Biomedical subjects
Publications and source records attributed to H Tsuda.
We describe a 42-year-old man with chronic thromboembolic pulmonary hypertension associated with protein S deficiency. He presented with unusual roentgenographic findings of migratory pulmonary infiltrates.
This study was conducted to examine the correlation between uterine vascularity and natural history of uterine leiomyoma. Seventy women with leiomyoma participated in this study. Measurements of uterine and leiomyoma volume, as well as blood flow characteristics of the main uterine artery and leiomyoma arteries, were made every 3 months for 1 year. Leiomyoma arteries could be detected in 52 (51.5%) of 101 leiomyomas. Leiomyoma volume increased in 24 (46.2%) of 52 leiomyomas with leiomyoma artery. However, the leiomyoma volume increased in only three (6.1%) of 49 leiomyomas without leiomyoma artery. No difference was found between the pulsatility index of the leiomyoma artery in the group with increased size and in the group with stable size. This study shows the vascularity of leiomyoma to be useful as a predictor of leiomyoma growth.
A 67-year-old man was admitted to our hospital with blood sputum. Adenocarcinoma was diagnosed by sputum cytological examination. A chest X-ray film showed a tumor shadow in the lower field of the right lung. The middle and lower lobes were resected and lymph node dissection was performed. Tumor was composed of well differentiated adenocarcinoma and spindle cell sarcomatous element, and diagnosed as so-called carcinosarcoma. Pathological staging was IIIA by pT1N2M0. Postoperative chemotherapy was not performed for side effect, so radiotherapy only was done. He died of recurrence and metastasis after about 1 postoperative year.
OBJECTIVE: To investigate the expression of costimulatory molecule CD80 on T cells of peripheral blood mononuclear cells (PBMC) in patients with systemic lupus erythematosus (SLE). METHODS: Monoclonal antibodies against CD80 were used for flow cytometry and expression of CD80 on PBMC was studied in 26 patients with SLE, 18 patients with rheumatoid arthritis (RA), 8 patients with mixed connective tissue disease (MCTD), and 22 healthy controls. RESULTS: CD80 was detected on CD3+ and CD19+ cells in patients with SLE and it was significantly higher than that of controls. In patients with SLE CD80 was expressed on CD4+ T cells (8.05+/-5.45%), significantly higher than in RA and controls, but was not highly expressed on CD8+ T cells (1.67+/-2.87%). CD80+CD4+ T cell phenotype analysis revealed CD45RA-, CD45RO+, and CD25+, or HLA-DR+ activated T cells. The percentage of CD80+ cells in CD4+ cells increased in the active stage of SLE, and was significantly correlated with the SLE disease activity index. CONCLUSION: CD80 can be expressed on activated CD4+ T cells in PBMC of patients with SLE in vivo and the appearance of these cells is associated with the disease activity in SLE.
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Recent epidemiological evidence points to a link between non-insulin dependent diabetes mellitus type II (NIDDM) and cancer of the colon, liver, pancreas, breast and endometrium. This appears to be due to the long period of hyperinsulinaemia which precedes the clinical phase of NIDDM, insulin promoting colon tumour development as well as acting as a hepatocarcinogen. Indeed, the hormone could play a central role in neoplasia, and its influence could explain the observed enhancing effects of obesity and a high fat diet, as well as the inhibition associated with physical exercise, dehydroepiandrosterone administration and high soluble fibre intake. Measures to decrease insulin levels, including lifestyle improvement and supplementation with agents known to decrease insulin resistance may therefore offer a general approach to prevention of cancer in a wide variety of organ sites of major clinical importance.
Clinical stage and lymph node status are the strongest prognostic factors of patients with breast cancer. The estimation of the patient prognosis would be more accurate and more specific and effective therapy could be performed, if the indicators of biological properties of individual cancers are combined with these conventional factors. As indicators of such biological properties, we list a number of histopathological factors and molecular biomarkers, including specific gene and chromosome alterations. These factors provide knowledge not only about the biological aggressiveness of breast cancer cells but also concerning the pattern of preferential metastasis sites and sensitivity to specific therapies.
The tumor-suppressive property of the connexin gap-junction proteins was postulated from the fact that their function of cell coupling is impaired in most cancer cells. However, in conflict with this notion, certain cancer cells are able to communicate through gap junctions despite their malignancy. To explain this phenomenon, we studied by using a dominant-negative strategy the effect on tumorigenicity of loss of intrinsic gap-junction intercellular communication (GJIC) in the rat bladder carcinoma cell line BC31, which shows both expression of connexin 43 (Cx43) and intercellular communication. In cells transfected with a mutant Cx43 with seven residues deleted from the internal loop at positions 130-136 (Cx43delta), transport of the resulting connexin protein to the plasma membrane occurred normally, but the GJIC of the cells was effectively abolished at the level of permeability of established gap junctions. Dominant-negative inhibition of GJIC by Cx43delta accelerated growth of BC31 cells in nude mice. In contrast, when GJIC in BC31 cells was artificially enforced by transfection of wild-type Cx43, the cells lost the capacity to grow in vivo. Decreased phosphorylation of Cx43delta suggested close interaction of the internal loop of connexin with its commonly phosphorylated domains in the C-terminal tail and involvement of this interaction in gap-junction permeability. Therefore, we conclude that the intrinsic GJIC observed in cancer cells should be considered a tumor-suppressor factor and that its level may influence malignant growth capacity.
Intracystic papillary tumors of the breast comprise intraductal papillomas and low-grade papillary carcinomas. To determine chromosomal alterations that may be characteristic of these tumors, chromosomes 3, 7, 17 and X were examined in 10 intraductal papillomas and 14 low-grade papillary carcinomas using multicolor fluorescent in situ hybridization. In papillry carcinomas, numerical/structural alterations in chromosome 17 and the accumulation of numerical alterations in chromosomes 3, 7 and X were detected in 21%(3/14) and 15%(2/13) of the cases, respectively. These changes were not detected in papillomas. Loss of chromosome 17p was detected in only one of the 11 DNA-diploid carcinomas, whereas alterations in all four chromosomes were present in a case of DNA-aneuploid carcinoma. Numerical alterations of chromosomes 3, 7, 17 and X do not appear to be involved in the development of low-grade papillary carcinomas with DNA diploidy, but rather accumulate during the formation of DNA-aneuploid carcinoma cells in association with other chromosome alterations.
We examined germline mutations in BRCA1 and BRCA2 in 23 Japanese breast cancer families, using PCR-SSCP analysis. The same nonsense mutation (exon 5, Leu63ter) of BRCA1 was detected in two defferent families. Three different mutations resulting in a truncated BRCA2 protein (exon 9, 20, 24) were detected in three different families, including one male case of breast cancer. One base substitution mutation in BRCA2, A10462G, was detected in the other two families. Although the mean age of onset for breast cancer in families with the BRCA1-mutation was 50 years, the age of onset in families with the BRCA2-mutation was from 28 to 43 years. Among the 23 families examined, two families had members with ovarian cancers, three had members with prostate cancers, and one had a pancreatic cancer. However, none of these families was positive for the BRCA1 orBRCA2 mutation. Histopathologically, we observed a prevalence of histological grade 3 in BRCA1/2-associated familial breast cancers, because of nuclear atypia, structural atypia and mitotic activity. It is suggested that BRCA2 may play a more important role than BRCA1 in Japanese familial breast cancers, and these mutations are related to the aggressive nature and highly proliferative activity of the tumors.
BACKGROUND: A reduction in local residual breast cancer is important to avoid local recurrence after breast conserving treatment (BCT). Previous studies suggested the usefulness of contrast-enhanced computed tomography (CE-CT) in detecting extensive intraductal component(EIC), which is associated with local recurrence. This study investigates the practical role of CE-CT in BCT. METHODS: In 130 women whose breasts were examined by CE-CT preoperatively, intraductal spread detected using ultrasound (US), mammography (MMG) and CE-CT, and EIC detected by histological examination were analyzed to determine possible correlations among the extent and subtypes of intraductal components. RESULTS: The sensitivities of EIC detection by US, MMG and CE-CT were 29%, 53% and 88%, respectively, and the corresponding specificities were 58%, 70% and 72%, respectively. In 6 patients, EIC could only be visualized using CE-CT. CE-CT demonstrated the extent of cancerous lesions more accurately than standard diagnostic modalities. Intraductal components with a higher histological grade tended to show stronger enhancement. Most false negative intraductal components obtained on CE-CT (6/7) were of a low histological grade. CONCLUSIONS: CE-CT is useful for visualizing EIC and small invasive foci of breast cancer, and can suggest the optimal extent of resection.
The influence of concomitant administration of bovine lactoferrin (bLF) on induction of aberrant crypt foci (ACF) by azoxymethane was investigated in male F344 rats. Two percent bLF and 3% Bifidobacterium longum (B. longum), as a positive control, significantly decreased the numbers of ACF as well as the total numbers of aberrant crypts reproducibly in three independent studies (2% bLF, P < 0.01; 3% B. longum, P < 0.05). Most importantly large size foci composed of four or more crypts were always significantly decreased by 2% bLF (P < 0.05). Additional investigation of the natural killer activity of spleen cells demonstrated enhancement by bLF (P < 0.01) and B. longum (P < 0.01) in line with the levels of influence on foci induction, indicating a possible role for elevated immune cytotoxicity in the observed inhibition.
An investigation was conducted to assess the chemopreventive potential of lycopene (LP), a naturally occurring hydrocarbon carotenoid found in tomatoes and their products, administered during the post-initiation stage in a multiorgan carcinogenesis model. One hundred eighteen B6C3F1 mice of both sexes were subjected to combined treatment with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU) and 1,2-dimethylhydrazine (DMH) from day 11 after birth to week 9 (DMD treatment) (groups 1 and 2) or their vehicles (group 3). Then group 1 received LP (25 or 50 ppm in drinking water) for 21 weeks from weeks 11 to 32. Group 2 served as a carcinogen alone control and group 3 was given only LP (25 or 50 ppm). All surviving animals were sacrificed at week 32 and the major organs, including the liver, lung, kidney and colon, were histologically examined. The incidences and multiplicities of lung adenomas plus carcinomas combined in male mice in group 1 receiving 50 ppm LP were significantly decreased as compared to the DMD alone or DMD and 25 ppm LP groups (75.0 versus 18.8%, P < 0.02; 0.94 +/- 0.17 versus 0.25 +/- 0.14, P < 0.001). No such effect was observed for females. Although hepatocellular carcinomas were lacking in the DMD and LP groups while two cases were found in the DMD alone group, this difference was not statistically significant. The values for aberrant crypt foci (ACF) and tumors in the colon and kidney did not show any significant variation among the carcinogen-treated subgroups. The results suggest that LP exerts a chemopreventive effect limited to male lung carcinogenesis when given in the post-initiation stage to B6C3F1 mice.
In order to determine the effects of single unsaturated fatty acids (UFAs) or combinations on establishment of lung metastatic colonies, UFAs were administered orally to CDF1 mice bearing s.c. implants of the highly metastatic colon carcinoma 26. Oleic acid (OA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrated significant inhibition. In the case of DHA, this inhibitory potential was markedly reduced by co-administration of linoleic acid (LA) or EPA. Furthermore, while tumor cells treated with DHA showed a very low potential for lung colony formation when injected i.v., this again being partially reversed by co-administration of EPA. UFAs were found to be well absorbed into tumor tissues after oral administration, causing marked changes in relative levels, the arachidonic acid (AA) content, in particular, being markedly decreased by treatment with DHA or EPA, but not with DHA plus EPA or with DHA plus LA. Investigation of the gelatinolytic activity of the 57-kDa and 92-kDa isoforms of type-IV collagenase (MMP-2 and MMP-9, respectively) showed a clear reduction in the former by treatment with OA, while DHA, but not DHA plus LA or EPA, caused a decrease in the 92-kDa isoform, which was well correlated with AA content in tumor tissues (r = 0.900, p < 0.001). These results suggest that inhibition of metastasis due to treatment with OA and DHA might be due to depressed type-IV collagenase activity.
We report a case of insulin-dependent diabetic fibrous mastopathy, which clinically simulated breast cancer. The patient is a 55-year-old woman with stony-hard breast lumps, who had been treated with insulin for diabetes mellitus. Mammmography revealed a highly-dense mass shadow in the left breast and ultrasonography detected hypoechoic lesions with acoustic shadows in both breasts, suggestive of malignancy. Excisional biopsy was performed for the left breast lump. On histopathological examination, this was fibrosis with dense lymphocytic infiltration around lobules, which is a characteristic feature of diabetic fibrous mastopathy
To obtain useful hypoxanthine phosphoribosyl-transferase (HPRT)-deficient mouse ES cell lines, two different methods were employed: (i) selection of spontaneous 6-TG-resistant mutants and (ii) gene targeting of the HPRT locus. The first approach resulted in the establishment of E14.1TG3B1, a spontaneous HPRT-deficient cell line with an insertional mutation of 203 bp in the third exon of the HPRT gene. The insert is highly homologous to the B2 mouse repetitive element and has all the expected retroposon characteristics, thus providing an example of gene inactivation by retroposon insertion. This clone exhibited stable 6-TG resistance and high germ-line transmission frequency. Thus E14.1TG3B1 is a useful ES cell line for modifying the mouse genome using the HPRT gene as a selection marker and for transmission at a high frequency into the mouse germ line. The second approach resulted in a 55-kb deletion of the mouse HPRT locus, demonstrating the feasibility of replacement-targeting vectors to generate large genomic DNA deletions.
Our study was designed to clarify the significance of silencing the E-cadherin gene, which is located on 16q22.1, due to CpG methylation during hepatocarcinogenesis. The CpG methylation status of primary hepatocellular carcinomas (HCCs) and corresponding liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, were assessed by digesting DNA with methylation-sensitive and non-sensitive restriction enzymes. CpG methylation around the promoter region of the E-cadherin gene was detected in 46% of liver tissues showing chronic hepatitis or cirrhosis and 67% of HCCs examined. Immunohistochemical examination revealed reduced E-cadherin expression in 59% of HCCs examined. CpG methylation around the promoter region correlated significantly with reduced E-cadherin expression in HCCs (p < 0.05). CpG methylation around the promoter region, which increases during the progression from a precancerous condition to HCC, may participate in hepatocarcinogenesis through reduction of E-cadherin expression, resulting in loss of intercellular adhesiveness and destruction of tissue morphology.
We report cases of breast cancer with extensive intraductal component (EIC), the extent of which could be detected only by contrast-enhanced computed tomography (CT) scan. One case was a 32-year-old woman who presented left nipple bloody discharge without breast mass palpation. Mammography (MMG), galactography and ultrasonography (US) showed no abnormalities. Contrast helical CT scan revealed numerous patchy enhancement in the upper-outer quadrant of the left breast. Histological examnation revealed invasive ductal carcinoma with a predominant intraductal component. The second case was a 36- year-old woman who had noticed a left breast mass 2.4 cm in diameter. MMG and US suggested a localized breast cancer. Contrast helical CT scan revealed numerous patchy enhancement throughout the mammary gland in addition to the index tumor near the nipple. Histopathological results indicated invasive ductal carcinoma with widely spread ELC. In these two cases, the extent of intraductal cancer also correlated well with the CT findings. Breast CT scan can be an effective tool for determining the extent of the intraductal component of breast cancer, which is an important factor when considering breast-conserving therapy.