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From the aerial parts of Crepidiastrum lanceolatum, six guaiane-type sesquiterpene glucosides, lanceocripidiasides A-F were isolated together with five known sesquiterpene glucosides, ixerin Y, crepidialanceosides A and B, and youngiasides A and D, two known megastigmane glucosides, icariside B1 and corchoionoside A, and benzyl 6'-O-beta-D-apiofuranosyl-beta-D-glucopyranoside. Structures were elucidated by spectroscopic analyses.

Background: Cytomegalovirus (CMV) diseases commonly occur in allograft recipients in the early post-transplant period. However, factors responsible for the high incidence of CMV diseases during this period are not yet fully defined., Methods: Wistar-Furth (WF; RT-1(u)) rats were inoculated with 10(4) plaque-forming units (PFU) of rat CMV (RCMV) intraperitoneally, and then transplanted with allogeneic lungs from Dark Agouti (DA; RT-1avl) rats or stimulated with 10(7) mitomycin C-treated spleen cells from DA rats by daily sub-cutaneous injections for 2 weeks. No immunosuppressive agent was used. Naive WF rats and WF rats grafted with syngeneic lungs or cells were used as controls. The level of RCMV replication in rats was assessed by infectious virus titers in tissues., Results: The virus titers in salivary glands of allogeneic and syngeneic lung graft recipients were significantly higher than in naive WF rats. The level of RCMV replication in rats stimulated with allogeneic spleen cells was significantly higher than in the syngeneic recipient rats: virus titers in the salivary gland of allogeneic and syngeneic recipients reached 4.61 +/- 0.33 and 4.00 +/- 0.37 log(10) PFU/g tissue, respectively, at 14 days post-infection (p = 0.015). The augmented viral replication in allogeneic recipients was confirmed by an increase in the number of RCMV antigen-positive macrophages present in tissue sections of the salivary gland., Conclusions: Acute lung allograft rejection and allogeneic spleen cell stimulation enhance CMV replication in the salivary gland of rats. Various responses to allogeneic antigens occurring in the process of acute allograft rejection could be risk factors for post-transplant CMV replication and infection.

Background: Several recent studies discuss bronchoscopic techniques for treating endobronchial lipoma, an extremely rare benign tumor., Objectives: To describe the epidemiology of endobronchial lipoma and to propose appropriate therapeutic policies for treating this tumor., Methods: We reviewed 64 cases of endobronchial lipoma: 33 cases previously reported in 30 different articles, and 31 case reports presented at thoracic meetings in Japan., Results: Of the 64 patients included in this study (50 male and 14 female; mean age, 60 years), 40 patients had endobronchial lipoma in the right lung and 23 patients had it in the left lung. The overwhelming majority of the tumors (n = 61) were found in the first three subdivisions of the tracheobronchial tree. Forty-eight patients (75%) were symptomatic, and their symptoms included cough, sputum, hemoptysis, elevated temperature, and dyspnea. Additionally, abnormal radiographic findings were reported for 51 patients (80%): 18 patients had atelectasis, 14 patients had infiltration or consolidation, 6 patients showed volume loss of the lung, and mass shadow was identified in 9 patients, and another abnormality including pleural effusion was found in 4 patients. Forty patients underwent surgical resection: 4 pneumonectomies, 24 lobectomies, 8 bilobectomies, and 4 resections by bronchotomy. Bronchoscopic resection was carried out in 17 cases: 7 cases by Nd-YAG laser, 5 cases by electrosurgical snaring forceps, and another 5 cases with a combined therapy using both procedures., Conclusions: Bronchoscopic resection should be considered as the first choice of treatment for endobronchial lipoma; however, surgical therapy is indicated for patients who show the possibility of a complicated malignant tumor, who have destructive peripheral lung disease, who have extrabronchial growth, or who may have technical difficulties during the bronchoscopic procedure.

The gene for mammalian O-sialoglycoprotein endopeptidase (Osgep) lies immediately adjacent to the gene for the APEX nuclease (Apex), a multifunctional DNA repair enzyme, in a head-to-head orientation. To clarify the regulation of these divergent genes, we studied their promoter regions with luciferase reporters. Deletion analysis of a fragment containing the entire mouse Apex gene suggested that cis-acting elements driving in the direction of Osgep are widely distributed in the mApex gene, in the antisense orientation. We investigated in detail cis-acting elements near the transcription initiation site of mOsgep. The spacer sequence between mOsgep and mApex was shown to have bidirectional promoter activity and it has been reported that two CCAAT boxes promote basal transcription in the direction of mApex. However, only one of the CCAAT boxes proximal to the transcription initiation site of mOsgep was important for transcription towards mOsgep. An Sp1-binding sequence was found to be involved in bidirectional transcription and a CRE/ATF-like sequence was shown to function as a repressor of mOsgep transcription. Quantitative RT-PCR showed that the mApex and mOsgep genes were expressed in all tissues examined and that expression of mOsgep was low compared with mApex.

Background: Minimal resection of small lung tumors is still controversial. This study was conducted to clarify whether this type of operation is acceptable., Methods: From January 1992 to December 1994, 73 patients were registered in a multiinstitutional trial of limited resection for peripheral lung tumors less than 2 cm in diameter. The operative procedure consisted of extended segmentectomy in which the cut line of the lung was beyond the burdened segment, confirming N0 disease by intraoperative lymph node examination of frozen sections. The operation was changed to other procedures if the report was positive., Results: All the patients were observed more than 5 years. There were no perioperative deaths and no major complications. A total of 55 patients were finally enrolled in this study. Ten patients died postoperatively, 4 of lung cancer and the remaining 6 died of other diseases, with no signs of recurrence. The 5-year survival rate, excluding these 6 patients, was 91.8%; for all patients including those who died it was 81.8%. A total of 18 patients were not included in this study for various reasons. The decrease in forced vital capacity was 11.3% +/- 9.8% compared with the preoperative value., Conclusions: Extended segmentectomy is an alternative method as a standard operation for patients with small peripheral lung tumors, and the loss of lung function is minimal. However, patient selection must be strict, with intraoperative pathologic examination, and a wide margin to the lesion beyond the burdened segment is mandatory.

Aims: To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients., Methods: Pre-operative serum levels of STN, sialyl Lewis(a)antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis., Results: Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P<0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patients. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis., Conclusions: Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer.

Objectives: During or after surgery, asthma attacks due to airway hyperresponsiveness (AHR) are likely to occur in patients with bronchial asthma. Preoperative administration of corticosteroid for prevention of perioperative asthma attacks is useful. We examined the mechanism of prevention of perioperative asthma attacks by the preoperative administration of corticosteroid in vitro., Design: Five patients with asthma were treated with 20 mg of prednisolone orally for 2 preoperative days and 80 mg of methylprednisolone IV immediately before and after surgery. In another five patients without asthma, no steroids were administered. A noncarcinomatous part of the resected tissue from each patient with lung cancer was passively sensitized with the serum of an atopic patient. In the patients without asthma, the tissue was treated with or without dexamethasone, and then mite antigen was added., Measurements: The culture supernatant and lung tissue were recovered, and the supernatant was assayed for histamine, leukotriene E(4) (LTE(4)), interleukin (IL)-5, and tumor necrosis factor (TNF)-alpha. Degranulation of mast cells was measured by tryptase staining of the lung tissue, and the expression of messenger RNA (mRNA) of IL-5 and TNF-alpha was determined by the reverse transcriptase-polymerase chain reaction method., Results: While preoperative administration of corticosteroid did not suppress the release of histamine and LTE(4) from the lungs of asthmatic patients, it completely suppressed IL-5 and TNF-alpha production at the mRNA level. The same results were obtained in lung tissues of nonasthmatic patients treated in vitro with dexamethasone., Conclusions: Our results suggest that corticosteroid treatment reduces AHR and prevents perioperative attacks of asthma primarily by suppressing the production of inflammatory cytokines.

Background: Proinflammatory cytokines, such as tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1), play important roles in acute allograft rejection. FR167653 is an inhibitor of these cytokines that acts through inhibition of the mitogen-activated protein kinase p38 pathway. We examined the effect of FR167653 on allograft rejection., Methods: We used Brown-Norway and Lewis rats as donors and recipients, respectively. We performed heterotopic cardiac transplantation. The control group consisted of untreated rats. In the experimental groups, recipients were intraperitoneally injected with FR167653 just after operation, followed by daily injection of the drug from Day 1 to 10. We divided 20 rats into 5 groups, which received varying doses of FR167653, ranging from 75 to 300 mg/kg/day., Results: In the control group, the mean graft survival was 6.8 +/- 0.3 days. FR167653 at 150 mg/kg/day significantly prolonged the survival period (up to 12.1 +/- 1.5 days, p = 0.002). Histologically, FR167653 markedly suppressed cellular infiltration on Day 5 post-transplantation. The serum level of TNF-alpha in the control group was persistently elevated from 9.3 +/- 3.9 pg/ml to 11.3 +/- 3.8 pg/ml, whereas FR167653 significantly suppressed the level to <1.4 +/- 1.4 pg/ml., Conclusions: FR167653 prolonged rat cardiac allograft survival by suppressing the action of proinflammatory cytokines.

In this study, we examined the preoperative serum levels of sialyl Lewisa, sialyl LewisX, sialyl Tn, and carcinoembryonic antigen in 243 colorectal cancer patients in order to clarify the role of these antigens as prognostic factors after curative surgery. The patients were divided into two groups: low and high antigen groups (lower and higher than a selected diagnostic-based cut-off value). Patients with high serum levels of sialyl Lewisa and carcinoembryonic antigen had shorter disease-free intervals than those with low serum levels of the respective antigen, although sialyl Lewisx and sialyl Tn showed no significant differences. Multivariate analysis revealed that three independent prognostic variables, including depth of tumor invasion, lymph node metastasis, and serum sialyl Lewisa level, did prove to have value in predicting disease-free interval. In conclusion, among the four antigens examined in this study, the preoperative serum level of sialyl Lewisa is the only independent prognostic variable for recurrence after curative resection of colorectal cancer.

In this paper we present a new technique for thymic cystectomy by video-assisted thoracic surgery. The thoracoscope was inserted using a Vein Harvest (Ethicon Endo-Surgery Co, Ltd, Cincinnati, OH) through a 5-cm subxyphoid incision. A Harmonic Scalpel (Ethicon Endo-Surgery) and Cherry Dissector (Ethicon Endo-Surgery) were used for dissection. The thymic cyst was successfully removed through the incision without thoracotomy. The advantage of this technique is that it is less invasive than video-assisted thoracic surgery through the thorax, removing the need for a thoracotomy.

Background: The normal, mature airway epithelium in experimental animals has a very slow cell turnover and minimal proliferation. The aim of this study was to investigate the expression of proliferating cell nuclear antigen (PCNA) as an index of bronchial cell proliferation in the Brown Norway to Lewis rat pulmonary allograft model with or without immunosuppression., Methods: Brown Norway left lungs were transplanted into Lewis recipients. Some recipients were treated with a high dose of cyclosporine and FK506. Lewis-to-Lewis donor-recipient combination was performed as a control. Lungs were excised on postoperative days 3 and 5. Routinely processed, paraffin-embedded sections were prepared and stained by PCNA. Counts of PCNA-positive cells in the perivascular cellular infiltrate and bronchial surface epithelium were compared with the histologic grade of rejection., Results: The PCNA index (percent of nuclei immunostaining for PCNA) in bronchial surface epithelium was significantly higher in allografts (21.0% +/- 3.1% at 3 days, 31.4% +/- 9.8 % at 5 days, p < 0.05) than in isografts (5.4% +/- 3.0% at 3 days, 4.7% +/- 4.6% at 5 days). The PCNA index was also greater in the perivascular infiltrates of rejecting lungs (23.9% +/- 3.7% at 3 days, 29.1% +/- 6.6% at 5 days). However, in the cyclosporine- and FK506-treated groups, the PCNA index in bronchial surface epithelium was suppressed to less than 5% at 3 and 5 days. Even at 50 days after transplantation, PCNA-positive cells were rare in bronchial epithelium of FK506-treated grafts., Conclusions: Bronchial epithelium in isografts has a relatively low rate of proliferation. In rejection, allografts have a very rapid cell turnover and proliferation. Proliferating epithelium may be a consequence of immune events or it may contribute to the pathogenesis of those events.

The expression of blood group antigens A, B, and H, as well as sialylated and nonsialylated forms of Lewis(a) and Lewis(x), was studied using immunohistochemical methods in normal and tumor tissues in the following cohort of patients: 51 patients with primary breast carcinoma, 13 with metastatic lymph node lesions, and 16 with benign tumors of the breast. As a control, normal tissue was obtained from a similar group of 22 patients with breast cancer. The noncancerous tissues expressed the same A/B/H antigens as the patients' red blood cells and also usually expressed Lewis-related antigens. Seventy-six percent of primary carcinomas failed to express the appropriate A/B/H antigens, and in one blood group A patient the tumor tissue expressed B antigen. In the metastatic lesions, Lewis(a)/sialyl Lewis(a) expression was reduced when compared with the primary tumors, but Lewis(x)/sialyl Lewis(x) antigens were still expressed. These results suggest a possible relationship between the metastatic behavior of the tumor and expression of the blood group antigens.

The deletion of chromosome 11q is observed frequently in tumors of the large intestine. To investigate the relationship between aberrations of chromosome 11 and histopathological features of colorectal carcinoma, we examined the frequency of chromosome aberrations using fluorescence in situ hybridization to 29 short-term cultured cells from surgical specimens. Numerical aberrations were not related to any factors. The deletion of chromosome 11 was frequently observed in larger (> or = 5 cm) and more invasive tumors (> or = T3 category) (p < 0.05). Furthermore, the incidence of aberrations tended to increase in Dukes' B. Although translocation of chromosome 11 was also found in 17% of cases, it was not associated with histopathological features. Our findings indicate that the deletion of chromosome 11 is closely related to the progression of colorectal carcinoma.

One hundred twelve patients (102 male and 10 female) underwent sleeve lobectomy for lung cancer from January 1969 to December 1991. Bronchopleural fistula occurred in 6 (5.6%), bronchovascular fistula in 2 (1.8%), pulmonary arterial occlusion in 2 (1.9%), anastomotic stricture or stenosis in 7 (6.3%), and local recurrence in 7 patients (6.3%). Early repair of bronchopleural fistula combined with an omentopexy achieved permanent closure of the fistula. Two patients who underwent a completion pneumonectomy for a pulmonary arterial occlusion died of respiratory failure. Two patients experienced uncontrollable bleeding into the bronchial tree through a bronchovascular fistula and sudden death. Completion pneumonectomy is indicated for a stricture due to scar formation. If pneumonectomy is precluded by poor pulmonary reserve, endoscopic excision using biopsy forceps is an alternative. Endoscopic resection is the treatment of choice for suture granulomas. Complications associated with bronchial or vascular anastomoses are serious and frequently fatal.