Successful treatment of cap polyposis by avoidance of intraluminal trauma: clues to pathogenesis.

"Cap polyposis" is a rarely-encountered condition in which distinctive inflammatory polyps are located from the rectum to the distal descending colon. Microscopically, the polyps consist of elongated, tortuous, and distended crypts covered by a "cap" of inflammatory granulation tissue. Although the pathogenesis is unknown, mucosal prolapse has been postulated to be an important etiological factor, given certain clinical and histological similarities. We describe two cases of cap polyposis with protein-losing enteropathy. One was treated successfully by avoidance of straining at defecation. Another resolved after double-barreled transverse colostomy. Both successful treatments support a causal link of polyposis to prolapse.

Frequent loss of copy number on the long arm of chromosome 21 in human esophageal squamous cell carcinoma.

To understand the molecular pathogenesis of human esophageal cancer, we performed a comparative genomic hybridization (CGH) analysis using 10 esophageal squamous cell carcinomas. Frequent gains of 1q, 3q, 7p, 7q, 8q, 11q, and 20q and losses of 3p, 4p, 4q, 5q, 9p, 11p, 11q, 13q, 18q, 21q, and Y were observed. Among these regions, 21q has not yet been investigated in detail. We performed an allelotype study using 55 squamous cell carcinomas of the esophagus and 20 microsatellite markers on 21q and found LOH in 36 cases (65%): 22 (61%) of 36 cases with LOH indicated allelic loss in all informative loci, suggesting loss of the whole chromosome arm 21q, and five smallest regions of overlap were found. Our present results suggest the existence of a tumor suppressor gene(s) that plays a role in the genesis of squamous cell carcinoma of the esophagus.

Port site recurrence of gallbladder cancer after laparoscopic surgery: two case reports of long-term survival.

More than 100 patients with port site recurrence after laparoscopic procedures have been reported, and in most cases recurrence has had a fatal outcome. Two patients who survived port site recurrence of unexpected gallbladder cancer after laparoscopic cholecystectomy are reported. Abdominal wall excision was performed in one patient, and thermoradiotherapy was performed in the other. Both patients have remained free of disease during long-term follow-up (82 and 45 months).

Probiotic bacteria stimulate gut epithelial cell proliferation in rat.

Probiotics are used for various intestinal diseases. However, their effects on gut epithelial cell proliferation have not been investigated. We administered 10(7) colony-forming units of Lactobacillus casei or Clostridium butyricum, or no probiotics (control) by gastric intubation once a day for seven days to rats fed an elemental diet. We estimated the crypt cell production rate of the jejunum, ileum, cecum, and distal colon. We also quantified cecal bacteria. Both probiotics increased the crypt cell production rate of the jejunum and ileum by 25-40%, of the cecum by 70%, and of the distal colon by more than 200% compared with control. Only minor variance in the cecal bacterial composition existed among the three groups. Probiotics enhanced gut epithelial cell proliferation in rats fed an elemental diet.

Detection of the cardiac function by fractal dimension analysis.

Nonlinearity in circulation control attracts attention because nonlinearity is thought to be essential in the function of the living body. Many investigators have pointed out that the analysis of heart rate variability in particular is important in the analysis of autonomic nerve and cardiac function evaluation. Heart rate variability shows nonlinear behavior. However, until the present, many reports have been premised on linearity; linear correlation by frequency analysis has been used by many studies. However, in terms of this methodology, there is a problem applying it to the nonlinear living body. Therefore, fractal and chaos methodology has been used. The ascertainment of cardiac function has become important in allowing the clinical stage of a ventricular assist system to be successful. The purpose of this study was cardiac function evaluation by a methodology that was premised on nonlinearity. Chaos and fractal theory was used as a nonlinear dynamic theory. As a methodology of measurement, the volume of the left ventricle was used rather than an electrocardiogram, the waveform of arterial blood pressure. The volume was measured using acoustic quantification (AQ) ultrasonic echocardiography. Using these methodologies, the time series of many patients were analyzed. For example, drug administration was attempted in this study, and it was found that some drugs like ACE inhibitors showed a significant effect upon nonlinear dynamics in the cardiovascular system. The result, which attempted cardiac function evaluation by these various methodologies, is reported.

The chimeric protein, PEBP2 beta/CBF beta-SMMHC, disorganizes cytoplasmic stress fibers and inhibits transcriptional activation.

The chromosomal inversion 16(p13;q22) associated with human acute myeloid leukemia generates the chimeric PEBP2 beta/CBF beta-SMMHC gene. The PEBP2 beta/CBF beta portion of the chimeric polypeptide harbors most of the amino acid sequence of the PEBP2 beta/CBF beta protein, the non-DNA binding subunit of the heterodimeric transcription factor, PEBP2/CBF, whereas the SMMHC portion of the chimera consists of the rod domain of the smooth muscle myosin heavy chain molecule. In this study we examined the subcellular localization of the chimeric protein and its effect both on stress fibers and transcriptional activation by transfecting cDNA into tissue culture cells. The localization of the chimera was investigated by immunocytochemical staining of cells and was found to be both cytoplasmic and nuclear. One aspect of the effect of expression of the chimera was a drastic alteration of cell morphology. The cells appeared elongated and possessed long cytoplasmic processes. Double fluorescent labeling revealed disorganization of the stress fibers and an altered F-actin staining pattern in the transfected cells. Studies using a deletion mutant showed that both the PEBP2 beta/CBF beta and SMMHC domains are necessary for the induction of the morphological alteration. A significant proportion of the chimeric protein was retained in the cytoskeleton after detergent extraction of the cells and could be recuperated as a membrane fraction, suggesting that this is one of the probable sites of action of the PEBP2 beta/CBF beta-SMMHC protein. Another effect of the chimeric protein was inhibition of transcriptional activation dependent on the PEBP2/CBF binding DNA sequence. However, deregulation of PEBP2/CBF site dependent transcription by itself was not sufficient to induce cell morphological changes. Taken together, these results indicate that the PEBP2 beta/CBF beta-SMMHC chimeric protein acts at two levels, at the level of stress fiber organization and at the level of transcriptional activation. We suggest that the action of PEBP2 beta/CBF beta-SMMHC depends to a great extent on whether it is located in the cytoplasm or in the nucleus.

[Frequent loss of heterozygosity on the long arm of chromosome 21 in human esophageal, squamous cell carcinoma].

We investigated human esophageal squamous cell carcinoma using microsatellite markers on the long arm of chromosome 21 (21q) and found frequent loss of heterozygosity (LOH). The frequency of LOH was more than 50% in most of the microsatellite markers examined. Whole chromosome deletion suspected cases were observed in 25% of all cases. No case with microsatellite instability was found. Three common regions of allelic loss were identified. The frequent LOH was observed from early stage in pTNM classification. An unknown tumor suppressor gene in the genesis of esophageal squamous cell carcinoma may exist in 21q.

Establishment and characterization of a murine cell-line derived from malignant fibrous histiocytoma of A/Jackson mouse.

A hard mass incidentally found in the right buttock of an elderly male A/J mouse was morphologically consistent with malignant fibrous histiocytoma; storiform-pleomorphic subtype. Diced pieces or suspensions of the tumor tissue were readily transplantable subcutaneously in the flank of mice of the strain. The tumor-bearing mice died mostly of rupture of the tumor into the thorax or abdomen within 4 weeks. Pulmonary and splenic metastasis were recognized only in a mouse which survived more than 10 weeks. A new cell-line was established from the original tumor without necessary cloning and was maintained in MEM (minimum essential medium) supplemented with 10% FCS for 6 months under 22 passages. Frozen stocks were then made, from which the recovery of the cells was successful. The cell growth, requiring about 20 hours for doubling of population, was a mixture of plump or stellate histiocytic cells and fibroblastic ones, both of which contained lipid droplets and retained phagocytic activity. The cell-line was designated as murine sarcoma Sendai (MuSS). Morphological versatility of the cultured cells suggested the origin of the neoplasm from multipotential, primitive mesenchymal cells.

Effect of valine-depleted total parenteral nutrition on fatty liver development in tumor-bearing rats.

Valine-depleted amino acid imbalance, while having a suppressive effect on tumor growth, may induce fatty liver. We administered valine-depleted total parenteral nutrition (TPN) solution to rats subcutaneously transplanted with ascites containing hepatoma AH-109A and examined the time course of the development of fatty liver. An accumulation of fatty vacuoles was observed in hepatocytes on day 4. To prevent the development of fatty liver in tumor-bearing rats, we administered a small amount of valine in addition to the valine-depleted imbalance solution via the central vein. Such treatment, however, resulted in neither the prevention of fatty liver development nor the suppression of tumor growth. To supply valine to the liver, we administered a low concentration of valine via the portal vein simultaneously with central venous administration of valine-depleted TPN solution. As a result, the peripheral blood valine level of these rats was < 0.5 that of the control group, but the valine in the liver was maintained at the same level as that of the control group, and accumulation of triacylglycerols in the liver was slight. However, the suppressive effect on tumor growth was maintained, as the tumor weight was suppressed to almost the same degree as that of rats administered only the valine-depleted solution.

Mutational analysis of the domain structure of mouse protein phosphatase 2Cbeta.

The structures of five distinct isoforms of mammalian protein phosphatase 2Cbeta (PP2Cbeta-1, -2, -3, -4 and -5) have previously been found to differ only at their C-terminal regions. In the present study, we performed mutational analysis of recombinant mouse PP2Cbeta-1 to determine the functional domains of the molecule and elucidate the biochemical significance of the structural differences in the isoforms. Differences in affinity for [32P]phosphohistone but not for [32P]phosphocasein were observed among the five PP2Cbeta isoforms. Deletion of 12 amino acids from the C-terminal end, which form a unique sequence for PP2Cbeta-1, caused a 35% loss of activity against [32P]phosphohistone but no loss of activity against [32P]phosphocasein. Deletion of up to 78 amino acids from this end did not cause any further alteration in activity, whereas deletion of 100 amino acids totally eliminated the activity against both [32P]phosphohistone and [32P]phosphocasein. On the other hand, deletion of 11 amino acids from the N-terminal end caused a 97% loss of enzyme activity, and further deletions caused a total loss of activity. Substitution of any of the six specific amino acids among 16 tested in this study, which were located among the 250 N-terminal residues, caused 98-100% loss of enzyme activity. Among these amino acids, three (Glu-38, -60 and -243) have recently been reported to be essential for the binding of metal ions in the catalytic site of the PP2C molecule [Das, Helps, Cohen and Barford (1996) EMBO J. 15, 6798-6809]. These observations indicate that PP2Cbeta is composed of at least two distinct functional domains, an N-terminal catalytic domain of about 310 amino acids and the remaining C-terminal domain, which is involved in determination of substrate specificity.

A prospective randomized trial of extended cervical and superior mediastinal lymphadenectomy for carcinoma of the thoracic esophagus.

BACKGROUND: Recurrence of thoracic esophageal carcinoma in the cervical and superior mediastinal lymph nodes occurs frequently and contributes to a poor prognosis. Extensive lymphadenectomy has been advocated. Findings in support of this to date, however, have been based on a comparison with historical controls. We herein report a prospective randomized trial of extended and conventional lymphadenectomy. METHODS: Cases of thoracic esophageal carcinoma meeting criteria predictive of complete resection were randomized into conventional and extended cervical and superior mediastinal lymphadenectomy groups. RESULTS: In the extended and conventional lymphadenectomy groups, respectively, mean operative time was 487 +/- 47 and 396 +/- 43 minutes, blood loss was 850 +/- 429 and 576 +/- 261 mL, node count was 82 +/- 22 and 43 +/- 15, hospital deaths occurred in 3% and 7%, 2-year survival was 83.3% and 64.8%, 5-year survival was 66.2% and 48.0%, and recurrence rate was 19.9% and 24.1%. CONCLUSION: Extended lymphadenectomy may prevent recurrence and prolong survival after resection of thoracic esophageal carcinoma.

The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures.

The Pebpb2/Cbfb gene encodes the non-DNA binding beta subunit of the heterodimeric transcription factor, PEBP2/CBF, and has been implicated in a subtype of human acute myeloid leukemia, as well as being indispensable for the development of definitive hematopoiesis in the murine fetal liver. By examining a subcellular localization of the PEBP2beta/CBFbeta protein in tissue culture cells, we could reveal an additional aspect of the protein other than to be a subunit of a transcription factor. Immunoblot and immunocytochemical staining showed that PEBP2beta/CBFbeta was mostly present in the cytoplasm. This PEBP2beta/CBFbeta was free from its DNA-binding partner, the alpha subunit of PEBP2/CBF, as judged by the electrophoretic mobility shift assays. Furthermore, a significant amount of PEBP2beta/CBFbeta was retained in the cytoskeleton preparation after detergent extraction of the cells and was found by double immunofluorescence to colocalize with the F-actin on stress fibers and the vinculin in membrane processes. Thus, the present study extends PEBP2beta/CBFbeta to be a cytoskeleton-affinitive as well as nuclear protein. The implications of these results are discussed.

Analysis of the p53 gene mutations in patients with multiple primary cancers of the oesophagus.

We investigated genetic alterations of the p53 gene in two patients with multiple primary oesophageal squamous cell carcinomas (ESCs). We found that each primary tumour could be distinguished by mutation of p53. Moreover, mutations detected in the p53 gene in metastatic lymph nodes were the same as those detected in at least one of the primary tumours. Our results presented the possibility of: (1) discrimination of primary and metastatic legions in patients with multiple primary ESCs; (2) determination of metastatic pathway to regional lymph nodes; and (3) application for the development of a better clinical management of patients with multiple primary ESCs.

Improvement of circulation in pedicled intestinal grafts: hemodynamics of the intestine after preparation of a sacrificial colonic graft.

BACKGROUND: To preserve postoperative digestive function in patients with esophageal carcinoma, jejunal or colonic segments on long vascular pedicles are transplanted and anastomosed between the esophagus and residual stomach. A postoperative survey showed pedicled jejunum transplantation to be superior in terms of digestive and absorptive functions, intraesophageal pressure, pH, and the quality of life of long-term postoperative survivors. Anastomotic leakage and necrosis of the pedicled intestinal graft are occasional complications; circulatory disorders of the pedicled intestine are a probable cause of both complications. STUDY DESIGN: To simulate pedicled jejunum transplantation, we prepared pedicled colonic segments from dogs and measured blood flow volume at the cut end of the oral side of the colonic segments using the hydrogen clearance method and at the nutrient vascular pedicle with an electromagnetic blood flowmeter. RESULTS: Resection of excess colon increased blood flow volume per unit weight of the colonic segment. CONCLUSIONS: It is essential to resect excess intestine and keep only the minimum length of pedicled intestinal graft needed for reconstruction of the esophagus.

Frequent association of alternative splicing of NER, a nuclear hormone receptor gene in cancer tissues.

We have detected frequent alternative splicing of a gene that encodes NER, a protein homologous to the retinoic acid receptors, in cancer cells. Western and immunohistochemical analyses disclosed accumulation of a large amount of the aberrant NER product, generated by alternative splicing that caused skipping of an exon corresponding to the DNA-binding domain, in the nucleoli of cells of cancer cell lines and primary cancer tissues. The aberrant protein was detected in 116 of 228 primary cancers developed in various tissues including breast and colon, but was absent in the corresponding normal tissues; it was also detected in 31 of 39 cancer cell lines. This observation may imply that the aberrant NER product has some relation to the development and/or progression of cancers in a variety of human tissues.

Effects of caloric intake on anticancer therapy in rats with valine-depleted amino acid imbalance.

Valine-depleted amino acid imbalance solution markedly inhibits tumor growth but causes fatty liver as a side effect. However, much remains unknown about the mechanism of the development of fatty liver. Valine-depleted amino acid imbalance solution containing various concentrations of calories was administered to tumor-bearing rats for four days by means of total parenteral nutritional methods to investigate the interaction of caloric intake and the development of fatty liver. Compared with the total parenteral nutrition control group the triglyceride content of the liver rose significantly in the group given valine-depleted amino acid imbalance solution with an increase in caloric intake. Plasma total protein and albumin significantly decreased. The very-low-density lipoprotein concentration in serum was also significantly lower than that in the control group. Valine-depleted amino acid imbalance caused hypoproteinemia, suggesting a fall in synthesis of apolipoproteins in the liver indispensable for lipid release. Along with the increase in the total caloric intake, triglyceride synthesis in the liver increased, resulting in augmentation of fatty content of the liver, probably because of the decreased lipid release.

[Intraoperative fluid infusion and blood transfusion in patients of esophageal cancer].

While patients with esophageal cancer are operated, a large quantity of non-functional extracelluler fluid (ECF) are appeared. Mediastinum, intestines, visceral vessels, wound of thoracotomy and laparotomy, etc, become so called "third space", then much water, Na are shifted and restored there. Moreover, plenty of water are evaporated from operated fields and lymph issues are active. A long time ago, intraoperative fluid infusion was little, but recently more fluid (Hartmann solution) are infused (8 approximately 10/ml/kg/hr). Intraoperative blood transfusion is often done because blood tends to lose. But it sometimes had serious side effects, example for GVHD (graft-versus-host disease), infections. In order to prevent from thease, autotransfusion and irradiation to transfused blood are recommended.