Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 91 records · Page 5Linked to original sources

PubMed2002

Diagnostic laparoscopy, serum CA125, and peritoneal metastasis in gastric cancer.

BACKGROUND AND STUDY AIMS: Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. We report on the utility of laparoscopy and its indications in the detection of peritoneal metastasis in gastric cancer. PATIENTS AND METHODS: A total of 39 patients with gastric cancer underwent laparoscopy and peritoneal cytology investigation in our department, between April 1992 and April 2000. Laparoscopic diagnosis for peritoneal metastasis (LP-P) was determined through macroscopic, pathological and cytological diagnoses. All the patients underwent diagnostic imaging with computed tomography (CT) and ultrasound before laparoscopy. Carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, and CA125 levels in serum and peritoneal fluid were measured using enzyme immunoassay. RESULTS: Laparoscopic diagnosis for peritoneal metastasis gave negative results in 21 patients and positive results in 18. All the patients with negative LP-P findings underwent surgery; 18 of the 21 patients showed no peritoneal metastasis, but three were diagnosed as having peritoneal metastasis, one at the pouch of Douglas and two at the mesentery. The diagnosis of all the patients with positive LP-P findings was finally confirmed as correct. The specificity, sensitivity, and accuracy of laparoscopy for peritoneal metastasis were 100 % (18/18, 95 % CI 0.82 - 1), 86 % (18/21, 95 % CI 0.64 - 0.97), and 92 % (36/39, 95 % CI 0.79 - 0.98), respectively. The specificity, sensitivity, and accuracy of diagnostic imaging for peritoneal metastasis were 100 % (18/18, 95 % CI 0.82 - 1), 38 % (8/21, 95 % CI 0.18 - 0.62), and 67 % (26/39, 95 % CI 0.50 - 0.81), respectively. All of the 11 patients showing high levels of serum CA125 (equal to or more than 35 U/ml) had peritoneal metastasis whereas 17 of the 26 patients with low levels of serum CA125 (less than 35 U/ml) did not ( P < 0.001). CONCLUSIONS: The sensitivity of laparoscopy for peritoneal metastasis was much higher than that of diagnostic imaging. Laparoscopy and serum CA125 level both predicted peritoneal metastasis, but the degree, volume, or distribution of peritoneal metastasis was disclosed only by laparoscopy. Laparoscopy is a useful way of detecting peritoneal metastasis in gastric cancer, and patients with an elevated level of serum CA125 are the best candidates for laparoscopy.

Adult↗

PubMed2002

Plasma leptin levels and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome.

BACKGROUND: The control of body weight and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) are important because both factors have significant effects on the mortality of these patients. It has recently been reported that OSAHS has a significant effect on the secretion of leptin, a hormone involved in the control of body weight and sympathetic nerve activity. In addition to the circadian rhythm of leptin secretion, the effects of one night of treatment with nasal continuous positive airway pressure (nCPAP) and the mechanism of the effects of nCPAP on nocturnal leptin secretion in patients with OSAHS has not yet been elucidated. METHODS: Blood samples were obtained at 21.00 hours, 00.00 hours, 03.00 hours, and 06.30 hours from 21 subjects with OSAHS (mean apnoea and hypopnoea index 52.4/h), with and without nCPAP treatment. Iodine-123 (I(123))-meta-iodobenzylguanidine (MIBG) imaging was used to evaluate myocardial sympathetic function before nCPAP treatment. RESULTS: Plasma leptin reached a peak level at 00:00 hours (p<0.01) in patients with OSAHS, both with and without nCPAP treatment. The first night of nCPAP treatment significantly decreased the plasma leptin levels at 03.00 hours (without nCPAP: mean (SE) 21.6 (4.7) ng/ml; with nCPAP: 19.3 (4.1) ng/ml, p<0.02) and at 06.30 hours (without nCPAP: 17.6 (3.8) ng/ml; with nCPAP: 15.2 (3.2) ng/ml, p<0.01). The magnitude of the decrease in leptin levels after nCPAP treatment was significantly correlated with cardiac sympathetic function measured before nCPAP treatment (p<0.03). CONCLUSIONS: Patients with OSAHS undergo nocturnal increases in leptin levels in spite of interruption of sleep due to apnoea and hypopnoea, a trend seen in normal subjects. Plasma leptin levels in patients with OSAHS decreased significantly after the first night of nCPAP treatment. Enhanced cardiac sympathetic function in these patients may contribute to the leptin levels before nCPAP treatment and vice versa.

3-Iodobenzylguanidine↗

PubMed2002

Quantitative trait loci on chromosomes 10 and 11 influencing mandible size of SMXA RI mouse strains.

Predicting the mandible size before the termination of growth of the maxillofacial bones is essential in pedodontics as well as for the predictions needed for genetic analysis. Here, Quantitative Trait Locus (QTL) analysis was used to detect the chromosomal regions responsible for the mandible length between the menton and gonion in an SMXA recombinant inbred strain of mice. Around the region 60 cM from the centromere in chromosome 10, the logarithm of the odds score showed a higher than suggestive level. Around the regions 13 cM and 16 cM in chromosome 11, two significant QTLs were detected. Analysis of genotypes from loci corresponding to those QTLs revealed a large mandible when the region between the markers Hba and D11Mit163 and D10Mit70 and D10Mit136 indicated the genotype from the A/J and SM/J alleles, respectively. These results suggest that the major gene(s) responsible for mandible length are located in these regions.

Animals↗

PubMed2002

Allelic imbalance and microsatellite instability in plasma DNA released from polyclonal pancreatic adenocarcinoma.

Evidence of circulating soluble DNA in blood-stream of cancer patients has emerged. Because the plasma DNA is largely derived from cancer cells, genetic analysis of plasma DNA is important to understand the molecular events occurred in cancer patient. Seven microsatellite markers in the soluble plasma DNA from patients with pancreatic adenocarcinoma and other pancreato-biliary malignant tumors were examined for microsatellite instability (MSI) and allelic imbalance (AI). A variety of genetic alterations including MSI and AI were detected in the plasma DNA. Some alterations were detected before recurrence of the tumor was verified. Analysis of five primary pancreatic adenocarcinomas by microdissection revealed that the heterogeneous nature of pancreatic tumors is associated with both MSI and AI in the same tumor. The presence of altered plasma DNA including MSI and/or AI from the same pancreatic cancer patient may be important evidence for the presence of these alterations in heterogeneous primary tumors. Analysis of plasma DNA could become one of the diagnostic or therapeutic measures for this type of pancreatic adenocarcinoma.

Aged↗

PubMed2002

[Bilateral sleeve upper lobectomy for metachronous squamous cell carcinoma of the lung; report of a case].

A 67-year-old man admitted to our hospital complaining cough. Bronchoscopic findings showed tumor at inlet of the left upper bronchus. Left upper sleeve lobectomy was performed. Six years 6 months later, he admitted to our hospital. Bronchoscopic findings showed tumor at inlet of the right upper bronchus. Right upper sleeve lobectomy was performed. He received radiation therapy, and discharged from the hospital 2 months after the operation. It is quite a rare case that the tumor lesions, to which bronchoplasty need to be applied, develop at 2 separate locations. This case proves that sleeve lobectomy can be applied to 2 separate locations successfully.

Aged↗

PubMed2002

Toxicological study of a glucose-added acetic acid maintenance infusion solution (VEEN 3G Inj.) local irritation test.

The local irritating effect of Veen 3G Inj. (glucose-added acetic acid maintenance infusion solution) was examined in male rabbits. We studied the local irritating effect of the infusion solution compared with that of Ringer's solution, 5% sulfobromophthalein sodium injection, distilled water for injection or glucose-added Ringer's solution. In the vascular irritation test, macroscopical and histopathological changes induced by the infusion solution were not observed in the vessels. Moreover, in the hemolytic test, hemolysis of rabbit erythrocyte was not observed in the mixture with the infusion solution. In the present study, no change suggesting irritation by the infusion solution was observed in the in vivo vascular irritation test using the auricular vein of rabbits or in the in vitro hemolytic test using rabbit erythrocyte. In conclusion, in clinical use the infusion solution produces extremely slight adverse effects, such as vessel pain and phlebitis on the injection site.

Animals↗

PubMed2002

E2F-4 mutation in hereditary non-polyposis colorectal cancer.

Defects in the DNA mismatch repair function are known to cause microsatellite instability (MSI) in hereditary non-polyposis colorectal cancer (HNPCC) as well as in a subset of sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at a coding region of trinucleotide microsatellite (CAG)n in a subset of human sporadic CRC with high-frequency MSI (MSI-H). In this study, we assessed mutations of E2F-4 in HNPCC as well as other target genes of defective DNA mismatch repair function. Eighteen colorectal cancer (CRC) patients from 13 kindreds meeting the Amsterdam criteria for HNPCC were analyzed and compared to sporadic CRC patients with MSI-H. We detected mutations of E2F-4 at the same repeat sequence in HNPCC. The frequency of the E2F-4 mutation in HNPCC was comparable with that in sporadic CRC with MSI-H. E2F-4 was considered to be one of the important target genes responsible for the carcinogenesis of HNPCC.

Base Pair Mismatch↗

PubMed2002

Genetic alterations of the ornithine decarboxylase gene in human colorectal cancers.

Ornithine decarboxylase (ODC), a critical regulatory enzyme for polyamine biosynthesis, is strictly regulated in human cells. Several studies suggested the importance of elevated enzymatic activity and altered biochemical characteristics of ODC in malignant cells. Because mutation of ODC in primary human hepatocellular carcinoma has been reported, we examined whether the genetic alterations, such as mutations or structural alterations of the gene, also account for the alteration of ODC activity in human colorectal cancer. No mutation or structural alteration in the ODC was detected in any of the colorectal tumors and normal tissues examined. These results suggest that a mutation or structural alteration of the ODC may not be involved in human colorectal carcinogenesis.

Blotting, Southern↗

PubMed2001

Notch1 inhibits differentiation of hematopoietic cells by sustaining GATA-2 expression.

Notch signaling is involved in cell fate decisions in many systems including hematopoiesis. It has been shown that expression of an activated form of Notch1 (aNotch1) in 32D mouse myeloid progenitor cells inhibits the granulocytic differentiation induced by granulocyte colony-stimulating factor (G-CSF). Results of the current study show that aNotch1, when expressed in F5-5 mouse erythroleukemia cells, also inhibits erythroid differentiation. Comparison of the expression levels of several transcription factors after stimulation for myeloid and erythroid differentiation, in the presence or absence of aNotch1, revealed that aNotch1 did not change its regulation pattern with any of the transcription factors examined, except for GATA-2, despite its inhibitory effect on differentiation. GATA-2 was down-regulated when the parental 32D and F5-5 were induced to differentiate into granulocytic and erythroid lineages, respectively. In these induction procedures, however, the level of GATA-2 expression was sustained when aNotch1 was expressed. To ascertain whether maintenance of GATA-2 is required for the Notch-induced inhibition of differentiation, the dominant-negative form of GATA-3 (DN-GATA), which acted also against GATA-2, or transcription factor PU.1, which was recently shown to be the repressor of GATA-2, was introduced into aNotch1-expressing 32D (32D/aNotch1) cells that do not express GATA family proteins other than GATA2. Both DN-GATA and PU.1 reversed the phenotype of 32D/aNotch1 inducing its differentiation when G-CSF was added. Furthermore, enforced expression of HES-1, which is involved in Notch signaling, delayed differentiation of 32D, and again this phenotype was neutralized by DN-GATA. These results indicate that GATA-2 activity is necessary for the Notch signaling in hematopoietic cells.

Animals↗

PubMed2001

Association of FcgammaRII with low-density detergent-resistant membranes is important for cross-linking-dependent initiation of the tyrosine phosphorylation pathway and superoxide generation.

IgG immune complexes trigger humoral immune responses by cross-linking of FcRs for IgG (FcgammaRs). In the present study, we investigated role of lipid rafts, glycolipid- and cholesterol-rich membrane microdomains, in the FcgammaR-mediated responses. In retinoic acid-differentiated HL-60 cells, cross-linking of FcgammaRs resulted in a marked increase in the tyrosine phosphorylation of FcgammaRIIa, p58(lyn), and p120(c-cbl), which was inhibited by a specific inhibitor of Src family protein tyrosine kinases. After cross-linking, FcgammaRs and tyrosine-phosphorylated proteins including p120(c-cbl) were found in the low-density detergent-resistant membrane (DRM) fractions isolated by sucrose-density gradient ultracentrifugation. The association of FcgammaRs as well as p120(c-cbl) with DRMs did not depend on the tyrosine phosphorylation. When endogenous cholesterol was reduced with methyl-beta-cyclodextrin, the cross-linking did not induce the association of FcgammaRs as well as p120(c-cbl) with DRMs. In addition, although the physical association between FcgammaRIIa and p58(lyn) was not impaired, the cross-linking did not induce the tyrosine phosphorylation. In human neutrophils, superoxide generation induced by opsonized zymosan or chemoattractant fMLP was not affected or increased, respectively, after the methyl-beta-cyclodextrin treatment, but the superoxide generation induced by the insoluble immune complex via FcgammaRII was markedly reduced. Accordingly, we conclude that the cross-linking-dependent association of FcgammaRII to lipid rafts is important for the activation of FcgammaRII-associated Src family protein tyrosine kinases to initiate the tyrosine phosphorylation cascade leading to superoxide generation.

Cells, Cultured↗

PubMed2001

Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization.

There is considerable controversy as to whether necrotic (lysate) or apoptotic tumor cells serve as the superior source of multiple tumor-associated antigens (TAAs) to pulse dendritic cells (DCs) for immunotherapeutic applications. Here, we show that standard procedures to induce apoptosis by UVB irradiation unequivocally result in a mixed population of viable, apoptotic, and necrotic tumor cells, necessitating additional purification. We used highly enriched apoptotic versus lysate of B16 melanoma cells to examine whether or not there are important distinctions between these two sources of TAAs for loading of DCs. Our results demonstrate that although some differences exist between the two forms of TAAs in expression of heat shock proteins, as well as production of interleukin-12 by pulsed DCs, their respective capacities to mature DCs phenotypically, as well as to elicit both effective immune priming and antitumor therapeutic efficacy in vivo when presented by DCs, are equivalent.

Animals↗

PubMed2001

Changes in BDNF-immunoreactive structures in the hippocampal formation of the aged macaque monkey.

We investigated the changes of brain-derived neurotrophic factor (BDNF)-immunoreactive structures in the hippocampal formation of aged macaques (Macaca fuscata fuscata). At adult stages (10 and 12 years), BDNF immunoreactivity occurred in the neurons of the dentate gyrus, the pyramidal neurons in the CA1, CA2, CA3 subfields and the subiculum, and the neurons in the CA4 subfield and the entorhinal cortex. The apical dendrites were also BDNF immunopositive. In aged monkeys (26, 30 and 32 years), the intensity of the BDNF-immunoreactivity declined significantly in cell bodies and dendrites of the neurons in the hippocampal formation except the CA2 pyramidal neurons. These findings indicate that BDNF is one of the vulnerable signal molecules during the aging process of the primate hippocampal formation.

Aging↗

PubMed2001

High frequency of low-level microsatellite instability in early colorectal cancer.

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Aged↗

PubMed2001

Nickel-promoted alkylative or arylative carboxylation of alkynes.

[reaction: see text]. Nickel-promoted alkylative or arylative carboxylation of terminal alkynes via a carbon dioxide fixation process was investigated. In the presence of a stoichiometric amount of a zero-valent nickel complex, the reaction of alkynes with CO2 gave a nickelacycle, which was reacted with various organozinc reagents under very mild conditions to provide beta,beta'-disubstituted, alpha,beta-unsaturated carboxylic acids in a highly regio- and stereoselective manner.

Journal Article↗

PubMed2001

Structural characterization and chromosomal localization of the MAGE-E1 gene.

Genes of the melanoma-associated antigen (MAGE) family are characterized by the expression of tumor antigens on a malignant melanoma recognized by autologous cytolytic T lymphocytes. We have previously identified novel members of the MAGE gene family expressed in human glioma and named them MAGE-E1a-c. In the present study, we have revealed the genomic structure of MAGE-E1 by sequence analysis of a human chromosome bacterial artificial chromosome clone containing the MAGE-E1 gene. The MAGE-E1 gene is composed of 13 exons, and three of these (exon 2, exon 3 and exon 12) are alternatively spliced in each variant (E1a-c). The open reading frame encoding the MAGE-E1 peptides initiates in exon 2 and ends in exon 13. We have also demonstrated that the MAGE-E1 gene is located in Xp11 through the analysis of radiation hybrid panels. The genomic structure of MAGE-E1 is markedly similar to that of MAGE-D and its chromosomal locus is also identical to that of MAGE-D, but these features contrast with those of other MAGEs. These results suggest that MAGE-D and -E1 may be evolutionarily distant from other members of the MAGE family, and the two may be ancestral genes for the others.

Alternative Splicing↗

PubMed2001

Differential osteopontin expression in lung cancer.

Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. Its expression is induced by a variety of stimuli such as TNF-alpha and Ras proto-oncogene. However, differential OPN expression and its regulation in each histologic type of lung cancer are not well established. In this study, we assessed expression of OPN in lung cancer tissues with immunohistochemical analysis. OPN was predominantly expressed in tumor cells of non-small cell lung cancer (NSCLC) tissues: 11 of 16 cases (68.8%) of squamous cell carcinoma (SCC), five of 24 cases (20.8%) of adenocarcinoma (AD), but only two of 18 cases (11%) of small cell lung cancer (SCLC). Expectedly, OPN was principally expressed in NSCLC cell lines (H322 cells and HL460 cells) but not in SCLC cell line (H69 cells) by Western blotting and Northern blotting. Interestingly, Ras-p21 was specifically co-expressed with OPN staining in eight of eight cases with SCC (100%), whereas it was demonstrated in three of ten cases (30%) with AD and only one of 18 cases (5%) with SCLC. Collectively, these results suggest that OPN is mainly expressed in NSCLC, especially among SCC. OPN expression may be tightly regulated by Ras oncogene, and its concomitant induction with Ras activation may play a crucial role in the development of SCC.

Adenocarcinoma↗

PubMed2001

Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ.

Interleukin-10 (IL-10) is a multifunctional cytokine that can exert suppressive and stimulatory effects on T cells. It was investigated whether IL-10 could serve as an immunostimulant for specific CD8(+) cytotoxic T cell (CTL) in vivo after vaccination and, if so, under what conditions. In tumor prevention models, administration of IL-10 before, or soon after, peptide-pulsed primary dendritic cell immunization resulted in immune suppression and enhanced tumor progression. Injection of IL-10, however, just after a booster vaccine significantly enhanced antitumor immunity and vaccine efficacy. Analysis of spleen cells derived from these latter animals 3 weeks after IL-10 treatment revealed that the number of CD8(+) CD44(hi) CD122(+) T cells had increased and that antigen-specific proliferation in vitro was enhanced. Although cytotoxicity assays did not support differences between the various treatment groups, 2 more sensitive assays measuring antigen-specific interferon-gamma production at the single-cell level demonstrated increases in the number of antigen-specific responder T cells in animals in the vaccine/IL-10 treatment group. Thus, IL-10 may maintain the number of antitumor CD8(+) T cells. In adoptive transfer studies, the ability of IL-10 to maintain CTL function could be enhanced by the depletion of CD4(+) T cells. This suggests that IL-10 mediates contrasting effects on both CD4(+) and CD8(+) T cells that result in either immune dampening or immune potentiation in situ, respectively. Appreciation of this dichotomy in IL-10 immunobiology may allow for the design of more effective cancer vaccines designed to activate and maintain specific CD8(+) T-cell effector function in situ.

Animals↗

PubMed2001

TrkB dimerization during development of the prefrontal cortex of the macaque.

To date, two subtypes of TrkB, a BDNF receptor, have been described. One is full-length TrkB (TK+), which has a tyrosine kinase-containing intracellular domain. The other is truncated TrkB (TK-), which has a short intracellular domain lacking the tyrosine kinase. In this study, we investigated the dimerization of TrkB subtypes in the developing monkey prefrontal cortex by means of cross-linking. At embryonic day 120, the TK+/TK+ and the 100 kDa/100 kDa homodimers were observed with BDNF stimulation. At the newborn stage, the TK+/TK+ and the TK-/TK- homodimers were observed with BDNF stimulation. At the adult stage, the TK-/TK- homodimer and the TK+/TK- heterodimer were formed by BDNF stimulation. The levels of all dimers increased in proportion to the concentration of BDNF. Moreover, the dimers were clearly formed within 5 min of treatment with BDNF. BDNF and NT-4/5 induced the dimers, whereas NT-3 formed slight dimers but NGF did not. Furthermore, anti-BDNF antibody inhibited the TrkB dimerization. Moreover, the intercellular binding proteins of TrkB were not cross-linked by BS3. Therefore, these results suggest that the change in dimerization among TrkB subtypes occurs during development of the monkey prefrontal cortex.

Animals↗