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Biomedical subjects

K Aizawa

Publications and source records attributed to K Aizawa.

At least 19 recordsLinked to original sources

Apoptosis and Bbcl-2 expression in gastric carcinomas: correlation withclinicopathological variables, p53 expression, cell proliferation and prognosis.

We investigated apoptosis and Bcl-2 expression in 221 advanced gastric carcinomas in correlation with clinicopathological variables, p53 expression, cell proliferation and prognosis, using the in situ DNA nick end labeling method and immunohistochemistry. Apoptosis was associated with high immunoreactivity of proliferating cell nuclear antigen. Bcl-2 expression correlated with a low apoptotic index and less malignant behavior of tumors. Prognostically, Bcl-2 expression was associated with a better prognosis, whereas p53 expression was the most important prognostic risk factor. Thus, apoptosis in gastric carcinomas is associated with cell proliferation, and Bcl-2 expression may have a prognostic importance as well as p53 expression.

Apoptosis

Selective removal of cholesterol esters in an arteriosclerotic region of blood vessels with a free-electron laser.

BACKGROUND AND OBJECTIVE: In advanced atheromatous atherosclerosis, a large amount of lipids, particularly cholesterol esters, accumulates on the arterial wall. The selective removal of cholesterol esters accumulated in the intracellular or extracellular spaces has clinical significance. In the present work, the authors investigated the removal of cholesterol esters by using a free-electron laser (FEL) in an arteriosclerotic region. STUDY DESIGN/MATERIALS AND METHODS: Thin films of cholesteryl oleate and albumin and the cross section of a rabbit artery were placed on an inverted microscope stage, and the changes caused by the FEL irradiation of 5.75 microm and 6.1 microm, with 1.5-3 mW on average, were monitored continuously by using a CCD camera in real time. RESULTS AND CONCLUSION: FEL irradiation at a wavelength of 5.75 microm, which is a stretching vibrational mode of the ester, was able to ablate cholesterol esters without affecting albumin. It can also remove cholesterol esters from rabbit arteriosclerotic arterial walls.

Albumins

Esophageal intramural metastasis from an adenocarcinoma of the gastric cardia: report of a case.

We report herein the rare case of a 65-year-old man found to have esophageal intramural metastasis from cancer of the gastric cardia. Endoscopic examination initially revealed an infiltrating ulcerative tumor of the gastric cardia involving the esophagogastric junction, as well as a submucosal tumor of the lower esophagus. A total thoracic esophagogastrectomy with lower mediastinal lymphadenectomy was performed, and the resected specimen demonstrated that both the cardia and esophageal tumors were adenocarcinomas with the same cellular differentiation. As lymphatic invasion and metastases to the paracardial and mediastinal lymph nodes were observed, the esophageal submucosal tumor was considered to be an intramural metastasis from the carcinoma of the gastric cardia resulting from extensive lymphatic spread. The patient died of recurrent disease 9 months after the resection. This case report serves to demonstrate that intramural metastasis may be a local indicator of the systemic spread of disease in patients with gastric carcinoma, as it is in esophageal carcinoma.

Adenocarcinoma

The effects of serum on cellular uptake and phototoxicity of mono-L-aspartyl chlorin e6 (NPe6) in vitro.

Previous reports showed that the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) binds to serum proteins. However, the influence of this binding on the cellular uptake and photodynamic therapy (PDT) phototoxicity of NPe6 is still undefined. In this paper, we studied how serum in medium affected the P388 cellular uptake and PDT phototoxicity of NPe6 in vitro. This was assessed by (1) detection of the red shift (654 nm Q band peak of absorption) induced by protein binding NPe6; (2) detection of intracellular concentration of NPe6 by HPLC and (3) measurements of the cell survival ratio after PDT by MTT assay. The 654 nm Q band peak of NPe6 shifted to 665 nm after binding of NPe6 and serum proteins. The protein-bound NPe6 cannot be uptaken by cells, thus there was no PDT phototoxicity. Nevertheless, phototoxicity recovered when the concentration of NPe6 excessed the serum protein binding ability or there was free serum protein in the medium. These data suggested that the cellular uptake of NPe6 is inhibited by serum components in the medium, and that only free NPe6 is accumulated by P388 cells even during relatively long incubations. The cytotoxicity of PDT mainly depends on the free NPe6 level in the medium.

Animals

Tumor recurrence in patients with early gastric cancer: a clinicopathologic evaluation.

We conducted a retrospective study on 711 patients with early gastric cancer. Twenty-two patients (4.0%) developed recurrent disease and 21 died of recurrence during this study. One hundred and sixty-three patients died of unrelated or unknown causes. The recurrence patterns of 22 patients were as follows: hematogeneous metastasis to the liver in 11 patients, peritoneal dissemination in 3, recurrence in the remnant stomach in 3, and in the distant lymphonodes in 1. The mean survival period of patients with recurrent disease was 50.4 months, and 7 of these patients (31.8%) died more than 5 years after surgery. A retrospective clinicopathologic evaluation of the 22 patients and 526 patients without recurrence revealed significant differences between the two groups with respect to mean age at the time of surgery (62.5 years in the recurrent group vs 57.3 years in the nonrecurrent group), tumor size (41.2 vs 30.6 mm), depth of invasion (submucosal cancer: 19 vs 256), lymphnode metastasis (11 vs 48), lymphatic (11 vs 89) and venous (7 vs 18) invasion, and operative curability (curability B: 8 vs 48). Three patients with intramucosal cancer who died of hematogenous and/or peritoneal recurrence within 7 years after surgery had neither lymphnode metastasis nor lymphatic or venous invasion, suggesting that new techniques are needed for prediction of recurrent disease in patient with early gastric cancer.

Adult

[A basic study of photodynamic therapy of experimental hepatoma with ME 2906].

We have studied effects of photodynamic diagnosis (PDD) and photodynamic therapy (PDT) in hepatoma as confirmed by the existence of hepatoma when using a new photosensitizer mono-L-aspartyl chlorin e6. Japanese white rabbits were selected to perform abdominal incision under intravenous anesthesia and transplant VX2 tumor cells into the liver left lobe for the hepatoma model. Hepatoma of 1 cm in diameter (at one week after transplantation) was used experimentally to radiate a semiconductor laser (664 nm, 200 J/cm2) for treatment.

Animals

Tumor spread and outcome of treatment in primary esophageal small cell carcinoma.

BACKGROUND: The most effective treatment for patients with esophageal small cell carcinoma has not yet been established because of the overall extremely poor prognosis regardless of the mode of treatment. The role of esophagectomy has been controversial in the management of patients with this disease. METHODS: The clinicopathologic characteristics of 13 patients with primary esophageal small cell carcinoma were retrospectively studied and the prognostic significance of various factors with respect to esophagectomy were evaluated. RESULTS: Lymph node metastases and distant metastases were found at the time of presentation in 92.3 and 46.2%, respectively. Two of nine patients treated by surgical resection for local-regional disease survived >5 years after radical esophagectomy with a projected 5-year survival rate of 22.2%. The remaining 4/13 patients were treated by nonsurgical modalities, but died of the disease within 10 months. A significant difference (P < 0.05) was detected between the survival curves of the two groups of patients. CONCLUSION: Radical esophagectomy may be an effective treatment modality in improving survival and the odds of a cure in patients with local-regional small cell carcinoma of the esophagus.

Aged

Change in chemical composition of lipids accumulated in atheromas of rabbits following photodynamic therapy.

BACKGROUND AND OBJECTIVE: Mono-L-aspartyl chlorin e6 (NPe6) has been used in the photodynamic therapy of neoplasms. This substance has been shown to accumulate in atheroma of rabbits. We evaluated the change in the lipid components of atheromas after photodynamic therapy with NPe6 using Fourier transform infrared (FTIR) microspectroscopy. STUDY DESIGN/MATERIALS AND METHODS: Rabbits were fed a cholesterol-rich diet for 20 weeks. Six hours after they were administered NPe6 (2 mg/kg), the atheroma present on the abdominal aorta was irradiated with a diode laser with 100 J/cm2 or 200 J/ cm2 of the tissue fluence. Tissue samples were prepared for FTIR and histological analysis. RESULTS: Specimens of atheroma from the untreated animals appeared as fatty streaks whose infrared spectra exhibited characteristic peaks at 1,738(-1) cm-1, 1,468 cm-1, 1,380 cm-1, and 1,174 cm-1, indicating the accumulation of cholesterol ester. Seven days after photodynamic therapy, FTIR microspectroscopic analysis showed a marked decrease in the peak intensity in the treated atheroma related to the =C=O ester bond at 1738 cm-1 with no concomitant increase in the intensity of the peaks related to free cholesterol. CONCLUSION: Findings suggest a dissociation of ester bonds and the depletion of cholesterol esters in the atheromas after photodynamic therapy with NPe6. The lipids accumulated in the atheroma were perhaps decreased or destroyed following such treatment.

Animals

Evaluating the rational extent of dissection in radical esophagectomy for invasive carcinoma of the thoracic esophagus.

To define the rational extent of dissection in radical esophagectomy for esophageal cancer, survival was studied according to nodal status in 154 patients undergoing extended radical esophagectomy. The incidence of cervical metastasis in patients with upper or middle esophageal tumors did not differ between those with favorable (grade N < or = 4) or unfavorable (grade N > or = 5) lymph node status, at 28.6% vs 20%, respectively. On the other hand, in patients with lower esophageal tumors, the incidence of cervical metastasis was significantly lower in those with favorable grade (grade N < or = 4) node status than in those with unfavorable grade (grade N > or = 5) node status, at 6.5% vs 46.7%, respectively. Survival did not differ in patients with upper or middle esophageal tumors according to whether they had regional (n = 42) or distant (n = 15) lymph node metastases, the 5-year survival rates being 11.6% vs 25%, respectively. However, in patients with lower esophageal tumors, none of 10 patients with distant node metastases survived for more than 4 years, whereas the survival rate was 43.7% at 5 years for 36 patients with regional node metastases. These results show that cervical lymphadenectomy should only be performed as part of radical esophagectomy in those patients with upper or middle esophageal cancer.

Adult

Down-regulatory role of surface CD4 molecules on autoreactive helper T cells during B cell activation.

MS202 is an IL-2-dependent Th2 clone reactive to auto-MHC class II antigens as previously reported. It expresses CD4, TCR-alphabeta, Thy 1.2 and H-2k on the cell membrane, as well as CD40 ligand. In order to investigate a functional role of surface CD4 molecules on Th2 cells during B cell activation, we attempted to establish a CD4- variant subclone derived from the CD4+ MS202, and its effect on B cell activation was examined. Briefly, MS202 was incubated with ethyl methanesulfonate to induce mutation followed by extensive treatment with anti-CD4 MoAb and complement. MS1.1.2, a representative subclone of resulting cell lines, was shown to lack CD4 molecules on the cell membrane, although it possessed almost the same amount of surface molecules other than CD4 compared with the original MS202 by analysis with flow cytometry. Interestingly, MS1.1.2 induced the maturation of B cells into IgM-producing cells more potently than MS202. This differentiative effect was markedly greater on activated B cells than resting B cells; each population was prepared from splenic B cells by a gradient separation method, but after treatment with anti-IgM antibodies, resting B cells responded to MS1.1.2, resulting in the secretion of a comparative amount of IgM. Furthermore, the effect of MS 1.1.2 on DNA synthesis of activated B cells was much greater than that of MS202. The present results suggest that surface CD4 molecules on Th2 cells may not be substantially required for B cell activation, and rather mediate a down-regulation signal to B cells.

Animals

Increased serum CA125 levels in plasma cell dyscrasias.

We report 2 cases of plasma cell dyscrasia presenting with significantly elevated serum CA125 levels. The serum levels of CA125 from these patients correlated well with their serum M-protein levels. One patient had an IgG-kappa type extramedullary plasmacytoma with the culture supernatant from lymph node plasma cells showing a considerably high level of CA125 activity. The serum IgG fraction purified using a protein A column was devoid of any detectable CA125 activity, negating that the serum IgG M-protein from this patient might respond with a false-positive result in the CA125 immunoradiometric assay. The other patient had an IgG-lambda type plasma cell leukemia with the culture supernatant from peripheral mononuclear cells also showing a high level of CA125 activity. These observations may suggest that in plasma cell dyscrasias the CA125 antigen is spontaneously produced by tumor cells.

Aged

Intramural metastases from thoracic esophageal cancer: local indicators of advanced disease.

The patterns of tumor spread and long-term survival of patients with (n = 54) and without (n = 270) intramural metastasis from esophageal cancer were investigated after either extended radical (n = 155) or less radical (n = 169) esophagectomy. The purpose was to evaluate whether extended radical esophagectomy has an impact on the long-term survival of patients with intramural metastases from the disease. The patients with intramural metastasis had significantly larger primary tumors (p < 0.01) and more frequent T4 tumors (p < 0.001), stage IV disease (p < 0.05), lymphatic invasion (p < 0.05), and lymph node metastasis (p < 0.01) than did those without intramural metastasis. The survival rates of patients with intramural metastases were significantly worse than those of patients without intramural metastases after resection (p < 0.001). No patient with intramural metastases survived more than 4 years after either extended or less radical esophagectomy, and there was no significant difference between the two survival curves. Therefore intramural metastases should be considered local indicators of advanced esophageal cancer, and radical esophagectomy may not be indicated for patients with intramural metastasis from the disease.

Aged

The relationship between quantitative changes in collagen and formation of wrinkles on hairless mouse skin after chronic UV irradiation.

Female albino hairless mice were irradiated chronically with sub-erythemal doses of UVB radiation. Collagen extracted from the irradiated or non-irradiated dorsal skin of mice was fractionated into neutral salt-soluble (NSC), acid-soluble (ASC) and insoluble fractions (ISC). An age-related exponential decrease in the content and proportion of acid-soluble collagen was found in each group. The contents and the proportions of ASC from irradiated mice were always significantly lower than those from age-matched control animals. Age-related slight decreases were observed in the contents (per fresh weight of tissues) of NSC, ISC and total collagen in the control group but decreases in these collagen contents after UVB irradiation were marked. A dramatic decrease in ASC occurred nearly concomitantly with wrinkle formation in the irradiated mice. The decrease of acid-soluble skin collagen in irradiated mice may play a role in the formation of wrinkles on hairless mouse dorsal skin.

Animals

Scanning electron microscopic analysis of acute photodynamic therapy for atherosclerotic plaques of rabbit aorta by using a pheophorbide derivative.

The aim of this study was to demonstrate acute efficacy of photodynamic therapy on atheromas by using a pheophorbide derivative, PH-1126. Cholesterol-fed atherosclerotic rabbits were injected intravenously with 1 mg/kg of PH-1126. Twenty-four hours later, PH-1126 selectively accumulated in atherosclerotic plaques. Then, atherosclerotic lesions in the upper thoracic aorta were treated by irradiation with a krypton ion laser at a wave-length of 647 nm. At 6 h after photodynamic therapy, the treated aorta was examined by scanning electron microscopy. Numerous teardrop-shaped cells were observed on the endothelial surface of the plaque irradiated at a total energy of 100 J/cm2. These cells were larger than monocytes and macrophages, and resembled foam cells in size and shape. The body of the teardrop-shaped cell resembled pumice stone, mainly because of the presence of globular elements in the cytoplasm. A part of the cell appeared to remain in the subendothelial space. These findings suggest that the cells may be foam cells from the intimal layer of atherosclerotic plaque that were expelled into the aortic lumen. It may become possible to flatten atheroma in a long-term period after photodynamic therapy using PH-1126 as a potent photosensitizer.

Animals