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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 271 records · Page 15Linked to original sources

The enabler cannula pump: a novel circulatory support system.

BACKGROUND: The enabler circulatory support system is a catheter pump which expels blood from the left or right ventricular cavity and provides pulsatile flow in the ascending aorta or pulmonary artery. It is driven by a bedside installed pulsatile driving console. The device can easily be implanted by a minimal invasive approach, similar to the Hemopump. PURPOSE: To demonstrate the hemodynamic performance of this new intracardiac support system. METHODS: In a series of 9 sheep, hemodynamic evolutions were recorded in various conditions of myocardial contractility (the non-failing, the moderately failing and the severely failing heart). Heart failure was induced by injection of microspheres in the coronary arteries. RESULTS: Introduction of the cannula through the aortic valve was feasible in all cases. Pump flow by the enabler was gradually increased to a maximum of 3.5 L/min. Diastolic (and mean) aortic blood pressure is significantly increased in the non-failing and moderately failing condition (counterpulsation mode). In heart failure, cardiac output is significantly increased by the pump (p < 0.0001). A drop in left atrial pressure (indicating unloading) is achieved in all conditions but reaches significant levels only during heart failure (p=0.0068). CONCLUSIONS: This new circulatory support system contributes to stabilization of the circulation in the presence of cardiac unloading. In heart failure it actually supports the circulation by increasing cardiac output and perfusion pressure.

Animals↗

Evaluation of intraoperative radiation therapy for unresectable pancreatic cancer with FDG PET.

UNLABELLED: This investigation was undertaken to evaluate 18F-labeled fluorodeoxyglucose (FDG) PET in monitoring patients after intraoperative radiotherapy (IORT) for unresectable pancreatic cancer and to compare its usefulness with CT. METHODS: FDG PET was performed in 12 consecutive unresectable ductal adenocarcinoma patients before (n = 12) and after IORT (0.7-11.9 mo, n = 14). In the follow-up period, FDG PET results after IORT were divided into three groups: early (0-2.0 mo after IORT, n = 7), intermediate (2.1-4.0 mo, n = 5) and delayed period (4.1 mo or later, n = 2). FDG uptake at 60 min after injection of 185 MBq FDG under fasting conditions was analyzed with standardized uptake value (SUV). Three parameters, the highest SUV in the tumor, the area of tumor showing SUV of more than 2.0 and the average SUV in the tumor area were calculated. Ratios of each parameter after IORT to that before IORT were defined as residual uptake ratio (RUR)-1, -2 and -3, respectively. Tumor regression after IORT was evaluated with CT as tumor size ratio (TSR) every 2 mo. RESULTS: Results of RUR-1 and -3 were consistent with tumor size measured by CT. They decreased in 10 patients with partial response and increased in 2 patients with no change, although these 2 patients had abscesses. RUR-3 decreased consistently as 0.65+/-0.33 in 2 mo, 0.51+/-0.39 in 4 mo and 0.24 in 4 mo or later after IORT, respectively. RUR-1 decreased in early period, but demonstrated no change through the remaining periods. There were discrepancies between the results of RUR-2 and those of the other RURs. CT results revealed a slow decrease in tumor size, because TSR was 0.91 +/-0.10, 0.76+/-0.11 and 0.70+/-0.18 in 2, 4 and 6 mo after IORT, respectively. RUR-3 was smaller than TSR at 2 mo (P < 0.05) and 4 mo (P = 0.056). These results indicate that the measurement of the average SUV in the tumor area with FDG PET could evaluate the local response of pancreatic cancer after IORT earlier and more markedly than with CT. CONCLUSION: FDG PET was useful in monitoring patients after IORT, because the decrease of metabolism in pancreatic tumor could be detected earlier than the decrease in tumor size.

Adenocarcinoma↗

Chronic heart failure model induced by coronary embolization in sheep.

OBJECTIVE: To create a model of chronic heart failure in a large animal. METHODS: Heart failure was induced in sheep by single intracoronary injection of polymer macrobeads, which were administered into left main coronary artery (n=3) or selectively into left anterior descending (n=4) or left circumflex (n=5) coronary artery. The animals were followed by echocardigraphy for 20 weeks. Measurements comprised fractional area change (FAC), and diastolic ventricular area (EDVA) and regional wall-thickening fraction (WT%). RESULTS: EDVA increased from 14.2+/-2.1 cm2 prior to embolization to 16.9+/-3.1 cm2 on day 1 (p<0.05), and remained significantly increased until completion of the follow-up period. FAC dropped from 47.9+/-4.6% at baseline to 29.3+/-4.4% on day 1 (p<0.001) and remained significantly depressed until 20 weeks later. In 9 selectively embolized animals WT% of the embolized area decreased from 33.8+/-8.0% at baseline to 5.3+/-2.6% on day 1 and remained significantly decreased. CONCLUSIONS: A simple model of chronic heart failure was developed. It shows relatively high stability over time and may prove beneficial in experimental work on ventricular assist devices.

Animals↗

[A case of anti-GM1 antibody positive HTLV-I associated myelopathy (HAM) with polyneuropathy].

We report a case of HTLV-I associated myelopathy (HAM) with polyneuropathy. A 59-year old man suffering from progressive paraparesis associated with subclinical polyneuropathy was admitted to our hospital. HTLV-I antibodies in the serum and CSF were positive, and a diagnosis of HAM was made. His laboratory investigation revealed elevated serum IgG and IgM anti GM-1 antibodies. The nerve conduction study showed a mild reduction in motor and sensory conduction velocity in all extremities. A sural nerve biopsy revealed active demyelination and globule-like changes, which are specific for HAM neuropathy. Anti-GM1 antibodies are frequently present in autoimmune motor neuropathy. They are thought to inflict a damage on both the myelin and axons of the peripheral nerves. Ours is believed to be the first case of HAM associated with anti-GM1 antibodies, although polyneuropathy is often associated with HAM. While it is not clear whether the lesion observed in HAM neuropathy results from the direct cytopathic effect of the virus or from the immune response, some immune-mediated reactions are thought to play an important role. This case suggests that a case of HAM with polyneuropathy should be examined for the presence of the anti-ganglioside antibodies. More investigations are needed to fully understand the mechanism of the HAM neuropathy.

Autoantibodies↗

The effects of organic solvents on trimethadione n-demethylation in rats.

Many organic solvents are frequently used as support solvents to dissolve chemicals in the study concerning drug metabolism mediated by cytochrome P450. However, some organic solvents used as the support solvents affect the chemical's metabolism. It has been reported that some organic solvents are metabolized by CYP2E1 or inhibit its enzymatic reaction. In this study we investigated the effects of organic solvents, such as acetonitrile (AN), dimethylsulfoxide (DMSO), ethanol (EtOH), methanol (MeOH), polyethylene glycol (PEG) and propylene glycol (PG) on TMO (trimethadione) metabolism, which is mainly mediated by CYP2E1 in the rat. In the in vivo study, male SD rats were pretreated with an organic solvent intraperitoneally at a dosage of 0.5, 1 or 2 mmol/kg 1 hour before TMO administration orally at the dose of 4 mg/kg. After 2 hours, serum concentrations of TMO and DMO were determined by gas chromatography/flame detection (CG/FTD) and the serum DMO/TMO ratio was employed for assessment of the metabolic capacity of TMO. In the in vitro study, hepatic microsomal fraction was used as an enzyme source of TMO N-demethylase and enzyme activities were determined by the production of DMO. Pretreatment with DMSO and PG decreased the DMO/TMO ratio in a dose-related manner in vivo study. Furthermore, in vitro study TMO N-demethylase activity was inhibited by DMSO, EtOH and PG with different potency in a concentration related manner. However, no remarkable effects were observed by AN or PEG both in vivo and in vitro study. These results indicated that there are variations in the inhibitory effects of these organic solvents on CYP2E1-mediated metabolism and AN and PEG will be useful solvents to dissolve chemicals in the metabolic study mainly mediated by CYP2E1.

Animals↗

[The significance of color duplex ultrasonography for the diagnosis of temporal arteritis].

We examined the usefulness of color duplex ultrasonography in patients suspected of having temporal arteritis. Five patients, who were all aged 70 or older, developed a new onset of localized headache with temporal artery abnormalities, and had an elevated erythrocyte sedimentation rate of > 100 mm/hour. The final diagnoses were temporal arteritis in three patients, polymyalgia rheumatica in one, and probable healed temporal arteritis in one. Color duplex ultrasonography showed stenoses, which were confirmed histologically as well, in the superficial temporal artery of all patients. The characteristic findings of active temporal arteritis were, however, demonstrated in only three biopsy specimens, and in the remaining two the stenoses were thought to be related to previous arteritis. The hypoechoic halo, which has been reported to be a characteristic finding of color duplex ultrasonography in active temporal arteritis, was detected in only one patient with active temporal arteritis and another one with probable healed temporal arteritis. No stenoses were demonstrated in the superficial temporal arteries of 30 control subjects (20 with at least one risk factor of atherosclerosis and 10 without it). Color duplex ultrasonography can therefore be considered a powerful method for detecting stenoses in the superficial temporal artery. Its ability to identify their etiology is, however, unsatisfactory, so that temporal artery biopsy remains undoubtedly the most reliable test for etiological evaluation. We thus recommend color duplex ultrasonography as a supplementary method for the diagnosis of temporal arteritis, because it can provide useful information concerning the appropriate site of temporal artery biopsy.

Aged↗

Detection of single-stranded cohesive ends in the genome of Bacillus thuringiensis temperate phage KK-88.

Cohesive ends (cos sites) were detected in the genome of temperate KK-88 phage in Bacillus thuringiensis after analysis of the phage DNA generated by the 3'-5' exonuclease activity of Klenow fragment of DNA polymerase I. In addition, unlike the 5'-protruding ends of coliphage lambda genome, the ends of KK-88 phage genome were found to be 3'-protruding. The restriction map of the phage genome was also constructed on the basis of position of the cos fragments.

Bacillus thuringiensis↗

Enhancement of nitroglycerin induced blood vessel relaxation in chronic renal failure model rats.

This study was designed to investigate the alternation of blood vessel relaxation in chronic renal failure (CRF) induced by adenine or partial-nephrectomy. The aorta was employed as the blood vessel material. CRF aorta relaxation in both adenine and partial nephrectomy induced rats increased when treated with glyceryl trinitrate (GTN). In the CRF animals, cGMP levels increased with the severity of CRF status. Aorta cytosolic glutathione S-transferase micro (GSTmicro) activity and enzyme contents increased with CRF. The effect of GTN on aortic vasorelaxation in both CRF statuses completely disappeared by the treatment with sodium nitoprusside. The effects of GTN were observed equally in both adenine- and partial nephrectomy-induced CRF rats. We concluded that alterations of aortic vasorelaxation by GTN in adenine- and partial nephrectomy-induced renal failure rats were caused by the enhancement of nitrogen monoxide production on the aortic blood vessel mediated by the induced GSTmicro in the aorta. This GSTmicro induction is peculiar to CRF since different CRF induction procedures produce the same results.

Adenine↗

Localization of Rho GTPase in sea urchin eggs.

We isolated the urho1 (urchin rho in English or uni rho in Japanese) gene from the sea urchin cDNA library which encodes a Rho GTPase. Anti-URho1 antibodies specifically recognized a 22 kDa protein in the extracts of echinoderm eggs. URho1 was concentrated in the cortices from both unfertilized and fertilized eggs as judged by immunoblot analysis. URho1 may bind directly to the cell membrane but not be a component of the cortical layer. Immunofluorescence microscopy revealed that URho1 is localized to the cleavage furrow and the midbody during cytokinesis.

Amino Acid Sequence↗

CD4(+) cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner.

Although it is well known that CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the suppression of cancer cell growth, the significance of CD4(+) CTLs in resistance to cancer is obscure. In an attempt to elucidate the role of CD4(+) CTLs in immunosurveillance of chronic myelogenous leukemia (CML), we examined the immunologic functions of bcr-abl b3a2 fusion peptide-specific CD4(+) CTL clones. Seven CD4(+) T-cell clones that responded to stimulation with b3a2 peptide, but not with b2a2 peptide or physiological counterparts bcr b3b4 and abl 1A-a2 peptides, were established from two healthy individuals. Restriction elements of these clones were HLA-DRB1*0901. These CD4(+) T-cell clones exhibited b3a2 peptide-specific and HLA-DRB1*0901-restricted cytotoxicity and produced interleukin-3 (IL-3), IL-4, IL-10, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor in response to bcr-abl peptide stimulation, indicating they were Th0 clones. The numbers of HLA-DRB1*0901-positive b3a2, but not those of b2a2-positive or HLA-DRB1*0901-negative CML cell colonies increased when CML cells were cultured with b3a2-specific CD4(+) CTL clones. These data suggest that bcr-abl-specific CD4(+) CTLs recognize CML cells in an antigen-specific and HLA-DR-restricted manner, and that they do not inhibit, but in fact augment, CML cell growth.

Amino Acid Sequence↗

Molecular cloning of feline CC-chemokine cDNAs.

cDNA clones of feline chemokines, MIP-1alpha, MIP-1beta and RANTES, were molecularly isolated with the purpose of using these sequences for future investigation of the inhibitory effects on lentivirus entry and their role in immunological functions. The feline MIP-1alpha and MIP-1beta cDNA clones spanned their entire coding regions encoding 93 and 92 amino acids, respectively. The amino acid sequences of feline MIP-1alpha and MIP-1beta compared to those of their human, mouse and rat counterparts showed similarities of 75.3-79.6% and 73.9-88.0%, respectively. Feline MIP-1alpha and MIP-1beta had four conserved cysteines with a structure made up of the first two cysteines that are characteristic of the CC-chemokine subfamily. The amino terminal of these MIP-1alpha and MIP-1beta sequences was distinctly hydrophobic, suggesting that they may function as signal peptides. A partial cDNA clone consisting of 193 bp was obtained for feline RANTES, and it also showed a high degree of sequence similarity to those of other species and contained the characteristic structure made up of adjacent cysteines. These molecular clones of feline chemokines will be useful in the examination of their inhibitory effect on the cellular entry of feline immunodeficiency virus.

Amino Acid Sequence↗

Molecular cloning of feline Fas antigen and Fas ligand cDNAs.

The Fas antigen (FasA) and Fas ligand (FasL) are key molecules which mediate apoptosis. For investigation of apoptosis in cats, we isolated molecular clones of feline FasA and FasL cDNAs by using the polymerase chain reaction (PCR) method to amplify cDNAs from feline lymphoma cell lines. These feline FasA and FasL clones contained complete open reading frames encoding 314 and 280 amino acids, respectively. These feline FasA and FasL cDNA clones had structures characteristic of the tumor necrosis factor (TNF) receptor family and TNF family, respectively. The deduced amino acid sequence of feline FasA and feline FasL, respectively showed 45.0%-60.0% and 75.0%-90.0% similarity with their human, mouse and bovine counterparts. These data will be helpful for investigating the role of the FasA and FasL system in apoptosis and for studying the various diseases associated with the deregulation of apoptosis in cats.

Amino Acid Sequence↗

Increased levels of CSF soluble CD27 in patients with primary central nervous system lymphoma.

The aim of this study is to determine the diagnostic value of cerebrospinal fluid (CSF) soluble CD27 (sCD27) as a tumor marker for primary central nervous system lymphoma (PCNSL). We examined sCD27 levels in CSF obtained from various types of brain tumor patients. Forty-two patients were studied (including 12 PCNSL patients) who had not received any therapy for their tumors. In all PCNSL cases, CSF sCD27 levels were more than 15 U/ml (median 84.5 U/ml, range 17-484 U/ml) and in other brain tumor cases, CSF sCD27 levels were all less than 15 U/ml. Our data suggest that CSF sCD27 levels are useful to distinguish PCNSL from other brain tumors.

Adolescent↗

Gene duplication and fusion have occurred frequently in the evolution of phosphagen kinases--a two-domain arginine kinase from the clam Pseudocardium sachalinensis.

In contrast to the 40 kDa arginine kinases from Molllusca and Arthropoda, the adductor muscle of the marine clam Pseudocardium sachalinensis contains an unusual arginine kinase consisting of an 86 kDa subunit. The cDNA encoding the 86 kDa arginine kinase was amplified by PCR and the cDNA-derived amino acid sequence of 724 residues was determined. The exact molecular mass for the protein was calculated to be 80941 Da. The amino acid sequence clearly indicates that Pseudocardium arginine kinase has a two-domain structure: the first domain residues 1-363 and the second domain 364-724. The two domains, which are separated by an intron of 176 bp in the gene, show 62% amino acid sequence identity. This two-domain arginine kinase from a mollusc represents yet another multiple-domain enzyme observed in the phosphagen kinase enzyme family. Two-domain and three-domain enzymes have been observed in three other diverse invertebrate groups. Thus, it is clear that gene duplication and subsequent fusion have occurred frequently, and likely independently, during the course of the evolution of this enzyme family. Comparison of the amino acid sequence in the GS region (a possible candidate for the guanidine substrate recognition site in the phosphagen kinase family) suggests that the first domain of Pseudocardium arginine kinase might not retain a complete enzyme activity, because the Asp-7 in the GS region, which is assumed to be involved in the recognition of the positive charge of arginine, was replaced by a Gly residue in the first domain.

Amino Acid Sequence↗

Molecular analyses of HLA class II-associated susceptibility to subtypes of autoimmune diseases unique to Asians.

It is well known that individuals positive for particular HLA-class II alleles show high risks for the development of Takayasu arteritis and other diseases caused by immunological disorders such as autoimmune diseases and allergies. HLA class II molecules present antigenic peptides to CD4+ T cells. Their extensive polymorphism affects the structures of peptides bound to HLA class II molecules to create individual differences in immune responses to antigenic peptides. To better understand the mechanisms for association between HLA class II alleles and susceptibility to autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative T cells. Many autoimmune diseases are observed in all ethnic groups, whereas the incidences of diseases, clinical manifestations and disease-susceptible HLA class II alleles are different among various ethnic groups for some autoimmune diseases. These phenomena suggest that differences in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may cause these differences. Therefore, comparisons among disease-susceptible HLA class II alleles, autoimmune self-peptides and clinical manifestations of autoimmune diseases in different ethnic groups would be helpful in determining the pathogenesis of the diseases. In this paper, we describe our recent findings on: (1) the uniqueness of both clinical manifestations and HLA-linked genetic background of Asian-type (optico-spinal form) multiple sclerosis; (2) the structural characteristics of peptides bound to HLA-DQ molecules susceptible to insulin-dependent diabetes mellitus; (3) the identification of a disease-related autoantigenic peptide presented by disease-susceptible HLA-DQ molecules in Asians-specific infant onset myasthenia gravis; and (4) a manipulation of human T cell response by altered peptide ligands, as a possible candidate for new and antigen-specific immuno-suppressive therapy against autoimmune diseases.

Alleles↗

An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice; an age-associated neurodegeneration animal model.

In order to characterize the early stage of mitochondrial dysfunction, we investigated the redox state and oxidative phosphorylation of the brain mitochondria from 2-month-old Senescence-accelerated mouse (SAM)P8 and SAMR1 mice; SAMP8 mice exhibit various signs of age-associated neurodegeneration and rapid mitochondrial dysfunction, although SAMR1 mice do not. The redox state was estimated as the reduction rate of Cu-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), the reduction of which is closely related to the electron leakage from the mitochondrial electron transport system in the brain, using electron spin resonance spectrometry (ESRS). The oxidative phosphorylation was measured polarographically. The SAMP8 mouse brain mitochondria demonstrated higher redox state and a higher activity of mitochondrial respiration with lower respiration control ratio than the mitochondria of SAMR1 mouse brains. This indicates that an inefficient hyperactive state can exist in the mitochondrial electron transport system before the age-associated mitochondrial dysfunction develops.

Aging↗