Application of a metatranscriptomics technology, CSI-Dx, for the detection of pathogens associated with prosthetic joint infections.

Preoperative identification of causal organism(s) is crucial for effective prosthetic joint infection treatment. Herein, we explore the clinical application of a novel metatranscriptomic (MT) workflow, CSI-Dx, to detect pathogens associated with prosthetic joint infection. MT provides insight into transcriptionally active microbes, overcoming limitations of culture-based and available molecular methods.

Vaccination counseling with and without excipient skin testing in patients with suspected allergic reactions to mRNA COVID-19 vaccines and patients with atopy.

Background: Allergic reactions have been reported with mRNA vaccines for COVID-19 prevention. Patients perceived to be at higher risk for a reaction may be referred to an allergist, although evaluation strategies may differ between allergists.

Objective: Our aim was to determine outcomes of COVID-19 vaccinations in patients evaluated by an allergist using different approaches.

A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases.

We report three new cases of a germline heterozygous gain-of-function missense (p.(Met1141Lys)) mutation in the C2 domain of phospholipase C gamma 2 (PLCG2) associated with symptoms consistent with previously described auto-inflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) syndrome and pediatric common variable immunodeficiency (CVID). Functional evaluation showed platelet hyper-reactivity, increased B cell receptor-triggered calcium influx and ERK phosphorylation.

Characterization of a Drosophila ortholog of the Cdc7 kinase: a role for Cdc7 in endoreplication independent of Chiffon.

Cdc7 is a serine-threonine kinase that phosphorylates components of the pre-replication complex during DNA replication initiation. Cdc7 is highly conserved, and Cdc7 orthologs have been characterized in organisms ranging from yeast to humans. Cdc7 is activated specifically during late G1/S phase by binding to its regulatory subunit, Dbf4.

Impact of resident participation in cataract surgery on operative time and cost.

Objective: To investigate the impact of resident participation in cataract surgery on operative time and cost.

Design: Retrospective chart review.

Participants: All patients who underwent phacoemulsification cataract surgery by an attending or resident surgeon of the Penn State Hershey Eye Center between July 1, 2004, and June 30, 2007.

Idiopathic hypertrophic pachymeningitis mimicking lymphoplasmacyte-rich meningioma.

A 28-year-old woman with a 6-year history of optic neuropathy and 8 years of hearing loss had enhancing dural lesions around the brain stem and in both internal auditory canals on MRI. Histopathology from cranial procedures performed in 1990 and 1993 was originally interpreted as inflammatory meningioma, now known as lymphoplasmacyte-rich meningioma (LRM). Because the clinical course was more consistent with a relapsing process, the original surgical specimens were restudied with additional immunocytochemical stains.

Role of the proteasome in TGF-beta signaling in lens epithelial cells.

Purpose: The durability of the ubiquitin proteasome pathway in the mammalian lens makes this enzyme system a potential contributor to certain cataracts and posterior capsular opacification (PCO). The present study addresses proteasome involvement in TGF-beta induced, cataract-associated gene activation in human lens cells.

Methods: HLE B-3 cells were treated with TGF-beta, in combination with the proteasome inhibitors MG-132 or lactacystin.

Proteome analysis of lens epithelia, fibers, and the HLE B-3 cell line.

Purpose: The purpose of this study is to compare the protein composition of the B-3 line of transformed human lens epithelial (HLE) cells to that of freshly dissected HLE cells. This provides baseline data on lens cell proteins from fresh lens cells and from the B-3 cell line, which is often used as a model system for the lens.

Methods: Human lens epithelial cells adherent to the lens capsule were dissected into central (undifferentiated) and peripheral (partially differentiated) populations.

Targeted disruption of specific steps of the ubiquitin-proteasome pathway by oxidation in lens epithelial cells.

Several steps in the ubiquitin-proteasome pathway have been shown to be inhibited in models of oxidative stress and aging. We have designed similar models of aging and oxidation in the HLE B-3 human lens epithelial cell line. Following hydrogen peroxide (H2O2) treatment, B-3 cells exhibited an expected activation of c-fos.

Duplicated regions of AF-4 intron 4 at t(4;11) translocation breakpoints.

Background: AF-4 is a common partner gene of MLL. AF-4 breakpoints occur in introns, but most AF-4 introns are uncharacterized.

Methods And Results: We cloned AF-4 intron 4 and examined the frequency of breakpoints in this intron.

Improved detection of posterior myocardial wall ischemia with the 15-lead electrocardiogram.

Background: A routine 12-lead electrocardiogram is commonly obtained to evaluate for possible acute myocardial infarction during the initial screening of patients with chest discomfort. Posterior myocardial infarction is commonly missed because it is not usually visible in the standard leads. In this study, we compared the sensitivity and specificity of posterior chest leads (V(7), V(8), and V(9)) and 12-lead electrocardiography in detecting posterior injury pattern during single-vessel percutaneous transluminal coronary angioplasty.

MLL genomic breakpoint distribution within the breakpoint cluster region in de novo leukemia in children.

Purpose: To assess translocation breakpoint distribution within the MLL genomic breakpoint cluster region (bcr), 40 cases of de novo leukemia in children were examined by karyotype and Southern blot analysis.

Patients And Methods: Criteria for inclusion were karyotypic or molecular rearrangement of chromosome band 11q23. Of the 40 cases, 31 occurred in infants.

RAS mutations in pediatric leukemias with MLL gene rearrangements.

Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene.

Panhandle polymerase chain reaction amplifies MLL genomic translocation breakpoint involving unknown partner gene.

We used a new approach called panhandle polymerase chain reaction (PCR) to clone an MLL genomic translocation breakpoint in a case of acute lymphoblastic leukemia of infancy in which karyotype analysis was technically unsuccessful and did not show the translocation partner. Panhandle PCR amplified known MLL sequence 5' of the breakpoint and 3' sequence from the unknown partner gene from a DNA template with an intrastrand loop schematically shaped like a pan with a handle. The 7-kb panhandle PCR product contained the translocation breakpoint in MLL intron 8.

The p53 gene in pediatric therapy-related leukemia and myelodysplasia.

We investigated the frequency of p53 mutations in 19 pediatric cases of therapy-related leukemia or myelodysplastic syndrome. Eleven children presented with acute myeloid leukemia, one with mixed-lineage leukemia, two with acute lymphoblastic leukemia, and five with myelodysplasia at times ranging from 11 months to 9 years after a primary cancer diagnosis. The primary cancers, which included 11 solid tumors and eight leukemias, were treated with various combinations of DNA topoisomerase II inhibitors, alkylating agents, or irradiation.

Clonal expansion of germline B-lineage acute lymphoblastic leukemia in severe combined immunodeficient mice.

CD19+ B lineage acute lymphoblastic leukemias (ALLs) with unrearranged Ig and TCR genes are designated germline B lineage ALLs. We used CDR3 PCR to determine whether pediatric germline B lineage ALLs contain minor subclones with rearranged Ig H V genes. In six of seven cases there were no PCR detectable CDR3 rearrangements.

Chromosome band 11q23 translocation breakpoints are DNA topoisomerase II cleavage sites.

Human leukemias with 11q23 translocations occur sporadically and after cancer treatment with DNA topoisomerase II-targeted drugs. To investigate this process, we examined DNA topoisomerase II cleavage in vitro in subclones of the normal 11q23 genomic homologue and a t(9;11) translocation breakpoint junction. Cleavage was assayed with limiting dilutions of enzyme in the presence or absence of epipodophyllotoxin and ATP.

Complex replication error causes p53 mutation in a Li-Fraumeni family.

We demonstrated a germline p53 replication error in two generations of a Li-Fraumeni family affected with liposarcoma, adrenocortical carcinoma, and osteosarcoma. The trinucleotide repeat mutation changed 5'-AGT GTG GTG GTG-3' at codons 215-218 to 5'-AGT TGG TTG GTG GTG-3'. The predicted protein would be elongated by one amino acid (val216-->trp leu) without a change in charge.

ALL-1 gene rearrangements in DNA topoisomerase II inhibitor-related leukemia in children.

We examined clinical, morphologic, and cytogenetic features and ALL-1 (MLL, Htrxl, HRX) gene rearrangements in 17 cases of secondary leukemia that occurred 11 months to 9 years from diagnoses of primary cancers in children who received topoisomerase II inhibitors or developed secondary leukemias typical of those associated with this therapy. Primary diagnoses included nine solid tumors and eight leukemias. Ten secondary leukemias were acute myeloid leukemia (AML), one was of mixed lineage, two were acute lymphoblastic leukemia (ALL), and four presented as myelodysplasia.

Malignant clear cell hidradenoma of the lip.

An interesting variety of cutaneous tumors of the head and neck, tumors of the eccrine differentiation, are seldom recognized. The most recent reports of these tumors appear in the dermatologic literature, probably due to the majority of them being located in the trunk and the extremities. Malignant varieties of these tumors do exist and must be treated as aggressively as more common tumors of the head and neck region.

Effect of pindolol and propranolol on sinus node recovery time and atrioventricular conduction intervals.

In a randomized, observer-blind study, the effect of incremental doses of pindolol 0.001, 0.002, 0.

Serum creatine kinase in marathon runners.

Serum creatine phosphokinase (CK) and CK-MB activity were determined in 21 trained runners participating in a marathon race (42.2 km). Enzyme activities immediately after the race increased two to three times compared with activities before the race.

Aortic valve replacement in patients with aortic stenosis. Effect on cardiac arrhythmias.

Twenty-four hour ambulatory electrocardiography was performed on 28 patients with aortic stenosis without significant coronary artery disease or aortic regurgitation. Compared to a control group of subjects with normal hearts proven by noninvasive and invasive testing, patients with aortic stenosis had higher (p = 0.0001) frequency of premature ventricular contractions (PVC) (3144 +/- 1425 versus 17 +/- 46) per 24 hours and higher (p = 0.