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Biomedical subjects

Y Fujiwara

Publications and source records attributed to Y Fujiwara.

At least 109 records · Page 6Linked to original sources

[Pulmonary complications following laparoscopic cholecystectomy in patients with abnormal spirometry].

The purpose of this study was to determine the incidence of postoperative pulmonary complications (PPC) and the value of preoperative spirometry to predict PPC after laparoscopic cholecystectomy. Sixty-four of 1372 patients (8%) showed abnormal spirometry data. One out of 1372 patients developed aspiration pneumonia. The patient had high risk factors for serious PPC such as ASA physical status 4.84 y/o, longer anesthesia duration (230 min), multiple brain infarction and low albuminemia. Thirty to 39% of patients with abnormal spirometry showed less severe PPC such as atelectasis, lung collapse and pleural effusion, and incidence was the similar with normal lung function patients. Postoperative blood gas analysis showed a slight increase in arterial carbon dioxide tension during oxygen therapy. However, none of the patients with abnormal spirometry and less severe PPC developed manifest PPC (pneumonia, respiratory failure). Less severe PPC disappeared within second to third postoperative days. We conclude that laparoscopic intervention significantly reduced the incidence of severe PPC and the preoperative spirometry was not recommended in patients with no pulmonary symptoms.

Aged↗

Bilirubin as a tracer for detecting gastroesophageal reflux.

PURPOSE: The usefulness of intraesophageal monitoring of bilirubin, in diagnosing gastroesophageal reflux, was studied. PATIENTS AND METHODS: Bilirubin concentration and pH at 5 cm oral and anal to the esophagogastric junction were monitored for 24 hours in 19 patients with reflux esophagitis. The duration of bilirubin presented and pH less than 4.0 were obtained as the holding time (HT) of bilirubin and acid, respectively. RESULTS: There was no difference between HT of bilirubin and acid in the stomach and esophagus. In the stomach, HT of bilirubin did not correlate with acid. Whereas, in both of bilirubin and acid, HT in the esophagus correlated significantly with that in the stomach. The correlation was more definite for bilirubin than acid. CONCLUSIONS: Bilirubin and acid presented in the upper stomach for sufficient period independently. Bilirubin monitoring was useful to evaluate the etiology of damaging the esophageal mucosa and causes of symptoms by estimating duodenogastro-esophageal reflux, which has synergistic effect with acid.

Adult↗

Proteoglycans synthesized by cultured bovine aortic smooth muscle cells after exposure to lead: lead selectively inhibits the synthesis of versican, a large chondroitin sulfate proteoglycan.

To investigate the effects of lead on the formation of extracellular matrix in the vascular wall, we characterized proteoglycans synthesized by cultured vascular smooth muscle cells after exposure to the metal by biochemical techniques. Confluent cultures of bovine aortic smooth muscle cells were metabolically labeled with [(35)S]sulfate or [(35)S]methionine/cysteine in the presence of lead nitrate. The amount of glycosaminoglycans (GAGs) was evaluated by the incorporation of [(35)S]sulfate into GAGs by the cetylpyridinium chloride precipitation method. The labeled proteoglycans were characterized by DEAE-Sephacel ion exchange chromatography and Sepharose CL-2B molecular sieve chromatography. The GAG M(r) and composition were analyzed by Sepharose CL-6B chromatography, and the core protein M(r) was analyzed by SDS-polyacrylamide gel electrophoresis, before and after digestion with papain or chondroitin ABC lyase. Lead significantly decreased the [(35)S]sulfate incorporation into GAGs accumulated in the cell layer and the conditioned medium. [(35)S]Sulfate-labeled proteoglycans obtained from the cell layer and the conditioned medium were separated into three peaks on DEAE-Sephacel chromatography and only the peak with the highest charge density was decreased by lead. The highly charged peak was eluted near the void volume on Sepharose CL-2B molecular sieve chromatography and sensitive to chondroitin ABC lyase on Sepharose CL-6B chromatography, indicating that lead selectively inhibits the synthesis of large and highly charged chondroitin/dermatan sulfate proteoglycans (CS/DSPGs). However, the size of chondroitin/dermatan sulfate chains of the CS/DSPGs was M(r) approximately 47000 in both the control and lead-treated cultures. On the other hand, lead decreased the accumulation of a large CS/DSPG with a core protein of approximately 450 kDa in the cell layer and the conditioned medium; the core protein was identified as versican core by Western blot analysis. It is therefore suggested that lead inhibits the synthesis of the versican core protein in vascular smooth muscle cells without a change in length of chondroitin/dermatan sulfate side chains. As a result, versican-poor extracellular matrix would be induced by lead in vascular smooth muscle cells.

Animals↗

New method for preparation of coumarins and quinolinones via Pd-catalyzed intramolecular hydroarylation of C-C triple bonds.

A new and general method has been developed for preparation of coumarins and quinolinones by intramolecular hydroarylation of alkynes. Various aryl alkynoates and alkynanilides undergo fast intramolecular reaction at room temperature in the presence of a catalytic amount of Pd(OAc)(2) in a mixed solvent containing trifluoroacetic acid (TFA), affording coumarins and quinolinones in moderate to excellent yields with more than 1000 turnover numbers (TON) to Pd. The methodology proved to tolerate a number of functional groups such as Br and CHO. On the basis of isotope experiments, a possible mechanism involving ethynyl chelation-assisted electrophilic metalation of aromatic C-H bonds by in-situ generated cationic Pd(II) species has been discussed. Also the involvement of vinylcationic species has been suggested.

Catalysis↗

Pd-catalyzed selective addition of heteroaromatic C-H bonds to C-C triple bonds under mild conditions.

Simple heteroarenes such as pyrroles and indoles undergo addition reactions to C-C triple bonds in the presence of a catalytic amount of Pd(OAc)(2) under very mild conditions, affording cis-heteroarylalkenes in most cases. The cleavage of aromatic C-H bonds is the possible rate-determining step in CH(2)Cl(2), and the addition of heteroaromatic C-H bonds to C-C triple bonds is in a trans-fashion.

Catalysis↗

Orientations and locations of local anesthetics benzocaine and butamben in phospholipid membranes as studied by 2H NMR spectroscopy.

This paper presents experimental evidence that an aromatic compound that has a quadrupole moment locates in a polar headgroup region in the lipid membranes, but not in a membrane interior hydrophobic region, and discusses correlation to the site of action of benzocaine and butamben on sodium channels. The 2H NMR spectra of benzocaine-d4, benzocaine-d5, butamben-d4, and butamben-d9 in the model membranes were observed. The 2H NMR spectra of perdeuterated palmitic acid and selectively deuterated palmitic acids at C2, C3, C5, C6, C9, or C10, which were inserted into the lipid membranes, were also observed. The phosphatidylserine (PS), phosphatidylcholine (PC), and liquid mixtures composed of PS, PC, and phosphatidylethanolamine (PE), which contain or do not contain cholesterol, were employed. A moment analysis was applied to the 2H NMR spectra of palmitic-d31 acid. An order parameter, S(CD), for each carbon segment was calculated from the observed quadruple splitting. We concluded that in the lipid mixture containing cholesterol, the aromatic rings of benzocaine and butamben locate around the glycerol moiety of the lipids and that when there exists no cholesterol, they locate a little more inside from the headgroup region, directing, in both cases, their amino groups upward (polar region) and the ethyl and butyl groups downward (hydrophobic region). These data cast a question on the site of action of the neutral local anesthetics in the sodium channels.

Anesthetics, Local↗

A role for the C3a anaphylatoxin receptor in the effector phase of asthma.

Asthma is a chronic inflammatory disease of the airways and lung mucosa with a strong correlation to atopy and acquired (IgE) immunity. However, many features of bronchial asthma, such as smooth muscle contraction, mucus secretion and recruitment of inflammatory cells, are consistent with the actions of complement anaphylatoxins, in particular C3a and C5a. Complement activation forms a central core of innate immune defence against mucosal bacteria, viruses, fungi, helminths and other pathogens. As a system of 'pattern-recognition molecules', foreign surface antigens and immune complexes lead to a proteolytic cascade culminating in a lytic membrane attack. The anaphylatoxins C3a and C5a are liberated as activation byproducts and are potent pro-inflammatory mediators that bind to specific cell surface receptors and cause leukocyte activation, smooth muscle contraction and vascular permeability. Here we show that in a murine model of allergic airway disease, genetic deletion of the C3a receptor protects against the changes in lung physiology seen after allergen challenge. Furthermore, human asthmatics develop significant levels of ligand C3a following intra-pulmonary deposition of allergen, but not saline. We propose that, in addition to acquired immune responses, the innate immune system and complement (C3a in particular) are involved in the pathogenesis of asthma.

Animals↗

Glutathione S-transferase-pi gene expression and platinum drug exposure in human lung cancer.

We examined the association between the gene expression levels of glutathione S-transferase-pi (GST-pi) and platinum drug exposure in human lung cancer. First we monitored GST-pi gene expression levels in two lung cancer cell lines and in peripheral mononuclear cells of ten previously untreated lung cancer patients after platinum drug exposure. Next we examined GST-pi gene expression levels in 40 lung cancer autopsy specimens. The GST-pi gene expression levels were assessed by the quantitative reverse transcription-polymerase chain reaction or Northern blot analysis. The GST-pi gene expression was not induced by platinum drugs either in vitro and in vivo within 24 h of exposure. In contrast, GST-pi gene expression levels in lung cancer tissues of patients who had been exposed to platinum drugs at least 1 month before death were significantly higher than that in those of patients who had not been exposed. These results suggest that GST-pi gene expression is associated with chronic exposure to platinum drugs in lung cancer and/or the stress response to xenobiotics.

Antineoplastic Agents↗

FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium.

We disrupted the FOG-2 gene in mice to define its requirement in vivo. FOG-2(-/-) embryos die at midgestation with a cardiac defect characterized by a thin ventricular myocardium, common atrioventricular canal, and the tetralogy of Fallot malformation. Remarkably, coronary vasculature is absent in FOG-2(-/-) hearts. Despite formation of an intact epicardial layer and expression of epicardium-specific genes, markers of cardiac vessel development (ICAM-2 and FLK-1) are not detected, indicative of failure to activate their expression and/or to initiate the epithelial to mesenchymal transformation of epicardial cells. Transgenic reexpression of FOG-2 in cardiomyocytes rescues the FOG-2(-/-) vascular phenotype, demonstrating that FOG-2 function in myocardium is required and sufficient for coronary vessel development. Our findings provide the molecular inroad into the induction of coronary vasculature by myocardium in the developing heart.

Animals↗

Prevention of cross-contamination during sampling procedure in molecular detection for cancer micrometastasis.

Reverse transcriptase-polymerase chain reaction (RT-PCR) techniques have been widely employed as an ultra-sensitive method for detection of micrometastases in patients with various types of malignancies. Messenger RNA of a specific marker gene is a target for RT-PCR amplification to examine the presence of micrometastases in body fluids or tissues obtained from human. We developed the RT-PCR assay specific for rat beta-actin mRNA, which cannot detect human counterpart and assessed how much contamination of rat tissues can influence the result of RT-PCR assay and how to avoid the influence of the contamination in RT-PCR assay.

Actins↗

Increased expression of the MRP5 gene is associated with exposure to platinum drugs in lung cancer.

To investigate the role of the multidrug resistance-associated protein (MRP1) homologue MRP5 in relation to platinum drug resistance, we examined the steady-state levels of the mRNAs for MRP5 in both lung cancer cell lines and peripheral mononuclear cells (PMN) after exposure to platinum drug and in normal lung and lung cancer tissue specimens. Firstly, we examined MRP5 gene expression levels in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) from 40 patients who had died from lung cancer. Next, we monitored MRP5 gene expression levels within 24 hr in both lung cancer cell lines incubated with cisplatin and in PMN from 10 previously untreated lung cancer patients after carboplatin administration alone. The MRP5 gene expression levels were assessed by quantitative reverse transcription polymerase chain reaction or RNase protection assay. The MRP5 expression levels in normal lung tissues and in tumors from patients exposed to platinum drugs during their lifetime were significantly higher than those in tissues from non-exposed patients. On the other hand, the MRP5 expression levels were not rapidly induced by platinum drugs either in lung cancer cell lines or in PMN within 24 hr. Our results suggest that increased expression levels of the MRP5 gene are associated with exposure to platinum drugs in lung cancer in vivo and/or the chronic stress response to xenobiotics.

ATP-Binding Cassette Transporters↗

Efficient activation of aromatic C-H bonds for addition to C-C multiple bonds

Efficient electrophilic metalation of aromatic C-H bonds leading to new C-C bond formation through regio- and stereoselective addition to alkynes and alkenes has been realized by a catalytic amount (0.02 to 5 mole percent) of palladium(II) or platinum(II) compounds in a mixed solvent containing trifluoroacetic acid at room temperature. Various arenes undergo unexpected selective trans hydroarylation to terminal or internal C&cjs0812;C bonds inter- and intramolecularly with high efficiency (up to a turnover number of 4500 for palladium), especially for electron-rich arenes, giving thermodynamically unfavorable cis-alkenes, and the oxygen- and nitrogen-containing heterocycles. The simplicity, generality, and efficiency of this process should be very attractive to the possible industrial application for the functionalization of arenes.

Journal Article↗

Mammaglobin B gene as a novel marker for lymph node micrometastasis in patients with abdominal cancers.

Mammaglobin B is a recently-isolated gene speculated to belong to the uteroglobin gene family and is overexpressed in primary breast cancers. We investigated mammaglobin B mRNA expression in various cancers of the digestive system. Given the absence of mammaglobin B expression in normal lymph nodes, we also assessed the usefulness of mammaglobin B as a marker for lymph node micrometastases in cancer patients. Mammaglobin B gene transcripts were frequently detected by reverse transcriptase-polymerase chain reaction (RT-PCR) assay in primary tumors of the esophagus (2/3), stomach (7/7), colon (15/15), pancreas (4/6), common bile duct (6/6), cholangioma (2/2) and gall bladder (1/1). Mammaglobin B overexpression was observed in three of 15 cases (20%) of colon cancer, suggesting its possible contribution to colon carcinogenesis. Down-regulated mammaglobin B expression was observed in hepatoma cells in comparison with corresponding non-cancerous livers (3/3). RT-PCR assay of mammaglobin B detected 14 of 15 histologically positive lymph nodes from patients with gastric cancer, colon cancer and cholangioma. Seven of 32 (22%), three of nine (33%), and three of seven (43%) histologically negative nodes from patients with gastric, colon and cholangiocellular carcinoma, respectively, were found to express mammaglobin B mRNA. Our results showed that expression of mammaglobin B was frequently detected in cancers originating in digestive organs, especially adenocarcinomas, and that mammaglobin B gene detected by RT-PCR may be a potentially useful molecular marker for lymph node micrometastases of various digestive organ cancers.

Abdominal Neoplasms↗

Molecular detection of metastatic pancreatic carcinoma cells using a multimarker reverse transcriptase-polymerase chain reaction assay.

BACKGROUND: The diagnosis of pancreatic carcinoma is often associated with a poor prognosis, because most patients already have advanced disease. A highly sensitive assay to detect the progression of pancreatic carcinoma would be of significant clinical utility. The authors developed multiple tumor mRNA markers for reverse transcriptase-polymerase chain reaction (RT-PCR) to detect metastatic tumor cells in the blood and tissue of patients with American Joint Committee on Cancer (AJCC) Stage II/III or IV pancreatic carcinoma. METHODS: An RT-PCR plus Southern blot assay was used to detect mRNA of tumor markers in blood and tissues. mRNA expression of the tumor progression markers MET (hepatocyte growth factor receptor gene c-met), GalNAc-T (beta1,4- N-acetyl-galactosaminyl-transferase), and beta-hCG (beta-human chorionic gonadotropin) was evaluated in 9 pancreatic carcinoma cell lines, 13 tumor biopsy specimens, 5 nonmalignant pancreatic tissue specimens, and blood from 33 pancreatic carcinoma patients and 32 healthy donors. RESULTS: The detection limit of the assay was 1 rhog, 10 rhog, and 10 rhog for MET, GalNAc-T, and beta-hCG mRNA expression, respectively. The pancreatic carcinoma cell lines expressed all three mRNA markers. Of blood specimens from 17 patients with AJCC Stage IV pancreatic carcinoma, 82%, 65%, and 76% were MET, GalNAc-T, and beta-hCG mRNA positive, respectively. Of blood specimens from 16 patients with AJCC Stage II/III disease, 88% were positive for at least 1 mRNA marker. CONCLUSIONS: A multiple molecular marker assay was developed to detect cancer cells in blood and tissue from patients with different stages of pancreatic carcinoma. The detection of cancer cells in the blood may be used as a marker of pancreatic tumor progression and may be useful in monitoring response to therapy.

Antigens, Neoplasm↗

Three-component coupling of acylphosphonates and two carbonyl compounds promoted by low-valent samariums: one-Pot synthesis of beta-hydroxyphosphonates

Three-component coupling of acylphosphonates and two carbonyl compounds leading to beta-hydroxyphosphonates has been achieved with low-valent samariums. Thus, acylphosphonates reacted with aldehydes in the presence of semicatalytic amounts of samarium metal or SmI(2) to give acyloxyphosphonates in good yields. The second coupling reaction of the acyloxyphosphonates with aldehydes or ketones promoted by SmI(2) afforded beta-hydroxyphosphonates instead of olefins. Moreover, these two reactions could be carried out in one pot.

Journal Article↗

Ermap, a gene coding for a novel erythroid specific adhesion/receptor membrane protein.

Ermap (erythroid membrane-associated protein), a gene coding for a novel transmembrane protein produced exclusively in erythroid cells, is described. It is mapped to murine Chromosome 4, 57 cM distal to the centromere. The initial cDNA clone was isolated from a day 9 murine embryonic erythroid cell cDNA library. The predicted peptide sequence suggests that ERMAP is a transmembrane protein with two extracellular immunoglobulin folds, as well as a highly conserved B30.2 domain and several phosphorylation consensus sequences in the cytoplasmic region. ERMAP shares a high homology throughout the entire peptide with butyrophilin, a glycoprotein essential for milk lipid droplet formation and release. A GFP-ERMAP fusion protein was localized to the plasma membrane and cytoplasmic vesicles in transiently transfected 293T cells. Northern blot analysis and in-situ hybridization demonstrated that Ermap expression was restricted to fetal and adult erythroid tissues. ERMAP is likely a novel adhesion/receptor molecule specific for erythroid cells.

Amino Acid Sequence↗