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Biomedical subjects

M Sugiyama

Publications and source records attributed to M Sugiyama.

At least 91 records · Page 5Linked to original sources
PubMed2001

Colonoscopic treatment of colon cancers.

Recent advances in endoscopic technology have enabled conservative treatment for patients with carcinoma in situ. The treatment of submucosally invasive carcinomas, or malignant polyps, is still controversial, however. The use of widely advocated histologic criteria, such as poorly differentiated histology (Grade III cancer), level 4 invasion or involved margin status, or lymphatic venous invasion as risk factors for adverse outcome, should be examined by multivariate analysis. Unfavorable histology at the invasive margin, PCNA, MUC-1 expression, and chromosomal abnormalities may be new candidates for prognostic indicators in patients with submucosally invasive carcinoma.

Carcinoma in Situ↗
PubMed2001

[Clinical utility and safety of diagnostic thoracoscopy].

The increasing use of thoracoscopy performed under local anesthesia has made contributions to the diagnosis of pleural disease with effusion. During the past 7 years, we have performed 100 such thoracoscopy procedures using a flexible fiberoptic bronchoscope. On the basis of our clinical findings, we are able to discuss the utility and safety of this procedure. The causes of pleural effusion were carcinomatous pleurisy in 72 cases, tuberculosis pleurisy in 15 cases, infection without tuberculosis in 4 cases, malignant pleural mesothelioma in 8 cases and one case of asbestosis. The success rate of thoracoscopic pleural biopsies were 97% for carcinomatous pleurisy, 100% for malignant pleural mesothelioma and 86% for tuberculosis pleurisy. This procedure was performed with no serious effect on blood pressure, oxygen saturation, monitored ECG or BGA data, and with no serious complications. Therefore, we concluded that this method is very useful for the diagnosis of pleural effusions and has few complications.

Adult↗
PubMed2000

Crystal structures of the transposon Tn5-carried bleomycin resistance determinant uncomplexed and complexed with bleomycin.

The transposon Tn5 carries a gene designated ble that confers resistance to bleomycin (Bm). In this study, we determined the x-ray crystal structures of the ble gene product, designated BLMT, uncomplexed and complexed with Bm at 1.7 and 2.5 A resolution, respectively. The structure of BLMT is a dimer with two Bm-binding pockets composed of two large concavities and two long grooves. This crystal structure of BLMT complexed with Bm gives a precise mode for binding of the antibiotic to BLMT. The conformational change of BLMT generated by binding to Bm occurs at a beta-turn composed of the residues from Gln(97) to Thr(102). Crystallographic analysis of Bm bound to BLMT shows that two thiazolium rings of the bithiazole moiety are in the trans conformation. The axial ligand, which binds a metal ion, seems to be the primary amine in the beta-aminoalanine moiety. This report, which is the first with regard to the x-ray crystal structure of Bm, shows that the bithiazole moiety of Bm is far from the metal-binding domain. That is, Bm complexed with BLMT takes a more extended form than the drug complexed with DNA.

Acetyltransferases↗
PubMed2000

Factors associated with preventable out-of-hospital nontraumatic cardiac arrest.

To identify ways to decrease the risk of out-of-hospital cardiac arrest (CA) caused by an acute coronary syndrome, we examined factors associated with the development of CA > or = 1 hour after symptom onset. Multivariate analysis revealed that a low level of physical activity, a history of diabetes mellitus, and a history of unstable angina are associated with out-of-hospital CA occurring > or = hour after symptom onset.

Adult↗
PubMed2000

Extracellular N-domain alone can mediate specific heterophilic adhesion between members of the carcinoembryonic antigen family, CEACAM6 and CEACAM8.

The domain(s) responsible for the specific heterophilic adhesion between two members of the carcinoembryonic antigen (CEA) family, CEACAM6 and CEACAM8, both of which with three extracellular domains, were investigated using Chinese hamster ovary (CHO) transfectants expressing chimeric antigens. Using a chimeric antigen in which the N-domain, a sole extracellular domain, of CEACAM3 was substituted with that of CEACAM6, it was shown that the N-domain of CEACAM6 alone was able to mediate specific adhesion to CEACAM8. Furthermore, the chimeric antigen was shown to bind significantly to chimeric CEA whose N-domain was substituted with that of CEACAM8, but not to unsubstituted CEA. These results demonstrate that the N-domain alone is sufficient and other domains of CEACAM6 or CEACAM8 are not required for this specific binding. We therefore propose a model of heterophilic interaction between the N-domains, which is distinct from that of CEA-CEA homophilic binding.

Animals↗
PubMed2000

Pancreatic duct cell carcinomas express high levels of high mobility group I(Y) proteins.

The high mobility group I (HMGI) family of proteins in mammals belongs to a group of nonhistone nuclear proteins known as architectural transcriptional factors. They function in vivo as both structural components of chromatin and auxiliary gene transcription factors. In an earlier study (N. Abe et al, Cancer Res., 59: 1169-1174, 1999), we demonstrated that the expression level of the HMGI(Y) gene/proteins was significantly increased in colorectal adenocarcinoma and colorectal adenoma with severe cellular atypia. In the current study, we analyzed HMGI(Y) expression in several human pancreatic lesions to investigate (a) whether HMGI(Y) overexpression is also observed in pancreatic carcinoma, and (b) the role of HMGI(Y) in the diagnosis of pancreatic neoplasms. To this end, HMGI(Y) expression was determined at the protein level by immunohistochemistry using a HMGI(Y)-specific antibody in 6 surgically resected specimens of nonneoplastic tissue (4 specimens of normal pancreatic tissue and 2 specimens of chronic pancreatitis tissue), 8 pancreatic cystic neoplasms (5 intraductal papillary mucinous adenomas, 1 serous cystadenoma, and 2 solid pseudopapillary tumors), and 15 duct cell carcinomas of the pancreas. Immunohistochemical analysis revealed intense nuclear staining in the pancreatic carcinoma cells, whereas only very faint nuclear staining was seen in the nonneoplastic cells. There was a strong correlation between HMGI(Y) protein overexpression and a diagnosis of carcinoma (P = 0.000018). Thus, an increased expression level of the HMGI(Y) proteins was clearly associated with the malignant phenotype in pancreatic tissue. In addition, a low level of protein expression was also apparent in two of the cystic neoplasms that exhibited cellular atypia, but not in those that did not exhibit cellular atypia. Based on these findings, we propose that the HMGI(Y) proteins could be closely associated with tumorigenesis in the pancreas and that HMGI(Y) could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignancies unambiguously from normal tissue or benign lesions.

Carcinoma↗
PubMed2000

Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells.

Bone morphogenetic protein (BMP)-2, a member of the BMP family, plays an important role in osteoblast differentiation and bone formation. To discover small molecules that induce BMP-2, a luciferase reporter vector containing the 5'-flanking promoter region of the human BMP-2 gene was constructed and transfected into human osteosarcoma (HOS) cells. By the screening of an in-house natural product library with stably transfected HOS cells, a fungal metabolite, compactin, known as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was isolated. The stimulation of the promoter activity by compactin seemed to be specific for BMP-2 gene in HOS cells, since it had little effect on BMP-4 or SV40 promoter activity and the stimulation was not observed in Chinese hamster ovary (CHO) cells. RT-PCR analysis and alkaline phosphatase assay revealed that compactin induced an increase in the expression of BMP-2 mRNA and protein. Like compactin, simvastatin also activated the BMP-2 promoter, whereas pravastatin did not. The statin-mediated activation of BMP-2 promoter was completely inhibited by the downstream metabolite of HMG-CoA reductase, mevalonate, indicating that the activation was a result of the inhibition of the enzyme. These results suggest that statins, if they are selectively targeted to bone, have beneficial effects in the treatment of osteoporosis or bone fracture.

Anti-Bacterial Agents↗
PubMed2000

Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers.

Smad family members are essential intracellular signaling components of the transforming growth factor-beta (TGF-beta) superfamily involved in a range of biological activities. The loss of sensitivity to TGF-beta is frequent in human lung cancers and inactivation of Smad family members are thought to play important roles in disruption of TGF-beta signaling. In the study presented here, we characterized the biological and biochemical functions of six Smad2 and Smad4 mutants, which we previously identified in human lung cancers. All mutant Smad2 and Smad4 were in fact found to be defective in transmitting growth inhibitory signals originating from TGF-beta and incapable of activating Smad/hFAST-1-mediated transcription. Transcriptional activation of plasminogen activator inhibitor type 1 (PAI-1) was impaired in four of the six mutants due to the defects in homo- and/or hetero-oligomerization with wild-type Smads. In contrast, the remaining two Smad mutants showed a modest reduction in the PAI-1 transcriptional activation and apparently retained the ability to oligomerize with wild-type Smads. Significant loss of growth inhibition and Smad/hFAST-1-mediated transcriptional activation by all of the six mutants suggested that Smad mutants are indeed functionally impaired Smad mutations and may play a role in lung tumorigenesis. Moreover, the present findings suggest that in addition to the impairment in the homo- and/or hetero-oligomerization, there may be an alternative mechanism producing disruption of TGF-beta signaling, involving hFAST-1-or possibly other transcriptional cofactor(s)-mediated transcriptional activation.

DNA-Binding Proteins↗
PubMed2000

The 1.5 A crystal structure of a bleomycin resistance determinant from bleomycin-producing Streptomyces verticillus.

Bleomycin (Bm)-binding protein, designated BLMA, which is a Bm resistance determinant from Bm-producing Streptomyces verticillus, was crystallized in a form suitable for X-ray diffraction analysis. The diffraction intensity data were collected up to a resolution of 1.5 A with a merging R-value of 0.054 at a completeness of 94 %. The BLMA structure, determined by the single isomorphous replacement method including the anomalous scattering effect (SIR-AS) at a resolution of 2.0 A, was refined at 1.5 A resolution. The final R-factor was 19.0 % and R(free) was 22.1 % including 91 water molecules. The crystal packing showed a dimer form, which was generated by arm exchange. The 1.5 A high-resolution experiment allowed an analysis of the side-chain disorder of BLMA. The structural comparison of BLMA with a homologous protein from Streptoalloteichus hindustanus, designated Shble protein, showed that a Ser100-Gly103 loop was farther from the groove, which is a Bm-binding site, in BLMA than in the Shble protein. Furthermore the hydrophobicity of the groove in BLMA is much lower than that in the Shble protein. The structural differences between these proteins may be responsible for the observation that a half-saturating concentration (K(1/2)) of Bm is higher for BLMA than for the Shble protein.

Acetyltransferases↗
PubMed2000

Rectal and vaginal immunization with a macromolecular multicomponent peptide vaccine candidate for HIV-1 infection induces HIV-specific protective immune responses.

An effective vaccine for human immunodeficiency virus (HIV) is needed to stimulate the immune response of the genital mucus to prevent mucosal transmission of the virus. We have developed a macromolecular multicomponent peptide vaccine candidate, VC1. Both rectal and vaginal immunization of VC1 mixed with cholera toxin (CT) induced HIV-1-specific IgA antibody in mouse fecal extract solution and vaginal wash. These antibody productions were enhanced by the combination with IL-4 or GM-CSF expressing plasmids. Either fecal extract or vaginal wash solution from immunized mice inhibited production of HIV-1IIIB p24 protein. The mononuclear cells from spleen, intestinal lymph nodes, or Peyer's patches from VC1- and CT-immunized mice released IFN-gamma or IL-4, when these cells were co-cultured with VC1 antigen. In addition, the regional lymphoid cells from rectal and vaginal region of mice immunized with VC1 and CT also elicited a substantial level of HIV-1-specific cytotoxic T cell (CTL) response. This CTL response was enhanced by the addition of IL-12 expressing plasmid. Our results clearly demonstrated that both rectal and vaginal immunization could induce systemic and mucosal immunities specific for HIV-1.

AIDS Vaccines↗
PubMed2000

Pylorus-preserving total pancreatectomy for pancreatic cancer.

Standard total pancreatectomy (TP) combined with gastric resection often results in uncontrollable diabetes and malnutrition. Pylorus-preserving total pancreatectomy (PPTP) and standard TP for pancreatic cancer were compared in terms of operative outcomes, nutritional recovery, and long-term survival. Twenty-four patients with pancreatic ductal adenocarcinoma (n = 14) or intraductal papillary mucinous carcinoma (N = 10) underwent PPTP (n = 10) or standard TP (n = 14). There were no significant differences in age, gender, or tumor type or stage between the PPTP and standard TP groups. Early (within 30 days of surgery) morbidity and mortality rates were 20% and 0% for PPTP and 29% and 7% for standard TP, respectively. Delayed gastric emptying occurred in 2 patients in each group. The incidence of late complications, including uncontrollable diabetes, diarrhea, and malnutrition, tended to be lower after PPTP (30%) than after standard TP (69%). Serum albumin and body weight at 6 months after surgery were significantly higher in the PPTP than in the standard TP group. Regardless of the tumor type, long-term survival did not differ significantly between patients receiving PPTP and those with standard TP. PPTP for pancreatic cancer improves nutritional recovery, without compromising long-term survival, compared with standard TP.

Adenocarcinoma↗
PubMed2000

Laparoscopic pancreatic cystgastrostomy.

Internal drainage of acute pancreatic pseudocysts is indicated 6 weeks after the first documentation of pseudocyst. It is also indicated for symptomatic chronic pseudocysts 6 cm or more in diameter. When pseudocysts are located in close contact with the posterior wall of the stomach, they are best drained by pseudocyst-gastrostomy. This procedure can also be completed making use of intragastric surgical techniques. Under standard laparoscopic observation, three intragastric ports are placed through the abdominal and anterior gastric walls, establishing working channels for a telescope and hand instruments. After the presence of pseudocysts is confirmed, the posterior wall of the stomach and the cyst wall can be incised by electrocautery. After a sufficient drainage orifice is made and the cyst contents are thoroughly debrided, the intragastric ports are removed and defects in the gastric wall are closed with sutures placed via the standard laparoscopic approach. This approach is much less invasive than the conventional approach, which entails a large gastrotomy in the anterior wall of the stomach. This procedure should be the method of choice when interventional radiology or endoscopic intervention fails to effectively drain retrogastric pseudocysts.

Drainage↗
PubMed2000

Endoscopic biliary stenting for treatment of persistent biliary fistula after blunt hepatic injury.

BACKGROUND: Surgical treatment for persistent biliary fistula after blunt hepatic injury is often technically difficult. Endoscopic treatment for such fistulas has been described only infrequently. METHODS: We reviewed 6 patients who underwent endoscopic biliary stent placement with (n = 1) or without (n = 5) sphincterotomy for persistent (12 to 138 days; mean 48 days) biliary fistula after blunt hepatic injury. RESULTS: ERCP showed bile leakage from a second-order or more peripheral branch of the intrahepatic bile ducts in 5 patients but failed to reveal the fistula in 1. Stent placement was successful without complications in all patients. Bile leakage resolved within 1 to 3 days in 5 patients. After 36 to 86 days, the stent was removed and ERCP confirmed disappearance of the fistula. These patients have remained asymptomatic for a mean of 2.6 years since stent removal. In the patient in whom ERCP had not shown a fistula, bile leakage continued despite successful stent placement. CONCLUSIONS: Endoscopic biliary stent placement is a rapid, safe and effective treatment for persistent post-traumatic biliary fistula demonstrated by ERCP.

Adult↗
PubMed2000

Genetic analysis of plant morphogenesis in vitro.

Plant morphogenesis in vitro such as somatic embryogenesis and adventitious organogenesis has provided useful systems for physiological, biochemical, and molecular biological studies on plant development. Advantages of the in vitro systems are currently being combined with genetic techniques to generate new insights into fundamental mechanisms of plant development. This article presents an overview of genetic analysis of plant morphogenesis in vitro including genetic variation of tissue culture responses, mutational analysis of somatic embryogenesis, and mutational analysis of adventitious organogenesis.

Cells, Cultured↗
PubMed2000

Difference in urinary LTE4 and 11-dehydro-TXB2 excretion in asthmatic patients.

Bronchoconstrictor cysteinyl leukotrienes (LT) and thromboxane (TX) A2 have been implicated in the pathogenesis of asthma. Determination of urinary leukotriene E4 (LTE4) and 11-dehydro-TXB2 levels are often used to assess cysteinyl LT and TXA2 production in humans. To define the potential role in the pathogenesis of asthma, we investigated the urinary LTE4 and 11-dehydro-TXB2 levels. LTE4 and 11-dehydro-TXB2 levels were determined using liquid chromatography/tandem mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS), respectively. Urinary LTE4 levels in asthmatic patients (192 +/- 122 pg/mg creatinine, n = 14) were significantly higher (P < 0.005) than those in healthy volunteers (55 +/- 16 pg/mg creatinine, n = 13), but no significant difference in 11-dehydro-TXB2 levels was observed. A significant inverse correlation (r = -0.821, P < 0.005) was found between urinary LTE4 levels and the forced expiratory volume in 1 s (FEV1) but no significant correlation was observed between urinary 11-dehydro-TXB2 levels and FEV1. The present findings suggest that cysteinyl LTs play a more important role in the pathogenesis of asthma than TXA2.

Adult↗
PubMed2000

Crystallization and preliminary X-ray diffraction studies of Streptomyces phospholipase A2 in a calcium-binding form.

Phospholipase A2 (PLA2) as a calcium-binding form, produced by Streptomyces violaceoruber, was crystallized in a form suitable for the diffraction analysis using the vapor diffusion method. Crystals were grown in 0.1 M Tris-HCl buffer (pH 8.5), 20 mM Ca2+ containing 50-60% (v/v) 2-methyl-2,4-pentanediol as a precipitant. They belong to the monoclinic space group P2(1), with the cell dimensions a=38.3 A, b=54.3 A, c=30.6 A, and beta=90.2 degrees. The crystals diffract the X-ray well and the diffraction intensity data were collected up to 1.6 A resolution. The crystal volume per unit mass, V(M) is 2.35 A3 Da(-1) with one molecule in the asymmetric unit, which corresponds to a solvent content of 47.7%.

Calcium↗