Eccrine angiomatous hamartoma with verrucous features.
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Biomedical subjects
Publications and source records attributed to T Tsuji.
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CD8+ cell-secreted CC-chemokines, MIP-1alpha, and MIP-beta have recently been identified as factors which suppress HIV. In this study we co-inoculated MIP-1alpha expression plasmid with a DNA vaccine constructed from HIV-1 pCMV160IIIB and pcREV, and evaluated the effect of the adjuvant on HIV-specific immune responses following intramuscular and intranasal immunization. The levels of both cytotoxic T lymphocyte (CTL) activity and DTH showed that HIV-specific cell-mediated immunity (CMI) was significantly enhanced by co-inoculation of the MIP-1alpha expression plasmid with the DNA vaccine compared with inoculation of the DNA vaccine alone. The HIV-specific serum IgG1/IgG2a ratio was significantly lowered when the plasmid was co-inoculated in both intramuscular and intranasal routes, suggesting a strong elicitation of the T helper (Th) 1-type response. When the MIP-1alpha expression plasmid was inoculated intramuscularly with the DNA vaccine, an infiltration of mononuclear cells was observed at the injection site. After intranasal administration, the level of mucosal secretory IgA antibody was markedly enhanced. These findings demonstrate that MIP-1alpha expression plasmid inoculated together with DNA vaccine acts as a strong adjuvant for eliciting Th1-derived immunity.
In this study, we determined the proliferation indices of liver metastatic tumours originating from colorectal carcinomas using Ki67 and argyrophil nucleolar organizer region associated proteins (AgNOR) stain. We examined the primary and metastatic tumours in 27 patients with liver metastasis and eight cases with non-metastatic colorectal carcinoma as a control.The number of AgNOR dots in metastatic tumours was significantly higher than in the respective primary tumours of the metastasis group or in non-metastatic colorectal carcinomas. The Ki67 labelling index was similar in all groups. The Ki67 labelling index and AgNOR counts did not correlate with each other. There was no significant relationship between proliferation indices and the duration of the disease-free period following hepatic resection for metastases or with prognosis after hepatectomy. We conclude that Ki67 and AgNOR are not useful indicators of prognosis in patients who undergo operation for liver metastasis of colorectal carcinomas.
BACKGROUND: Adhesion molecules are closely involved in the development and growth of metastatic tumours. METHODS: We examined the expression of two adhesion molecules in liver metastatic tumours originating from colorectal carcinomas and correlated the expression of E-cadherin (EC) and CD44 variant exon 6 (v6) in these tumours with prognosis after hepatic resection. We examined 39 primary colorectal and 44 liver metastatic tumours obtained from 39 patients and 30 non-metastatic colorectal carcinomas as controls. The expression of EC in primary colorectal carcinomas of the metastasis group was significantly lower than in the non-metastasis group (P < 0.05). The expression of EC was low in metastatic liver tumours. RESULTS: The expression of CD44v6 in primary colorectal carcinomas of the metastasis group was significantly higher than in the non-metastasis group (P < 0.01). Expression of CD44v6 was high in metastatic liver tumours. However, there was no correlation between the expression of EC and CD44v6 or between each of these molecules and clinicopathological features of primary and metastatic tumours. Negative expression of EC and CD44v6 was a poor prognostic factor for survival after hepatic resection. CONCLUSIONS: Our results indicate that the lack of expression of EC and CD44v6 in liver metastases of colorectal cancer is associated with poor survival after surgery.
BACKGROUND: Diffuse submucosal cysts of the stomach have been suggested as a predisposing condition for the development of gastric cancer, especially multiple cancers. We report here two cases of diffuse submucosal cysts of the stomach associated with multiple gastric cancers which were detected during endoscopic follow-up. METHODS AND RESULTS: The first patient was a 75-year-old man and the second patient was a 72-year-old man. In the first case, we performed an endoscopic examination every year and detected an advanced cancer and two early cancers on the fifth year of the follow up. Because one of these cancers was advanced, we examined the second patient endoscopically every six months. In this patient, we detected two early cancers after 1.5 years follow up. CONCLUSIONS: We suggest that patients with this disorder should be examined regularly by endoscopy for the detection of gastric cancer, preferably every six months.
Flavins are thought to be important chromophores for chronic photo-induced skin injury, but the mechanism is not well known. We have reported that the primary cytotoxicity remaining in ultraviolet A-irradiated riboflavin solution is attributable to hydrogen peroxide. Because the dermis is more hypoxic than the atmosphere, we investigated the cytotoxicity of riboflavin solution during and after ultraviolet A irradiation under hypoxia. Riboflavin solution showed stronger cytotoxicity during irradiation under hypoxia than under air. Riboflavin solution that had been irradiated under hypoxia at lower ultraviolet A doses showed stronger cytotoxicity and contained more hydrogen peroxide than solution irradiated under air at the same doses. At higher ultraviolet A doses, however, the cytotoxicity and hydrogen peroxide quantity were similar in riboflavin solutions irradiated under different oxygen conditions. The effect of a singlet oxygen quencher, sodium azide, on the induction of cytotoxicity and production of hydrogen peroxide by ultraviolet A irradiation of riboflavin solution was examined. The presence of sodium azide in the solution during ultraviolet A irradiation suppressed the cytotoxicity and hydrogen peroxide production to similar levels at various ultraviolet A doses regardless of oxygen conditions. At the maximum suppression by sodium azide, hydrogen peroxide production decreased to 10% of the unsuppressed production. About 40% of the oxygen molecules of hydrogen peroxide produced was thought to be derived from oxygen dissolved in the riboflavin solution.
Integrin alpha3beta1 (VLA-3) is an adhesion receptor for extracellular matrix proteins including various isoforms of laminin. We have isolated mouse genomic clones encoding the integrin alpha3 subunit and deduced the exon/intron organization. The mouse integrin alpha3 subunit gene is encoded by 26 exons spanning 40 kb. The exon/intron structure of the integrin alpha3 subunit gene resembles that of the integrin alpha6 subunit gene, but differs somewhat from those of other members of the integrin family. We have demonstrated that the cytoplasmic domain splicing variants of the alpha3 subunits (alpha3A and alpha3B) are generated by alternative exon usage. We also cloned the 5'-flanking region and performed a preliminary analysis of its promoter activity in various tumor cell lines with different degrees of integrin alpha3 expression. Following transfection, activity in the luciferase assay was found to be roughly correlated with the expression level of integrin alpha3 as measured by flow cytometry. Furthermore, the luciferase assay was performed with normal and SV-40- or polyoma virus-transformed fibroblasts. In mouse, human, and hamster fibroblasts, higher levels of luciferase expression were observed in transformed cells than in normal cells. This result is consistent with our previous finding that integrin alpha3 expression at both the protein and mRNA levels is enhanced upon oncogenic transformation of fibroblasts by tumor viruses.
RATIONALE AND OBJECTIVES: To investigate the dose-dependency and half-life of decay of the signal reduction by super-paramagnetic iron oxides on three different spin-echo images in a rat model of cirrhosis. METHODS: For normal and cirrhotic liver, signal intensities were measured 15 minutes after injection of Resovist (range, 1-40 mumol Fe/kg) on three different spin-echo images. Subsequently, recovery of signal intensity was monitored up to 2 weeks after injection. RESULTS: The dose-dependency of efficacy was somewhat less at all doses and imaging parameters in cirrhotic liver. However, the submaximal effect was obtained at a dose of 20 mumol Fe/kg, the same as in normal liver. The rate of decay of the efficacy in cirrhotic liver was similar to or faster than that in normal liver. CONCLUSIONS: The dose-dependency and rate of decay of efficacy of Resovist in cirrhosis were similar to those in normal liver, although the efficacy was less in cirrhotic liver and both the dose-dependency and rate of decay of efficacy were dependent on imaging parameters.
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We report a 70-year-old woman who developed recurrent multiple ulcers and residual atrophic scars on her legs and feet. The histology showed fibrinoid material in the dermal vessel walls causing partial to complete occlusion of the lumina. Capillary tufting and dilatation were also noted in the dermis. There was no vasculitis or panniculitis. Extravasated red blood cells were seen throughout the dermis; these were engulfed by benign-appearing histiocytes around the dermal-fat junction. As she was generally well and there was no evidence of the presence of cytophagic cells in her extracutaneous organs, she was diagnosed with regional phagocytic histiocytoses supposedly triggered by extravasated red blood cells.
The first case of Mucha-Habermann disease-like drug eruptions due to Tegafur is reported. A 59-year-old man noticed various skin lesions after he had taken 300 mg of Tegafur daily for about 200 days. The patient had papulonecrotic eruptions on his trunk and extremities. The histology from a papular lesion revealed epidermal necrosis surrounded by spongiosis, perivascular inflammatory infiltrations composed of lymphocytes and erythrocytes, and endothelial swelling. The etiology of Mucha-Habermann disease is not known, but an immune mechanism may be supported by our case.
Adenocarcinoma with signet ring cells (ASRC) is a rare skin neoplasm whose histology shows a solid tumor intermingled with signet ring cells in variable numbers. There have been only ten reported cases. All were elderly males affected on the eyelids except for a single case in the axilla. Two new patients with ASRC of the axilla are described. In both of them, immunohistochemical studies revealed neoplastic cells that had differentiated toward apocrine glands. These are the second and third reported cases of ASRC in the axilla, one of them is the first ASRC case in a female. It seemed that the apocrine sweat gland or aberrant breast tissue in the axilla were possible origins of these tumors.
Tubulin binding agents (TBAs) reduce tumor perfusion and inhibit mitosis of tumor cells in solid tumors, but it is not clear which effects contribute to the suppression of solid tumor growth. We evaluated the antivascular and antimitotic effects of several TBAs, combretastatin A-4 (CS A-4) phosphate, AC-7700, a novel CS A-4 derivative, colchicine, E7010, and vinblastine, on subcutaneous (s.c.) murine colon26 adenocarcinoma (c26). Tolerable doses of vinblastine and E7010) strongly inhibited tumor growth and induced mitotic arrest of tumor cells without affecting tumor perfusion. Colchicine had no effect on tumor growth and perfusion. When the injected dose was increased to the lethal range, however, these drugs markedly reduced tumor perfusion and caused necrosis of tumor tissue. Within the tolerable dose range, AC-7700 both strongly suppressed tumor growth and reduced tumor perfusion, and CS A-4 phosphate also exhibited a moderate antivascular effect. To evaluate the contribution of antivascular activity of TBAs to tumor growth suppression, excluding their direct cytotoxic effect on tumor cells, we established c26/acr, which is resistant to TBAs in vitro. Although E7010 showed a reduced suppressive effect on s.c. c26/acr tumor growth as compared with its effect on wild-type c26, AC-7700 remained potent against both cell lines. These results indicate that TBAs exert antivascular and antimitotic effects on solid tumors with marked differently effective dose ranges from agent to agent, and that the antivascular effect of TBAs inhibits solid tumor growth independently of the direct cytotoxic effect on tumor cells.
AC-7700, a novel combretastatin A-4 derivative, suppresses the growth of solid tumors by inhibiting tumor perfusion. We evaluated the antitumor activity of AC-7700 on solid tumors in two experimental models, an advanced tumor model (murine colon 26 (c26) adenocarcinoma, colon 38 (c38) adenocarcinoma, MethA fibrosarcoma, Sarcoma 180 (S180), Lewis lung carcinoma (3LL), human LS180 adenocarcinoma) and an orthotopically transplanted tumor model (c26), compared with that of cisplatin (CDDP). The maximum tolerable dose (MTD) of CDDP suppressed early-stage c26 and c38 tumor growth when treatment was started after the tumor volume (TV) reached 0.2-0.5 cm3, but it showed reduced activity against the same tumors at an advanced growth stage when TV exceeded 2 cm3. At its MTD, AC-7700 was active against all tumors tested except 3LL in both early and advanced growth stages, reducing the tumor mass and having a curative effect in advanced c38 tumors. AC-7700 was also effective on orthotopically transplanted c26 tumors, showing a comparable activity to that on subcutaneous tumors. Unlike flavon acetic acid, which damages tumor vasculature by inducing endogenous tumor necrosis factor-alpha production, AC-7700 potently suppressed the growth of advanced c26 tumors in athymic as well as euthymic mice. These results suggest that AC-7700 is a novel antivascular agent that may have potent activity against advanced-stage cancer in the clinical setting.
AIMS/BACKGROUND: Extracellular matrix (ECM) may affect the function and phenotype of hepatocytes. Phenotypic changes of hepatocytes in diseased liver were investigated with reference to ECM composition. METHODS: Immunohistochemistry was performed on biopsied liver samples from chronic viral hepatitis (CVH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and normal patients, using monoclonal antibodies for laminin, type IV collagen, cytokeratin 19 (CK19) and epithelial glycoprotein (EGP), a protein homologous to nidogen. RESULTS: In normal controls, both EGP and CK 19 were expressed exclusively on biliary epithelia. Laminin and type IV collagen were expressed around portal bile ducts and blood vessels. Although type IV collagen was expressed in Disse's space, laminin was scarcely expressed. In all pathological livers, both EGP and CK 19 were expressed in proliferated bile ductules. In CVH with piecemeal necrosis, EGP was expressed on periportal hepatocytes, while CK19 expression was limited to a few hepatocytes. Laminin was expressed in Disse's space of periportal sinusoids, where EGP was expressed on hepatocytes. EGP expression on hepatocytes and laminin deposition in Disse's space were rare in PBC and PSC liver. CONCLUSION: These results suggest that hepatocytes transform into a phenotype similar to biliary epithelia and, laminin deposition in Disse's space (capillarization of sinusoids) may play a role in this phenotypic change.
AIMS/BACKGROUND: Activated liver macrophages in chronic hepatitis express a high affinity receptor for IgG named FcgammaRI. This study was performed to find the difference in FcgammaRI expression between chronic hepatitis B (CHB) and C (CHC) with reference to histological activity. METHODS: Consecutive patients with CHB (20 cases) and CHC (25 cases) were enrolled in the study. Inflammatory activity was evaluated using the modified histological activity index (HAI). FcgammaRI-positive macrophages were quantitatively measured by computer assisted morphometry. RESULTS: Total HAI score was significantly higher in CHB than in CHC. Confluent necrosis was observed in significantly higher frequency in CHB at Stages 3 5 than in CHC. The percentage area of FcgammaRI-positive macrophages was significantly higher in CHB than in CHC. In CHB, the percentage area of FcgammaRI-positive macrophages correlated with total HAI (<0.01) as well as the degree of confluent necrosis (<0.01), interface hepatitis (<0.05) and portal inflammation (<0.05). FcgammaRI-positive macrophages accumulated mainly at the site of confluent necrosis. In CHC, no correlation was observed between activated macrophages and any histological categories. CONCLUSION: These results suggest that FcgammaRI-positive macrophages are associated with confluent necrosis in CHB, which is more common in CHB patients than in CHC.