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S Uchino

Publications and source records attributed to S Uchino.

At least 91 records · Page 5Linked to original sources

Immune cell migration through the arterial wall in the murine lung during a pulmonary inflammatory response.

Perivascular accumulation of leukocytes in the lung was induced by intratracheal administration of sheep erythrocyte antigen to primed mice. The route of migration of intravascular leukocytes to the perivascular space in the lung, in particular from arteries, and the structure of lymphatic vessels among the aggregated leukocytes were examined by transmission electron microscopy. Leukocytes--lymphocytes, granulocytes, monocytes and macrophages--were demonstrated to adhere to the endothelial surface and to migrate between endothelial cells to reach the internal elastic lamina of arteries. Becoming conspicuously constricted, the leukocytes penetrate through this elastic lamina. They further migrate through the smooth muscle layer to the interstitium, passing through the external elastic laminar region. At 2 days after antigen administration, dilated lymphatic vessels containing large numbers of leukocytes in the lumen and bearing endothelial gaps open to the interstitium began to be seen. The lymphatic walls were more convoluted and richer in pinocytotic vesicles than those prior to antigen challenge. This study confirms the light microscopic findings by Curtis et al. (1990) that arteries, besides veins, venules and capillaries, may represent a major route of inflammatory cell entry into the lung parenchyme in an acute and vigorous immune response. In addition, lymphatic vessels were suggested to be newly formed for the transport of fluid and immune cells from the sites of inflammation in the lung.

Animals↗

[LEOPARD syndrome].

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Abnormalities, Multiple↗

Immunohistochemical detection of K-sam protein in stomach cancer.

The K-sam gene, originally isolated as an amplified gene from the stomach cancer cell line KATO-III, is characterized by its preferential amplification in the undifferentiated type (diffuse type) of stomach cancer and encodes one of the receptors for heparin-binding growth factors or fibroblast growth factors. The K-sam gene has been isolated by different methods and has been designated BEK, TK14, and Cek2. The receptor for keratinocyte growth factor was also found to be encoded by the same gene. To examine the expression of the K-sam protein in stomach cancer, polyclonal antibody pK1-2 was raised against the extracellular domain of the gene product. This antibody detected K-sam proteins by Western blot and flow cytometry analyses in stomach cancer cell lines KATO-III and HSC39, in which the K-sam gene is amplified and overexpressed. By immunohistochemical analysis, 20 of 38 cases of the undifferentiated type of advanced stomach cancer were K-sam positive, whereas none of 11 cases of the differentiated or intestinal type revealed K-sam staining. The K-sam product was observed predominantly in diffusely infiltrative lesions. In one autopsy case, the K-sam protein was detected only focally in the primary tumor, whereas markedly increased staining for the K-sam product was detected diffusely in the metastasized tumor in the lymph node and liver. These results suggest that K-sam overexpression is associated with the malignant phenotype of the undifferentiated type of stomach cancer, such as infiltrative growth and metastasis.

Amino Acid Sequence↗

High amplification of the hst-1 gene correlates with haematogenous recurrence after curative resection of oesophageal carcinoma.

Amplification of the hst-1 gene was examined in 82 patients with oesophageal carcinoma by dot blot hybridization to assess the potential of haematogenous recurrence after curative resection. Intensity of amplification was considered negative (one- to twofold increase) in 45 patients, low (three-sixfold increase) in 19 and high (greater than sevenfold) in 18. Haematogenous recurrence after curative resection was found in seven of eight patients with high amplification and was significantly higher in such patients than in those without amplification (P < 0.05). The finding that sevenfold or greater amplification of the hst-1 gene seems to be associated with haematogenous recurrence of oesophageal cancer after resection may serve to assess the clinical outcome.

Adult↗

Malposition of a totally implantable venous access catheter in the azygous vein: report of a case.

We report herein the case of a 2-year-old girl with short bowel syndrome who developed chest pain 2 weeks after a totally implantable central venous access catheter had been surgically placed to facilitate total parenteral nutrition. A lateral chest X-ray and contrast flow study subsequently revealed that the catheter tip had been inserted into the azygous vein. Although this complication is very rare, it may be encountered more commonly with the increasing use of this type of venous access. Thus, we believe that a lateral chest X-ray should be routinely performed on all patients following catheter insertion to check for possible malposition of the tip in the azygous vein.

Catheters, Indwelling↗

Expression and characterization of the zeta 1 subunit of the N-methyl-D-aspartate (NMDA) receptor channel in a baculovirus system.

Using a baculovirus expression vector system, the zeta 1 subunit of the mouse N-methyl-D-aspartate (NMDA) receptor channel was expressed in Spodoptera frugiperda insect cells. The peptide corresponding to the C-terminus of the zeta 1 subunit was synthesized by using the multiple antigen peptide (MAP) system, and an antibody to the synthetic peptide was produced. Immunoblotting using the newly developed antibody revealed the major 122-kDa and the minor 104-kDa protein bands. The effect of tunicamycin on the immunoblots and [35S]methionine/[35S]cysteine metabolic radiolabeling suggested that the two bands corresponded to glycosylated and non-N-glycosylated forms, respectively. Membranes prepared from insect cells infected with the recombinant virus had the binding activity of antagonist ligand 5,7-[3-3H]dichlorokynurenate (DCKA) of a glycine recognition domain of the receptor. Both immunofluorescence labeling and the [3H]DCKA binding assays also showed a greater level of expression (Bmax = 51 pmol/mg protein) in the insect cells. The ligand binding characteristics of the receptors expressed in insect cells suggested that the single zeta 1 subunit protein has glycine antagonist binding properties comparable to those of the native NMDA receptor channels. The lack of DCKA-binding activity of the non-N-glycosylated NMDA receptor expressed in the presence of tunicamycin suggested that N-linked oligosaccharide is essentially required for expression of a functional receptor in insect cells. This is the first report describing the importance of N-glycosylation for the acquisition of ligand binding to NMDA receptor channel subunit protein.

Animals↗

Intratumoral heterogeneity of hst-1 gene amplification in esophageal carcinoma with reference to DNA stem line heterogeneity.

Amplification of the hst-1 gene was examined in 112 neoplastic lesions from 27 patients with esophageal carcinoma. Ninety specimens were separately obtained from two or more sections of each individual primary tumor with DNA stem line heterogeneity and 22 specimens were obtained from metastatic lymph node lesions. The assessment was that hst-1 gene amplification within each individual primary tumor was identical in all 27 cases (100%) and that the intensity of amplification in the primary tumor matched that in the metastatic lesion in 18 of 22 cases (82%). When we examined 33 endoscopic biopsy specimens from esophageal carcinoma in the same manner, the intensity of hst-1 gene amplification in the specimens was similar to that obtained in surgical specimens from 26 of the 33 patients (79%). These results suggest that hst-1 gene amplification might occur in a homogeneous manner as a relatively early genetic event prior to lymph node metastasis, and that therefore, prior to surgical treatment, it can be evaluated from a single biopsy specimen.

Adult↗

Analysis of regional differences of p53 mutation in advanced gastric carcinoma: relation to heterogeneous differentiation and invasiveness.

In order to examine the correlation of p53 mutation with heterogeneous histological differentiation and invasiveness of gastric carcinoma, we analyzed 46 areas (three to six per case) that were different histologically and anatomically in 12 advanced gastric carcinomas, shown previously to be positive for p53 mutation, using immunohistochemical, polymerase chain reaction-single strand conformation polymorphism, and direct DNA sequencing analyses. DNA derived from different sites in nine cases had the same pattern of p53 mutation, even in cases manifesting heterogeneous histology within a single tumor. Site difference of the p53 mutation was found in three cases: two showed no mutation in superficial tumor areas but presence of mutation in deep-infiltrating areas. In contrast, one case contained a mutation in the superficial area but not in the deep-infiltrating area. These results suggest that in most cases, tumor cells forming a single advanced gastric carcinoma, even though they may present a heterogeneous histology and deep invasion, seem to be derived from the same cellular clone.

Base Sequence↗

[DNA stemline heterogeneity as preoperative prognostic factor in esophageal cancer].

Flow cytometric nuclear DNA analysis was performed on 36 preoperative endoscopic biopsy specimens and 89 surgically resected specimens of esophageal carcinomas without preoperative radiotherapy. Carcinomas with aneuploid or DNA stem-line heterogeneity had a higher frequency of lymph node metastasis (p < 0.01). The correspondence rate of nuclear DNA ploidy patterns was 97% between biopsy and resected specimens, and that of heterogeneity was 72%. Though only six cases showed heterogeneity in biopsy specimens out of 12 cases which showed heterogeneity in resected specimens, preoperative detection of heterogeneity was supposed to be more accurate by an increase of biopsy specimens. DNA analysis of biopsy specimens may be a possible indicator of the malignant potential of esophageal carcinoma.

Biopsy↗

Overexpression of c-erbB-2 protein in gastric cancer. Its correlation with long-term survival of patients.

BACKGROUND: Overexpression of c-erbB-2 protein in breast cancer has been reported to be associated with poor prognosis. However, clinical significance of c-erbB-2 protein overexpression has not been demonstrated clearly in gastric cancer. METHODS: Immunohistochemical reactivity to c-erbB-2 protein was examined in formalin-fixed, paraffin-embedded tissue sections from patients with gastric cancer. RESULTS: First, primary stomach cancers in 106 patients were examined. Among 58 cases of papillary or well- to moderately differentiated tubular adenocarcinoma, staining of c-erbB-2 protein was positive on the plasma membrane of cancer cells in 8 cases (14%). Conversely, among 47 cases of poorly differentiated adenocarcinoma or signet ring cell carcinoma, positive staining of c-erbB-2 protein was detected in one case only (2%), where the histopathologic type was poorly differentiated adenocarcinoma with a cohesive structure. Among tubular adenocarcinomas, no significant association was shown between overexpression of c-erbB-2 protein and the depth of tumor invasion, extent of lymph node metastasis, or tumor location. To investigate the correlation between the staining of c-erbB-2 protein and prognosis in gastric cancer, an additional 108 cases of papillary or well- to moderately differentiated tubular adenocarcinoma invasive as far as the muscularis propria were examined immunohistochemically for expression of c-erbB-2 protein. Twelve cases (11%) showed positive staining on the plasma membrane, and their survival curve showed a significantly poorer prognosis (P < 0.01). CONCLUSIONS: These results suggest that overexpression of c-erbB-2 protein occurs selectively in cohesive gastric cancer, and it can be considered an important prognostic indicator.

Adenocarcinoma↗

p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer.

Mutation of the p53 tumour-suppressor gene in exons 5 through 8 was examined in 118 cases of gastric cancer (59 early gastric cancers and 59 advanced gastric cancers) using PCR-SSCP (polymerase-chain-reaction-single-strand-conformation polymorphism) analysis and direct sequencing. In early gastric cancer, mutations were found in 15 of 41 (37%) cases of the cohesive type, i.e., papillary adenocarcinoma, well to moderately differentiated tubular adenocarcinoma, and poorly differentiated adenocarcinoma with solid nests or focal tubular structures, but were not detected in 18 cases of the non-cohesive type, i.e., signet-ring-cell carcinoma and poorly differentiated adenocarcinoma growing in a scattered manner. In advanced gastric cancer, 25 of 59 (42%) cases of the cohesive type had p53 mutation. No significant association was found between p53 mutation and other histopathological parameters such as macroscopic classification, lymph-node involvement and depth of tumour invasion. Fifteen of 25 (60%) mutations in the advanced gastric-cancer group were accompanied by allele loss at the p53 gene locus. Eighty-three percent of mutations in early gastric cancer and 52% of mutations in advanced gastric cancer showed G:C-to-A:T transition, almost exclusively at CpG dinucleotide mutational hot spots, indicating that the spectrum of p53 mutation was similar to that of colorectal cancer. These data suggest that the p53 mutation occurs selectively in gastric cancer of the cohesive type from the intramucosal cancer stage.

Adenocarcinoma↗

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↗

[The intensity of hst-1 gene amplification and malignant potential of esophageal carcinoma in relation to intratumoral heterogeneity].

Amplification of hst-1 gene is associated with poor prognosis in patients with esophageal carcinoma. Since there is a high frequency of DNA stem-line heterogeneity, we studied intratumoral heterogeneity of hst-1 amplification, and evaluated whether or not the intensity of hst-1 amplification is associated with the malignant potential of esophageal carcinoma. A total of 73 patients with esophageal carcinoma who had undergone esophagectomy were studied. Intratumoral heterogeneity of hst-1 amplification was examined in two to four sections of tumour specimens which showed mainly DNA heterogeneity in 27 of these patients. The judgement of hst-1 amplification in the same tumor was identical in all of the 27 patients, although its intensity was not identical in some cases. And in 73 patients, postoperative recurrence in organs showed a high incidence (78%) in the hst-1 amplification group with a high intensity (over 7-fold). Therefore, hst-1 amplification exceeding 7-fold can serve as an indicator to predict the high grade of malignant potential of esophageal carcinoma.

DNA, Neoplasm↗

Mutations in a putative agonist binding region of the AMPA-selective glutamate receptor channel.

The region preceding putative transmembrane segment M1 of the glutamate receptor (GluR) channel is well conserved among subunits and has been proposed to constitute a part of the agonist binding site. The functional significance of this region was examined by introducing point mutations into charged residues of the alpha 1 subunit of the mouse alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective GluR channel. The dose-response relationships of the mutant receptors were studied after expression in Xenopus oocytes by injection of the mutant alpha 1 subunit-specific mRNA together with the wild-type alpha 2-subunit-specific mRNA. Variable changes in the EC50 values for different agonists were found for the replacement of glutamic acid 398 by lysine and for the replacement of lysine 445 by glutamic acid. These residues may be involved in selective interaction of the GluR channel with agonists.

Amino Acid Sequence↗

Frequent loss of heterozygosity at the DCC locus in gastric cancer.

We examined 28 cases of surgically resected gastric cancer, excluding the diffuse type, for loss of heterozygosity (LOH) on 12 chromosomal arms using polymorphic DNA markers. LOH on chromosome 18q was detected in 61% (14 of 23) of the cases by the probes OLVIIA8, OLVIIE10, p15-65, SAM 1.1, and OS-4, and a putative common region showing LOH included the locus of the DCC tumor suppressor gene. LOH on chromosome 17p was also frequently found (8 of 19 or 42% of the cases) by the probes p10-3 and pHF12-1, and in 5 of these 6 cases the LOH on chromosome 17p was accompanied by LOH on chromosome 18q. On the other hand, the incidence of LOH was 30% or less using probes pHRnES, pHF12-65, p-c-mybE2.6, NJ3 3.2, pHF12-8, pHINS6.0, p9D11, hp2-alpha, pCMM6, and P1A5 on chromosomes 1q, 5, 6q, 7q, 9, 11p, 13q, 16q, 20, and 22q, respectively. LOH on chromosome 18q was frequent irrespective of the depth of tumor invasion, whereas the incidence of LOH on chromosome 17p was higher in the cases in which the tumor invaded beyond the muscularis propria than in those in which tumor invasion was limited to the submucosa and muscularis propria. These results suggest that LOH on chromosome 18q occurs at an earlier stage than LOH on chromosome 17p and that the inactivation of tumor suppressor genes located on chromosome 17p and 18q (e.g., the p53 and DCC genes) is critically involved in the development of the majority of gastric cancers. While alteration of the p53 gene is observed in various human cancers, that of the DCC gene is considered to occur more selectively in gastrointestinal cancers.

Chromosome Deletion↗

Structure and distribution of the lymphatic vessels in the parietal pleura of the monkey as studied by enzyme-histochemistry and by light and electron microscopy.

The entire distribution of lymphatics in whole mount preparations of the Japanese monkey was studied using the enzyme-histochemical technique reported by KATO et al. (1990, 1991). In this staining, the lymphatic endothelium was colored dark brown by its positive 5'-nucleotidase activity, while most blood vessels (especially arterioles) were colored blue due to their positive alkaline phosphatase reaction. The whole mount preparations of the pleura treated enzyme-histochemically clearly indicated the distribution, branching patterns and running courses of lymphatic vessels. They revealed numerous short blind-ending knobs which represented the initial portions of lymphatics. These knobs were seen near the surface of the parietal pleura along its entire extent. In the costal and diaphragmatic pleura, the lymphatics ran parallel to the intercostal muscle fibers, but perpendicular to the tendinous and muscular fibers of the diaphragm; they formed ladders, independent of the courses of blood vessels. In the mediastinal pleura, lymphatic vessels showed a tree-like branching accompanying blood vessels. Under the light microscope, toluidine-blue stained semithin sections revealed the initial part of lymphatics as a small irregularly outlined cavity (7-10 microns in diameter) surrounded by a dense connective tissue. This lymphatic dilation was sometimes located close to a thin mesothelial layer. Such a structure suggesting a "stoma" was seen near the attachment of the muscular diaphragm to the sternum and along the borders of the ribs. Transmission electron microscopy revealed an occasional interruption in the mesothelium. This stoma continued to a submesothelial cavity whose base comprised an attenuated endothelium of an extended lymphatic vessel.

5'-Nucleotidase↗

Close association of peptidergic nerves with lymphocytes in canine and monkey ileal villi.

Intimate association of peptidergic nerves with lymphocytes of canine and monkey ileal villi was demonstrated by immunohistochemistry and transmission electron microscopy. A swollen, presumably terminal, portion of nerves containing large cored vesicles and small clear vesicles was in direct contact with a lymphocyte. The apposing membranes of the nerve and lymphocyte were thickened and darkened, being separated by a narrow uniform space. The lymphocyte-associated nerves contained immunoreactivity for substance P(SP), calcitonin gene-related peptide (CGRP) or vasoactive intestinal polypeptide (VIP), localized in large-cored vessels. These result support the hypothesis that peptidergic nerves may play a regulatory role in mucosal immune responses.

Animals↗

High incidence of nuclear accumulation of p53 protein in gastric cancer.

The accumulation of p53 protein in the nuclei of cancer cells is known to correlate well with the presence of mutations in the p53 gene. We therefore investigated the immunohistochemical reactivity of the anti-p53 antibody, PAb1801, in specimens taken from 149 cases of primary gastric cancer and processed by acetone fixation, in order to elucidate the incidence and clinicopathological significance of p53 alterations in gastric cancer. Thirty-four out of 99 (34%) advanced gastric cancers and 11 out of 50 (22%) early gastric cancers showed positive reactions in the nuclei. The nuclei of non-cancerous cells, including gastric glandular epithelial cells, however, were not stained. Histopathologically, a nuclear accumulation of p53 protein was seen frequently in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures (43/101, 43%), but was rarely seen in signet-ring cell carcinoma, mucinous adenocarcinoma or poorly-differentiated adenocarcinoma growing in a scattered manner (2/48, 4%). There was no correlation between stainability of p53 protein and clinicopathological features such as depth of tumor invasion, microscopic lymphatic invasion, microscopic venous invasion, nodal involvement and clinicopathological stage in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures. The results suggest papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures to share a common carcinogenetic pathway in which mutation of the p53 gene has an important role to play at a relatively early stage. Additionally, we showed the applicability of immunohistochemical detection of p53 protein in endoscopic biopsy material routinely formalin-fixed. The current method may be of some help in routine practice in discriminating between normal, precancerous and cancer cells in the stomach.

Adenocarcinoma↗