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1.
JCEM Case Rep ; 1(3): luad062, 2023 May.
Article in English | MEDLINE | ID: mdl-37908580

ABSTRACT

Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder characterized by genetic and epigenetic changes on the chromosome 11p15.5 region, which includes genes that are important for fetal and postnatal growth. Children with BWS have a higher chance of having hypoglycemia, hyperinsulinemia, and malignancies early in life, although hypoglycemia caused by an insulinoma that develops later in life has not been reported. We describe the diagnosis of insulinoma in a 53-year-old man with BWS in this case report. This is the first case report of insulinoma in an adult with this syndrome.

2.
Cureus ; 14(2): e22551, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35345729

ABSTRACT

Acute disseminated encephalomyelitis (ADEM) is a rare monophasic immune-mediated inflammatory disorder characterized by multifocal demyelinating lesions of the central nervous system. Clinically, it is distinguished by a variety of acute neurological deficits, including varying degrees of mental state changes and white matter abnormalities detected by magnetic resonance imaging (MRI). We present a challenging case of a young woman who developed ADEM as a result of chronic cannabis abuse. This, to the best of our knowledge, is the second case report of ADEM linked to cannabis abuse.

3.
Nat Commun ; 11(1): 6277, 2020 12 08.
Article in English | MEDLINE | ID: mdl-33293555

ABSTRACT

Compound heterozygous recessive or polygenic diseases could be addressed through gene correction of multiple alleles. However, targeting of multiple alleles using genome editors could lead to mixed genotypes and adverse events that amplify during tissue morphogenesis. Here we demonstrate that Cas9-ribonucleoprotein-based genome editors can correct two distinct mutant alleles within a single human cell precisely. Gene-corrected cells in an induced pluripotent stem cell model of Pompe disease expressed the corrected transcript from both corrected alleles, leading to enzymatic cross-correction of diseased cells. Using a quantitative in silico model for the in vivo delivery of genome editors into the developing human infant liver, we identify progenitor targeting, delivery efficiencies, and suppression of imprecise editing outcomes at the on-target site as key design parameters that control the efficacy of various therapeutic strategies. This work establishes that precise gene editing to correct multiple distinct gene variants could be highly efficacious if designed appropriately.


Subject(s)
CRISPR-Cas Systems/genetics , Gene Editing/methods , Genetic Therapy/methods , Glycogen Storage Disease Type II/therapy , Alleles , Cells, Cultured , Computer Simulation , Gene Transfer Techniques , Glycogen Storage Disease Type II/genetics , Humans , Induced Pluripotent Stem Cells , Infant , Inheritance Patterns , Liver/cytology , Male , Models, Genetic , Mutation , Primary Cell Culture
4.
iScience ; 23(7): 101324, 2020 Jul 24.
Article in English | MEDLINE | ID: mdl-32659722

ABSTRACT

The orosomucoid-like (Ormdl) proteins play a critical role in sphingolipid homeostasis, inflammation, and ER stress, all of which are associated with obesity and ßcell dysfunction. However, their roles in ß cells and obesity remain unknown. Here, we show that islets from overweight/obese human donors displayed marginally reduced ORMDL1-2 expression, whereas ORMDL3 expression was significantly downregulated compared with islets from lean donors. In contrast, Ormdl3 was substantially upregulated in the islets of leptin-deficient obese (ob/ob) mice compared with lean mice. Treatment of ob/ob mice and their islets with leptin markedly reduced islet Ormld3 expression. Ormdl3 knockdown in a ß cell line induced expression of pro-apoptotic markers, which was rescued by ceramide synthase inhibitor fumonisin B1. Our results reveal differential expression of Ormdl3 in the islets of a mouse model and humans with obesity, highlight the potential effect of leptin in this differential regulation, and suggest a role for Ormdl3 in ß cell apoptosis.

5.
Acta Haematol ; 136(4): 229-232, 2016.
Article in English | MEDLINE | ID: mdl-27701158

ABSTRACT

Acquired hemophilia is a relatively rare clinical presentation, and most cases present with acquired FVIII inhibitor. The co-occurrence of inhibitors to multiple coagulation factors is uncommon. These autoantibodies may induce spontaneous life-threatening bleeding in patients who have had no previous bleeding disorder. Herein, we present a patient with postpartum acquired FVIII and FIX inhibitors who developed intramuscular hematoma and hemothorax during follow-up. She was then treated with activated prothrombin complex concentrate and methylprednisolone.


Subject(s)
Factor VIII/immunology , Hemophilia A/blood , Autoantibodies/blood , Female , Hematoma , Hemorrhage , Humans , Pregnancy
6.
Angiology ; 67(3): 239-44, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25969567

ABSTRACT

Endothelial-specific molecule 1 (endocan) is expressed by endothelial cells and may have a major role in the regulation of cell adhesion and in the pathogenesis of inflammatory disorders. We aimed to assess change in endocan levels after 3 months of lifestyle change recommendations and guideline-based treatment. Diabetic patients (n = 77) who had neither chronic kidney disease nor chronic inflammatory disease were included. After baseline evaluation, the patients were advised lifestyle changes, and their medical treatment was determined individually according to recommendations of the American Diabetes Association (ADA) guidelines. At the end of third month patients were reevaluated. Baseline endocan levels were significantly increased in the study group compared with the control group. The third-month laboratory workup showed significant reductions in hemoglobin A1c, urinary albumin-to-creatinine ratio (UACR), and endocan levels. Only δ-UACR was independently correlated with δ-endocan in multivariate linear regression analysis. Our findings suggest that serum endocan concentrations are elevated in patients with type 2 diabetes and decrease following anti-hyperglycemic treatment. Furthermore, decrease in endocan concentrations might be associated with improved glycemic control and reductions in UACR.


Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Type 2/therapy , Hypoglycemic Agents/therapeutic use , Neoplasm Proteins/blood , Proteoglycans/blood , Risk Reduction Behavior , Adult , Aged , Albuminuria/blood , Albuminuria/etiology , Albuminuria/prevention & control , Biomarkers/blood , Blood Glucose/metabolism , Combined Modality Therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetic Nephropathies/blood , Diabetic Nephropathies/etiology , Diabetic Nephropathies/prevention & control , Diet , Down-Regulation , Exercise , Female , Glycated Hemoglobin/metabolism , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prospective Studies , Time Factors , Treatment Outcome
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