Expression of matrix metalloproteinase matrilysin (mmp-7) was induced by activated ki-ras via ap-1 activation in sw1417 colon cancer cells

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metallo-proteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.     

Closure of a large bronchial fistula with a latissimus dorsi myocutaneous flap

We describe a case of a large bronchial fistula and empyema after right upper lobectomy that was treated successfully with open window thoracostomy followed by a latissimus dorsi myocutaneous flap and limited thoracoplasty. A latissimus dorsi myocutaneous flap can provide immediate airtight closure of a large bronchial fistula, allowing lavage and curettage of the empyema cavity to reduce the chance of postoperative infection. An important aspect of this technique is that the deepithelialized skin side rather than muscle is sutured to an opening of the bronchus. As compared with other techniques, a latissimus dorsi myocutaneous flap is superior in that it requires a single incision and does not require an intraop-erative change of position. In addition, the technique causes little dysfunction of the chest and shoulder and preserves the vascular supply to ensure the viability of the flap even if it was divided in a previous operation.     

Nevus Lipomatosus Cutaneous Superficialis of the Clitoris

BACKGROUND: Nevus lipomatosus cutaneous superficialis (NLCS) is a relatively rare condition. Although NLCS can affect any region of the entire body, no case of NLCS in the clitoris has ever been reported. OBJECTIVE: To report a case of NLCS of the clitoris that presented manifestations that were similar to female pseudohermaphrodism. METHODS: This is a case report and review of the literature. RESULTS: A congenital, soft, skin-colored lesion of the clitoris in a 1-year-old girl resembled female pseudohermaphrodism. It was resected, and the histologic diagnosis was NLCS. Postoperatively, there was no subsequent change in the lesion during the 3-year follow-up period. CONCLUSION: We reported a case of congenital solitary NLCS of the clitoris. Although NLCS might be a relatively rare condition, we should consider it in the differential diagnosis of female pseudohermaphrodism.     

The Protective Role of Glutathione, Cysteine and Vitamin C against Oxidative DNA Damage Induced in Rat Kidney by Potassium Bromate

The roles of glutathione (GSH), cysteine, vitamin C., liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO₃) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO₃ i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO₃ i.p. treatment, which itself caused no change. Administration of KBrO₃ itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO₃ lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO₃ were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO₃.     

Aortic arch replacement with proximal first technique.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) without retrograde cerebral perfusion (RCP) has a strict time limit. We modified a surgical technique for anastomosis to shorten the period of DHCA and unilateral cerebral perfusion (UCP). METHODS: Between March 1993 and August 2001, retrospective analysis was done on 23 consecutive patients, who underwent aortic arch replacement with branches. The patients were divided into two groups: DHCA group and UCP group. The DHCA group, in which DHCA alone and without additional cerebral perfusion was performed, comprised of nine patients. Proximal aortic anastomosis was performed first during systemic cooling; then both the brachiocephalic artery and left carotid artery were reconstructed with the branches of the artificial graft during circulatory arrest; thereafter, cerebral and coronary perfusions were resumed. The UCP group, in which DHCA was not used but right hemisphere perfusion during deep hypothermia was performed when the origin of brachiocephalic artery was safely clamped, consisted of 14 patients. RESULTS: Mean time of DHCA was 18.8+/-4.2 minutes and that of right hemisphere perfusion time was 11.0+/-3.8 minutes, respectively. Twenty-one patients survived the surgery (91.3%), and two (8.7%) died during hospitalization. Transient cerebral complication occurred in four patients in the DHCA group and all recovered. Logistic regression analysis revealed that DHCA was the only parameter to significantly influence temporary neurological dysfunction. There was no other significant difference between the two groups. CONCLUSION: With our modified and simple surgical technique for aortic arch repair, we were able to successfully shorten the DHCA time and right hemisphere perfusion time. However, because DHCA was the only parameter to significantly influence temporary neurological dysfunction, some form of continuous cerebral perfusion at deep hypothermia may be a safer method to preserve cerebral function.     

Outcomes in patients with interrupted aortic arch and associated anomalies: a 20-year experience.

OBJECTIVE: The surgical results for the repair of interrupted aortic arch (IAA) have evolved in recent years. We report our results for staged repair of this complex congenital malformation. METHODS: Sixty-five patients (mean age, 16.9+/-41.7 days) were diagnosed with IAA and referred for surgical therapy. The surgical management strategy at our institution between 1982 and 2005 has been one-stage complete repair (n=13) or staged repair (n=52) in selected patients. Non-complex patients (group I, n=51) had a ventricular septal defect (87%), aortopulmonary window (8%), and left ventricular outflow tract obstruction (27%). Group II (n=14) were patients with Taussig-Bing double outlet right ventricle (n=6) or truncus arteriosus (n=8). Method of staged repair of IAA was to transect and turn down the left carotid artery and anastomosis it to the descending aorta (n=41) or graft interposition (n=2) combined with a pulmonary artery (PA) banding followed in a few months by delayed ventricular septal defect (VSD) closure and PA de-banding. RESULTS: There were 5 early and 10 late deaths. The actuarial survival including early mortality was 92% at 1 year, 81% at 5 years, and 76% at 10 and 15 years. There was an 81% 15-year survival for children in group I compared with a 54% for children in group II (p<0.001). Risk factors for increased mortality by univariate analysis were as follows: (1) primary aortic anastomosis (p=0.03), (2) presence of complex anomalies (p=0.05), and (3) initial IAA repair performed before 1994 (p=0.05). Actuarial freedom from any type of aortic reoperation or intervention was 86% at 1 year, 69% at 5 years, and 60% at 10 and 15 years. Univariate and multivariate analyses identified no tested variables as risk factors for reoperation. The majority (86%) was in New York Heart Association (NYHA) class I, and 14% remained in NYHA class II. During the postoperative course there were no neurologic deficits, seizures, and growth disturbances in any patient. CONCLUSION: Staged repair of IAA using a left carotid artery turn down can be safely applied in IAA patients with and without other intracardiac anomalies with good results. Use of the left carotid artery for arch reconstruction did not result in any detectable neurological events or growth disturbances later in life. Associated anomalies played an important role in outcomes. The long-term probability for reoperation and/or reintervention remains high regardless of operative technique.     

Chromosome analysis of brain tumors in childhood

We performed a chromosome analysis of 26 pediatric brain tumors, including 20 primitive neuroectodermal tumors (PNETs), 5 astrocytomas, and I immature teratoma. Specimens were treated with collagenase, placed in overnight or short-term cultures, and harvested for chromosome analysis. Numerical and/or structural abnormalities were noted in 14 of the 20 PNETs and 4 of the 5 astrocytomas. In 13 PNETs, so-called medulloblastoma in the cerebellum, an i(17q) was the most frequent structural abnormality, accounting for 30% (4/13). Double minute chromosomes (dmin) were observed in one tumor. Near-diploidy was demonstrated in three of these PNETs, hyperdiploidy in three, and near-tetraploidy in three. We could not find any correlation of these cytogenetic findings with the prognosis. In the remaining seven PNETs other than medulloblastoma, the karyotypes of five PNETs demonstrated a variety of numerical and structural abnormalities. As to the astrocytomas, losses of chromosomes 7 and 9 with dmin were observed in two, and structural abnormalities of chromosomes 1 and 17 were also observed in two tumors. In our limited cases, however, we could not find the same chromosome abnormalities that are well known in adult astrocytomas. A congenital immature teratoma showed hyperdiploidy with increased numbers of chromosomes 3, 6, and 12. We conclude that i(17_q) is an important chromosome abnormality in medulloblastomas, and that the oncogenesis of pediatric astrocytomas might be different cytogenetically from that of adult astrocytomas.