Arteriovenous malformation of the gallbladder: CT and angiographic findings

We encountered a case of arteriovenous malformation (AVM) of the gallbladder in a patient with hepatocellular carcinoma (HCC). Contrast-enhanced computed tomography (CT) showed serpentine vessels around and within the gallbladder wall. Angiography showed dilated and tortuous cystic arteries, a racemose vascular network, and early-filling cystic veins. Transcatheter arterial embolization of two cystic arteries feeding the AVM was performed with platinum microcoils prior to transcatheter arterial chemoembolization for HCC to prevent embolic particles from flowing into these arteries. Follow-up contrast-enhanced CT showed blood flow in the gallbladder AVM, which appeared to be fed by the arterial collaterals.     

CURRENT STATUS AND EVALUATION OF LAPAROSCOPIC SURGERY FOR GASTRIC CANCER

Laparoscopic gastrectomy for gastric cancer was developed in Japan and has been established as a treatment for early gastric cancer thanks not only to improvements in technology and medical equipment but also to great efforts made by surgeons. With increasing numbers of surgeons performing the procedure and extending its indication to some advanced gastric cancers, it has achieved an important position in the treatment of gastric cancer together with endoscopic mucosal resection and open surgery. In clinical practice, it has been accepted as a safe, minimally invasive and radical treatment for early gastric cancer through several clinical studies and case–control studies. A large‐scale randomized controlled trial to evaluate laparoscopic gastrectomy as an acceptable procedure for early gastric cancer is being prepared. In order to extend the indication to some advanced gastric cancers, first, we need to collect more cases of laparoscopic gastrectomy for advanced cancer and start a phase II study in the experienced hospitals.     

S100A11 gene identified by in-house cDNA microarray as an accurate predictor of lymph node metastases of gastric cancer

Gastric cancer is one of the most common malignancies in the world, and in Asian countries its incidence and mortality rates are very high. Worldwide, Japan ranks first in the incidence of this type of cancer for both sexes. To shed light on the mechanisms underlying the development and/or progression of gastric cancer, we compared the expression profiles in gastric cancer cells obtained from surgical dissection of 20 gastric adenocarcinoma specimens with those in the corresponding non-cancerous mucosa, by cDNA microarray analysis. In total, 8,000 cDNA clones were randomly picked up and their 5'-end nucleotide sequences were determined. On the basis of sequence information, 4,608 independent clones were selected and used to produce the cDNA microarray. We identified 26 genes that were commonly up-regulated and 44 genes that were commonly down-regulated in cancerous tissues. To validate the cDNA microarray analysis, real-time PCR was performed. We found that gene S100A11 expression was associated with the development of lymph node metastases. S100A11 gene expression was clearly up-regulated in specimens from patients with lymph node metastases relative to those from patients without lymph node metastases. S100A11 gene expression status was useful to distinguish gastric cancers with lymph node metastases from those without lymph node metastasis. This genome-wide information contributes to an improved understanding of molecular changes during the development of gastric cancers. It may also help clinicians predict the development of lymph node metastases and assist researchers in identifying novel therapeutic targets for patients with gastric cancer.     

Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with apoptosis induction in esophageal cancer cells.

PURPOSE: The histone deacetylase inhibitor FK228 shows strong activity as a potent antitumor drug but its precise mechanism is still obscure. The purpose of this study is to reveal the effect of FK228 on gene expression in the cell and to determine the mechanism of the antitumor activity of FK228 for further clinical applications. EXPERIMENTAL DESIGN AND RESULTS: Microarray analysis was applied to verify the gene expression profiles of 4,608 genes after FK228 treatment using human esophageal squamous cell cancer cell lines T.Tn and TE2. Among them, peroxiredoxin 1 (Prdx1), a member of the peroxiredoxin family of antioxidant enzymes having cell growth suppression activity, as well as p21(WAF1), were significantly activated by FK288. In addition, FK228 strongly inhibited the cell growth of T.Tn and TE2 by the induction of apoptosis. Further, chromatin immunoprecipitation analysis revealed that FK228 induced the accumulation of acetylated histones H3 and H4 in Prdx1 promoter, including the Sp1-binding site. In mouse xenograft models of T.Tn and TE2 cells, FK228 injection resulted in significant tumor regression as well as activated Prdx1 expression in tumor tissues. Prdx1 suppression by RNA interference hindered the antitumor effect of FK228. CONCLUSION: Our results indicate that the antitumor effect of FK228 in esophageal cancer cells is shown at least in part through Prdx1 activation by modulating acetylation of histones in the promoter, resulting in tumor growth inhibition with apoptosis induction.     

Overexpression of bradykinin type 2 receptors on glioma cells enhances bradykinin-mediated blood-brain tumor barrier permeability increase

Variations in the expression levels of bradykinin (BK) type 2 receptors (B2R) in different brain tumors may explain variable increases in BK-mediated blood-brain tumor barrier (BTB) permeability. This study investigated whether elevation of the B2R expression levels on glioma cells enhances BK-mediated BTB permeability increases. Stable transfectants of C6 rat glioma cells overexpressing B2R were established by transfection with recombinant vectors harboring rat B2R cDNA sequence. Elevated B2R expression levels in transfectants were confirmed by quantitative real-time PCR, Western blots, and [3H]-BK binding studies. BTB permeability was quantified with autoradiography and expressed as a unidirectional transport constant, Ki, for [14C]-alpha-aminoisobutyric acid (AIB: Mr 103), using a rat brain tumor model. Baseline Ki values in tumors overexpressing B2R were not significantly higher than in control tumors. Ki values after BK treatment in tumors overexpressing B2R, however, were significantly higher than in control tumors. Western blots confirmed that B2R expression levels in vivo in tumors overexpressing B2R remained higher than in control tumors. These results suggested that alteration of B2R expression levels on tumor cells could modulate BK-mediated BTB permeability. Therefore, B2R expression levels in human glioma could be used to analyze the treatment results of patients undergoing treatment involving BK-modulated BTB permeability.     

NMDA receptor-mediated mechanism of ketamine-induced facilitation of glutamatergic excitatory synaptic transmission

The effect of ketamine on CA1-field EPSPs (fEPSPs) in rat hippocampal slices was investigated. Ketamine (100 microM) facilitated fEPSPs at 0.05 Hz. The fEPSP facilitation was suppressed completely by AP-5 and partially by propranolol, and also by an increase in stimulation frequency. These results indicate that ketamine facilitates excitatory synaptic transmission by activating NMDA receptors via beta-adrenoceptors under conditions in which NMDA receptor channel block is slight.     

Obstetrical anesthesia for parturient patients with HELLP syndrome

In the period from April 1995 to March 2000, 11 parturient patients were diagnosed as having HELLP syndrome and underwent Caesarian section at our institution. All of the patients also had eclampsia or preeclampsia. Six of the operations were performed under general anesthesia and 5 were performed under regional anesthesia (one epidural and 4 spinal blocks). Subarachnoid anesthesia was well tolerated and clinically serious decreases in blood pressure with onset of block were not common. In the cases in which general anesthesia was used, control of blood pressure was difficult and the Apgar scores of the babies were low. No major complications occurred during the postoperative periods. Anesthetic management of a parturient patient with HELLP syndrome is modeled on the underlying preeclamptic condition. Determination of the appropriate anesthetic should be based on the patient's condition, condition of the fetus, and the urgency of the situation.     

Different mechanisms of development and maintenance of experimental incision-induced hyperalgesia in human skin

BACKGROUND: To determine the mechanisms of postoperative pain, the effects of local anesthesia on development and maintenance of surgical incision-induced hyperalgesia were evaluated in a crossover, double-blinded, placebo-controlled human study using 17 subjects. METHODS: An experimental 4-mm-long incision through skin, fascia, and muscle was made in the volar forearm of each subject. In experiment 1, 1% lidocaine or saline in a volume of 0.2 ml was subcutaneously injected into the incision site pretraumatically and posttraumatically. In experiment 2, a 5-cm-long strip of skin was subcutaneously injected with 0.2 ml of 1% lidocaine near the incision site pretraumatically and posttraumatically. Flare, spontaneous pain, and primary and secondary hyperalgesia to punctate mechanical stimuli were assessed after the incision had been made. RESULTS: Pretraumatic lidocaine injection prevented the occurrence of spontaneous pain and development of flare formation that was found surrounding the incision site immediately (1 min) after the incision had been made. The lidocaine suppressed primary hyperalgesia more effectively than did posttraumatic block, but only for the first 4 h after the incision. The preincision block prevented development of secondary hyperalgesia, whereas posttraumatic block did not significantly affect the fully developed secondary hyperalgesia. The area of flare formation and the area of secondary hyperalgesia did not extend over the strip of the skin that had been pretraumatically anesthetized, whereas the posttraumatic block did not significantly reduce the area of fully developed secondary hyperalgesia. CONCLUSIONS: Pretraumatic injection of lidocaine reduces primary hyperalgesia more effectively than does posttraumatic injection, but only for a short period after incision. The spread of secondary hyperalgesia is mediated peripheral nerve fibers, but when secondary hyperalgesia has fully developed, it becomes less dependent on or even independent of peripheral neural activity originating from the injured site.     

Intracerebroventricular morphine produces antinociception by evoking gamma-aminobutyric acid release through activation of 5-hydroxytryptamine 3 receptors in the spinal cord

BACKGROUND: It has been generally considered that supraspinal morphine activates the serotonergic descending inhibitory system and releases serotonin (5-hydroxytryptamine [5-HT]) in the spinal cord, producing antinociception through activation of 5-HT receptors. The involvement of a spinal gamma-aminobutyric acid-mediated (GABAergic) system is also suggested in supraspinal morphine antinociception. It has been reported that spinal GABAergic system contributes to 5-HT3 receptor-mediated antinociception. In this study, the authors investigated the contribution of spinal 5-HT3 receptor and the GABAergic system in the intracerebroventricular morphine-induced antinociception. METHODS: Male Sprague-Dawley rats were used. Using the spinal microdialysis method, concentrations of 5-HT and GABA were measured after intracerebroventricular morphine administration. The effect of intracerebroventricular naloxone or spinal perfusion of a selective 5-HT3 receptor antagonist 3-tropanyl-indole-3-carboxylate methiodide on the spinal release of GABA after intracerebroventricular morphine administration was also examined. In the behavioral study, involvement of 5-HT3 receptors or GABAA receptors in the intracerebroventricular morphine-induced antinociceptive effect was investigated using the tail-flick test. RESULTS: Intracerebroventricular morphine (40 nmol) significantly increased spinal GABA and 5-HT release. Evoked spinal GABA release was reversed by intracerebroventricular naloxone (40 nmol) or spinal perfusion of 3-tropanyl-indole-3-carboxylate methiodide (1 mm). In the behavioral study, intracerebroventricular morphine produced significant antinociception. Intrathecal administration of either GABAA receptor antagonist bicuculine or 3-tropanyl-indole-3-carboxylate methiodide but not vehicle reversed the morphine-induced antinociceptive effect. CONCLUSION: Intracerebroventricular morphine evokes spinal GABA release via the activation of 5-HT3 receptors in the spinal cord, resulting in antinociceptive effect.     

Rho-kinase and myosin II activities are required for cell type and environment specific migration

Cell migration is important in the development of atherosclerotic lesions. Macrophages and smooth muscle cells migrate into the subendothelial space of arteries, leading to plaque formation. Long-term inhibition of the activity of Rho-kinase induces a regression of atherosclerotic coronary lesions, probably by preventing migration of macrophages and smooth muscle cells. Previous reports concerning the effect of Rho-kinase inhibitors on cell migration are contradictory, however. We examined here the cell type specificity of Rho-kinase inhibitors and found that migration of endothelial cells, macrophages, and smooth muscle cells was inhibited by treatment with Rho-kinase inhibitors in a dose-dependent fashion in a three-dimensional migration assay, whereas that of fibroblasts and epithelial cells was not inhibited. Myosin II inhibitor prevented cell migration in a manner similar to Rho-kinase inhibitors. In contrast, in a two-dimensional migration assay, cell migration was not inhibited by Rho-kinase or myosin II inhibitors for any of the cell types examined. Taken together, these results indicate that Rho-kinase inhibitors suppress migration of specific cell types under specific conditions through the regulation of myosin II activity. Our findings suggest that Rho-kinase is the therapeutic target of atherosclerosis accompanied with invasion by leukocytes and smooth muscle cells.