Creating a Diverse Physician Workforce Through Training in Diversity, Bias, and Selection: An Innovative Approach to Preparing Medical Students as Future Academic Leaders.

Medical students are the future of academic medicine. They will serve as admissions committee members, deans, and program directors with responsibility for selecting future physicians. At the same time, schools and programs are working to diversify the physician workforce to care for diverse patient populations.

Competency-based education in transitioning nurse practitioner students from education into practice.

Competency-based education (CBE) provides a framework for nursing programs including those educating nurse practitioners (NPs). The basic assumption of CBE is that the student will demonstrate acquisition of the identified essential knowledge, skills, and attitudes expected for the designated educational process before leaving the learning environment. The work done to date in developing competencies and progression indicators provides the critical basis to move toward a common language and clear expectations for the continuum of linear progression of proficiency.

Neutrophils contain prolyl endopeptidase and generate the chemotactic peptide, PGP, from collagen.

Prolyl endopeptidase (PE), a protease that cleaves after proline residues in oligopeptides, is highly active in brain and degrades neuropeptides in vitro. We have recently demonstrated that PE, in concert with MMP's, can generate PGP (proline-glycine-proline), a novel, neutrophil chemoattractant, from collagen. In this study, we demonstrate that human peripheral blood neutrophils contain PE, which is constitutively active, and can generate PGP de novo from collagen after activation with LPS.

[Synthesis of olean-18(19)-ene derivatives from betulin].

The rare olean-18(19)-ene triterpenoids moradiol and moronic acid were synthesized from betulin, and their antiviral properties were investigated.

The presence of a matrix-derived neutrophil chemoattractant in bronchiolitis obliterans syndrome after lung transplantation.

Lung transplantation is a therapeutic modality frequently used in end-stage lung disease. Unfortunately, lung transplant recipients have poor clinical outcomes, often due to the development of bronchiolitis obliterans syndrome (BOS). This process is often characterized by the pathologic findings of obliterative bronchiolitis: neutrophil influx and extracellular matrix remodeling leading to luminal obstruction and airway inflammation.

[Transformation of betulin diacetate by the Prins reaction].

The interaction of betulin diacetate with formaldehyde by the Prins reaction in various media was studied. As a result, 3beta,28-di-O-acetyl-30-hydroxymethyl-(20)29-lupene, 3beta-acetyl-28-hydroxy-(20)29-lupene, and 3beta,28-di-O-acetoxy-19-(5',6'-dihydro-2'H-pyran-4'-yl)-20,29,30-trinorlupane were obtained.

[Synthesis and antiviral activity of lupane triterpenoids with modified cycle E].

A reductive transformation of the peroxide products of ozonolysis of derivatives of 3beta-O-acetyl-22(17-->28)-abeo-lupa-17(28),20(29)-diene and the subsequent intramolecular ketalization led to a compound with a trioxane fragment. This is a new approach to a skeletal modification of triterpenoid cycle E. An activity of the synthesized compounds was found toward the viruses of type A influenza and herpes simplex.

Possible therapeutic vaccines for canine myasthenia gravis: implications for the human disease and associated fatigue.

Myasthenia gravis (MG) is caused by T cell-dependent antibodies reactive with acetylcholine receptors. These autoreactive antibodies cause muscle weakness by interfering with neuromuscular transmission via removal of acetylcholine receptors from the neuromuscular junction as well as changing the architecture of the junction itself. Consequently, muscle fatigue is a debilitating aspect of MG often leading to more general feelings of tiredness not directly due to muscle weakness.

A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation.

We describe the tripeptide neutrophil chemoattractant N-acetyl Pro-Gly-Pro (PGP), derived from the breakdown of extracellular matrix (ECM), which shares sequence and structural homology with an important domain on alpha chemokines. PGP caused chemotaxis and production of superoxide through CXC receptors, and administration of peptide caused recruitment of neutrophils (PMNs) into lungs of control, but not CXCR2-deficient mice. PGP was generated in mouse lung after exposure to lipopolysaccharide, and in vivo and in vitro blockade of PGP with monoclonal antibody suppressed PMN responses as much as chemokine-specific monoclonal antibody.

[Synthesis and antiviral activity of amides and conjugates of betulonic acid with amino acids].

Betulonic acid amides with aliphatic and heterocyclic amines and with L-amino acids were synthesized by the acid chloride method. Betulonic acid amide and L-methionine derivatives of betulonic acid and its 3-oxime effectively inhibit the influenza A virus. Betulonic acid octadecylamide is active against the herpes simplex type 1 virus.

[Synthesis and antiviral activity of ureides and carbamates of betulinic acid and its derivatives].

Ureides and carbamates of betulinic acid and its derivatives were prepared in good yields by interaction of betulinic acid, betulonic acid, and betulonic acid 3-oxime with amines, amino acids, and alcohols. Ureides of betulonic acid containing L-Val and L-Met residues were found to be effective against herpes simplex type 1 virus. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2003, vol.

[Study of pharmacological properties of betulin bishemiphthalate].

The results of pharmacological tests showed that betulin bishemiphthalate possesses hepatoprotector, antioxidant, and immunotropic properties. Administered in combination with hydroxymethyluracil, that betulin bishemiphthalate prevented the loss of experimental animals upon irradiation.

[Synthesis and antiviral activity of hydrazides and substituted benzalhydrazides of betulinic acid and its derivatives].

New nitrogen-containing derivatives of betulinic and betulonic acids, hydrazides and N'-benzalhydrazides, were synthesized. Their antiviral activities toward of influenza A virus, herpes simplex type I virus, enterovirus ECHO6, and HIV-1 were studied in vitro. Betulinic acid 3-oxime was found to have the highest activity against the influenza virus.

Prevention and reversal of experimental autoimmune myasthenia gravis by a monoclonal antibody against acetylcholine receptor-specific T cells.

We have recently described an algorithm to design, among others, peptides with complementarity contour to autoimmune epitopes. Immunization with one such peptide resulted in a monoclonal antibody (mAb), termed CTCR8, that specifically recognized Vbeta15 containing TCR on acetylcholine receptor (AChR) alpha-chain residue 100-116-specific T cells. CTCR8 was found to label the cell surface of AChR100-116-specific T cell lines and clones, immunoprecipitate the TCR from such cells, and block their proliferative responses to AChRalpha100-116.

An IgM anti-MBP Ab in a case of Waldenstrom's macroglobulinemia with polyneuropathy expressing an idiotype reactive with an MBP epitope immunodominant in MS and EAE.

In a previously described case of Waldenstrom's Macroglobulinemia, complicated by polyneuropathy, the IgM/lambda monoclonal antibody (mAb) was highly reactive with myelin basic protein (MBP). Given our demonstration that V lambda x, a recently described murine lambda variable region gene product, can itself bind MBP as well as confer MBP reactivity to an Ab, the possibility of a shared idiotypy between murine V lambda x and this human IgM/lambda anti-MBP was investigated. We characterized the epitope specificity of the macroglobulinemia patient's MBP-reactive IgM/lambda using indirect ELISA procedures with MBP, a citrullinated isomer of MBP termed C8, or peptide fragments of MBP as the coating antigens and monospecific Ab to V lambda x as the secondary Ab.

[Synthesis of the lupane group triterpenoids and there hepatoprotective activity].

Hemisuccinates, hemiphthalates, acetylsalicylates, cinnamates, and p-methoxycinnamates of lupeol, betulin, and 3-O-acetylbetulin were synthesized via interaction with corresponding acid anhydrides or acid chlorides. A number of betulin esters in position 3 and 28 were shown to exhibit a pronounced hepatoprotective effect similar to that of betulin and silibor. These experimental data were in a good agreement with the computer prediction of their biological activity.

Highly related immunoglobulin light chain sequences in different multiple sclerosis patients.

Although immunoglobulin G and free light (L) chains of oligoclonal origin in cerebrospinal fluid (CSF) are the most common immunologic abnormalities in multiple sclerosis (MS), it is unknown whether homologous CSF L chain sequences are present in different individuals with MS. Using Southern blotting, a particular kappa (kappa) L chain variable region (V) probe was recently found to hybridize to Vkappa cDNA from CSF B cells from almost one half of the MS patients tested but only 10% of normal or other neurologic disease controls [Zhou, S.-R.

Preferential association of V lambda x light chains with gamma 2a heavy chains in naturally occurring human myelin basic protein reactive antibodies.

Active immunization with myelin basic protein (MBP) induces experimental allergic encephalomyelitis (EAE) in a variety of animal species, including rats and mice. We have previously described the ability of the newly described mouse lambda (lambda) variable (V) region V lambda x, to confer MBP reactivity to an Ab. In this report, we have evaluated the heavy (H) chain isotype distribution of V lambda x-bearing Abs in normal mouse serum.

Prevention of experimental autoimmune myasthenia gravis by a monoclonal antibody to a complementary peptide for the main immunogenic region of the acetylcholine receptors.

We have previously reported that a complementary peptide (denoted RhCA 67-16), encoded by RNA complementary to that of the Torpedo acetylcholine receptor (AChR) main immunogenic region (MIR), AChR residues alpha 61-76, induces polyclonal and monoclonal Ab reactive with Ig against the AChR MIR. RhCA 67-16 vaccination also protected against the development of experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. In the present report, we found that a mAb (denoted TCM 240, IgG1 kappa) against RhCA 67-16 recognized three different idiotypic Ab (mAb 6, mAb 35, and mAb 198), which were previously reported by others to recognize the AChR MIR and to cause EAMG.

Murine V lambda x and V lambda x-containing antibodies bind human myelin basic protein.

Myelin basic protein (MBP) is highly immunogenic and a known autoantigen capable of inducing experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis. We have previously described a murine monoclonal antibody (mAb), F28C4, directed against the encephalitogenic MBP peptide acetyl (Ac) 1-9, which contains a V lambda x light chain. Considering the rarity of V lambda x usage, we determined whether other Abs having V lambda x light chains shared similar antigen (Ag) specificity.

A V lambda x-bearing monoclonal antibody with similar specificity and sequence to encephalitogenic T cell receptors.

The fine specificity of mAb F28C4 to myelin basic protein (MBP), acetyl residues 1-9, has been compared with the previously described specificity of an encephalitogenic T cell clone, PJR-25. F28C4 has been found to express a cross-reactive idiotope (CRI) that is shared with MBP acetyl peptide 1-9-specific TCR. The CRI seems to be located at or near the Ag-combining site of F28C4 and the TCR and, thus, might possibly result from overlapping epitope specificity.

Role of leukocyte-derived pro-opiomelanocortin peptides in endotoxic shock.

The immune and neuroendocrine systems communicate and maintain homeostasis through various mechanisms, including the use of common signal and recognition molecules and the use of similar processes. This type of integrated network has profound effects on the onset and outcome of certain disease states, including endotoxic shock, in which a cascade of mediators influence the pathophysiologic responses. We have found that some of the common signal molecules shared between the immune and neuroendocrine systems are the peptide hormones adrenocorticotropin (ACTH) and endorphins (END).

Detection of growth hormone and growth hormone-releasing hormone-related messenger RNA in rat leukocytes by the polymerase chain reaction.

To validate that growth hormone (GH) and growth hormone-releasing hormone (GHRH) can be produced by leukocytes, we have assessed the presence of GH and GHRH-related mRNA in leukocyte cultures by reverse transcription and the polymerase chain reaction. A sample of the polymerase chain reactions were size-fractionated by electrophoresis in a 0.8% agarose gel and examined with ultraviolet light after ethidium bromide staining.

Corticotropin-releasing factor upregulates expression of two truncated pro-opiomelanocortin transcripts in murine lymphocytes.

Lymphocytes harbor a pro-opiomelanocortin (POMC) mRNA. In this report, a novel procedure was used to study the exonic arrangement of this transcript in lymphocytes. Poly(A)+ mRNA, purified from both corticotropin-releasing factor (CRF)-treated and nontreated lymphocytes, was selectively reverse-transcribed using an antisense oligonucleotide primer complementary to the 3' junction of the translated/nontranslated region of exon 3 of POMC.