Halothane and propofol modulation of gamma-aminobutyric acidA receptor single-channel currents

Halothane and propofol enhance the activity of the gamma-aminobutyric acid (GABA) system, which is one of the most important systems in the mechanism of anesthesia. To determine whether halothane and propofol enhance GABAergic responses by the same mechanism, we performed single-channel patch-clamp experiments with rat cortical neurons in primary culture. Each of the open-time and closed-time distributions of GABA(A) receptor single channels was expressed by a sum of fast and slow time constants. Neither halothane nor propofol changed the single-channel conductance. Halothane increased the probability of the channel being open via a prolongation of the slow phase of open time, whereas propofol increased the channel open probability via a shortening of the slow phase of closed time. Thus, although both halothane and propofol augmented the channel open probability, thereby causing an increase in charge transfer during inhibitory transmitter action, they acted by different mechanisms.     

Smad3 deficiency attenuates renal fibrosis, inflammation,and apoptosis after unilateral ureteral obstruction

BACKGROUND: Transforming growth factor-beta (TGF-beta) has been implicated in the development of renal fibrosis induced by unilateral ureteral obstruction (UUO). However, there is little information on signaling pathways mediating TGF-beta activity involved in molecular and cellular events leading to renal fibrosis induced by UUO. In this study, we sought to determine whether Smad3, a major signaling component of TGF-beta, mediated renal fibrosis induced by UUO. METHODS: Renal fibrosis, inflammation, and apoptosis induced by UUO were macroscopically and histologically compared between wild-type mice and Smad3 null mice. RESULTS: Gross appearance of the kidney after UUO showed relatively intact kidney in Smad3 null mice [Smad3(-/-) mice] when compared with that of wild-type mice [Smad3(+/+) mice]. Renal interstitial fibrosis based on the interstitial area stained with Aniline-blue or Sirius red solution was significantly attenuated in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Deposition of type I and type III collagens were also significantly reduced in the obstructed kidney of Smad3(-/-) mice. In addition, the numbers of myofibroblasts, macrophages, and CD4/CD8 T cells infiltrated into the kidney after UUO were significantly attenuated in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Furthermore, terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining after UUO showed significantly reduced number of tubular apoptotic cells in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Endogenous Smad pathway was activated in the obstructed kidney after UUO in wild-type mice as judged by the increase of phosphorylated Smad2 or phosphorylated Smad2/3-positive cells in renal interstitial area. CONCLUSION: Smad3 deficiency attenuated renal fibrosis, inflammation, and apoptosis after UUO, suggesting that Smad3 was a key molecule mediating TGF-beta activity leading to real fibrosis after UUO.     

Three-dimensional anisotropy contrast imaging of gliomatosis cerebri: two case reports

BACKGROUND: Magnetic resonance imaging (MRI) can provide a preoperative diagnosis of gliomatosis cerebri, but the findings sometimes do not correspond with the clinical symptoms or histologic findings. CASE DESCRIPTION: Three-dimensional anisotropy contrast (3DAC) imaging was used to assess damage to the neuronal fibers in two patients with gliomatosis cerebri who presented with only mental deterioration. Conventional MRI depicted markedly abnormal findings consisting of widespread areas of abnormally high signal intensity in the corpus callosum and in the bilateral white matter in both cases. In contrast, 3-D AC imaging showed no abnormality except for small dark areas in the corpus callosum or white matter. CONCLUSION: 3-D AC imaging provides more accurate information about damage to the neuronal fibers in cases of gliomatosis cerebri than other MRI techniques.     

Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma

It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchymal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination.     

Reactive angioendotheliomatosis of the intestine

We present a case of reactive angioendotheliomatosis (RAE) of the colon, featuring intravascular proliferation of endothelial cells with histologic resemblance to glomeruloid hemangioma. A 19-year-old Japanese male with an anal fistula was diagnosed endoscopically with Crohn's disease. Six months later, he was hospitalized for fever and abdominal pain. Emergency resection of ileocecum and splenic flexure of the colon was undertaken to control massive intestinal hemorrhage, and in all parts of the resected colon, foci of many small vessels with intravascular proliferation of endothelial cells were noted throughout the layers. Moreover, solid proliferation of endothelial cells was seen in the submucosa at the base of open ulcers. Two small granulomas, compatible with Crohn's disease, were also evident in the muscle layer of the terminal ileum. No other hemangiomas or hemangioma-like structures were observed with CT scans, and the vascular lesions were histologically diagnosed as RAE. The pathogenesis of this disorder is unknown, and most cases occur in skin with systemic disease. The present case might thus be a first case of RAE of the intestine without cutaneous involvement. Whether there is a relation with coexistent enteritis suggestive of Crohn's disease needs to be clarified.     

A case of multiple cerebral infarction accompanied by a cor triatriatum

A cor triatriatum is a congenital malformation of the heart which, in almost all cases, is diagnosed in childhood, whereas adult cases are very rare. The hemodynamics of the cor triatriatum is similar to that of mitral stenosis, which sometimes, but rarely, causes embolism. We present a case of multiple cerebral infarctions accompanied with a cor triatriatum. A 57-year-old female suddenly displayed impaired consciousness and hemiparesis immediately after cranioplasty for another disease, and was diagnosed by a diffusion weighted MRI as having multiple infarctions. A transesophageal echocardiography detected a membrane-like, echo-dense structure across the left atrium, suggesting a cor triatriatum. We suspect that her multiple infarctions were caused by embolism due to a cor triatriatum. Here, we discuss the relationship between her embolic stroke and the cor triatriatum, with references to literature on the subject.     

Evaluation of radiation therapy for keloid using electron beam

In radiation therapy for keloid, electron beams are delivered to the skin through a lead shield hollowed into the shape of the keloid. The shape of a postoperative keloid scar is linear, causing the irradiation shield to be long and narrow. This lead shield is put on the surface of the skin. Therefore, it is considered that beam data used in general external irradiation are not applicable to irradiation for keloid. Therefore, we used a water equivalent phantom and measured beam data by using chambers or film dosimeters. Experimental conditions were the same as those of actual radiotherapy for keloid. As a result of this procedure, the radiation technique was optimized. Electron energy and thickness of the bolus, thickness of the lead shield, margins such that the planning target volume would receive the necessary dose, and the method of MU calculation all were determined. It was suggested that these experiments were useful to establish the appropriate technique in irradiation for keloid.     

Suppression of postoperative systemic inflammatory response syndrome with clarithromycin following lung cancer surgery

We examined whether clarithromycin (CAM), a 14-membered macrolide, can control the postoperative systemic inflammatory response syndrome that occurs following lung cancer surgery. In the control group (n = 16), prophylactic antibiotics (flomoxef) were administered for 4-7 days following surgery. In the CAM group (n = 10), 400 mg/day of CAM were administered orally for 14 days prior to surgery and for 7 days following surgery, in addition to the postoperative administration of flomoxef. The incidence and duration of the systemic inflammatory response syndrome in the CAM group (30%, 0.3 days) were significantly lower than those in the control group (81%, 1.6 days). There were no significant differences between the control and CAM groups in both the amount and frequency of nonsteroidal anti-inflammatory drugs following surgery. In conclusion, our study suggests that CAM may suppress the postoperative systemic inflammatory response syndrome in lung cancer patients.