Conformational stability and activity of p73 require a second helix in the tetramerization domain.

p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additional alpha-helix that is not present in the structure of the p53 OD. Deletion of this helix causes a dissociation of the OD into dimers; it also causes conformational instability and reduces the transcriptional activity of p73. Moreover, we show that ODs of p73 and p63 strongly interact and that a large number of different heterotetramers are supported by the additional helix. Detailed analysis shows that the heterotetramer consisting of two homodimers is thermodynamically more stable than the two homotetramers. No heterooligomerization between p53 and the p73/p63 subfamily was observed, supporting the notion of functional orthogonality within the p53 family.

Smoking-related changes in the background lung of specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course.

AIMS: To assess the pathological findings in lobectomy specimens, to correlate them with smoking history and postoperative course and to compare the findings with those in smoking-related interstitial lung disease. METHODS AND RESULTS: Patients who had undergone lobectomy for lung cancer were reviewed. Subjects included 230 non-smokers and 587 smokers, of whom 572 had a known smoking index (SI). They were classified into mild, moderate and heavy smokers. Centrilobular emphysema (CLE), respiratory bronchiolitis, airspace enlargement with fibrosis (AEF), the presence of foci resembling usual interstitial pneumonia pattern (UIP/P) and the rate of postoperative respiratory failure were assessed. The incidence of AEF was 6.5% in mild smokers, and 17.7% in moderate smokers (P < 0.01) with lower lobe predominance. There were significant correlations (P < 0.01) between AEF and CLE and AEF and UIP/P. The rate of respiratory failure after lobectomy was 6%, and 10% in patients having UIP/P with or without AEF, but was not seen in patients with AEF alone (P < 0.01). CONCLUSIONS: AEF is an important smoking-related change in the lung that appears to correlate with the smoking history, and its distinction from UIP/P may be important.

Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study.

Intravenous fluorouracil and leucovorin is the standard adjuvant treatment for stage III colon cancer. However, oral adjuvant chemotherapy is attractive because it has low toxicity and greater convenience. We investigated the benefits of oral protein-bound polysaccharide K (PSK) with tegafur/uracil (UFT) as an adjuvant in stage II and III colorectal cancer. Patients were assigned to groups that received either 3 g PSK plus 300 mg UFT, or 300 mg UFT alone orally each day for a 2-year period following intravenous mitomycin C. Of 207 registered patients, 205 with stage II (n=123) or III (n=82) were analysed. The 5-year disease-free survival was 73.0% (95% CI 65.6-80.4%) with PSK (n=137) and 58.8% (95% CI 47.1-70.5%) in the controls (n=68) (P=0.016). Polysaccharide K reduced the recurrence by 43.6% (95% CI 4.5-66.7%) and mortality by 40.2% (95% CI -12.5 to 68.3%). The 5-year survival was 81.8% (95% CI 75.3-88.2%) in the PSK group and 72.1% (95% CI 61.4-82.7%) in the control group (P=0.056). In stage III patients, disease-free and overall survivals in patients receiving PSK were increased significantly: 60.0% (95% CI 47.1-72.9%) and 74.6% (95% CI 63.0-86.1%) in the PSK group as compared with 32.1% (95% CI 14.8-49.4%) and 46.4% (95% CI 28.0-64.9%) in the controls (P=0.002 and 0.003, respectively). Polysaccharide K prevented recurrence, particularly lung metastases (P=0.02; odds ratio 0.27; 95% CI 0.09-0.77). In the models, the presence of regional metastases (relative risk, 2.973; 95% CI 1.712-5.165; P<0.001), omission of PSK (relative risk, 2.106; 95% CI 1.221-3.633; P=0.007), and higher primary tumour (relative risk, 4.398; 95% CI 1.017-19.014; P=0.047) were each significant indicators of recurrence. Adverse effects were mild and compliance was good. Oral PSK with UFT reduced recurrence in stage II and III colorectal cancer, and increased survival in stage III.

Mutations in the ST7/RAY1/HELG locus rarely occur in primary colorectal, gastric, and hepatocellular carcinomas.

Human cancers frequently show a loss of heterozygosity on chromosome 7q31, which indicates the existence of broad-range tumour-suppressor gene(s) at this locus. Truncating mutations in the ST7 gene at this locus are seen frequently in primary colon cancer and breast cancer cell lines. Therefore, the ST7 gene represents a novel candidate gene for the tumour suppressor at this locus. However, more recent studies have reported that ST7 mutations are infrequent or absent in primary cancer and cell lines. To ascertain the frequency of mutations of the ST7 gene in cancer cells, we examined mutations in the ST7 coding sequence in 48 colorectal, 48 gastric, and 48 hepatocellular carcinomas using polymerase chain reaction-single-strand conformational polymorphism and direct sequencing. We detected somatic mutations, which were located near the exon-intron junction in intron 8, in only three out of 144 cases. We conclude that mutations in the ST7 gene are rare in primary colorectal, gastric, and hepatocellular carcinomas.

[Traumatic diaphragmatic hernia repaired by video-assisted thoracic surgery; report of two cases].

Two cases of traumatic diaphragmatic hernia treated by video-assisted thoracic surgery (VATS) were experienced. Both a 67-year-old female (left side) and a 44-year-old female (right side) was admitted to our hospital in a traffic accident. These patients were diagnosed as diaphragmatic hernia by chest magnetic resonance imaging (MRI). We tried VATS to this trauma, but the combined mini-thoracotomy for 7 cm in length was necessary to replace sliding organs for both cases. The rupture of diaphragm was repaired by direct suture of 2-0 viclyl. VATS will be recommended in the hernia of the diaphragm.

An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control.

BACKGROUND: Size regulation is fundamental in developing multicellular organisms and occurs through the control of cell number and cell size. Studies in Drosophila have identified an evolutionarily conserved signaling pathway that regulates organismal size and that includes the Drosophila insulin receptor substrate homolog Chico, the lipid kinase PI(3)K (Dp110), DAkt1/dPKB, and dS6K. RESULTS: We demonstrate that varying the activity of the Drosophila insulin receptor homolog (DInr) during development regulates organ size by changing cell size and cell number in a cell-autonomous manner. An amino acid substitution at the corresponding position in the kinase domain of the human and Drosophila insulin receptors causes severe growth retardation. Furthermore, we show that the Drosophila genome contains seven insulin-like genes that are expressed in a highly tissue- and stage-specific pattern. Overexpression of one of these insulin-like genes alters growth control in a DInr-dependent manner. CONCLUSIONS: This study shows that the Drosophila insulin receptor autonomously controls cell and organ size, and that overexpression of a gene encoding an insulin-like peptide is sufficient to increase body size.

The DD5 gene of the decapod crustacean Penaeus japonicus encodes a putative exoskeletal protein with a novel tandem repeat structure.

A gene, named DD5, was identified in the penaeid prawn Penaeus japonicus and its cDNA cloned and sequenced. DD5 is expressed in the epidermal cells underlying the exoskeleton and the transcripts are detected specifically during the postmolt stage of the molt cycle. Sequence analysis of the conceptual protein product suggests that the DD5 protein is a component of the exoskeleton. The bulk of the protein consists of tandem repeats of a unit sequence of approximately 100 amino acids. The repeated sequences are highly homologous to one another and each of them includes a variant of the Rebers--Riddiford consensus sequence.

The resection of non-hepatic intraabdominal recurrence of gastric cancer.

BACKGROUND/AIMS: Surgical resection of hepatic or pulmonary metastases from gastrointestinal cancer has been recognized as a curative modality in some patients. However, the role and outcome of the surgical management of a non-hepatic intraabdominal recurrence of gastrointestinal cancer have not been clearly delineated. METHODOLOGY: We treated 5 patients for non-hepatic intraabdominal recurrence of gastric carcinoma surgically. All the resected specimens were microscopically identified as recurrent gastric cancer. Three of 5 patients received postoperative chemotherapy. The clinicopathological findings were analyzed according to the general rules for gastric cancer study. RESULTS: The lymph nodes were dissected for lymph node metastases. Surgical resection of the tumors combined with total gastrectomy, esophagectomy, or colectomy was performed for the local and peritoneal recurrences. All of the recurrent tumors were macroscopically resected with curative states. One patient died of sepsis 54 days after surgery. Three patients died of recurrent gastric cancer: 2 within 1 year of surgery and 1 after 3 years. One patient still survives disease free 3 years and 6 months after the 2nd operation. CONCLUSIONS: Surgical resection for non-hepatic intraabdominal recurrence of gastric cancer is the treatment of choice for selected patients. Surgical resection followed by adjuvant chemotherapy may improve the outcome of these patients.

Soluble E-selectin as a marker of disease activity in pustulosis palmaris et plantaris.

In this study, we investigated a possible correlation between adhesion molecules and activity of pustulosis palmaris et plantaris (PPP). Serum levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecules 1 (sICAM-1) and tumour necrosis factor alpha (TNF-alpha) in 30 untreated PPP patients were examined, and compared with those in 20 healthy subjects. Values in 10 PPP patients were re-examined after treatment. Serum levels of sE-selectin and TNF-alpha in untreated PPP patients were significantly higher than those in healthy subjects. There was a statistically significant correlation between the disease activity and serum levels of sE-selectin in untreated PPP patients. Furthermore, disease activity of PPP was higher in patients who smoked and during the summer, with elevation of serum sE-selectin levels. Serum levels of sE-selectin were downregulated with the recovery from PPP. These results suggest that sE-selectin may play a role in the pathogenesis of PPP and could be a reliable marker of its disease activity.

Segmental pancreatectomy for mucin-producing pancreatic tumors.

BACKGROUND/AIMS: Segmental pancreatectomy for benign tumors of the neck of the pancreas was reported in 1993. Mucin-producing carcinomas are generally regarded as low-grade malignancies as compared with ductal cell carcinomas of the pancreas. We report herein our experience with a segmental pancreatectomy for mucin-producing pancreatic tumors. METHODOLOGY: Three patients with mucin-producing tumors of the pancreatic body underwent a segmental pancreatectomy. After the pancreatic tumor had been located with intra-operative ultrasonography (US), the medial pancreas centered on the tumor was resected. The margin of the retained pancreas was submitted for histopathologic inspection intra-operatively to prevent retained disease. A conduit for draining the pancreatic juice consisted of a jejunal Roux-en-Y loop between the left and cephalic portions of the pancreas. Histologically, the 3 tumors were identified as a cystadenocarcinoma, an intraductal papillary adenocarcinoma, and a cystadenoma with a focus of borderline malignancy. The functional result was evaluated with oral glucose tolerance and pancreatic function diagnostic (PFD) testing. Pancreatic juice drainage was confirmed using magnetic resonance cholangiopancreatography (MRCP). RESULTS: Neither technical failure nor operative death occurred in any of the patients. The patients have been followed-up for between 33 months and 77 months after surgery and all are disease free. The oral glucose tolerance test and PFD test results were all within the normal range. MRCP showed good pancreatic juice drainage in the 2 patients examined. CONCLUSIONS: Segmental pancreatectomy may be an appropriate surgical procedure for mucin-producing pancreatic tumors, to prolong survival and to preserve endocrine and exocrine function.

Interplay of Notch and FGF signaling restricts cell fate and MAPK activation in the Drosophila trachea.

The patterned branching in the Drosophila tracheal system is triggered by the FGF-like ligand Branchless that activates a receptor tyrosine kinase Breathless and the MAP kinase pathway. A single fusion cell at the tip of each fusion branch expresses the zinc-finger gene escargot, leads branch migration in a stereotypical pattern and contacts with another fusion cell to mediate fusion of the branches. A high level of MAP kinase activation is also limited to the tip of the branches. Restriction of such cell specialization events to the tip is essential for tracheal tubulogenesis. Here we show that Notch signaling plays crucial roles in the singling out process of the fusion cell. We found that Notch is activated in tracheal cells by Branchless signaling through stimulation of &Dgr; expression at the tip of tracheal branches and that activated Notch represses the fate of the fusion cell. In addition, Notch is required to restrict activation of MAP kinase to the tip of the branches, in part through the negative regulation of Branchless expression. Notch-mediated lateral inhibition in sending and receiving cells is thus essential to restrict the inductive influence of Branchless on the tracheal tubulogenesis.

Hydrogenation of 1-Hexene and Hexadienes by Ultrafine Pd Particles Supported on the Surface of PrPO(4) Hollow Particles.

Novel fine polymer particles containing ultrafine Pd particles dispersed on the surface of core shell [core, poly(styrene-co-acrylic acid); shell, PrPO(4)]-type microspheres were prepared by the emulsifier-free emulsion polymerization of styrene with acrylic acid followed by the addition of PdCl(2) and a mixture of Pr(NO(3))(3) and NaH(2)PO(2). Pyrolysis of the resulting polymer particles at 900 degrees C provides organic polymer-free hollow particles (diameter, 473-586 nm) composed of Pd metal and PrPO(4). Hydrogenation of 1-hexene, trans-1,3-hexadiene, trans-1,4-hexadiene, and 1,5-hexadiene using the resulting Pd/PrPO(4) particles (reactant/Pd = 500 mol/mol) as catalyst revealed very high activity, especially for hydrogenations of 1-hexene and 1,5-hexadiene as compared with conventional Pd particles/Al(2)O(3) and Pd particles on powdered PrPO(4). Copyright 1999 Academic Press.

Gastric emptying after segmental gastrectomy for early cancer in the middle part of the stomach.

BACKGROUND/AIMS: We evaluated the quality of life and gastric emptying in patients who had undergone a segmental gastrectomy to treat early gastric cancer in the middle part of the stomach. METHODOLOGY: Thirty patients were considered in this study. Their mean age was 65.5 years (range: 44-83). All of the patients were free from recurrence of their cancer in the follow-up period. This ranged from 5 to 50 months (mean 30). Patients were interviewed at regular intervals to assess their quality of life and to note particular complaints. The upper gastrointestinal tract was assessed endoscopically. A gastric emptying study was performed at 3, 6, and 12 months after surgery. The meal used in this dual-phase study had solid and liquid phases. For the solid phase, 74 MBq of 99mTc sulfur colloid was injected into an egg, which was then hard-boiled. For the liquid phase, 18.5 MBq of (111)In-diethyltriaminopenta acetic acid (DTPA) were mixed into 150 ml of a commercial, elentary liquid diet. RESULTS: Three months after surgery, the patients' main complaints were gastric stasis (25%), heartburn (8%) and belching (8%). The patients gradually became asymptomatic following surgery. Fifty-nine percent were asymptomatic at the 3-month follow-up, 84% at 6 months, and 92% at 12 months. There was no evidence of reflux esophagitis or gastritis after the 3-month follow-up. One patient developed a complicated duodenal ulcer. Initially, the patients all had prolonged gastric emptying of the dual phase meal, compared to normal individuals. The T1/2 for liquid meal emptying was 87+/-18 min at 3 months, 77+/-20 min at 6 months and 50+/-5 min at 1 year after surgery. The last value is the same as for healthy individuals. Solid meal emptying was still prolonged, with an emptying rate of 36+/-9.7% at 2 hours, one year after surgery. CONCLUSIONS: Segmental gastrectomy patients experienced prolonged gastric emptying in the early post-operative period. This improved in the first year after surgery. The quality of life for patients who underwent segmental gastrectomy has been reasonably good in the follow-up period to date.

Endoscopic balloon dilation for benign esophageal anastomotic stricture: factors influencing its effectiveness.

BACKGROUND/AIMS: The aim of this study was to identify factors that might affect the results of treating benign anastomotic stricture of the esophagus with balloon dilation. METHODOLOGY: Balloon dilation was performed on 35 patients with benign esophageal anastomotic stricture of the upper (esophageal cancer: 18) or lower (gastric cancer: 15, esophageal varices: 2) esophagus. The procedure was considered effective when patients were able to maintain a solid diet more than 12 months after the last dilation. The follow-up period ranged from 15-130 months (mean: 51 months). RESULTS: A total of 245 dilations were performed, with an average of 6.6 dilations per patient. Treatment was effective in 29 patients (83%). Balloon dilation was successful when treating strictures shorter than 12 mm in length. The strictures were significantly shorter in patients treated effectively (5.6 vs. 30.8 mm). The diameter of the stricture did not affect the results. All the strictures in the lower esophagus and all those resulting from stapled anastomoses were treated successfully, while the effectiveness of treating strictures in the upper esophagus or those resulting from hand-sewn anastomoses was 67% and 57%, respectively. Strictures without prior leakage were treated effectively 92% of the time, while the success rate fell to 56% if there was a preceding leak. An average of 4.4 dilations were performed in effective cases, while the average was 17.5 dilations in ineffective cases. The number of repeat dilations was correlated with the length of the stricture. CONCLUSIONS: Balloon dilation can successfully treat strictures shorter than 12 mm long. The correlation equation may be used to predict the number of repeat dilations and treatment results, and is useful for deciding when to use an alternative method to balloon dilation.

Segmental gastrectomy for early cancer in the mid-stomach.

BACKGROUND/AIMS: We modified the surgical procedure for segmental gastrectomy, which is normally used for peptic ulcers, to treat early gastric cancer of the mid-stomach. In this paper, we describe the surgical technique and its results. METHODOLOGY: The location of the tumor was confirmed by intra-operative endoscopic examination. An area 2 cm proximal and distal to the tumor was marked with sutures. Firstly, the lymph nodes were dissected from around the perigastric and along the left gastric and common hepatic arteries. Then, a segmental gastrectomy was performed. The greater omentum, omental sac, and vagal nerve, including the hepatic, pyloric and celiac rami, were left intact. An end-to-end gastrogastrostomy was performed using Gambee's sutures and 4-0 monofilament polydioxanone. Gastric drainage was not necessary. RESULTS: We performed segmental gastrectomies on 30 patients. Tumors less than 1 cm in diameter were found in 4 patients; 1.1-2 cm in 14, 2.1-5 cm in 11, and a tumor exceeding 5.1 cm in one patient. The cancer was confined to the mucosa in 23 patients; in the other 7, it had penetrated the submucosa. No lymph node metastases were found but 2 patients had microscopic invasion or permeation of the lymphatic vessels. One patient required post-operative balloon dilation of the pyloric sphincter for delayed gastric emptying. The remaining patients had no post-operative complications. To date, 29 patients, excluding one who died in a traffic accident, have survived disease-free for a mean of 30 months (range: 7-51). Their body weight and dietary volume returned to pre-operative levels within 12 months of surgery. CONCLUSIONS: Patients who underwent segmental gastrectomy have had a reasonably good quality of life in the post-operative follow-up to date.

[A case of sleeve resection of the left main bronchus for tuberculous bronchial lesion].

A 31-year-old woman was admitted to our center with left chest pain and dyspnea after treatment of pulmonary tuberculosis. Chest X-ray film showed atelectasis of left lower lobe and left deviation of the mediastium. Bronchofiberscopy revealed obstruction of the left main bronchus. Chest MRI showed intermediate intensity at the left main bronchus and very high intensity at the peripheral bronchus. We performed sleeve resection of the left main bronchus and anastomosed end to end with absorbable monofilament sutures. Postoperative course was uneventful. Bronchoplasty for tuberculous obstructive lesion is a useful procedure.