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Biomedical subjects

Alexandra F Freeman

Publications and source records attributed to Alexandra F Freeman.

15 recordsLinked to original sources
PubMed2026

Establishment of human induced pluripotent stem cell lines and isogenic gene-corrected controls from three patients with prolidase deficiency.

Prolidase deficiency is an autosomal recessive inborn error of metabolism caused by pathogenic variants in the PEPD gene. To date, close to 200 patients have been reported worldwide with a poorly understood pathomechanism. The PEPD gene encodes an enzyme that is involved in the final steps of collagen degradation. Urine amino acid analysis or specific dipeptide analysis can establish the biochemical diagnosis. In this study, we reprogrammed peripheral blood mononuclear cells (PBMCs) from three prolidase deficient patients into induced pluripotent stem cell (iPSC) lines and additionally generated isogenic controls using CRISPR-Cas9 genome editing. The pathogenic PEPD variants identified in our patients were NP_000276.2:p.? (NIHTVBi032-A), NP_000276.2:p.(Ile415Asn)/NP_000276.2:p.(Trp326Ter) (NIHTVBi033-A), and NP_000276.2:p.(Arg265Ter) (NIHTVBi034-A). These iPSC lines are valuable models to help investigate the pathomechanism of prolidase deficiency.

Humans↗
PubMed2007

Persistent bacterial infections and primary immune disorders.

Mycobacteria, Salmonella and Helicobacter species have all evolved mechanisms to evade host defenses and cause persistent infection in humans. Host control of mycobacteria and Salmonella is largely achieved by the IFN-gamma/IL-12 pathway. Immune disorders affecting this pathway are characterized by disseminated infections with environmental or nontuberculous mycobacteria. Helicobacter is a predominantly extracellular bacterium that uses its remarkable genetic diversity (as well as other mechanisms) in order to evade host defenses. The importance of humoral immunity in containing Helicobacter infections to the mucosal surface is illustrated by the primary immune disorder, X-linked agammaglobulinemia in which patients are prone to chronic bacteremia and skin infections by Helicobacter and related species such as Flexispira and Campylobacter. Exploration of these particular infections in their specific immune defects sheds light on both host and bacterial mechanisms that have implications for pathogenesis and therapy.

Bacterial Infections↗
PubMed2006

Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome.

Hyper IgE recurrent infection syndrome (HIES, or Job's syndrome) is a primary immunodeficiency characterized by recurrent skin and lung infections, eczema, elevated serum immunoglobulin E (IgE) levels, and various connective tissue and skeletal system abnormalities including characteristic facies, scoliosis, joint hyperextensibility, retained primary dentition, craniosynostosis, osteopenia, and pathologic fractures. We have identified two patients with aneurysmal coronary artery disease. One was a forty-three-year-old man with HIES and coronary artery aneurysms and ectasia identified on cardiac catheterization following myocardial infarction. The other was a 48-year-old man with coronary artery ectasia-aneurysm identified after cardiac catheterization for evaluation of chest pain. Although connective tissue abnormalities are common in HIES, this is the first report of coronary artery aneurysms in HIES. Further studies are necessary to determine the incidence, pathogenesis, and optimal therapy of these arterial abnormalities in HIES.

Adult↗
PubMed2006

Kawasaki disease: summary of the American Heart Association guidelines.

Kawasaki disease is an acute vasculitis of childhood that predominantly affects the coronary arteries. The etiology of Kawasaki disease remains unknown, although an infectious agent is strongly suspected based on clinical and epidemiologic features. A genetic predisposition is also likely, based on varying incidences among ethnic groups, with higher rates in Asians. Symptoms include fever, conjunctival injection, erythema of the lips and oral mucosa, rash, and cervical lymphadenopathy. Some children with Kawasaki disease develop coronary artery aneurysms or ectasia, ischemic heart disease, and sudden death. Kawasaki disease is the leading cause of acquired heart disease among children in developed countries. This article provides a summary of the diagnostic and treatment guidelines published by the American Heart Association.

Child↗
PubMed2006

Pneumocystis jiroveci infection in patients with hyper-immunoglobulin E syndrome.

The hyper-immunoglobulin E syndrome is a primary immunodeficiency characterized by recurrent pyogenic skin and lung abscesses, dermatitis, and elevated serum immunoglobulin E levels. Pneumocystis jiroveci (formerly Pneumocystis carinii) is not typically associated with hyper-immunoglobulin E syndrome. We identified 7 patients with hyper-immunoglobulin E syndrome with P. jiroveci detected in respiratory or pulmonary pathology specimens. In 5 patients it was the sole pathogen, and in 2 other patients it contributed to a polymicrobial etiology. No consistent prophylaxis was given, and there have been no recurrences on long-term follow-up. Our experience suggests that P. jiroveci can cause pneumonia in patients with hyper-immunoglobulin E syndrome both with and without chronic lung disease.

Adolescent↗
PubMed2006

Linezolid-resistant Staphylococcus aureus in two pediatric patients receiving low-dose linezolid therapy.

We report 2 sisters with hyper-IgE syndrome treated with daily suppressive dosages of linezolid (LZD) who developed LZD-resistant Staphylococcus aureus carrying the G2576T mutation in the 23S rRNA gene. Molecular typing suggested transmission of the resistant strain from one sister to the other. LZD-susceptible S. aureus was isolated 2 months after LZD discontinuation. LZD-resistant S. aureus remains rare but may occur while receiving suppressive therapy.

Acetamides↗
PubMed2005

Chronic granulomatous disease presenting with eosinophilic inflammation.

Chronic granulomatous disease (CGD), a rare immunodeficiency, typically presents with recurrent infections caused by catalase-positive organisms. We report 2 patients with CGD who presented with eosinophilic inflammatory conditions recognized before the diagnosis of CGD. Both patients had significant urologic disease. Physicians should be aware of the association of CGD with eosinophilic inflammatory conditions.

Achromobacter denitrificans↗
PubMed2004

Pasteurella aerogenes hamster bite peritonitis.

Pasteurella multocida has been reported to cause peritoneal dialysis-associated peritonitis after a cat bite or scratch to the catheter. We report a teenager with hamster bite peritonitis caused by P. aerogenes, an organism predominantly isolated from swine.

Adolescent↗
PubMed2004

Streptococcus pneumoniae empyema necessitatis.

Empyema necessitatis is a rare complication of empyema characterized by extension of suppuration from the pleural space through the chest wall. The most common etiologies are tuberculosis and actinomycosis. We describe a 1-year-old boy with Streptococcus pneumoniae empyema necessitatis and review previously reported cases.

Anti-Bacterial Agents↗
PubMed2004

Antimicrobial susceptibilities of invasive pediatric Abiotrophia and Granulicatella isolates.

Abiotrophia and Granulicatella species have been associated with various infections. Antimicrobial susceptibility data for these nutritionally variant streptococcus-like organisms, especially for pediatric isolates, are very limited. Little is known about the genetic bases of their resistance mechanisms. We report the results of identification to bacterial species level, antimicrobial susceptibility testing, macrolide resistance testing, and detection of genes encoding that resistance for a collection of 15 pediatric clinical isolates from normally sterile sites. Our results indicate that the prevalence of beta-lactam and macrolide resistance is high and that both erm and mef are found in these isolates.

Base Sequence↗
PubMed2004

A new complication of stem cell transplantation: measles inclusion body encephalitis.

Measles inclusion body encephalitis (MIBE) is a disease of the immunocompromised host and typically occurs within 1 year of acute measles infection or vaccination. We report a 13-year-old boy who had chronic granulomatous disease and presented 38 days after stem cell transplantation with afebrile focal seizures that progressed despite multiple anticonvulsants. After an extensive diagnostic evaluation, brain biopsy was performed, revealing numerous intranuclear inclusion bodies consistent with paramyxovirus nucleocapsids. Measles studies including reverse transcriptase-polymerase chain reaction and viral growth confirmed measles virus, genotype D3. Immunohistochemistry was positive for measles nucleoprotein. Despite intravenous ribavirin therapy, the patient died. MIBE has not been described in stem cell recipients but is a disease of immunocompromised hosts and typically occurs within 1 year of measles infection, exposure, or vaccination. Our case is unusual as neither the patient nor the stem cell donor had apparent recent measles exposure or vaccination, and neither had recent travel to measles-endemic regions. The patient had an erythematous rash several weeks before the neurologic symptoms; however, skin biopsy was consistent with graft-versus-host disease, and immunohistochemistry studies for measles nucleoprotein were negative. As measles genotype D3 has not been seen in areas where the child lived since his early childhood, the possibility of an unusually long latency period between initial measles infection and MIBE is raised. In addition, this case demonstrates the utility of brain biopsy in the diagnosis of encephalitis of unknown cause in the immunocompromised host.

Adolescent↗
PubMed2003

Inflammatory pulmonary nodules in Kawasaki disease.

Symptomatic pulmonary manifestations of Kawasaki disease (KD) are uncommon. However, epidemiologic, radiologic, and histologic studies have indicated that respiratory symptoms and findings occur in KD and suggest that the KD agent may have a respiratory portal of entry. We report on three young infants with KD who developed pulmonary nodules, in addition to coronary artery aneurysms. Two patients had pathologic specimens available, one from biopsy and the other from autopsy. The nodules had predominantly mononuclear cell infiltrates, which were within the lung parenchyma and infiltrating vessel walls. Immunohistochemical studies of the nodules, using antibodies to common leukocyte antigen (LCA) and factor VIII-related antigen, confirmed the inflammatory nature of the lesions and showed capillary proliferation. IgA plasma-cell infiltration was observed in the nodule, consistent with previous KD findings of IgA plasma-cell infiltration in the vessel walls, kidneys, pancreas, and upper respiratory tract. The two patients with nonfatal KD were treated with intravenous immunoglobulin and aspirin, with resolution of the nodules. We propose that when pulmonary involvement occurs in KD, it ranges from subclinical interstitial micronodular infiltrates to larger inflammatory pulmonary nodules. These pulmonary infiltrates and nodules likely reflect the host response to the etiologic agent of KD, and may resolve with the disease process. Recognition of this pulmonary complication of KD may enable cautious observation of such lesions for spontaneous resolution.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Is noma neonatorum a presentation of ecthyma gangrenosum in the newborn?

Noma neonatorum was suggested as a distinct entity characterized by a gangrenous process of the nose, oral cavity, eyelids and perineum that was almost universally fatal in premature infants with Pseudomonas sepsis. We report the first case of noma neonatorum in a 26-week-gestation twin born in the United States. Our case is consistent with previous descriptions of noma neonatorum; however, we question the distinction between noma neonatorum and a neonatal presentation of ecthyma gangrenosum.

Diagnosis, Differential↗