Electrophysiological Properties of a Novel Ca2+-Activated K+ Channel Expressed in Human Osteoblasts

Intracellular Ca²⁺ mobilization plays important roles in cell survival, proliferation, and differentiation of osteoblasts. In this study, we identified a novel type of Ca²⁺-activated K⁺ channel in human osteoblasts and investigated its physiological roles. Using RT-PCR methods and single-channel analysis in the patch-clamp technique, we found that BK and IK channels were genetically expressed in human osteoblasts and had electrophysiological properties similar to those reported previously for the channels in other organs (conductance, voltage dependence, and sensitivity to intracellular Ca²⁺). Taking advantage of the fact that ATP induces elevation of the intracellular Ca²⁺ concentration in human osteoblasts, we successfully demonstrated that ATP-induced hyperpolarization was effectively inhibited by the IK channel blockers charybdotoxin and clotrimazole and by a P2 purinergic receptor antagonist, suramin, but not by the BK channel blockers tetraethylammonium chloride and iberiotoxin under the current-clamp mode of whole-cell clamp. The present study is the first to demonstrate the electrophysiological properties and functional expression of IK channels in human osteoblasts, findings which suggest that IK channels are regulators of membrane potential that give rise to intracellular Ca²⁺ mobilization by physiological stimulation.     

The antigenic binding sites of autoantibodies to factor XII in patients with recurrent pregnancy losses

Recently, numerous studies have suggested an association between factor XII (FXII) deficiency and recurrent pregnancy losses, and between autoantibodies to FXII and recurrent pregnancy losses. Autoantibodies to FXII rather than FXII deficiency may be a risk factor for recurrent pregnancy losses. To know the pathogenesis of autoantibodies to FXII, epitope mapping study was done. Seventeen anti-FXII antibody positive recurrent pregnancy loss patients were chosen for this study. We used synthetic peptides in inhibition and direct binding studies to identify the antigenic binding site of autoantibodies to FXII. Among plasmas from 17 recurrent pregnancy loss patients who were positive for autoantibodies to FXII, 13 patients (76.5%) recognized amino acids 1-30, the amino-terminal heavy chain region that is known as factor XII binding site to platelet glycoprotein Ibalpha.     

Treatment of thoracic esophageal carcinoma invading adjacent structures

T4 esophageal cancer is defined as the tumor invading adjacent structures, using tumor-node-metastasis (TNM) staging. For clinically T4 thoracic esophageal carcinoma, multimodality therapy, that is, neoadjuvant chemoradiotherapy (CRT) followed by surgery or definitive CRT, has generally been performed. However, the prognosis of patients with these tumors remains poor. Another strategy is needed to achieve curative treatment. In the present article, the treatment strategies employed to date are reviewed. Furthermore, the strategies for these malignancies are reassessed, based on our experiences. R1/2 and R0 resections are regarded as those with residual and no tumor after surgery. The present data show that patients who underwent R1/2 resection after neoadjuvant CRT experienced little survival benefit, while complete response (CR) cases after definitive CRT had comparatively better results. Therefore, curative surgery should not be attempted without down-staging, and definitive CRT should be the initial treatment. Then surgery is indicated for the eradication of residual cancer cells. Close surveillance is essential for early detection of relapse even after CR, because the operation will gradually become increasingly difficult due to post-CRT fibrosis. In conclusion, multimodality therapy consists of definitive CRT followed by R0 resection, which can be the treatment of choice for T4 esophageal carcinoma. These challenging treatments have the potential to constitute the most effective therapeutic strategy.     

Two patients with acute rotavirus encephalitis associated with cerebellar signs and symptoms

Rotavirus, one of the major causes of severe gastroenteritis in children, occasionally causes central nervous system complications. Recently several patients with acute encephalitis/encephalopathy due to rotavirus associated with cerebellar signs and symptoms have been reported. The condition is characterized by disturbances of consciousness at onset and cerebellar signs and symptoms such as hypotonia, ataxia, dysmetria, and speech disorders, including mutism, slow speech, and dysarthria at convalescence. We report two patients (3-year-old girl, 2-year-old boy) who developed acute encephalitis due to rotavirus and showed cerebellar signs and symptoms. Both patients had characteristic history of consciousness disturbances subsequent to several days of diarrhea, vomiting and fever, and cerebellar symptoms such as hypotonia, ataxia, dysmetria, and speech disorders during the recovery period. Electroencephalography showed diffuse high-voltage delta wave activity in each patient. Brain magnetic resonance imaging showed cerebellar edema in the acute phase followed by cerebellar atrophy on follow-up images in both patients. In the first patient, diffusion-weighted images (DWI) revealed high signals at the left cerebellar peduncle region and apparent diffusion coefficient (ADC) maps showed decreased ADC values of the lesion in the acute phase. The first patient had dysmetria at 1-year follow-up. However, she had normal motor and cognitive functions and could lead her daily life without impairment. In the second patient, no further symptoms were apparent at 1-year follow-up. Acute encephalitis/encephalopathy due to rotavirus with cerebellar signs and symptoms might be diagnosed on DWI, by demonstrating decreased ADC values in acute phase.     

Correlation between magnetic resonance imaging and clinical profiles of periventricular leukomalacia.

Magnetic resonance imaging (MRI) findings of 70 children with periventricular leukomalacia (PVL), examined between 1 year 2 months and 8 years of age (mean: 2 years 4 months of age), were analysed. Neurological assessments were made between 1 year 3 months and 15 years (mean: 4 years 9 months). The possible correlations between MRI findings and clinical profiles of PVL were investigated using three parameters of the MRI findings. The grade of ventriculomegaly correlated well with the severity of cerebral palsy (CP) but not with the severity of mental impairment. The grade of reduction of periventricular white matter correlated well with the severity of CP and mental impairment, and is the most reliable parameter for neurological prognosis. The degree of periventricular hyperintensity on T2-weighted images did not correlate well with severity of CP, but correlated to some degree with mental impairment. There was a significantly lower degree of periventricular hyperintensity in children at less than 28 weeks of gestation than at 28 or more weeks of gestation, but no significant difference in other parameters. The periventricular hyperintensity should be evaluated in view of the gestational age.     

Surgical management of umbilical basal cell carcinoma: Published work review and the optimal depth of surgical excision

Basal cell carcinoma (BCC) is a common malignant skin tumor. However, BCC that arise at the umbilicus is rare. We present three cases of umbilical BCC. Each BCC was excised at a different depth level, and all deep surgical margins were negative. All patients had no evidence of local recurrence or metastasis during the follow‐up periods (12, 24, and 52 months). Reviewing the reported cases of umbilical BCC, the BCC cells did not seem to invade into the umbilical scar in most cases, and the deepest invasion levels of tumor cells were up to the middle layer of the subcutaneous tissue. However, the dermatological surgeons have to consider the possibility of surgical excision down to and including the umbilical attachment to the peritoneum, and intraoperative margin assessment should be necessary to avoid the risk of excessive or incomplete excision.     

Acquired agminated melanocytic nevus in the acral area is a potential mimicker of acral lentiginous melanoma: A three-case series report and published work review

Agminated nevus refers to a clustered group of melanocytic nevi confined to a localized area of the body. It rarely involves acral skin, but recognition of acquired agminated nevus (AAN) in the acral area is clinically important because it may mimic acral lentiginous melanoma (ALM). However, acral AAN has only been described in a few case reports and its clinical characteristics remain unclear. We report three additional cases of acral AAN to further analyze the differential points between ALM. Clinical images, including those of dermoscopy, of three cases of acral AAN were reviewed. The lesions were located on the sole or lateral border of the foot. All acral AAN were flat and large in size (>20 mm in greatest dimension), and associated with asymmetry and irregular border. However, no parallel ridge pattern suggesting ALM was observed on dermoscopy. In two patients, the lesions on the sole were totally resected; microscopic evaluation of these two lesions confirmed junctional nests of banal melanocytes. AAN lesions on the sole with chronic mechanical pressure are slightly larger and more diffuse; thus, they may be more likely to be overdiagnosed as malignancy upon inspection than those in the non-acral area. Understanding the concept of the disease and careful dermoscopic evaluation leads to an accurate diagnosis.