Evidence that the nucleotide exchange and hydrolysis cycle of G proteins causes acute desensitization of G-protein gated inward rectifier K+ channels

The G-protein gated inward rectifier K⁺ channel (GIRK) is activated in vivo by the Gβγ subunits liberated upon G_i-coupled receptor activation. We have recapitulated the acute desensitization of receptor-activated GIRK currents in heterologous systems and shown that it is a membrane-delimited process. Its kinetics depends on the guanine nucleotide species available and could be accounted for by the nucleotide exchange and hydrolysis cycle of G proteins. Indeed, acute desensitization is abolished by nonhydrolyzable GTP analogues. Whereas regulators of G-protein signaling (RGS) proteins by their GTPase-activating protein activities are regarded as negative regulators, a positive regulatory function of RGS4 is uncovered in our study; the opposing effects allow RGS4 to potentiate acute desensitization without compromising GIRK activation.     

Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms

Glioblastoma (GBM) is the most mortality brain cancer in the world. Due to high invasion and drug resistance cause the poor prognosis of GBM. Naringenin, an ingredient of citrus, exhibits many cellular functions such as antioxidant, anti‐inflammation, and anticancer. Naringenin inhibits the migration of bladder and lung cancer via modulation of MMP‐2 and/or MMP‐9 activities, Naringenin inhibits migration and trigger apoptosis in gastric cancer cells through downregulation of AKT pathway. However, the effects of naringenin in GBM still remain to be elucidated. In this study, we reveal the molecular mechanisms of naringenin in the inhibition of migration and invasion in GBM. No overt alternation of cell proliferation was found in of GBM 8901 cells treated with different concentration of naringenin. Slight decreased cell viability was found in GBM 8401 cell treated with 200 and 300 μM naringenin. Significant reduction of migration and invasion as assayed by Boyden chamber analysis was found in of GBM cells treated with 100, 200, and 300 μM naringenin. Zymography analysis also revealed that the activities of MMP‐2 and MMP‐9 of GBM cells were significantly inhibited in response to 100, 200, or 300 μM naringenin treatment. Proteins of MMP‐2 and MMP‐9 were downregulated in naringenin treated GBM cells. In addition, naringenin also attenuated the activities of ERK and p38. Naringenin decreased mesenchymal markers (snail and slug) expression as revealed by Western blot analysis. Taken together, our findings indicated that naringenin eliminated the migration and invasion of GBM cells through multiple mechanisms including inhibition of MMPs, ERK, and p38 activities and modulation of EMT markers. Our results also suggested that naringenin may be a potential agent to prevent metastasis of GBM.     

Aortic squamous metaplasia in a patient with aortoesophageal fistula secondary to thoracic aortic aneurysm: An autopsy case

Aortoesophageal fistula (AEF) is highly lethal. A 74‐year‐old man presented with hematemesis and consciousness loss. He had a long‐term history of hypertension and gout. Computed tomography revealed an aneurysm of the distal descending thoracic aorta, which was treated by insertion of an aortic stent graft. After 24 days of stenting, endoscopic examination revealed an AEF. After 6 months of stenting, he died owing to mediastinitis. On autopsy, macroscopically, we found a 4 × 2.5‐cm, oval, well‐circumscribed AEF. We identified squamous epithelium in the area surrounding the AEF that covered the thoracic aorta inner cavity. Immunohistochemical analysis revealed that the squamous epithelium in the thoracic aorta was positive for p63 and 34βE12. In conclusion, we encountered a long‐term AEF case with aortic squamous metaplasia. To the best of our knowledge, human aortic metaplasia has never been reported. In the present case, aortic squamous metaplasia retained continuity with the esophageal squamous epithelium; therefore, the migration of the squamous epithelium through the AEF may have been induced by aortic erosion.     

Repeated bonding of fixed retainer increases the risk of enamel fracture

The aim of this study was to investigate the influences of repeated bonding, using 2 different orthodontic adhesive systems, on the shear bond strength (SBS) and the enamel surface morphology. Sixty premolars were divided into 2 groups (n = 30), and either Transbond XT (T group) or Fuji Ortho LC (F group) adhesives were used. SBS was measured 24 h after bonding, using a universal testing machine. Then, the enamel surfaces were investigated and the mode of failure was described using adhesive remnant index (ARI) scores. After each debonding, 10 teeth from each group were examined by scanning electron microscopy to determine the penetration of adhesives, the length of resin tags, and the state of the enamel surface. The other teeth were subjected to two more bonding/debonding procedures. In T group, the second debonding sequences had significantly higher bond strengths than the other sequences. The length of resin tags was greatest in the second debonding sequence, although there was no significant difference. In F group, the SBS increased with further rebonding and the failure mode tended towards cohesive failure. In both groups, the ARI scores increased with rebonding. Enamel loss could have occurred with both adhesives, although the surfaces appeared unchanged to the naked eye. From this study, we suggest that enamel damage caused by repeated bonding is of concern. To prevent bond failure, we should pay attention to the adhesion method used for bondable retainers.     

Comparison of mesiodistal tooth crown diameters and arch dimensions between modern Mongolians and Japanese

The purposes of this study were to establish normative data for mesiodistal tooth crown diameters and arch dimensions in Mongolian adults and to compare them with those of Japanese adults. The study materials comprised dental casts of 100 modern Mongolian and 100 Japanese subjects (50 males, 50 females for each) with Angle Class I normal occlusion. The mean ages were 20 years 8 months for the Mongolian subjects and 20 years 0 months for the Japanese subjects. On the dental casts, the mesiodistal tooth crown diameters (excluding wisdom teeth) and dental arch dimensions were measured. The following arch dimensions were measured: inter-canine lingual, inter-premolar lingual, inter-molar lingual, inter-molar central, coronal arch length, basal arch length, and basal arch width. In the Mongolian samples, significant sex differences were noted, and most of the items were significantly larger in males than in females. Significant differences between the Mongolian and Japanese samples were mainly noted in the premolar and molar regions, rather than in the anterior region, and were significantly smaller in the Mongolian samples. In the Mongolian samples, the molar section widths and basal arch width and length were significantly larger in males and females compared with the Japanese samples. These results suggest that the tooth crown size and arch dimensions in the Mongolian samples differed from those in the Japanese samples, and that establishment of the clinical norm for Mongolian adults might be helpful in formulating treatment plans for Mongolian patients, given that these parameters are the basic tools for diagnosis.     

Two forms of diffuse alveolar damage in the lungs of patients with acute respiratory distress syndrome

Acute respiratory distress syndrome is a severe disease, the treatment and pathophysiology of which are not completely established. The pathology of acute respiratory distress syndrome involves diffuse alveolar damage, which comprises severe alveolar epithelial cell damage, hyaline membrane formation, and festinate myofibroblast proliferation and fibrosis in the intra-alveolar spaces. We performed a clinicopathologic investigation of 26 autopsy cases of diffuse alveolar damage. Three cases of them were diagnosed as acute interstitial pneumonia that is idiopathic illness and resembles pathologically organizing diffuse alveolar damage. Immunohistochemical staining for types I and IV collagen, α-smooth muscle actin, and Ki-67 was carried out, and the sites of myofibroblast proliferation and type I collagen production were examined. All diffuse alveolar damage cases in the proliferative phase showed intra-alveolar myofibroblast proliferation. When diffuse alveolar damage was diagnosed pathologically as being due to severe infection, all 7 patients showed multiple organ dysfunction syndrome, whereas only 2 of 7 patients showed interstitial myofibroblast proliferation. When diffuse alveolar damage was attributed to tumor treatment with chemotherapy or to drug toxicity, 3 of 16 patients showed multiple organ dysfunction syndrome; 15 of 16 showed interstitial myofibroblast proliferation, 3 of 3 acute interstitial pneumonia patients did not show multiple organ dysfunction syndrome; and 3 of 3 acute interstitial pneumonia showed marked interstitial myofibroblast proliferation. These results suggest that the pathophysiologic mechanism of diffuse alveolar damage caused by severe infection is one of systemic circulation disturbance, although the mechanism underlying diffuse alveolar damage due to tumor with chemotherapy or drug toxicity appears to involve interstitial pneumonia-like lesions that are similar to acute interstitial pneumonia.     

Arterial Reconstruction during Pancreatoduodenectomy in Patients with Celiac Axis Stenosis—Utility of Doppler Ultrasonography

Celiac axis stenosis is found at an incidence of 2%–24% in the general population. During pancreatoduodenectomy in patients with celiac axis stenosis, division of the gastroduodenal artery from the common hepatic artery may cause acute ischemia of the upper abdominal organs, such as the liver, stomach, or spleen. Under these circumstances, the clinical indications of arterial reconstruction remain controversial. Between 1994 and 2003, seven patients with celiac axis stenosis (n = 4) or occlusion (n = 3) underwent pancreatoduodenectomy at our hospital. Arterial reconstruction, including division of the median arcuate ligament, was conducted in two patients; the replaced right hepatic artery was preserved in one patient, and no vascular refinement was undertaken in the remaining four of the seven patients. In two of the four patients without arterial reconstruction or preservation, the serum levels of liver enzymes were markedly elevated (> 800 IU/l) on postoperative day 1, and these patients subsequently developed liver abscesses. Two patients who underwent arterial reconstruction and three patients who showed no decrease in intrahepatic arterial flow under Doppler ultrasonography after clamping of the gastroduodenal artery developed no ischemic complications. Although our experience is limited, when intraoperative Doppler ultrasonography indicates a decrease in the hepatic arterial signals, we believe that reconstruction of the hepatic artery will be necessary to minimize ischemic complications in the liver in patients with celiac axis stenosis.     

Complications and Long-Term Sequelae of Bladder Fistula Repair

Bladder fistulas involve an abnormal connection between bladder and either vagina or intestine. In this review chapter, we cover the etiology, clinical presentation, and various surgical approaches to repairing vesicovaginal and enterovesical fistulas. The long-term sequela after surgical repair includes recurrent incontinence, lower urinary tract symptoms, infection, and vaginal stenosis. Strategies to approach fistula repair to minimize these complications are emphasized.     

Magnetic resonance imaging of anomalous fetuses

Magnetic resonance imaging (MRI) has been used sparingly in obstetrics. The reasons for this relate mainly to cost, availability, difficulty obtaining clear images because of fetal movement, and the convenience and utility of ultrasound. However, MRI use is expanding and has the potential to play an important role in selected problem pregnancies. We studied the pregnancies of five women whose fetuses showed anomalies by ultrasound. These included cases of a large body wall defect, a diaphragmatic hernia, hydrocephalus, Meckel-Gruber syndrome, and iniencephaly with a diaphragmatic hernia (the iniencephaly sequence). Three of these examinations followed fetal neuromuscular blockade, and two were associated with oligohydramnios without fetal paralysis. Paralysis provided superior images. The fetal central nervous system, subcutaneous tissue, and liver imaged particularly well. This study illustrates that MRI can enhance and even clarify certain information provided by ultrasound.