Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF‐β‐disrupted diffuse‐type gastric carcinoma

Diffuse‐type gastric carcinoma is characterized by rapid progression and poor prognosis. High expression of transforming growth factor (TGF)‐β and thick stromal fibrosis are observed in this type of gastric carcinoma. We have previously shown that disruption of TGF‐β signaling via introduction of a dominant negative form of the TGF‐β type II receptor (dnTβRII) into diffuse‐type gastric cancer cell lines, including OCUM‐2MLN, caused accelerated tumor growth through induction of tumor angiogenesis in vivo. In the present study, we show that TGF‐β induces upregulation of expression of tissue inhibitor of metalloproteinase 2 (TIMP2) in the OCUM‐2MLN cell line in vitro, and that expression of TIMP2 is repressed by dnTβRII expression in vivo. Transplantation of the OCUM‐2MLN cells to nude mice exhibited accelerated tumor growth in response to dnTβRII expression, which was completely abolished when TIMP2 was coexpressed with dnTβRII. Although the blood vessel density of TIMP2‐expressing tumors was only slightly decreased, the degree of hypoxia in tumor tissues was significantly increased and pericytes covering tumor vasculature were decreased by TIMP2 expression in OCUM‐2MLN cells, suggesting that the function of tumor vasculatures was repressed by TIMP2 and consequently tumor growth was reduced. These findings provide evidence that one of the mechanisms of the increase in angiogenesis in diffuse‐type gastric carcinoma is the downregulation of the anti‐angiogenic protein TIMP2. (Cancer Sci 2010; 101: 2398–2403)     

B7-H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma

B7-H1 is a member of the B7 family that inhibits the function of T-cells through its receptor programmed death-1 (PD-1). We examined B7-H1 expression in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) and found that it was constitutively expressed in both clinical samples and cell lines. In anaplastic lymphoma kinase–positive (ALK⁺) ALCL cells, B7-H1 expression was suppressed by the blocking of extracellular signal-regulated kinase (ERK) signaling and upregulated by the augmentation of ERK activity by phorbol 13-myristate 12-acetate stimulation, suggesting that B7-H1 expression is regulated by ERK signaling pathway in ALCL. ERK is one of the downstream mediators of nucleophosmin (NPM)/ALK signaling in ALK⁺ALCL, and pharmacological inhibition of ALK was shown to dephosphorylate ERK and down-regulate B7-H1. The involvement of NPM/ALK in B7-H1 expression was also demonstrated by introducing the construct into human non-ALCL lymphoid cell lines, which resulted in B7-H1 expression. In the case of HL, B7-H1 expression was shown to be dependent on the ERK and p38 mitogen-activated protein kinase (MAPK) signaling pathways. These results suggest that B7-H1 expression is controlled by common ERK signaling pathways in ALCL and HL cells. Our findings provide a potentially effective immunotherapeutic strategy for these B7-H1-expressing tumors. ( Cancer Sci 2009)     

Analysis of cross infection using genomic fingerprinting in nosocomial urinary tract infection caused by Enterococcus faecalis

To evaluate cross infection and a possible outbreak of Enterococcus faecalis urinary tract infection (UTI) in our urology ward, we studied the DNA fingerprinting of E. faecalis strains isolated from nosocomial UTI patients, in the period 1982–1996, using arbitrarily primed polymerase chain reaction (AP-PCR) analysis. The serovar and amplified products of DNA extracted from clinically isolated urinary E. faecalis strains by the AP-PCR method were analyzed, and the respective isolation periods of E. faecalis-positive UTI patients were investigated. There were nine patients with E. faecalis UTI between March and May 1994 and all strains isolated from their urine specimens were serovar type 7. AP-PCR revealed that five of the nine isolates had the same pattern. It appeared that these strains had caused the outbreak of E. faecalis UTI. Cross-infection between patients with E. faecalis UTI was demonstrated by genomic fingerprinting, suggesting that cross infection had occurred via urinary catheters or by hand contact in our ward. We may, therefore, reasonably conclude that we should beware of the transmission of urinary E. faecalis and take countermeasures against its dissemination. Received: April 8, 1998 / Accepted: October 14, 1998     

Diagnosis of peripheral pulmonary lesions using a bronchoscope insertion guidance system combined with endobronchial ultrasonography with a guide sheath

We developed a bronchoscope insertion guidance system that produces virtual images by extracting the bronchi by automatic threshold adjustment, and searching for the bronchial route to the determined target. We used this system in combination with a thin bronchoscope and endobronchial ultrasonography with a guide sheath (EBUS-GS), and evaluated its practicability, usefulness and safety.The subjects were 31 patients with 32 peripheral pulmonary lesions. Computed tomography (CT) data were transferred into this system, and virtual bronchial images were automatically produced by setting the lesion as the target. While virtual images with the target were displayed for comparison with real images by the system, a thin bronchoscope was advanced to the target bronchus. Transbronchial biopsy (TBB) was then performed by EBUS-GS.The system automatically produced virtual images to a median of fifth- (third- to seventh-) order bronchi. In all patients, the thin bronchoscope could be guided along the planned route, and observation to a median of fifth- (third- to seventh-) order bronchi was possible. Thirty lesions (93.8%) were successfully visualized by EBUS, and 27 (84.4%) could be pathologically diagnosed. In lesions ≤30 mm in size, the EBUS visualization yield was 91.7% (22/24), and the diagnostic yield was 79.2% (19/24). The median total examination time was 22.3 (9.8–41.5) min.In summary, using the bronchoscope insertion guidance system, virtual images can be readily produced, and the bronchoscope can be successfully guided to the target. This method is promising as a routine examination method in the biopsy of peripheral pulmonary lesions.     

Effectiveness of ropivacaine and fentanyl for postoperative epidural analgesia following thoracic surgery

BACKGROUND: Epidural ropivacaine is now a common drug used for postoperative analgesia. However, little information is available concerning regression of sensory blockade and analgesia following prolonged epidural infusion of ropivacaine. We investigated the efficacy of ropivacaine and fentanyl for postoperative analgesia after thoracic surgery. METHODS: Thirty patients undergoing thoracic surgery were enrolled. After surgery with general and thoracic epidural anesthesia, continuous epidural infusion of 0.2% ropivacaine+fentanyl (1.67 microg x ml(-1)) was started at a rate of 6 ml x h(-1) for patients whose height was more than 155 cm and 4 ml x h(-1) for those below 155 cm with possibility of an additional bolus injection of 3 ml at least every 60 min. RESULTS: An additional epidural injection of 3 ml produced a decrease in VAS without significant changes of vital signs. The greatest VAS was 10+/-25 mm in the incision site and 36+/-38 mm in the ipsilateral shoulder. Sensory blockade was sustained until the morning after the day of surgery. Also blood pressure and heart rate were stable throughout the observation period. There were no adverse effects except for slight nausea in three patients. CONCLUSIONS: A bolus of 3 ml with continuous 4-6 ml x h(-1) epidural injection of ropivacaine plus a small dose of fentanyl would decrease postoperative pain with stable vital signs in patients after thoracic surgery.     

Recurrence and extension of lobar hemorrhage related to cerebral amyloid angiopathy: multivariate analysis of clinical risk factors

BACKGROUND: Many recent studies have analyzed clinical risk factors for the recurrence and extension of intracerebral hemorrhage. However, they have not been investigated in patients with lobar hemorrhage related to cerebral amyloid angiopathy (CAA). METHODS: We studied 40 surgically treated patients with lobar hemorrhage diagnosed histologically as being related to CAA. To determine clinical factors influencing the recurrence and hematoma size their clinical data (demographics, medical history, and radiographic and laboratory data) were examined retrospectively and subjected to multivariate analysis. RESULTS: Twelve patients (30%) had recurrent lobar hemorrhage. Twenty-one patients had a small hematoma and 19 had a large hematoma. Hypertension was the only significant clinical factor influencing the recurrence of CAA-related lobar hemorrhage. There was no significant clinical factor influencing the hematoma size of CAA-related lobar hemorrhage. CONCLUSIONS: The history of hypertension is associated with an increase in the recurrence of CAA-related lobar hemorrhage.     

Apoptosis in rat jejunal mucosa is regulated partly through the central nervous system, which controls feeding behavior

AIM: The aim of this study was to investigate whether central nervous system-related feeding behavior regulates mucosal apoptosis in rat small intestines. METHODS: The test solutions used in this study were an H(1) receptor antagonist (chlorpheniramine maleate), 2-deoxy-D-glucose, leptin, and 1-deoxy-D-glucosamine (2-amino-1,5-anhydro-2-deoxy-D-glucitol). Test solutions were injected into the third cerebroventricles of rats. Feeding behavior and jejunal apoptosis were evaluated both with and without truncal vagotomy. Intestinal apoptosis was evaluated by percentage fragmented DNA, electrophoresis, and TUNEL staining. RESULTS: Chlorpheniramine and 2-deoxy-D-glucose elicited feeding, whereas leptin and 1-deoxy-D-glucosamine suppressed feeding. The test solutions, which elicited feeding (0.24 and 24 micromol/rat of chlorpheniramine and 2-deoxy-D-glucose, respectively), suppressed mucosal apoptosis in the rat jejunum 1 h after cerebroventricular infusion. In contrast, the test solutions, which suppressed feeding (8 and 24 micromol/rat of leptin and 1-deoxy-D-glucosamine, respectively), induced jejunal mucosal apoptosis 3 h after infusion. The effects of the test solutions on feeding behavior and changes in apoptosis were not affected by truncal vagotomy. CONCLUSION: The central nervous system, which regulates feeding behavior, might control intestinal function through the regulation of intestinal apoptosis.     

Posttraumatic tricuspid insufficiency successfully repaired by conventional technique

A 22-year-old man developed exertional dyspnea 2 years after blunt chest trauma due to a horse kick. Preoperative echocardiography showed severe tricuspid insufficiency (TI) caused by chordal rupture and prolapse of the anterior leaflet. A novel repair technique, the "clover technique," was applied, but was unsuccessful in this case. The valve was then repaired successfully using conventional techniques, that is, insertion of an artificial chordae, plication of the prolapsing leaflet, and DeVega's annuloplasty. We present here a brief review of posttraumatic TI, and discuss effective and less expensive techniques for repair.     

Endoscopic closure of perforations caused by EMR in the stomach by application of metallic clips

BACKGROUND: The number of complications associated with use of EMR for early-stage gastric cancer, including perforation, has increased with the increasing use of this procedure. Endoscopic clip application was performed in patients who sustained a perforation as a result of EMR for gastric neoplasm. PATIENTS AND METHODS: Seven patients who underwent endoscopic application of metallic clips to close perforations were studied. The omental patch method was applied in one case with a large perforation. OBSERVATIONS: In all patients, endoscopic clip application successfully closed the perforation of the stomach, which occurred after EMR. No patient required laparotomy. CONCLUSIONS: The technique of endoscopic clip application might be useful for treatment of patients who sustain a perforation caused by EMR.