975 to 1983 (n = 796) were questioned regarding the specialty they entered after graduation and whether they remained in that specialty as of March, 1988. NCL and surgery specialties showed a net loss of practitioners during the study period (P less than 0.005) and CL showed a net gain (P less than 0.005). When physicians changed specialties, the direction of change occurred from NCL and surgery to CL (P less than 0.05). Change from CL to NCL and surgery occurred infrequently.

Career Choice↗
PubMed1989

The role of calcium in gonadotropin-releasing hormone induction of follicle-stimulating hormone release by the pituitary gonadotrope.

Binding of gonadotropin-releasing hormone (GnRH) to the pituitary gonadotrope induces activation of a membrane associated calcium channel, resulting ultimately in luteinizing hormone release. The role of calcium mobilization in GnRH-induced follicle-stimulating hormone (FSH) release was explored using anterior pituitary glands from female rats in a perifusion tissue culture system. While perifusion with GnRH (10 ng/ml) induced a constant level of gonadotropin release, the calcium channel blocker verapamil (10(-4)M) depressed FSH release, as did dantrolene (10(-4)M), an antagonist of intracellular calcium mobilization. When the calcium ionophore A23187 (10(-5) M) was substituted for GnRH, FSH release was not only maintained but increased. Antagonism of the activity of calmodulin (CAM) with trifluoperazine (10(-4)M), however, did not depress FSH release. Cellular content of cAMP and cGMP increased in response to GnRH. When FSH secretion was ionophoretically induced by A23187, however, little cAMP was detected. These results support a role for calcium mobilization in the second messenger cascade underlying GnRH-induced FSH release. The role for calcium in the disparate release of FSH and LH were further discussed in the context of these data.

Animals↗
PubMed1987

The response of cultured gonadotrophs to inhibin: the role of calcium mobilization.

The role of calcium mobilization and calmodulin activation in the induction of the selective suppression of follicle stimulating hormone (FSH) release by the gonadal protein inhibin was assessed employing a rat gonadotroph monolayer culture system. Inhibin, in porcine follicular fluid (60 microliters/ml), did inhibit FSH release in the face of GnRH stimulation. Antagonism of calcium mobilization with verapamil (10(-4) M) and dantrolene (10(-4) M) failed to restore the FSH response when administered with GnRH and inhibin. Trifluoperazine (10(-4) M), a calmodulin antagonist acted similarly. Cellular calmodulin content increased in response to gonadotropin-releasing hormone (GnRH), as did the concentration of cGMP, while both responses were prevented by the administration of inhibin. Trifluoperazine suppressed cGMP concentration to levels below baseline. These data suggest that while calmodulin and the cyclic nucleotides do not mediate the cellular response to inhibin, they may play a role in the control of gonadotropin synthesis. A link may exist between calmodulin, the concentration of which increased in response to GnRH and was suppressed by inhibin, and the elevation of cellular cGMP content induced by GnRH. Further investigation is warranted to assess a possible action of inhibin which is antagonistic to that of calcium in the transduction of GnRH stimulation into FSH release by the pituitary gonadotroph.

Animals↗
PubMed1987

Cyclic nucleotides and suppression of follicle-stimulating hormone release by inhibin.

The relative roles of the cyclic nucleotide messengers cAMP and cGMP in the suppression of follicle-stimulating hormone (FSH) secretion in response to inhibin (IBN) were assessed employing rat gonadotropes in monolayer culture. While exposure of cells to gonadotropin-releasing hormone (GnRH) induced a significant increase in the amounts of both FSH and luteinizing hormone (LH) released into the culture medium, these responses were dampened by the administration of IBN (in porcine follicular fluid). Addition of cGMP to the system failed to restore FSH release, while cAMP restored basal FSH release. Modulation of nucleotide metabolism with theophylline, sodium nitroprusside, and a protein kinase inhibitor failed to overcome the IBN-induced suppression of FSH release. The cellular content of calmodulin increased in response to GnRH, a response antagonized by IBN. Cellular levels of cGMP were also increased by GnRH, but this response was unaltered by IBN. The administered drugs all failed to reverse these effects of IBN. These data indicate that the IBN-induced suppression of FSH release is not dependent upon the cyclic nucleotides cAMP and/or cGMP. However, a role in the maintenance of basal FSH synthesis and release for cAMP is indicated.

Animals↗
PubMed1986

In vitro chemosensitivity of J-82 human bladder cancer cells.

While chemotherapy offers a valuable adjunct to surgery in the management of intravesical bladder cancer, an accurate in vitro predictive test for chemosensitivity has yet to be developed. Drug sensitivity of the human bladder cancer cell line J-82 was assessed using monolayer, stem cell and [3H]thymidine incorporation assays. The 72-h monolayer assay provided a rapid reflection of in vitro drug sensitivity and when combined with the labeling index the results generally paralleled those obtained with the soft agar stem cell assay without the associated large commitment of time and labor. It is suggested that 72-h monolayer assay alone or in combination with [3H]thymidine labeling index may offer valuable insight into the chemotherapeutic response of bladder tumors.

Antineoplastic Agents↗
PubMed1986

Verapamil enhanced in vitro chemosensitivity of a murine bladder carcinoma, FCB.

The in vitro enhancement of chemotherapeutic efficacy by verapamil, a calcium antagonist, was assessed using FCB, a transplantable murine transitional cell carcinoma. Exponentially growing FCB cells were partially resistant to treatment with both thiotepa (10(-4) M) and Adriamycin (10(-5) M), however, there was a significant reduction in cell growth when either agent was administered in combination with verapamil (10(-5) M); the effect was evident over a wide range of drug concentrations (10(-4) - 10(-9) M). There was also a pronounced inhibition of DNA precursor incorporation when verapamil was used in combination with either agent. Fluorometric analysis of Adriamycin uptake indicated that verapamil caused an increase in the intracellular concentration of the agent. The data presented are consistent with the postulate that verapamil enhances chemotherapeutic efficacy by altering cellular permeability to the cytotoxic agents. Our study indicates that the use of verapamil in combination with cytotoxic agents for intravesical chemotherapy of bladder tumors may prove to be beneficial in human patients.

Animals↗
PubMed1986

A simplified technique for rapid immunofluorescent assessment of cellular hormonal content.

Currently applied techniques for immunofluorescent staining of cultured cells are time consuming and not amenable to experimental design. Monolayers of rat anterior pituitary cells were stained in situ with rabbit follicle-stimulating hormone antiserum. Excision of the culture surfaces produced samples that were easy to handle and score for immunoreactivity without sacrificing resolution. The staining of in situ monolayers of cultured cells allows for assessment of both the secretory behavior and the hormonal content of the cells.

Animals↗
PubMed1985

A convenient method for in situ processing of cultured cells for cytochemical localization by electron microscopy.

The effects of various exogenous agents on subcellular structures is of importance to many investigators and can be critically evaluated by the use of cytochemical techniques and transmission electron microscopy. Therefore various cell culture techniques have become increasingly important in biological research in order to help determine these effects. Presently, most existing methods for processing anchorage-dependent cultures for electron microscopy utilize cells grown on either glass or plastic substrates. Therefore various coating substances have been applied to the culture surfaces to facilitate removal of the sample, however, incomplete separation and sample fracture often results. Here we present a simple method of in situ processing of samples for electron microscopy involving the use of detachable chamber slides. This method allows for the use of a quick processing procedure that results in a complete separation of the sample from the glass slide.

Animals↗
PubMed1985

Systemic influence of intravesical chemotherapy with verapamil.

The influence of the calcium blocker verapamil (VR) on systemic toxicity resulting from the intravesical instillation of Adriamycin (ADM) and thiotepa (THT) was assessed in mice. Eighty per cent of the animals receiving THT + VR developed a generalized alopecia. Data gathered at necroscopy failed to reveal any trauma to the major organs or the presence of a drug-induced myelosuppression. Combination of ADM and VR did not produce an enhancement of systemic toxicity, manifest as myelosuppression. The drug combination did not produce a cardiomyopathy as assessed by histologic examination. The use of VR in combination with antineoplastic agents posed no more of a threat to the animals than did the use of cytotoxin alone.

Animals↗
PubMed1985

The calcium channel blocker verapamil and cancer chemotherapy.

Verapamil is an agent which inhibits the transmembrane flux of calcium ions and is used clinically in the management of cardiac arrhythmias. Combination of this calcium antagonist with antineoplastic agents results in the establishment of chemosensitivity in tumor cells resistant to accepted chemotherapeutic agents and, to a lesser degree, potentiates the efficacy of such compounds in drug-sensitive malignancies. Preliminary indications are that the clinical role of such a potentiation of efficacy would not be limited by an increase in generalized toxicity in non-malignant tissues. Data accumulated indicates a verapamil-induced inhibition of the ability of resistant cells to actively extrude chemotherapeutic agents, possibly due to a decrease in calmodulin activity as a result of a drug-induced alteration of the intracellular calcium environment. The results of preclinical trials to date indicate a role for verapamil in augmenting currently accepted chemotherapeutic regimens.

Animals↗
PubMed1985

Determination of [3H]TdR-labelling indices of cultured cells grown on detachable chamber slides.

The in vitro effects of xenobiotic agents on the incorporation of DNA precursors was determined using a detachable chamber slide assembly. The technique presented allows for the comparative assessment of several agents, even when a limited number of cells is available. The use of a glass slide also potentiates the use of higher magnifications with a greater resultant resolution than that achievable with past methods.

Autoradiography↗
PubMed1984

Verapamil enhancement of chemotherapeutic efficacy in human bladder cancer cells.

The calcium influx blocker verapamil has been used to overcome drug resistance in several tumor systems. The possible in vitro enhancement of drug efficacy was assessed in bladder cancer cell line T24. Combination of thiotepa and doxorubicin hydrochloride with verapamil significantly reduced the survival and growth of T24 cells after as little as 1 hour of drug exposure. An increase in doxorubicin hydrochloride-induced inhibition of [3H]thymidine uptake resulted when verapamil was administered. However, this trend was not demonstrated when combined with thiotepa. It appears that verapamil enhances thiotepa-induced cytotoxicity while it potentiates the antimitotic nature of doxorubicin hydrochloride. The data presented is consistent with the postulate that verapamil alters active efflux of drug from malignant cells and suggests that verapamil has a role in the clinical management of bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

A proposal for a more efficient board.

Under traditional organizational patterns, trustees generally do not have the time, and consequently the personal preparation, to do their jobs well. This article presents recommendations for making better use of trustees' limited time through better board structuring and more effective board committees, as well as a proposal to pay directors' fees to hospital trustees.

Administrative Personnel↗