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Biomedical subjects

T E Norris

Publications and source records attributed to T E Norris.

At least 19 recordsLinked to original sources

Molecular cloning of the guinea-pig IL-5 receptor alpha and beta subunits and reconstitution of a high affinity receptor.

The functional IL-5 receptor is a heteromeric complex consisting of an alpha and beta subunit. The cloning, sequencing and expression of guinea-pig IL-5Ralpha and beta subunits is described. The guinea-pig IL-5Ralpha subunit cDNA encodes a protein of M(r)47 kDa, which is 72 and 66% homologous to the human and murine orthologs, respectively. Three guinea-pig IL-5Rbeta subunit cDNA clones were isolated, which differ in the N-terminus and are 56-64% homologous to the human and murine IL-5Rbeta subunits. Expressing human IL-5Ralphabeta and guinea-pig IL-5Ralphabeta(1)in the baculovirus-insect cell system resulted in recombinant receptors which bound hIL-5 with high affinity (K(d)=0.19 and 0.11 nM, respectively). Expressing just gpIL-5Ralpha was not sufficient to demonstrate binding. This contrasts with the human receptor, where hIL-5Ralpha alone can bind hIL-5 with high affinity. gpIL-5Ralphabeta(1)bound both hIL-5 and mIL-5 with comparable affinity (K(i)=0.10 and 0.06 nM), similar to that seen with hIL-5Ralphabeta. Thus, both the heteromeric hIL-5R and gpIL-5Ralphabeta(1)can bind multiple IL-5 orthologs with high affinity whereas the murine IL-5R is selective for the murine ligand.

Amino Acid Sequence↗

Educating generalist physicians for rural practice: how are we doing?

Although about 20 percent of Americans live in rural areas, only 9 percent of physicians practice there. Physicians consistently and preferentially settle in metropolitan, suburban and other nonrural areas. The last 20 years have seen a variety of strategies by medical education programs and by federal and state governments to promote the choice of rural practice among physicians. This comprehensive literature review was based on MEDLINE and Health STAR searches, content review of more than 125 relevant articles and review of other materials provided by members of the Society of Teachers of Family Medicine Working Group on Rural Health. To the extent possible, a particular focus was directed to "small rural" communities of less than 10,000 people. Significant progress has been made in arresting the downward trend in the number of physicians in these communities but 22 million people still live in health professions shortage areas. This report summarizes the successes and failures of medical education and government programs and initiatives that are intended to prepare and place more generalist physicians in rural practice. It remains clear that the educational pipeline to rural medical practice is long and complex, with many places for attrition along the way. Much is now known about how to select, train and place physicians in rural practice, but effective strategies must be as multifaceted as the barriers themselves.

Career Choice↗

Office procedures. Esophagogastroduodenoscopy.

This article describes diagnostic esophagogastroduodenoscopy and its use by primary care physicians. Included in the discussion are reviews of indications and contraindications, patient preparation (including sedation and monitoring), equipment and supplies needed, pertinent normal anatomy, techniques, and applicable common pathologic findings.

Procedural Sedation↗

On-line delivery of continuing medical education over the World-Wide Web: an on-line needs assessment.

OBJECTIVE: On-line continuing medical education (CME) courses offer at least two potential advantages: They are extremely convenient and relatively inexpensive. Before expanding our department's 2-year-old on-line category 1 accredited CME program, we conducted a survey to assess the need for more courses of this type and to document those topics of most interest to our responders. MATERIALS AND METHODS: An on-line survey form was designed and linked to the home page of our departmental Web server. The 8-month survey asked whether responders were interested in earning category 1 CME hours, how many hours they desired, how much they were willing to pay for each hour, and which topics would interest them most. Responders were also asked to specify their medical practice and medical specialty. All responses were tabulated, and simple descriptive statistics were calculated. RESULTS: Our survey received 317 responses: 188 from physicians, 42 from radiology technologists, 11 from physician assistants and nurse practitioners, and the remainder from 26 other categories of practice. Physician specialties identified included 86 diagnostic radiologists, 24 internists, 18 emergency medicine specialists, 15 family practitioners, and 45 from 14 other specialties. Responses came mainly from the United States; however, 32 responses were received from 15 other countries. The median number of on-line CME hours desired was 15 (range, 1-1324). Physician responders were willing to pay a median amount of $10 per credit hour (range, $0-400). The most commonly suggested topic was general radiology, followed by general reviews of MR imaging, CT, sonography, and various organ-based specialties in radiology such as mammography, neuroradiology, and musculoskeletal radiology. CONCLUSION: Physicians and many other health care workers are interested in on-line CME and are willing to pay for such a service. This information, as well as the suggested topics collected in this survey, may prove helpful in planning future offerings of on-line CME.

Attitude of Health Personnel↗

Which procedures should be taught in family practice residency programs?

BACKGROUND: Family practice residencies lack clear guidelines defining which procedures should be included in their curricula. The American Academy of Family Physicians (AAFP) Task Force on Procedures developed a recommendation (approved by the AAFP Board of Directors) that can be used to create a set of procedures that should be taught in residencies. The task force recommendation is based on procedures taught in most family practice residencies and performed by most practicing family physicians. METHODS: The AAFP Task Force on Procedures surveyed all family practice residency programs and departments to determine which procedures they were teaching. The task force also surveyed a representative sample of practicing family physicians to find out which procedures they were performing. RESULTS: Residency programs and departments returned 397 surveys (74.1% response), and the sample of 4,400 practicing physicians returned 2,028 surveys (46.1% response). The survey data identified 69 procedures as being taught in most family practice residencies, and 30 of these procedures as being performed by most practicing family physicians. CONCLUSIONS: Many procedures can be identified as being taught in most family practice residencies or performed by most practicing family physicians. Fewer procedures are performed by practicing family physicians than are taught in residencies.

Clinical Competence↗

A fellowship in rural family medicine: program development and outcomes.

BACKGROUND AND OBJECTIVES: Many strategies have been used by academic institutions to address the shortage of rural family physicians. Fellowship training in rural family medicine represents one approach. METHODS: Tacoma Family Medicine developed a fellowship program of this type. Five years of operations are described, including applicants, educational outcomes, rural outcomes, and adverse outcomes. RESULTS: An adequate applicant pool does exist, composed of both applicants from residency and from practice. A curriculum of advanced obstetrics, electives, and a rural experience has been successful. Unforeseen problems included a strained relationship with family practice residents in the program and competition for community preceptors. CONCLUSIONS: Family practice residencies with a mission of rural training are encouraged to consider the strategy of a rural fellowship.

Curriculum↗

Geographic distribution, supply, and need for generalist physicians in Alaska.

This study provides the first comprehensive description of Alaska's geographic distribution of generalist physicians relative to population. All 443 generalist care physicians (family, general, general internal medicine, and pediatric) or their office managers were questioned about their specialties, ZIP codes, employers, populations served, and hours spent per week offering direct patient care. The results indicated a 30% overall shortage of generalist physicians for the state, representing roughly 141 full-time-equivalent generalists relative to national practice patterns and trends of health maintenance organizations. Of 17 primary health care areas, including the Anchorage area, 15 showed a need for additional generalist physicians. Most areas had a 20 to 40% shortage. Concerns about transportation and financial barriers to access to care, especially in remote regions, were raised. Other needs emphasized included knowledge of contributions of midlevel health care professionals, Alaska Native versus non-Native care, efforts to train and retain physicians in Alaska, and the need for longitudinal tracking of practice patterns.

Alaska↗

Are rural family physicians comfortable performing cesarean sections?

BACKGROUND: Provision of obstetric care in the United States requires the capacity to perform cesarean sections. It is unknown who actually performs these procedures in rural hospitals and whether nonobstetricians feel comfortable performing cesarean sections. METHODS: We conducted a telephone survey of the 41 rural hospitals in Washington State, asking about the obstetric services offered and the composition and obstetrical practices of physician staff. A supplementary questionnaire was sent to the 112 family physicians providing obstetric services in the subset of hospitals with 50 or fewer beds, asking whether they performed cesarean sections. Eighty-six responded, for a response rate of 75%. RESULTS: Thirty-one (75%) of the rural hospitals provide obstetric services; of the 31 hospitals, 19 (61%) had no obstetricians on staff. In these hospitals the majority of physicians on staff both practice obstetrics and perform cesarean sections. Family physicians performed the majority of cesarean sections in all but the eight largest rural hospitals; even in these large hospitals (mean annual deliveries, 785), family physicians performed 28% of the cesarean sections. Most family physicians who performed cesarean sections felt very comfortable performing these operations. There was a strong association between the number of cesarean sections performed in formal residency training settings and the family physician's comfort level. CONCLUSIONS: Cesarean sections remain an important service in those rural hospitals providing obstetric services. Most Washington State rural hospitals depend on family physicians for this operative intervention. Physicians' comfort in doing cesarean sections appears to be closely related to prior formal training during residency. This relationship suggests that training programs preparing future rural physicians need to ensure adequate training in this area for their residents.

Adult↗

Two decades of experience in the University of Washington Family Medicine Residency Network: practice differences between graduates in rural and urban locations.

This study describes how graduates of the University of Washington Family Medicine Residency Network who practice in rural locations differ from their urban counterparts in demographic characteristics, practice organization, practice content and scope of services, and satisfaction. Five hundred and three civilian medical graduates who completed their residencies between 1973 and 1990 responded to a 27-item questionnaire sent in 1992 (84% response rate). Graduates practicing outside the United States in a specialty other than family medicine or for fewer than 20 hours per week in direct patient care were excluded from the main study, leaving 116 rural and 278 urban graduates in the study. Thirty percent of graduates reported practicing in rural counties at the time of the survey. Rural graduates were more likely to be in private and solo practices than urban graduates. Rural graduates spent more time in patient care and on call, performed a broader range of procedures, and were more likely to practice obstetrics than urban graduates. Fewer graduates in rural practice were women. A greater proportion of rural graduates had been defendants in medical malpractice suits. The more independent and isolated private and solo practice settings of rural graduates require more practice management skills and support. Rural graduates' broader scope of practice requires training in a full range of procedures and inpatient care, as well as ambulatory care. Rural communities and hospitals also need to develop more flexible practice opportunities, including salaried and part-time positions, to facilitate recruitment and retention of physicians, especially women.

Chi-Square Distribution↗

The cloned neurotensin receptor mediates cyclic GMP formation when coexpressed with nitric oxide synthase cDNA.

Rat neurotensin (NT) receptor (NTR) cDNA was subcloned into the pRC-CMV expression vector and transfected into 293 cells, and cellular clones that stably expressed the NTR were isolated and characterized. [3H]NT binding to membranes prepared from the NTR cDNA-transfected cells displayed specificity and saturability, with an apparent Kd of 1.25 nM and a Bmax of 43.4 pmol/mg of protein (approximately 3.5 x 10(6) binding sites/cell). NT stimulated an increase in [3H]inositol phosphate levels in the NTR-expressing cells up to 2500% of basal levels. The response was time and dose dependent, with an EC50 of 10.4 nM. NT also stimulated cAMP formation in these cells, with an EC50 of 27.0 nM. In addition, NT evoked an increase in the level of intracellular calcium. Approximately 60% of the calcium rise was attributable to the release of intracellular stores and 40% was attributable to calcium influx. Although NTR occupancy has been shown to stimulate cGMP formation in several brain preparations and cell lines, NT was unable to mediate cGMP synthesis in the NTR-expressing 293 cells. We found that 293 cells have guanylate cyclase activity but have undetectable levels of nitric oxide synthase (NOS) activity. Because it was possible that the production of nitric oxide is required as the mediator of NT-induced cGMP synthesis, we subcloned NOS cDNA into the pCEP4 expression vector and transiently expressed it in the NTR cells. We report that NT increased cGMP levels up to 375% of basal levels when NOS cDNA was coexpressed and that the increase was completely inhibited by the NOS inhibitor N omega-nitro-L-arginine. NT-induced cGMP accumulation was time and dose dependent, with an EC50 of 1.7 nM. To our knowledge, this is the first report of NT mediating cGMP formation with a cloned receptor and the first evidence that NT-induced cGMP accumulation requires the production of nitric oxide.

Adenylyl Cyclases↗

Human tau isoforms confer distinct morphological and functional properties to stably transfected fibroblasts.

Tau protein is a neuronal microtubule-associated protein that promotes the assembly and stability of microtubules. To evaluate the biological significance of tau isoform diversity, NIH-3T3 cells were stably transfected with cDNAs encoding each of the six isoforms present in human brain. Cells expressing different isoforms developed distinct morphologies. Cell lines expressing 3-repeat tau isoforms developed large flat cell bodies while cells expressing 4-repeat isoforms had small, round cell bodies. All transfected cell lines, except those expressing the shortest tau isoform, displayed very long thin neurite-like processes. Tau colocalized with microtubules in both the cell body and the long processes in all of the tau-transfected cells. Tau also displayed a diffuse amorphous staining pattern that was concentrated around the cell nucleus. Microtubule bundling was not enhanced in any of the transfected cells as compared to untransfected controls. The transfected cells showed increased resistance to colchicine treatment. Thus, different tau isoforms can confer unique cellular morphologies to 3T3 cells and can alter the susceptibility of these cells to a microtubule depolymerizing agent.

3T3 Cells↗

Tau protein induces bundling of microtubules in vitro: comparison of different tau isoforms and a tau protein fragment.

Expression of tau protein in non-neuronal cells can result in a redistribution of the microtubule cytoskeleton into thick bundles of tau-containing microtubules (Lewis et al.: Nature 342:498-505, 1989; Kanai et al.: J Cell Biol 109:1173-1184, 1989). We reconstituted microtubule bundles using purified tubulin and tau in order to study the assembly of these structures. Taxol-stabilized tubulin polymers were incubated with various concentrations of recombinant human tau and examined by electron microscopy. With increasing concentrations of tau 3 (tau isoform containing three microtubule binding domains) or tau 4 (isoform containing four microtubule binding domains) the microtubules changed orientation from a random distribution to loosely and tightly packed parallel arrays and then to thick cables. In contrast, tau 4L, the tau isoform containing four microtubule binding domains plus a 58-amino acid insert near the N-terminus, showed minimal bundling activity. tau 4-induced bundling could be inhibited by the addition of 0.5 M NaCl or 0.4 mM estramustine phosphate, conditions which are known to inhibit tau binding to microtubules. A tau construct that contained only the microtubule binding domains plus 19 amino acids to the C-terminus was fully capable of bundling microtubules. Phosphorylation of tau 3 with cAMP-dependent protein kinase had no effect on its ability to induce microtubule bundling. These results indicate that tau protein is directly capable of bundling microtubules in vitro, and suggests that different tau isoforms differ in their ability to bundle microtubule filaments.

Cytoskeleton↗

Documentation of experience: preventive medicine for family physicians. The AAFP Commission on Quality and Scope of Practice.

The AAFP, the American Medical Association and the Joint Commission on Accreditation of Healthcare Organizations clearly agree on the principle that privileges should be based on documented evidence of training, experience and demonstrated current competence. Because of the broad nature of the specialty, family physicians will often be required to provide evidence of competence when requesting hospital privileges. The best defense against difficulties in credentialing and our best hope to continue providing the services to our patients for which we are trained are to create and keep current a strong documentation system of personal training and experience.

Accreditation↗