From the vantage point of her personal experience, the author examines milestones since the 1960s which have changed the medical library profession and helped shape the Medical Library Association. The advent of automation, including cataloging with OCLC and online literature searching through the SUNY Biomedical Communication Network, was a dramatic event that transformed the work and priorities of librarians, fulfilling the dreams of earlier visionaries. The application of technology in libraries led to an increased demand for education and training for librarians. The Medical Library Association responded with continuing education programs, and a series of important reports influenced how the association filled its role in professional development. Legislation providing federal funding, such as the Medical Library Assistance Act, resulted in a period of expansion for libraries and their services. The Medical Library Association has developed a legislative agenda to influence action in areas such as copyright. In the future, health sciences librarians must take a leadership role.
A discriminant analysis was conducted to investigate how an essay, a mathematics/science type of essay, a college scholastic ability test, and grade point average affect acceptance to a pre-med course at a Korean medical school. Subjects included 122 and 385 applicants for, respectively, early and regular admission to a medical school in Korea. The early admission examination was conducted in October 2007, and the regular admission examination was conducted in January 2008. The analysis of early admission data revealed significant F values for the mathematics/science type of essay (51.64; P<0.0001) and for grade point average (10.66; P=0.0014). The analysis of regular admission data revealed the following F values: 28.81 (P<0.0001) for grade point average, 27.47 (P<0.0001) for college scholastic ability test, 10.67 (P=0.0012) for the essay, and 216.74 (P<0.0001) for the mathematics/science type of essay. Since the mathematics/science type of essay had a strong effect on acceptance, an emphasis on this requirement and exclusion of other kinds of essays would be effective in subsequent entrance examinations for this premed course.
College Scholastic Ability Test; Entrance Examination; Essay; General Point Average; Mathematics/Science; Medical School
An increasing number of resources are becoming available to support the professional development of scientists transitioning to studying science education. CBE-Life Sciences Education is adding to the available professional development resources by launching a new type of essay, titled Research Methods.
Recent advances involving high-throughput techniques for data generation and analysis have made familiarity with basic bioinformatics concepts and programs a necessity in the biological sciences. Undergraduate students increasingly need training in methods related to finding and retrieving information stored in vast databases. The rapid rise of bioinformatics as a new discipline has challenged many colleges and universities to keep current with their curricula, often in the face of static or dwindling resources. On the plus side, many bioinformatics modules and related databases and software programs are free and accessible online, and interdisciplinary partnerships between existing faculty members and their support staff have proved advantageous in such efforts. We present examples of strategies and methods that have been successfully used to incorporate bioinformatics content into undergraduate curricula.
Introduction The development of professional behaviour is an important objective for students in Health Sciences, with reflective skills being a basic condition for this development. Literature describes a variety of methods giving students opportunities and encouragement for reflection. Although the literature states that learning and working together in peer meetings fosters reflection, these findings are based on experienced professionals. We do not know whether participation in peer meetings also makes a positive contribution to the learning experiences of undergraduate students in terms of reflection. Aim The aim of this study is to gain an understanding of the role of peer meetings in students’ learning experiences regarding reflection. Method A phenomenographic qualitative study was undertaken. Students’ learning experiences in peer meetings were analyzed by investigating the learning reports in students’ portfolios. Data were coded using open coding. Results The results indicate that peer meetings created an interactive learning environment in which students learned about themselves, their skills and their abilities as novice professionals. Students also mentioned conditions for a well-functioning group. Conclusion The findings indicate that peer meetings foster the development of reflection skills as part of professional behaviour.
Reflection; Peer meetings; Professional behaviour; Teaching; Collaborative learning
Thoracic sarcoidosis is a common disease, with well-described and recognizable radiographic features. Nevertheless, most physicians are not familiar with the rare atypical often-confusing manifestations of thoracic sarcoid. Although these findings have been previously reviewed, but more recent advances in imaging and laboratory science, need to be incorporated. We present a review of literature and illustrate the review with unpublished data, intended to provide a more recent single comprehensive reference to assist with the diagnosis when atypical radiographic findings of thoracic sarcoidosis are encountered. Thoracic involvement accounts for most of morbidity and mortality associated with sarcoidosis. An accurate timely identification is required to minimize morbidity and mortality. It is essential to recognize atypical imaging findings and relate these to clinical manifestations and histology.
Atypical; cardiology; chest; radiology; sarcoidosis
Certain statements concerning the relation of posture and movement which have become traditional are re-examined--in particular, the statement 'Movement (that is, pysiological movement) consists of a series of postures. The theme of the essay is the posture--that is, postural activity--should be regarded as a function in its own right and not merely as a component of movement and, secondly, that expressions such as a' series of postures' or 'a change of posture' are not valid as definitions of physiological movement is general, but describe only movement which is part of the postural function. Voluntary movement consists of much more than a series of postures and its significance, ordinarily, is not postural.
Ultrasound (US) is the most commonly used imaging method for studying urinary tract disorders in dogs, as it is easy to perform, inexpensive and provides excellent contrast resolution in real-time. However, US examination of dogs presents a series of technical difficulties, and the US operator must therefore have a longstanding experience and access to high-quality equipment including a range of different probes to achieve a correct diagnosis. The aim of this mini-pictorial essay is to describe US findings and patterns which permit identification of the most common pathologies of the urinary tract in dogs. The technical difficulties that may be encountered are also evaluated as well as integration with other imaging modalities (traditional X-ray, computed tomography, magnetic resonance imaging).
Ultrasound; Canine pathology; Urinary system; Sonography
Protein secretion systems are molecular nanomachines used by Gram-negative bacteria to thrive within their environment. They are used to release enzymes that hydrolyze complex carbon sources into usable compounds, or to release proteins that capture essential ions such as iron. They are also used to colonize and survive within eukaryotic hosts, causing acute or chronic infections, subverting the host cell response and escaping the immune system. In this article, the opportunistic human pathogen Pseudomonas aeruginosa is used as a model to review the diversity of secretion systems that bacteria have evolved to achieve these goals. This diversity may result from a progressive transformation of cell envelope complexes that initially may not have been dedicated to secretion. The striking similarities between secretion systems and type IV pili, flagella, bacteriophage tail, or efflux pumps is a nice illustration of this evolution. Differences are also needed since various secretion configurations call for diversity. For example, some proteins are released in the extracellular medium while others are directly injected into the cytosol of eukaryotic cells. Some proteins are folded before being released and transit into the periplasm. Other proteins cross the whole cell envelope at once in an unfolded state. However, the secretion system requires conserved basic elements or features. For example, there is a need for an energy source or for an outer membrane channel. The structure of this review is thus quite unconventional. Instead of listing secretion types one after each other, it presents a melting pot of concepts indicating that secretion types are in constant evolution and use basic principles. In other words, emergence of new secretion systems could be predicted the way Mendeleïev had anticipated characteristics of yet unknown elements.
cell envelope; nanomachine; macromolecular complex; channel; targeting
Crossed immunoelectrophoresis of Triton X-100 solubilized proteins from normal and abnormal platelets was performed with rabbit antibodies raised against normal platelets. In Bernard-Soulier platelets protein 13 was not detected, and neither the amphiphilic (probably GP Ib) nor the hydrophilic (glycocalicin) glycocalicin-related proteins were seen when monospecific antiglycocalicin antiserum was used. The most prominent precipitate, 16, and platelet fibrinogen, 24 were not detected in platelets of two patients with type I thrombasthenia, whereas in one patient with type II thrombasthenia fibrinogen was clearly detected, but the amount of protein 16 remained severely reduced. Protein 16 was heavily labeled after lactoperoxidase-catalyzed 125I iodination of normal platelets, and was precipitated by IgG-L, an alloantibody from a polytransfused thrombasthenic patient. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) or protein 16 cut out from immunoplates showed two 125I-labeled glycoprotein bands, which migrate as GP IIb and GP IIIa. SDS-PAGE of 125I-labeled type I thrombasthenic platelets showed no periodic acid-Schiff bands or peaks of radioactivity in the GP IIb and GP IIIa regions, whereas in the GP I region both the periodic acid-Schiff band intensity and the radiolabeling were within the normal range. Autoradiography after crossed immunoelectrophoresis of iodinated thrombasthenic platelets showed that the bulk of radioactivity was bound to protein 17. This glycoprotein, which was also present in normal and Bernard-Soulier platelets, migrates in the GP I region on SDS-PAGE. Thus, the bulk of radioactivity observed in the GP I region after SDS-PAGE is associated with protein 17 and not with glycocalicin.
We have studied a patient with a congenital bleeding disorder and phenotypic manifestations typical of Bernard-Soulier syndrome, including giant platelets with absent ristocetin-induced von Willebrand factor binding. Two monoclonal antibodies reacting with distinct epitopes in the amino-terminal domain of the alpha-chain of glycoprotein (GP) Ib were used to estimate the number of GP Ib molecules on the platelet membrane. In the patient, binding of one antibody (LJ-Ib10) was approximately 50% of normal, while binding of the other (LJ-Ib1) was absent. Binding of both antibodies was reduced to approximately 50% of normal in the mother and one sister of the propositus, and their platelets exhibited approximately 70% of normal von Willebrand factor binding. Immunoblotting studies confirmed the presence of GP Ib alpha, as well as GP IX, in patient platelets. Antibody LJ-Ib10, but not LJ-Ib1, could immunoprecipitate the patient's GP Ib alpha from surface-labeled proteins. Thus, platelets from the propositus contained a structurally and functionally altered GP Ib-IX complex lacking a specific antibody epitope and the ability to bind von Willebrand factor. In contrast, the binding of human alpha-thrombin to the patient's platelets was normal, and three classes of binding sites with high, intermediate, and low affinity could be detected. These studies define a distinct variant form of Bernard-Soulier syndrome and provide evidence, based on a naturally occurring mutant molecule, that the amino-terminal region of GP Ib alpha contains a von Willebrand factor-binding domain distinct from the high affinity thrombin-binding site. Use of different monoclonal antibodies with distinct epitope specificities appears to be essential for a correct identification of variant Bernard-Soulier syndrome.
Two hereditary platelet disorders, Bernard-Soulier syndrome and Glanzmann's thrombasthenia, are characterized by selective deficiencies of platelet membrane glycoproteins. Murine monoclonal antibodies were developed against platelet membrane glycoprotein Ib and against the glycoprotein IIb/IIIa complex. A rapid whole blood assay for the deficiency of these glycoproteins was developed and used to study whole blood samples from six patients with Glanzmann's thrombasthenia and three patients with Bernard-Soulier syndrome. Patients with type I and type II Glanzmann's thrombasthenia were easily detectable with this assay. This permits the diagnosis of these disorders on 200 microliters of whole blood within 2 h of blood sampling.
A patient with a lymphoproliferative disorder developed bleeding associated with a prolonged bleeding time and a selective defect of platelet aggregation in response to ristocetin. The patient's purified IgG was shown to inhibit aggregation of washed normal platelets by ristocetin and von Willebrand factor (F VIII:vWF). By Western blotting, it was shown that antibody bound specifically to an antigen of Mr 210,000 present on normal platelets but missing on platelets from patients with congenital Bernard-Soulier syndrome (BSS). Binding was effected by the F(ab)2 portion of the IgG, indicating the presence of an autoantibody rather than an immune complex. These results suggest that the 210,000-Mr protein is involved in the interaction of F VIII:vWF with platelets. Furthermore, we have demonstrated the apparent absence of an additional protein on congenital BSS platelets. Heat-aggregated IgG was also shown to bind to the 210,000-Mr protein, suggesting that this protein may function as an Fc receptor on platelets. The relationship of the 210,000-Mr protein to glycoprotein Ib and the precise role of this protein in the interaction of platelets with F VIII:vWF need to be characterized.
Leucine-rich repeats are a conserved structural motif, of yet undefined significance, found in a group of proteins from different species. Among these are the four components of the human platelet glycoprotein Ib-IX-V complex, a membrane receptor that performs an essential role in the thrombogenic function of platelets by interacting with the adhesive protein, von Willebrand factor. We have found that a single amino acid substitution (Ala156-->Val) within one of the six leucine-rich repeats in the alpha-subunit of glycoprotein Ib results in a variant form of the congenital bleeding disorder, Bernard-Soulier syndrome, characterized by giant dysfunctional platelets. Genetic studies of the propositus and his family members were complemented by immunological and functional analysis of expressed recombinant GP Ib alpha fragments to demonstrate that the observed mutation is the cause of defective von Willebrand factor binding. These studies define the molecular basis of the Bernard-Soulier syndrome within this family and demonstrate that structural integrity of a leucine-rich repeat is necessary for normal function of the glycoprotein Ib-IX-V receptor complex and, possibly, for normal platelet morphology.
Previous reports have described conflicting results concerning the glycoprotein (GP) and protein composition of Bernard-Soulier platelets. In view of this controversy we have analyzed the platelets of four Bernard-Soulier patients using improved single and two-dimensional sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis procedures. An absence of staining for carbohydrate of membrane GP Ib was characteristic for the platelets of each patient. Major periodate-Schiff staining bands corresponding to membrane GP IIb, IIIa, and IIIb were clearly detected and their presence was confirmed by two-dimensional SDS-polyacrylamide gel electrophoresis. The protein content of the Bernard-Soulier platelets was increased two- to fourfold. However, analysis of their protein composition using 7-12% acrylamide gradient gels showed normal polypeptide profiles. Lactoperoxidase-catalyzed 125I-labeling of the Bernard-Soulier platelet surface proteins was followed by SDS-polyacrylamide gel electrophoresis and autoradiography. No labeling in the Ib position was detected whereas the other major membrane GP, including Ia and IIa, were normally located. In contrast, GP Ib was clearly detected by periodate-Schiff staining and autoradiography when normal human platelets that had been exhaustively treated with neuraminidase before the lactoperoxidase-catalyzed iodination were analysed. No abnormalities were detected in the GP patterns of membranes isolated from the patients' erythrocytes. Only a severe molecular abnormality or possible deletion of GP Ib could account for this major platelet lesion in the Bernard-Soulier syndrome.
The platelet membrane receptor for quinidine- and quinine-dependent antibodies was studied in three patients with the Bernard-Soulier syndrome (BSS) and in normal subjects with immunologic techniques based on the release of 51Cr from labeled platelets. The receptor could not be detected on BSS platelets but was present on platelets from each of 180 normal subjects. BSS platelets reacted normally with other allo- and autoantibodies. In confirmation of previous reports, BSS platelets were found to be deficient in glycoproteins Ib and Is. However, after apparently total cleavage of these proteins from the membrane of normal platelets by controlled hydrolysis with trypsin or chymotrypsin, 80% of the drug-dependent antibody receptor activity was retained. These observations suggest the existence of an additional, hitherto unrecognized membrane defect in Bernard-Soulier platelets.
Platelets from two patients with Bernard-Soulier disease showed a reduction in their ability to bind human thrombin. Thrombin binding studies in the high affinity range showed 1,500 sites for the Bernard-Soulier platelets as against 4,000 for normal controls. However, the dissociation constant was the same for both normals and patients (4.4 nM) indicating identical affinity for thrombin at the available sites. In the low affinity range, the Bernard-Soulier platelets showed 8,800 thrombin binding sites as against 24,000 for the controls, but again with identical values of Kd (37 nM). In addition, platelets from these Bernard-Soulier patients showed a decreased rate of aggregation with thrombin at both optimal (300 mU/ml) and suboptimal (60 and 120 mU/ml) thrombin concentrations. The decreased amount of thrombin which can bind to Bernard-Soulier platelets and the decrease in thrombin-induced aggregation may partly explain the hemostatic defect in these patients. In addition, the identical ratios of high affinity and low affinity binding sites in normals and in patients (0.37 and 0.36, and 0.36, respectively) supports the idea of a single class of binding sites for thrombin on the platelet surface.
The antibiotic ristocetin only aggregates platelets in the presence of plasma von Willebrand factor. Platelets from patients with Bernard-Soulier syndrome do not aggregate upon addition of ristocetin although, in contrast to von Willebrand's disease, plasma levels of factor VIII complex (factor VIII clotting activity, von Willebrand factor activity, and von Willebrand antigen) are normal. The membrane surface of normal platelets was modified and compared to the surface of platelets from a patient with Bernard-Soulier syndrome in an attempt to identify the receptor involved in von Willebrand factor-ristocetin-induced aggregation. After the incubation of washed normal platelets with a preparation of ristocetin previously shown to contain a proteolytic contaminant, the aggregation response is significantly decreased on addition or normal plasma. Analaysis by gel electrophoresis of such platelets when stained for carbohydrate revealed a decrease in the relative amounts of membrane glycopro-eins. Chymotrypsin-treated normal platelets had less membrane glycoproteins in addition to giving a reduced aggregation response in ristocetin-induced aggregation. Staining of gels for protein and carbohydrate indicated that there was an extensive change in the surface of Bernard-Soulier platelets, whereas those from patients with von Willebrand's disease appeared the same as normal. Platelets from patients were labeled by the lactoperoxidase iodination technique. Not only was the relative intensity of staining of platelet-specific proteins and glycoproteins changed in Bernard-Soulier platelets, but the iodination of the glycoproteins on the membrane surface relative to other membrane constituents was lower. In contrast, platelets from patients with von Willebrand's disease showed a normal exposure of membrane components. These data suggest therefore that membrane glycoproteins may play a functional role in ristocetin-induced aggregation.
The platelets from three patients with Bernard-Soulier syndrome have been analyzed by surface-labeling coupled with two-dimensional gel electrophoresis and compared with normals. As well as the previously described absence or deficiency in glycoprotein (GP) Ib(alpha) it could be shown that GP Ib beta and an additional low molecular weight glycoprotein GP17 were not detectable using carbohydrate-labeling methods or deficient to the same extent as the GPIb alpha subunit. In addition, the thrombin cleavable glycoprotein could not be detected using carbohydrate-labeling methods in two patients and was deficient in a third. This finding was confirmed in a fourth patient by one-dimensional gel electrophoresis. Thus, the changes in the membrane of Bernard-Soulier platelets are more complex than previously thought.