Functional evaluation of pallid mice with genetic emphysema.

Studies on pallid mice models of genetic emphysema have conventionally focused on morphological or biochemical evaluations. However, it is important to consider the functional aspects. We evaluated the exercise capacity and respiratory function in male pallid mice and male C57BL/6J mice at 3, 6, 12, and 15 months of age. The functional evaluations were conducted using a treadmill and a pulmonary function analysis device. The morphology of the lungs was analyzed on the basis of mean linear intercept (Lm) values. The body weights of the pallid mice at 12 and 15 months were significantly lower than those of the age-matched C57BL/6J mice. The pallid mice showed deterioration in exercise capacity from 6 months, as indicated by the trends in running distance. At 6, 12, and 15 months, the pallid mice showed significantly higher pulmonary compliance and significantly lower forced expiratory volume in 20 ms (FEV(20 ms))/vital capacity (VC) values in comparison with the corresponding values for the C57BL/6J mice. In the morphological analysis of the pallid mice, emphysema was detected from 12 months, and the mice showed a significantly larger Lm at 12 months. The exercise capacity and lung function in the pallid mice significantly deteriorated from 6 months, at which time no pathological changes in the lung were detected. The deterioration in the exercise capacity and pulmonary function preceded the microscopic morphological changes.

Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase expression in tumor tissue, regarding the efficacy of postoperatively administered UFT (tegafur+uracil) in patients with non-small cell lung cancer.

BACKGROUND: UFT (tegafur + uracil) has been reported to be effective as an adjuvant in postoperative chemotherapy for non-small cell lung cancer (NSCLC) in a randomized prospective study. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were investigated in resected tumors and the relationship between their expression and clinical factors in NSCLC patients was examined. PATIENTS AND METHODS: Fifty-four NSCLC patients had undergone complete surgical resection and lymph node dissection, and had been administered UFT post-surgery. The TS and DPD expression in the tumor tissues was evaluated by immunohistochemical staining. The relationship between TS and/or DPD expression and clinicopathological factors was examined. RESULTS: There were 38 TS-negative and 16 TS-positive cases, and 22 DPD-negative and 32 DPD-positive cases. There was no significant difference between the patients with TS or DPD and those without TS or DPD in age, gender, histological type or p-stage. The 5-year survival rates of patients positive and negative for TS were 50.0 and 89.5%, while 10-year survival rates were 23.3 and 79.7%, respectively (p<0.001). The 5-year survival rates of TS-positive and TS-negative patients in p-stage I were 54.6 and 95.5%, while 10-year survival rates were 22.7 and 95.5%, respectively (p<0.001). There was no significant difference between DPD-positive and DPD-negative patients in prognosis. CONCLUSION: The oral administration of UFT after surgery might improve the survival of NSCLC patients when TS levels in tumor tissues are low. Immunohistochemical evaluation of TS and DPD expression may be useful for predicting the efficacy of UFT after complete resection in NSCLC.

Chromosomal aneusomy (chr 1, 11, 17) detected by fluorescence in situ hybridization may be a prognostic factor in breast cancer.

The relationship between clinicopathological findings and the long-term prognosis was investigated in 42 breast cancer patients in whom aneusomy was detected for chromosomes 1, 11 and 17. The frequencies of aneusomy of those chromosomes were 78.6%, 47.5% and 52.5%, respectively, and more than 90% of anomalies consisted of polysomy. The relationship between aneusomy and the clinicopathological findings showed a statistical correlation with a high histological grade in the case of polysomy of chromosome 17 compared with disomy, indicating a tendency for a high incidence of lymph node metastasis. Analysis of the survival data revealed that the prognosis was poor when there was polysomy of chromosomes 1 or 11. These results indicate the possibility that aneusomy of chromosomes 1, 11 and 17 can serve as prognostic factors of poor outcome in breast cancer patients.

Lung regeneration: implantation of fetal rat lung fragments into adult rat lung parenchyma.

OBJECTIVE: The capability of regeneration of lung tissues in adults is limited after chronic destruction. Bone marrow-derived stem cells, retinoic acid, growth factors, and other approaches have been attempted to promote or facilitate this process. We hypothesized that fetal lung tissues, with great potential for growth and differentiation, could be used for lung regeneration. METHODS: Day 17 fetal lung tissue fragments at the pseudoglandular stage of lung development from Lewis rats were implanted into adult Lewis rat lungs. For group 1, fetal lung fragments were injected into the adult left lung parenchyma; for group 2, fetal fragments were injected with the left lung partially resected; for group 3, adult fragments were injected; and for groups 4 and 5, fetal fragments were implanted into the omentum and subcutaneous tissue, respectively. RESULTS: The grafts implanted into pulmonary parenchyma were differentiated with opening of the alveolar space after 4 weeks and were advanced further with morphologic features similar to those of neonatal lungs after 8 and 12 weeks. The implants were connected with pulmonary circulation determined by means of perfusion with India ink. These changes appeared to be further enhanced in animals with partial lung resection that might have facilitated the maturation of implanted fetal lung tissues through mechanical factors, soluble factors, or both. Fetal lung tissues did not mature when implanted into the omentum or subcutaneous tissue. Adult lung fragments did not expand after being reimplanted back into the same animal. CONCLUSIONS: Fetal lung tissue might be an option for further investigation into lung regeneration.

Lower axillary dissection in breast cancer surgery may be candidate for cases with early breast cancer.

Lower axillary lymph node dissection (lower parts of both the level I and II elements below the second intracostobrachial nerve) and level I and II lymph node dissection were performed on breast cancer patients (n = 54), and the results with the two methods were compared in terms of the status of detected lymph node metastases. For Stage I, N0 cases, the results for pathological classification lymph node metastases (pN) were in agreement between the two dissection methods. And, the occurrence of operated arm swelling wasn't recognized when a side effect was examined with the case (n = 28) that only lower axillary dissection was carried out in case of an operation for breast cancer. Accordingly, it was surmised that lower axillary dissection provides accurate pN information for Stage I, N0 cases. These results indicate that lower axillary dissection has the potential to become an effective, standard surgical procedure for breast cancer patients whose preoperative disease stage is Stage I.

Progressive increase of CD4(+)/CD45RC(-) lymphocytes after allograft rat lung transplantation: a marker of acute rejection.

BACKGROUND: Acute rejection remains one the most serious problems in lung transplantation. Although biopsy has been used for assessing the dysfunction of grafts, it is difficult to determine rejection at an early stage. Lymphocyte infiltration and activation play an important role in acute rejection of transplanted organs, and the dynamic change of lymphocyte subpopulations might be a marker to determine graft rejection after lung transplantation. METHODS: A rat lung transplant model was used. Graft-infiltrating lymphocytes in lung tissues were examined by means of histology, and isolated cells were analyzed by means of flow cytometry. Phenotypes of lymphocytes in the regional and remote lymph nodes, spleen, peripheral blood, and bronchoalveolar lavage fluid were also measured by means of flow cytometry. RESULTS: After allograft transplantation, increased lymphocytes were seen in allografts but not in isografts. In allografts the percentage of T cells increased from day 1 to day 5, whereas that of B cells was decreased. The CD4(+)/CD8(+) ratio decreased in allografts. The proportion of CD4(+)/CD45RC(-) cells increased in the allografts, which was mainly due to the increase of CD45RC(-) cells in the total CD4(+) cells. Similar changes were found in regional mediastinal lymph nodes but not in the mesenteric lymph nodes, spleen, or peripheral blood. Thus this is a specific response to lung allografts. Importantly, CD45RC(-) cells were significantly increased in the bronchoalveolar lavage fluid. CONCLUSION: Significant change of lymphocyte subpopulations is a sign of lymphocyte activation. Increased CD4(+)/CD45RC(-) cells in lung allografts could be an early marker of acute rejection, which can be examined by means of lung lavage and flow cytometry.