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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 397 records · Page 22Linked to original sources
PubMed1997

Variable deposition of amyloid beta-protein (A beta) with the carboxy-terminus that ends at residue valine40 (A beta 40) in the cerebral cortex of patients with Alzheimer's disease: a double-labeling immunohistochemical study with antibodies specific for A beta 40 and the A beta that ends at residues alanine42/threonine43 (A beta 42).

Amyloid beta-protein (A beta) deposits in the cerebral cortices of patients with Alzheimer's disease (AD) were investigated immunohistochemically to determine their carboxy terminal sequences. Antibodies specific for A beta terminating at residue valine40 (A beta 40) and at residues alanine42/threonine43 (A beta 42) were used. Virtually all parenchymal A beta deposits were positive for A beta 42. Many of these deposits were also partially or completely labeled for A beta 40. The degree of A beta 40 labeling varied from area to area within a given brain and from AD case to AD case. In contrast to parenchymal deposits, A beta 40 labeled essentially all the vascular deposits which constitute amyloid angiopathy (AA), with A beta 42 occurring variably in some of these deposits. Occasional AA was found, however, in which A beta 42 predominated or was exclusively deposited. Such a diversity of A beta species, both in brain parenchyma and in AA, suggests that multiple C-terminal processing mechanisms occur in the cell types responsible for these deposits.

Aged↗
PubMed1997

Influence of thrombopoietin on platelet activation in myeloproliferative disorders.

Although thrombopoietin itself does not influence platelet aggregation, it enhances platelet activation in response to certain agonists. We evaluated the effects of thrombopoietin on platelet activation using platelet-rich plasma from 16 patients with myeloproliferative disorders (MPD group) and 16 healthy volunteers (control group). Preincubation with thrombopoietin significantly enhanced platelet aggregation stimulated by ADP, collagen, or epinephrine in the MPD group as well as the control group. However, aggregation induced by 3 micro ADP or 16 microM epinephrine showed significantly less augmentation by thrombopoietin in the MPD group than in the control group. Thrombopoietin significantly shortened the lag time between the addition of 3 microM ADP or 16 microM epinephrine and initiation of secondary aggregation and the lag time between addition of 2 microg/ml collagen and initiation of aggregation in both groups. When platelet-rich plasma was used without adjustment of the platelet count, thrombopoietin itself induced aggregation in two patients. Hypoaggregation after addition of 0.5 microg/ml collagen was observed in seven out of nine patients with normal thrombopoietin levels and only one of six patients with high levels (P = 0.04). Enhancement of 0.5 microg/ml collagen-induced aggregation by thrombopoietin was seen in five out of nine patients with normal thrombopoietin levels and none of the six patients with elevated levels (P = 0.04). These results indicate that platelet activation by certain agonists is enhanced by thrombopoietin in patients with these diseases as well as in normal controls and that the serum thrombopoietin level may regulate the function of circulating platelets in vivo.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

Irgasan DP 300 (5-chloro-2-(2,4-dichlorophenoxy)-phenol) induces cytochrome P450s and inhibits haem biosynthesis in rat hepatocytes cultured on Matrigel.

1. The effect of Irgasan DP 300 (5-chloro-2-(2,4-dichlorophenoxy)phenol) on cytochrome P450 (P450) induction and haem biosynthesis was studied in rat hepatocytes cultured on Matrigel. 2. Irgasan DP 300 significantly induced 7-benzyloxyresorufin O-debenzylase activity, followed by 7-pentoxyresorufin O-depentylase and 7-ethoxyresorufin O-deethylase activities. 4-Nitrophenol hydroxylase, testosterone 6 beta-hydroxylase and methoxyresorufin O-demethylase activities were also slightly increased. The maximum induction of these enzyme activities was obtained at the same concentration of 125 microM in the culture medium. 3. Immunochemical blots using anti-rat cytochrome P450 antibodies revealed that Irgasan DP 300 preferably induced CYP2B1/2 along with a slight increase in 3A. These results indicate that Irgasan DP 300 is a phenobarbital-type inducer. 4. In the absence of exogenous 5-aminolevulinic acid (ALA), slight increases in protoporphyrin IX (2.6-fold) and coproporphyrin III (1.3-fold) were observed in the Irgasan DP 300-treated cultures. In contrast, when 75 microM ALA was present, Irgasan DP 300 (250 microM) caused an extensive accumulation of uroporphyrin I (13-fold). 5. Irgasan DP 300 inhibited rat hepatic uroporphyrinogen III synthase in vitro. 6. These results indicate that Irgasan DP 300 produced accumulation of hydroxymethylbilane in rat hepatocytes by inhibiting uroporphyrinogen III synthase, and consequently an accumulation of uroporphyrin I.

Aminolevulinic Acid↗
PubMed1997

Temporal and regional profiles of cytoskeletal protein accumulation in the rat brain following traumatic brain injury.

To characterize the cytoskeletal aberration due to traumatic injury, temporal and regional profiles of changes in immunoreactivity of microtubule-associated protein 2 (MAP2), neurofilament heavy subunit protein (NFH) and heat shock protein 72 (HSP72) were investigated after different magnitudes of traumatic brain injury by fluid percussion. The experimental rat brain was perfusion-fixed at 1, 6 and 24 hours after traumatic brain injury. Conventional histological staining has demonstrated that the mildest traumatic brain injury (1.0 atm) induced no neuronal loss at the impact site and that neuron loss was apparent when traumatic brain injury was increased to 4.3 atm. The mildest traumatic brain injury, however, caused a significant increase in HSP72 immunoreactivity in the superficial cortical layers at the impact site as early as 1 hour after the injury. In the case of severe traumatic brain injury (4.3 atm), neuron loss was apparent in the area at the impact site, but the increase in HSP72 immunoreactivity was moderate, and it was observed only after 6 hours in the deep cortical layers under the necrotic area. The increased immunostaining of MAP2 was demonstrated in damaged axons and neuronal perikarya in the wider area surrounding the impact site at 6 and 24 hours after the injury. Six and 24 hours after the injury, perikaryal accumulation of neurofilament was observed, and the accumulated neurofilament was mostly phosphorylated. These results indicate that the severe traumatic brain injury of 4.3 atm triggers the abnormal accumulation of cytoskeletal proteins in neuronal perikarya, most probably due to an impairment of axonal transport. It is implied that the increased expression of HSP72 may be involved in the protective process of neurons after traumatic brain injury.

Animals↗
PubMed1997

An impedance matching of femoral-popliteal arterial grafts: a theoretical study.

We have proposed a mathematical method to investigate the matching conditions for an arterial graft in the femoral-popliteal region from a mechanical stand-point. Pulsatory blood flow, arterial wall motions, and conservation law are expressed by linear dynamical equations based on strict mechanical and constitutional considerations. To express the physiological blood flow in an actual arterial system, the tethering effects from the surrounding tissue and wall tensions were incorporated. The physiological parameters of arterial wall and tethering were utilized from reported experimental data. By complex analysis, mathematical expressions for the local impedance and reflection coefficient were obtained. They include not only blood properties such as viscosity and density, but also arterial properties including elastic modulus, radius, Poisson ratio, wall thickness, wall tension, frequency, and tethering effects from surrounding tissue. A matching condition was defined for minimizing the local impedance and reflection coefficient. The biophysical background was to reduce any mechanical mismatches, thus minimizing the disturbance of the flow velocity profile and shear stress distribution within the artery. Impedance matching in turn diminishes the negative factors for graft substitution represented by intimal hyperplasia and thrombosis. The calculated impedance and reflection coefficient inversed parabolically to functions of the resistance of the host artery, and there was one host arterial resistance that minimized the impedance and reflection coefficient. The present analysis revealed that for matching host artery with an elevated resistance, the dynamic elastic modulus of the wall of the graft that minimizes the impedance and reflection coefficient was increased. This indicates that for a host artery with a high resistance, an impedance matched stiff wall graft is preferable. For a large radius and a compliant host artery on the other hand, a large compliant graft should be linked. The present theoretical matching conditions will prevent anastomotic hyperplasia and thrombosis in graft substitution.

Blood Vessel Prosthesis↗
PubMed1997

Long-term evaluation of a nonpulsatile mechanical circulatory support system.

Antithrombogenicity of a centrifugal pump (CP) developed in our institute is provided by a central balancing hole (BH) in the impeller. A current CP, the National Cardiovascular Center (NCVC)-2, was ameliorated to improve antithrombogenicity, whereby the BH diameter was widened to improve self washout flow velocity, and an edge of the thrust bearing was rounded off to minimize flow separation. Effects of these modifications were assessed in a long-term in vivo experiment. The antithrombogenicity, hemolytic property, and mechanical durability of the NCVC-2 were investigated in 3 goats. The NCVC-2 was installed paracorporeally between the left atrium and the aorta and driven as long as possible at rotating speeds of about 2,800 rpm. The NCVC-2 ran for 50, 200, and 367+ days. The mean bypass flow rates were 6.8, 5.0, and 5.3 L/min, respectively. Creatinine, blood urea nitrogen (BUN), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) did not increase until one week before termination. Plasma free hemoglobin was kept to a level less than 15 mg/dl, except for the last week of the second case. These results indicate that the NCVC-2 has excellent antithrombogenicity, an acceptable hemolytic property and the necessary durability for prolonged use.

Alanine Transaminase↗
PubMed1997

Noninvasive pump flow estimation of a centrifugal blood pump.

A flow rate estimating method was investigated for a centrifugal blood pump developed in our institute. The estimated flow rate was determined by the power consumption, the rotating speed of the motor, and the hematocrit value. The power consumption and the rotating speed of the motor were measured with a wattmeter. The examinations were performed in a closed mock loop filled with goat blood with hematocrit values of 21.5%, 28%, 34%, and 42%. Measured values of blood viscosity were 2.47, 3.09, 3.71, and 5.07 mPa.s at a share rate of 37.5/s, respectively. A linear correlation between the power consumption and the pump flow rate was observed in all hematocrit values. But variations in hematocrit caused a difference in the flow rate up to 1.1 L/min at the same power consumption and rotating speed. Effects of blood viscosity on the flow estimation were corrected by the hematocrit value. The value of the coefficient of determination, R2, between the estimated flow rate and the measured flow rate was 0.988. These results may indicate that the flow estimating method calculated by the power consumption of the motor, the rotating speed, and the hematocrit value is useful in the clinical situation.

Animals↗
PubMed1997

Productive and lytic infection of human CD4+ type 1 helper T cells with macrophage-tropic human immunodeficiency virus type 1.

It is generally recognized that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) is the predominant population during the acute and asymptomatic phases of HIV-1 infection. Here, we compared the proliferation and syncytium-inducing activities of different HIV-1 strains in primary CD4+ T cells expressing various helper T (Th)-type cytokine profiles. The macrophage-tropic HIV-1 strains HIV-1JR-CSF, HIV-1NFN-SX, and HIV-1SF162 could proliferate vigorously and generate syncytia in primary CD4+ T cells irrespective of their Th subtype, in contrast to the T-cell-line-tropic HIV-1 strains HIV-1NL4-3 and HIV-1IIIB, which favored non-type 1 Th conditions. These results indicate that macrophage-tropic HIV-1 may be more invasive and virulent, since it kills more CD4+ Th1 cells than T-cell-line-tropic HIV-1 during the early stages of HIV-1 infection, when the Th1 immune response is dominant.

Giant Cells↗
PubMed1997

Enhancement of glucose uptake in stunned myocardium: role of glucose transporter.

This study quantifies the myocardial glucose uptake and clarifies the pathway of augmented glucose uptake in myocardium reperfused after a brief period of ischemia (stunned myocardium). The glucose uptake rate was determined from the time course of the sugar phosphate (SP) resonance in rat myocardium (d[SP]/dt) with 31P nuclear magnetic resonance after the substitution of glucose with its analog 2-deoxyglucose. The d[SP]/dt in stunned myocardium [1.03 +/- 0.05 (SE) micromol x g wet wt(-1) x min(-1); n = 8] increased significantly compared with nonischemic control myocardium (0.18 +/- 0.03 micromol x g wet wt(-1) x min(-1); n = 8; P < 0.0001), reaching the maximal stimulatory uptake rate during exposure to insulin (1.05 +/- 0.04 micromol x g wet wt(-1) x min(-1); n = 8). Twenty minutes after reperfusion, the d[SP]/dt was still augmented (0.41 +/- 0.05 micromol x g wet wt(-1) x min(-1); n = 5; P < 0.05 vs. control myocardium). To elucidate further the mechanism of augmented glucose uptake, N6-(L-2-phenylisopropyl)-adenosine (PIA; 100 micromol/l), a potent blocker of the glucose transporter, was administered to stunned hearts and, as a control, to insulin-stimulated hearts. PIA significantly and comparably inhibited the increase in d[SP]/dt in stunned myocardium (0.36 +/- 0.07 micromol x g wet wt(-1) x min(-1); n = 4; P < 0.0001 vs. without PIA) and in insulin-stimulated myocardium (0.38 +/- 0.02 micromol x g wet wt(-1) x min(-1); n = 4; P < 0.0001 vs. without PIA). These results indicate that the augmented glucose uptake in stunned myocardium is maintained by the glucose transporter, the amount of which is almost equal to that which can be maximally recruited by insulin.

Adenosine Triphosphate↗
PubMed1997

Mitochondrial abnormalities in a murine model of primary carnitine deficiency. Systemic pathology and trial of replacement therapy.

Mitochondrial abnormalities and effectiveness of replacement therapy were examined in a murine model of systemic carnitine deficiency, namely the juvenile visceral steatosis (JVS) mouse. Homozygous JVS mice revealed severe lipid deposition and abnormal mitochondria in liver, heart, skeletal muscle, and kidney, but there was no pathological change in the nervous system, though they showed cerebral signs. There were numerous ragged-red fibers in muscles, but enzyme activities of the respiratory chain were intact. Histograms of oxidative and nonoxidative muscle fibers showed an increase in small and oxidative muscle fibers in 4-week-old JVS mice, but this difference no longer existed in 8-week- or 1-year-old JVS mice. On the contrary, Mn-superoxide dismutase immunostaining of muscle showed a focal increase in every age of JVS mice. With L-carnitine treatment, JVS mice could survive for a year, but to some extent, there were the same pathological changes as those seen in untreated mice.

Animals↗
PubMed1997

Transforming growth factor-beta1 induces a mesenchyme-like cell shape without epithelial polarization in thyrocytes and inhibits thyroid folliculogenesis in collagen gel culture.

Transforming growth factor-beta1 (TGFbeta1) induces a mesenchyme-like cell shape in some epithelial cell types. To clarify the role of TGFbeta1 in the morphological regulation of thyrocytes, we performed collagen gel culture of porcine thyrocytes with serum-free medium. TGFbeta1-nontreated cells organized follicles. In contrast, the cells treated with 10 ng/ml TGFbeta1 became spindle shaped, i.e. they resembled mesenchymal fibroblasts, and did not form follicles. To characterize the spindle-shaped cells, we examined the fine structures and expression of thyroglobulin (Tg) and cytoskeletal proteins using electron microscopy, immunohistochemistry, and immunoblotting. TGFbeta1-nontreated cells had microvilli at the apical side facing follicle lumen and had basal lamina at the basal side in contact with collagen gel. TGFbeta1-treated cells showed both microvilli and basal lamina at the basal side. TGFbeta1-nontreated cells expressed Tg, whereas TGFbeta1-treated cells showed no expression. TGFbeta1-nontreated cells barely expressed vimentin, but they expressed enough cytokeratin. TGFbeta1-treated cells extensively displayed vimentin along with the change in shape to become spindle-like and retained a decreased expression of cytokeratin. TSH (10 mU/ml) did not essentially influence any TGFbeta1 effects on the cells. These results indicate that TGFbeta1 induces a mesenchyme-like cell shape accompanied by cytoskeletal molecular change and the loss of both epithelial polarization and a function in thyrocytes, and that it results in inhibiting thyroid folliculogenesis with or without TSH.

Animals↗
PubMed1997

Nuclear concentration of gold labeled-testosterone-bovine serum albumin conjugate injected intravenously in the hormone-target cells of rat.

We examined whether testosterone-bovine serum albumin conjugate (testosterone-BSA) showed similar distribution to radiolabeled testosterone in vivo, by injecting 2-nm colloidal gold labeled-testosterone-BSA (testosterone-BSA-gold) from rat tail vein. The testosterone-BSA-gold with the silver enhancement became visible as silver deposits under electron microscope in nuclei of Leydig cells, Sertoli cells, spermatogonia, spermatocytes and spermatids in the testis, those of the epithelial cells in the seminal vesicle and of the cardiac muscle cells in the heart of rat killed 2 h after the injection. Few deposits were present on the non-target cell nuclei in thymus and spleen. In the liver cells, the deposits were observed in the cytoplasm, but few in the nucleus. At high-power magnification without silver enhancement, the gold particles were found in the target cell nuclei in the testis. In control rat injected with BSA labeled with 2-nm colloidal gold, the percentages of nuclei showing the deposits were fewer than those in the rat injected testosterone-BSA-gold in the target cells. The deposits were also few in the nuclei of non-target cells in control rat. These results suggest that testosterone-BSA-gold is useful for morphological study of testosterone target cells, and imply that BSA conjugated with testosterone can enter the target cell nuclei of the rat.

Animals↗
PubMed1997

Nuclear translocation of gold labeled-testosterone-bovine serum albumin conjugate through the nuclear double membranes in rat spermatids.

We have demonstrated that testosterone-bovine serum albumin conjugate labeled with 2-nm colloidal gold (testosterone-BSA-gold) injected into the vascular system of rat becomes visible as silver deposits on the sections of tissues embedded in epoxy resin after silver enhancement and enters the androgen-target cell nuclei, e.g. round spermatids, but not the non-target cell nuclei. The diameter of the silver deposits depends on the duration of silver enhancement. In this study, to make clear the transfer route of testosterone-BSA-gold into the round spermatid nucleus, the testis of rat injected testosterone-BSA-gold was observed under electron microscope after silver enhancement for short periods of time. The small silver deposits were present on the cell membrane, vesicles, Golgi region, acrosome, subacrosomal space, both the post-acrosomal and the subacrosomal nuclear envelope, and the nucleoplasm in the cap-phase spermatids. The silver deposits were also found in the perinuclear cisterna of post-acrosomal nuclear envelope, but not in the nuclear pore. When the spermatids were observed at high-power magnification without the silver enhancement, the outer nuclear membrane showed many irregular invaginations toward the inner nuclear membrane in the post-acrosomal nuclear envelope. Furthermore, a double-membrane-like vesicle seemed to be present in the nuclear envelope. In the vesicle, the gold particles were present along the inner membrane. These results suggest that testosterone-BSA-gold can enter the nucleoplasm through some route provided by the nuclear double membranes in both the post-acrosomal and the subacrosomal nuclear envelope.

Acrosome↗
PubMed1997

Immunosuppressive effects of gallic acid and chebulagic acid on CTL-mediated cytotoxicity.

Gallic acid (GA) and chebulagic acid (CA) were isolated from the extract of a herbal medicine, kashi (myrobalans: the fruit of Terminalia chebula) as active principles that blocked the cytotoxic T lymphocyte (CTL)-mediated cytotoxicity. GA and CA inhibited the killing activity of CD8+ CTL clone at IC50 values of 30 microM and 50 microM, respectively. Granule exocytosis in response to anti-CD3 stimulation was also blocked by GA and CA at the equivalent concentrations.

Animals↗
PubMed1997

Establishment of a standardized assay system of fibronectin activity using fibronectin-mediated cell adhesion.

An in vitro assay of fibronectin (FN) was established based on the adhesion of baby hamster kidney (BHK) cells through the cell-binding domain of FN. Each well of a microtiter plate was coated with samples or various concentrations of standard FN. Bovine serum albumin was further coated to prevent the non-specific adhesion of the cells. Various numbers of BHK cells were plated and incubated. After washing out the non-attached cells, the number of attached cells was measured using neutral red (NR)-staining. The conditions for the assay were optimal when 1 x 10(5) cells/well were plated and incubated for 90 min. The linear relationship between the concentration of FN coated and the absorbance of NR was observed in the range of 0.1-1.0 micro/ml of FN. The inhibition of cell binding by the peptides containing an Arg-Gly-Asp (RGD) sequence demonstrated that this assay system depended on FN-mediated cell adhesion through the major cell-binding domain.

Animals↗
PubMed1997

Characterization of the protein and glycan moieties in different forms of bovine lactoferrin.

The BrCN cleavage of lactoferrin-a or -b (LF-a or LF-b) led to the observation of four fragments by SDS-PAGE, whose molecular masses were 77, 58, 52, and 30 kDas, or 74, 54, 47, and 30 kDas, respectively. N-Terminal amino acid sequence analyses show that the sequences of 58, 52, and 30 kDa fragments (residues 64-471, 130-471, and 472-689) of LF-a coincide with those of the 54, 47, and 30 kDa fragments of LF-b. respectively. All these fragments, which were positive by PAS staining, were not stained after being treated with glycopeptidase F. This treatment changed the 58 and 52 kDa fragments of LF-a to the 54 and 47 kDa fragments, respectively, whose molecular masses were the same as those of the treated fragments of LF-b. The 58 and 52 kDa fragments of LF-a bound to the lectin, Ricinus communis agglutinin, while the 54 and 47 kDa fragments of LF-b hardly bound to it.

Animals↗