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Biomedical subjects

K Sumiyoshi

Publications and source records attributed to K Sumiyoshi.

At least 37 records · Page 2Linked to original sources

Regulation of complement C3 synthesis by interleukin-1 and transforming growth factor-beta in rat non-transformed intestinal epithelial cell line, IEC-6.

Intestinal epithelial cells are an important source of many biologically active molecules that modulate immune responses in the mucosa. The purpose of this study was to demonstrate the synthesis of complement C3 component in the rat non-transformed crypt-like intestinal epithelial cell line, IEC-6. Unstimulated IEC-6 cells secreted a low level of C3 protein and showed weak expression of C3 mRNA. The addition of interleukin (IL)-1 beta induced a dose- and time-dependent increase in C3 production. These effects of IL-1 beta were observed at a concentration as low as 0.01 ng/ml and reached a plateau at a concentration of 5 ng/ml. The effects were observed at the mRNA level as early as 6 h after the beginning of incubation. Transforming growth factor (TGF)-beta alone had no effect. However, TGF-beta at low concentrations (0.001-1 ng/ml) enhanced the effect of IL-1 beta in increasing C3 production; this enhancement was not observed at high concentrations (5-10 ng/ml). These effects of TGF-beta were also observed at the mRNA level. The present findings indicate that intestinal epithelial cells are indeed capable of synthesizing complement C3 in response to IL-1 beta and TGF-beta.

Animals↗

Interleukin 4 acts as an inducer of decay-accelerating factor gene expression in human intestinal epithelial cells.

BACKGROUND & AIMS: Decay-accelerating factor (DAF) protects host tissues from the attack of autologous complement activation. In this study, we attempted to define the cytokine regulation of DAF messenger RNA (mRNA) expression in human intestinal epithelial cells. METHODS: The effects of cytokines on DAF mRNA accumulation were evaluated by Northern blot analysis. The DAF protein expression was analyzed by both immunoprecipitation and immunoblotting. RESULTS: Interleukin (IL)-4 induced a marked increase in DAF mRNA accumulation in HT-29 cells. In this line, IL-1 beta evoked only weak induction, and IL-6, IL-8, IL-10, and interferon gamma had no effect. The effect of IL-4 was observed in a dose-dependent manner and confirmed at the protein level. The increase in DAF mRNA accumulation reached a maximum at 3-6 hours and then gradually decreased. These effects of IL-4 on DAF mRNA and protein expression were also observed in T84 cells. The mRNA stability studies suggested that IL-4 regulates DAF gene expression mainly at the transcriptional level. CONCLUSIONS: In human intestinal epithelial cells, IL-4 acts as a potent inducer of DAF mRNA expression, suggesting a cytoprotective role for IL-4 against autologous complement activation.

CD55 Antigens↗

Local secretion of complement C3 in the exocrine pancreas: ductal epithelial cells as a possible biosynthetic site.

BACKGROUND & AIMS: The complement system participates in the local immune system in various tissues. In this study, we investigated the local secretion of complement C3 into the pancreatic fluid and attempted to determine a possible biosynthetic site. METHODS: C3 protein in human pancreatic fluid was analyzed by, immunoblotting. The C3 messenger RNA (mRNA) expression in several pancreatic carcinoma cell lines was analyzed by the polymerase chain reaction and/or Northern blotting. The secretion of C3 by these pancreatic carcinoma cells was assessed by metabolic labeling and immunoprecipitation experiments. RESULTS: In five samples of human pancreatic fluid, C3 was detected as a molecule composed of alpha and beta chains. C3 mRNA expression was observed in the ductal cell carcinoma lines (PANC-1 and MIA PaCa-2) but not in the acinar cell line (HPC-YO and AR-42J). C3 production in these cells was enhanced by interleukin 1 beta and tumor necrosis factor alpha at both the protein and the mRNA levels. CONCLUSIONS: (1) Complement C3 is secreted into the exocrine fluids of the pancreas. (2) Ductal epithelial cells are possible biosynthetic sites for C3. (3) The proinflammatory cytokines, interleukin 1 beta and tumor necrosis factor alpha are effective stimulators of local C3 production in the pancreas.

Adult↗

Oesophageal cancer coexisting with colorectal lesions.

OBJECTIVE: To investigate the incidence of colorectal lesions in patients who present with oesophageal cancer. DESIGN: Prospective open study. SETTING: University hospital, Japan. SUBJECTS: 135 of 218 patients who presented with squamous cell carcinoma of the oesophagus during the seven year period 1988-1994 were randomly allocated to have a barium enema examination. INTERVENTIONS: Barium enema examinations, and if colorectal lesions were found, colonoscopy and biopsy. MAIN OUTCOME MEASURE: Incidence of coexistent colorectal lesions. RESULTS: No abnormal findings were found in 52 (39%), diverticula were present on 37 (27%), benign polypoid lesions in 51 (38%), and malignant lesions in 6 (4%). We examined the clinical and histopathological details of all patients to see if it was possible to distinguish the patients at high risk of developing oesophageal and colorectal cancer but could find no differences among the groups. CONCLUSION: Asymptomatic colorectal lesions are relatively common in patients with squamous cell carcinoma of the oesophagus in Japan.

Aged↗

Carcinogenesis and histogenesis of esophageal carcinoma.

Dysplasia is one of the most important subjects regarding carcinogenesis of the esophagus, because there is continuing controversy as to whether esophageal dysplasia is a cancerous lesion or a noncancerous lesion. In this study, it is histopathologically shown that dysplasia has a close correlation with cancer itself and that there is no substantial difference in the cell proliferative activity of dysplasia and intraepithelial carcinoma. These findings thus show that dysplasia has as high a potential for malignancy, thus it should be treated as an extremely early cancerous lesion of the esophagus to substantially improve the long term results of this disease. Conversely, esophageal carcinoma with glandular and/or mucus-secreting components is commonly found in addition to the ordinary component of squamous cell carcinoma, which indicates that this type of esophageal tumor originates not only from the squamous epithelium but also from the esophageal mucus gland or the ductal epithelium. These findings support the concept of field carcinogenesis in esophageal carcinoma.

Carcinoma↗

Prospective randomized study of hyperthermia combined with chemoradiotherapy for esophageal carcinoma.

From January 1988 to June 1992, 66 patients with resectable squamous cell carcinoma of the thoracic esophagus underwent preoperative adjuvant therapy. These patients were prospectively divided into two treatment groups; 32 were treated with radiofrequency wave local hyperthermia combined with chemoradiotherapy (hyperthermochemoradiotherapy; HCR), while the remaining 34 patients were treated with chemoradiotherapy alone (CR). There were no procedural complications in either group and the postoperative mortality was zero. In the HCR group, no viable cancer cells were found within the entire 5 mm-width slices of the resected specimen in eight patients (25%), while only two (5.9%) in the CR group (P < 0.05) demonstrate no viable cancer cells. The cumulative 3-year survival rate was 50.4% in the HCR group and 24.2% in the CR group. The present prospective trial demonstrated that the addition of hyperthermia to chemoradiotherapy resulted in a better local control and an improved long-term survival when treating patients with advanced esophageal carcinoma.

Adult↗

Gas-forming liver abscess following transcatheter hepatic arterial embolization for an iatrogenic intrahepatic pseudoaneurysm: report of a case.

We herein describe a case of gas-forming pyogenic liver abscess following transcatheter hepatic arterial embolization (THAE) for an iatrogenic intrahepatic pseudoaneurysm in a 74-year-old woman. Hemobilia developed 19 days after percutaneous transhepatic cholangio-drainage was performed for the purpose of percutaneous cholangioscopic lithotripsy for the treatment of post-gastrectomy choledocholithiasis. Celiac arteriography disclosed a saccular aneurysm in the right hepatic artery. The pseudoaneurysm was successfully occluded by THAE with gelatin powder and a stainless steel coil of the Gianturco type. Ten days after successful THAE, abdominal computed tomography revealed a gas-containing cavity, which suggested the presence of a gas-forming abscess, in the posterior hepatic segment, and percutaneous transhepatic abscess drainage was performed. Thus, impaired hepatic perfusion following effective THAE and coexisting cholangitis may play an important role in the development of a gas-forming pyogenic liver abscess.

Aged↗

The prognostic significance of the cytophotometric DNA content and its relationship with the argyrophilic nucleolar organizer regions (AgNOR) and proliferating cell nuclear antigen (PCNA) in oesophageal cancer.

We examined the DNA pattern, AgNOR number and PCNA-positive ratio (PCNA ratio) from biopsy specimens of oesophageal carcinoma, and attempted to identify any prognostic factors for oesophageal carcinoma. DNA analysis: the cell nuclear DNA content was measured and the distribution pattern of the DNA content was grouped into four types according to the ploidy pattern (n = 182). The survival rate of patients with high-ploidy tumours (type III and IV) was shorter than that for low-ploidy tumours (type II), (P < 0.05). AgNOR number (n = 99) and PCNA ratio (n = 41): the AgNOR number and PCNA ratio were measured from 100 cancer cells in each specimen. Both the high-AgNOR-number patients (> or = 5) and the high-PCNA-ratio patients (> or = 35) demonstrated poorer prognoses than the low-rate patients (P < 0.05). These results suggest that the DNA pattern, AgNOR number and PCNA ratio may thus reflect the proliferative activity of tumours and therefore also offer the possibility of interdependence among these three factors.

Aged↗

Histological suggestions of 'paratransformation' in oesophageal squamous cell carcinoma.

We have postulated that oesophageal squamous cell carcinoma arises from multifocal areas and not from one cell, and we present the circumstantial evidence for field carcinogenesis in oesophageal cancer. Among 290 cases examined with oesophageal squamous cell carcinoma, lymphatic permeation or intramural metastasis was evident in 110 cases. Of these carcinomatous transformation of the epithelium adjacent to either lymphatic vessel permeation or intramural metastasis of the squamous cell carcinoma was recognized in six cases. It is considered that the cancer tissue either in the lymphatic vessel or intramural metastasis promotes a malignant transformation of the squamous epithelium over these foci. 'Paratransformation' is therefore thought to be one of the potential models of origin for oesophageal squamous cell carcinoma.

Aged↗

[Reevaluation of precancerous lesion of squamous cell carcinoma].

One hundred fifty-nine cases of esophageal carcinoma were reviewed retrospectively. There were 75 dysplastic lesions in 32 cases (20.1%). Although the continuity of dysplastic lesions to the areas of carcinoma was not so frequent (48.0%), it was more often encountered in severe rather than in moderate or mild dysplasia, which suggested some relationship between the severity of dysplasia and carcinoma. Using a silver colloid staining technique, nucleolar organizer region-associated proteins (NOR) were studied in paraffin sections of 22 normal epithelia, 22 dysplasias, 17 carcinomas in situ (CIS), and 14 invasive carcinomas. The mean numbers of NOR in the nucleus were 1.77 +/- 0.14 (mean +/- SD) in normal epithelium, 2.16 +/- 0.30 in dysplasia, 2.78 +/- 0.51 in CIS, and 3.67 +/- 0.85 in invasive carcinoma. On the other hand, the NOR number in the atypical layer of the dysplasia was 2.60 +/- 0.39, which was almost the same level as that of CIS. These results suggest that atypical layers in esophageal dysplasia already have the same level of proliferative activity judging from the NOR numbers. Immunohistochemical staining for P53 protein revealed that, in the 13 cases with positive staining of the cancer tissue, 79.1% of dysplastic lesions were also positively stained. These results suggested that, although dysplasia was not carcinoma because of the restriction in the mucosa without invasion, the biological nature of dysplasia might be considered as serious a lesion as carcinoma itself.

Carcinoma, Squamous Cell↗

[Strategy for the treatment of esophageal carcinoma].

Esophageal carcinoma is classified as one of the most malignant neoplasms owing to the difficulty of early detection, frequent lymph node metastasis, and high incidence of recurrence even after curative resection of the lesion. According to the increase of early cases of esophageal carcinoma with the progress of the diagnostic technique, endoscopic mucosal resection and blunt resection of the esophagus have come to be performed in cases with quite early carcinoma or poor risk factors. Hyperthermo-chemo-radiotherapy (HCR) is extremely effective for esophageal carcinoma, especially for the advanced cases. The 1-, 3- and 5-year survival rates of the cases treated with preoperative HCR and chemo-radiotherapy (CR) were 64.6, 35.0 and 23.9%, against 46.9, 20.0 and 3.4%, respectively. The prognosis of the cases treated with HCR was significantly better than that for cases treated with CR. Moreover, for far-advanced esophageal carcinoma cases, palliative therapy such as intubation should be performed to assure quality of life (QOL). Strict follow-up including postoperative combined therapies is required for an improved prognosis in esophageal carcinoma.

Combined Modality Therapy↗

[A case of amylase producing lung cancer].

The patient was a 72-year-old man, who was admitted to our hospital because of cough. Chest X-rays showed a mass shadow in the right lower lung field. Amylase activities in serum and urine were extremely high. Amylase isozyme pattern identified salivary type amylase. Cytological examination of the sputum suggested adenocarcinoma. Amylase activities in serum and urine gradually decreased with the administration of chemotherapy. Afterwards, pleural effusion increased, and the amylase activity in pleural fluid was also extremely high. Pleural fluid also showed adenocarcinoma. Enzyme-labeled antibody method (PAP) on this specimen from pleural fluid proved that tumor cells were producing amylase ectopically.

Adenocarcinoma↗

Disseminated subcutaneous Nocardia asteroides abscesses in a patient after bone marrow transplantation.

We describe an unusual case of disseminated subcutaneous abscesses caused by Nocardia asteroides in a 17-year-old female with AML undergoing allogeneic BMT. She was receiving immunosuppressive therapy with CYA and a corticosteroid for acute GVHD, and maintenance therapy with ganciclovir for interstitial pneumonia (IP) caused by CMV, but was not neutropenic. The subcutaneous abscesses spread from the primary infection on her right anterior leg to both thighs, the left buttock, both upper arms, the left forearm and right shoulder, indicating hematogenous dissemination. Nocardia asteroides was identified from biopsy material in culture. The patient was successfully treated with a combination of trimethoprim/sulfamethoxazole (TMP/SMX) and minocycline, given for 3 months. The possibility of nocardiosis should be considered in the differential diagnosis of such patients.

Abscess↗

Plasminogen activator system in human breast cancer.

We measured antigen levels of 2 kinds of plasminogen activator, tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (UK), as well as those of their primary inhibitors, type-I plasminogen activator inhibitor (PAI-1) and type-2 plasminogen activator inhibitor (PAI-2), in tissue extracts from benign and malignant breast tumors. Tumor tissue samples from 40 fibroadenomas and 40 breast cancers were examined. t-PA antigen levels were the same in the 2 groups. Malignant tumors contained higher levels of UK antigen than did benign tumors. In the case of breast cancer, UK antigen levels of tumors with axillary lymph-node involvement were significantly higher than those of tumors without lymph-node involvement. PAI-1 and PAI-2 antigen levels of breast-cancer tissue samples were higher than those of fibroadenoma samples. PAI-1 antigen levels of carcinomas with lymph-node involvement were also significantly higher than those of carcinomas without node involvement. PAI-2 antigen levels, on the contrary, were higher in carcinomas without node involvement. UK, PAI-1 and PAI-2 antigen levels are potentially excellent independent factors for prediction of the metastatic potential of breast cancers.

Breast Neoplasms↗

Intragenic homozygous deletion of the WT1 gene in Wilms' tumor.

One example of intragenic homozygous deletion of the WT1 gene on chromosome 11p13 was found after screening 42 samples of Wilms' tumor DNA from Japanese patients. After construction of a restriction map for the genomic sequence covering the 3' half of the gene, the deletion was analysed at the nucleotide sequence level. The deletion occurred in the patient's germline on his paternal chromosome, and most of the short arm of his maternal chromosome 11 was subsequently lost in the tumor. The size of the deletion was about 8 kb, removing exons 6 and 7 and resulting in premature termination. The deletion seemed to be created by recombination between short homologous sequences found in an Alu repeat, with a 16-bp duplication left at the junction. This case conforms to a two-hit model for the genesis of a certain group of tumors, and supports the hypothesis that WT1 is one of the recessive oncogenes responsible for Wilms' tumor.

Base Sequence↗