PKCα suppresses osteoblastic differentiation

Protein kinase C (PKC) plays an essential role in cellular signal transduction for mediating a variety of biological functions. There are 11 PKC isoforms and these isoforms are believed to play distinct roles in cells. Although the role of individual isoforms of PKC has been investigated in many fields, little is known about the role of PKC in osteoblastic differentiation. Here, we investigated which isoforms of PKC are involved in osteoblastic differentiation of the mouse preosteoblastic cell line MC3T3-E1. Treatment with G?6976, an inhibitor of PKCα and PKCβI, increased alkaline phosphatase (ALP) activity as well as gene expression of ALP and Osteocalcin (OCN), and enhanced calcification of the extracellular matrix. Concurrently, osteoblastic cell proliferation decreased at a concentration of 1.0 μM. In contrast, a PKCβ inhibitor, which inhibits PKCβI and PKCβII, did not significantly affect osteoblastic differentiation or cell proliferation. Knockdown of PKCα using MC3T3-E1 cells transfected with siRNA also induced an increase in ALP activity and in gene expression of ALP and OCN. In contrast, overexpression of wild-type PKCα decreased ALP activity and attenuated osteoblastic differentiation markers including ALP and OCN, but promoted cell proliferation. Taken together, our results indicate that PKCα suppresses osteoblastic differentiation, but promotes osteoblastic cell proliferation. These results imply that PKCα may have a pivotal role in cell signaling that modulates the differentiation and proliferation of osteoblasts.     

Double cancer of the cystic duct and gallbladder associated with low junction of the cystic duct

We report a case of double cancer of the cystic duct and gallbladder associated with low junction of the cystic duct. A 73-year-old woman was admitted to the hospital complaining of upper abdominal pain. Endoscopic retrograde cholangiography showed a stenotic lesion in the lower common bile duct and no visualization of the cystic duct or gallbladder. Enhanced computed tomography revealed a heterogeneously enhanced tumorous lesion around the lower bile duct in the pancreatic head. A diagnosis of cancer arising from the cystic duct that entered the lower part of the common hepatic duct was made by intraductal ultrasonography, which showed an intraluminal protruding lesion in the cystic duct. Isolated gallbladder cancer was also diagnosed, by abdominal computed tomography. She underwent pancreaticoduodenectomy with dissection of regional lymph nodes. Histological examination revealed moderately differentiated adenocarcinoma of the cystic duct and well-differentiated adenocarcinoma of the gallbladder. Double cancer of the cystic duct and gallbladder is extremely rare, and this case also suggests a relationship between a low junction of the cystic duct and neoplasm in the biliary tract.     

Esophageal intubation: Can it be avoided with the airway scope (Pentax-AWS)?

Airway scope (AWS) is a rigid indirect laryngoscope with integrated tube guidance and can improve laryngeal exposure compared to the conventional direct laryngoscope. It is expected that the clear and improved laryngeal view obtained with AWS can eliminate the risk of esophageal intubation. We, however, experienced 3 cases of esophageal intubation out of 600 clinical cases with AWS in 15 month after its market release. Two cases were by novice anesthesiologists with fewer than 10 intubation experiences with AWS. Although they had had more than 100 intubation experiences with Macintosh laryngoscope, they did not have sharp eye for incorrect intubation with AWS. The third case was performed by an experienced laryngoscopist but it was difficult to identify the glottic opening because patient had distracted airway anatomy due to laryngeal tumor. In all cases esophageal intubation was immediately noticed and airway was secured uneventfully. We conclude that intubation under vision with improved laryngeal view is still not sufficient to prevent esophageal intubation.     

Cecal volvulus in cerebral palsy: Report of a case

A rare case of cecal volvulus in cerebral palsy that was preoperatively diagnosed and surgically treated without complications is herein reported. A 45-year old man, who had been treated for cerebral palsy as a result of a neonatal cerebral hemorrhage, was admitted to our hospital because of abdominal pain and vomiting. A plain abdominal X-ray film showed evidence of a huge quantity of gas in the left abdomen. Using a gastrographin enema from the colonoscope, an obstruction of the ascending colon was revealed with tapering of the lumen. A computed tomography scan showed a grossly dilated air-distended bowel in the left abdomen and soft tissue with internal architecture containing swirling strands of soft tissue and fat attenuation. An emergency laparotomy was performed. During the laparotomy the ileocecal region, which was unfixed at the retroperitoneum, was found to be twisted counterclockwise by 360° around the mesentery with the terminal ileum, thus resulting in a diagnosis of cecal volvulus. We therefore conducted an ileocecal resection. Cecal volvulus is an uncommon form of intestinal obstruction with a high mortality rate and may present considerable difficulty in diagnosis. Although cecal volvulus is rare as a cause of intestinal obstruction, it should be included in the differential diagnosis of bowel obstruction in cerebral palsy.     

Viability of liver grafts from fasted donor rats: relationship to sinusoidal endothelial cell apoptosis

Previous studies have shown that livers from fasted donors appear to tolerate long-term preservation better than livers from fed donors, but the mechanism is not clear. Some studies have shown that the apoptosis of sinusoidal endothelial cells (SEC) appeared to be a pivotal mechanism of ischemia/reperfusion injury in liver transplantation. The purpose of the present investigation was to evaluate the relation of SEC apoptosis to liver viability in rats after liver transplantation, comparing findings for fasted and fed donors. Wistar rats were used as donors and recipients. The fed group had access to solid feed and water ad libitum. The fasted group was allowed access only to water for 4 days prior to liver harvest. All rat livers were preserved with University of Wisconsin (UW) solution at 2 °C for 24 h. After preservation, the livers were orthotopically transplanted, and survival time was measured. Apoptosis was determined by in-situ staining for apoptotic cells, using a TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay and electron microscope (EM) examination separately. The 14-day survival rates after 24-h preservation were 0% (0/11) for recipients of livers from fed donors and 91% (10/11) for recipients of livers from fasted donors. There was no significant difference in the numbers of TUNEL-positive SEC after 24-h preservation between the two groups. However, at 6 h after transplantation, the number of TUNEL-positive SEC was significantly higher in the fed group than in the fasted group. These results suggest that donor fasting decreases SEC apoptosis after reperfusion alone, and that this may be related to the protection of the liver graft from reperfusion injury. Received: December 22, 2000 / Accepted: February 15, 2001     

Tumor location affects the results of simple excision for multiple osteochondromas in the forearm

BACKGROUND: The effectiveness of excision of osteochondromas in controlling the progression of forearm and wrist deformity remains an issue of controversy. The purpose of this study was to analyze the effectiveness of tumor excision in the correction of forearm and wrist deformity due to multiple osteochondromas in children, with an interpretation of the results based on different patterns of deformity. METHODS: Fourteen forearms in thirteen children with a follow-up of more than twenty-four months (average, fifty-three months) were included in the study. The forearms were divided into two groups on the basis of the location of the tumor and the pattern of deformity. In Group 1 (six forearms), the osteochondroma was only in the distal aspect of the ulna and caused compression of the radius. In Group 2 (eight forearms), tumors were in both the distal aspect of the ulna and the ulnar side of the distal part of the radius and were in contact with each other. Radial length, ulnar shortening, radial bowing, the radial articular angle, and carpal slip were measured as radiographic parameters. Ulnar shortening and radial bowing were expressed as a percentage of the radial length to make it possible to compare data between the individuals. Each parameter was evaluated before surgery and at the time of final follow-up. RESULTS: In Group 1, the percentage of ulnar shortening and the percentage of radial bowing had improved at the time of final follow-up; however, in Group 2, both the radial articular angle and the percentage of radial bowing had deteriorated significantly after the tumor excision (p = 0.049 and p = 0.017, respectively), even though the percentage of ulnar shortening showed no change. CONCLUSIONS: The effectiveness of simple excision of osteochondromas of the distal aspect of the forearm is influenced by the tumor location and is related to the pattern of the deformity. Simple tumor excision can correct the forearm deformity in patients with an isolated tumor of the distal part of the ulna. Conversely, in patients with tumors involving the distal part of the ulna and the ulnar side of the distal end of the radius, tumor excision alone is a less promising procedure for the correction of the deformity. LEVEL OF EVIDENCE: Prognostic Level IV.     

Bladder-Sparing Extended Resection of Locally Advanced Rectal Cancer Involving the Prostate and Seminal Vesicles

Purpose Total pelvic exenteration (TPE) is the standard procedure for locally advanced rectal cancer involving the prostate and seminal vesicles. We evaluated the feasibility of bladder-sparing surgery as an alternative to TPE. Methods Eleven patients with advanced primary or recurrent rectal cancer involving the prostate or seminal vesicles, or both, underwent bladder-sparing extended colorectal resection with radical prostatectomy. The procedures performed were abdominoperineal resection (APR) with prostatectomy (n = 6), colorectal resection using intersphincteric resection combined with prostatectomy (n = 4), and abdominoperineal tumor resection with prostatectomy (n = 1). Local control and urinary and anal function were evaluated postoperatively. Results Cysto-urethral anastomosis (CUA) was performed in seven patients and catheter-cystostomy was performed in four patients. Coloanal or colo-anal canal anastomosis was also performed in four patients. There was no mortality, and the morbidity rate was 38%. All patients underwent complete resection with negative surgical margins. After a median follow-up period of 26 months there was no sign of local recurrence, and ten patients were alive without disease, although distant metastases were found in three patients. Five patients had satisfactory voiding function after CUA, and three had satisfactory evacuation after intersphincteric resection (ISR). Conclusion These bladder-sparing procedures allow conservative surgery to be performed in selected patients with advanced rectal cancer involving the prostate or seminal vesicles, without compromising local control.     

Effect of ventralis intermedius thalamotomy on the area in the sensorimotor cortex activated by passive hand movements: fMR imaging study

Stereotactic ventralis intermedius (Vim) thalamotomy is effective for essential tremor (ET) of the limb, but the effect on the activity of the sensorimotor cortex is still unclear. The functional changes in this cortical area of patients with ET after Vim thalamotomy were investigated using functional magnetic resonance (fMR) imaging. Six patients underwent Vim thalamotomy for medically intractable ET, predominantly in the right hand. 1.5-tesla fMR imaging was performed using the blood oxygenation level-dependent sequence, before and after Vim thalamotomy, during passive movements with right wrist flexion and extension. Before and after images were analyzed using SPM99 software. Activation in the sensorimotor cortex and supplementary motor area evoked by wrist passive movement was observed both before and after surgery. Group analysis of changes in the blood oxygenation level-dependent response revealed a significantly smaller activated area postoperatively. Activation at the fundus of the central sulcus was characteristically decreased. All patients showed marked improvement in tremor after Vim thalamotomy. No patient experienced neurological deficits. fMR imaging showed that activation at the fundus of the central sulcus evoked by passive wrist movement was suppressed after Vim thalamotomy in ET patients, probably due to disruption of the thalamocortical pathway. The fundus of the central sulcus (Brodmann area 3a) is likely to be one of the key relays in the tremor circuit.     

Possible roles of 5-HT in vein graft failure due to intimal hyperplasia 5-HT, nitric oxide and vein graft

For vascular occlusive disease, an autologous vein graft is the most suitable conduit for arterial reconstruction. Intimal hyperplasia, resulting from the migration and proliferation of vascular smooth muscle cells, is a major obstacle to patency after vein grafting. The degree to which the function of nitric oxide (NO) in the vein graft is preserved has been reported to be associated with the magnitude of intimal hyperplasia. Serotonin (5-HT) is released from platelets in the vascular system and plays physiological roles in controlling the vascular tone. The subtype receptors contributing to the 5-HT-induced mechanical responses vary by vessel type (artery and vein) and among species (dogs, rabbits, rats, and so on). Recent studies have demonstrated that 5-HT induces vasoconstriction through the activation of 5-HT_2A receptors in smooth muscle cells or vasodilatation through the activation of endothelial 5-HT_1B receptors in arteries from various animals. However, the effects of 5-HT have not been clarified in grafted veins. We herein demonstrate the responses to 5-HT in un-operated veins and then autogenous vein grafts. Next, we describe the effects of chronic in vivo administration of Rho-kinase inhibitors and 5-HT_2A receptor antagonists, both of which reduce the 5-HT-induced contraction and intimal hyperplasia in vein grafts. Further studies targeting 5-HT are required to evaluate its possible benefits for autologous vein grafts with respect to vasospasm, function, and patency.