Graves’ Disease Presenting with Complete Atrioventricular Block

Hyperthyroidism commonly causes tachyarrhythmias such as sinus tachycardia and atrial fibrillation. Impaired atrioventricular conduction is a very rare complication of hyperthyroidism. We report a case of a patient with hyperthyroidism due to Graves’ disease presenting with syncope and complete atrioventricular block. Because lack of awareness of atypical presentation in patients with hyperthyroidism may delay diagnosis and treatment, the recognition that hyperthyroidism can be one of the reversible causes of complete atrioventricular block is important

Penicillium mexicanum : An Unrecorded Fungal Species Isolated from Air Samples Collected in Korea

We report the first discovery of Penicillium mexicanum in Korea. Fungal strains were isolated from air samples collected in Taean-gun, Chungcheongnam-do, Korea. The strain was identified based on its morphological characteristics, as well as molecular phylogenetic analysis of the internal transcribed spacer (ITS), β-tubulin (BenA), and calmodulin (CaM) regions. This strain exhibited a high sequence similarity to the reference sequences of P. mexicanum. These findings enhance our understanding of fungal biodiversity in Korea and underscore the importance of continuous monitoring of fungal species

A Novel Acremonium Species Isolated from Air Samples in Korea

AbstractThe aim of this study was to characterize a new fungal species, Acremonium conglutinatum, isolated from air samples collected in Wando, South Korea. Phylogenetic analysis based on the internal transcribed spacer and large subunit regions revealed its unique position within the genus Acremonium. The isolated strain displayed distinct morphological characteristics, including ellipsoid or bent-ellipsoid conidia formed in clusters on the phialides. These features differentiate the new species from closely related species within the genus. This study describes the morphological and molecular characteristics of A. conglutinatum and emphasizes its phylogenetic relationships with other Acremonium spp. The identification of this novel species contributes to our understanding of the diversity and ecological role of Acremonium

Identification and characterization of D410E, a novel mutation in the loop 3 domain of CaSR, in autosomal dominant hypocalcemia and therapeutic approaches with novel calcilytics, AXT914

Background: Autosomal dominant hypocalcemia (ADH) is a rare disorder characterized by benign hypocalcemia, inappropriately low parathyroid hormone (PTH) levels and mostly hypercalciuria. ADH can be caused by activating mutations of the calcium-sensing receptor (CaSR) gene located on chromosome 3q13.3-21. Calcium-sensing receptor plays a pivotal role in the regulation of calcium homeostasis and is abundantly expressed in parathyroid gland, thyroid C cell, and renal tubular system. Activation of CaSR by increased Ca2+ inhibits PTH secretion, stimulates calcitonin secretion, and promotes urinary Ca2+ excretion, and thereby maintains the Ca2+ at the normal level. Herein, we report a novel activating mutation in the CaSR gene in a Korean family with ADH. Meanwhile, antagonist of the CaSR, calcilytics could be a therapeutic option in the treatment of ADH. Method: We identified a 55-yr-old woman with mild hypocalcemia (7.7 mg/dL) and hypercalciuria (24-hr urine Ca: 868 mg/d) caused by missense mutations of the CaSR gene. She showed low normal serum PTH level (10.14 pg/mL). We performed mutational analysis of the genes encoding GCMB, pre-pro-PTH and CaSR using PCR-amplified genomic DNA in her family members. The ability of wild-type and mutant CaSR to activate the MAPK signaling cascade was assessed by examining phosphorylation of ERK1/2. Intacellular Ca2+ concentration was measured by Fura-2 dye. Blocking of CaSR with calcilytics, AXT914 was also tested by Fura-2 with a variety of concentrations. Result: Direct sequencing analysis of the CaSR gene showed that the proband and her daughter possess a T to A transition at nucleotide 1230 resulting in a D410E missense mutation in exon 4 of the CaSR. No mutation was detected in GCMB and Prepro-PTH genes. HEK293 cells were stably transfected with plasmids encoding wild-type or mutant CaSR genes. Escalation of the extracellular Ca2+ concentration from 0.5 to 5.0 mM resulted in increased phosphorylation of ERK1/2 and escalation of the extracellular Ca2+ concentration from 1.0 to 10 mM resulted in increased intracellular Ca2+ detected by Fura-2 in mutant CaSR-expressing cell than wild-type-expressing one. These results indicate that D410E mutation of CaSR is associated with ADH in this family. Finally, AXT914 successively blunted the increased intracellular signaling via CaSR. Conclusion: Over 60 activating mutations in the CaSR gene have been identified to cause ADH so far. Here we add one more activating mutation that causes ADH. This could be of interest because this novel mutation occurred in the loop 3 region of the VFT domain in CaSR where little was known to be important in its function. Further clinical study is needed to validate the effectiveness of calcilytics in the treatment of ADH in vivo

Genetic Analysis of Multiple Endocrine Neoplasia Type 1 () Leads to Misdiagnosis of an Extremely Rare Presentation of Intrasellar Cavernous Hemangioma as MEN1

BackgroundMultiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands). MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above.MethodsA 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma) 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1.ResultsGenomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion.ConclusionThere is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma could be suspected

Flightless-1 inhibits ER stress-induced apoptosis in colorectal cancer cells by regulating Ca2+ homeostasis

The endoplasmic reticulum (ER) stress response is an adaptive mechanism that is activated upon disruption of ER homeostasis and protects the cells against certain harmful environmental stimuli. However, critical and prolonged cell stress triggers cell death. In this study, we demonstrate that Flightless-1 (FliI) regulates ER stress-induced apoptosis in colon cancer cells by modulating Ca2+ homeostasis. FliI was highly expressed in both colon cell lines and colorectal cancer mouse models. In a mouse xenograft model using CT26 mouse colorectal cancer cells, tumor formation was slowed due to elevated levels of apoptosis in FliI-knockdown (FliI-KD) cells. FliI-KD cells treated with ER stress inducers, thapsigargin (TG), and tunicamycin exhibited activation of the unfolded protein response (UPR) and induction of UPR-related gene expression, which eventually triggered apoptosis. FliI-KD increased the intracellular Ca2+ concentration, and this upregulation was caused by accelerated ER-to-cytosolic efflux of Ca2+. The increase in intracellular Ca2+ concentration was significantly blocked by dantrolene and tetracaine, inhibitors of ryanodine receptors (RyRs). Dantrolene inhibited TG-induced ER stress and decreased the rate of apoptosis in FliI-KD CT26 cells. Finally, we found that knockdown of FliI decreased the levels of sorcin and ER Ca2+ and that TG-induced ER stress was recovered by overexpression of sorcin in FliI-KD cells. Taken together, these results suggest that FliI regulates sorcin expression, which modulates Ca2+ homeostasis in the ER through RyRs. Our findings reveal a novel mechanism by which FliI influences Ca2+ homeostasis and cell survival during ER stress. Cancer: Protein enhances survival of tumor cells under stress A cytoskeletal protein that helps tumors avoid cell death offers a promising new drug target for fighting cancer. A team led by Jang Hyun Choi and Sun Sil Choi of the Ulsan National Institute of Science and Technology, South Korea, detailed how a protein called Flightless I (FliI) that normally regulates the remodeling of structural filaments in the cell can, in colorectal cancer cells, serve as a tumor promoter through its action on calcium levels. Typically, cells respond to chronic stress by altering calcium signaling to promote their own death. In tumors, however, FliI maintains normal calcium levels to enhance cell survival even in the face of chemotherapy and other stressful stimuli. Suppressing FliI activity could thus help sensitize cancer cells to other stress- and death-inducing drug regimens