Nuclear accumulation of annexin A2 contributes to chromosomal instability by coilin-mediated centromere damage.

Most human cancers show chromosomal instability (CIN), but the precise mechanisms remain uncertain. Annexin A2 is frequently overexpressed in human cancers, and its relationship to tumorigenesis is poorly understood. We found that annexin A2 is overexpressed in the nuclei of CIN cells compared with cells with microsatellite instability (MIN). Ectopic annexin A2 expression in MIN cells results in a high level of aneuploidy and induces lagging chromosomes; suppression of annexin A2 in CIN cells reduces such CIN signatures with apoptosis of highly aneuploid cells. Ectopic expression of annexin A2 in MIN cells reduces the expression of centromere proteins. Conversely, annexin A2-knockdown in CIN cells increases the expression of centromere proteins. Moreover, the endogenous expression levels of centromere proteins in CIN cells were greatly reduced compared with MIN cell lines. The reduced expression of centromere proteins likely occurred due to aberrant centromere localization of coilin, a major component of the Cajal bodies. These results suggest that nuclear accumulation of annexin A2 has a crucial role in CIN by disrupting centromere function.

Lamin B2 prevents chromosome instability by ensuring proper mitotic chromosome segregation.

The majority of human cancer shows chromosomal instability (CIN). Although the precise mechanism remains largely uncertain, proper progression of mitosis is crucial. B-type lamins were suggested to be components of the spindle matrix of mitotic cells and to be involved in mitotic spindle assembly; thus, B-type lamins may contribute to the maintenance of chromosome integrity. Here, using a proteomic approach, we identified lamin B2 as a novel protein involved in CIN. Lamin B2 expression decreased in colorectal cancer cell lines exhibiting CIN, as compared with colorectal cancer cell lines exhibiting microsatellite instability (MIN), which is mutually exclusive to CIN. Importantly, lamin B2 knockdown in MIN-type colorectal cancer cells induced CIN phenotypes such as aneuploidy, chromosome mis-segregation and aberrant spindle assembly, whereas ectopic expression of lamin B2 in CIN-type colorectal cancer cells prevented their CIN phenotypes. Additionally, immunohistochemical analysis showed a lower expression of lamin B2 in cancer tissues extracted from patients with sporadic colorectal cancer (CIN-type) than that from patients with hereditary non-polyposis colorectal cancer (HNPCC; MIN type). Intriguingly, mitotic lamin B2 in MIN cancer cells was localized outside the spindle poles and mitotic lamin B2 localization was diminished in CIN cancer cells, suggesting an important role of lamin B2 in proper mitotic spindle formation. The obtained results suggest that lamin B2 maintains chromosome integrity by ensuring proper spindle assembly and that its downregulation causes CIN in colorectal cancer.

[Carcinomatous pericarditis successfully treated with thoracoscopic pericardial fenestration; report of a case].

We report a case of malignant pericardial effusion after lung cancer surgery treated with thoracoscopic pericardial fenestration. The patient was admitted to our hospital because of dyspnea. Computed tomography (CT) and ultrasound cardiography (UCG) revealed cardiac tamponade which was diagnosed as carcinomatous pericarditis by cytology. We attempted to inject 25 mg of cisplatin (CDDP) into the pericardial space twice. The response of the treatment was unexpectedly poor for the patient. The thoracoscopic pericardial fenestration was performed and the patient was discharged without a drainage tube on the 17th postoperative day. Malignant pericardial effusion is a common complication of advanced cancers and is often associated with significant morbidity. Thoracoscopic pericardial fenestration appears to be a safe, effective and minimally invasive treatment for patients with malignant pericardial effusion. This surgery might also have a favorable effect on the improvement of the quality of life for patients with malignant pericardial effusion resistant to chemotherapy.

[Metastatic carcinoma of the adrenal gland from large cell neuroendocrine carcinoma; report of a case].

A 69-year-old man had undertaken left upper lobectomy (ND 2 a) with partial resection of the left lower lobe under the diagnosis of a primary lung cancer, T2N0M0, stage IB in June, 2002. The histopathological diagnosis was large cell neuroendocrine carcinoma (LCNEC), T3N0M0, stage IIB. The patient was discharged on postoperative day 25. Abdominal computed tomography (CT) revealed an enhanced tumor in the left adrenal lesion, 3 cm in diameter, in October, 2003. Magnetic resonance imaging (MRI) showed a slightly low intensity mass on T1-weighted imaging and slightly high intensity on T2-weighted imaging without invasion to other organs. Tumor marker, NSE was slightly elevated on blood examination. Left adrenalectomy was performed with a surgical margin. Histopathologically, the tumor was diagnosed as metastasis of LCNEC. There is no evidence of recurrence for a year after surgery. Although a prognosis of LCNEC is poor in general, we should consider the resection of metastatic carcinoma of the adrenal gland from LCNEC for long-term survival expectantly.

[Modified bentall operation using composite graft without resection of aortic valve].

A 27-year-old male whose diagnoses were aortic dissection (Stanford A), aortic regurgitation, annulo-aortic ectasia, and Marfan syndrome underwent modified Bentall operation using composite graft and total arch replacement. Modification of proximal suture without resection of aortic valve like intravalvular implantation might have resulted in good recovery without blood transfusion. Another 63-year-old male who suffered from spontaneous aortic rupture with aortic regurgitation also underwent modified Bentall operation in the similar manner as the first case with good result. Spontaneous aortic rupture reported here is a rare case, and operation is thought to be prerequisite for the patient who suffers from this disease to survive.

[A report of three surgical cases in a family of Marfan syndrome].

A family of 3 patients with Marfan syndrome was reported. All of them had surgical interventions in cardiovascular disorders such as DeBakey type I, III aortic dissection and thoracoabdominal aortic aneurysm. In 2 patients, multiple surgical treatments were performed for aneurysmal dilatation of the distal false lumen or another lesions of the treated aorta. Since cardiovascular lesions of Marfan syndrome are systemic and progressive, the postoperative long term follow-up, including systemic evaluation of the arterial system, is essential to detect the latent cardiovascular complications. Careful examining the family with Marfan syndrome is necessary to discover any cardiovascular abnormalities in these people early.

Ulcerative colitis after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

A 54-year-old woman with peripheral T cell lymphoma in second complete remission (CR) received an autologous peripheral blood stem cell transplant (PBSCT). Antibiotic-resistant bloody diarrhea, and fever developed 110 days after transplant. Blood and stool cultures were negative. Skin rash was not observed. Barium enema and colonoscopy showed typical features of pancolonic-type ulcerative colitis (UC). Endoscopic biopsies confirmed the diagnosis of UC. Mesalazine and immunosuppressive therapy improved symptoms dramatically. We detected serum antibodies against synthetic tropomyosin (TM) peptide when UC was diagnosed. We postulate that autoimmunity including autoreactive anti-TM antibodies may be involved in the pathogenesis of UC after autologous PBSCT in this patient.

Long-term survival and late-onset complications of cancer patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation.

The antitumor effect of high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered superior to that of conventional chemotherapy. However, the long-term benefits of this strategy in Japan remain unclear. Therefore, in this study, 109 cancer patients enrolled between 1989 and 1999 were treated with HDC and auto-PBSCT. Patients were evaluated for long-term survival and late-onset complications, including secondary malignancy. The mean number of CD34+ cells harvested per apheresis was larger in the group receiving high-dose cytosine arabinoside or high-dose etoposide plus granulocyte colony-stimulating factor (G-CSF) than in the group receiving conventional chemotherapy plus G-CSF. The 5-year overall survival rates for non-Hodgkin's lymphoma patients in first complete remission (CR) (83.2%), second or subsequent CR (74.1%), or first partial remission (PR) (66.7%) at the time of transplantation were significantly higher than those with no remission (35.7%) at the time of transplantation (first CR, P < .05; second or subsequent CR, P < .05; first PR, P < .05). The 5-year overall survival (OS) rates for breast cancer was 40.8%, and the disease-free survival rate was extremely low (8.8%). The 5-year OS rates for chemotherapy-sensitive and chemotherapy-resistant diseases at the time of transplantation were 32.7% and 35.7%, respectively, a difference that was not considered significant. The 5-year OS for germ cell tumor was 80.0%, and the disease-free survival rate was 77.9%. The rate of therapy-related death was 8.2%. The occurrence rate of secondary malignancy was 0.9%. Late-onset complications were observed in 4 cases (glomerulonephritis, interstitial pneumonitis, ulcerative colitis, and acute myelogenous leukemia). At 3.7%, the occurrence rate was not very high, but most complications of auto-PBSCT were life threatening and interfered with patients' quality of life. A careful follow-up is required for at least 2 years after transplantation, because the mean occurrence time of late-onset complications is 16.7 months posttransplantation.

Congenital cystic adenomatoid malformation of the lung with an esophageal cyst: report of a case.

The authors report the case of a 7-month-old girl found to have both congenital cystic adenomatoid malformation of the lung (CCAM) and esophageal cyst. She suffered repeated episodes of pneumonia and exhibited signs of respiratory distress on admission to our hospital. Chest radiography and magnetic resonance imaging (MRI) showed 2 different kinds of cystic lesions. Resection of the lower lobe of the right lung and excision of the posterior mediastinal cyst were performed. Histologic examination showed Stocker type I CCAM and esophageal cyst. Coexistence of both CCAM and esophageal cyst is extremely rare. The authors speculate that the pathologies of this case originated from a regional disturbance of common embryologic origin during 2 different phases of lung-bud foregut malformations.

Decreased expression of signaling lymphocytic-activation molecule-associated protein (SAP) transcripts in T cells from patients with rheumatoid arthritis.

The function of Epstein-Barr virus (EBV)-specific cytotoxic T cells is disturbed in rheumatoid arthritis (RA) patients but the mechanism for this disturbance has remained unknown. In a recent study searching for the causative gene of X-linked lymphoproliferative syndrome, the gene possibly linked to EBV-specific cytotoxic T cells or NK cell-mediated cytotoxic activity to EBV-infected cells was discovered, and its product is now referred to as signaling lymphocytic-activation molecule-associated protein (SAP) or Src homology 2 domain-containing protein (SH2D1A). In the present study, we attempted to investigate the involvement of the SAP gene in RA using a quantitative real-time PCR; the expression level of SAP transcripts in peripheral leukocytes or T cells was examined for patients with RA. The expression level of SAP transcripts in peripheral leukocytes of 21 RA patients was significantly lower than that of 13 normal individuals (P = 0.0007), four patients with palindromic RA, 11 with inactive systemic lupus erythematosus (SLE) or 17 with chronic renal diseases. The decreased expression of SAP transcripts in RA patients was also observed in peripheral CD2(+) T cells compared with normal individuals. There was no mutation in the coding region of SAP cDNAs derived from peripheral leukocytes of five RA patients. The decreased expression of SAP transcripts in peripheral leukocytes or T cells of RA patients might lead to the failure of the immune system to eliminate the EBV-infected synovial lining cells in joints of RA patients. Our findings have suggested that decreased expression of the SAP gene might be involved in the onset or progress of RA.

[Off-pump coronary artery bypass grafting: comparison between standard CABG and off-pump CABG].

UNLABELLED: We have performed 321 cases of coronary artery bypass grafting (CABG), between October 15 1995 and November 20 2000. We have evaluated the operative results of 142 cases (44.2%) of conventional CABG and 179 cases (55.8%) of off-pump CABG performed during this period. The average numbers of bypassed grafts was 3.53 for conventional CABG, and 1.62 for off-pump CABG. The total number of 369 grafts were anastomosed to 501 coronary arteries for conventional CABG, and 283 grafts were anastomosed to 290 coronary arteries for off-pump CABG. RESULTS: Although two saphenous veins were occluded, the early postoperative patency rate was 100% for conventional CABG using RITA, LITA, GEA and RA. Three site of stenosis in 18 LITAs and 2 in 16 RITAs were recognized in off-pump CABG without the use of stabilizers. One site of stenosis in 130 LITAs and 3 string signs in 44 GEA were recognized in off-pump CABG with the use of stabilizers. Postoperative angiography in 52 off-pump CABG cases at one year later showed no new lesion. CONCLUSION: The use of stabilizers and LIMA suture enables adaptation of the MIDCAB procedure to a wider range of coronary artery bypass procedures, and a higher graft patency can be expected.

[Minimally invasive direct coronary artery bypass performed via diaphragmatic approach].

From October 1996 until August 2000, coronary artery bypass grafting (CABG) for right coronary artery was performed via diaphragmatic approach. This procedure was done in 18 patients consist of 13 male and 5 female ranging in age from 47 to 81 years old. Ten of 18 cases were performed coronary bypass reoperation. Right gastroepiploic artery was used in 16 cases, and branched radial artery or saphenous vein graft from gastroduodenal artery was used in one case. Bypassed region in right coronary artery was segment 3 in 9 cases, right posterior descending artery in 8 and right atrio-ventricular branch in one. All grafts were patent in postoperative cardiac catheterization. This approach was desirable for the case, which bypass grafting to right coronary artery is necessary, on account of avoiding injury of patent bypassed graft by median sternotomy in re-do CABG. For the patient whose stomach had been resected, bypass grafting from gastroduodenal artery with radial artery or saphenous vein graft to right coronary artery is useful procedure.

Laparoscopic surgery in infants with intra-abdominal cysts: two case reports.

OBJECTIVES: We report two cases of infants found to have congenital omental cystic lesion with torsion and ovarian cyst treated by laparoscopy-assisted surgery (LAS). METHODS: A laparoscope was inserted by an open method. The intra-abdominal pressure was maintained at 8 mm Hg. We diagnosed the cystic lesions with torsion. At aspirator was used to aspirate the cystic content and remove the cyst. RESULTS: No intra- or postoperative complications were encountered. Oral intake was commenced on postoperative day 2 in both patients. The cosmetic results following LAS were excellent. CONCLUSIONS: We conclude that LAS is suitable for the management of omental cystic lesions with torsion and ovarian cyst in nursing infants. An aspirator is useful in preventing spillage of cystic contents in patients with intra-abdominal cystic lesion.

GST-pi gene-transduced hematopoietic progenitor cell transplantation overcomes the bone marrow toxicity of cyclophosphamide in mice.

Autologous transplantation of bone marrow cells (BMCs) transduced with the multidrug resistance 1 (MDR1) gene or dihydrofolate reductase (DHFR) gene has already been applied in clinical chemoprotection trials. However, anticancer drugs frequently used in high-dose chemotherapy (HDC), such as alkylating agents, are not relevant to MDR1 or DHFR gene products. In this context, we have previously reported that glutathione S-transferase-pi (GST-pi) gene-transduced human CD34(+) cells showed resistance in vitro against 4-hydroperoxicyclophosphamide, an active form of cyclophosphamide (CY). In the present study, a subsequent attempt was made in a murine model to evaluate the effectiveness of transplantation of GST-pi-transduced BMCs to protect bone marrow against high-dose CY. The gene transfection was carried out retrovirally, employing a recombinant fibronectin fragment. Transfection efficiency into CFU-GM was 30%. After the transplantation, recipient mice (GST-pi mice) received three sequential courses of high-dose CY. As the chemotherapy courses advanced, both shortening of recovery period from WBC nadir and shallowing of WBC nadir were observed. In contrast to the fact that three of seven control mice died, possibly due to chemotoxicity, all seven GST-pi mice were alive after the third course, at which point the vector GST-pi gene was detected in 50% of CFU-GM derived from their BMCs and peripheral blood mononuclear cells. When BMCs obtained from these seven mice were retransplanted into secondary recipient mice, 20% of CFU-GM from BMCs showed positive signals for vector GST-pi DNA after 6 months. These data indicate that the GST-pi gene can confer resistance to bone marrow against CY by being transduced into long-term repopulating cells.

The occurrence of a strangulated ileus due to a traumatic transmesenteric hernia: report of a case.

We report herein the case of a 6-year-old boy in whom a strangulated ileus was caused by a traumatic transmesenteric hernia. The boy had fallen from his bicycle and suffered a severe blow to the abdomen. Abdominal pain and vomiting developed 10 h after the accident and he was admitted to our hospital. Abdominal ultrasonogram and computed tomogram demonstrated ascites, intestinal wall thickening with fluid, and an engorged radiating mesenteric vasculature. Thus, an emergency laparotomy was performed which revealed bloody ascites, a strangulated ileus, and torsion with a transmesenteric hernia. The necrotic intestine was resected and an anastomosis was performed. Macroscopic and microscopic findings revealed a traumatic mesenteric rent. The unusual presentation of this case is discussed.

Histological estimation of the efficacy of endoscopic laser coagulation therapy for diffuse antral vascular ectasia.

We present the case of a 72-year-old woman with successful control of repeated episodes of bleeding from diffuse antral vascular ectasia (DAVE) by laser coagulation therapy. In addition to DAVE, the patient also suffered from severe iron deficiency anaemia (due to recurrent bleeding), liver cirrhosis, and huge tumours of hepatocellular carcinoma (HCC). She was referred from another hospital after failure to stop her bleeding episodes. Endoscopic examination revealed diffuse speckled telangiectasia over most of the stomach (from antrum to the upper portion of the body) and large numbers of blood clots. The patient had received repeated blood transfusions, haemostatic drugs, and H2 receptor antagonists at the other hospital, without improvement of the repeated bleeding. She underwent three sessions of endoscopic laser coagulation therapy for the lesions at our hospital after the final diagnosis of DAVE had been made based on the characteristic histological findings of biopsied specimens. This treatment improved her general condition and stopped the bleeding from the gastrointestinal tract even without fasting. Unfortunately, however, her liver function gradually worsened due to HCC and previous massive bleeding, and she finally died of liver failure three months after the last laser session. Autopsied specimens obtained from the patient's stomach revealed that macroscopic diffuse speckled telangiectasia and microscopic typical vasodilatation in mucosal and submucosal layers of gastric tissue had disappeared in the treated areas but not all portions of the DAVE lesion. These histological findings for the treated areas, in addition to the clinical improvement of bleeding, suggest that endoscopic laser coagulation therapy may be useful and one of the first choices in treatment for DAVE.

Hearing loss in infants with congenital diaphragmatic hernia treated without extracorporeal membrane oxygenation: report of two cases.

The authors report the cases of 2 infants with congenital diaphragmatic hernia (CDH) treated without extracorporeal membrane oxygenation (ECMO) therapy who were discovered to have hearing loss at 1 year of age. Both boys had been diagnosed as having CDH antenatally and were treated with surgery and high-frequency oscillatory (HFO) therapy. The patterns of hearing loss were consistent with sensorineural deafness and believed to be associated with HFO therapy, prolonged mechanical ventilation, and a high pH.

Immunocytochemical analysis of cellular infiltrates in human appendicitis.

This study was conducted to determine the immunologic cellular composition in human appendicitis and its association with the development of perforated appendicitis. Appendiceal specimens from 27 patients with acute appendicitis were immunostained to detect lymphocyte surface markers. Moreover, the lymphocyte surface markers of peripheral blood were analyzed by laser flow cytometry in 12 patients. Helper T lymphocytes (CD4) were present in all the patients, while B lymphocytes (CD19), natural killer (NK) cells (CD56), and cytotoxic T lymphocytes (CD8) were present in 7 (70%), 10 (100%), and 9 patients (90%) with perforated appendicitis, and in 12 (63.2%), 10 (58.8%), and 6 (54.5%) patients without perforation, respectively. There were significant differences between the patients with a perforated appendix and those without perforation, in the positivity rate for CD8 and CD56 cells (P < 0.05). The number of cells positive for CD56, being NK cells, in the blood from the patients with perforation was significantly lower than that in the blood from those without perforation (P < 0.05). The infiltration of a greater number of cytotoxic T lymphocytes and NK cells was observed in the appendices from patients with perforated appendicitis than in those from patients with nonperforated appendicitis.