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Biomedical subjects

T Uyama

Publications and source records attributed to T Uyama.

At least 37 records · Page 2Linked to original sources

Finding of the same antigens in the polychaete, Pseudopotamilla occelata, as those in the vanadium-rich ascidian, Ascidia sydneiensis samea.

The polychaete Pseudopotamilla occelata is the first animal revealed to contain high levels of vanadium besides ascidians. The present experiment disclosed that P. occelata has the same antigens with those in the ascidian Ascidia syndneiensis samea, which were recognized by two types of antibodies, a polyclonal antibody against vanadium-associated proteins extracted from blood cells and a monoclonal antibody against vanadocytes in the vanadium-rich ascidian A. sydneiensis samea. There is, therefore, a possibility that similar mechanism works on the accumulation of vanadium between the Polychaeta and the Ascididae.

Animals↗

The expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer.

Recently, it was suggested that splice variants of the surface glycoprotein CD44 (CD44v) were associated with tumor metastasis in some cancers. We examined the expression of variant forms of CD44 in 31 non-small cell lung carcinomas (NSCLCs) and in 8 normal lung tissue samples by reverse transcription-PCR (RT-PCR). CD44v3, CD44v5, CD44v6, and CD44v7 were not expressed or were weakly expressed in normal lung tissue (0 of 8). In contrast, CD44v3, CD44v5, CD44v6, or CD44v7 was expressed in 28 of 31 (90.3%) NSCLCs. Additionally, we examined the expression of CD44v6, which has been shown to be related to metastasis, in 5 normal lungs and 30 NSCLCs by RT-PCR and immunohistochemical analysis to clarify which cells express CD44v6 in NSCLC specimens. Thirty-six of 61 (59%) NSCLCs variably expressed CD44v6 by RT-PCR, and cancer cells were selectively immunostained by anti-CD44v6 antibodies in 23 of 30 (76.7%) NSCLCs. The results of immunohistochemical analysis almost correlated with those of RT-PCR. NSCLCs with lymph node metastasis expressed significantly more v6 exon than did those without lymph node metastasis [23 of 29 (79.3%) versus 13 of 32 (40.6%); P < 0.01]. There was a significant association between the intensity of v6 expression by RT-PCR and the frequency of cases showing lymph node metastasis (Cochran-Armitage's test, P < 0.002). In conclusion, this study demonstrated that in NSCLC, a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC.

Adult↗

A dose-response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients.

Mutations of the p53 tumor suppressor gene are frequent in lung cancers. It is suggested that p53 mutations are associated with smoking-induced lung carcinogenesis. We examined p53 mutations in 53 lung cancers by analyzing reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) to ascertain the association between p53 mutations and smoking. Twenty-five (47%) of 53 lung cancers carried p53 mutations. A discriminant analysis showed that the Brinkman index (0.156) and gender (0.140) significantly influenced p53 mutations. Furthermore, there was a dose-response relationship between the quantity of cigarettes consumed and the frequency of p53 mutations in lung cancer patients (P < 0.001). In patients with adenocarcinoma, the frequency of p53 mutations correlated with the amount of the tobacco smoked (P < 0.05). We suggest that the p53 gene is a target of particular carcinogen in tobacco smoke.

Adenocarcinoma↗

Difference in cytokine production in acute and chronic rejection of rat lung allografts.

In Brown Norway to Lewis rat lung transplantation, short-term administration of cyclosporine produces permanent adoption of allografts; however, the adopted grafts show symptoms of chronic rejection. To clarify the difference in cytokine production in acute an chronic rejection of the allografts, an immunohistochemical study was performed. In acute rejection, positive cells for respective cytokines were observed in infiltrating cells, increasing in number as the days after transplantation passed, and reaching a maximum on the fifth day. The strongest reactivity was observed perivenously. In chronic rejection, TNF-alpha positive cells were observed in the perivascular and peribronchial regions, especially around class II positive epithelia. The number of positive cells was, however, less than that in the vascular phase of acute rejection. Few cells were positive for IL-1 beta, IFN-gamma and, unexpectedly, for IL-4. These facts indicate the functional difference of infiltrating cells between acute and chronic rejection.

Animals↗

Myasthenia gravis induces the activation and maturation of lymphocytes in thymoma.

The biological differences between lymphocytes separated from thymoma patients with myasthenia gravis (MG) and those separated from thymoma patients without MG was examined. We investigated whether lymphocytes in thymoma (Th-L) of patients with and without MG could react to interleukin-2 (IL-2) to develop cytolytic activity against K562 and lympho kine-activated killer (LAK) activity, and their phenotypic changes during incubation with IL-2. Sixteen thymoma patients who consisted of eight patients with MG and eight patients without MG were investigated. Th-L of all MG patients could react to IL-2 to develop LAK activity. Th-L of all of MG patients also developed cytolytic activity against K562 target cells. Cytolytic activity against K562 and LAK activity from Th-L of the MG patients were significantly higher than those from Th-L of the patients without MG (P < 0.01, P < 0.01). The proportions of CD3+ and CD4-/CD8+ cells of Th-L of MG patients increased significantly during the incubation period with IL-2 (P < 0.05, P < 0.05). The proportion of CD4+/CD8+ cells of Th-L of patients with MG decreased significantly (P < 0.05) during incubation with IL-2. On the other hand, there was no significant phenotypic change in Th-L of the patients without MG. These results indicate that MG induces the functional and phenotypic activation and functional and phenotypic maturation of Th-L.

Adult↗

A Malignant Phyllodes Tumor of the Breast in a 6-Year Old Girl.

We recently encountered a 6-year-old girl with a malignant phyllodes tumor of the breast. The patient's mother noticed a tumor on the right breast of her first doughter at 8 months after from her birth. The baby was brought to the Second Depertment of Surgery, University of Tokushima, at age 20 months. We recommended removal of the 3.5 x 2.9 cm tumor in the right breast, but it was not done. Next, she visited our department at 6 years of age because the tumor had gradually enlarged, reaching a size of 4.3 &timus; 4.0 cm. She underwent excisional resection of the tumor, and the tumor was diagnosed as a malignant phyllodes tumor of the breast coexisting with a borderline phyllodes tumor. To our knowledge, this is the youngest reported case of a malignant phyllodes tumor of the breast. Moreover, the malignant lesion was positive for estrogen receptor (ER) and showed strong proliferating cell nuclear antigen (PCNA) staining. On the other hand, the borderline part was negative for ER and showed weak PCNA staining. Thus, in the present case, the expression of ER, the exposure to estrogen (for example, the mother's estrogen during gestation) and increase in the proliferation rate may have played important roles in the mechanism of the transformation of the phyllodes tumor.

Journal Article↗

Difference in thymidylate synthetase activity in involved nodes compared with primary tumor in breast cancer patients.

Thymidylate synthetase (TS) is a key enzyme as a methyl donor in the methylation reaction from dUMP to dTMP. TS activity was assessed in various tissue of mammary disorders. The descending order of TS activity was as follows: cancer-positive nodes, primary cancers, cancer-negative nodes, benign lesions, and normal parenchyma. Significant differences in TS activity were found between the positive nodes and each of the other tissues (p < 0.01). In node-positive cases, a significant correlation in TS activity was found between the primary cancers and positive nodes (r = 0.616, p = 0.033). There was no correlation between the nodal status and the TS activity in primary cancers. In 11 of 12 cases, the TS activity of positive nodes was higher than the 'calculated' TS activity of the primary cancer, which was defined as the TS activity per unit weight of cancer cells. A significant correlation was found between the calculated TS activity and the mitotic frequency in primary cancers (r = 0.697, p = 0.0001). On the other hand, a significant correlation could not be found between the TS activity and the mitotic frequency in positive nodes (r = 0.364, p = 0.244).

Breast↗

Granulocyte-macrophage colony-stimulating factor augments lymphokine-activated killer activity from pleural cavity mononuclear cells of lung cancer patients without malignant effusion.

The role of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in augmentation of lymphokine-activated killer (LAK) cell induction by interleukin-2 (IL-2) from pleural cavity mononuclear cells (PCMNCs) was examined in sixteen patients with resectable primary lung cancer not associated with malignant effusion. None of the patients had received any anticancer therapy prior to this study. Incubation of PCMNCs of patients without malignant effusion with GM-CSF for 4 days in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer-resistant Daudi cells. This result was obtained by using the 4 h 51Cr-release assay. PCMNCs and blood mononuclear cells (BMNCs) were harvested simultaneously from pleural cavity lavage fluid and peripheral blood in lung cancer patients. The LAK activity developed from PCMNCs and BMNCs following incubation with IL-2 for 4 days, but the LAK activity from PCMNCs was significantly lower than that from BMNCs (P < 0.05). Incubation of PCMNCs with GM-CSF augmented the LAK activity from PCMNCs to a level as high as that from BMNCs. These results suggest that the combined use of GM-CSF with IL-2 may result in augmentation of LAK activity developed from PCMNCs of lung cancer patients without malignant effusion.

Aged↗

Defective bronchus-associated lymphoid tissue in long-term surviving rat lung allografts.

In a previous study we found that a local immune response did not develop in the bronchus-associated lymphoid tissue (BALT) of infected rat allografts. We hypothesized that the BALT in rat lung allografts was damaged after allotransplantation. Therefore, we investigated three prerequisites for a normal function of the BALT, i.e., its structure, the uptake of antigens, and the lymphocyte migration to the BALT in three groups of rats (n = 10 each): (1) Brown Norway(BN)-to-Lewis (LEW) allografts; (2) LEW-to-LEW isografts; and (3) normal LEW rats. All rats were immunosuppressed with CsA (injected on days 2 and 3). Six mo after transplantation the structure of the BALT and the uptake of intrabronchially injected carbon particles in the BALT were determined histologically; the migration of intravenously injected, fluoroscein-isothiocyanate labeled lymphocytes to the BALT was determined immunohistochemically. In the allografts the BALT was defective in all three investigated aspects. It was reduced in size and lymphocyte density and was largely replaced by fibrous tissue. Twenty-four h after administration no carbon particles and only a few labeled lymphocytes were found in the BALT. In contrast, in the syngeneically transplanted and nontransplanted lungs the BALT consisted of a large and dense collection of lymphocytes. In these BALTs large numbers of carbon particles and labeled lymphocytes were found. In conclusion, after allogeneic transplantation the BALT in the lung becomes defective in structure and function. The BALT is most likely damaged by rejection, since the BALT is syngeneic lung transplants was perfectly normal.

Animals↗

Immunological detection of a vacuolar-type H(+)-ATPase in vanadocytes of the ascidian Ascidia sydneiensis samea.

Ascidians belonging to the family Ascidiidae are known to accumulate vanadium from seawater in their blood cells, concentrating vanadium by a factor of 10(7). Among several different types of blood cell, the signet ring cells have both high levels of vanadium and a low pH. These observations suggest the possibility that proton ions concentrated by a H(+)-ATPase are energetically linked to the accumulation of vanadium. In the present experiments, therefore, we made an immunological search for a H(+)-ATPase in the vacuolar membranes of the signet ring cells, as a first step in our attempts to clarify the energetics of the accumulation of vanadium by these cells. Antibodies raised against the 72-kDa and 57-kDa subunits of a vacuolar-type H(+)-ATPase from bovine chromaffin granules reacted with the vacuolar membranes of signet ring cells. Immunoblotting analysis confirmed that specific antigens in ascidian blood cells actually reacted with the antibodies. Furthermore, addition of bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibited the uptake of protons by the vacuoles of signet ring cells. Thus, the addition of bafilomycin A1 inhibited the pumping function of the vacuoles of signet ring cells, with resultant neutralization of the contents of the vacuoles.

Animals↗

Significant Correlation between the Presence of Type W Collagen in the Duct Wall and the Development of Wide Intraductal Cancerous Extension in Breast Cancer.

To identify the characteristics of cases with an wide intraductal cancerous extension (WICE), we examined the relationship between WICE and type IV collagen distribution, and the relationship between WICE and the content of the proliferation-associated proteins in human breast cancer. The immunohistochemical distribution of type IV collagen and proliferating cell nuclear antigen (PCNA) were investigated in formalin-fixed tissue sections from 21 breast cancer cases. We demonstrated a significant correlation (p=0.014) between the presence of WICE and immunostaining of type IV collagen in the cancerous ducts (ducts occupied by cancer cells) in the central invasive area of breast cancer. However, no correlation was found between the presence of WICE and the PCNA index (percentage of positive cells per 1000 tumor cells). These findings suggest that the lack of the process of the loss of type IV collagen in the duct wall is more important than the nature of the tumor cells in the development of WICE.

Journal Article↗

Pleural-changes in the lung allograft during acute rejection.

To ascertain the cause of pleural fibrosis in lung allografts, pleural changes were investigated in rat syngeneic and allogeneic lung grafts. The pleura of lung syngeneic grafts showed no pathological changes except for mild edema on the first day after transplantation. In lung allografts, recipient cells migrated into the subpleural tissue early after transplantation (latent phase). In the vascuar phase, recipient lymphocytes in the subpleural tissue increased in number, while almost all alveolar structures were free from infiltration. Both CD4-positive and CD8-positive cells infiltrated in almost equal numbers with macrophages. The subsets of infiltrating cells were similar to those of the perivascular and peribronchial areas. In the late vascular or alveolar phase, fibroblasts were observed among the infiltrating cells, and fibrotic changes started. In the destructive phase, collagen formation with marked pleural thickening was dominant. Pulmonary acute rejection should be treated at least up to the late vascular phase to prevent pleural fibrosis.

Acute Disease↗

Pathogenesis of late airway changes in long-term surviving lung allografts.

Late airway changes are frequently observed in long-term surviving rat lung allografts. In this present study, we investigate this problem using the mixed lymphocyte reaction, graft-versus-host assay (popliteal lymph node assay), skin grafting from the donor strain to the lung allograft recipient, and histology to evaluate this problem. The results show that spleen cells from recipient rats with long-term surviving lung allografts possessed alloreactivity in mixed lymphocyte reaction against both donor and third-party ACI antigens. Suppressor cell activity was not detected in spleen cells from these recipient rats. The popliteal lymph node assay showed that the response to recipient spleen cells was detectable but weaker than that of naive spleen cells from the same strain. Mean survival time of skin grafts from the donor strain to long-term allograft survivors was significantly longer than that between donor and recipient strains. Chest roentgenograms revealed opacification of long-term surviving lung allografts at 2 to 3 wk after skin transplantation that was coincident with the rejection of the skin grafts, and histologic examination of the lung allografts revealed changes compatible with acute rejection. We conclude that alloreactivity can be demonstrated in rats with long-term surviving lung allografts and suggest that late airway changes in these lungs are immunologically mediated.

Animals↗

Application of electrical impedance analysis for diagnosis of a pulmonary mass.

The electrical impedance of a pulmonary mass was measured in 53 patients of whom 44 had primary lung cancer, 5 had metastatic lung tumor, and 4 had organizing pneumonia. Because biologic tissue can be regarded, electrically, to consist of extracellular resistance (Re), intracellular resistance (Ri), and the electrical capacitance of the cell membrane (Cm), these three parameters were calculated from the measured electrical impedance of tissue by a curve-fitting technique using a computer program. The Re of lung tissue was significantly greater (p < 0.01) and the Cm of lung tissue was significantly less (p < 0.01) than that of a pulmonary mass. The Re of malignant tumors (both lung cancer and metastatic tumors) was significantly greater (p < 0.01) and the Cm of malignant tumors was significantly less (p < 0.01) than that of organizing pneumonia. With this information, we used a biopsy needle to diagnose nine intrathoracic lesions. This technique additionally allowed us to confirm the proximity of the needle tip of the mass. The electrical impedance of the lung mass was measured through the biopsy needle using a modified impedance analysis system before the biopsy was performed. There were no false-negative results, and one false-positive result. The rapid measurement of the electrical impedance of a pulmonary mass, preoperatively, may be of value in the clinical evaluation of a pulmonary mass both by facilitating needle guidance and by permitting diagnosis based on electrical impedance.

Aged↗

[Two cases of thyroid cancer resected with trachea].

We described two patients of thyroid cancer with tracheal invasion. A 54-aged female visited our hospital with complaint of the neck pain. Echography showed a tumor in the right lobe of the thyroid. In operation the thyroid tumor invaded the trachea and right recurrent nerve. A 24-aged male visited our hospital with complaint of a mass of the left side neck. Echography showed a tumor in the left lobe of the thyroid. In operation the thyroid tumor invaded the trachea, lymph node and left recurrent nerve. In these two cases we could find thyroid tumors invaded into the trachea by echography. We re-evaluated the utility of echography.

Adult↗

Diagnosis and surgical treatment of small papillary carcinomas of the thyroid gland.

The preoperative and pathological findings of 38 cases of small papillary carcinoma of the thyroid gland measuring < or = 10 mm in diameter and 74 cases of large papillary carcinoma measuring more than 10 mm were compared. In the small carcinoma cases, the sensitivity of palpation, ultrasonography, and fine-needle aspiration biopsy (FNAB) was higher than that of computed tomography and soft tissue roentgenography of the neck. Therefore, palpation, US, and FNAB should be instituted as reliable diagnostic methods, but other examinations seem unsuitable as methods for preoperative qualitative diagnosis. No definite correlation was found between the intraglandular dissemination and the size of the carcinoma, and the frequency of metastasis was relatively high even in the small carcinoma cases. If the patient elects to undergo surgery, subtotal thyroidectomy with lymph node dissection should be performed for small thyroid carcinomas as well as large carcinomas.

Adult↗