Search Results (8)

99mTc-pyrophosphate (PYP) scintigraphy is widely used for the noninvasive evaluation of transthyretin cardiac amyloidosis. Although interpretation primarily focuses on myocardial uptake, confirmation of appropriate systemic radiotracer biodistribution is essential. We report a case in which an examination presumed to be 99mTc-PYP scintigraphy demonstrated free 99mTc-pertechnetate-like biodistribution. A 75-year-old woman with chronic kidney disease and conduction disturbance underwent 99mTc-PYP scintigraphy for suspected cardiac amyloidosis. The initial study, recorded as the administration of 740 MBq 99mTc-PYP, was imaged 3 h after injection. Planar imaging showed mild apparent activity over the cardiac region; however, SPECT/CT demonstrated no definite myocardial uptake. Instead, intense uptake was observed in the stomach and thyroid gland, with complete absence of skeletal activity. This distribution was inconsistent with correctly administered 99mTc-PYP and suggested free 99mTc-pertechnetate biodistribution, likely due to radiopharmaceutical preparation or administration error. A repeat 99mTc-PYP scan 1.5 months later showed expected skeletal uptake without gastric or thyroid activity and again demonstrated no myocardial uptake. The study was interpreted as negative for cardiac amyloidosis. Gastric and thyroid uptake with absent skeletal activity on presumed 99mTc-PYP scintigraphy should be considered nondiagnostic rather than negative. Full article

This scoping review explores the expression patterns and molecular features of sarcoglycans (SGs) in non-muscle organs, challenging the long-standing assumption that their function is confined to skeletal and cardiac muscle. By analyzing evidence from both animal models and human studies, the review highlights the widespread presence of SG subunits in organs, including the nervous system, glands, adipose tissue, oral mucosa, retina, and other structures, with distinct regional and cell-type-specific patterns. Studies on the central nervous system demonstrate a widespread “spot-like” distribution of SG subunits in neurons and glial cells, implicating their involvement in synaptic organization and neurotransmission. Similarly, SGs maintain cellular integrity and homeostasis in glands and adipose tissue. At the same time, the altered expression of SGs is associated with pathological conditions in the gingival epithelium of the oral mucosa. These findings underscore the multifaceted roles of SGs beyond muscle, suggesting that they may contribute to cellular signaling, membrane stability, and neurovascular coupling. However, significant gaps remain regarding SG post-translational modifications and functional implications in non-muscle organs. Future research integrating molecular, cellular, and functional approaches in animal models and human tissues is essential to fully elucidate these roles and explore their potential as therapeutic targets in various diseases. Full article

Background: Mediastinal mass syndrome represents a major threat to respiratory and cardiovascular integrity, with difficult evidence-based risk stratification for interdisciplinary management. Methods: We conducted a narrative review concerning risk stratification and difficult airway management of patients presenting with a large mediastinal mass. This is supplemented by a case report illustrating our individual approach for a patient presenting with a subtotal tracheal stenosis due to a large cyst of the thyroid gland. Results: We identified numerous risk stratification grading systems and only a few case reports of regional anesthesia techniques for extracorporeal membrane oxygenation patients. Clinical Case: After consultation with his general physician because of exertional dyspnea and stridor, a 78-year-old patient with no history of heart failure was advised to present to a cardiology department under the suspicion of decompensated heart failure. Computed tomography imaging showed a large mediastinal mass that most likely originated from the left thyroid lobe, with subtotal obstruction of the trachea. Prior medical history included the implantation of a dual-chamber pacemaker because of a complete heart block in 2022, non-insulin-dependent diabetes mellitus type II, preterminal chronic renal failure with normal diuresis, arterial hypertension, and low-grade aortic insufficiency. After referral to our hospital, an interdisciplinary consultation including experienced cardiac anesthesiologists, thoracic surgeons, general surgeons, and cardiac surgeons decided on completing the resection via median sternotomy after awake cannulation for veno-venous extracorporeal membrane oxygenation via the right internal jugular and the femoral vein under regional anesthesia. An intermediate cervical plexus block and a suprainguinal fascia iliaca compartment block were performed, followed by anesthesia induction with bronchoscopy-guided placement of the endotracheal tube over the stenosed part of the trachea. The resection was performed with minimal blood loss. After the resection, an exit blockade of the dual chamber pacemaker prompted emergency surgical revision. The veno-venous extracorporeal membrane oxygenation was explanted after the operation in the operating room. The postoperative course was uneventful, and the patient was released home in stable condition. Conclusions: Awake veno-venous extracorporeal membrane oxygenation placed under local anesthetic infiltration with regional anesthesia techniques is a feasible individualized approach for patients with high risk of airway collapse, especially if the mediastinal mass critically alters tracheal anatomy. Compressible cysts may represent a subgroup with easy passage of an endotracheal tube. Interdisciplinary collaboration during the planning stage is essential for maximum patient safety. Prospective data regarding risk stratification for veno-venous extracorporeal membrane oxygenation cannulation and effectiveness of regional anesthesia is needed. Full article

Despite playing a key role in digestion, there is only a broad characterization of the spatiotemporal development of the three glandular regions of the stomach (cardiac, fundic and pyloric) in the weaned pig. Hence, the objective of this experiment was to explore the differential expression (DE) of a panel of key genes within the three glandular regions of the stomach. Eight pigs were sacrificed at d 8 post-weaning, and three mucosal samples were collected from each stomach’s glandular regions. The expression of a panel of genes were measured using QPCR. The true cardiac gland region was characterized by increased expression of PIGR, OLFM4, CXCL8 and MUC2 relative to the two other regions (p < 0.05). The fundic gland region was characterized by increased expression of ATP4A, CLIC6, KCNQ1, HRH2, AQP4, HDC, CCKBR, CHIA, PGA5, GHRL and MBOAT4 compared to the two other regions (p < 0.05). The pyloric gland region was characterized by exclusive expression of GAST (p < 0.05). A transition region between the cardiac and fundic region (cardiac-to-oxyntic transition) was observed with a gene expression signature that resembles a cross of the signatures found in the two regions. In conclusion, unique gene expression signatures were identifiable in each of the glandular regions, with a cardiac-to-oxyntic transition region clearly identifiable in the post-weaned pigs’ stomachs. Full article

The 22q11.2 deletion syndrome is a multisystemic disorder characterized by a marked variability of phenotypic features, making the diagnosis challenging for clinicians. The wide spectrum of clinical manifestations includes congenital heart defects—most frequently conotruncal cardiac anomalies—thymic hypoplasia and predominating cellular immune deficiency, laryngeal developmental defects, midline anomalies with cleft palate and velar insufficiency, structural airway defects, facial dysmorphism, parathyroid and thyroid gland hormonal dysfunctions, speech delay, developmental delay, and neurocognitive and psychiatric disorders. Significant progress has been made in understanding the complex molecular genetic etiology of 22q11.2 deletion syndrome underpinning the heterogeneity of clinical manifestations. The deletion is caused by chromosomal rearrangements in meiosis and is mediated by non-allelic homologous recombination events between low copy repeats or segmental duplications in the 22q11.2 region. A range of genetic modifiers and environmental factors, as well as the impact of hemizygosity on the remaining allele, contribute to the intricate genotype-phenotype relationships. This comprehensive review has been aimed at highlighting the molecular genetic background of 22q11.2 deletion syndrome in correlation with a clinical multidisciplinary approach. Full article

Nrf2 is the dominant cellular stress response factor that protects cells through transcriptional responses to xenobiotic and oxidative stimuli. Nrf2 malfunction is highly correlated with many human diseases, but the underlying molecular mechanisms remain to be fully uncovered. GATA4 is a conserved GATA family transcription factor that is essential for cardiac and dorsal epidermal development. Here, we describe a novel interaction between Drosophila Nrf2 and GATA4 proteins, i.e., cap‘n’collar C (CncC) and Pannier (Pnr), respectively. Using the bimolecular fluorescence complementation (BiFC) assay—a unique imaging tool for probing protein complexes in living cells—we detected CncC–Pnr complexes in the nuclei of Drosophila embryonic and salivary gland cells. Visualization of CncC–Pnr BiFC signals on the polytene chromosome revealed that CncC and Pnr tend to form complexes in euchromatic regions, with a preference for loci that are not highly occupied by CncC or Pnr alone. Most genes within these loci are activated by the CncC–Pnr BiFC, but not by individually expressed CncC or Pnr fusion proteins, indicating a novel mechanism whereby CncC and Pnr interact at specific genomic loci and coactivate genes at these loci. Finally, CncC-induced early lethality can be rescued by Pnr depletion, suggesting that CncC and Pnr function in the same genetic pathway during the early development of Drosophila. Taken together, these results elucidate a novel crosstalk between the Nrf2 xenobiotic/oxidative response factor and GATA factors in the transcriptional regulation of development. This study also demonstrates that the polytene chromosome BiFC assay is a valuable tool for mapping genes that are targeted by specific transcription factor complexes. Full article

Caprine arthritis encephalitis virus (CAEV) is a monocyte/macrophage-tropic lentivirus that primarily infects goats resulting in a well-recognized set of chronic inflammatory syndromes focused on the joint synovium, tissues of the central nervous system, pulmonary interstitium and mammary gland. Clinically affected animals generally manifest with one or more of these classic CAEV-associated tissue lesions; however, CAEV-associated renal inflammation in goats has not been reported in the peer-reviewed literature. Here we describe six goats with chronic, multisystemic CAEV infections in conjunction with CAEV-associated renal lesions. One of the animals had CAEV antigen-associated thrombotic arteritis resulting in infarction of both the kidney and heart. These goats had microscopic evidence of inflammatory renal injury (interstitial nephritis) with detectable renal immunolabeling for CAEV antigen in three of six animals and amplifiable proviral sequences consistent with CAEV in all six animals. Cardiac lesions (vascular, myocardial or endocardial) were also identified in four of six animals. Within the viral promoter (U3) region, known transcription factor binding sites (TFBSs) were generally conserved, although one viral isolate had a duplication of the U3 A region encoding a second gamma-activated site (GAS). Despite the TFBS conservation, the isolates demonstrated a degree of phylogenetic diversity. At present, the clinical consequence of CAEV-associated renal injury is not clear. Full article

Angiotensinogen (AGT) and aldosterone play key roles in the regulation of blood pressure and are implicated in the pathogenesis of cardiovascular diseases. DNA methylation typically acts to repress gene transcription. The aldosterone synthase gene CYP11B2 is regulated by angiotensin II and potassium. DNA methylation negatively regulates AGT and CYP11B2 expression and dynamically changes in response to continuous promoter stimulation of each gene. High salt intake and excess circulating aldosterone cause DNA demethylation around the CCAAT-enhancer-binding-protein (CEBP) sites of the ATG promoter region, thereby converting the phenotype of AGT expression from an inactive to an active state in visceral adipose tissue and heart. A close association exists between low DNA methylation at CEBP-binding sites and increased AGT expression in salt-sensitive hypertensive rats. Salt-dependent hypertension may be partially affected by increased cardiac AGT expression. CpG dinucleotides in the CYP11B2 promoter are hypomethylated in aldosterone-producing adenomas. Methylation of recognition sequences of transcription factors, including CREB1, NGFIB (NR4A1), and NURR1 (NR4A2) diminish their DNA-binding activity. The methylated CpG-binding protein MECP2 interacts directly with the methylated CYP11B2 promoter. Low salt intake and angiotensin II infusion lead to upregulation of CYP11B2 expression and DNA hypomethylation in the adrenal gland. Treatment with the angiotensin II type 1 receptor antagonist decreases CYP11B2 expression and leads to DNA hypermethylation. A close association between low DNA methylation and increased CYP11B2 expression are seen in the hearts of patients with hypertrophic cardiomyopathy. These results indicate that epigenetic regulation of both AGT and CYP11B2 contribute to the pathogenesis of cardiovascular diseases. Full article