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Biomedical subjects

H Nagai

Publications and source records attributed to H Nagai.

At least 19 recordsLinked to original sources
PubMed2007

CLCP1 interacts with semaphorin 4B and regulates motility of lung cancer cells.

We previously established a highly metastatic subline, LNM35, from the NCI-H460 lung cancer cell line, and demonstrated upregulation of a novel gene, CLCP1 (CUB, LCCL-homology, coagulation factor V/VIII homology domains protein), in LNM35 and lung cancer specimens. In this study, we focused on the potential roles of that gene in cancer metastasis. First, we established stable LNM35 RNAi clones, in which CLCP1 expression was suppressed by RNAi, and found that their motility was significantly reduced, although growth rates were not changed. Next, in vitro selection of a phage display library demonstrated that a phage clone displaying a peptide similar to a sequence within the Sema domain of semaphorin 4B (SEMA4B) interacted with LNM35. Immunoprecipitation experiments confirmed interaction of CLCP1 with SEMA4B, regulation of CLCP1 protein by ubiquitination and proteasome degradation enhanced in the presence of SEMA4B. These results are the first to indicate that CLCP1 plays a role in cell motility, whereas they also showed that at least one of its ligands is SEMA4B and that their interaction mediates proteasome degradation by CLCP1. Although the physiological role of the interaction between CLCP1 and SEMA4B remains to be investigated, this novel gene may become a target of therapy to inhibit metastasis of lung cancers.

Amino Acid Sequence↗
PubMed2006

Antifogging effects of a socket-type device with the superhydrophilic, titanium dioxide-coated glass for the laparoscope.

BACKGROUND: Lens fogging during laparoscopic surgery extensively deteriorates operative field visibility and may provoke serious complications. METHODS: A simulation model study was conducted using a conventional laparoscope, a conventional laparoscope plus heating (100 degrees C, 10 s), a conventional laparoscope plus surfactant, and a conventional laparoscope plus both a titanium dioxide (TiO2)-coated glass (with > or = 15 h of preoperative ultraviolet irradiation) and a water supply. For each, the time from laparoscope insertion into the peritoneal cavity to fogging-induced interruption of surgery was measured. RESULTS: The TiO2-coated glass had unique verified properties of exerting antifogging effects on the oil film after 15 or more hours of previous ultraviolet irradiation, and of inversely accelerating fogging after less than 15 h of previous ultraviolet irradiation. The clinical study showed later fogging with the TiO2-coated glass model, which successfully completed surgery without retraction of the laparoscope from the peritoneal cavity, as compared with the other models. CONCLUSION: An antifogging device using superhydrophilic TiO2-coated glass was very effective in preventing fogging during laparoscopic surgery.

Animals↗
PubMed2006

Suppression of replication fork progression in low-dose-specific p53-dependent S-phase DNA damage checkpoint.

The S-phase DNA damage checkpoint is activated by DNA damage to delay DNA synthesis allowing time to resolve the replication block. We previously discovered the p53-dependent S-phase DNA damage checkpoint in mouse zygotes fertilized with irradiated sperm. Here, we report that the same p53 dependency holds in mouse embryonic fibroblasts (MEFs) at low doses of irradiation. DNA synthesis in p53 wild-type (WT) MEFs was suppressed in a biphasic manner in which a sharp decrease below 2.5 Gy was followed by a more moderate decrease up to 10 Gy. In contrast, p53-/- MEFs exhibited radioresistant DNA synthesis below 2.5 Gy whereas the cells retained the moderate suppression above 5 Gy. DNA fiber analysis revealed that 1 Gy irradiation suppressed replication fork progression in p53 WT MEFs, but not in p53-/- MEFs. Proliferating cell nuclear antigen (PCNA), clamp loader of DNA polymerase, was phosphorylated in WT MEFs after 1 Gy irradiation and redistributed to form foci in the nuclei. In contrast, PCNA was not phosphorylated and dissociated from chromatin in 1 Gy-irradiated p53-/- MEFs. These results demonstrate that the novel low-dose-specific p53-dependent S-phase DNA damage checkpoint is likely to regulate the replication fork movement through phosphorylation of PCNA.

Animals↗
PubMed2006

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolated from patients with community-acquired pneumonia and molecular analysis of multidrug-resistant serotype 19F and 23F strains in Japan.

A nationwide study was undertaken to determine the susceptibility to penicillin and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated from 114 adult patients with community-acquired pneumonia over 22 months at 20 hospitals and medical centres in different regions in Japan. All but five isolates were from sputum. Forty-eight isolates (42.1%) were susceptible, 40 (35.1%) showed intermediate resistance (MIC, 0.12-1.0 microg/ml) and 26 (22.8%) were resistant (MIC, >or=2.0 microg/ml) to penicillin G. All isolates were susceptible to ceftriaxone (breakpoint 1 microg/ml), imipenem (4 microg/ml) and vancomycin (4 microg/ml). Most were resistant to erythromycin, clarithromycin and azithromycin; only two were resistant to levofloxacin. Differences were found in the distribution of serotypes among isolates showing susceptibility to penicillin (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and 23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25 strains of serotype 19F had a single DNA profile, pattern A, a pattern closely similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A strains were not susceptible to penicillin but carried the macrolide resistance gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous but six were highly similar (pattern b) yet distinct from the Spanish multidrug-resistant 23F clone although possibly related to the Taiwan multidrug-resistant 23F clone. The pattern b strains were not susceptible to penicillin and also harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the pandemic multidrug-resistant serotypes should be intensified.

Anti-Bacterial Agents↗
PubMed2006

Retroperitoneal hand-assisted laparoscopic surgery for endoscopic adrenalectomy.

Although hand-assisted laparoscopic surgery (HALS) is very common in various laparoscopic procedures, it is rarely used for retroperitoneal endoscopic adrenalectomy because of the small working area. The authors evaluate HALS in endoscopic adrenalectomy with respect to its use as a rescue procedure in complicated cases. In their department, 47 patients underwent endoscopic adrenalectomies between 1998 and 2004. Mainly because of complicated anatomy, three primary aldosteronism cases were converted to retroperitoneal HALS. This involved making an additional 6 cm skin incision, into which the surgeon's left hand was inserted, with the palm used to create a sufficient visual field and working area. The fingers were used for tactile sensation and blunt resection. For these three cases, successful retroperitoneal HALS in endoscopic adrenalectomy resulted in no mortality or morbidity. These findings indicate that this procedure is a feasible technique for complicated benign adrenal tumor cases.

Adrenalectomy↗
PubMed2006

Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain.

Rifampicin, an antibacterial drug, is highly effective in the treatment of tuberculosis and leprosy. Recently, it has been reported to have neuroprotective effects in in vitro and in vivo models. This study was designed to elucidate its neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity (known as an in vivo mouse model of Parkinson's disease). Mice were injected intraperitoneally (i.p.) with MPTP (10 mg/kg) four times at 1-h intervals, and brains were analyzed 3 or 7 days later. Rifampicin at 20 mg/kg (i.p., twice) had protective effects against MPTP-induced neuronal damage (immunohistochemical changes in tyrosine hydroxylase) in both the substantia nigra and striatum. Rifampicin also protected against the MPTP-induced depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. The maximal concentrations of rifampicin between 30 and 240 min after a single rifampicin injection (20 mg/kg, i.p.) were 2.6 microM (at 30 min) in plasma and 0.77 microM (at 60 min) in striatum. Next, the effects of rifampicin on oxidative stress [lipid peroxidation in mouse brain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. At 1 microM or more, rifampicin significantly inhibited both lipid peroxidation in the striatum and free radical production. These findings suggest that in mice, rifampicin can reach brain tissues at concentrations sufficient to attenuate MPTP-induced neurodegeneration in the nigrostriatal dopaminergic neuronal pathway, and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Epigenetic silencing of AXIN2 in colorectal carcinoma with microsatellite instability.

Mutation or epigenetic silencing of mismatch repair genes, such as MLH1 and MSH2, results in microsatellite instability (MSI) in the genome of a subset of colorectal carcinomas (CRCs). However, little is yet known of genes that directly contribute to tumor formation in such cancers. To characterize MSI-dependent changes in gene expression, we have now compared transcriptomes between fresh CRC specimens positive or negative for MSI (n=10 for each) with the use of high-density oligonucleotide microarrays harboring >44,000 probe sets. Correspondence analysis of the expression patterns of isolated MSI-associated genes revealed that the transcriptome of MSI+ CRCs is clearly distinct from that of MSI- CRCs. Such MSI-associated genes included that for AXIN2, an important component of the WNT signaling pathway. AXIN2 was silenced, apparently as a result of extensive methylation of its promoter region, specifically in MSI+ CRC specimens. Forced expression of AXIN2, either by treatment with 5'-azacytidine or by transfection with AXIN2 cDNA, resulted in rapid cell death in an MSI+ CRC cell line. These data indicate that epigenetic silencing of AXIN2 is specifically associated with carcinogenesis in MSI+ CRCs.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Isolation and characterization of synovial cells from the human temporomandibular joint.

BACKGROUND: The synovial tissues with temporomandibular disorders (TMDs) often show chronic inflammatory changes and the synovial cells participate in the pathogenic processes of TMDs. The synovial membrane is composed of a synovial lining layer and a connective sublining layer. The synovial lining layer is made up of two kinds of cells: macrophage-like type A and fibroblastic type B cells. The aim of this study was to isolate and characterize synovial cells from the human temporomandibular joint (TMJ). METHODS: Synovial cells were isolated using an explant culture method. Then, we characterized the cultured synovial cells (SGA2 cells) using immunocytochemistry. RESULTS: SGA2 cells expressed the fibroblastic markers vimentin and prolyl 4-hydroxylase; they also expressed laminin and heat shock protein 27, all of which are markers of type B cells. However, some cells expressed the macrophage marker CD68. These CD68-positive cells simultaneously expressed laminin. CONCLUSIONS: We isolated and cultured synovial type B cells from the human TMJ, and identified the presence of intermediate type synovial lining cells, having the phenotypic properties of both type A and type B cells, among the synovial lining cells.

Antigens, CD↗
PubMed2006

Simultaneous colorectal and liver resections for synchronous colorectal metastases.

BACKGROUND: The surgical strategy for the treatment of colorectal cancer and synchronous hepatic metastases remains controversial. Many surgeons fear anastomotic leakage and intraperitoneal abscesses when performing a one-step procedure. They prefer a two-step procedure with a liver resection 2 to 3 months after resection of the colorectal primary lesion. SUBJECTS AND METHODS: We analysed medical records from April 1994 to April 2002 for a total of 42 patients with colorectal cancer and synchronous liver metastases who underwent simultaneous liver and colorectal resections with a primary anastomosis. Special attention was paid to data on surgical procedures, postoperative morbidity, and mortality. RESULTS: Forty-two patients, 24 men and 18 women, were studied. Median operating time was 6.50 hours (3.75-11.0 hours), and median blood loss was 1522 ml (range 288 to 5650 ml). Postoperative complications included pleural effusion in 4 patients, ileus in 3, anastomotic leakage in 2, intraperitoneal pelvic abscesses in 1, pneumonia in 1, bile leakage in 1, atelectasis in 1, and wound infection in 1. There was no perioperative mortality. CONCLUSION: Simultaneous colorectal resection with a primary anastomosis and hepatectomy for synchronous liver metastases is considered a safe procedure.

Adult↗
PubMed2006

Evaluation of the position, mobility, and morphology of the disc by MRI before and after four different treatments for temporomandibular joint disorders.

OBJECTIVES: The purpose of this study was to evaluate changes in disc position, mobility, and morphology in patients with temporomandibular joint disorders (TMD) in response to four different treatments, splint therapy, pumping manipulation, arthrocentesis, and arthroscopic surgery, using magnetic resonance imaging (MRI). METHODS: Eighty-five joints (85 patients) with unilateral internal derangement or osteoarthritis that were successfully treated were included in this study. The patients were divided into four groups as follows: splint therapy group, pumping manipulation group, arthrocentesis group, and arthroscopic surgery group. Changes in the disc position, mobility, and morphology before and after treatment were compared among the four groups using MRI. RESULTS: All discs showed anterior disc displacement (ADD) without reduction before treatment. Only 10% of the joints became ADD with reduction after treatment, and the other joints remained ADD without reduction in spite of treatment. Discs treated by arthroscopic surgery were located more anteriorly compared with pre-treatment. In pre-treatment MRI, the rate of stuck disc increased as the stage of the treatment advanced. In post-treatment MRI, all temporomandibular joints (TMJs) had mobile discs. The disc deformity advanced after arthrocentesis and arthroscopic surgery. CONCLUSIONS: Even though clinical signs and symptoms were alleviated by treatment, most discs remained ADD without reduction on MRI in spite of treatment. This suggests that the four treatments do not necessarily improve the position and deformity of the disc, and that arthroscopic surgery advances the deformity and anterior displacement of the disc. Disc mobility is important for improving clinical signs and symptoms.

Adolescent↗
PubMed2006

Frequent involvement of ras-signalling pathways in both polypoid-type and flat-type early-stage colorectal cancers.

The development of colorectal neoplasms proceeds mainly via the adenoma-carcinoma sequence. BRAF and RASSF1A are members of Ras-signaling pathways, but the roles of their aberrations in colorectal carcinogenesis remain unclear. The authors studied mutations of the BRAF and K-ras genes, RASSF1A promoter methylation, and p53 overexpression in 43 polypoid-type and 30 flat-type early-stage colorectal cancers. No tumor simultaneously showed any combination of K-ras mutations, BRAF mutations, and RASSF1A promoter methylation. Three of the 73 tumors (4.1%) had BRAF mutations. All BRAF mutation-positive tumors were flat-type cancers, not associated with coexisting adenoma or p53 overexpression. RASSF1A promoter methylation was detected in 12 out of 73 tumors (16.4%), and the proportion of positive cases was similar in polypoid-type and flat-type cancers. BRAF mutations, K-ras mutations, and RASSF1A promoter methylation independently participate in early-stage colorectal carcinogenesis. BRAF mutations are involved only in flat-type cancers, whereas RASSF1A promoter methylation is involved in both polypoid-type and flat-type cancers. Thus, BRAF mutations most likely participate in de novo colorectal carcinogenesis, K-ras mutations in the adenoma-carcinoma sequence of colorectal carcinogenesis, and RASSF1A promoter methylation in both cascades.

Adenocarcinoma↗
PubMed2005

CT virtual pancreatoscopy: a new method for diagnosing intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

BACKGROUND: We sought to validate computed tomographic virtual pancreatoscopy (CT-VP) created by multidetector row CT (MD-CT) in the clinical diagnosis of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: Five cases of pancreatic IPMNs were included in this study. A nasopancreatic drainage tube was inserted and the pancreatic duct was filled with contrast medium, after which an upper abdominal scan was performed by MD-CT. CT-VP and three-dimensional (3D) CT pancreatographic images were created using a workstation and compared with images by conventional diagnostic techniques. All cases were evaluated by endoscopic retrograde pancreatography (ERP) and three cases of main duct type were assessed by intraoperative real pancreatoscopy (RP). RESULTS: In the main duct cases, papillary projections in the main pancreatic duct and branch orifices were clearly detected by CT-VP. These lesions and structures were confirmed by intraoperative RP, and the CT-VP images were clearer than RP images. In branch cases, a surface-rendering method allowed protruding lesions to be clearly detected in the dilated branches. CONCLUSION: Compared with conventional ERP or RP, CT-VP and 3D-CT pancreatographic images were finer in quality, and the procedures were less invasive, faster, and less expensive. The potential shown by CT-VP with 3D-CT pancreatography in the clinical diagnosis of pancreatic IPMNs suggests that this approach may replace ERP in the near future.

Adenocarcinoma, Mucinous↗
PubMed2005

Retroperitoneoscopic living donor nephrectomy: a safe and minimally invasive procedure for the donor.

A living kidney donor surgery must be safe and minimally invasive. In addition the removed kidney must be in good condition. Retroperitoneoscopic nephrectomy has the advantage that it does not risk intra-abdominal organ injuries and provides direct access to the renal artery/vein despite the small working space. An abdominal wall-lifting method combined with the pneumoretroperitoneum provides sufficient space to use a hand skillfully in retroperitoneoscopic surgery. Introduction of hand-assisted retroperitoneoscopic living donor nephrectomy with the abdominal wall-lifting method yielded safer and easier operations as well as shorter warm ischemia (mean: 3 minutes; 7 seconds) and operative times (mean: 3 hours; 28 minutes) in the current 10 cases. The procedure is a useful alternative to procure a kidney graft.

Adult↗
PubMed2005

Proviral status of HTLV-1 integrated into the host genomic DNA of adult T-cell leukemia cells.

Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and leukemic cells always carry the proviral genome monoclonally integrated into their host genomes at the same sequence site, designated as the monoclonal integration. Using Southern blot hybridization (SBH) and sequenced tagged site polymerase chain reaction assays, we examined the proviral status in 558 clinical specimens from 350 patients who are suspected to have ATL. A total of 321 specimens (57.5%) from 241 patients showed positive results for the monoclonal integration according to SBH, using EcoR1 and Pst1. The 241 patients consisted of 136 patients (56.4%) with the complete provirus (C-type), 62 patients (25.7%) with a defective provirus (D-type), and 43 patients (17.8%) with multibands (M-type). The incidence of the D- and M-types were in the order of smoldering, chronic, and acute subtypes of ATL, suggesting that such an aberrant proviral status is generated on the way to multistep carcinogenesis and is subsequently clinically important for the malignant behavior of the disease. Moreover, our data showed that the partial deletion of the proviral genome is initiated first at the site of the gag region and spreads into the sites of the pol and env regions, whereas the long terminal repeats and pX regions are almost always conserved. These results suggest that analysis of the proviral status provides useful diagnostic and virologic-oncological information about ATL and HTLV-1 pathology, especially the important role of pX gene in tumorigenesis.

Adult↗
PubMed2004

Induction of drug-metabolizing enzymes and transporters in human bronchial epithelial cells by beclomethasone dipropionate.

Inhaled steroids are the most potent anti-inflammatory therapy commonly used in bronchial asthma. There are, however, a small number of asthmatic patients who do not respond to inhaled steroid-treatment. The stimulation of metabolism and excretion of inhaled drugs at bronchial tissues might lead to a decrease in the effect of the drugs, although the molecular mechanism of this resistance is unclear. In this study, we found that beclomethasone dipropionate (BDP) stimulated the expression of mRNAs for uridine 5'-diphosphate glucuronosyl transferase 2B4 and 2B11, and transporters such as multidrug resistance P-glycoprotein, multidrug resistance-associated protein 1 and 2 in cultured bronchial epithelial cells. It is possible that the individual differences of expression of drug metabolizing enzymes and transporters and their enhancement with BDP are implicated in the individual differences of reactivity over steroid medical treatment.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2004

Tracheoesophageal fistula secondary to chemotherapy for malignant B-cell lymphoma of the thyroid: successful surgical treatment with jejunal interposition and mesenteric patch.

We report a case of tracheoesophageal fistula (TEF) secondary to chemotherapy for primary thyroid lymphoma. A 65-year-old man with a short history of a rapidly enlarging neck mass was diagnosed as having thyroid lymphoma of diffuse, large B-cell type. The TEF occurred during the first course of chemotherapy including cyclophosphamide, doxorubicin, vincristine and prednisolone. After placing a feeding gastrostomy without oral intake, eight cycles of chemotherapy were completed and complete remission was achieved. Although the cervical mass disappeared, TEF and esophageal stenosis persisted. Total thyroidectomy and resection of the stenotic cervical esophagus were carried out followed by interposition of the revascularized jejunum and its mesenteric patch to cover the TEF. This seems to be the first report of a TEF caused by chemotherapy for primary thyroid B-cell lymphoma. A variety of treatments for TEF including simple closure, tracheal resection, colonic bypass and muscle flap have been reported with low success rates. Our procedure using a jejunal mesenteric patch seems to be unique and may be a new treatment strategy for TEF.

Aged↗