Lentiviral vectors for precise expression to treat X-linked lymphoproliferative disease.

X-linked lymphoproliferative disease (XLP1) results from gene mutations affecting the SLAM-associated protein (SAP). A regulated lentiviral vector (LV), XLP-SMART LV, designed to express SAP at therapeutic levels in T, NK, and NKT cells, is crucial for effective gene therapy. We experimentally identified 34 genomic regulatory elements of the gene and designed XLP-SMART LVs to emulate the lineage and stage-specific control of SAP.

Chemotherapy Can Synergize With Adoptive Immunotherapy to Inhibit Medulloblastoma Growth.

Background/aim: In the age of ever-increasing developments in targeted cancer treatments, new immune-based approaches for brain tumor therapy represent an attractive avenue. Despite encouraging pre-clinical data, results in patients have been sub-optimal, likely due to tumor-induced immune suppression and intrinsic resistance to immune attack. Chemotherapy and biologic agents may be able to disrupt these mechanisms and restore tumor sensitivity to immune attack.

AT1R Activating Autoantibodies in Hematopoietic Stem Cell Transplantation.

Angiotensin II type 1 receptor activating autoantibodies (AT1R-AAs) have gained attention in solid organ transplant as non-HLA antibodies associated with rejection, vasculopathy, and graft dysfunction. These antibodies have also been reported in the context of pre-eclampsia, scleroderma, and isolated hypertension. Here, we present 3 post-hematopoietic stem cell transplant (HSCT) cases with patients demonstrating elevated levels of AT1R-AAs detected within the first year post-HSCT.

Novel Gene Mutation in a Newborn with Severe Congenital Neutropenia: Case Report and Literature Review.

Severe neutropenia is defined as an absolute neutrophil count (ANC) of less than 0.5 × 10 /L. Severe congenital neutropenia (SCN) is an inborn disorder with maturation arrest of granulocytes due to various genetic abnormalities, which may lead to immunodeficiency.

Busulfan Pharmacokinetics in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Gene Therapy.

The pharmacokinetics of low-dose busulfan (BU) were investigated as a nonmyeloablative conditioning regimen for autologous gene therapy (GT) in pediatric subjects with adenosine deaminase-deficient severe combined immunodeficiency disease (ADA SCID). In 3 successive clinical trials, which included either γ-retroviral (γ-RV) or lentiviral (LV) vectors, subjects were conditioned with BU using different dosing nomograms. The first cohort received BU doses based on body surface area (BSA), the second cohort received doses based on actual body weight (ABW), and in the third cohort, therapeutic drug monitoring (TDM) was used to target a specific area under the concentration-time curve (AUC).

Primary Renal Ewing Sarcoma in Children and Young Adults.

The Ewing sarcoma family of tumors (ESFT) are high-grade small round blue cell malignancies traditionally presenting in children and adolescents. The most common site of primary disease is bone, though extraskeletal primary sites are well-recognized. We present 6 cases of primary ESFT of the kidney and 1 case of the adrenal gland.

Burkitt-like lymphoma in a pediatric patient with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition that predisposes to multiple malignancies, most commonly colorectal carcinoma, but has rarely been associated with lymphoma. We discuss one patient found to have Burkitt-like Lymphoma (BLL) with 11q aberration in the setting of previously undiagnosed FAP. We review the literature of FAP and associated malignancies and the provisional WHO classification of Burkitt-like lymphoma with 11q aberration.

Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations.

Deficiency of adenosine deaminase (ADA, EC3.5.4.

A Heat Vulnerability Index and Adaptation Solutions for Pittsburgh, Pennsylvania.

With increasing evidence of global warming, many cities have focused attention on response plans to address their populations' vulnerabilities. Despite expected increased frequency and intensity of heat waves, the health impacts of such events in urban areas can be minimized with careful policy and economic investments. We focus on Pittsburgh, Pennsylvania and ask two questions.

Resveratrol increases cerebral glycogen synthase kinase phosphorylation as well as protein levels of drebrin and transthyretin in mice: an exploratory study.

Alzheimer's disease (AD) is characterized by intraneuronal β-amyloid plaques and hyperphosphorylated tau, leading to neuronal cell death and progressive memory losses. This exploratory work investigates if dietary resveratrol, previously shown to have broad anti-aging effects and improve AD pathology in vivo, leads to neuroprotective changes in specific protein targets in the mouse brain. Both wild-type and APP/PS1 mice, a transgenic AD mouse model, received control AIN-93G diet or AIN-93G supplemented with resveratrol.

Heart arachidonic acid is uniquely sensitive to dietary arachidonic acid and docosahexaenoic acid content in domestic piglets.

This study determined the sensitivity of heart and brain arachidonic acid (ARA) and docosahexaenoic acid (DHA) to the dietary ARA level in a dose-response design with constant, high DHA in neonatal piglets. On day 3 of age, pigs were assigned to 1 of 6 dietary formulas varying in ARA/DHA as follows (% fatty acid, FA/FA): (A1) 0.1/1.