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A K Davis

Publications and source records attributed to A K Davis.

At least 19 recordsLinked to original sources
PubMed1998

Spontaneous activity regulates calcium-dependent K+ current expression in developing ascidian muscle.

1. In embryonic ascidian muscle, outward K+ currents develop in two stages: the initial expression of a slowly activating, voltage-gated K+ current (IKv) near the time of neurulation is followed about 6 h later by a rapidly activating calcium-activated K+ current (IK(Ca)). During this 6 h interval, inward Ca2+ currents (ICa) appear and the inward rectifier (IK(IR)), the sole resting conductance, is transiently downregulated. These events predict a period of spontaneous activity. The following experiments were designed to test this prediction and to examine the relevance of spontaneous activity for muscle cell development. 2. By recording activity in cell-attached patches, we have found that muscle cells generate spontaneous action potentials during this 6 h window of time when IK(IR) is downregulated and outward K+ currents are slow. Action potentials occur at a mean frequency of 13.9 min-1.3. When activity is blocked by the transient application of the Ca2+ channel blocker Cd2+, IK(Ca) fails to develop. This disruption is specific for IK(Ca): IK(IR) and ICa develop normally in activity-blocked cells. Application of Cd2+ either before or after the window of activity has no effect. 4. The reappearance of IK(IR) and the development of IK(Ca) and the mature form of ICa are all prevented by transcription blockers, with a sensitive period corresponding to the period of activity. 5. These data show that, although the expression of three channel types depends on transcription during the period of spontaneous activity, only the development of IK(Ca) depends on activity.

Animals↗
PubMed1998

Emerging lessons of the Interdisciplinary Generalist Curriculum (IGC) Project.

The Interdisciplinary Generalist Curriculum Project (IGC) was funded in 1993 by the Health Resources and Services Administration with the goal of developing innovative preclinical generalist curricula in ten of the nation's medical and osteopathic schools. The IGC successfully completed two competitive cycles in which ten schools were awarded three-year contracts. Although the long-term goal of the project is to increase the proportion of medical students choosing generalist careers, much has been learned thus far about the processes of curricular change and interdisciplinary cooperation. Drawing on information from school reports, site visits, external evaluations, academic presentations, and annual project meetings, this report presents the emerging lessons learned in the key areas of interdisciplinary collaboration, recruitment and retention of community preceptors, faculty development, and integration of generalist-related components into the four-year medical school curriculum. These lessons should prove useful for other schools embarking upon significant curricular innovations.

Career Choice↗
PubMed1997

Long-term evaluation of a substance abuse fellowship program in family medicine.

BACKGROUND: Faculty development fellowship programs provide avenues for physicians to develop careers in academic medicine. However, the long-term impact of these programs has not been evaluated. This paper examines the impact of an 18-month substance abuse faculty development fellowship administered by the Society of Teachers of Family Medicine (STFM) 7 years after the fellowship's completion. METHODS: Fellows were interviewed by telephone. Their CVs were examined to assess how their present substance abuse teaching, clinical, research, administrative, scholarly, and networking activities compared with those prior to the fellowship. RESULTS: Initially, fellows contributed modules to an STFM publication and increased substance abuse teaching in their home institutions. Seven years later, fellows reported increased activity in substance abuse teaching, clinical, administrative, and research activities over those prior to the fellowship and attributed these increases to the fellowship. Fellows' CVs reflected increased publications, presentations, and networking activities with each other, including the creation of the STFM Group on Substance Abuse. CONCLUSIONS: In a 7-year follow-up, STFM's substance abuse fellowship program met its original goals, strengthened the academic and professional achievements of the fellows, and fostered the development of several fellows as leaders within the substance abuse field.

Faculty, Medical↗
PubMed1996

Co-ordinated modulation of Ca2+ and K+ currents during ascidian muscle development.

1. The development of Ca2+ and K+ currents was studied in ascidian muscle cells at twelve embryonic stages from gastrulation to the mature cell, a period of 24 h. A high degree of co-ordination occurs between the development of the inwardly rectifying K+ current (IK(IR)), which sets the resting potential, and Ca2+ and outward K+ currents, which determine action potential waveform. 2. At neurulation IK(IR), which had been present since fertilization, begins to decrease, reaching 12% of its previous density in 6 h. IK(IR) then immediately begins to increase again, reaching its previous density in another 6 h. 3. When IK(IR) begins to decrease, a high-threshold inactivating Ca2+ current and a slowly activating voltage-gated K+ current appear. 4. When IK(IR) returns to its previous density, two new currents appear: a sustained Ca2+ current with the same voltage dependence, but different conotoxin sensitivity than the inactivating Ca2+ current; and a Ca(2+)-dependent K+ current, which activates 8-10 times faster and at potentials 20-30 mV more negative than the voltage-dependent K+ current. 5. The transient downregulation of IK(IR) destabilizes the resting potential and causes spontaneous action potentials to occur. Because IK(IR) is absent when only a slowly activating high-threshold outward K+ current is present, these action potentials are long in duration. 6. The return of IK(IR) and the appearance of the rapidly activating Ca(2+)-dependent K+ current eventually terminate this activity. The action potentials of the mature cell occur only on stimulation, and are 10 times shorter in duration than those in the immature cell.

Action Potentials↗
PubMed1995

Nitric oxide synthase activity in placentae from women with pre-eclampsia.

The syncytiotrophoblast (ST) cell layer of the human villous placenta expresses nitric oxide (NO) synthase. Because NO is a potent relaxant of vascular smooth muscle and inhibitor of platelet activity, we postulated that exaggerated intervillous aggregation of platelets and reduced fetoplacental blood flow in pre-eclampsia result from reduced expression of NO synthase (and production of NO) by the ST. Conversion of [3H]arginine to [3H]citrulline and Lineweaver-Burk transformation were used to derive the Vmax and K(M) of NO synthase. Contrary to our expectations, the Vmax was not significantly different between villous placenta obtained from nulliparous normal and pre-eclamptic women (n = 11 each). The Vmax and K(M) were 22.3 +/- 2.3 pmol/mg per min and 1.3 +/- 0.1 microns, and 22.0 +/- 2.7 pmol/mg per min and 1.4 +/- 0.1 microns, for villous placenta from the nulliparous normal and pre-eclamptic women, respectively. The Vmax and K(M) of placental NO synthase were also comparable among multiparous normal and pre-eclamptic women, as well as women with gestational hypertension. When compared with the enzyme activity of the villous, that of the basal plate was reduced by approximately one-half in all placentae. The calcium-independent activity was consistently 40-fold less than the calcium-dependent activity, and it was similar between villous and basal plate, and between placentae from normal and hypertensive women. We suggest that expression of NO synthase is not different in placentae obtained from normal and pre-eclamptic women.

Adult↗
PubMed1995

Proteoglycans are present in the transverse tubule system of skeletal muscle.

The transverse tubule system (T-tubule, T-system) of skeletal muscle is a membranous network that penetrates the interior of myofibers. The T-system is continuous with the sarcolemma and therefore provides a path for membrane excitation to reach internal myofibrils. In this study we demonstrate that T-tubules in elasmobranch fish, frog, and rat skeletal muscle contain a matrix of chondroitin sulfate proteoglycans. We used anti-T1, a mouse monoclonal antibody that recognizes a rare chondroitin sulfate epitope, for immunolocalization and biochemical studies. First, we find that T1 immunoreactivity colocalizes with a T-tubule marker, the dihydropyridine receptor alpha 2 subunit, in both frog and fish muscle. Secondly, the distribution of T1 immunoreactivity exactly matches the different distribution of T-tubules in rat and frog muscle. In rat muscle, two bands of T1 immunoreactivity are detected per sarcomere, a distribution that corresponds to the T-tubules located at the two A-I junctions of each sarcomere. In frog muscle, we detect one band of T1 immunoreactivity per sarcomere that corresponds to the one T-tubule per sarcomere located at the Z line. Lastly, we have isolated and biochemically characterized T1 antigenicity from fish skeletal muscle. Like extracellular matrix proteoglycans of cartilage, T1 antigenicity requires denaturing conditions to be solubilized. In fish muscle, two chondroitin sulfate proteoglycans bear T1: a heavily glycosylated proteoglycan with a molecular mass of about 1000 kDa, and a smaller proteoglycan that has a mobility on SDS-PAGE like a protein of molecular mass 280 kDa. We propose that proteoglycans function as structural components in the T-system. The proteoglycans may form a matrix, like the one formed by the cartilage proteoglycans they resemble, that can withstand the cytosolic osmotic pressures present in muscle cells and therefore may prevent the T-tubule from collapsing. We present a quantitative argument in support of this hypothesis.

Animals↗
PubMed1995

The interdisciplinary generalist curriculum project: a national medical school demonstration project.

The United States is facing the challenge of producing more generalists for the physician workforce. The Primary Care Organizations' Consortium (PCOC) has responded by focusing on how medical education can be modified to enhance and support medical students' interest in and commitment to generalism early in their training. Evolving from PCOC's developmental work, the five-year Interdisciplinary Generalist Curriculum (IGC) Project was developed to encourage the nation's schools of medicine and colleges of osteopathic medicine to implement interdisciplinary generalist curricula in the preclinical years. Funded by the Division of Medicine in the Bureau of Health Professions of the Health Resources and Services Administration (HRSA), the IGC Project has successfully developed and implemented a nationally competitive medical school demonstration project. Thirty-three schools submitted proposals for an IGC Project award; nine were selected for site visits, from which five were chosen to receive three-year awards. Rigorous attention to creating and maintaining an interdisciplinary focus has characterized the first phase of the IGC Project. Shared leadership among the Executive Committee's project director and two project codirectors and parity in representation among the three disciplines of family medicine, internal medicine, and pediatrics on the Advisory Committee have formed a critical foundation for interdisciplinary functioning within the project. Growing national interest in generalist training and other funding initiatives have contributed to acceptance of the IGC Project. The high level of interest in the IGC Project and the successful interdisciplinary collaboration during the first phase would indicate that the interdisciplinary process can be replicated to move the nation's medical education institutions toward the production of needed generalist physicians.

Curriculum↗
PubMed1995

Comparison of ionic currents expressed in immature and mature muscle cells of an ascidian larva.

We have compared the voltage-gated ion channels present in larval ascidian muscle at two developmental stages: muscle precursor cells just after the terminal cell division and mature contractile muscle, 7-11 hr later. All precursor cells express a high-threshold transient Ca current and a slowly activating delayed K current, and about half the cells express a low-threshold transient Ca current. An inwardly rectifying K current, which had been present from fertilization until just before the terminal cell division, is absent. Mature muscle retains two of the tailbud currents: the low-threshold transient Ca current and the slow delayed K current, although at larger densities, and also expresses a high-threshold Ca current that is similar in most respects to the precursor cell current but that lacks inactivation. In addition, mature muscle expresses two rapidly activating outward K currents, one voltage and one Ca dependent, that generate a composite outward K current that is eight times larger and activates eight times faster than the tailbud K current. Mature muscle also reexpresses the inward rectifier. We propose that the transient absence of the inward rectifier and the slow activation of the delayed K current early in development create a window of developmental time when spontaneous electrical activity is likely.

Action Potentials↗
PubMed1993

Expression of nitric oxide synthase by syncytiotrophoblast in human placental villi.

The endogenous biosynthesis of nitric oxide (NO) is increased during gestation. To begin our investigation of a possible tissue source (or sources), we examined the placenta. We postulated that analogous to the endothelium of blood vessels, the syncytiotrophoblast (STr) cell layer that lines the intervillous blood space of the human placenta would express NO synthase. Our results show that human placental villi express a calcium- and calmodulin-sensitive form of NO synthase, located mainly in the microsomal cell fraction. By in situ hybridization using a riboprobe generated from human endothelial NO synthase cDNA, we observe NO synthase mRNA expression in STr. The STr also shows NADPH-diaphorase staining, indicating the presence of NO synthase, and most likely other flavin-containing enzymes involved in sex steroid metabolism. NO synthase activity was also detected in the villi of a complete mole placenta (which lacks fetal vessels), further supporting a trophoblastic origin. Our findings suggest a previously unrecognized role for STr-derived NO in placental function.

Amino Acid Oxidoreductases↗
PubMed1993

Educational strategies for clinicians.

Largely because of a lack of training, many primary care physicians are unaware of how they can prevent, detect, or manage substance abuse within their clinical practice. The educational process used to develop a teaching unit can be simplified by initially asking a few directed questions. The answers to these questions determine what needs to be taught while facilitating the subsequent steps of determining learning goals and objectives and selecting appropriate teaching materials and strategies. Evaluating the teaching unit on at least a cursory level provides useful information for future planning. A variety of curriculum manuals and clinical text parts can be readily incorporated into teaching units. These same sources can alternatively be adapted to an individual's own self-directed course of study. Incorporation of experimental educational strategies is especially useful in substance abuse instruction. Including recovering individuals, attendance at self-help group meetings, and role play exercises are all useful experimental strategies for engaging the learner. Tapping into organizational resources and networking with others involved in similar activities enhances one's potential through the sharing of information and through the synergism created by networking with others.

Alcoholism↗
PubMed1988

Substance abuse units taught by four specialties in medical schools and residency programs.

Four medical specialty organizations conducted a survey of 294 departments in 98 medical schools and 1,124 residency programs to identify the number and type of curriculum units on substance abuse offered by these specialties. A curriculum unit was defined as a formal block of teaching on substance abuse. A total of 251 (85 percent) of the medical school departments and 828 (74 percent) of the residency programs responded. Of those, 175 (70 percent) of the medical school departments and 479 (58 percent) of the residency programs reported offering at least one curriculum unit on substance abuse. There was considerable variation among the four specialties in the number and percentage of departments or programs reporting such units. Overall, a majority of the units addressed both alcohol and other drugs, were required, and included a clinical component. Evaluations of content and teaching strategies are needed to examine the quality and adequacy of substance abuse training.

Curriculum↗
PubMed1986

Effects of tissue preincubation and hypoxia on CA3 hippocampal neurons in the in vitro slice preparation.

Using the in vitro hippocampal slice preparation, we studied the electrophysiological properties of pyramidal cells in tissue that was 'preincubated' (2-6 h in a large, static volume of oxygenated bathing medium) before being placed in an interface chamber for study. Striking differences were found in 'preincubated' vs 'non-preincubated' CA3 cells. The preincubated cells had more negative resting potentials, higher input resistance, lower threshold for stimulus-evoked burst discharge and larger hyperpolarizing afterpotentials. Cells in the preincubated CA3 region were also more likely to show spontaneous synchronized burst discharge, but were relatively resistant to hypoxia-induced spreading depression. CA1 cells were less dramatically affected by preincubation, showing little difference from their non-preincubated counterparts. Possible mechanisms involved in the CA3 preincubation effect, including glial buffering alterations and changes in Na+, K+-ATPase activity, are discussed.

Animals↗
PubMed1984

Alcoholism curriculum development: an examination of the process.

Alcoholism is one of several topics that may be integrated into family medicine clerkship teaching. This article focuses on the process of curriculum development in alcoholism. The process is traced from its beginnings in a third-year clerkship to its integration into the medical school curriculum and other areas of medical education. Strengths and pitfalls in this project are discussed. Enlisting community support and field testing newly developed strategies are emphasized as successful methods. Less successful in this project, though equally important, are faculty development and long-term evaluation. Recommendations for curriculum development in similar projects are made.

Alcoholism↗