Liberation of an interaction domain from the phosphotransfer region of CheA, a signaling kinase of Escherichia coli.

The CheA protein of Escherichia coli is a histidine autokinase that donates its phosphate groups to two target proteins, CheY and CheB, to regulate flagellar rotation and sensory adaptation during chemotactic responses. The amino-terminal third of CheA contains the autophosphorylation site, determinants needed to interact with the catalytic center of the molecule, and determinants needed for specific recognition of its phosphorylation targets. To understand the structural basis for these activities, we examined the domain organization of the CheA phosphotransfer region by using DNA sequence analysis, limited proteolytic digestion, and a genetic technique called domain liberation. Comparison of the functionally interchangeable CheA proteins of E. coli and Salmonella typhimurium revealed two extensively mismatched segments within the phosphotransfer region, 22 and 25 aa long, with sequences characteristic of domain linkers. Both segments were readily susceptible to proteases, implying that they have an extended, flexible structure. In contrast, the intervening segments of the phosphotransfer region, designated P1 and P2 (roughly 140 and 65 aa, respectively), were relatively insensitive, suggesting they correspond to more compactly folded structural domains. Their functional properties were explored by identifying portions of the cheA coding region capable of interfering with chemotactic behavior when "liberated" and expressed as polypeptides. P1 fragments were not inhibitory, but P2 fragments blocked the interaction of CheY with the rotational switch at the flagellar motor, leading to incessant forward swimming. These results suggest that P2 contains CheY-binding determinants which are normally responsible for phosphotransfer specificity. Domain-liberation approaches should prove generally useful for analyzing multidomain proteins and their interaction targets.     

Railways of the nineties

What killed the railways was that they were run by people who really liked choo-choos. This also is the Achilles' heel of hospitals. They are run by people fascinated with big white buildings and all they contain.     

Syncope-related trauma: rationale and yield of diagnostic studies

BACKGROUND: Syncope occasionally occurs in trauma patients. The most appropriate and cost-effective evaluation for such patients is unknown. METHODS: Trauma patients admitted to a Level I trauma center with a diagnosis of syncope or possible syncope between 1988 and 1994 were reviewed. History, physical examination, and past medical history were noted, as were the results of tests done as part of the syncope evaluation. RESULTS: Eighty-eight patients were reviewed; 45% had been injured in falls. Thirteen patients who remembered their entire injury and denied syncope as a cause had negative evaluations. History, physical examination, and admission laboratory values were helpful in diagnosis 59% of the time. Subsequent evaluation provided useful diagnostic information 30% of the time. No patients with normal admission electrocardiograms (EKGs) had cardiac causes for their syncope. CONCLUSIONS: (1) Patients with possible syncope without loss of consciousness require no further evaluation. (2) A cerebrovascular evaluation should be the initial diagnostic approach in patients with signs and symptoms suggestive of stroke or transient ischemic attack. (3) Possible syncope patients with normal admission EKGs should undergo computed tomography of the head and electroencephalography. Those with abnormal EKGs should undergo echocardiography.     

Improving communication among health professionals through education: a pilot study

Communication can be thought of as a message that is sent, received, and understood. Each discipline of the health profession has its own jargon and means of expressing ideas in shorthand. These separate forms of communicating are effective among those of the same background but are often at the root of misunderstandings between professional groups. This article reviews communication theory and traces the difficulties created when inter-disciplinary teams of healthcare try to work together and communicate. As multi-disciplinary teams are increasingly dealing with the complex problems of today's healthcare system, clear communication and understanding has never been more important. If educators could assist in creating an understanding of vocabulary used for decision processes, communication could improve. The authors of this study performed a multi-stage Delphi survey that grouped terms used by administrators and clinicians and produced a lexicon of corresponding terms. An expert panel then reviewed and modified the list. The result is a lexicon that can be useful to assist clinicians and administrators to communicate with each other. By utilizing clinical terminology, or vice versa, instead of management or clinical jargon, some of the translation done by administration or clinicians could be reduced. Examples of how the lexicon can be utilized are provided in the article. This includes using it in health administration education to demonstrate the variances in clinical/managerial terms. It could also be provided as a primer to physicians, nurses, and other health professionals who assume administrative positions to enhance their communication with administrators.     

Dental examinations for quality control: peer review versus self-assessment.

This paper reports the dental care norms for restorative dentistry collected from examinations of 1,466 patients in 105 dental offices in Washington State during 1976. These results are part of a larger study, "Assessment of Care and Continuing Dental Education," being conducted by the University of Washington with the endorsement and cooperation of the Washington State Dental Association. Treatments in volunteer offices were evaluated either by colleagues (peer review) or by the practitioner himself (self-assessment). Two hundred twenty-four of 1,196 eligible dentists volunteered for the study. Patients from the practitioners' offices were randomly selected from office files by project staff. The study tests the proposition that, using standardized clinical evaluation procedures and comparable samples of treatment, dentists will be more critical of their own work than that of others. Results suggest a generally high level of care provided by volunteer practitioners and that self-assessments were significantly more critical than peer review.     

Clinical pharmacology of moclobemide, a new reversible monoamine oxidase inhibitor

The clinical pharmacology of the new reversible monoamine oxidase (MAO) inhibitor, moclobemide, was examined in three separate studies in healthy male volunteers. In a single oral dose study, moclobemide (25-150 mg) was rapidly absorbed from the gastrointestinal tract and had a relatively short plasma half-life (mean 1.3 h after 150 mg). A decrease in the plasma concentrations of the noradrenaline metabolite 4- hydroxy-3-methoxyphenylglycol (HMPG), however, indicated a longer time to peak pharmacodynamic effect and longer duration of activity. Assay of platelet MAO activity did not reveal any evidence of irreversible inhibition of the B form of the isoenzyme. Single oral doses of moclobemide (150 and 300 mg) significantly lowered the threshold to the cardiovascular effects ('cheese reaction') of intravenous tyramine. However, after repeated administration of 100 mg three times daily for over 2 weeks, moclobemide caused significantly less potentiation than did phenelzine (15 mg three times per day) on the cardiovascular effects of oral tyramine, a clinically more relevant model. The MAO-B inhibitor, selegiline (5 mg once daily), also lowered the oral tyramine threshold significantly. Moclobemide was generally well tolerated by these healthy volunteers.     

Epidermotropic neuroendocrine carcinoma

Epidermotropic neuroendocrine carcinoma (NEC) is rare. Based on such a case in an 88-year-old woman with a facial NEC showing epidermotropism with a pagetoid growth pattern, we asked whether several similar tumors involving the epidermis could be easily differentiated by immunohistochemical methods. We constructed a panel of control cases (2 each) for NEC, clear cell Bowen's disease (CCBD), Paget's disease (PD), superficial basal cell carcinoma (SBCC), cutaneous T-cell lymphoma (CTTL), and superficial spreading malignant melanoma (SSMM) to compare with our patient. A panel of antibodies including epithelial membrane antigen (EMA), neuron specific enolase (NSE), AE1/3 cytokeratin (CK), carcinoembryonic antigen (CEA), leukocyte common antigen (LCA), S-100, and HMB-45 were applied. Cutaneous NEC controls and our patient's tumor were strongly positive for EMA and NSE and had paranuclear dot-like cytoplasmic positivity for CK. CCBD was moderate to strong for CK. PD was strong for CEA. SBCC was essentially negative for all. CTLL was strong for LCA. SSMM was strong for S-100 and HMB-45. Controls were either negative or weak for the antibodies not mentioned. We conclude that this antibody panel can reliably differentiate these epidermotropic or juxtaepidermal tumors in diagnostic dermatopathology and should be applied to lesions requiring separation beyond H & E capabilities, especially with superficial shave biopsies showing small cell "Pagetoid" growth patterns.