Hyunsu Lee

Leptin promotes KATP channel trafficking by AMPK signaling in pancreatic β-cells

Leptin is a pivotal regulator of energy and glucose homeostasis, and defects in leptin signaling result in obesity and diabetes. The ATP-sensitive potassium (KATP) channels couple glucose metabolism to insulin secretion in pancreatic β-cells. In this study, we provide evidence that leptin modulates pancreatic β-cell functions by promoting KATP channel translocation to the plasma membrane via AMP-activated protein kinase (AMPK) signaling. KATP channels were localized mostly to intracellular compartments of pancreatic β-cells in the fed state and translocated to the plasma membrane in the fasted state. This process was defective in leptin-deficient ob/ob mice, but restored by leptin treatment. We discovered that the molecular mechanism of leptin-induced AMPK activation involves canonical transient receptor potential 4 and calcium/calmodulin-dependent protein kinase kinase β. AMPK activation was dependent on both leptin and glucose concentrations, so at optimal concentrations of leptin, AMPK was activated sufficiently to induce KATP channel trafficking and hyperpolarization of pancreatic β-cells in a physiological range of fasting glucose levels. There was a close correlation between phospho-AMPK levels and β-cell membrane potentials, suggesting that AMPK-dependent KATP channel trafficking is a key mechanism for regulating β-cell membrane potentials. Our results present a signaling pathway whereby leptin regulates glucose homeostasis by modulating β-cell excitability.

Prodromal dizziness in vestibular neuritis: frequency and clinical implication

Although vestibular neuritis (VN) usually includes a single attack of prolonged vertigo (lasting more than 1 day), we have previously observed several patients with VN who experienced paroxysmal dizziness prior to onset of the continuous dizziness typical for VN. Since vertebrobasilar territory strokes may also be heralded by recurrent isolated dizziness (usually vertigo), there exists the possibility of diagnostic confusion between VN and stroke-related vertigo. We thus sought to characterise the features of transient dizziness prior to the prolonged vertigo attack of VN. From March 2006 to August 2007, 255 consecutive patients with VN were recruited at four dizziness clinics of University Hospital in Korea. All patients met the clinical diagnostic criteria for VN including sudden onset of prolonged vertigo (more than 1 day) with unidirectional, spontaneous, horizontal nystagmus with a torsional component, absence of other auditory or neurological findings, reduced or absent caloric response and no previous history of neuro-otological diseases.1 Asymmetry of vestibular function was calculated using the Jongkees formula, and caloric paresis was defined by a response difference of 25% or more between the ears. Patients with an onset of transient dizziness within 7 days before VN attack were considered to have prodromal dizziness. On admission, all patients were carefully interviewed by authors …

A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs. DOI: http://dx.doi.org/10.7554/eLife.22772.001

Variations of the cubital superficial vein investigated by using the intravenous illuminator.

The purpose of this study was to report variations of the cubital superficial vein patterns in the Korean subjects, which was investigated by using venous illuminator, AccuVein. The 200 Korean subjects were randomly chosen from the patients and staff of the Keimyung University Dongsan Medical Center in Daegu, Korea. After excluding the inappropriate cases for detecting venous pattern, we collected 174 cases of right upper limbs and 179 cases of left upper limbs. The superficial veins of the cubital fossa were detected and classified into four types according to the presence of the median cubital vein (MCV) or median antebrachial vein. The type II, presenting the both cephalic and basilic vein connected by the MCV, was most common (177 upper limbs, 50.1%). Although the most common type in male and female was different as type I (108 upper limbs, 49.3%) and type II (75 upper limbs, 56.0%), respectively, statistical significance was not detected (P=0.241). The frequency of the each types between right and left upper limbs was also not different (P=0.973). Among 154 subjects who were observed the venous pattern in the both upper limbs, 76 subjects (49.3%) had the same venous pattern. Using AccuVein to investigate the venous pattern has an advantage of lager scale examination compared to the cadaver study. Our results might be helpful for medical practitioner to be aware of the variation of the superficial cubital superficial vein.

An unusual case of neuro-Behçet’s disease presenting with reversible basilar artery occlusion

Neuro-vasculo-Behçet’s disease is considered a venous vessel disease generally in the form of cerebral venous thrombosis. Arterial involvement has been rarely reported. We present a patient with neuro-Behçet’s disease who developed reversible basilar artery occlusion. To the best of our knowledge, this is the first case of neuro-Behçet’s disease presenting with reversible basilar artery occlusion. Behçet’s disease should be considered in the differential diagnosis of basilar artery occlusion.

Mutation of the TERT promoter leads to poor prognosis of patients with non‑small cell lung cancer

Mutations in the promoter region of telomerase reverse transcriptase (TERT) and alterations in telomere length (TL) have been the focus of research in various types of cancer. In the present study, the frequency and clinical characteristics of TERT promoter mutations and TL were studied in non-small cell lung cancers (NSCLC). TERT promoter mutations and TL were analyzed in 188 patients using DNA sequencing and the reverse transcription-quantitative polymerase chain reaction, respectively. The TERT promoter mutation rate was observed to be 2.2% (4/188 NSCLC cases), and it was significantly associated with regional lymph node invasion (P<0.001). No significant difference in TL was observed between the patients with and without TERT promoter mutations. TL was decreased in males (P=0.058 vs. females) and smokers (P=0.008 vs. non-smokers). Survival analyses demonstrated poor prognoses for patients with NSCLC with TERT promoter mutations (P<0.001). Multivariate survival analyses demonstrated that TERT promoter mutations were an independent prognostic marker for poor overall survival (P=0.045). The results of the present study demonstrated that TERT promoter mutation was not frequent in NSCLC; however, it may have value as a prognostic marker in NSCLC.

Are PIK3CA Mutation and Amplification Associated with Clinicopathological Characteristics of Gastric Cancer

Alterations in mitochondrial DNA (mtDNA) have been studied in various cancers. However, the clinical value of mtDNA copy number (mtCN) alterations in gastric cancer (GC) is poorly understood. In the present study, we investigated whether alterations in mtCNs might be associated with clinicopathological parameters in GC cases. mtCN was measured in 109 patients with GC by real-time PCR. Then, correlations with clinicopathological characteristics were analyzed. mtCN was elevated in 64.2% of GC tissues compared with paired, adjacent, non- cancerous tissue. However, the observed alterations in mtCN were not associated with any clinicopathological characteristics, including age, gender, TN stage, Lauren classification, lymph node metastasis, and depth of invasion. Moreover, Kaplan-Meier survival curves revealed that mtCN was not significantly associated with the survival of GC patients. In this study, we demonstrated that mtCN was not a significant marker for predicting clinical characteristics or prognosis in GC.

A radial artery originating from the thoracoacromial artery

AbstractPurpose The purpose of this case report is to report a rare vascular variation in the upper limbs because of its clinical importance and embryological implication.MethodsDuring the educational dissection of a 73-year-old Korean male cadaver`s right upper limb, we found a variant branch which is originated from the thoracoacromial artery.ResultsThe variant branch from the thoracoacromial artery ran to the distal forearm in the deep fascia. Because it finally coursed like the radial artery in the forearm and the palm, we defined the variant artery as superficial brachioradial artery (SBRA). In the cubital region a little below the intercondylar line, the brachial artery gave off a small communicating branch to SBRA, and continued as the ulnar artery.ConclusionsWe reported this unique variation and discussed its clinical and embryological implication.

Low frequency of the lateral thoracic artery originating from the thoracoacromial artery

We read with great interest the recent article titled ‘‘The lateral thoracic artery revised’’ by Loukas et al. [4] published online in Surgical and Radiological Anatomy (doi:10.1007/s00276-013-1234-x). Anatomy textbooks define that the lateral thoracic artery (LTA) usually originates from the second part of Axillary artery (AA). LTA arose from the first or third part of AA either on its own or as a common trunk with one or more of the other branches. However, above study with large cases demonstrated that most of LTA (67.6 %, 568/840) arose from the thoracoacromial artery (TAA) and only 17.2 % (143/840) of that originated from AA. LTA also originated from the thoracodorsal or subscapular arteries in about 3–4 % of cadavers. Within an abundant concern about this variation, we also collected the data of the branching pattern of AA in 189 arms until now (Fig. 1). According to our data, LTA arose directly from second and third parts of AA in 59.7 % (113/189) and 9.5 % (18/189) of cases, respectively. It also originated from TAA (2.6 %, 5/189) and the subscapular artery (21.6 %, 41/189). Except the studies by DeGaris and Swatley [2], Pandey and Shukla [5], and Loukas et al. [4], most of the studies demonstrated that LTA from TAA was rare; moreover, LTA arose from the subscapular artery more frequently. Our result was in agreement with previous studies in Koreans by Kang et al. [3] and Japanese by Adachi [1], suggesting racial difference of branching pattern of AA. Considering clinical importance of knowledge about its anatomy, the pattern of the lateral thoracic artery should be clarified apparently. Though there may be ethnic diversity in this arterial pattern, its big difference could be caused by different classification or definition of the branches of the axillary artery. Therefore, we would like to mention that multiple center study was needed to clarify the branching pattern of AA with larger cases.

Is Mitochondrial DNA Copy Number Associated with Clinical Characteristics and Prognosis in Gastric Cancer

Alterations in mitochondrial DNA (mtDNA) have been studied in various cancers. However, the clinical value of mtDNA copy number (mtCN) alterations in gastric cancer (GC) is poorly understood. In the present study, we investigated whether alterations in mtCNs might be associated with clinicopathological parameters in GC cases. mtCN was measured in 109 patients with GC by quantitative real-time PCR. Then, correlations with clinicopathological characteristics were analyzed. mtCN was elevated in 64.2% of GC tissues compared with paired, adjacent, non-cancerous tissue. However, the observed alterations in mtCN were not associated with any clinicopathological characteristics, including age, gender, TN stage, Lauren classification, lymph node metastasis, and depth of invasion. Moreover, Kaplan-Meier survival curves revealed that mtCN was not significantly associated with the survival of GC patients. In this study, we demonstrated that mtCN was not a significant marker for predicting clinical characteristics or prognosis in GC.