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Biomedical subjects

H Kitada

Publications and source records attributed to H Kitada.

At least 19 recordsLinked to original sources

Activation of the alternative complement pathway by Agaricus blazei Murill.

Components of Agaricus blazei Murill have been demonstrated to have a wide range of immunopotentiating activities. The present study was designed to evaluate the effect of A. blazei Murill upon activation of the complement system in human serum in vitro. Additional studies were performed to determine the cytotoxic effect of complement-opsonized particles of A. blazei Murill against human tumor cells in culture. A fine particle of A. blazei Murill (ABP), prepared by mechanical disruption, was used throughout the experiments. ABP activated the human complement system via the alternative pathway in human serum. Activation of the alternative pathway was both time- and dose-dependent. When the particles from fruiting bodies of A. blazei Murill (ABP-F) were reacted with human serum, the formation of complement-opsonized ABP, iC3b-ABP-F complexes, and binding of the complexes to human peripheral blood monocytes, were demonstrated in vitro by immunofluorescence. Further, the resident human peripheral nucleated cells incubated in the presence of iC3b-ABP-F complexes inhibited the proliferation of human tumor cell line TPC-1 in vitro.

Adult↗

Effect of FR167653 on pancreatic ischemia-reperfusion injury in dogs.

BACKGROUND: The role of inflammatory cytokines is still unclear in ischemia-reperfusion injury of the pancreas. We investigated the effect of FR167653 (FR), a newly developed compound that is a potent suppressor of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on ischemia-reperfusion injury of the isolated pancreatic tail in dogs. METHODS: The tail of the pancreas was subjected to ischemia for 90 minutes. During occlusion of the vascular inflow, the head of the pancreas was removed. A control group (n = 14) and an FR treatment group (n = 11) were evaluated for survival rate, tissue blood flow, arterial oxygen pressure (Pao(2)), serum amylase and lipase levels, glucose and insulin, liver enzymes, creatinine, IL-1beta mRNA in the peripheral blood, and histopathology. RESULTS: Six of the 14 control animals and 2 of the 11 FR-treated animals died. The FR treatment group showed lower amylase (P=.037) and lipase (P =.030) levels, lower IL-1beta mRNA expression (P =.033), and less pancreatic tissue damage (P =.041) than did the control group, but there was no remarkable change in endocrine function (P =.422). Pao(2) during the acute phase in the FR treatment group was maintained (P=.009), but pulmonary tissue was damaged. Results of biochemical and histologic examinations of the liver and kidneys were unremarkable. CONCLUSIONS: FR ameliorates ischemia-reperfusion injury of the pancreas and reduces the production of inflammatory cytokines that may contribute to secondary damage to distant organs.

Animals↗

Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tumor development initiated by N-nitrosobis(2-hydroxypropyl)amine in rats.

The effects of antibiotics and anti-inflammatory drugs on the promotion stage of lung carcinogenesis initiated with N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats were investigated in two experiments with a similar protocol. In experiment 1, rats received tap water containing 2000 p.p.m. BHP for 12 weeks followed by basal diet or basal diet containing 0.02% erythromycin (EM), 0. 04% ampicillin (ABPC), 1.5% sho-saiko-to, 0.02% EM plus 1.5% sho-saiko-to or 0.04% ABPC plus 1.5% sho-saiko-to for 8 weeks after BHP administration. The development of adenocarcinomas (AC), squamous cell carcinomas (SqC) and adenosquamous carcinomas (ASqC) was completely inhibited in rats given ABPC plus sho-saiko-to and the numbers of lung lesions including alveolar hyperplasias, adenomas and carcinomas were decreased in rats given EM plus sho-saiko-to or ABPC plus sho-saiko-to. Neutrophil and macrophage infiltration into alveolar spaces of the lung were also markedly suppressed. In experiment 2, rats received BHP in the same manner as in experiment 1 and basal diet or basal diet containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC plus 0.006% piroxicam and 0.04% ABPC plus 0.75% ougon for 8 weeks. The incidence and number of carcinomas, including ACs, SqCs and ASqCs were decreased in rats given ABPC plus piroxicam or ABPC plus ougon. Bacteria, mainly Escherichia coli, were detected in broncho-alveolar lavage of rats receiving BHP. The results suggest that chronic inflammation might be involved in the progression of lung carcinogenesis by BHP in rats and its suppression may therefore be useful as a chemopreventive strategy in lung cancer clinics.

Adenocarcinoma↗

Three-phase bone scintigraphy and viability of vascularized bone grafts for mandibular reconstruction.

Three-phase bone scintigraphy was undertaken to check the anastomotic patency and monitor the viability of vascularized bone grafts. Ten consecutive patients who underwent vascularized bone grafting of the mandible were reviewed. A successful clinical outcome was achieved in 8 patients. The graft failed in 2 patients. In this series, 3-phase bone scintigraphy of radiolabeled (99m)Tc-methylene-diphosphonate was performed at 7 days, and at 1, 3, 6, and 12 months after reconstruction. Assessments made using 3-phase bone images were compared with the clinical findings. The clinical outcome of the cases presented in our series correlated extremely well with 3-phase bone images. Three-phase bone scintigraphy is a useful method for the assessment of patency and viability of vascularized bone grafts. The use of this method can be very helpful in assessing the anastomotic patency and viability of a graft which for clinical reasons is suspected of being non-viable.

Aged↗

Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir.

Xenopus laevis oocytes were used as a gene expression system to characterize the carrier-mediated transport of valacyclovir (vacv), the L-valine ester prodrug of the acyclic nucleoside acyclovir (acv). A significant increase in the uptake of [3H]vacv by Xenopus laevis oocytes injected with human intestinal peptide transporter (hPepT1) cRNA compared to the uptake by water injected oocytes indicated that vacv was translocated by hPepT1. Vacv uptake was found to be concentration dependent, saturable (K(m) = 5.94 +/- 1.91 mM and Jmax = 1.68 +/- 0.25 nmoles/hr/oocyte), pH dependent, and inhibited by various known substrates of hPepT1 but not by acv, valine or pentaglycine. Vacv also inhibited the uptake of 14C-glycylsarcosine, a known substrate of hPepT1, in a concentration-dependent manner (Ki = 4.08 +/- 1.02 mM). These results demonstrate that human intestinal peptide transporter hPepT1 has broad specificity since it recognizes vacv as a substrate even though it lacks a typical peptide bond.

Acyclovir↗

[Intra-arterial infusion chemotherapy for advanced endometrial cancer before surgical treatment].

Nine cases of advanced uterine body cancer (stage III: 8, stage IVa: 1) were treated by intra-arterial infusion chemotherapy before curative operation. This treatment produced primary tumors smaller than half sizes in eight cases. Necrotic changes were found in over two-thirds of the lesions in six cases. This chemotherapy enabled us to operate curatively in seven cases. After the operations, we performed various types of treatment including intra-arterial infusion chemotherapy. No evidences of disease have been found in four cases, but there is no significant difference between the groups receiving and not receiving the intra-arterial infusion chemotherapy (n = 16) in terms of survival rate of stage III. Further study of the prognosis is necessary.

Adenocarcinoma↗

Adenoid cystic carcinoma of the esophagus: report of a case.

The case of a 70-year-old Japanese woman with adenoid cystic carcinoma (ACC) of the esophagus is presented herein. The patient presented with progressive dysphagia, and an upper gastrointestinal series and esophagogastroscopy revealed a protruding tumor located in the middle portion of the esophagus. Ultrasonography (US) and computed tomography (CT) suggested a lymph node metastasis between the left lobe of the liver and the esophagocardiac junction. Histopathologic examination of a biopsy specimen showed squamous cell carcinoma (SCC) and a subtotal esophagectomy was performed under the preoperative diagnosis of esophageal carcinoma. However, the histopathologic diagnosis of the resected specimen proved to be ACC of the esophagus with a lymph node metastasis around the left gastric artery. We report the clinicopathological findings of this case and briefly discuss the clinical implications of ACC.

Aged↗

Pancreatic tumor formed by infiltration of adult T-cell leukemia cells.

CONCLUSION: We have described a case of pancreatic tumor formed by adult T-cell leukemia (ATL) cell infiltration. BACKGROUND: The patient was diagnosed as chronic ATL hematologically with the findings of increased number of atypical lymphocytes, ATL cells in the peripheral blood, and positive human T-cell leukemia virus type I (HTLV-I) antibody in the serum. The pancreatic tumor was identified by ultrasonography and computed tomography as a diffusely swollen tumor from the body to the tail of the pancreas. Biopsy specimen confirmed the ATL cell infiltration into the pancreas immunohistochemically, and Southern blot analysis showed the integration of HTLV-I proviral DNA both in the pancreas and in the peripheral blood. RESULTS: The pancreatic tumor diminished spontaneously without chemotherapy when ATL cells in the peripheral blood disappeared by spontaneous regression.

Aged↗

Frequent mutations of Ki-ras but no mutations of Ha-ras and p53 in lung lesions induced by N-nitrosobis(2-hydroxypropyl)amine in rats.

Point mutations of the Ki-ras and p53 genes in rat lung lesions induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) were investigated by polymerase chain reaction-single strand conformation polymorphism analysis followed by direct sequencing using paraffin-embedded tissues. Male Wistar rats 6 wk old were given 2000 ppm BHP in drinking water for 15 wk. Another group was given drinking water without BHP. The rats were killed 20-27 wk after the beginning of the experiment. Lung adenomatous and squamous lesions, including carcinomas, were induced. The frequencies of Ki-ras mutations were 40% (six of 15) in alveolar hyperplasias, 36% (five of 14) in adenomas, 72% (18 of 25) in adenocarcinomas, 20% (three of 15) in squamous metaplasias, 50% (three of six) in squamous cell carcinomas, and 50% (five of 10) in adenosquamous carcinomas. The mutations were all G-->A transitions at the second position of codon 12; no other mutations were detected. However, Ha-ras mutations in exons 1 and 2 and p53 mutations in exons 5, 6, and 7 were not detected in adenocarcinomas and squamous cell carcinomas. These results indicate that Ki-ras mutation is an early genetic event in some adenomatous and squamous lung carcinogeneses and that Ki-ras mutations can cause benign lesions to convert to malignant lesions. The results also show that Ha-ras and p53 mutations are not involved in rat lung carcinogenesis induced by BHP.

Adenocarcinoma↗

Inhibitory effects of N,N'-diphenyl-p-phenylenediamine on the early stage of the enhanced hepatocarcinogenesis caused by coadministration of ethionine and a choline-deficient L-amino acid-defined diet in rats.

Effects of N,N'-diphenyl-p-phenylenediamine (DPPD), an antioxidant, on liver carcinogenesis caused by a choline-deficient L-amino acid-defined (CDAA) diet containing ethionine were studied in Fischer 344 rats. Male animals, 6 weeks old, were fed a CDAA diet, a choline-supplemented L-amino acid-defined (CSAA) diet or a CDAA diet containing 0.05% ethionine with or without 0.2% DPPD. Histological changes and lesions positive for gamma-glutamyltransferase (GGT) were analyzed 12 weeks after the beginning of the experiment. The levels of 8-hydroxyguanine (8-OHGua) in DNA and 2-thiobarbituric acid-reacting substances (TBARS) were measured as the parameters for cellular oxidative damage after 4 and 11 days of treatment. Expression of c-myc and c-Ha-ras was also investigated in relation to cell proliferation after 2, 4, 8 and 11 days. Histologically, development of diffuse fatty liver observed in rats fed a CDAA diet was inhibited, while massive oval cell proliferation and cholangiofibrosis resulted from the addition of ethionine with/without DPPD. The sizes but not numbers of GGT-positive lesions seen in the liver of rats fed a CDAA diet were increased and the levels of 8-OHGua formation and TBARS generation were also increased by the ethionine supplement. Both numbers and sizes of GGT-positive lesions were decreased and the level of TBARS, but not 8-OHGua, was decreased by adding DPPD. The increased expression of c-myc and c-Ha-ras detected in the liver of rats fed a CDAA diet was further increased by addition of ethionine and again reduced by DPPD. These results indicate that an antioxidant DPPD can inhibit the early stage of enhanced hepatocarcinogenesis caused by coadministration of ethionine and a CDAA diet, by blocking cellular oxidative damage as well as c-myc and c-Ha-ras expression.

Amino Acids↗

Disturbance of the cell cycle with colchicine enhances the growth advantage of diethylnitrosamine-initiated hepatocytes in rats.

The effect of cell cycle disturbance due to colchicine on the induction of enzyme-altered foci during liver regeneration in rats was studied. For initiation, diethylnitrosamine (DEN) at a dose of 10 mg/kg was injected intraperitoneally and partial hepatectomy (PH) was performed 4 h thereafter. Colchicine at doses of 0, 0.1, 0.25 and 0.5 mg/kg was injected intraperitoneally 1 and 3 days after the initiation, followed by application of selection pressure consisting of 2-acetylaminofluorene (AAF) and carbon tetrachloride (CCl4) administration. As end point lesions, gamma-glutamyltransferase (GGT)-positive enzyme-altered foci were assayed at week 5. There was no significant effect of colchicine on numbers of foci. However, a significant, dose-dependent increase in the area of GGT-positive lesions in the groups treated with colchicine was observed. Bromodeoxyuridine labeling indices were higher in foci induced in colchicine-treated rats than in the untreated rats. In a separate experiment, serum glutamic pyruvic transaminase was not increased significantly after DEN and colchicine treatment, and the mitotic index at 6 days after PH was increased in the liver of colchicine-treated rats. These results suggest that the cell cycle disturbance induced by colchicine causes more pronounced selective growth of cells initiated by DEN and colchicine, and this experimental model may be useful for analyzing the mechanisms underlying that growth advantage and the effects of cell cycle abnormalities in liver carcinogenesis.

Animals↗

Prevention by methionine of enhancement of hepatocarcinogenesis by coadministration of a choline-deficient L-amino acid-defined diet and ethionine in rats.

The effects of methionine on hepatocarcinogenesis induced by coadministration of a choline-deficient L-amino acid-defined (CDAA) diet and ethionine were examined. F344 male rats were divided into 4 experimental groups. Groups 1 and 2 received the CDAA diet and a choline-supplemented L-amino acid-defined (CSAA)++ diet, respectively. Group 3 received the CDAA diet containing 0.05% ethionine, and group 4 the CDAA diet containing 0.05% ethionine and 0.47% methionine. Animals were killed after 12 weeks of treatment. Histologically, the CDAA diet induced intracellular fat accumulation and foci. In contrast, ethionine caused not only foci, but also hyperplastic nodules, cholangiofibrosis and the proliferation of oval cells without such fat accumulation. Methionine abolished the development of all of the liver lesions induced by coadministration of the CDAA diet and ethionine. To investigate the effects of methionine on induction of c-myc and c-Ha-ras expression, as well as generation of 8-hydroxyguanine (8-OHGua) and 2-thiobarbituric acid-reacting substances (TBARS), by coadministration of the CDAA diet and ethionine, subgroups of 3 to 5 animals were killed at 2, 4, 8, or 11 days after the beginning of the experiment. Coadministration of the CDAA diet and ethionine markedly enhanced the level of expression of c-myc and c-Ha-ras, 8-OHGua formation and TBARS generation as compared with the CDAA or CSAA diet within 11 days, and methionine blocks these actions. These results indicate that addition of methionine prevents the induction of c-myc and c-Ha-ras expression, 8-OHGua formation and TBARS generation, as well as hepatocellular lesions, by coadministration of the CDAA diet and ethionine in rats, and suggest a possible involvement of oxidative stress and gene expression in hepatocarcinogenesis by these agents.

Amino Acids↗

Renal glomerular fibrosis in two pigs.

Massive deposition of collagen fibrils was found in the renal glomeruli of two pigs. The affected pigs were a 6-month-old female hybrid pig with systemic mycobacteriosis and a retired sow showing azotemia. Microscopically, various amounts of a homogeneous eosinophilic substance were deposited within the expanded mesangium of almost all renal glomeruli in both cases. The deposit was also seen occasionally on the glomerular capillary walls in the sow. Capillary lumens were occluded in the glomerular segments with heavy deposition. Obsolescent glomeruli were often surrounded by lymphoid cells. The deposited substance was Congo red negative and stained deep blue with Heidenhain's azan staining. Immunohistochemical evaluation revealed that the major component of the homogeneous substance was type-III collagen. Electron microscopic examination showed that the deposits were masses of fibrils of variable length, width, and shape. The fibrils had transverse bands with a periodicity of approximately 60 nm, consistent with collagen fibrils. These glomerular changes were identical to those of collagenofibrotic glomerulonephropathy that has recently been described as a new glomerular disease in humans. The glomerular lesion may be the result of unusual production of type-III collagen by mesangial cells.

Animals↗

[A case of histological complete remission by preoperative intraarterial infusion chemotherapy].

We experienced a case of histological complete remission by preoperative intraarterial infusion chemotherapy in the treatment of histologically diagnosed endometrial cancer of well differentiated type. MRI demonstrated invasion of the myometrium to a depth of more than 1/2 and left partial parametrium. This patient was given intra-uterine arterial infusion chemotherapy twice (CDDP & ADM ia, CPA iv). Radical hysterectomy was done 3 weeks after intraarterial infusion chemotherapy. The extirpated uterus was histologically complete remission. Thus, in this case shows that intraarterial infusion chemotherapy is effective for neo-adjuvant chemotherapy of endometrial cancer.

Adenocarcinoma↗

Expression of cripto in human pancreatic tumors.

The expression of cripto gene product was examined immunohistochemically in 45 surgically resected pancreatic tumors, including 32 invasive ductal carcinomas, 4 intraductal papillary adenocarcinomas, 4 intraductal papillary adenomas, 2 mucinous cystadenomas, 2 islet cell tumors, and one solid and cystic tumor, and compared with that in 32 areas of accompanying chronic pancreatitis present in the cases of invasive ductal carcinomas and 5 non-tumorous areas of pancreas without pancreatitis. All pancreatic ductal tumors including adenomas and carcinomas showed positive staining with no difference in terms of staining intensity among intraductal tumors and invasive carcinomas with or without mucin hypersecretion. Islet cell tumors were positively stained but the solid and cystic tumor was negative. Duct epithelial cells and acinar cells were negative but islet cells were positive in the pancreas tissues without pancreatitis. Cells arranged in duct-like structures in areas of accompanying chronic pancreatitis were positively stained. The results suggest that cripto expression might be associated with a growth advantage of tumor cells and also with differentiation to form duct-like structures.

Biomarkers, Tumor↗