Search PubMed⌕ Search

Biomedical subjects

M Suzuki

Publications and source records attributed to M Suzuki.

At least 109 records · Page 6Linked to original sources

[Induction chemotherapy and radical resection for primary nonseminomatous mediastinal germ cell tumor (NSGCT); report of a case].

A 15-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor. The tumor was visualized by chest radiography 3 months prior to admission. Computed tomography (CT) revealed a heterogeneous solid tumor located in the anterior mediastinum. Although CT-guided needle biopsy had been performed twice, histologic diagnosis could not be confirmed. We believed this tumor to be nonseminomatous mediastinal germ cell tumor (NSGCT) and started intensive chemotherapy with cisplatin (CDDP) without histologic diagnosis because his serum AFP level was rapidly increasing. After 2 courses of chemotherapy, his serum AFP level returned to the normal range and surgical resection of the tumor with part of right lung was performed. Histopathological examination revealed that the tumor consisted of mature teratoma and yolk sac tumor. He underwent 1 course of chemotherapy post-operatively because a small number of viable cells were histopathologically recognized in the yolk sac component. At the time of writing, the patient is alive without any evidence of recurrence.

Adolescent↗

[Spinal cord protection and operative results of the thoracoabdominal aortic aneurysm].

The purpose of this study was to review retrospectively recent results in 75 patients undergoing thoracoabdominal aortic operations using the technique of distal aortic perfusion with segmental aortic clamping. Between July 1997 and November 2003, 46 males (61%) and 29 females (39%) were treated. The patients ranged in age from 26 to 82 (mean 63 +/- 13) years. Indications for surgery included dissecting thoracoabdominal aortic aneurysm (n = 28), atherosclerotic thoracoabdominal aortic aneurysm (n = 46), and traumatic aneurysm (n = 1). Emergency operation was performed in 8 (11%). The extent of aneurysm was Crawford type I in 12 patients, type II in 19, type III in 34, and type IV in 10. Profound hypothermic circulatory arrest was used in 3 patients and retrograde segmental clamping technique in 5. Cerebrospinal fluid drainage and naloxone hydrochloride administration were performed as adjunctive methods since February 2000. There were 6 (8%) in-hospital deaths. The overall incidence of postoperative paraplegia or paraparesis was 8% (6/75). Although the survival rate has improved, the problem of a complete prevention of ischemic spinal cord injury on the thoracoabdominal aortic operations remains unsolved. The multimodality approach is needed to reduce the risk of this devastating complication.

Adult↗

[Total arch replacement with reconstruction of non-coronary sinus for acute type A aortic dissection after previous coronary artery bypass grafting; report of a case].

A 73-year-old man, who underwent coronary artery bypass grafting (CABG) 2 years previously, had suffered from acute type A aortic dissection with concomitant mild to moderate aortic regurgitation. A median resternotomy was performed. Arterial and venous cannulae were inserted into the femoral artery and vein to institute a cardiopulmonary bypass. The intimal tear was existed just above the sino-tubular junction. As the non-coronary sinus was involved in the dissection severely, it was resected in a scallop-shaped configuration. The aortic graft was tailored accordingly and anastomosis was performed in a curviliner fashion following the edge of scallop and the horizontally between the right and left coronary sinuses. Next, total arch replacement was performed using an aortic arch branched graft. Postoperative course was uneventful. Aortography revealed no aortic regurgitation and good patency of bypass graft.

Acute Disease↗

Proinsulin C-peptide increases nitric oxide production by enhancing mitogen-activated protein-kinase-dependent transcription of endothelial nitric oxide synthase in aortic endothelial cells of Wistar rats.

AIMS/HYPOTHESIS: Recent studies have suggested that proinsulin C-peptide improves vascular functions, possibly through nitric oxide (NO) production. To clarify the molecular mechanisms of vascular NO production induced by C-peptide, we examined the effects of C-peptide on NO production and NO synthase expression in rat aortic endothelial cells in connection with mitogen-activated protein kinase (MAPK) activation. METHODS: Aortic endothelial cells were isolated from female Wistar rats, cultured to confluence, and serum-starved for 24 h before treatment with C-peptide. Nitric oxide production was measured by the DAF-2 fluorescence dye method and relative amounts of endothelial nitric oxide synthase (eNOS) protein and its mRNA were semi-quantified by western blot and RT-PCR analyses respectively. Activation of MAPK was estimated by western blot detection of activity-related phosphorylation and in vitro kinase assay. RESULTS: Stimulation of cells with C-peptide for 3 h doubled NO production, which was suppressed by the NO synthase inhibitor, N(G)-nitro- L-arginine methyl ester (L-NAME). Stimulation also increased mRNA and protein contents of eNOS in a manner sensitive to the transcription inhibitor actinomycin D. It did not affect inducible NO synthase mRNA. C-peptide also induced rapid phosphorylation and activation of extracellular signal-regulated kinase (ERK, also known as p44/42MAPK), but not of p38MAPK. In cells pretreated with the ERK inhibitor PD98059 the C-peptide-elicited increase of NO production and eNOS was abrogated in a dose-dependent manner; suppression of ERK phosphorylation induced by C-peptide also occurred. CONCLUSIONS/INTERPRETATION: Our results show that C-peptide increases NO production by increasing eNOS protein contents through ERK-dependent up-regulation of eNOS gene transcription. This could explain some actions of C-peptide on the vasculature, indicating a pivotal role for C-peptide in vascular homeostasis.

Animals↗

Globular adiponectin upregulates nitric oxide production in vascular endothelial cells.

AIMS/HYPOTHESIS: Adiponectin, also called ACRP30, is a novel adipose tissue-specific protein that has been shown to improve insulin sensitivity and to exert anti-atherogenic effects. It is known that knockout mice lacking endothelial NO synthase (eNOS) develop hypertension, insulin resistance, hyperlipidaemia, and show augmented ischaemia-reperfusion damage. Thus, we examined whether globular adiponectin activates eNOS to produce NO. METHODS: To analyze NO production in bovine aortic endothelial cells (BAE), NOx (nitrite and nitrate) was measured in the medium with an automated NO detector/high-performance liquid chromatography system. eNOS activation was assessed by phosphorylation of the enzyme and its activity was evaluated by citrulline synthesis in human umbilical vein endothelial cells (HUVEC). eNOS mRNA and protein expressions in HUVEC were evaluated by Realtime PCR and Western blot analysis. RESULTS: Gobular adiponectin increased NO production in BAE. It also caused eNOS phosphorylation and potentiated eNOS activity in HUVEC. In addition, globular adiponectin up-regulated the eNOS gene to increase protein expression in HUVEC. CONCLUSION/INTERPRETATION: Globular adiponectin increases NO production through two mechanisms, namely, by activation of eNOS enzyme activity and via an increase in eNOS expression. Activation and up-regulation of eNOS could explain some of the observed vasoprotective properties of globular adiponectin, as well as its beneficial effects on the cardiovascular system.

Adiponectin↗

An algorithm for mapping the catheter tip position on a fluorograph to the three-dimensional position in magnetic resonance angiography volume data.

This paper proposes an algorithm which maps the position of a catheter tip on a fluorograph to the 3D position in magnetic resonance angiography (MRA) data. This algorithm was assessed for its accuracy. We designed an algorithm consisting of a registration step and a recognition step. The registration step registers MRA and fluorography data using a digital subtraction angiography (DSA) image. The recognition step recognizes the position in the MRA data corresponding to the catheter tip position on a fluorograph. We checked the accuracy of the recognition step by employing an artificial data set consisting of 3D image data (64 x 64 x 64 matrix) and its projection image (92 x 92 matrix) and the accuracy of the registration step with the aid of three of the 3D time-of-flight MRA data sets (256 x 256 matrix and 60 slices) and their projection images in the form of DSA images. The accuracy of the recognition step depended upon that of the registration. When there was no misregistration, all of the mean errors were less than 0.2 mm. The mean errors of the registration step were 0.273 mm and 0.226 mm, respectively, for the longitudinal shift along the X and Y axes, 0.478 degrees, 1.203 degrees and 0.208 degrees, respectively, for the rotation angles around the X, Y and Z axes and 0.020 times for the magnification. The mean image error between the projection image of the registered MRA data and that of the MRA data which were employed as the DSA image was 0.034 mm.

Algorithms↗

Expression of an artificial Cl- channel in microperfused renal proximal tubules.

To better understand the process of fluid movement driven by Cl- conductance, a Cl- channel-forming peptide was delivered to the luminal membrane of microperfused rabbit renal proximal tubules. When the peptide (NK4-M2GlyR) was perfused, a significant new conductance was observed within 3 min and stabilized at 10 min. Alteration of the ion composition revealed it to be a Cl(-)-specific conductance. Reabsorption of Cl- (JCl) was increased by NK4-M2GlyR, but not by a scramble NK4-M2GlyR sequence, suggesting that the active peptide formed de novo Cl- channels in the luminal membrane of the perfused tubules. In the presence of the peptide, reabsorption of fluid (Jv) was dramatically increased and JNa and JCa were concomitantly increased. We propose that introduction of the new Cl- conductance in the luminal membrane leads to a coordinated efflux of water across the membrane and an increase in cation translocation via the paracellular pathway, resulting in an increase in Jv. This novel method could prove useful in characterizing mechanisms of fluid transport driven by Cl- gradients.

Animals↗

Contrast-enhanced MRA for investigation of cerebral arteriovenous malformations.

We evaluated contrast-enhanced MRA (enhanced 3-D fast gradient-echo [efgre3d] with spectral inversion recovery) for identification of 15 intracranial arteriovenous malformations (AVMs) in 14 patients. Demonstration of the feeding arteries was classified as good for 16 examinations on maximum-intensity projections and multiprojection volume reconstruction images. The nidus was seen well in all patients. Definition of the draining veins was good or fair except for one poor result. Therapeutic effects were clearly demonstrated in three follow-up series. Contrast-enhanced MRA using efgre3d is useful for delineation of AVMs and for follow-up after treatment.

Adult↗

Endogenous GABA in the commissural subnucleus of the NTS inhibits the carotid chemoreceptor reflex via GABA A receptors in rats.

Using urethane-chloralose anesthetized rats, we investigated which GABA receptor is responsible for the action of endogenous GABA on the carotid chemoreceptor reflex in the commissural subnucleus of the nucleus tractus solitarius (commNTS). Microinjection of the selective GABA uptake inhibitor nipecotic acid (40 nmol) into the commNTS attenuated the increases in respiration (respiratory movement and rate) and the elevation in arterial blood pressure elicited by carotid chemoreceptor stimulation. These effects were completely antagonized by premicroinjection of the GABA(A) antagonist bicuculline (20 pmol), but not of the GABA(B) antagonist 2-OH-saclofen (400 pmol), into the same site. These findings suggest that endogenous GABA mainly acts on GABA(A) receptors, and inhibits the chemoreceptor reflex in the commNTS in rats.

Animals↗

Interaction of Bombyx mori nucleopolyhedrovirus BRO-A and host cell protein laminin.

The Bombyx mori nucleopolyhedrovirus (BmNPV) contains five baculovirus repeated ORF ( bro) genes, all of which are expressed as delayed early genes. We have recently reported that BmNPV BRO proteins, specially BRO-A and BRO-C, contain a nucleic acid binding activity and are involved in nucleosome structures in nuclei of infected cells. To further understand the function of bro-a gene, we looked for factors interacting with BmNPV BRO-A using the yeast two-hybrid system. Fifteen clones obtained from a cDNA library of mock-infected cells and one from a library prepared at 2 h postinfection (p.i.) were found to comprise one distinct gene, which was identified as the Bombyx homolog (bLaminin) of Drosophila laminin beta1. A direct interaction between BRO-A and N-terminal region of bLaminin was demonstrated by in vitro pull-down experiments. Further pull-down assays using BmN cell extracts and anti-laminin antibodies also showed interaction of both proteins. In addition, two more clones were obtained from cDNA library of 12 h p.i. and were found to encode BRO-A itself, indicating that BRO-A forms an oligomer. Taken together, we propose that BRO-A may function as a laminin binding protein.

3' Flanking Region↗

Phase II study of exatecan mesylate (DX-8951f) as first line therapy for advanced non-small cell lung cancer.

BACKGROUND: Exatecan mesylate (DX-8951f) is a water soluble analogue of camptothecin that inhibits topoisomerase I. This multi-centre phase II study evaluated the activity of single agent exatecan in previously untreated patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically or cytologically proven stage IIIb or IV NSCLC were treated with exatecan 0.5 mg/m(2) per day by 30 min intra-venous (i.v.) infusion for 5 days every 3 weeks to a maximum of six cycles. Measurable disease was documented prior to study entry and patients were re-staged every two cycles. Pharmacokinetic (PK) sampling was performed during cycle one. RESULTS: 39 patients (32 patients ECOG performance status 0 or 1; 29 male and ten female; mean age 63 years) were entered into the study. Thirty-three completed at least two cycles of exatecan and 11 completed six cycles. Two patients (5.1%, 95% C.I. 0.3-21.3%) had a partial response, 7 (18.0%) minor response and 8 (20.5%) stable disease. Median time to tumour progression (TTP) was 88 days and median overall survival 262 days. The main toxicity was reversible neutropenia. PK analysis of exatecan demonstrated a mean clearance of 2.28 l/h per m(2), volume of distribution 18.2 l/m(2) and mean elimination half-life of 7.9 h. CONCLUSIONS: Exatecan mesylate has limited activity in advanced NSCLC and is not recommended for further evaluation as a single agent in this tumour type. PK data from this trial supports results established in phase I studies.

Adult↗

Effects of n-3 polyunsaturated fatty acids on indomethacin-induced changes in eicosanoid production and blood flow in the gastric mucosa of rats.

We investigated the effects of n-3 polyunsaturated fatty acids (PUFAs) on non-steroidal anti-inflammatory drug (NSAID)-induced changes in microcirculation and eicosanoid production in the gastrointestinal mucosa. We measured gastric mucosal blood flow using laser Doppler flowmetry, assessed the fatty acid composition in the mucosal phospholipids, and quantified the production of prostaglandin E2 (PGE2), leukotriene B4, and leukotriene C4 (LTB4 and C4) from the mucosa with the stimulation of calcium ionophore 20 min after an injection of indomethacin or vehicle in rats fed a diet containing different compositions of alpha-linolenic acid. Four weeks after the initiation of the test diet the arachidonic acid level in gastric mucosal phospholipids was significantly lower in the perilla group than in the other three groups. Conversely, alpha-linolenic acid and eicosapentaenoic acid (EPA) were significantly higher in the perilla group than in the other three groups. The percent of gastric mucosal blood flow in the three groups administered indomethacin were significantly lower than that in the control group injected with vehicle alone. The percent of gastric mucosal blood flow in the perilla group was significantly higher than that in the corn group. LTB4 and LTC4 production from the gastric mucosa in the soybean and corn groups were significantly higher than those in the control group, and the LTC4 production in the perilla group was significantly lower than that in the corn group. There were no significant differences in PGE2 production among the four groups. Our results suggest that alpha-linolenic acid affectively suppressed the indomethacin-induced decreases in gastric mucosal blood flow by increasing EPA and decreasing the levels of arachidonic acid and LTC4 in the gastric mucosa.

Animals↗

Anesthesia-related mortality and morbidity over a 5-year period in 2,363,038 patients in Japan.

BACKGROUND: Statistical data of mortality and morbidity related to anesthesia have not been reported in Japan since World War II. The need to comprehensively examine the events of cardiac arrest as well as mortality prompted the first national study in Japan. METHODS: Confidential questionnaires were sent to all Japan Society of Anesthesiologists Certified Training Hospitals every year from 1994 through 1998. Collected data were analyzed for incidence of cardiac arrest and other critical events during anesthesia and surgery, and their outcomes within 7 postoperative days. The principal causes of the critical incidents were also analyzed. RESULTS: With an average response rate of 39.9%, a total of 2,363,038 cases were documented over 5 years. The average incidence per year of cardiac arrest during surgery due to all etiologies and that totally attributable to anesthesia was 7.12 [95%CI: 6.30,7.94] and 1.00 [0.88, 1.12]) per 10,000 cases, respectively. The average mortality per year in the operating room or within 7 postoperative days due to all etiologies and that totally attributable to anesthesia was 7.18 [6.22, 8.13] and 0.21 [0.15, 0.27] per 10,000 cases, respectively. The two principal causes of cardiac arrest during anesthesia and surgery due to all etiologies were massive hemorrhage (31.9%) and surgery (30.2%), and those totally attributable to anesthesia were drug overdose or selection error (15.3%) and serious arrhythmia (13.9%). Preventable human errors caused 53.2% of cardiac arrest and 22.2% of deaths in the operating room totally attributable to anesthesia. CONCLUSIONS: The rates in Japan of cardiac arrest and death during anesthesia and surgery due to all etiologies as well as those totally attributable to anesthesia are comparable to those of other developed countries.

Anesthesia↗

Gray matter features of schizotypal disorder patients exhibiting the schizophrenia-related code types of the Minnesota Multiphasic Personality Inventory.

OBJECTIVE: Previous studies have suggested that several code types of the Minnesota Multiphasic Personality Inventory (MMPI) are useful markers for identifying schizophrenia. We hypothesized that schizotypal disorder (STD) patients with such schizophrenia-related code types have the morphological brain abnormalities associated with schizophrenia. METHOD: Voxel-based morphometric analysis with statistical parametric mapping (SPM) 99 software was used to investigate the differences in brain morphology between 14 STD patients with the schizophrenia-related code types of the MMPI and 28 normal individuals. RESULTS: The STD patients showed significantly decreased gray matter volume in the insular regions bilaterally and in the left entorhinal cortex, compared with the controls. CONCLUSION: Our findings suggest that STD patients with the schizophrenia-related code types have volume reductions in these regions as an endophenotype that overlaps with schizophrenia.

Adolescent↗

Hofbauer cell activation and its increased glucose-6-phosphate dehydrogenase activity in second trimester-spontaneous abortion: an ultrastructural dual staining enzyme-cytochemical study.

PROBLEM: While activated/phagocytosing phagocytes infiltrating to the chorioamnion are considered to be one of the causal agents of preterm labor onset, whether placental villous macrophages (Hofbauer cells) are activated/phagocytosing in this condition is not known. METHOD OF STUDY: We concomitantly localized two important phagocytosis-related enzymes, acid phosphatase (ACP) and glucose-6-phosphate dehydrogenase (G6PD), in Hofbauer cells in second trimester placental villi, and compared them with those from infection-related second trimester-spontaneous abortion (miscarriage) placentas. RESULTS: There were two types of Hofbauer cells. The first cells exhibited ACP stainings confined to the lysosomes, suggesting that they are dormant/non-activated cells. Approximately two-thirds of these cells showed weak G6PD labeling on the cytosolic side of endoplasmic reticula, and G6PD labeling was hardly recognizable in the remaining one-third. The second cells, possessing large phagosomes, showed marked ACP labeling in the phagosomes, suggesting that they are activated/phagocytosing cells. All these cells exhibited G6PD labeling, and in 'bursting cells' (possibly hyperactivated cells) G6PD deposits were marked. The percentage of activated cells in miscarriage placentas was significantly higher (44.8 +/- 6.0%) than that in gestational age-matched controls (17.4 +/- 5.3%). CONCLUSIONS: These observations indicated that (1) G6PD activity increased in activated/phagocytosing Hofbauer cells, and (2) the percentage of phagocytosing cells increased in infection-related miscarriage placentas. Hofbauer activation and G6PD may play an role in the pathogenesis/pathophysiology of preterm labor onset.

Abortion, Spontaneous↗

Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c release.

Bax mediates cytochrome c release and apoptosis during neurodevelopment. Brain mitochondria that were isolated from 8-day, 17-day, and adult rats displayed decreasing levels of mitochondrial Bax. The amount of cytochrome c released from brain mitochondria by a peptide containing the BH3 cell death domain decreased with increasing age. However, approximately 60% of cytochrome c in adult brain mitochondria could be released by the BH3 peptide in the presence of exogenous human recombinant Bax. Mitochondrial Bax was downregulated in PC12S neural cells differentiated with nerve growth factor, and mitochondria isolated from these cells demonstrated decreased sensitivity to BH3-peptide-induced cytochrome c release. These results demonstrate that immature brain mitochondria and mitochondria from undifferentiated neural cells are particularly sensitive to cytochrome c release mediated by endogenous Bax and a BH3 death domain peptide. Postnatal developmental changes in mitochondrial Bax levels may contribute to the increased susceptibility of neurons to pathological apoptosis in immature animals.

Animals↗

Recombinant single-chain antibodies with various oligopeptide tails for targeted gene delivery.

The single-chain antibody (scFv) made by recombinant DNA technology is one of the most useful tools for basic research and clinical applications. To develop a novel targeted gene delivery method, we engineered the scFv gene for the antibody against human epidermal growth factor (EGF) receptor by connecting with DNA sequences for various oligopeptides with negative or positive charges. The resulting recombinant genes encoding artificial scFv with negative or positive tails were expressed in Escherichia coli and yeast Pichia pastris. In E. coli, all the scFv with negatively charged tails were expressed but mainly as an insoluble form, whereas those with positively charged tails were barely expressed. In yeast P. pastris, all the scFv with negatively charged tails were efficiently expressed and secreted into the culture medium. Addition of high salt into the yeast culture increased their secretion. Purification procedure was established for the scFv with the longest negatively charged tail (D4S x 5), yielding 5 mg/l with a purity of over 95%. The scFv-D4S x 5 was designated as a recombinant immunoporter, which was then mixed with plasmid DNA and polyethylenimine (PEI). The resulting DNA/PEI/immunoporter complex (designated recombinant immunogene) exhibited efficient gene delivery to EGF receptor overexpressing A431 tumor cells.

Antibodies↗