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Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 487 records · Page 27Linked to original sources
PubMed1998

Fibroblast growth factor-2 free from extracellular matrix is increased in papillary thyroid carcinomas and Graves' thyroids.

Fibroblast growth factor (FGF)-2 is stored in the extracellular matrix (ECM). We hypothesized that FGF-2 is mobilized from the ECM and binds to receptors on the surface of FGF-2 responsive cells during thyroid enlargement. To test this hypothesis, we estimated levels of FGF-2 free from ECM in thyroids by comparing the efficiency of two methods for FGF-2 extraction (low salt and high salt). Because the high salt concentration (more than 1.5 M NaCl) is necessary to release FGF-2 from the normal ECM, FGF-2 extracted by low salt is indicative of ECM-free FGF-2. Human papillary thyroid carcinomas, normal part thyroid, and Graves' thyroid tissues were homogenized separately in an extraction buffer containing either 0 M NaCl (low salt) or 2.0 M NaCl (high salt), and the concentration of FGF-2 in the extracts was measured by enzyme-linked immunosorbent assay (ELISA). The yields of low and high salt extracts of immunoreactive (ir)FGF-2 from papillary carcinomas (low salt: 40.0 +/- 7.5, high salt: 233 +/- 53 ng/g tissue, mean +/- SE) were significantly higher than those of normal thyroid tissues extracted by the corresponding salt concentration (low salt: 14.6 +/- 1.8, high salt: 123 +/- 12 ng/g tissue). On the other hand, the extractable irFGF-2 from Graves' thyroid tissues (low salt: 25.2 +/- 2.5, high salt: 135 +/- 24 ng/g tissue) were not significantly different from that of normal thyroid tissues. However, the ratio of the extractable irFGF from carcinomas and Graves' thyroids by low salt to that by high salt (0 M/2 M ratio = 0.206 +/- 0.051, 0.209 +/- 0.025) were significantly higher than that of normal thyroids (0.120 +/- 0.014) (p < 0.05). These results suggest that intratissue ECM-free FGF-2 is increased in papillary thyroid carcinomas and Graves' thyroid tissues, and therefore a greater amount of FGF-2 may be available for stimulation of FGF-2 responsive cells.

Blotting, Western↗
PubMed1998

Rho1p-Bni1p-Spa2p interactions: implication in localization of Bni1p at the bud site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae.

Rho1p is a yeast homolog of mammalian RhoA small GTP-binding protein. Rho1p is localized at the growth sites and required for bud formation. We have recently shown that Bni1p is a potential target of Rho1p and that Bni1p regulates reorganization of the actin cytoskeleton through interactions with profilin, an actin monomer-binding protein. Using the yeast two-hybrid screening system, we cloned a gene encoding a protein that interacted with Bni1p. This protein, Spa2p, was known to be localized at the bud tip and to be implicated in the establishment of cell polarity. The C-terminal 254 amino acid region of Spa2p, Spa2p(1213-1466), directly bound to a 162-amino acid region of Bni1p, Bni1p(826-987). Genetic analyses revealed that both the bni1 and spa2 mutations showed synthetic lethal interactions with mutations in the genes encoding components of the Pkc1p-mitogen-activated protein kinase pathway, in which Pkc1p is another target of Rho1p. Immunofluorescence microscopic analysis showed that Bni1p was localized at the bud tip in wild-type cells. However, in the spa2 mutant, Bni1p was not localized at the bud tip and instead localized diffusely in the cytoplasm. A mutant Bni1p, which lacked the Rho1p-binding region, also failed to be localized at the bud tip. These results indicate that both Rho1p and Spa2p are involved in the localization of Bni1p at the growth sites where Rho1p regulates reorganization of the actin cytoskeleton through Bni1p.

Actins↗
PubMed1998

Identification of the gene loci that predispose to rheumatoid arthritis.

We have searched the human genome for genes that predispose to rheumatoid arthritis (RA) using fluorescence-based microsatellite marker analysis and affected sib-pair linkage study. A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic microsatellite marker loci. Markers were amplified by the PCR using fluorescence-tagged primers and sized based on the difference of CA repeats on DNA. Linkage analysis was made using maximum lod score (MLS). The MLS for D1S214 and D8S556 was 3.27 and 3.33, while the MLS for the HLA-DRB1 region was <3.0. According to detailed analysis by single-point analysis using MAPMAKER/SIBS, the MLS for D1S253 and D1S214 was 3.77 and 3.58. The MLS by multipoint analysis was 6.13 for D1S253. The MLS for D8S556 by single-point analysis was 4.20. The MLS for DXS1232 was 2.35 by single-point analysis, whereas the MLS for the region 2 cM right to DXS1232 and the region between DXS1227 and DXS1200 was 3.03 and 2.93 by multi-point analysis. Three principal chromosome regions of linkage, D1S253/214, D8S556 and DXS1232, have been identified which we call RA1, RA2 and RA3 for RA disease loci.

Arthritis, Rheumatoid↗
PubMed1998

Gastrointestinal cancer metastasis and lymphogenous spread: viewpoint of animal models of lymphatic obstruction.

Primary gastrointestinal cancer frequently spreads to the mesentery, omentum and other parts of the peritoneum and these deposits are generally considered to be induced by intraperitoneal seeding from the primary lesion. In this work, we examined the spread of gastrointestinal cancer from the viewpoint of lymphogenous metastasis using a rat model of mesenteric lymph vessel obstruction. With these models, we carried out mesenteric lymphangiography on the fourth and sixth postoperative days (five animals each) to examine morphological changes in the lymph vessels and lymph flow. In model animals with mesenteric lymph vessel obstruction, re-celiotomy, performed on the fourth postoperative day, revealed marked mesenteric edema and enlargement of the mesenteric lymph nodes, suggestive of lymph retention. We also carried out mesenteric lymphangiography and obtained images of extensive mesenteric lymph vessels and reflux of lymph distal to the obstruction point in all five animals. On the sixth postoperative day, we obtained lymphangiographic images of lymphatico-venous communication in the mesentery in all five animals. Thus in animals with lymph vessel obstruction, the lymph flow appeared to change to lymphatico-venous communication or reverse lateral flow. In clinical cases, it is conceivable that lymph retention and reflux of lymph induced by lymph vessel obstruction sometimes play a role in the mechanism of intraperitoneal cancer dissemination and hematogenous metastasis.

Animals↗
PubMed1998

Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is a very common disorder. Patients with OSAS are at an increased risk for cardiovascular events. It has also been reported that a 25% rise in factor VII clotting activity (FVIIc) is associated with a 55% increase in ischaemic heart disease death during the first 5 years. We examined the effects of nasal continuous positive airway pressure (NCPAP) treatment on FVIIc in patients with OSAS. FVIIc was investigated prospectively in 15 patients with OSAS before (mean +/- SEM apnoea and hypopnoea index (AHI) 61.5 +/- 4.2 and after (AHI 3.0 +/- 0.9) NCPAP treatment for immediate relief, at 1 month after treatment and at over 6 months. FVIIc levels gradually decreased after NCPAP treatment. After 6 months of NCPAP treatment, FVIIc levels had decreased significantly (before 141.1 +/- 11.7% vs. after 6 months 110.7 +/- 6.2%; p < 0.01). Six of the seven patients whose FVIIc levels were over 140% before the NCPAP treatment had FVIIc levels below 130% after 6 months or 1 year of NCPAP treatment. This decrease in FVIIc after long-term NCPAP treatment could improve mortality in OSAS patients. If patients, especially obese ones, present with high FVIIc of unknown origin, it would be prudent to check for OSAS.

Adult↗
PubMed1998

Evaluation of abnormal regional ventilation in patients with lung cancer using three-dimensional display of dynamic 133Xe SPET.

Preliminary studies were carried out of regional ventilation in lung cancer using three-dimensional (3D) display of dynamic pulmonary 133Xe single photon emission tomography (SPET). Transaxial equilibrium and washout images were obtained from SPET data acquired with an acquisition time of 30 s using a triple-detector SPET system in 39 patients with lung cancer. After reconstructing colour-illuminated, surface-rendered 3D images of equilibrium and 3-min washout (WO3), a single 3D fusion display was created from these two different time-course image sets, in which the 3D WO3 image indicating 133Xe retention was visible through the 3D equilibrium image delineating lung contours. The extent of retention was assessed using the 133Xe retention index, defined as the ratio of summed pixels of the segmented WO3 data to those of the segmented equilibrium data. 133Xe SPET was highly sensitive and specific for the presence of regional ventilation abnormalities associated with endobronchial tumour or bronchial compression due to enlarged lymph nodes. These abnormalities were demonstrated irrespective of the presence or absence of secondary changes distal to the tumour on the chest computed tomography scan. The geometrically realistic 3D fusion display enhanced anatomic localization of the regional ventilation abnormalities compared to the information from multislice tomograms, and the 133Xe retention index correlated well with %FEV1 (r = 0.828). This topographic 3D display for 133Xe SPET allows better perception of anatomic localization and extent of 133Xe retention. It will be useful for assessing regional ventilatory function in patients with lung cancer.

Adenocarcinoma↗
PubMed1998

Clinical significance of serum hyaluronic acid as a fibrosis marker in chronic hepatitis C patients treated with interferon-alpha: histological evaluation by a modified histological activity index scoring system.

The aim of the present study was to investigate the histological changes effected by interferon (IFN) treatment and to evaluate the clinical significance of serum hyaluronic acid (HA) as a marker of fibrosis. Forty-nine patients with chronic hepatitis C treated with IFN-alpha were divided into three groups according to the existence of viraemia: sustained complete responders (CR), complete responders with relapse (PR) and non-responders (NR). Needle biopsy sections of the liver taken before and at the end of IFN treatment were assessed according to the modified histological activity index (HAI) scoring system. Serum fibrosis markers, including HA, were measured at needle biopsies. Biopsies of CR at the end of treatment showed a significant improvement in fibrosis and necroinflammatory scores. More significant correlation was observed between fibrosis scores and serum levels of HA before IFN treatment (r = 0.607, P < 0.0001) than those between fibrosis scores, on the one hand, and peptide of type III procollagen (PIIIP; r = 0.531, P = 0.0004) or type IV collagen 7S domain (type IV-C; r = 0.241, P = 0.1062) on the other. Moreover, serum HA levels fell significantly in patients in whom fibrosis improved (P = 0.011). This is the first paper describing the advantages of the modified HAI scoring system over others in estimating the effect of IFN-alpha; the results also indicate that serum HA can be useful in monitoring liver fibrosis in chronic hepatitis C patients treated with IFN-alpha.

Adult↗
PubMed1998

Spontaneous rupture of the uterus caused by placenta percreta at 28 weeks of gestation: a case report.

Placenta percreta is a rare complication of pregnancy. Rupture of the uterus due to placenta percreta is one of the most urgent obstetrical catastrophes. Recently, we observed a patient who developed placenta percreta accompanied by spontaneous uterine rupture at 28 weeks of gestation. A 29-year old gravida 3, para 1, who had a history of one cesarean section and one miscarriage with dilatation and curetage, was seen at 28 weeks of gestation. An acute abdomen and shock were diagnosed. Immediate laparotomy revealed a transverse rupture on the fundus of the uterus. A hysterectomy was performed. Pathological examination of the uterus showed placenta percreta. Rupture of the uterus due to placenta percreta before the onset of labor is extremely rare.

Adult↗
PubMed1998

The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1.

The AML1-CBFbeta transcription factor complex is essential for the definitive hematopoiesis of all lineages and is the most frequent target of chromosomal rearrangements in human leukemia. In the t(8;21) translocation associated with acute myeloid leukemia (AML), the AML1(CBFA2/PEBP2alphaB) gene is juxtaposed to the MTG8(ETO/CDR) gene. We show here that the resultant AML1-MTG8 gene product specifically and strongly interacts with an 85-kDa phosphoprotein. Molecular cloning of cDNA indicated that the AML1-MTG8-binding protein (MTGR1) is highly related to MTG8 and similar to Drosophila Nervy. Comparison of amino acid sequences among MTGR1, MTG8, and Nervy revealed four evolutionarily conserved regions (NHR1 to NHR4). Ectopic expression of AML1-MTG8 in L-G murine myeloid progenitor cells inhibits differentiation to mature neutrophils and induces cell proliferation in response to granulocyte colony-stimulating factor (G-CSF). Analysis with C-terminal deletion mutants of AML1-MTG8 indicated that the region of 51 residues (488 to 538), which contains NHR2, is essential for the induction of G-CSF-dependent cell proliferation. Immunoprecipitation analysis indicates that this region is required for AML1-MTG8 to form a stable complex with MTGR1. Overexpression of MTGR1 stimulates AML1-MTG8 to induce G-CSF-dependent proliferation of L-G cells and to interfere with AML1-dependent transcription. These results suggest that AML1-MTG8 could function as a complex with MTGR1 and that the complex might be important in promoting leukemogenesis.

Amino Acid Sequence↗
PubMed1998

Anticancer effects of preoperative chemotherapy on colorectal carcinoma.

This study was designed to evaluate the efficacy of preoperative chemotherapy and to investigate the relationship between the histopathologic response and prognosis in patients with colorectal carcinoma. Thirty-six previously untreated patients with advanced colorectal carcinoma were consecutively enrolled in this study and received preoperative N-(2-tetrahydrofuryl-5-fluorouracil (FT-207) by suppository. The histopathologic response was investigated. Histopathologically, 14 patients had no response, 19 responded slightly, 2 moderately and 1 had a complete response to the chemotherapy. The extent of the histopathologic response to chemotherapy was greater in the deeper layers of the invaded tissue. There was no relation between the location of the tumor and the extent of the histopathologic response. Based on clinical cancer staging, the overall 5-year survival rate was 100% in patients with Duke's A and Duke's B cancer and 45% in patients with Duke's C cancer; the 3-year survival rate was 25% in patients with Duke's D cancer. The 5-year survival rate for those with a positive histopathologic response to chemotherapy was 71%, whereas that for the nonresponders was 79%. Mild chemotherapy in the form of FT-207 suppositories was found to be effective histopathologically. However, no relationship was seen between the histopathologic response and survival rate.

Adult↗
PubMed1998

Histopathological study of the effect of phacoemulsification-aspiration on iris muscles.

Phacoemulsification-aspiration (PEA) followed by peripheral iridectomy was performed in 10 patients, and the dissected iris fragments were examined by electron microscopy. Organic changes such as cytoplasmic vacuolation and lamellar formation were observed in both the sphincter and dilator muscles of the pupil. No changes in the axons were detected. The same findings were observed when a simian eye was examined after PEA. These results indicate that PEA causes injury to iris muscles.

Aged↗
PubMed1998

Evidence for the existence of CCK-producing cells in rat pancreatic islets.

BACKGROUND: Although the existence of cholecystokinin-like immunoreactivity (CCK-LI) in rat pancreas had been reported previously, it was never clearly demonstrated whether CCK is produced in rat pancreatic islets. AIMS: The purpose of this study was to elucidate the source of the CCK-LI, the molecular properties of CCK, and the expression of the CCK gene in islet cells. METHODS: Immunohistochemical studies of rat pancreas were carried out with different rabbit antisera against CCK-8 and CCK-related peptide including N-terminal CCK-33 (1-22) and gastrin-17, and colocalization with known islet hormones including insulin, glucagon, somatostatin, and pancreatic polypeptide was investigated. The major molecular form of CCK in the islets was determined by HPLC. RT-PCR and in situ hybridization were performed to demonstrate the presence of the CCK transcript in the pancreas. RESULTS: CCK-LI was found in the center of the islets, colocalized with insulin in B cells. The major molecular form of CCK in the islets was CCK-8. A 350-nucleotide fragment of PCR-amplified CCK cDNA was detected in the islet as well as the duodenum by RT-PCR. In situ hybridization showed that CCK messenger RNA was located in a large portion of the islets, and this was consistent with the immunohistochemical findings. CONCLUSION: CCK messenger RNA and immunoreactivity are expressed in adult rat pancreatic islets, indicating that CCK-producing cells are present in adult rat islets.

Animals↗
PubMed1998

Targeting of soybean-derived sterylglucoside liposomes to liver tumors in rat and mouse models.

The blood clearance, tissue uptake and antitumor efficacy against liver metastasis of M5076 reticulosarcoma in mice and against primary liver cancer in rats of doxorubicin (DOX) encapsulated in two types of liposomes, with and without a soYbean-derived sterylglucoside mixture (SG), were examined. Liposomes entrapping DOX were composed of dipalmitoylphosphatidylcholine (DPPC), SG and cholesterol (Ch) at a molar ratio of 6:1:3, (SG-liposomes) and 6:0:4 (non-SG-liposomes). Pharmacokinetic analysis of drug disposition was based on the area under the curve (AUC) for liposomes up to 24 h following i.v. injection. SG-liposomes showed lower DOX concentrations in blood and higher concentrations in liver compared with non-SG-liposomes. The highest AUC of SG-liposomes in tissue was in liver, 2.4 times higher than that of the free drug. The antitumor efficacy of SG-liposomes was compared with that of free DOX and non-SG-liposomes at a dose of 5 mg DOX/kg. SG-liposomes displayed stronger antitumor activity than the free drug and non-SG-liposomes in murine reticulosarcoma M5076 tumor models and primary liver cancer models reflecting accumulation in hepatocytes. The antitumor activity of SG-liposomes in rats with primary liver cancer was significantly higher compared with free DOX and non-SG-liposomes (ILS: 92.7%).

Animals↗
PubMed1998

Association of liposomes containing a soybean-derived sterylglucoside mixture with rat primary cultured hepatocytes.

Dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Ch) liposomes containing a soybean-derived sterylglucoside mixture (SG) (SG-liposomes) are effective for targeting hepatocytes in mice. We investigated uptake of SG-liposomes to hepatocytes compared with that via the galactose receptor. The association of SG-liposomes entrapping calcein was examined at 4 degrees C or 37 degrees C, changing incubation time and the SG concentration of the liposomes, and using the inhibitor on the galactose receptor in rat primary cultured hepatocytes. The amount of liposomes recovered with hepatocytes was determined by measuring the concentration of calcein and imaged with confocal laser scanning microscopy in the cultured cells. The association of SG-liposomes at 4 degrees C was significantly decreased compared with that at 37 degrees C as that of liposomes containing lactosylceramide (LC) (LC-liposomes) that were already known to be taken up by hepatocytes via the asialoglycoprotein receptor. While the association of SG-liposomes at both 4 degrees C and 37 degrees C increased with the increase of incubation time, the association of SG-liposomes at 37 degrees C was almost saturated after 1 h. The association of SG-liposomes pretreated with concanavalin A was significantly decreased (to about 40% of that without pretreatment at 37 degrees C) and was at the same level as the association of SG-liposomes and non-SG-liposomes at 4 degrees C. The association of the SG-liposomes by hepatocytes incubated for I h at 37 degrees C was almost saturated at about 2.0 nmol SG/mg protein. The association of the SG-liposomes with hepatocytes was not inhibited in the presence of LC-liposomes. The affinity of the galactose residue for hepatocytes appeared to be similar to that of the glucose residue in the liposomes, because the amount of sugar residue and the association of SG-liposomes and LC-liposomes were almost the same values. These results suggest that SG-liposomes may be associated with hepatocytes not by a galactose receptor-mediated endocytosis.

Animals↗