Phacoemulsification and aspiration (PEA) has become the most popular cataract surgery, due to the establishment of safe surgical techniques and development of associated instruments. However, corneal endothelial damage still represents a serious complication, as excessive damage can lead to irreversible bullous keratopathy. In addition to causes such as mechanical or heat injuries, free radical formation due to ultrasound has been posited as another cause of corneal endothelium damage in PEA. Ultrasound in aqueous solution induces cavitation, directly causing water molecule disintegration and resulting in the formation of hydroxylradicals, the most potent of the reactive oxygen species. Considering the oxidative insult to endothelial cells caused by free radicals, their presence in the anterior chamber may represent one of the most harmful factors during these procedures. Indeed, some researchers have recently started to evaluate PEA from the perspective of oxidative stress. Conversely, the major ingredient in ophthalmic viscosurgical devices (OVDs), which are indispensable for maintaining the anterior chamber in PEA surgery, is sodium hyaluronate, a known free radical scavenger. OVDs can thus be expected to provide some anti-free radical effect during PEA procedures. In addition, since commercially available OVDs display different properties regarding retention in the anterior chamber during PEA, the anti-free radical effect of OVDs is likely to depend on behavior during irrigation and aspiration. The present study followed standard PEA procedures in an eye model and measured hydroxylradicals in the anterior chamber using electron spin resonance. The kinetics of free radical intensity and effects of several OVDs during clinical PEA were also demonstrated. These studies may be of significance in re-evaluating OVDs as a chemical protectant for corneal endothelium, since the OVD has thus far only been regarded as a physical barrier. In addition, many reports about corneal endothelium damage during PEA have been published, but objective evaluation of various damaging factors has been difficult. The present assay of free radicals in a simulation of clinical PEA offers the first method to quantitatively assess stress on the corneal endothelium.


抄録全体を表示

Epithelial cells of the gastrointestine undergo a rapid cell-renewal and originate from stem cells throughout the life of the organisms. Previous studies have provided a solid body of evidence to show that the epithelial cell-renewal is under the strict control of cell-cell and cell-extracellular matrix (ECM) interactions between the epithelium and the connective tissue. Especially, the microenvironment around the stem cells called "niche" is thought to play important roles in this control, and its disruption leads to diseases or disorders such as cancer in the human gastrointestine. Although understanding how the niche affects the stem cells is clinically important, its mechanisms still remain mostly unknown at the molecular level, possibly due to difficulties in the identification of the stem cells in the gastrointestine. Recent progress in cell and molecular biology is gradually beginning to shed light on some of the key signaling pathways in the cell-renewal of the intestinal epithelium, such as Wnt/T-cell factor (TCF)/β-catenin, Notch, Sonic hedgehog (Shh)/bone morphogenetic protein (BMP) signaling pathways, which are also involved in embryonic organogenesis and/or adult carcinogenesis. At present, only fragmentary information is available on their precise functions in the intestine. Nevertheless, there is a growing body of evidence that such signaling pathways have conservative functions in the intestine throughout terrestrial vertebrates, suggesting the usefulness of experimental animals to clarify molecular mechanisms regulating epithelial cell-renewal. In this article, I review some recent findings in this field, with particular focus on our studies using the Xenopus laevis intestine, where the stem cells form the mammalian-type intestinal epithelium under the control of connective tissue during metamorphosis. This Xenopus experimental system will certainly serve as a useful model for the study of the intestinal niche, whose clarification is urgently needed in regenerative medicine.


抄録全体を表示

Endogenous carbon monoxide (CO) production has been recently observed to be an index of the inflammatory response, reflecting various insults in critically ill patients. Major surgery is supposed to modulate the production of CO by transcriptional regulation of heme oxygenase (HO). CO is easy to measure as carboxyhemoglobin (CO-Hb) by spectrophotometry; however, whether CO-Hb can be used as an index reflecting surgical insults is unknown. We investigated changes in CO generation during coronary artery bypass graft by measuring CO-Hb concentrations and the expression of HO in circulating blood as well as the expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The expression ratios of heme oxygenase-1 (HO-1), TNF-α, and IL-1β significantly increased after surgery, and these values correlated significantly with one another. CO-Hb concentrations significantly increased after surgery; however, many of those values during artificial ventilation with high inspired oxygen fraction were within normal limits. Furthermore, changes in CO-Hb concentrations were small when preoperative values were high. On the whole, CO-Hb concentrations significantly but weakly correlated with the expression ratios of the inflammatory mediators. However, they did not correlate in the patients who showed higher preoperative CO-Hb concentrations. These data indicate that CO-Hb concentrations can, in general, reflect the inflammatory response induced by surgical insult; however, CO-Hb measurement may not be a useful form of clinical monitoring because of the limited degree of changes, the variation of baseline values, and the necessity for the management under fixed conditions.


抄録全体を表示

Mucinous cystic ovarian tumors sometimes contain calcifications, but the frequency and significance of such calcifications in diagnostic radiology are not well understood. We therefore retrospectively investigated the radiological and histopathological evidence of calcifications in 44 cases of ovarian mucinous cystic tumors (22 benign, 13 borderline, and 9 malignant) and 21 cases of ovarian serous cystic tumors (6 benign and 15 malignant) in which a non-contrast CT scan was performed. The shape and distribution of the calcifications in the mass lesion were assessed both radiologically and histopathologically.Calcifications were noted in 34.1% of mucinous cystic tumors on CT scans and 56.8% in histopathological studies, and they were found in two locations, intramural and intra-cystic, according to the histopathological findings. Intramural calcifications were frequent in benign tumors, and intra-cystic calcifications were frequent in proliferating tumors. Calcifications (psammoma bodies) were noted in 4.7% of serous cystic tumors on CT scans and 14.3% in histopathological studies. CT was not sufficiently sensitive in the detection of intra-cystic calcification in mucinous tumors and psammoma bodies in serous tumors. However, the presence of intramural calcifications may be a good indicator of mucinous tumors. Understanding the frequency and morphology of the calcifications in these neoplasms is one of the keys to making a correct diagnosis.


抄録全体を表示

Purpose: A minimally invasive thoracoscopic surgery offers several options in diagnosis and surgical treatment in the field of pediatric surgery. We would like to review our surgical experience and to assess the clinical outcomes and problems encountered during thoracoscopic surgery in children and adolescents focusing on children less than 6 years old.Patients and Methods: In 1992 and 2003, 977 patients underwent thoracoscopic surgery for chest diseases. Among them, from 1994 to 2003, 71 children and adolescents underwent thoracoscopic surgery. The thoracoscopic surgical procedures were classified into thoracoscopic surgery (TS) and video-assisted thoracic surgery (VATS). TS was performed through three or four trocar ports. VATS was performed through a small chest incision (minithoracotomy) with one or two trocar ports.Results: There was no morbidity or mortality associated with the thoracoscopic surgical procedures. None of the patients required a conversion to standard thoracotomy. The thoracoscopic surgical procedures were feasible in 71 children and adolescents with chest diseases including spontaneous pneumothorax, pulmonary nodules, diffuse pulmonary disease, pulmonary sequestration, and mediastinal tumors, and in those with palmar hyperhidrosis. TS was performed on two of five children with benign diseases including diffuse pulmonary disease and mediastinal bronchogenic cyst. VATS was performed on three children with pulmonary sequestration, lymphoid interstitial pneumonia and mediastinal Ewing's sarcoma. In one child with lymphoid interstitial pneumonia, the thoracoscopic surgery was converted to VATS because adhesion did not allow TS. The TS allowed rapid histological diagnosis and surgical treatment for benign pulmonary diseases and mediastinal cyst. Patients who were suffering from disease-related symptoms obtained complete relief with an uneventful postoperative course and quickly returned to their normal life. A boy who underwent lobectomy showed a normal growth rate for 4 years postoperatively. In the case of malignant chest diseases, the combination of chemotherapy and VATS was an effective treatment strategy.Conclusions: We considered that the thoracoscopic approach is a rapid and simple method in the therapeutic diagnosis and surgical treatment of children and adolescents, even in children less than 6 years old. Cosmetic benefits were also obtained for girls. However, the most important consideration is the decision on a treatment strategy made by both pediatrician and thoracic surgeon.


抄録全体を表示

Objective: While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro.Design: Prospective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2; a cannabinoid antagonist, AM281; and ion-channel antagonist.Setting: University research laboratorySubjects: Thirty guinea pigs (20 for in vivo study, 10 for in vitro) Measurements and main results: Colonic motility was monitored in vivo using telemetry via a force transducer attached to the guinea pig taenia caecum. Taenias isolated from other guinea pigs were studied in vitro to assess cannabinoid effects on muscle contractions evoked pharmacologically or electrically. Immediately after cannabinoid injection in conscious guinea pigs, taenial relaxation began peaking at 30 to 40 min. In animals pretreated with AM281, a CB1 cannabinoid receptor antagonist, cannabinoid evoked relaxation was less evident. In vitro, cannabinoids suppressed KCl-induced taenial contractions; this suppression was opposed by charybdotoxin, a Ca²⁺-activated K⁺-channel inhibitor, but not AM281. Cannabinoids decreased amplitude of repeated contractions evoked by electrical stimulation (an effect inhibited by AM281) but not muscle tension.Conclusions: Cannabinoids decreased intestinal tract tension in vivo, apparently via central CB1 receptors. This differs from peristaltic suppression.


抄録全体を表示

Limited information is available about histopathological reactions to the implanted endocardial electrodes of pacemakers (PM). Gross anatomic and histologic studies of tissue reactions to PM electrodes were made in thirteen autopsy cases (nine men and four women, ages 25∼89 years, mean age 71.8) who died two months to twenty-one years after PM implantation. Nine of them had complete atrioventricular (AV) block, three had sick sinus syndrome, and one had bradycardia-tachycardia syndrome. The direct causes of death were not related to their PM. The tip with projecting tines was implanted in the right ventricle in all patients. At the contact area between the electrode and the endocardium, no tissue reaction was observed in one patient with a history of over sixteen years of PM implantation. However, cardiomyocytes under the tip had been replaced by fibrotic tissue in many other patients. In two patients in particular where the electrode had been implanted at the apex of each right ventricle, all cardiomyocytes had disappeared and only fibrotic tissue and adipose tissue were observed under the tip. These findings suggest that mechanical stress caused by attaching the tip tightly damages cardiomyocytes and brings about changes in the pacing thresholds. In three patients, a space was seen between the tip and the endocardium. A fibrous sheath covering the electrode extended to the tip and formed a thick fibrous cap. This non-excitable fibrous cap acted as a virtual electrode and possibly affected the elevation of the threshold in these patients. In four patients, extensive myocardial fibrosis due to disease, e. g. previous myocardial infarction, dilated cardiomyopathy, amyloidosis, or sarcoidosis, was found in the area surrounding the tip and also might affect the elevation of the threshold. We concluded that elevation of pacing thresholds after PM implantation is not due to reactive endocardial thickening. The space between the tip and the endocardium is occupied by a fibrous sheath, and an overly tight attachment damages cardiomyocytes causing replacement fibrosis. Thus, it is not desirable in some patients to insert the electrodes into the apex, where the myocardium is thin. To avoid the elevation of thresholds, development of further devices is necessary to allow electrode fixation to the endocardium with a more suitable pressure level.


抄録全体を表示

We report 45- and 61-year-old women with generalized prurigo nodularis-like eruption whose clinical, histologic and immunopathologic features were consistent with the diagnosis of pemphigoid nodularis. In one case, nodular lesions preceded the onset of generalized blistering by two years and in the other, no definite blister nor erosion was seen except for some appearing on the soles during the course of the disease. Western immunoblotting of EDTA-separated epidermal extracts revealed that the 230-kD bullous pemphigoid (BP) antigen was recognized by circulating autoantibodies in the patient sera, but the 180-kD BP antigen was not. The 180-kD BP antigen was recognized weakly by immunoblotting of the 180-kD BP antigen NC16a domain fusion protein, which shows high detection sensitivity. These findings suggested that weak reactivity of autoantibodies with either whole or a part of the 180-kD BP antigen molecule in some way accounts for negligible or localized blister-formation in this disorder. However, no particular change was noted in the reactivity with 180-kD BP antigen between the patient serum obtained before and after the development of generalized blistering. It is possible that different factors from the changes in serum reactivity with BP antigens may be involved in initiating generalized blistering.


抄録全体を表示

We describe successful resection of rapidly enlarging liver metastases from an α-fetoprotein-producing gastric cancer, as these usually carry a dismal prognosis.A 68-year-old woman underwent distal gastrectomy for an α-fetoprotein-producing gastric cancer without liver metastasis. The tumor was a moderately differentiated tubular adenocarcinoma with invasion of the muscularis propria. Venous and lymphatic invasion were noted, as was metastasis to lymph nodes along the greater curvature. Serum α-fetoprotein was 331 ng/mL before gastrectomy, decreasing to 18.6 ng/mL by postoperative day 28. At 2 months after operation, computed tomography detected no metastasis, but at 4 months α-fetoprotein increased to 2,190 ng/mL, and at 5 months liver tumors were detected by ultrasonography and computed tomography. Serum α-fetoprotein increased to 5,673 ng/mL, and serum PIVKA2 concentration was 18 mAU/ml just before operation. Extended left hepatectomy was performed. The resected specimen of segment 4 contained two well-defined tumors, measuring 5×4 cm and 2×2 cm, while that of segment 5 contained a similar-appearing tumor measuring 2×2 cm. The resected tumors had the same histologic appearance as the previously removed gastric cancer. The tumor cells were immunohistochemically reactive for α-fetoprotein. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. Serum α-fetoprotein decreased to 20 ng/mL by postoperative day 15, and to 5 ng/mL by 2 months after operation. For 5 months since operation, no recurrence has become evident, and serum α-fetoprotein has remained within the normal range.


抄録全体を表示