A summary of the main themes and findings presented at the ASM Intermountain Branch meeting (2024).

The annual meeting for the Intermountain Branch was held in April 2024 on the campus of Brigham Young University. There were 127 branch members from Utah, Idaho, and Nevada who attended the meeting and were composed of undergraduate students, graduate or medical students, and faculty. This report highlights the diversity of, and the emerging trends in, the research conducted by American Society for Microbiology members in the Intermountain Branch.

Improved quality of colon cancer surveillance after implementation of a personalized surveillance schedule.

Background: Early detection of recurrence through surveillance after curative surgery for primary colon cancer is recommended. We previously reported inadequate quality of surveillance among patients operated for colon cancer. These poor results led to the introduction of a personalized surveillance schedule.

Successful systemic high-dose ribavirin treatment of respiratory syncytial virus-induced infections occurring pre-engraftment in allogeneic hematopoietic stem cell transplant recipients.

Introduction: Respiratory syncytial virus (RSV) is a frequent cause of respiratory tract infectious disease (RTID) in allogeneic hematopoietic stem cell transplant (HSCT) recipients associated with a high mortality once infection has progressed from upper RTID (URTID) to lower RTID (URTID). Aerosolized ribavirin (RBV) is considered a cornerstone of treatment, but is expensive and has toxic side effects on patients and staff. In this study, RSV infection was detected by polymerase chain reaction (PCR) from routinely collected throat swabs in HSCT patients.

Adaptor protein Lnk binds to and inhibits normal and leukemic FLT3.

Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase with important roles in hematopoietic progenitor cell survival and proliferation. It is mutated in approximately one-third of AML patients, mostly by internal tandem duplications (ITDs). Adaptor protein Lnk is a negative regulator of hematopoietic cytokine signaling.

Severe maternal morbidity and near misses in a regional reference hospital.

Objective: To investigate severe maternal morbidity/near misses in a tertiary public maternity in the state of Rio de Janeiro, using different identification criteria.

Methods: This is a cross-sectional study, performed in a regional reference hospital between June and October 2009, on severe maternal morbidity/near miss cases identified from the log books of the maternity hospital and review of medical records. This study focused on women who, during pregnancy, delivery, or the postpartum period, showed no clinical symptoms compatible with the defining criteria for severe maternal morbidity/near miss of Waterstone et al, Mantel et al.

Enhanced immune response after a second dose of an AS03-adjuvanted H1N1 influenza A vaccine in patients after hematopoietic stem cell transplantation.

Seroconversion rates following influenza vaccination in patients with hematologic malignancies after hematopoietic stem cell transplantation (HSCT) are known to be lower compared to healthy adults. The aim of our diagnostic study was to determine the rate of seroconversion after 1 or 2 doses of a novel split virion, inactivated, AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HSCT recipients (ClinicalTrials.gov Identifier: NCT01017172).

Adaptor protein Lnk binds to PDGF receptor and inhibits PDGF-dependent signaling.

Objective: Platelet-derived growth factor receptors α and β (PDGFRA, PDGFRB) are frequently expressed on hematopoietic cells and regulate cellular responses such as proliferation, differentiation, survival, and transformation. Stimulation by autocrine loops or activation by chromosomal translocation makes them important factors in development of hematopoietic disorders. Interaction with the ligand PDGF results in activation of the tyrosine kinase domain and phosphorylation of tyrosine residues, thereby creating binding sites for molecules containing Src homology 2 domains.

Identification of defects in the transcriptional program during lineage-specific in vitro differentiation of CD34(+) cells selected from patients with both low- and high-risk myelodysplastic syndrome.

Objective: Development of myelodysplastic syndrome (MDS) is suggested to follow a multistep pathogenesis and is characterized by accumulation of molecular defects of the hematopoietic stem/progenitor cells, resulting in aberrant differentiation and proliferation.

Materials And Methods: To detect alterations within the transcriptional program in MDS-derived CD34(+) cells during lineage-specific differentiation, we performed serial gene expression analysis of in vitro differentiated erythro-, granulo-, and megakaryopoietic cells using oligonucleotide microarrays (HG-U133A, Affymetrix, Santa Clara, CA, USA). For selected genes, expression data were confirmed using real-time polymerase chain reaction.

Adaptor protein Lnk inhibits c-Fms-mediated macrophage function.

The M-CSFR (c-Fms) participates in proliferation, differentiation, and survival of macrophages and is involved in the regulation of distinct macrophage functions. Interaction with the ligand M-CSF results in phosphorylation of tyrosine residues on c-Fms, thereby creating binding sites for molecules containing SH2 domains. Lnk is a SH2 domain adaptor protein that negatively regulates hematopoietic cytokine receptors.

Identified hidden genomic changes in mantle cell lymphoma using high-resolution single nucleotide polymorphism genomic array.

Objective: Mantle cell lymphoma (MCL) is a lymphoma characterized by aberrant activation of CCND1/cyclin D1 followed by sequential genetic abnormalities. Genomic abnormalities in MCL have been extensively examined by classical cytogenetics and microarray-based comparative genomic hybridization techniques, pointing out a number of alterations in genomic regions that correlate with the neoplastic phenotype and survival. Recently, single nucleotide polymorphism genomic microarrays (SNP-chip) have been developed and used for analysis of cancer genomics.

Prediction of qualitative outcome of oligonucleotide microarray hybridization by measurement of RNA integrity using the 2100 Bioanalyzer capillary electrophoresis system.

RNA quality is critical to achieve valid results in microarray experiments and to save resources. The RNA integrity number (RIN) can be measured with minimal sample consumption by microfluidics-based capillary electrophoresis. To determine whether RIN can predict the qualitative outcome of microarray hybridization, we measured RIN in total RNA samples from 484 different experiments by the 2100 Bioanalyzer system and correlated with the percentage of present calls (%pc) of downstream oligonucleotide microarrays.

Expression of the adaptor protein Lnk in leukemia cells.

Objective: Tyrosine kinases are involved in cytokine signaling and are frequently aberrantly activated in hematological malignancies. Lnk, a negative regulator of cytokine signaling, plays critical nonredundant roles in hematopoiesis. By binding to phosphorylated tyrosine kinases, Lnk inhibits major cytokine receptor signaling, including c-KIT; erythropoietin receptor-Janus kinase 2 (JAK2); and MPL-JAK2.

Lnk inhibits myeloproliferative disorder-associated JAK2 mutant, JAK2V617F.

The JAK2 mutation JAK2V617F is found frequently in patients with myeloproliferative disorders (MPD) and transforms hematopoietic cells to cytokine-independent proliferation when expressed with specific cytokine receptors. The Src homology 2 (SH2) and pleckstrin homology (PH) domain-containing adaptor protein Lnk (SH2B3) is a negative regulator of hematopoietic cytokine signaling. Here, we show that Lnk is a potent inhibitor of JAK2V617F constitutive activity.

Novel acyl sulfonamide LY573636-sodium: effect on hematopoietic malignant cells.

LY573636-sodium is a promising anti-tumor agent, which causes growth arrest and apoptosis of a variety of human solid tumors in vitro and in vivo. Moreover, studies have shown that the compound is selectively toxic towards tumor cells over their normal counterparts. This targeted effect makes LY573636 a candidate for combined therapy regimens in patients with advanced or resistant cancers.

Adaptor protein Lnk associates with Tyr(568) in c-Kit.

The adaptor protein Lnk is expressed in haemopoietic cells and plays a critical role in haemopoiesis. Animal model studies demonstrated that Lnk acts as a broad inhibitor of signalling pathways in haemopoietic lineages. Lnk belongs to a family of proteins sharing several structural motifs, including an SH2 (Src homology 2) domain which binds phosphotyrosine residues in various signal-transducing proteins.

Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells.

Cucurbitacins have long been utilized for their abortifacient and anti-inflammatory effects; however, little is known about their mechanism of action. In this study, we have demonstrated robust antiproliferative effects of CuB on various leukemia and lymphoma cell lines, as well as on primary mononuclear bone marrow cells derived from patients with acute myeloid leukemia or myelodysplastic syndrome. Myeloid leukemic cells treated with CuB exhibit significant S-phase cell cycle arrest, enlarged cell size, multinucleation, and enhanced expression of a monocytic- and granulocytic-specific CD11b.

Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders.

Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL.

Severe rhabdomyolysis, acute renal failure and posterior encephalopathy after 'magic mushroom' abuse.

We report the case of a 25-year-old, hepatitis C-infected man, who presented with severe rhabdomyolysis and acute renal failure, and later developed posterior encephalopathy with cortical blindness after the ingestion of magic mushrooms. Conventional respiratory and cardiovascular support including mechanical ventilation, continuous veno-venous hemodialysis and corticosteroids led to improvement and the patient recovered completely over the following months. Magic mushrooms are becoming increasingly fashionable among drug users, as they are believed to be more harmless than other hallucinogenic designer drugs.

Combat burn life support: a military burn-education program.

The Advanced Burn Life Support Course has been used to train military physicians and nurses for more than 16 years. Although it useful for teaching the fundamentals of burn care, the course is designed for a civilian audience, covers only the first 24 hours of burn care, and presumes the availability of a burn center for patient transfer. In preparation for hostilities in Iraq, we developed several add-on modules to the standard Advanced Burn Life Support course to meet specific needs of military audiences.

Arterial-venous carbon dioxide tension difference during severe hemorrhage and resuscitation.

Purpose: To define clinically useful markers for determining the adequacy of resuscitation after hemorrhage.

Design: Prospective study of 20 Yorkshire swine, using an established model for hemorrhagic shock in swine.

Background And Methods: Clinically useful markers for assessing the adequacy of resuscitation after hemorrhage do not exist.

Cerebral electrophysiologic effects of resuscitation with hypertonic saline-dextran after hemorrhage.

When brain injury accompanies hemorrhage, resuscitation with hypertonic saline (HS) improves intracranial pressure (ICP) and elastance; however, its effect on brain function after a traumatic or ischemic insult has not been assessed. This study compares the electrophysiologic response to hemorrhage and resuscitation with 7.5% NaCl + 6% dextran (HSD), 6% hetastarch (HE), or 0.

A comparison of the cerebral and cardiovascular effects of complete resuscitation with isotonic and hypertonic saline, hetastarch, and whole blood following hemorrhage.

Hemorrhagic shock and closed head injury often accompany severe trauma. Hypertonic saline may be beneficial in these patients, but few have examined its properties when sufficient volume is infused to achieve sustained resuscitation. Solutions of 6% NaCl (HS), 0.