Developmental failure of the intra-articular ligaments in mice with absence of growth differentiation factor 5.

OBJECTIVE: To show the phenotypic characteristics of the knee joints in brachypodism mice (bp mice), which carry a functional null mutation of the growth differentiation factor 5 (GDF5) gene, we investigated the adult and embryonic bp mice. METHOD: Radiographic and macroscopic examinations of the knee joint of adult bp mice were performed. A histological examination of the knee joint of bp mice from E12.5 to E18.5 was also performed. RESULTS: Radiographic and macroscopic examinations of the adult bp mice showed anterior dislocation, hypoplastic condyles, and absence of the intra-articular ligaments. Safranin O staining of knee joints of the embryonic bp mice showed severe hypoplasty of the chondroepiphyses and intra-articular ligaments at E16.5. There was no difference in the number and location of 5-bromo-2'-deoxyuridine (BrdU)-positive cells between wild-type and bp mice through E12.5 to E14.5. A terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) study showed excessive cell death of mesenchymal cells of the future knee joint in bp mice at E12.5 and E13.5. CONCLUSION: bp mice exhibit developmental failure of the condyles and intra-articular ligament of the knee joints.

Identification of differentially expressed genes in psoriasis using expression profiling approaches.

To identify differentially expressed genes which play causal roles in pathogenesis and maintenance for psoriasis, we used BodyMapping and introduced amplified fragment length polymorphism approaches. From the BodyMap database, we selected 2007 genes which specifically expressed in epithelial tissues. Among 2007 genes, we surveyed genes which differentially expressed in involved or uninvolved psoriatic lesional skin samples compared with atopic dermatitis, mycosis fungoides, and normal skin samples. As a result of surveying 2007 genes, 241 genes were differentially expressed only in involved psoriatic skin but not in the other samples. Hierarchical cluster analysis of gene expression profiles showed that 13 independent psoriatic-involved skin samples clustered tightly together, reflecting highly similar expression profiles. Using the same 2007 gene set, we examined gene expression levels in five serial lesions from distal uninvolved psoriatic skin to involved psoriatic plaque. We identified seven genes such as alpha-1-microglobulin/bikunin precursor, calnexin, claudin 1, leucine zipper down-regulated in cancer 1, tyrosinase-related protein 1, Yes-associated protein 1, and unc-13-like protein (Coleonyx elegans) which show high-expression levels only in uninvolved psoriatic lesions. These seven genes, which were reported to be related to apoptosis or antiproliferation, might have causal roles in pathophysiology in psoriasis.

Bronchopleural fistula after lung cancer surgery. Multivariate analysis of risk factors.

BACKGROUND: To elucidate retrospectively the risk factors for bronchopleural fistulae after lung cancer surgery. METHODS: The subjects were 1,177 patients with lung cancer who underwent surgery between 1983 and 1997. Twenty-two clinical factors were examined by logistic analysis. RESULTS: Bronchopleural fistulae were observed in 35 patients (32 males, 3 females) with a mean age of 64 years. Eighteen (51%) of 35 patients died of BPF-related complications. The significant risk factors obtained by univariate analysis were male gender, heavy smoking, current smoking, low level of %FVC, metastases to lymph nodes, squamous cell carcinoma, increased WBC, decreased albumin, advanced postsurgical stage, sleeve lobectomy, and resection of the right lower lobe or middle and lower lobe. The significant risk factors noted by multivariate analysis were heavy smoking (30 or more pack/years), current rather than past smoking, metastases to lymph nodes, decreased albumin (3.5 mg/dl or less), and resection of the right lower lobe or middle and lower lobe. CONCLUSIONS: The above risk factors must be taken into account before surgical techniques followed by adequate perioperative management are selected.

B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells.

Dendritic cells (DCs), unique antigen-presenting cells (APCs) with potent T cell stimulatory capacity, direct the activation and differentiation of T cells by providing costimulatory signals. As such, they are critical regulators of both natural and vaccine-induced immune responses. A new B7 family member, B7-DC, whose expression is highly restricted to DCs, was identified among a library of genes differentially expressed between DCs and activated macrophages. B7-DC fails to bind the B7.1/2 receptors CD28 and cytotoxic T lymphocyte-associated antigen (CTLA)-4, but does bind PD-1, a receptor for B7-H1/PD-L1. B7-DC costimulates T cell proliferation more efficiently than B7.1 and induces a distinct pattern of lymphokine secretion. In particular, B7-DC strongly costimulates interferon gamma but not interleukin (IL)-4 or IL-10 production from isolated naive T cells. These properties of B7-DC may account for some of the unique activity of DCs, such as their ability to initiate potent T helper cell type 1 responses.

Fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

BACKGROUND: A new strategy in the treatment of squamous cell carcinoma of the tracheobronchial tree is the detection and eradication of preinvasive bronchial lesions before they become invasive cancers. It is, however, difficult to detect preinvasive lesions by conventional white-light bronchoscopy alone. PURPOSE: we conducted a detailed investigation on the use of fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. METHODS: 64 participants with sputum cytology suspicious or positive for malignancy were examined with both white light and fluorescence bronchoscopy (LIFE group). Earlier to this study, before fluorescence bronchoscopy became available in our institute, 48 participants having sputum cytology suspicious or positive for malignancy were examined with white light bronchoscopy alone (control group). Biopsy specimens for pathological examinations were taken of all abnormal areas discovered by white light or fluorescence bronchoscopy examination. RESULTS: In sputum cytology suspicious or positive for malignancy, the diagnosis of preinvasive bronchial lesions was greatly enhanced in the LIFE group as compared with the control group (45 vs. 7 lesions). The percentage of participants with preinvasive bronchial lesions was also significantly higher in the LIFE group than in the control group (40.6 vs. 12.5%, P = 0.00087, respectively). CONCLUSIONS: Our study suggests that the use of fluorescence bronchoscopy in addition to conventional white-light examination could greatly enhance the detection and localization of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

Long-term survival achieved by resection of metastases in the liver and lung in a patient with recurrent colonic cancer: report of a case.

A 58-year-old man who underwent a potentially curative resection of cancer of the sigmoid colon at another hospital was subsequently followed up at our hospital. A lateral segmentectomy was performed for a solitary hepatic metastasis, and partial resection of right S1 was later carried out for a pulmonary metastasis. Another pulmonary metastasis was found 6 years after his third operation and to minimize the area to be resected, bronchial arterial infusion chemotherapy was performed twice. A 51% reduction in the size of the tumor was achieved, so a right upper lobectomy and wedge resection of the bronchus were performed. The patient remains alive 14 years after the initial resection of colonic cancer. This case is considered noteworthy because it demonstrates the potential effectiveness of local adjuvant chemotherapy and the possibility of extended survival in a patient who has undergone resection of both hepatic and pulmonary metastases from colonic cancer.

Ki-67 immunostaining and other prognostic factors including tobacco smoking in patients with resected nonsmall cell lung carcinoma.

BACKGROUND: To estimate the effectiveness of expression of the tumor proliferative marker Ki-67 antigen (Ki-67) as a postoperative prognostic marker, the authors analyzed Ki-67 expression and its correlation with postoperative survival and other clinicopathologic factors, including preoperative smoking habits, in patients with resected nonsmall cell lung carcinoma (NSCLC). METHODS: A total of 156 patients with resected NSCLC at the study institution were investigated. Postoperative survival rates were estimated based on demographic and clinicopathologic factors, including Ki-67 expression and preoperative tobacco smoking habits. RESULTS: The overall postoperative 5-year survival rate in patients with high Ki-67 labeling indices (>/= 20%) was 39.6% compared with 67.7% in patients with low Ki-67 labeling indices. This finding was significant for all resected cases and for each pathologic disease stage (P < 0.05). The postoperative 5-year survival rate in patients with a history of heavy smoking (>/= 30 pack-years) was 47.6% compared with 62.5% for other patients (P = 0.027). This result was especially significant in patients with International Union Against Cancer Stage I disease and in patients with nonsquamous cell carcinoma (P < 0.03). The authors also observed a positive correlation between the Ki-67 labeling index and preoperative smoking habits (P = 0.0002). Multivariate analysis demonstrated that lymph node involvement, tumor differentiation, and Ki-67 labeling index were significant prognostic factors in NSCLC (P < 0.01). CONCLUSIONS: Tumor Ki-67 expression is a strong prognostic factor in NSCLC, especially adenocarcinoma. It may be hypothesized that tobacco mutagenicity may play a role in the growth and extension of NSCLC, which is one of the major impediments to postoperative survival in patients with a history of heavy smoking.

[General anesthesia for a patient on hemodialysis with arteriosclerosis obliterans].

A 48-year-old man with arteriosclerosis obliterans was scheduled for axillofemoral bypass. He had chronic renal failure and on hemodialysis (HD) for 22 years. On the morning of the day of surgery he received HD and two hours later anesthesia was induced with fentanyl 300 micrograms and midazolam 6 mg, and maintained with fentanyl, nitrous oxide and intermittent isoflurane. The common carotid artery was cannulated to measure arterial blood pressure because arteries in extremities were not available. Internal jugular vein at the other side of the arterial catheterization was cannulated to measure central venous pressure. Crystalloid and blood transfusion was performed to adjust hemodynamics and central venous pressure. Hemodynamics were stable during surgery and no complication occurred regarding the common carotid arterial line. The common carotid artery was useful for blood pressure monitoring in a patient whose extremities were not available. Midazolam and fentanyl could give stable hemodynamics to a patient with arteriosclerosis obliterans and chronic renal failure.

[Pulmonary hyalinizing granuloma diagnosed by thoracoscopy].

A 36-year-old woman was examined by our hospital for pulmonary coin shadows in both lungs, as disclosed on chest X-ray films. She had no subjective complaints other than allergic rhinitis, but exhibited hypergam-maglobulinemia, particularly in IgE. Inhalative allergen tests were positive for three types of allergens, but no autoimmune disease was detected. Although transbronchial and percutaneous fine needle biopsies failed to obtain enough specimens because of the wandering shadow a thoracoscopic biopsy was effective because of the subpleural location of the target lesions. The histologic findings were consistent with pulmonary hyalinizing granuloma, with extensive, hyalinized lamellar collagen bundles arranged haphazardly in the central area. Infiltration by lymphocytes and plasma cells, together with the destruction of bronchiolar and vessel walls, were observed in the marginal areas. No amyloid deposits or lymphocytic monoclonality were observed in the lesion. Twenty-five months after the biopsy, the patient's clinical and radiographic data had not changed.

[Anesthetic management of a patient with Saber-sheath trachea].

A 65-year-old man was scheduled for total gastrectomy. Preoperative chest radiograph showed significant narrowing of the trachea. On chest CT scan the trachea was U-shaped (tracheal index = 36%) and was diagnosed as saber-sheath trachea. During general anesthesia we took care to reduce the irritation by the endotracheal tube, particularly during intubation, and to avoid excessively high airway pressure. The trachea was watched carefully by bronchoscopy after intubation and during extubation not to neglect any complication. There was no complication after the operation.

[Detection of early hilar lung cancers with fluorescence bronchoscopy].

The development of fluorescence bronchoscopy has made it possible to diagnose locally superficial hilar lung cancers such as carcinoma in situ, and in some cases atypical squamous metaplasia thought to be precancerous lesions. The selection of a treatment modality can be difficult for early hilar lung cancers due to problems associated with multiple lung carcinomas and the large number of heavy smokers afflicted. Many patients also have decreased pulmonary function. If carcinoma in situ and microinvasive carcinomas can be detected early, it may be possible to treat them radically with a less invasive method than surgery, such as endoscopic laser therapy. Centrally arising squamous cell carcinoma of the tracheobronchial tree, especially in heavy smokers, is thought to develop in multiple stages from squamous metaplasia, to atypical squamous metaplasia, followed by carcinoma in situ, and finally invasive cancer. However, it is hoped that preventive medicine for lung cancer will be established whereby patients with localized atypical squamous metaplasia detected by fluorescence bronchoscopy can be carefully monitored and motivated to stop smoking, and also administered chemopreventive agents.

Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 zeta chain of T-cell receptor complex and antigen-specific T-cell responses.

One of the important mechanisms of immunosuppression in the tumor-bearing status has been attributed to the down-modulation of the CD3 zeta chain and its associated signaling molecules in T cells. Thus, the mechanism of the disappearance of CD3 zeta was investigated in tumor-bearing mice (TBM). The decrease of CD3 zeta was observed both in the cell lysate and intact cells. Direct interaction of T cells with macrophages from TBM (TBM-macrophages) induced the decrease of CD3 zeta, and depletion of macrophages rapidly restored the CD3 zeta expression. We found that treatment of such macrophages with N-acetylcysteine, known as antioxidant compound, prevented the decrease of CD3 zeta. Consistent with this result, the addition of oxidative reagents such as hydrogen peroxide and diamide induced the decrease of CD3 zeta expression in T cells. Consequently, the loss of CD3 zeta resulted in suppression of the antigen-specific T-cell response. These results demonstrate that oxidative stress by macrophages in tumor-bearing status induces abnormality of the T-cell receptor complex by cell interactions with T cells. Therefore, our findings suggest that oxidative stress contributes to the regulation of the expression and function of the T-cell receptor complex.