Search PubMed⌕ Search

Biomedical subjects

M Nagasawa

Publications and source records attributed to M Nagasawa.

At least 37 records · Page 2Linked to original sources

Enhanced hepatic lipid peroxidation in patients with primary biliary cirrhosis.

OBJECTIVE: The mechanisms responsible for hepatic injury have not been fully clarified in primary biliary cirrhosis (PBC). It has recently been suggested that hepatic lipid peroxidation may be involved in the pathogenesis of PBC. The aims of the current study were to determine whether patients with PBC have evidence of enhanced hepatic lipid peroxidation and to evaluate its relationship to clinicopathological features. METHODS: Immunohistochemical detection of 4-hydroxynonenal (HNE) protein adducts was performed in the liver biopsies of 20 patients with PBC. Histological stages of PBC were evaluated. Orcein or Victoria blue staining was performed for detection of copper-associated proteins. The size of bile ducts was defined as the smallest diameter between the subepithelial basement membranes. RESULTS: All 20 patients had immunodetectable HNE protein adducts in the cytoplasm of damaged, but also intact, biliary cells. The mean diameter of bile ducts with HNE protein adducts was smaller than those without the adducts (61.0 +/- 1.9 vs 122.5 +/- 24.4 microm, respectively, p < 0.01). Out of 20 patients, 6 (30%) also had immunodetectable HNE protein adducts in hepatocytes preferentially located around the portal tracts. Most of the patients with hepatocytic HNE protein adducts had copper-associated protein granules in hepatocytes around the portal tracts and were classified as histological stage 3, whereas all of the patients without the adducts lacked copper-associated protein granules and were classified as histological stage 1 or 2. The patients with hepatocytic HNE protein adducts had higher levels of serum total bilirubin than did those without the adducts (2.9 +/- 0.9 vs 0.7 +/- 0.1 mg/dl, respectively, p < 0.01). CONCLUSIONS: Hepatic lipid peroxidation can occur in PBC and may be an early event in bile duct destruction. At advanced stages of PBC, hepatocellular lipid peroxidation may play a role in hepatocyte injury during cholestasis.

Aldehydes↗

Effects of ZNC-2381, a new oral compound, on several hepatic injury models and on hepatocellular apoptosis in mice and rats.

The hepatoprotective effect of ZNC-2381 (1-(4-aminophenyl) methyl-3-(3-nitrophenyl)-1,3-dihydroimidazo[4,5-b]pyridine-2-one), a novel 2-one dihydroimidazopyridine derivative, has been evaluated in several experimental models of hepatic injury. In mice, oral ZNC-2381, administered at doses of 3, 10 or 30 mgkg(-1), 1 h before induction of hepatic injury with concanavalin A, dose-dependently inhibited increases in serum alanine aminotransferase (ALT) activity. Apoptosis of liver cells, as indicated by DNA fragmentation (nucleosome assay) and DNA-ladder formation (electrophoresis), was also inhibited dose-dependently. ZNC-2381 dose-dependently inhibited concanavalin A-induced increases in serum tumour necrosis factor (TNF)-alpha levels, and TNF-alpha mRNA expression in the liver. Oral ZNC-2381 also dose-dependently inhibited increases in serum ALT activity in mice with hepatic injury induced by Propionibacterium acnes and a bacterial lipopolysaccharide (LPS) or D-galactosamine-LPS, and in rats with D-galactosamine-induced hepatic injury. These results indicate that oral ZNC-2381 inhibits cytokine (TNF-alpha) production and cytokine-related hepatocellular apoptosis, and might thus prevent different types of hepatic injury.

Alanine Transaminase↗

Evaluation of portosystemic collaterals by SPECT imaging after endoscopic variceal sclerotherapy: usefulness for predicting recurrence.

UNLABELLED: Bleeding from esophageal varices is a major cause of morbidity and mortality in cirrhotic patients. Identification of patients at high risk for bleeding is particularly important. The aim of this study was to determine whether detection of portosystemic collaterals by SPECT could predict the outcome of endoscopic injection sclerotherapy of esophageal varices and be useful for selecting appropriate therapy. METHODS: Sixty-two patients with liver cirrhosis who were considered at high risk of bleeding were treated with endoscopic injection sclerotherapy. Endoscopy was performed every 3 mo after therapy or until bleeding occurred. Before and within 2 wk after therapy, tomographic images of intra-abdominal blood pool were constructed by SPECT. RESULTS: Before therapy, the following portosystemic collateral routes were observed: coronary veins in 53 (85.5%) of 62 patients, short gastric veins in 8 patients (12.9%), splenorenal shunts in 10 patients (16.1%), and paraumbilical veins in 6 patients (9.7%). Patients positive for imaging of coronary veins were divided into 3 groups on the basis of changes in images after therapy: complete responders (n = 17), whose coronary vein images disappeared completely; partial responders (n = 18), whose images became smaller; and nonresponders (n = 18), whose images did not change significantly before or after therapy. The rates of recurrence after endoscopic injection sclerotherapy until 6 mo in complete responders (4/17, 23.5%) and partial responders (7/18, 38.9%) were significantly less (P < 0.05) than that in nonresponders (11/13, 84.6%). The rate of recurrence of esophageal varices until 6 mo in nonresponders treated with additional submucosal injection sclerotherapy (1/5, 20.0%) was significantly less (P < 0.05) than that in nonresponders without additional submucosal injection sclerotherapy (11/13, 84.6%). CONCLUSION: Abdominal blood-pool SPECT, a noninvasive method, is useful for evaluating the therapeutic effectiveness of endoscopic sclerotherapy, for predicting the recurrence of varices, and for selecting appropriate management after sclerotherapy.

Collateral Circulation↗

[Effects of 4-hydroxybenzoic acid methyl ester on the Ca(2+)-related functions of skinned skeletal muscle fibers from the guinea pig].

The amide-linked local anesthetics can be used safely in patients susceptible to malignant hyperthermia (MH). 4-Hydroxybenzoic acid methyl ester contained as a preservative in local anesthetic solution was suspected to have triggered MH in a patient who had received nerve block with lidocaine solution. The author investigated the effects of 4-hydroxybenzoic acid methyl ester on Ca(2+)-related functions of the skeletal muscle using saponin-treated skinned fibers from the extensor digitorum longus muscle of guinea pigs. 4-Hydroxybenzoic acid methyl ester accelerated the Ca2+ induced Ca2+ release (CICR) rate from the sarcoplasmic reticulum (SR) in a dose-dependent manner, and the Ca2+ concentration-CICR rate curves were shifted to the left with 4-hydroxybenzoic acid methyl ester at concentrations above 30 microM. 30 microM of 4-hydroxybenzoic acid methyl ester is associated with a plasma concentration of lidocaine intoxication which induces general convulsion. Ca2+ uptake, initial rate of Ca2+ uptake by the SR and Ca2+ sensitivity of the contractile system were not affected by 100 microM of 4-hydroxybenzoic acid methyl ester. These results suggest that amide-type local anesthetic solutions and agents containing 4-hydroxybenzoic acid methyl ester as a preservative may trigger MH in MH susceptible patients, if they are accidentally administered into the blood vessel.

Anesthetics, Local↗

[Proceeding of the workshop "What an ideal clinical microbiological laboratory should be". The 33rd in-service training course for medical technologists of university hospitals in 1999].

In the workshop of the 33rd in-service training course for University Hospital Medical Technologists in 1999(sponsorship: the ministry of Education), all groups of participants were charged with discussing an ideal clinical microbiology laboratory. In conclusion, the successful operation of the ideal system of clinical microbiology should require a high level of competence in every staff member of the hospital. It must not be focused solely on the sophistication of laboratory methods. We must modify our behavior effectively and establish a good collaborative partnership with physicians and other health care professionals.

Clinical Laboratory Techniques↗

["What an ideal clinical microbiological laboratory should be"--from the position of medical technologist].

The evolution of the microbiology laboratory is necessary for correspondence to the transfiguration of infection and contribution to clinical applications. Especially, the correspondence of emergency tests such as smear strain and antigen detection, the report added value and the infection surveillance in team medical treatment are indispensable. Also, medical technologists need to be knowledge able about techniques related to infection overall, and participation in infection diagnosis and social responsibility are indispensable.

Japan↗

[The effects of human atrial natriuretic peptide on the pediatric recipients of living-related renal transplantation].

We evaluated the effects of human natriuretic peptide (hANP) on the recipients of living-related renal transplantation in children. Anesthesia was maintained with nitrous-oxide and isoflurane in oxygen. The recipients were divided into two groups: the hANP group (n = 8) received continuous infusion of hANP (0.1 microgram.kg-1.min-1), and the control group (n = 5) received no hANP infusion. Intravenous hANP infusion was started at the loading time of fresh frozen plasma in the recipients until the 12 hours after operation. There were no differences between the groups with regards to age, height, body weight, changes in heart rate and systolic arterial pressure, urine volume during operation, and the levels of blood uremic nitrogen and creatinine. The hANP group showed minimal change in CVP during operation and body weight between the values during and after operation compared with control group. The control group needed significantly more fluid than hANP group during operation. We concluded that continuous i.v. hANP infusion in the pediatric recipients of living-related renal transplantation was useful for maintaining sufficient urination and prevention of heart failure or lung edema.

Anesthesia, General↗

Inactivation of NF-kappaB by EBV BZLF-1-encoded ZEBRA protein in human T cells.

We have previously shown that the EBV ZEBRA protein (also denoted EB1, Z, or Zta) encoded by the BZLF open reading frame is expressed in primary human thymocytes and in human T lymphoblastoid cell lines infected by EBV. Expression of EBV-encoded gene products in T lymphocytes could contribute to viral pathogenesis during acute EBV infection as well as in individuals coinfected with EBV and HIV. HPB-ALL and Jurkat T lymphoblastoid cell lines transiently and stably expressing ZEBRA were characterized in this work. Expression of ZEBRA protein in human T lymphoblastoid cells was associated with decreased expression of an NF-kappaB reporter gene, altered expression of the NF-kappaB p50 protein subunit, and decreased DNA binding by components of NF-kappaB. These observations suggest that inactivation of NF-kappaB transcription by ZEBRA in EBV-infected T cells may be a novel mechanism of viral pathogenesis analogous in part to over-expression of the endogenous cytoplasmic inhibitor of NF-kappaB, IkappaBalpha.

DNA-Binding Proteins↗

Molecular identification of a eukaryotic, stretch-activated nonselective cation channel.

Calcium-permeable, stretch-activated nonselective cation (SA Cat) channels mediate cellular responses to mechanical stimuli. However, genes encoding such channels have not been identified in eukaryotes. The yeast MID1 gene product (Mid1) is required for calcium influx in the yeast Saccharomyces cerevisiae. Functional expression of Mid1 in Chinese hamster ovary cells conferred sensitivity to mechanical stress that resulted in increases in both calcium conductance and the concentration of cytosolic free calcium. These increases were dependent on the presence of extracellular calcium and were reduced by gadolinium, a blocker of SA Cat channels. Single-channel analyses with cell-attached patches revealed that Mid1 acts as a calcium-permeable, cation-selective stretch-activated channel with a conductance of 32 picosiemens at 150 millimolar cesium chloride in the pipette. Thus, Mid1 appears to be a eukaryotic, SA Cat channel.

Amino Acid Sequence↗

Descending necrotizing mediastinitis with sternocostoclavicular osteomyelitis and partial thoracic empyema: report of a case.

We present herein the case of a 50-year-old woman in whom descending necrotizing mediastinitis originating from an anterior neck abscess spread to the left upper bony thorax, resulting in osteomyelitis of the left sternocostoclavicular articulation and left partial thoracic empyema. Transcervical mediastinal irrigation and drainage was performed with aggressive antibiotic therapy, followed by resection of the left sternocostoclavicular joint and debridement of the anterior mediastinum. The patient had an uneventful postoperative course, and her left arm and shoulder mobility was well preserved.

Abscess↗

EBV infection induced transformation of benign T lymphoproliferative state in patient with chronic active EBV infection into malignant lymphoma: implication of EBV infection as additive oncogenic factor in tumorigenesis.

An 11-year-old girl with chronic EBV (Epstein-Barr virus) infection, who later developed malignant lymphoma in the lung, is reported. She had an increased number of V alpha2, V beta8, CD3, CD4, and HLADR positive activated lymphocytes (20-30% of total lymphocytes) in peripheral blood. One year later, she developed lymphoma in the lung, which was V alpha2, V beta8, CD3, CD4, HLADR and IL2Rbeta positive. At that time, the population in the peripheral blood increased up to 40%, but there was no evidence of lymphoma in the bone marrow. In situ hybridization revealed lymphoma cells were EBER-1 positive but gp350/220 and LMP mRNA negative. The EBV genome was detected in the tumor, but not in the peripheral T cells. Clonal analysis of the lymphoma cells revealed monoclonal rearrangement of the TcRbeta and gamma gene, however, investigation of the terminal repeat of EBV gene did not show the monoclonal pattern. These results indicate that infection of EBV into clonally activated T cells was related with transformation from benign lymphoproliferative disease to malignant lymphoma in this patient.

Child↗

Molecular epidemiological study of a mass outbreak caused by enteropathogenic Escherichia coli O157:H45.

We made a molecular analysis of O157:H45 Escherichia coli isolated from a mass outbreak that occurred in Obihiro City. Using DNA analysis, we confirmed this infection case as a mass outbreak. Although the isolates expressed O157 antigen, they did not produce Vero toxin. We concluded they were enteropathogenic E. coli (EPEC) because they had a bfp gene and an EAF plasmid, and further they exhibited local adherence to HEp-2 cells. We believe this is the first report of a mass outbreak by O157 EPEC, and we suggest that PCR using eae- and bfp-specific primers and HEp-2 adherence assay are useful to identify EPEC.

Disease Outbreaks↗

Characterization of the angR gene of Vibrio anguillarum: essential role in virulence.

The ability to utilize the iron bound by high-affinity iron-binding proteins in the vertebrate host is an important virulence factor for the marine fish pathogen Vibrio anguillarum. Virulence in septicemic infections is due to the presence of a highly efficient plasmid-encoded iron transport system. AngR, a 110-kDa protein component of this system, appears to play a role in both regulation of the expression of the iron transport genes fatDCBA and the production of the siderophore anguibactin. Therefore, study of the expression of the angR gene and the properties of its product, the AngR protein, may contribute to the understanding of the mechanisms of virulence of this pathogen. In this work, we present genetic and molecular evidence from transposition mutagenesis experiments and RNA analysis that angR, which maps immediately downstream of the fatA gene, is part of a polycistronic transcript that also includes the iron transport genes fatDCBA and angT, a gene located downstream of angR which showed domain homology to certain thioesterases involved in nonribosomal peptide synthesis of siderophores and antibiotics. In order to dissect the specific domains of AngR associated with regulation of iron transport gene expression, anguibactin production, and virulence, we also generated a panel of site-directed angR mutants, as well as deletion derivatives. Both virulence and anguibactin production were dramatically affected by each one of the angR modifications. In contrast to the need for an intact AngR molecule for anguibactin production and virulence, the regulation of iron transport gene expression does not require the entire AngR molecule, since truncation of the carboxy terminus carrying the nonribosomal peptide synthetase cores, as well as the site-directed mutations, resulted in derivatives that retained their ability to regulate gene expression which was only abolished after truncation of amino-terminal sequences containing helix-turn-helix and leucine zipper motifs and a specialized heterocyclization and condensation domain found in certain nonribosomal peptide synthetases. The evidence, while not rigorously eliminating the possibility that a separate regulatory polypeptide exists and is encoded somewhere within the 5'-end region of the angR gene, strongly supports the idea that AngR is a bifunctional protein and that it plays an essential role in the virulence mechanisms of V. anguillarum. We also show in this study that the angT gene, found downstream of angR, intervenes in the mechanism of anguibactin production but is not essential for virulence or iron transport gene expression.

Animals↗

[Effects of human atrial natriuretic polypeptide in a patient with acute pulmonary edema during living-related kidney transplantation].

A 19-year-old female was scheduled for living-related kidney transplantation under general anesthesia. Eight units of fresh frozen plasma were infused in 30 minutes before the recanalization of renal vessels. Twenty minutes after the first urination, end-tidal-CO2 suddenly increased showing CVP of 18 mmHg. We considered that she had developed acute pulmonary edema. Continuous hANP infusion was initiated at the rate of 0.1 microgram.kg-1.min-1. By this infusion, end-tidal-CO2 and CVP gradually decreased and operation was concluded successfully. This case demonstrates that hANP works also on the transplanted kidney.

Acute Disease↗

[In vitro activities of 23 antimicrobial agents against 4,993 gram-positive and gram-negative bacterial strains isolated from multicenter of Japan during 1994--in vitro susceptibility surveillance.Levofloxacin-Surveillance Group].

In a surveillance study conducted during 1994 at 24 medical institutes from different geographical areas of Japan, the susceptibility of clinical isolates to twenty three comparative agents, such as ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin, ampicillin, clavulanic acid/amoxicillin, oxacillin, piperacillin, cefaclor, cefotiam, cefdinir, cefclidin, ceftazidime, cefpirome, imipenem, aztreonam, vancomycin, minocycline, chloramphenicol, clarithromycin, sulfamethoxazole/trimethoprim, amikacin, and gentamicin, were tested by the standard broth micro-dilution method. A total of 4,993 isolates tested in this study included Streptococcus pneumoniae, methicillin susceptible Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), coagllase negative streptococci (CNS), Enterococcus faecalis, Enterococcus faecium, Enterobactericeae, Pseudomonas aeruginosa from patients with urinary tract infections or respiratory tract infections, and Haemophilus influenzae. For MSSA, S. pneumoniae, Enterobacteriaceae, and H. influenzae, more than 70% of the isolates was susceptible to fluoloquinolones. However, resistance occurred in more than 50% of MRSA and P. aeruginosa isolated from UTI. Fluoroquinolones were found to be effective against high level penicillin-resistant S. pneumoniae, the third generation cephem-resistant Enterobacteriaceae and ampicillin-resistant H. influenzae.

Anti-Bacterial Agents↗