Search PubMed⌕ Search

Biomedical subjects

N Maeda

Publications and source records attributed to N Maeda.

At least 181 records · Page 10Linked to original sources
PubMed1999

Prognosis for pedunculated hepatocellular carcinoma.

We retrospectively compared the outcome of 13 patients at our institution and that of 163 reported cases of pedunculated hepatocellular carcinoma (HCC) with that of conventional HCC subdivided by tumor diameter (group A: less than 2 cm; group B: 2-5 cm, group C: more than 5 cm). The survival of patients with pedunculated HCC in the 163 reported cases was no different from that of group B, but less favorable than in group A (p < 0.01) and more favorable than in group C (p < 0.01). Among the 163 patients with pedunculated HCC, the 113 cases of surgically treated patients had higher survival than the 21 patients treated with transcatheter arterial embolization (n = 16) or transcatheter arterial infusion chemotherapy (n = 5) (p < 0.01) and than 29 conservatively treated patients (p < 0.001). A total of 70 patients out of 163 (42%) died within 1 year after diagnosis. Additionally, almost all cases of pedunculated HCC showed histologically moderately or poorly differentiated characteristics according to Edmondson and Stainer's classification or the WHO classification. These results suggest that pedunculated HCC has not a favorable prognosis if appropriate surgical resection has not been performed very early within a few months because of its rapid progressive nature.

Adult↗
PubMed1999

Low-cholesterol and high-fat diets reduce atherosclerotic lesion development in ApoE-knockout mice.

We have investigated the effect of most common oils used in human nutrition on the development of atherosclerosis in apoE-knockout mice. Seven groups of animals, separated according to sex, were fed for 10 weeks either chow diet or the chow diet 10% (wt/wt) enriched with different oils (palm, coconut, 2 types of olive oil, and 2 types of sunflower oil) without addition of cholesterol. At the end of this period, plasma lipid parameters were measured and vascular lesions scored. None of the diets induced changes in plasma cholesterol concentrations, whereas plasma triglycerides were uniformly reduced in all diet groups. Some diets caused significant reductions in the size of atherosclerotic lesions in males and others in females; males responded most to sunflower oils and females to palm oil and one olive oil (II). The lesion reduction in males consuming sunflower oils was associated with the decrease of triglycerides in triglyceride-rich lipoproteins, whereas the decrease in females consuming olive oil II or palm oil was accompanied by an increase in plasma apoA-I. The increase in plasma apoA-I in the latter condition, is mainly due to overexpression of hepatic message elicited by a mechanism independent of apoE ligand. The data suggest that the different diets modulate lesion development in a gender specific manner and by different mechanisms and that the development of atherosclerosis, due to genetic deficiencies, may be modulated by nutritional maneuvers that may be implemented in human nutrition.

Animals↗
PubMed1999

Apo E structure determines VLDL clearance and atherosclerosis risk in mice.

We have generated mice expressing the human apo E4 isoform in place of the endogenous murine apo E protein and have compared them with mice expressing the human apo E3 isoform. Plasma lipid and apolipoprotein levels in the mice expressing only the apo E4 isoform (4/4) did not differ significantly from those in mice with the apo E3 isoform (3/3) on chow and were equally elevated in response to increased lipid and cholesterol in their diet. However, on all diets tested, the 4/4 mice had approximately twice the amount of cholesterol, apo E, and apo B-48 in their VLDL as did 3/3 mice. The 4/4 VLDL competed with human LDL for binding to the human LDL receptor slightly better than 3/3 VLDL, but the VLDL clearance rate in 4/4 mice was half that in 3/3 mice. On an atherogenic diet, there was a trend toward greater atherosclerotic plaque size in 4/4 mice compared with 3/3 mice. These data, together with our earlier observations in wild-type and human APOE*2-replacement mice, demonstrate a direct and highly significant correlation between VLDL clearance rate and mean atherosclerotic plaque size. Therefore, differences solely in apo E protein structure are sufficient to cause alterations in VLDL residence time and atherosclerosis risk in mice.

Animals↗
PubMed1999

Hypertension associated with decreased testosterone levels in natriuretic peptide receptor-A gene-knockout and gene-duplicated mutant mouse models.

Mice lacking the gene (Npr1) encoding the natriuretic peptide receptor A (NPRA) have hypertension with elevated blood pressure and cardiac hypertrophy. In particular, Npr1 gene-deficient male mice exhibit lethal vascular events similar to those seen in untreated human hypertensive patients. Serum testosterone levels tend to be lower in hypertensive male humans than in normal males without hypertension, but the genetic basis for this tendency remains unknown. To determine whether Npr1 gene function affects the testosterone level, we measured serum testosterone in male hypertensive mice lacking a functional Npr1 gene, wild-type animals with two copies, and the gene-duplicated littermates expressing four copies of the gene. In the Npr1 gene-knockout (zero-copy) mice, the serum testosterone level was 62% lower than that in the two-copy control mice (80+/-10 ts. 120+/-14 ng/ml, respectively; P < 0.005). Serum testosterone in the four-copy mice was 144% (P < 0.005) of that in the two-copy wild-type control mice. To investigate the role of NPRA in testicular steroidogenesis, we analyzed atrial natriuretic peptide (ANP)-dependent guanylyl cyclase activation, accumulation of intracellular cGMP, and testosterone production in purified primary Leydig cells from animals with zero, two, or four copies of the Npr1 gene. Leydig cells lacking the Npr1 gene did not show ANP-stimulated guanylyl cyclase activation or cGMP accumulation and had no ANP-dependent testosterone production. ANP stimulation of Leydig cells from the four-copy males elicited a 2-fold greater production of cGMP compared to that in the two-copy wild-type counterparts (260+/-12 vs. 126+/-7 pmol/l x 10(6) cells; P < 0.001). Similarly, ANP-dependent testosterone production in Leydig cells was nearly twice as high in four-copy mice as in two-copy wild-type controls (561+/-18 vs. 325+/-11 ng/l x 10(6) cells; P < 0.001). ANP-dependent guanylyl cyclase activation and production of cGMP in Leydig cells increased progressively with the number of Npr1 gene copies. Our results establish the existence of an alternate mechanism for testicular steroidogenesis that is stimulated by NPRA-dependent cGMP signaling, in addition to that mediated by gonadotropins, via a cAMP pathway. These findings demonstrate the role of Npr1 gene function in the maintenance of serum testosterone levels and testicular steroidogenesis and provide a genetic link between hypertension associated with decreased NPRA and low testosterone levels.

Animals↗
PubMed1999

Evidence for stanniocalcin gene expression in mammalian bone.

Stanniocalcin (STC) acts as a regulator of calcium and phosphate homeostasis in an endocrine manner in bony fish. Recently, complementary DNAs encoding human and mouse STC have been characterized, and the messenger RNA (mRNA) expression was identified in various tissues, such as kidney, small intestine, prostate, thyroid, and ovary. Because previous studies concerning the effects of fish STC on mammalian bone have been discussed, there is a good possibility that mammalian STC is a local factor in bone. Here, we demonstrated STC mRNA expression in neonatal mouse calvaria, the primary cultured mouse osteoblast-rich fractions, and human and mouse osteoblastic cell lines. We also mapped the cellular distribution of the STC mRNA in femur and calvaria in developing mice. Several transcripts with a major 4-kb band were detected in all samples. The cellular distribution of the mRNA expression corresponded closely to osteoblasts in both femur and calvaria. Significant labeling of the STC mRNA was also identified in chondrocytes but not in osteoclasts and other bone marrow elements. These results are the first evidence that hormone may be actually expressed in osteoblasts and chondrocytes, and they strongly implicate the involvement of local STC in both endochondral and membrane bone as an autocrine/paracrine factor.

Aging↗
PubMed1999

Structural characterization of recombinant human erythropoietins by fluorophore-assisted carbohydrate electrophoresis.

Routine analysis of the carbohydrate moieties of a glycoprotein is critical for ensuring the consistent quality of biopharmaceutical products. Fluorophore-assisted carbohydrate electrophoresis (FACE) is a recently introduced method for the separation, by polyacrylamide gel electrophoresis, of oligosaccharides labeled with 8-amino-naphthalene-1,3,6-trisulphonic acid (ANTS). In this study, we have evaluated the applicability of the FACE method to analysis of the carbohydrate moieties of three different recombinant human erythropoietins (rHuEPOs), two Chinese hamster ovary (CHO) cell-derived rHuEPOs, and one baby hamster kidney (BHK) cell-derived rHuEPO. The N-linked oligosaccharides released from the rHuEPOs were labeled with ANTS. Enzymic sequence analysis of the N-linked oligosaccharides was performed by the FACE method. The results showed that the FACE method was useful for the analysis of sialo-, asialo-, and agalacto-oligosaccharides in the same gel. Its usefulness for rapidly and reliably revealing the oligosaccharide profiles of given glycoproteins, and its reproducibility were also confirmed in this study. In conclusion, the method can be used for evaluating the quality consistency of recombinant glycoprotein products in terms of the carbohydrate moiety.

Animals↗
PubMed1999

[Metastatic tumor of renal pelvis and ureter from prostatic cancer: a case report].

An 86-year-old man was admitted to our hospital with a complaint of gross hematuria. Urological examination revealed right hydronephrosis and poorly differentiated adenocarcinoma of the prostate with bone metastases. Abdominal computed tomographic scan and retrograde pyelography showed thickening of the ureteral wall with irregular stenosis in the right upper ureter. Right nephroureterectomy demonstrated diffuse lymphatic infiltration of PSA-positive cancer cells in the submucosa and muscle layer of the ureter as well as renal pelvis. This is the 6th reported case of metastatic ureteral tumor from prostate cancer in the Japanese literature.

Adenocarcinoma↗
PubMed1999

[Two-step ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer: a case report].

A 35-year-old male had advanced nonseminomatous germ cell tumor (stage IIIC, embryonal cell carcinoma) which proved refractory to conventional PVB combined chemotherapy. He was then treated with an ultra high-dose chemotherapy consisting of carboplatin (1.5 g/m2) and etoposide (1.3 g/m2), followed by the transplantation of peripheral blood stem cells (PBSCT) with a total of 1.9 x 10(5)/kg granulocyte colony-forming cells (CFU-GM). Because he developed lung metastasis, escalated doses of carboplatin (2.0 g/m2), and etoposide (1.8 g/m2) combined with cyclophosphamide (7.0 g/m2) were given with peripheral blood stem cell transplant of 3.2 x 10(5)/kg CFU-GM. He has remained free of any recurrence without maintenance therapy.

Adult↗
PubMed1998

Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II.

The classically recognized functions of the renin-angiotensin system are mediated by type 1 (AT1) angiotensin receptors. Whereas man possesses a single AT1 receptor, there are two AT1 receptor isoforms in rodents (AT1A and AT1B) that are products of separate genes (Agtr1a and Agtr1b). We have generated mice lacking AT1B (Agtr1b -/-) and both AT1A and AT1B receptors (Agtr1a -/-Agtr1b -/-). Agtr1b -/- mice are healthy, without an abnormal phenotype. In contrast, Agtr1a -/-Agtr1b -/- mice have diminished growth, vascular thickening within the kidney, and atrophy of the inner renal medulla. This phenotype is virtually identical to that seen in angiotensinogen-deficient (Agt-/-) and angiotensin-converting enzyme-deficient (Ace -/-) mice that are unable to synthesize angiotensin II. Agtr1a -/-Agtr1b -/- mice have no systemic pressor response to infusions of angiotensin II, but they respond normally to another vasoconstrictor, epinephrine. Blood pressure is reduced substantially in the Agtr1a -/- Agtr1b -/- mice and following administration of an angiotensin converting enzyme inhibitor, their blood pressure increases paradoxically. We suggest that this is a result of interruption of AT2-receptor signaling. In summary, our studies suggest that both AT1 receptors promote somatic growth and maintenance of normal kidney structure. The absence of either of the AT1 receptor isoforms alone can be compensated in varying degrees by the other isoform. These studies reaffirm and extend the importance of AT1 receptors to mediate physiological functions of the renin-angiotensin system.

Adrenal Glands↗
PubMed1998

beta-Microseminoprotein/prostatic secretory protein is a member of immunoglobulin binding factor family.

Human seminal plasma contains a factor that binds human IgG, designated as immunoglobulin binding factor (IgBF). Under reducing condition IgBF interacts with anti-Leu-11b, a murine monoclonal antibody raised against human FcgammaRIII/CD16. IgBF shows no binding activity under non-reducing condition. Three components having IgBF activity were separated by HPLC and their amino acid sequences determined. The main IgBF showed structural identity to beta-microseminoprotein (beta-MSP), prostatic secretory protein of 94 amino acids (PSP94) and beta-inhibin. The slight variation in the reported sequences of these proteins has been attributed to analytical error. In the present study the molecular masses of main IgBF and beta-MSP/PSP94 were found to be identical by mass spectrometry. In addition, a large component of IgBF and a shorter beta-MSP consisting of 93 amino acids were identified. The binding of beta-MSP for human IgG and anti-Leu-11b antibody is demonstrable only under reducing condition, determined by Western blot analysis. The present data clearly show that IgBF is a family composed of at least three isoforms. One of the members is beta-MSP/PSP94. This family should be designated as IgBF.

Amino Acid Sequence↗
PubMed1998

Astrocytes modulate nitric oxide production by microglial cells through secretion of serine and glycine.

We investigated lipopolysaccharide (LPS)-induced nitric oxide (NO) production by rat microglia in neuron-microglia and astrocyte-microglia cocultures to evaluate the influence of neurons and astrocytes on microglial activity. Microglial cells solely cultured in medium devoid of serine (Ser), glycine (Gly) hardly expressed inducible NO synthase (iNOS), while those cocultured with neurons and astrocytes expressed iNOS. When microglial cells and astrocytes were separately cultured by using tissue culture inserts, which allowed the microglial cells to be exposed to only diffusible factors arising from astrocytes, NO production was significantly enhanced. On the other hand, neurons, when separated from microglial cells by the inserts, could not activate microglial cells possibly due to lacking of direct contact between neurons and microglial cells. NO production in pure microglial cultures was significantly enhanced in the presence of Ser/Gly at concentrations higher than 25 microM. Conditioned media obtained from microglia culture and neuron-microglia coculture contained less than 10 microM of Ser and Gly, while media from astrocyte culture and astrocyte-microglia coculture contained 33-41 microM Ser and 20-26 microM Gly. Accordingly, astrocytes modulate the activity of microglial cells by secreting Ser and Gly. The present study proposes a novel metabolic coupling between astrocytes and microglial cells via amino acids.

Animals↗
PubMed1998

Interleukin 3 prevents delayed neuronal death in the hippocampal CA1 field.

In the central nervous system, interleukin (IL)-3 has been shown to exert a trophic action only on septal cholinergic neurons in vitro and in vivo, but a widespread distribution of IL-3 receptor (IL-3R) in the brain does not conform to such a selective central action of the ligand. Moreover, the mechanism(s) underlying the neurotrophic action of IL-3 has not been elucidated, although an erythroleukemic cell line is known to enter apoptosis after IL-3 starvation possibly due to a rapid decrease in Bcl-2 expression. This in vivo study focused on whether IL-3 rescued noncholinergic hippocampal neurons from lethal ischemic damage by modulating the expression of Bcl-xL, a Bcl-2 family protein produced in the mature brain. 7-d IL-3 infusion into the lateral ventricle of gerbils with transient forebrain ischemia prevented significantly hippocampal CA1 neuron death and ischemia-induced learning disability. TUNEL (terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling) staining revealed that IL-3 infusion caused a significant reduction in the number of CA1 neurons exhibiting DNA fragmentation 7 d after ischemia. The neuroprotective action of IL-3 appeared to be mediated by a postischemic transient upregulation of the IL-3R alpha subunit in the hippocampal CA1 field where IL-3Ralpha was barely detectable under normal conditions. In situ hybridization histochemistry and immunoblot analysis demonstrated that Bcl-xL mRNA expression, even though upregulated transiently in CA1 pyramidal neurons after ischemia, did not lead to the production of Bcl-xL protein in ischemic gerbils infused with vehicle. However, IL-3 infusion prevented the decrease in Bcl-xL protein expression in the CA1 field of ischemic gerbils. Subsequent in vitro experiments showed that IL-3 induced the expression of Bcl-xL mRNA and protein in cultured neurons with IL-3Ralpha and attenuated neuronal damage caused by a free radical-producing agent FeSO4. These findings suggest that IL-3 prevents delayed neuronal death in the hippocampal CA1 field through a receptor-mediated expression of Bcl-xL protein, which is known to facilitate neuron survival. Since IL-3Ralpha in the hippocampal CA1 region, even though upregulated in response to ischemic insult, is much less intensely expressed than that in the CA3 region tolerant to ischemia, the paucity of IL-3R interacting with the ligand may account for the vulnerability of CA1 neurons to ischemia.

Animals↗
PubMed1998

Microglial cells prevent nitric oxide-induced neuronal apoptosis in vitro.

Apoptotic neuronal death is known to occur in the developing brain and in the mature brain of patients with ischemic and degenerative disorders. Although microglial cells are known to become activated in specific conditions, it has not been elucidated whether they enhance or prevent neuronal apoptosis. The present study was intended to observe how microglial cells are involved in neuronal death. When rat primary cortical neurons were incubated with a nitric oxide (NO) donor sodium nitroprusside (SNP; 300 microM) for 10 min, neuronal death occurred 12-16 hr later. The NO-induced neuronal death was inhibited by cycloheximide, and the SNP-treated neurons were characterized by nuclear fragmentation and intact cell membrane under electron microscopy. Agarose gel electrophoresis demonstrated DNA fragmentation of the SNP-treated neurons. Thus, the NO-induced neuronal death appeared to be apoptosis. When neurons were cocultured with rat primary microglial cells, the SNP treatment failed to induce the neuronal death. Because microglia-conditioned medium also prevented apoptotic neuronal death, microglial cells were considered to secrete antiapoptotic factors. The microglia-conditioned medium rescued neurons even when they were added to neuronal cultures after the SNP treatment, implying that the factors acted on neurons in a manner other than scavenging NO. Interleukin-3, interleukin-6, macrophage colony-stimulating factor, and basic fibroblast growth factor, which are known to be secreted by microglial cells, were not effective in preventing NO-induced neuronal death. Among microglia-derived substances, tumor necrosis factor alpha and plasminogen, which are heat-labile proteins, inhibited neuronal apoptosis. The neuroprotective action of the microglia-conditioned medium, however, still remained, even after it was heated. These findings suggest that microglial cells protect neurons against NO-induced lethal damage by secreting heat-labile and heat-stable neuroprotective factors in vitro.

Animals↗
PubMed1998

Involvement of receptor-like protein tyrosine phosphatase zeta/RPTPbeta and its ligand pleiotrophin/heparin-binding growth-associated molecule (HB-GAM) in neuronal migration.

Pleiotrophin/heparin-binding growth-associated molecule (HB-GAM) is a specific ligand of protein tyrosine phosphatase zeta (PTPzeta)/receptor-like protein tyrosine phosphatase beta (RPTPbeta) expressed in the brain as a chondroitin sulfate proteoglycan. Pleiotrophin and PTPzeta isoforms are localized along the radial glial fibers, a scaffold for neuronal migration, suggesting that these molecules are involved in migratory processes of neurons during brain development. In this study, we examined the roles of pleiotrophin-PTPzeta interaction in the neuronal migration using cell migration assay systems with glass fibers and Boyden chambers. Pleiotrophin and poly-L-lysine coated on the substratums stimulated cell migration of cortical neurons, while laminin, fibronectin, and tenascin exerted almost no effect. Pleiotrophin-induced and poly-L-lysine-induced neuronal migrations showed significant differences in sensitivity to various molecules and reagents. Polyclonal antibodies against the extracellular domain of PTPzeta, PTPzeta-S, an extracellular secreted form of PTPzeta, and sodium vanadate, a protein tyrosine phosphatase inhibitor, added into the culture medium strongly suppressed specifically the pleiotrophin-induced neuronal migration. Furthermore, chondroitin sulfate C but not chondroitin sulfate A inhibited pleiotrophin-induced neuronal migration, in good accordance with our previous findings that chondroitin sulfate constitutes a part of the pleiotrophin-binding site of PTPzeta, and PTPzeta-pleiotrophin binding is inhibited by chondroitin sulfate C but not by chondroitin sulfate A. Immunocytochemical analysis indicated that the transmembrane forms of PTPzeta are expressed on the migrating neurons especially at the lamellipodia along the leading processes. These results suggest that PTPzeta is involved in the neuronal migration as a neuronal receptor of pleiotrophin distributed along radial glial fibers.

Animals↗
PubMed1998

Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2.

To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we generated mice with a human APOE*2 allele in place of the mouse Apoe gene via targeted gene replacement in embryonic stem cells. Mice expressing human apoE2 (2/2) have virtually all the characteristics of type III hyperlipoproteinemia. Their plasma cholesterol and triglyceride levels are both twice to three times those in (normolipidemic) mice that are expressing human apoE3 (3/3) made in an identical manner. The 2/2 mice are markedly defective in clearing beta-migrating VLDL particles, and spontaneously develop atherosclerotic plaques, even on a regular diet. An atherogenic diet, high in fat and cholesterol, exacerbates development of atherosclerosis and xanthomas in the 2/2 mice. Thus, comparisons between the 2/2 and 3/3 mice unequivocally demonstrate that a single amino acid difference (Arg158 Cys) in the apoE protein is sufficient to cause type III HLP and spontaneous atherosclerosis in mice.

Animals↗
PubMed1998

Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol.

The effects of dietary cholesterol on brain amyloid precursor protein (APP) processing were examined using an APP gene-targeted mouse, genetically humanized in the amyloid beta-peptide (Abeta) domain and expressing the Swedish familial Alzheimer's disease mutations. These mice express endogenous levels of APP holoprotein and abundant human Abeta. Increased dietary cholesterol led to significant reductions in brain levels of secreted APP derivatives, including sAPPalpha, sAPPbeta, Abeta1-40, and Abeta1-42, while having little to no effect on cell-associated species, including full-length APP and the COOH-terminal APP processing derivatives. The changes in levels of sAPP and Abeta in brain all were negatively correlated with serum cholesterol levels and levels of serum and brain apoE. These results demonstrate that secreted APP processing derivatives and Abeta can be modulated in the brain of an animal by diet and provide evidence that cholesterol plays a role in the modulation of APP processing in vivo. APP gene-targeted mice lacking apoE, also have high serum cholesterol levels but do not show alterations in APP processing, suggesting that effects of cholesterol on APP processing require the presence of apoE.

Alzheimer Disease↗
PubMed1998

In situ hybridization analysis of stanniocalcin mRNA expressing cells in the mouse kidney.

Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fish in which it regulates calcium and phosphate homeostasis. A mammalian homologue has recently been isolated and STC mRNA is expressed in many tissues including kidney. Mammalian STC appears to inhibit renal phosphate reabsorption in rats, and its immunoreactive cells were detected in specific segments of the renal tubules in humans and rats. We used in situ hybridization with a digoxigenin-labelled cRNA for STC to characterize the intrarenal distribution of STC mRNA in mice. The labelling was detected in most of the cells in nephron tubules and glomerular mesangial cells, suggesting that STC is synthesized in the nephron system and acts in an autocrine/paracrine fashion.

Animals↗