Search PubMed⌕ Search

Biomedical subjects

T Iwanaga

Publications and source records attributed to T Iwanaga.

At least 181 records · Page 10Linked to original sources
PubMed1994

[Promotion of hematogenous metastasis in relation to endothelial cell injury by treatment with anticancer drugs].

It has been reported that anticancer drugs at high concentration increase experimental hematogenous metastasis owing to endothelial injury. In this study, we evaluate the effects of anticancer drugs at clinical doses on endothelial cells in the process of metastasis. To do so, we have developed in vitro assay methods which can assess endothelial cell retraction and barrier function against invasion by tumor cells. 5-FU at clinical doses caused neither retraction nor decreasing barrier function, however, ADR and MMC caused retraction of endothelial cells and increased invasion by tumor cells. These effects reached maximum 12 hours after treatment with ADR or MMC, and the number of liver metastases was also significantly increased in in vivo study when tumor cells were injected via portal vein at 12 hours after administration of ADR. It was suggested that some kinds of anticancer drugs at the clinical dose may increase hematogenous metastasis in treatments.

Animals↗
PubMed1994

[An extended operation for scirrhous gastric cancer--its significance and procedure].

We have been performing an extended operation for scirrhous gastric cancer, namely left upper abdominal exenteration plus Appleby's method, and compared the prognosis among macroscopic subtype classifications. The surgical procedure of left upper abdominal exenteration plus Appleby's method is to resect the neighboring organs of the stomach in an en bloc fashion. It consists of total gastrectomy, partial pancreatectomy, splenectomy, transverse colectomy, cholecystectomy, resection of the left adrenal gland, and ligation and resection of the common hepatic artery. D4 lymph node dissection is carried out. Extended operations were performed for 45 cases of P0-1 scirrhous gastric cancer in 1983-1990. There were 25, 17 and 3 cases of giant fold type, erosive type and stenotic type scirrhous gastric cancers, respectively. Positive lymph node metastases were found in 64% of giant fold type cases and 82% of erosive type cases. In Po, T3-4 cases, cytology of intraoperative peritoneal lavage was positive in 27% of giant fold type cases and 50% of erosive type cases. Although there were no obvious macroscopic invasions found during the operative procedure, later histological study showed invasion to the left adrenal gland in 14% of giant fold type cases and 0% of erosive type cases, and invasion to the transverse colon in 21% of giant fold type cases and 15% of fold type and erosive type scirrhous gastric cancer according to the histological invasion of transverse colon were 25% in positive cases and 27% in negative cases (p = 0.27), 0% in positive cases and 27% in negative cases (p = 0.27), respectively. In giant fold type scirrhous gastric cancer, the extended operation is favorable. In erosive type scirrhous gastric cancer, peritoneal dissemination is observed with a high incidence. Therefore, prophylactic therapy is significant.

Adenocarcinoma, Scirrhous↗
PubMed1994

[Working hours of maternal and child health service personnel by type of occupation and municipality].

The working hours of maternal and child health service personnel were surveyed to describe the characteristics of maternal and child health activities by municipality in 1989. Questionnaires were sent to 24 health centers and the 122 municipalities they represent, and responses from 19 health centers and 103 municipalities were received. The results were as follows: 1) Of all health service personnel, the working hours for public health nurses per 100 births per year was the highest, followed by maternal and child health volunteers, office workers, nurses and physicians. 2) Total working hours increased with number of births per year. 3) No significant correlation was found in total working hours of personnel in health centers with those in the municipalities they represent. Total working hours of personnel of health centers and the municipalities they represent decreased as population size increased. 4) The number of types of occupation involved in maternal and child health service increased as the size of population of the municipality increased. 5) Of the total working hours for all types of occupations, the proportion of working hours for public health nurses averaged about 40% to 50%. 6) The proportion of working hours for infant health examinations increased with increasing population size of the municipality. However, the proportion of the hours for planning and evaluation decreased with increasing population size of the municipality. From this survey, it appears that maternal and child health activities by municipalities differed according to the population size of the municipality.

Child↗
PubMed1994

[A multi-institutional study for prevalence, diagnosis and treatment of deep fungal infection in gastrointestinal surgery].

A multi-institutional study was conducted for prevalence, diagnosis and treatment of deep fungal infection in gastrointestinal surgery. Forty five cases including thirty six complete cases were entered basing on the diagnostic criteria and the mortality of complete cases was 17%. By the administration of miconazole (MCZ), clinical response rate was obtained in 87%, mycological radiation rate in 82% and valuable rate in 71%, with occurrence of side effects in 20%. Fungal endophthalmitis was found in 41% (12/29 cases). beta-glucan [the toxinometer method (T), the Seikagaku-Kogyo method (S)] and candida antigen [the C and-Tec method (C)] were monitored as sero-diagnostic methods, the positive rates for all cases, fungemia, and mycosis of which were 63, 83, 62% (T), 88, 100, 92% (S) and 52, 83, 50% (C), respectively. After mycological re-classification, the positive rates of the T method and endophthalmitis, and the mortality rates were 86, 60, 38% in fungemia, 63, 43, 23% in urinary tract infection, 64, 80, 7% in TPN infection, and 33, 17, 33% in drain infection, respectively. High association of endophthalmitis was found in TPN infection. The beta-glucan assay and a prospective ophthalmoscopic examination are useful for the early diagnosis of deep fungal infection and it is reasonable to treat patients in gastrointestinal surgery by MCZ when mycosis is confirmed or suspected.

Digestive System Surgical Procedures↗
PubMed1993

Increased expression of sialyl Lewisx antigen correlates with poor survival in patients with colorectal carcinoma: clinicopathological and immunohistochemical study.

We have previously shown that sialyl Lewisx antigen (sLex) (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAC-R) has an important functional role in defining the invasion and metastasis of human colorectal carcinoma. The results were derived from the clinical specimens obtained at surgery or experimental metastasis of human colon carcinoma variant expressing different levels of sLex in nude mice. In the present study, we immunohistochemically examined 132 human colorectal carcinomas for the expression of sLex to investigate whether this antigen expression could serve as a prognostic parameter. The tumors were divided into two groups: sLex positive and sLex negative. The incidence of sLex positive was correlated with the depth of tumor invasion, the presence of the lymph node metastasis, lymphatic invasion, and the disease stage. The difference was statistically significant (P = 0.0026; P = 0.0002; P = 0.003; P = 0.0013; respectively). Based on the data on 114 patients who underwent curative resections, incidence of the disease recurrence was assessed. The sLex-positive patients had higher incidence of recurrence in distant organs, especially in the liver, than that of the sLex-negative patients. The 5-year disease free survival rates of sLex-positive and -negative patients were 57.7 and 89.1%, respectively (P = 0.0002). The difference of 5-year overall survival rates between the two were also significant (sLex positive, 58.3%; sLex negative, 93.0%: P < 0.0001). By Cox multivariate analysis, sLex expression levels remained the best discriminant of disease-free survival (P = 0.035) and overall survival (P = 0.0081). These results suggest that increased expression of sLex is correlated with the extent of malignancy and high incidence of recurrence and consequently with survival of colorectal carcinoma patients. Thus sLex may prove to be a potent marker of recurrence in colorectal carcinoma patients.

Adult↗
PubMed1993

Cellular uptake of phosphorothioate oligodeoxynucleotides is negatively affected by cell density in a transformed rat tracheal epithelial cell line: implication for antisense approaches.

Antisense oligodeoxynucleotides have been used to specifically inhibit the expression of a variety of genes. In the process of testing phosphorothioate oligodeoxynucleotides (S-oligos) as specific inhibitors of transforming growth factor alpha synthesis, we observed that the efficiency of cellular uptake of S-oligos was not constant throughout the culture period but decreased as the cell densities increased. Our data suggest that the mechanism by which oligonucleotides enter cells is negatively affected by increased cell density. These results emphasize the importance of determining uptake kinetics before designing and interpreting antisense experiments using phosphorothioate oligonucleotides.

Animals↗
PubMed1993

Gastric remnant cancer as a metachronous multiple lesion.

The pathological characteristics and natural history of 35 gastric remnant cancers after partial gastrectomy for a malignant condition and 16 gastric cancers after gastrectomy for benign conditions were compared. Gastric remnant cancer following malignant disease was characterized by a well defined rather than diffuse appearance (in 43 versus 12 per cent of gastric remnant cancers after benign conditions, P < 0.05), location away from the anastomosis (83 versus 25 per cent, P < 0.05) and a shorter interval after the first operation (5-14 versus > or = 20 years, P < 0.01). The 15- and 16-year survival rates appeared to be worse for gastric remnant cancer after malignant than after benign disease, but there was no statistically significant difference between the two groups in a generalized Wilcoxon test. In the former, direct invasion to adjacent organs was frequently observed. These findings suggest that gastric remnant cancer after gastrectomy for malignancy may be a metachronous multiple lesion, while that following benign disease may occur as a new cancer caused by the partial gastrectomy. To improve the survival of patients with cancer after gastrectomy for malignancy, a rational extended operation may be useful.

Adult↗
PubMed1993

Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self-superantigens and processed DR alpha-derived peptide.

We have established a set of transgenic mouse lines in which the HLA-DRA gene was expressed in different cell types. In one line (DR alpha-24), DR alpha E beta b molecules were expressed on thymic medullary and cortical epithelial cells and all lineages of bone marrow-derived antigen-presenting cells (APC) except for thymic macrophages. By contrast, expression of the molecules in another line (DR alpha-30) was found on thymic medullary and cortical epithelial cells but not on bone marrow-derived APC in the thymus and periphery. To evaluate the role of thymic epithelial cells in acquisition of T cell tolerance, comparative analysis of DR alpha-24 and DR alpha-30 was performed. In DR alpha-30, T cells expressing TcR V beta 5 and V beta 11 were eliminated to comparable levels to those in DR alpha-24, suggesting that expression of the DR alpha E beta b molecules on thymic epithelial cells are sufficient for clonal deletion of the self-superantigen-reactive T cells. In addition, CD4+ T cells from DR alpha-30 as well as those from DR alpha-24 were tolerant to DR alpha-derived peptide/I-Ab complex expressed on spleen cells from DR alpha-24 even in the presence of exogenous interleukin-2. These observations suggest that expression of the DR alpha chain in thymic epithelial cells could induce T cell tolerance directed toward naturally processed DR alpha-derived peptide bound to I-Ab molecules, probably via clonal deletion of the self-reactive T cells.

Animals↗
PubMed1993

Expression of nucleoside diphosphate kinase/nm23 gene product in human pancreatic cancer: an association with lymph node metastasis and tumor invasion.

The expression of nucleoside diphosphate (NDP) kinase/nm23 has been reported to be inversely related to metastasizing potential of experimental cells and human breast cancer. In the present study, levels of NDP kinase/nm23 gene product in curatively resected human pancreatic adenocarcinomas were examined immunohistochemically using anti-NDP kinase antibody. Immunoreactivity for NDP kinase varied between tumors. Of 31 pancreatic tumors examined, 17 (55%; positive staining group) showed strong immunoreactivity for the NDP kinase, while 14 (45%; negative staining group) showed low or no immunoreactivity. Positive staining was associated with higher incidence of lymph node metastasis (13/17; 77%) and perineural invasion (13/17; 77%) than negative staining (5/14, 36%, P < 0.03; 4/14, 29%, P < 0.01, respectively). Positive staining was also associated with shorter overall survival and relapse-free survival than negative staining (P < 0.01, P < 0.01, respectively). No significant difference in age, sex, size, location of tumor, serum carcinoembryonic antigen (CEA) level, or histological type was found between the two groups. These results showed that, in contrast to the reports on breast cancer, NDP kinase/nm23 expression in human pancreatic cancer is positively associated with lymph node metastasis or perineural invasion and with poor prognosis. These, together with other previous reports, suggest that NDP kinase may play an important role in cancer progression or aggressiveness by altering its expression in a tissue-specific manner.

Adenocarcinoma↗
PubMed1993

Level of serum gastrin as a predictor of liver metastasis from colorectal cancer.

There have been no reports on the relationship between serum gastrin level and liver metastasis in human colorectal cancer. One hundred forty patients who underwent surgery for colorectal cancer (T2 or more) were enrolled in this study. Fasting serum gastrin level was determined prior to the surgery. Incidence of liver metastasis was significantly (P < 0.01) higher in patients with a serum gastrin level of > or = 150 pg/ml (37 percent; 14/38) than in those with a serum gastrin level of < 150 pg/ml (12 percent; 12/102). As for the tumors with venous invasion, liver metastasis was detected in 11 of 55 patients (20 percent) with a serum gastrin level of < 150 pg/ml; however, it was detected in 11 of 19 patients (58 percent) with a serum gastrin level of > or = 150 pg/ml (P < 0.01). These results suggest that serum gastrin serves as a useful predictor of liver metastasis from colorectal cancer and that the predictability of liver metastasis can be improved when both serum gastrin level and venous invasion are considered.

Adult↗
PubMed1993

Aggregation of macrophages in the tips of intestinal villi in guinea pigs: their possible role in the phagocytosis of effete epithelial cells.

Numerous macrophages were found aggregated in the lamina propria at the tips of villi in the small intestine of guinea pigs. These macrophages extended their pseudopodia into the epithelial lining and internalized fragments of effete enterocytes in their phagosomes. The epithelium of the villus tips was found to be infiltrated with numerous lymphocytes. They possessed electron-dense granules characteristic of natural killer cells, and actively interdigitated with the enterocytes. The latter were either fragmented or extensively lost in their basal cytoplasm, often leaving an attenuated apical cytoplasm of the cell. Immunohistochemical labeling using bromodeoxyuridine demonstrated that at 96 h after its administration, immunolabeled nuclei were encountered in the cytoplasm of macrophages in the lamina propria at the villus tips. These findings suggest that in the guinea pig, effete enterocytes are not simply exfoliated into the lumen, but are damaged by intraepithelial lymphocytes possessing a natural killer cytotoxicity, and subsequently phagocytosed by subepithelial macrophages.

Animals↗
PubMed1993

A novel mechanism for disposing of effete epithelial cells in the small intestine of guinea pigs.

BACKGROUND: We previously showed that at the villus tips in the small intestine of guinea pigs effete enterocytes are not simply exfoliated into the lumen but phagocytosed by subepithelial macrophages, leaving only a thin apical cell portion in the epithelial lining. The aim of the present study is to investigate the fate of these apical pieces of enterocytes. METHODS: The ileum of guinea pigs was perfusion-fixed and processed for transmission and scanning electron microscopic observation. RESULTS: The apical cytoplasmic plates were found to be pushed by neighboring enterocytes and protruded from the epithelial surface, finally being pinched off into the lumen. In this process observed at the villus tips, the junctional complexes between the apical cytoplasmic plate and the adjacent enterocytes were preserved until the pinching-off of the plate. Luminal cell elements revealed a rich existence of cup-shaped or spherical cell fragments covered with microvilli; nuclei were never observed in the luminal fragments. CONCLUSIONS: The findings in the small intestine of the guinea pig are the first to account for the mechanism of the epithelial barriers being preserved while apoptotic enterocytes drop out at the tips of the villi.

Animals↗
PubMed1993

Nerve terminals associated with the central lacteal lymphatics in the duodenal and ileal villi of the monkey.

An intimate association of nerve fibers with the central lacteal endothelium was demonstrated in the duodenum and ileum of the monkey by immunohistochemistry and transmission electron microscopy. In the basal portion of the central lacteal, nerve fibers containing large cored vesicles and small clear vesicles were located closely beneath the lacteal endothelium. Identification of nerves was performed by immunohistochemistry using antisera against substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide, gastrin-releasing peptide and neuropeptide Y. These nerves contained immunoreactivities for SP and CGRP only. Some of the nerves, either singly or in a dense bundle, indented the endothelial cells to form a conspicuous cushion protruding into the lumen. The attenuated endothelium covering the cushion occasionally was failing, and the nerves were exposed to the lumen. Tight of occasionally subendothelial nerve terminals bundles formed a synapse-like association between themselves: a swollen axonal profile was invaginated by a finger-like projection of another axon, the latter being filled with synaptic vesicles. These results suggest that the central lacteal lymphatics might be afferently monitored, presumably with regard to the luminal pressure, and, at the same time, efferently modulated by these nerves.

Animals↗
PubMed1993

Species-differences in the process of apoptosis in epithelial cells of the small intestine: an ultrastructural and cytochemical study of luminal cell elements.

Our previous study demonstrated that in the small intestine of guinea pigs, apoptotic epithelial cells at the villus tips were phagocytosed by lamina propria macrophages, leaving only apical cytoplasmic plates, which thereafter were domed and extruded into the lumen. This finding contrasts with the generally accepted view that effete epithelial cells are simply exfoliated into the lumen. In order to explain this discrepancy, the present study examined luminal cell elements of the small intestine in the guinea pig, rat and mouse; the latter two have been favored species for studying the kinetics of intestinal cells. Light and electron microscopic observations indicated that the luminal fluid of the guinea pig contained numerous cytoplasmic fragments covered with long microvilli and not containing a nucleus; these fragments corresponded with the apical cytoplasm of apoptotic epithelial cells. In the rat and mouse, in contrast, luminal cell elements were represented by round cell bodies possessing a nucleus and microvillous border; the nucleus displayed compaction and segregation of chromatin at the periphery, a microscopic figure characteristic of apoptosis. As far as the rat and mouse are concerned, the present findings support the accepted view that epithelial cells undergoing apoptosis are exfoliated as total, nucleus-containing cells. In the guinea pig, in contrast, only an apical thin plate of effete cells is shed off, as our previous studies have suggested.

Animals↗
PubMed1993

Lateritin, a new inhibitor of acyl-CoA:cholesterol acyltransferase produced by Gibberella lateritium IFO 7188.

A new inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), designated lateritin, was isolated from the mycelial cake of Gibberella lateritium IFO 7188 by successive purification procedure of solvent extraction, silica gel column chromatography and reverse phase HPLC. Spectroscopic analyses of the compound yielded 4-methyl-6-(1-methylethyl)-3-phenylmethyl-1,4-perhydrooxazine-2,5- dione as the proposed structure. Lateritin inhibited rat liver ACAT activity by 50% at a concentration of 5.7 microM. This inhibition was time-dependent and irreversible.

Animals↗
PubMed1993

Palliative surgical treatment for recurrent and non-resectable hepatocellular carcinoma.

Of 275 patients who had a radical hepatic resection for HCC, 143 (52%) experienced recurrences. Of these 143 patients, the liver was the site of first recurrence in 130 patients (91%). The first form of therapy for recurrent patients was transarterial chemoembolization (TACE) in 82 (74%), hepatic resection in 15 (14%) and percutaneous ethanol injection in 6 (5%) of the 111 patients who received regional therapy. Post-recurrent survival rates of TACE and hepatic resection were 37%, 77% at 3 years and 17%, 77% at 5 years, respectively. Wrapping therapy was performed in seven patients, two of whom had received repeat TACE for intrahepatic recurrence; the remaining 5 were unresectable cases. After wrapping therapy, the area of previous collateral feeders was be supplied by the hepatic artery. The high level of AFP decreased dramatically. This procedure resulted in a complete response in 2 patients, a partial response in 3 and no change in 2. Overall survival was 4-54 months, and the median survival was 18 months. Two patients are still alive, 18 and 20 months after the procedure.

Adult↗