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Biomedical subjects

S Morikawa

Publications and source records attributed to S Morikawa.

At least 37 records · Page 2Linked to original sources

Increased arterial wall stiffness limits flow volume in the lower extremities in type 2 diabetic patients.

OBJECTIVE: To document an association between arterial wall stiffness and reduced flow volume in the lower-extremity arteries of diabetic patients. RESEARCH DESIGN AND METHODS: We recruited 60 consecutive type 2 diabetic patients who had no history or symptoms of peripheral arterial disease (PAD) in the lower extremities and normal ankle/brachial systolic blood pressure index at the time of the study (non-PAD group) and 20 age-matched nondiabetic subjects (control group). We used an automatic device to measure pulse wave velocity (PWV) in the lower extremities as an index of arterial wall stiffness. At the popliteal artery, we evaluated flow volume and the resistive index as an index of arterial resistance to blood flow using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. RESULTS: Consistent with previous reports, we confirmed that the non-PAD group had an abnormally higher PWV compared with that of the control group (P < 0.001). To further demonstrate decreased flow volume and abnormal flow pattern at the popliteal artery in patients with a higher degree of arterial wall stiffness, we assigned the 60 non-PAD patients to tertiles based on their levels of PWV. In the highest group, magnetic resonance angiograms of the calf and foot arteries showed decreased intravascular signal intensity, indicating the decreased arterial inflow in those arteries. The highest group was also characterized by the lowest late diastolic and total flow volumes as well as the highest resistive index among the groups. From stepwise multiple regression analysis, PWV and autonomic function were identified as independent determinants for late diastolic flow volume (r(2) = 0.300; P < 0.001). CONCLUSIONS: Arterial wall stiffness was associated with reduced arterial flow volume in the lower extremities of diabetic patients.

Aged↗

[The effect of negative emotion on eyewitness functional field of view].

This study examined whether the functional field of view was shrunk by negative emotion. The functional field of view was determined in terms of the number detection task, in which a number presented for a brief exposure peripherally in one of the four video screen corners. Participants watched either negative emotional or neutral event on the screen. Emotion was evaluated by means of self-ratings of mood adjective checklist, and the results showed that tensional arousal increased in participants who watched the negative emotional event. After watching the video participants were asked to report whether they noticed the number. Participants who watched the emotional event were able to detect fewer numbers than participants who watched the neutral event. This result suggests that the functional field of view shrank because of negative emotion. Peripheral memory decrement reported in previous studies might be due to the shrinkage of the functional field of view.

Adult↗

[Tumor ablation with MRI navigation--a novel method of microwave coagulation therapy for hepatic tumor].

Fifty-eight patients with hepatic tumor which consisted of 22 hepatocellular carcinomas and 36 metastatic liver tumors were treated by microwave coagulation therapy with MRI navigation. The tumors were located in all segments of liver except S1. In 24 cases among them, the abdominal approach was difficult, because the tumors were located just below the diaphragm. These cases were selected for thoracoscope-assisted microwave ablation under MR-guidance across the diaphragm. All MR data were collected on a vertically oriented open MRI system (0.5 T SIGNA SP/i system: GE Medical Systems). The microwave electrode was introduced into the liver through a 14G needle via a percutaneous puncture with real-time MR image navigation. Microwave ablations at 60 W for 60 seconds were repeated several times depending on the tumor size. MR imaging may be employed as a reliable guide for percutaneous puncture. Moreover, sufficient safety margin could be obtained for hepatic tumor ablation. MR-guided microwave thermoablation therapy is a feasible method of treatment for hepatic tumors.

Carcinoma, Hepatocellular↗

Human T-cell leukemia virus type I tax activates transcription of the human monocyte chemoattractant protein-1 gene through two nuclear factor-kappaB sites.

Infection by human T-cell leukemia virus type (HTLV) I leads to adult T-cell leukemia and is also associated with the neurodegenerative disease HTLV-I-associated myelopathy/tropical spastic paraparesis. Leukocytes are attracted to sites of inflammation by chemokines. One such chemokine is monocyte chemoattractant protein (MCP)-1, a member of the C-C subfamily of chemokines. We investigated whether HTLV-I infection causes up-regulation of MCP-1, which may in turn cause recruitment of leukocytes to HTLV-I-infected areas. We now report that MCP-1 mRNA levels are elevated in HTLV-I-infected T-cell lines, when compared with uninfected ones. We further confirmed secretion of MCP-1 by HTLV-I-infected T-cell lines. MCP-1 mRNA was also expressed in leukemic cells from patients with adult T-cell leukemia. The 5' transcriptional regulatory region of the MCP-1 gene was activated by the HTLV-I-encoded transactivator Tax in the human T-cell line Jurkat, in which endogenous MCP-1 is induced by Tax. By using site-specific point mutations, we have identified two closely spaced nuclear factor (NF)-kappaB sites, A1 and A2, to be important for Tax-mediated transactivation of the MCP-1 gene. Through the use of an electrophoretic mobility shift assay, we demonstrated that Tax induced NF-kappaB binding to both MCP-1 kappaB sites. This is the first report to demonstrate that Tax can transactivate the MCP-1 gene through the induction of NF-kappaB. Our results thus reveal how Tax disrupts the normally regulated MCP-1 gene and leads to its constitutive expression in HTLV-I-infected cells. These findings may have important implications for our understanding of HTLV-I-associated diseases.

Binding Sites↗

[Physical characteristics of medical students at UOEH (1979-1996)].

The purpose of this study is to explore future directions for health and physical education at UOEH. To do so, the authors first analyzed data taken from physical fitness tests conducted for newly incoming medical students every year since UOEH was founded more than twenty years ago. It was seen that male students tended to be overweight, but that the level of their physical fitness was about the same as the national average. We then managed to obtain data from a physical fitness test conducted for about 50 members of the 1997 graduating class just after their graduation. The results from comparing these data with those taken six years before showed a remarkable tend: that is, the males who had been already over-weight when they became freshmen, tended to gain more weight over the six years spent at UOEH. This paper examines the causes of these results, and an ideal future Japanese university health and physical education plan.

Adult↗

Identification and characterization of the RNA helicase activity of Japanese encephalitis virus NS3 protein.

The NS3 protein of Japanese encephalitis virus (JEV) contains motifs typical of RNA helicase/NTPase but no RNA helicase activity has been reported for this protein. To identify and characterize the RNA helicase activity of JEV NS3, a truncated form of the protein with a His-tag was expressed in Escherichia coli and purified. The purified JEV NS3 protein showed an RNA helicase activity, which was dependent on divalent cations and ATP. An Asp-285-to-Ala substitution in motif II of the JEV NS3 protein abolished the ATPase and RNA helicase activities. These results indicate that the C-terminal 457 residues are sufficient to exhibit the RNA helicase activity of JEV NS3.

Adenosine Triphosphatases↗

New haplotype of familial Creutzfeldt-Jakob disease with a codon 200 mutation and a codon 219 polymorphism of the prion protein gene in a Japanese family.

We report a new haplotype of familial Creutzfeldt-Jakob disease (CJD) with a codon 200 mutation and a codon 219 polymorphism of the prion protein gene in a Japanese family. There were four cases diagnosed with CJD neuropathologically, one of which was identified with a codon 200 mutation (glutamic acid to lysine) and a codon 219Lys polymorphism on the same allele. Clinicopathologically, two cases had a long clinical course, whereas the others were similar to the cases with a codon 200 mutation. Three cases was diagnosed with the panencephalopathic-type CJD neuropathologically and the other was diagnosed with the subacute spongiform encephalopathy, a subtype of CJD. We consider that the clinicopathological features in familial CJD are not steadily uniform and that it is impossible to state definitely from this study whether the codon 219 polymorphism influences the clinicopathological aspects in familial CJD with a codon 200 mutation (glutamic acid to lysine).

Aged↗

1H- and 31P-magnetic resonance spectroscopy and imaging as a new diagnostic tool to evaluate neuropathic foot ulcers in Type II diabetic patients.

AIMS/HYPOTHESIS: We studied 36 Type II (non-insulin-dependent) diabetic patients without occlusive arterial diseases in the lower extremities and 12 age-matched and sex-matched non-diabetic subjects to clarify the association between diabetic polyneuropathy and foot ulcers using 1H- and 31P-magnetic resonance spectroscopy and imaging. METHODS: The 36 diabetic patients consisted of 12 patients with superficial foot ulcers and 24 patients free from this disease. We measured fat to water and phosphocreatine to inorganic phosphate (PCr:Pi) ratios and calculated the intracellular pH of resting plantar muscles by depth-resolved surface-coil spectroscopy using an 1H-31P double tuned coil. Furthermore, foot vasculature, fat and PCr contents of plantar muscles were visualised by phase-contrast angiography, T1-weighted spin-echo imaging and 31P-chemical shift imaging. RESULTS: The 12 foot ulcer patients showed a reduced PCr to Pi ratio (p < 0.001) and peripheral nerve functions (p < 0.01-0.001) but an increased fat to water ratio (p < 0.001) and intracellular pH (p < 0.001) compared with the 24 patients without ulcers. From stepwise multiple regression analyses, motor nerve function as well as severity of nephropathy was associated with both fat to water and PCr to Pi ratios. When these patients were categorised into three groups based on their level of motor nerve function, the frequency of foot ulcers of the lowest group was higher than that of the highest group. CONCLUSION/INTERPRETATION: Our findings indicated that motor nerve dysfunction in diabetic patients was closely associated with impaired energy metabolism, fatty infiltration and increased intracellular pH of plantar muscles and high frequency of foot ulcers. These new techniques could contribute to help clarify the predisposing factors for foot ulcers.

Aged↗

Usefulness of waveform analysis of popliteal artery in type II diabetic patients using gated magnetic resonance 2D-cine-PC imaging and 31P spectroscopy.

AIMS/HYPOTHESIS: We studied 76 patients with Type II (non-insulin-dependent) diabetes mellitus and 16 age-matched non-diabetic subjects (control group) to clarify qualitative and quantitative abnormalities of waveform and flow volume of the popliteal artery. METHODS: The 76 diabetic patients comprised 16 patients with occlusive arterial disease in the lower extremities [arteriosclerosis obliterans (ASO) group] and 60 patients free from this disease (non-ASO group). We flow analysed the popliteal artery and measured the phosphocreatine to inorganic phosphate ratio of resting plantar muscles to identify risk factors for foot lesions using gated magnetic resonance two-dimensional cine-mode phase-contrast imaging and 31P spectroscopy. RESULTS: The control and non-ASO groups had a triphasic waveform with systolic, early and late diastolic components. All ASO patients had an abnormal monophasic waveform and a lower ankle brachial index than that of the control and non-ASO groups. To clarify the mechanism of reduced flow volume of lower extremities, we assigned the 60 patients of the non-ASO group to the three subgroups based on their levels of total flow volume of the popliteal artery. The lowest group showed an abnormal triphasic waveform with lower amplitudes of systolic and late diastolic components and flow velocities in foot arteries than those of the highest group although ABI was similar. From stepwise multiple regression analysis, late diastolic flow volume was identified as an independent determinant for the phosphocreatine to inorganic phosphate ratio (r2 = 0.484, p < 0.001). CONCLUSION/INTERPRETATION: Waveform analysis of popliteal artery provides a powerful tool for identifying impaired peripheral circulation caused by either occlusive arterial disease or increased arterial resistance in diabetic patients.

Adult↗

Openings between defective endothelial cells explain tumor vessel leakiness.

Leakiness of blood vessels in tumors may contribute to disease progression and is key to certain forms of cancer therapy, but the structural basis of the leakiness is unclear. We sought to determine whether endothelial gaps or transcellular holes, similar to those found in leaky vessels in inflammation, could explain the leakiness of tumor vessels. Blood vessels in MCa-IV mouse mammary carcinomas, which are known to be unusually leaky (functional pore size 1.2-2 microm), were compared to vessels in three less leaky tumors and normal mammary glands. Vessels were identified by their binding of intravascularly injected fluorescent cationic liposomes and Lycopersicon esculentum lectin and by CD31 (PECAM) immunoreactivity. The luminal surface of vessels in all four tumors had a defective endothelial monolayer as revealed by scanning electron microscopy. In MCa-IV tumors, 14% of the vessel surface was lined by poorly connected, overlapping cells. The most superficial lining cells, like endothelial cells, had CD31 immunoreactivity and fenestrae with diaphragms, but they had a branched phenotype with cytoplasmic projections as long as 50 microm. Some branched cells were separated by intercellular openings (mean diameter 1.7 microm; range, 0.3-4.7 microm). Transcellular holes (mean diameter 0.6 microm) were also present but were only 8% as numerous as intercellular openings. Some CD31-positive cells protruded into the vessel lumen; others sprouted into perivascular tumor tissue. Tumors in RIP-Tag2 mice had, in addition, tumor cell-lined lakes of extravasated erythrocytes. We conclude that some tumor vessels have a defective cellular lining composed of disorganized, loosely connected, branched, overlapping or sprouting endothelial cells. Openings between these cells contribute to tumor vessel leakiness and may permit access of macromolecular therapeutic agents to tumor cells.

Animals↗

A human B-lineage dendritic cell line, HBM-noda and its potential role in human T-cell leukemia/lymphoma virus type I infection.

An Epstein-Barr virus-transformed B-cell line, HBM-Noda (Noda), that has a dendritic morphology as well as several characteristic features of dendritic cells (DC) has been established. We therefore refer to Noda as B-lineage DC. Although human T-cell leukemia/lymphoma virus type I (HTLV-I) exhibit substantial cellular tropism, the roles of DC in HTLV-I infection remain unknown. To further clarify the characteristics of Noda cells, we performed infection experiments using a concentrated HTLV-I fraction from the adult T-cell leukemia cell line, HPB-ATL-2. Noda, as well as other cell lines examined, were sensitive to HTLV-I infection as detected by proviral DNA using polymerase chain reaction, but most infected Noda cells underwent necrosis within 7 days. The most striking feature of Noda cells was the abundant expression of viral antigen (p19) on the cell surface following infection (approximately day 4), probably due to strong viral adsorption. In cocultivation experiments using Noda cells at day 1 of post-infection and peripheral blood activated T cells, we detected a few (1.3%) viral antigen expressing T cells after 5 days of coculture by flow cytometry. These results suggest that B-lineage DC such as Noda cells play a role in the establishment of HTLV-I infection at an early phase.

Adult↗

Single-tube multiplex PCR for rapid and sensitive diagnosis of subgenus B and other subgenera adenoviruses in clinical samples.

We developed a new diagnostic method of subgenus (Sub) B adenovirus (Ad) in clinical samples using non-nested polymerase chain reaction (PCR). Sequences of the conserved hexon-coding region of representative strains of eight serotypes (3, 7, 11, 14, 16, 21, 34 and 35) of Sub B Ad were heterogeneous. In order to distinguish Ad serotype 3 (Ad 3) and Ad 7 from the other serotypes of Sub B Ad, and to differentiate Ad 3 and 7 from each other, 3 different downstream primers were designed based on the sequence heterogeneity. By a single-tube PCR method using a combination of 6 primers including the 3 new primers, Ads demonstrated to amplify 188, 206, 284, and 301 bp DNA fragments for Ad 3, Ad 7, other Sub B Ads, and non-Sub B Ads, respectively. A total of 114 clinical samples were selected to evaluate the direct applicability of our PCR. The results were compared with previous culture results. Sixty-seven out of 71 (94%) Sub B Ad culture-positive samples, and 15 out of 19 (79%) Sub C or E-positive samples amplified products of the expected size. Two of 20 (10%) culture-negative samples from pharyngoconjunctival fever patients were identified as Ad 3 by the PCR. Four samples, from which non-Ad viruses were isolated, were negative by the PCR. The present study might provide a rapid and sensitive diagnosis method for infections caused by Sub B Ads.

Adenovirus Infections, Human↗

A fatal case of fulminant myocarditis with human herpesvirus-6 infection.

We report a case of fulminant myocarditis after steroid pulse therapy for acute hepatitis. Serological studies demonstrated a four-fold increase in the antibodies against human herpesvirus-6 (HHV-6) IgG, and a PCR showed the existence of HHV-6 virus DNA. HHV-6 virus DNA was also isolated from the liver and the heart. We believe that exacerbation of fulminant myocarditis was probably associated with the reactivation of HHV-6 due to the immunosuppressive state of the host.

Antibodies, Viral↗

Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells.

The effect of various 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the induction of HMG-CoA reductase and low density lipoprotein (LDL) receptor mRNA were quantitatively determined in the cultured human hepatoma cell line Hep G2 by means of a ribonuclease protection assay. Lipophilic inhibitors including mevastatin, simvastatin, atorvastatin and NK-104 were able to increase the levels of mRNAs for HMG-CoA reductase and the LDL receptor, but the hydrophilic inhibitor pravastatin was not effective in Hep G2 cells as had previously been reported. The LDL receptor mRNA was induced by NK-104 most effectively between 0.1 to 10 microM among the lipophilic inhibitors, whereas the degrees of induction of HMG-CoA reductase mRNA by these inhibitors did not differ significantly from each other. When cells were treated with a 200-fold excess of the IC50 concentration of each inhibitor, NK-104 was able to induce LDL receptor mRNA most effectively. These results indicate that the effect of HMG-CoA reductase inhibitors on the upregulation of mRNA for reductase and LDL receptor are different from each other and among these lipophilic inhibitors. NK-104 is most effective in inducing LDL receptor mRNA in Hep G2 cells.

Atorvastatin↗

Expression of CXCR4 in the brain of feline immunodeficiency virus infected cat.

Advances in understanding the mechanisms of human immunodeficiency virus (HIV)-1 entry have revealed that the cell surface CD4 expression alone is insufficient and needs an additional molecule on its surface for the viral entry. These are G-protein coupled seven transmembrane (7-TM) family molecules (chemokine receptor) and amongst them one is CXCR4. Feline homologue of CXCR4 acting as a co-receptor for feline immunodeficiency virus (FIV) entry is already reported for the Crandle feline kidney cells strain (CrFK) of FIV. An experiment was carried out to search the expression of CXCR4 retrospectively in FIV (CrFK) infected cat brain tissues using immunohistochemically in the formalin fixed paraffin sections against 12G5, a mouse monoclonal antibody to CXCR4. We observed the expression of this receptor in feline neurons, astrocytes and in some vascular endothelial cells. The study of expression of CXCR4 in the brain, which is one of the many chemokine receptors in the central nervous system, may provide further insight into the interactions between brain cells, pathogens, and the immune system, and help understand the pathogenesis of HIV dementia.

AIDS Dementia Complex↗

Identification of the canarypox virus thymidine kinase gene and insertion of foreign genes.

We mapped the canarypox virus (CaPV) thymidine kinase (TK) gene within a 5.8-kbp XbaI fragment of the genome by Southern blotting using the fowlpox virus (FPV) TK gene as a probe. Nucleotide sequence analysis of the fragment revealed seven open reading frames (ORFs) showing gene organization similar to that of FPV. The TK gene contained in this region had an ORF of 179 amino acids encoding a polypeptide with a putative molecular mass of 20.0 kDa. An A/T-rich region and a transcription termination signal, TTTTTAT, were found upstream and at the end of the ORF, which is consistent with poxvirus early gene regulation. The consensus sequence of the late promoter TAAAT also overlapped with the initiation codon of the ORF. The amino acid sequence similarity between the TK genes of CaPV and FPV, avipoxviruses, was 64.2%, which was lower than the similarities between vaccinia and variola orthopoxviruses (97.2%) and between Shope fibroma and myxoma leporipoxviruses (82.6%). However, the monophyly of avian clades of CaPV and FPV was supported by phylogenetic analysis. We then inserted the genes encoding lacZ, luciferase (luci), and envelope of human T-lymphotropic virus type 1 (HTLV-1 env) into the TK gene of CaPV to evaluate its suitability as an expression vector. The recombinant viruses obtained were unstable, although the foreign genes were expressed efficiently in the mammalian cells infected with the viruses.

Amino Acid Sequence↗

Effects of blood sugar level on rat transient focal brain ischemia consecutively observed by diffusion-weighted EPI and (1)H echo planar spectroscopic imaging.

The effects of blood sugar level on transient focal brain ischemia were examined by consecutive diffusion-weighted EPI and (1)H echo planar spectroscopic imaging. A remote-controlled rat intraluminal suture middle cerebral artery occlusion (MCAO) model was prepared. Animals were divided into three experimental groups: control, 1 g/kg, and 2 g/kg glucose groups (n = 6 for each). Saline or glucose was infused intraperitoneally 30 min prior to MCAO. The glucose-loaded groups showed increased lactate accumulation and marked decreases in average diffusion coefficient in the ischemic region during 40-min MCAO. These changes were correlated with blood sugar levels at the onset of MCAO. After reperfusion, all rats in the control and 1 g/kg groups recovered from the ischemic changes, but three rats with marked hyperglycemia in the 2 g/kg group showed irreversible changes. The adverse effects of hyperglycemia on transient focal brain ischemia were clearly demonstrated by sequential 2D images. Magn Reson Med 42:895-902, 1999.

Animals↗