Mutations in the p53 tumor suppressor gene occur in more than 50% of human cancers. In response to various cellular stresses, such as DNA damage, the p53 protein rapidly accumulates by posttranscriptional mechanism(s) and activates the expression of genes that play a major role in cellular responses leading to cell cycle arrest, DNA repair and apoptosis as a transcriptional activator. In particular, the induction of apoptosis is considered to be an important function in tumor suppression by p53. Recently, two BH3-only members of the Bcl-2 family, Noxa and PUMA, have been identified as p53 target genes^1,2. Furthermore, the analysis of mice doubly deficient in multidomain Bcl-2 family proteins, Bax and Bak, revealed that apoptosis induced by the BH3-only protein is completely dependent on Bax and Bak³. More recently, it was demonstrated using gene knockout mice^4,5 that Noxa and PUMA function as the effectors of p53-induced apoptosis. These analyses revealed that p53-induced apoptosis is regulated by these Bcl-2 family proteins. In this photogravure, the regulation of these Bcl-2 family proteins in p53-induced apoptosis was visualized by fluorescent protein fusion and immune fluorescence methods.

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As trauma is the leading cause of death for persons 1 to 24 years in Japan, the trauma system must be established to save lives and to reduce serious sequelae. However, the trauma system has not been evaluated since 2000. In May 2002, it revealed that the deaths of about 40% of expired trauma patients who arrived at emergency centers with some vital signs were probably preventable. This result increased the awareness of the need for establishing the trauma system. Then, the Japan Prehospital Trauma Evaluation and Care program for emergency medical technicians was developed, the doctor helicopter system was promoted, the Japan Advanced Trauma Evaluation and Care program for physicians was developed, and the trauma registry program was started. The extension of the procedures that can be performed by Japanese paramedics should be extended with the establishment of a medical control system. However, the key to securing quality regional trauma care is to designate a trauma care hospital as a trauma center and to transport severely injured patients there as rapidly as possible.

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Mutations of Bruton's tyrosine kinase (Btk), which is critical for B cell development and function, cause X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Although the severity of the clinical phenotype differs between the two species, xid mice are considered useful for evaluating treatment strategies for XLA patients. Hematopoietic stem cells (HSCs; 1∼3×10⁵)from xid mice were transduced with an HIV vector containing the human Btk (hBtk) gene under the control of the internal murine stem cell virus (MSCV) promoter and injected into 4-week-old xid mice. Thirty weeks later, the copy number of the integrated HIV vector was over 0.2 per cell in both bone marrow and spleen, but serum concentrations of IgM and IgG3 and the antibody response to nitrophenol (NP)-Ficoll challenge were not restored. The number of differentiated B cells (IgM^lowIgD^high) was increased, while the peritoneal B1 cell count remained low. These results indicate that HIV-mediated expression of hBtk in bone marrow stem cells partially promotes B cell development, but is not sufficient for the restoration of B cell function in xid mice.

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Aim: The aim of this study is to report the feasibility of a newly developed intra-abdominal fan retractor system for use in gynecologic laparoscopic surgery. Methods: Five hundred women undergoing gasless laparoscopic surgery using the abdominal wall lifting device were included in the study. The intraoperative and postoperative courses, and complications were examined. Results: The intra-abdominal retractor system provided adequate exposure in all cases, except for one patient with morbid obesity. Neither the presence of the intra-abdominal retractor blades nor the mechanical arm interfered with the placement of instruments during surgery. No complications related to the use of gasless laparoscopy were encountered in this study period. Conclusion: The new intra-abdominal fan retractor system is feasible in gynecologic laparoscopic surgery.

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Aim: The aim of the present study was to compare the hemodynamic features of portal hypertension in rats with early cirrhosis with those of rats with advanced cirrhosis following common bile duct ligation (CBDL). Methods: A total of 53 male Sprague-Dawley rats were used. Hemodynamics were evaluated under conscious and unrestrained conditions 4 weeks and 8 weeks after CBDL, and 4 weeks after a sham operation. Arterial pressure and portal pressure were measured directly via catheters placed in the right femoral artery and main portal vein, respectively. The cardiac index and organ (splanchninc organs, brain, kidneys and lungs) blood flow were determined by the reference sample method using ¹⁴¹Ce-labeled microspheres (15 μm in diameter). Arterial levels of endothelin-1 and nitrate/nitrite, as well as liver function variables, were also determined. Results: Portal pressure was significantly higher 8 weeks after CBDL (15.8±2.1, n=8)than 4 weeks after CBDL (13.9±2.1 mmHg, n=12, p<0.05), and the hyperdynamic circulation of the early period was attenuated (p<0.05). Although hepatic artery blood flow 4 and 8 weeks after CBDL was higher than that after sham operation (p<0.05), portal territory blood flow was not increased. There was a significant positive correlation between portal pressure and portal territory blood flow 8 weeks after CBDL (r=0.822, n=8, p=0.012). In rats with anemia 4 weeks after CBDL, the hemoglobin concentration was negatively correlated with portal territory blood flow (r=-0.597, n=12, p=0.040). Conclusion: Portal pressure was higher 8 weeks after CBDL than 4 weeks after CBDL and increased with portal territory blood flow, suggesting that portal hypertension is maintained by a mechanism consistent with the forward flow theory. Anemia might exacerbate the hyperdynamic systemic circulation 4 weeks after CBDL.

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During laparoscopic myomectomy, it is difficult to determine the actual blood loss volume because physiological saline is used for lavaging to detect the bleeding point or to ensure no active bleeding site. We attempted to estimate blood loss by measuring the waste irrigation fluid's hemoglobin (Hb) concentration using HemoCue^® (HemoCue, Angelholm, Sweden). Twenty-three women enrolled in our study. After the end of laparoscopic myomectomy, the waste irrigation fluid's Hb content was measured using HemoCue^®. We estimated blood loss using the following formula. Estimated blood loss (ml)= [waste irrigation fluid volume (ml)]×[Hb concentration in waste irrigation fluid (g/l)]÷[patient's preoperative Hb level (g/l)]. The demographic data of the patients showed 35.4 years in age, 159.6 cm in height, and 50.7 kg in weight (mean). The total lavage fluid's Hb level ranged between 0.2∼4.7 (g/l). The total blood loss estimation was calculated and ranged between 17.6∼725.2 ml. There was no significant correlation between the calculated blood loss and the difference in Hb level (Hb level on the first postoperative day minus preoperative Hb level). The HemoCue^® needs only 10 mcl of blood and it takes only about 45 seconds to produce the result. Furthermore, the HemoCue^® is a reliable device for measurement of blood hemoglobin concentration. Our method is easy and quick to perform, and blood loss estimation and surgeon's experience (subjective method) show accordance.

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We report a male patient with primary biliary cirrhosis (PBC) who developed limited scleroderma (l-SSc) and pulmonary hypertension (PHT). He had noticed shortness of breath seven months earlier, which slowly progressed before admission. Sclerodactyly and telagiectasia of the fingers and chest wall were found. Chest X-ray and Doppler echocardiography suggested the presence of PHT. Histologic examination of the liver (needle biopsy) revealed stage two PBC, and histologic findings of the skin (obtained from the dorsum of right finger IV) were compatible with l-SSc. Direct measurement of pulmonary arterial pressure revealed PHT with normal capillary wedge pressure during right heart catheterization. A striking increment of plasma thromboxane B₂ across the lungs was found, which suggested that thromboxane A₂ (precursor of thromboxane B₂) contributed considerably to a rise in pulmonary vascular resistance leading to PHT.

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We describe a patient with a ruptured and rapidly enlarging secondary tumor of the liver metastasized from an α-fetoprotein (AFP)-producing gastric cancer. The ruptured liver metastasis was successfully treated by transarterial embolization (TAE) followed by hepatic resection. A 65-year-old woman was admitted to our hospital with residual gastric cancer. No liver metastasis was detected by preoperative computed tomography (CT), or ultrasonography, and total gastrectomy was performed. Microscopically, the tumor was a poorly differentiated adenocarcinoma invading no deeper than the subserosa, with positive staining for AFP and positive staining for Ki67 in approximately 80% of the tumor cells. Severe venous and lymphatic involvements were evident. The serum AFP level was 100 ng/ml at 3 weeks after the total gastrectomy, but decreased to 16 ng/ml by the end of postoperative month 3. At 6 months, the patient was referred and readmitted to our hospital with sudden severe pain in the upper abdomen. She was admitted in a state of shock with laboratory findings of anemia. A liver tumor surrounded by effusion was detected in segment 8 and diagnosed as a ruptured liver metastasis. Emergency arteriography revealed a large hypervascular tumor, and a TAE performed promptly thereafter was successful in improving the blood pressure. A second TAE was performed 2 months after first TAE due to a dramatic elevation of serum AFP to 180,000 ng/ml. The second TAE decreased the patient's serum AFP to 2,200 ng/ml, but the level remained in the abnormal range. A right hepatectomy was performed after confirming the absence of other detectable metastatic tumors. The resected specimen contained a well-defined tumor, measuring 6×6 cm that appeared almost necrotic under microscope. Over the 6 years since the hepatectomy, no recurrence has appeared and serum AFP has remained within the normal range.

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Congenital bilateral anophthalmia and microphthalmia are rare conditions, with overall prevalence in one study set at 1.0 per 10,000 births⁹. We report here a case of congenital bilateral severe microphthalmia with mental retardation and cerebral palsy. The patient was man aged 38 years with a chromosome aberration, namely a balanced translocation: 46, XY, t (2;6)(q31;q24). He had no other malformations apart from the severe microphthalmia. CT of the head showed no significant abnormal findings in the brain, but rudimentary eyeballs and external ocular muscles in the bilateral orbits. There was no family history of anophthalmia, microphthalmia, mental retardation or cerebral palsy. His mother had not used any medications or excessive alcohol during gestation. Putative genes of anophthalmia and microphthalmia reported to date include PAX6 (Glaser T et al 1994⁶) and CHX10 (Ferda Percin E et al 2000⁵). Further, some loci of these conditions have been reported (Graham CA et al 1991⁷; Bessant DAR et al 1998³; Morle L et al 2000⁴: Forrester S et al 2001¹: Ng D et al 2002⁸). To our knowledge, however, this is the first report of nonsyndromic microphthalmia or anophthalmia with chromosome 2q31 or 6q24 aberration. We consider that the putative gene may be located on the brake points of chromosome 2 and 6.

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A 73-year-old male with C type liver cirrhosis and poor liver function reserve was diagnosed with hepatocellular carcinoma (HCC)(Segment V, 2×2 cm in diameter) and underwent open microwave coagulation therapy (MCT). Ten months later, a movable hard mass about the size of a quail egg was palpable at the left supra-clavicular lymph node (LN)(Virchow's LN) and blood tests revealed an elevated serum α-fetoprotein (AFP) level of 26.7 ng/dl. Abdominal and chest CT showed no evidence of recurrence in liver or lung, and no metastases of abdominal LN. Barium and bone scintigraphy revealed no abnormal spots. The affected left supra-clavicular LN was extirpated. The tumor was confirmed to be an LN metastasis from HCC by histopathological examination. After the operation, the patient developed uncontrollable pleural effusion and ascites, and intrahepatic and abdominal LN metastases were visible on abdominal CT with great haste. He died 1.5 months after the LN was extirpated. We herein report a case of HCC treated by MCT which later resulted in a solitary Virchow's LN metastasis in the absence of any abdominal LN or recurrence in the liver or lung.

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