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Biomedical subjects

N Sasaki

Publications and source records attributed to N Sasaki.

At least 37 records · Page 2Linked to original sources
PubMed2003

Two cases with transient lipoprotein lipase (LPL) activity impairment: evidence for the possible involvement of an LPL inhibitor.

UNLABELLED: Two independent severe hypertriglyceridemic infants with transiently impaired lipoprotein lipase (LPL) activity were observed and the causes were explored. Both infants were female, born prematurely with low birth weight and developed hypertriglyceridemia (Fredrickson type V hyperlipidemia: high VLDL and low LDL/HDL) a few months after birth. While mass levels of their post-heparin plasma LPL and apoprotein C-II (apo C-II), a physiological activator of LPL, were normal, their post-heparin plasma LPL activities were remarkably impaired. Both of their mothers' post-heparin plasma LPL activities were slightly or moderately impaired as well, without a decrease in the LPL mass level. No mutations in the genes for LPL and apo C-II were detected in either patient. In an in vitro study with their serum at onset, we could not detect any distinct circulating inhibitors for LPL. There was no data supporting infection or autoimmune diseases, which might have an impact on LPL activity, during the follow-up period. Levels of their plasma triglyceride (TG) and total cholesterol (TC) were decreased quickly by a dietary intervention with medium-chain triglyceride (MCT) milk and kept normal even after stopping the intervention at around age 1 year. However, their low post-heparin LPL activity persisted and returned to normal at around age 2 years. Their low HDL cholesterol levels persisted even after recovery of the TG and TC levels, although lecithin:cholesterol acyltransferase (LCAT) and cholesterol-ester-transfer protein (CETP), two key enzymes of HDL metabolism, were normal throughout the course. The exact reasons why their post-heparin LPL activities were impaired for a certain period and why their HDL cholesterol levels have remained low are still unclear. CONCLUSION: Transiently impaired LPL activity with no defect in LPL enzyme induced severe hypertriglyceridemia in infants. The transient occurrence of inhibitor(s) for LPL was proposed.

Child↗
PubMed2003

The movement protein gene is involved in the virus-specific requirement of the coat protein in cell-to-cell movement of bromoviruses.

Brome mosaic virus (BMV) requires the coat protein (CP) for cell-to-cell movement whereas Cowpea chlorotic mottle virus (CCMV), from the same genus, does not. Chimeric viruses created by exchanging the movement protein (MP) gene between the viruses can move from cell to cell. We show that interference in CP expression impaired the movement of the chimeric CCMV with the BMV MP gene but not of the chimeric BMV with the CCMV MP gene. We thus conclude that the MP gene plays a crucial role in determination of the virus-specific CP requirement in bromovirus cell-to-cell movement.

Amino Acid Sequence↗
PubMed2003

Mechanisms of cytosolic Ca2+ suppression by prostaglandin E2 receptors in rat melanotrophs.

We have previously reported that voltage-dependent Ca2+ (VDC) channels of rat melanotrophs are inhibited by prostaglandin E2 (PGE2). In this study, mechanisms involved in the inhibitory actions of PGE2 receptors of rat melanotrophs were analysed using reverse transcriptase-polymerase chain reaction (RT-PCR), Ca2+-imaging and whole-cell, patch-clamp techniques with recently developed EP agonists, each of which is selective for the known four subclasses of EP receptors (EP1-4). PGE2 reversibly suppressed the cytosolic Ca2+ concentration ([Ca2+]i). The maximum reduction in [Ca2+]i by PGE2 was comparable to that by dopamine or to that by extracellular Ca2+ removal. RT-PCR analysis of all four EP receptors revealed that EP3 and EP4 receptor mRNAs were expressed in the intermediate lobe. The effects of PGE2 to suppress [Ca2+]i were mimicked by the selective EP3 agonist, ONO-AE-248, whereas three other EP agonists, ONO-DI-004 (EP1), ONO-AE1-259 (EP2) and ONO-AE1-329 (EP4), had little or no effect on [Ca2+]i. All four G-protein activated inward rectifying K+ (GIRK) channel mRNAs were identified in intermediate lobe tissues by RT-PCR. Dopamine concentration-dependently activated GIRK currents, whereas PGE2 did not activate GIRK currents, even at the concentration causing maximal inhibition of VDC channels. These results suggest that PGE2 acts on EP3 receptors to suppress Ca2+ entry of rat melanotrophs by selectively inhibiting VDC channels of these cells. We have compared the possible cellular and molecular mechanisms of inhibition by dopamine and PGE2.

Animals↗
PubMed2003

Angiotensin II-type 1 receptor interaction upregulates vascular endothelial growth factor messenger RNA levels in retinal pericytes through intracellular reactive oxygen species generation.

The renin-angiotensin system has been implicated in the development and progression of atherosclerosis, thereby contributing to adverse cardiovascular events. However, its role in diabetic retinopathy remains to be elucidated. Since pericyte loss and dysfunction have been considered as one of the characteristic changes of the early phase of diabetic retinopathy, we investigated the effects of angiotensin II (Ang II) on the growth and function of bovine cultured retinal pericytes. Ang II stimulated intracellular reactive oxygen species (ROS) generation in pericytes in a dose-dependent manner. Telmisartan, a newly developed Ang II type 1 receptor antagonist, completely inhibited ROS generation in pericytes induced by Ang II. Ang II decreased DNA synthesis in pericytes, which was significantly prevented by an antioxidant N-acetylcysteine. Furthermore, telmisartan or N-acetylcysteine were found to completely inhibit the Ang II-induced upregulation of vascular endothelial growth factor messenger RNA levels in pericytes. The present results suggest that Ang II-type 1 receptor interaction could induce pericyte loss and dysfunction through intracellular ROS generation, thus being involved in the development and progression of diabetic retinopathy.

Acetylcysteine↗
PubMed2003

Nifedipine inhibits apoptotic cell death of cultured endothelial cells induced by tumor necrosis factor-alpha.

Impaired endothelial cell (EC) growth and function have been suggested to be an initial event that leads to the development of atherosclerosis. We have very recently found that nifedipine, one of the most popularly used dihydropyridine-based calcium antagonists, prevented EC monocyte chemoattractant protein-1 production elicited by tumor necrosis factor-alpha (TNF-alpha through its antioxidative properties. However, the effects of nifedipine on EC growth and apoptosis are not fully understood. In this study, we investigated whether nifedipine could inhibit tumor necrosis factor (TNF)-alpha-induced growth retardation and apoptotic cell death in human umbilical vein ECs (HUVECs). TNF-alpha inhibited EC proliferation, which was significantly blocked by nifedipine or antioxidant N-acetylcysteine (NAC). Nifedipine or NAC was also found to significantly inhibit apoptotic cell death of TNF-alpha-exposed HUVECs. Our present study suggests that nifedipine may play a protective role against the development and progression of atherosclerosis by promoting EC repair through its antioxidative properties.

Acetylcysteine↗
PubMed2002

Changes in osteoprotegerin and markers of bone metabolism during glucocorticoid treatment in patients with chronic glomerulonephritis.

It is well known that long-term glucocorticoid treatment causes osteoporosis, but the precise mechanism remains unclear. Recently, osteoprotegerin (OPG) has been identified as a cytokine that inhibits osteoclast differentiation. We have previously demonstrated that serum OPG is suppressed by glucocorticoids. Therefore, the present study was carried out to clarify the interrelationships between OPG and other markers of bone metabolism during glucocorticoid treatment. Thirteen patients (7 men, 6 women; 44.1 +/- 5.9 years old) with chronic glomerulonephritis who were to be treated with glucocorticoids for the first time were chosen for this study. Markers of bone metabolism, including serum OPG, osteocalcin (OC), bone-specific alkaline phosphatase activity (bAP), parathyroid hormone (PTH), tartrate-resistant acid phosphatase (TRAP), and bone mineral density (BMD), were measured before and during the treatment period. Glucocorticoids significantly reduced BMD of the lumbar spine in the 6 month treatment period (p < 0.01). Serum OPG was decreased significantly by glucocorticoids within 2 weeks (p < 0.001), and serum TRAP, a marker of bone resorption, was markedly increased (p < 0.001). On the other hand, there were no remarkable changes in serum PTH. Serum OC and bAP, markers of bone formation, were transiently reduced during the treatment period (p < 0.01). Furthermore, only serum OPG was positively and independently correlated with percentage BMD of age-matched reference (%AMR). These findings imply that glucocorticoid-induced bone loss develops rapidly via enhanced bone resorption and suppressed bone formation. Moreover, the increased bone resorption caused by glucocorticoids may be, at least in part, mediated by inhibition of OPG, not increment of PTH.

Adult↗
PubMed2001

Helicobacter pylori infection and the development of gastric cancer.

BACKGROUND: Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. METHODS: We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. RESULTS: Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia were at significantly higher risk for gastric cancer. We detected gastric cancers in 21 (4.7 percent) of the 445 patients with nonulcer dyspepsia, 10 (3.4 percent) of the 297 with gastric ulcers, 5 (2.2 percent) of the 229 with gastric hyperplastic polyps, and none of the 275 with duodenal ulcers. CONCLUSIONS: Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpus-predominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.

Adult↗
PubMed2001

Pollen tube attraction by the synergid cell.

In flowering plants, guidance of the pollen tube to the embryo sac (the haploid female gametophyte) is critical for successful fertilization. The target embryo sac may attract the pollen tube as the final step of guidance in the pistil. We show by laser cell ablation that two synergid cells adjacent to the egg cell attract the pollen tube. A single synergid cell was sufficient to generate an attraction signal, and two cells enhanced it. After fertilization, the embryo sac no longer attracts the pollen tube, despite the persistence of one synergid cell. This cessation of attraction might be involved in blocking polyspermy.

Culture Techniques↗
PubMed2001

Circulating matrix metalloproteinases and their inhibitors in patients with Kawasaki disease.

BACKGROUND: Accelerated matrix breakdown caused by the increased activity of matrix metalloproteinases (MMPs) and/or the quantitative imbalance between MMP and tissue inhibitor of MMP (TIMP) have been implicated in several pathological conditions. MMP and TIMP may also be involved in the destruction of the coronary arterial wall and the resultant coronary arterial lesions in Kawasaki disease. METHODS AND RESULTS: Plasma levels of MMPs, neutrophil elastase, and TIMPs were measured by enzyme-linked immunoassay in 57 patients with Kawasaki disease and no coronary arterial lesions (group 1) and in 8 patients with Kawasaki disease and coronary arterial lesions (group 2). Blood samples were obtained before and after intravenous gamma globulin therapy and in the convalescent stage. Levels of MMPs, neutrophil elastase, and TIMPs were significantly higher in Kawasaki disease patients before gamma globulin therapy than in 18 age-matched afebrile control subjects and 17 age-matched febrile disease control subjects (P<0.01). More importantly, the pre-gamma globulin MMP9 level and MMP9/TIMP2 ratio and post-gamma globulin MMP3 level and MMP3/TIMP1 ratio were significantly higher in group 2 than in group 1 patients (P<0.05). Although MMP levels in febrile disease controls were significantly higher than those of afebrile controls, the MMP/TIMP ratios of febrile disease controls and afebrile controls were comparable. CONCLUSIONS: These data suggest that patients with Kawasaki disease and high levels of MMP and/or MMP/TIMP are susceptible to coronary arterial lesions. Studies of the effects of MMP inhibitors on coronary outcome may provide evidence that MMP is a viable therapeutic target for the prevention of coronary arterial lesions due to Kawasaki disease.

Child, Preschool↗
PubMed2001

Chain aggregation in dilute solutions of poly(methyl methacrylate) below the phase-separation temperature.

For dilute solutions of poly(methyl methacrylate) in isoamyl acetate with the molecular weight M(w)=4.4 x 10(6), the phase-separation process was studied by static light-scattering measurements. The dilute solutions in the concentration range from 1.4 x 10(-4) to 3.8 x 10(-4) g/cm(3) were quenched to about 16 K below the phase-separation temperature, and the aggregation processes of polymer chains were measured over a period of several hours. By analyzing the light-scattering data with the Guinier plot, the weight-averaged molecular weight (w) and z-averaged square radius (1/2)(z) for clusters of polymer chains were determined as a function of time t(min) and concentration c (g/cm(3)). The growth of clusters was represented by the exponential forms (w)/M(0)=e(gct) and (z)/R(2)(0)=e(hct) as a function of ct, where M(0) and R2(0) were the values at t=0, and the constants g and h were determined to be g=11.6 and h=7.5. A double-logarithmic plot of (w) versus (1/2)(z) yielded a straight line with the slope D=3.06+/-0.02. These characteristic features of the chain aggregation process were compared with the Smoluchowski equation for cluster-cluster aggregation with the collision kernel (i+j) for i-mer and j-mer. The observed slow growth of clusters was attributed to the reaction- limited cluster aggregation. The chain density in a cluster was found to increase with an increase of the cluster size, resulting in the slope D exceeding 3.

Journal Article↗
PubMed2001

Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease.

Advanced glycation end products (AGE) and the receptor for AGE (RAGE) have been implicated in the chronic complications of diabetes mellitus (DM), and have been reported to play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we established a polyclonal anti-RAGE antibody, and examined the immunohistochemical localization of amyloid beta protein (Abeta), AGE, and RAGE in neurons and astrocytes from patients with AD and DM. Our anti-RAGE antibody recognized full-length RAGE (50 kd) and N-terminal RAGE (35 kd) in human brain tissue. Abeta-, AGE-, and RAGE-positive granules were identified in the perikaryon of hippocampal neurons (especially from CA3 and CA4) in all subjects. The distribution and staining pattern of these immunopositive granules showed good concordance with each antibody. In AD, most astrocytes contained both AGE-and RAGE-positive granules and their distribution was almost the same. Abeta-positive granules were less common, but Abeta-, AGE-, and RAGE-positive granules were colocalized in one part of a single astrocyte. In DM patients and control cases, AGE-and RAGE-positive astrocytes were very rare. These finding support the hypothesis that glycated Abeta is taken up via RAGE and is degraded through the lysosomal pathway in astrocytes. In addition to the presence of AGE, the process of AGE degradation and receptor-mediated reactions may contribute to neuronal dysfunction and promote the progression of AD.

Aged↗
PubMed2001

Site-specific single amino acid changes to Lys or Arg in the central region of the movement protein of a hybrid bromovirus are required for adaptation to a nonhost.

A hybrid Cowpea chlorotic mottle virus (CCMV) [CCMV(B3a)] in which the CCMV 3a movement protein gene is replaced by the 3a (B3a) gene of Brome mosaic virus cannot infect cowpea systemically. Previously, analysis of RNA3 cDNA clones constructed from cowpea-adapted mutants derived from CCMV(B3a) revealed that a single codon change in the B3a gene allowed CCMV(B3a) to infect cowpea systemically. In this study, to extend the analysis of the CCMV(B3a) adaptation mechanism, we directly sequenced B3a gene RT-PCR products prepared from 28 cowpea plants in which cowpea-adapted mutants appeared, and found seven patterns of a codon change localized at five specific positions in the central region (Ser(118), Glu(132), Glu(138), Gln(178), and Ser(180)). All of the patterns involved an amino acid change to Lys or Arg. Mutational analysis of the B3a gene demonstrated that a single codon change resulting in either Lys or Arg at any of the five positions was sufficient for the adaptation of CCMV(B3a) to cowpea. In contrast, CCMV(B3a) variants with a codon change resulting in Lys or Arg at three other positions (137, 155, and 161) in the B3a gene not only showed lack of systemic infection of cowpea but also showed weakened initial cell-to-cell movement in the inoculated leaves and diminished B3a accumulation in protoplasts. These results suggest that adaptive changes in the B3a gene are site-specifically selected in cowpea plants.

Adaptation, Physiological↗
PubMed2001

Inferior vena cava occlusion catheter for pediatric patients with heart disease: for more detailed cardiovascular assessments.

Traditional evaluation of cardiac function is too often limited by reliance on measurements with complex interdependence between cardiac properties and loading factors. Analysis by ventricular pressure-volume (P-V), -area (P-A), or -dimension (P-D) relations during inferior vena caval (IVC) occlusion independently quantifies ventricular properties and loading conditions, providing detailed information about cardiovascular dynamics. However, there has been no appropriate size of balloon catheter that can effectively occlude IVC of pediatric patients, hindering the application of P-V (P-A, or P-D) analysis to children with heart disease despite its potential benefit. To address this problem, we have developed a new balloon catheter for IVC occlusion in children. The catheter effectively occluded IVC in 92 pediatric patients with varying forms of heart disease who underwent cardiac catheterization, yielding end-systolic pressure-area relations. Thus a newly developed balloon catheter would contribute to establishing more accurate and detailed cardiovascular assessments in children with heart disease. Cathet Cardiovasc Intervent 2001;53:392-396.

Adolescent↗
PubMed2001

A case of tuberculous peritonitis monitored by gallium-67 scintigraphy.

An 18-year-old man was admitted to our hospital for further examination of fever of unknown origin and ascites. Ga-67 scintigraphy revealed diffuse increased uptake throughout the abdomen. He was diagnosed with tuberculous peritonitis and began the treatment for tuberculosis (rifampicin, 450 mg/day orally and isoniazid, 300 mg/day orally, and 0.75 g of streptomycin by intramuscular injection 2 times a week). One year after starting the treatment, Ga-67 scintigraphy revealed accumulation of radioactivity in the upper abdomen, but the diffuse accumulation in the abdomen decreased. A specimen obtained by tumor biopsy under ultrasonic guidance revealed a tuberculous granuloma. Percutaneous injection was performed in the tumor with 1.0 g of streptomycin. On Ga-67 scintigraphy performed 2 weeks after the injection of streptomycin, the accumulation of radioactivity in the upper abdomen had disappeared. These findings suggest that Ga-67 scintigraphy is useful for diagnosis and observation during treatment of tuberculous peritonitis.

Adolescent↗
PubMed2001

Mesenteric desmoid with uptake on gallium-67 citrate scintigraphy.

A 72-year-old man was hospitalized for further evaluation of a space-occupying lesion in the abdomen. Magnetic resonance imaging revealed a tumor 40 mm in diameter in the abdomen. Anterior Ga-67 citrate scintigraphy revealed a region of accumulation of radioactivity in the abdomen corresponding to the tumor. Mesenteric desmoid was diagnosed on the basis of histological findings for the excised tumor. These finding suggested that mesenteric desmoid may be one of the tumors which show high uptake of Ga-67.

Abdominal Pain↗