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M Noda

Publications and source records attributed to M Noda.

At least 235 records · Page 13Linked to original sources
PubMed1998

Expression of Nedd2/ICH-1 (caspase-2) in the developing rat retina.

Expression and localization of Nedd2/ICH-1 (caspase-2) were examined in the developing rat retina. The expression of Nedd2 mRNA was conspicuous in the prenatal period and down-regulated in the postnatal period. In contrast, the expression of an alternatively spliced form of Nedd2 encoding a truncated protein, which has been shown to protect against programed cell death (PCD), was faint in the prenatal period but increased gradually in the postnatal period. Nedd2 immunoreactivity was observed in almost all cells of the ganglion cell layer (GCL) during the perinatal period, when some nuclei in the GCL showed pyknosis or fragmentation. Nedd2-positive cells in the neuroblastic layer (NBL) were present in patches at embryonic day 19, and began to assume a stratified arrangement at postnatal day 3, when nuclei showing PCD were observed in places across the NBL. At postnatal day 14, only faint Nedd2 immunoreactivity was observed in the GCL and the inner nuclear layer, and no Nedd2 immunoreactivity was present in the outer nuclear layer. These findings demonstrate the cell type- and differentiation-specific patterns of the Nedd2 expression in the developing retina.

Alternative Splicing↗
PubMed1998

Increase of nerve regeneration capacity by new neurotrophic pyrimidine derivative MS-430.

1. We studied whether a new neurotrophic pyrimidine compound, MS-430, can increase the regeneration length of the transected sciatic nerve in a silicone chamber gap of 14 mm. 2. The average length of regenerated myelinated axons in ten cases was 9.0+/-0 mm in the control group, 2.8+/-1.9 mm in the 1 mg/kg/day of the MS-430 group and 5.0+/-5.1 mm in the 3 mg/kg/day of the MS-430 group, indicating that the average length was significantly larger in the 3-mg group than that in the control group (P<0.05). 3. The results clearly showed that the MS-430 has promoting effects on nerve regeneration.

Animals↗
PubMed1998

Osteoblastic cells regulate mi gene expression in cultured bone marrow cells.

The microphthalmia (mi) gene encodes a bHLH-Zip protein and certain mutations in this gene are known to result in osteopetrosis. We examined mi gene expression in murine bone marrow (BM) cells and calvaria-derived osteoblastic (OB) cells. The mi message level in BM cells was three- to four-fold higher than that in OB cells. The mi message level in BM cells alone was not enhanced by 1,25(OH)2 vitamin D3 (vitamin D) which induces TRAP-positive multinucleated cells, but was enhanced two-fold by the addition of conditioned medium obtained from cultures of OB cells. The mi message levels in BM cells were also enhanced by macrophage colony-stimulating factor (M-CSF). The mi message levels in cocultures of BM cells and osteoblastic MC3T3-E1 cells, which do not support osteoclastogenesis, were similar to those in the cocultures of BM cells and OB cells. Cocultures of BM cells with MC3T3-E1 cells did not yield TRAP-positive multinucleated cells, but they did maintain osteoclast progenitor cells. These findings suggest that mi is expressed in BM cells that may be under the control of OB cells.

Animals↗
PubMed1998

Expression of the PEBP2alphaA/AML3/CBFA1 gene is regulated by BMP4/7 heterodimer and its overexpression suppresses type I collagen and osteocalcin gene expression in osteoblastic and nonosteoblastic mesenchymal cells.

PEBP2alphaA/AML3/CBFA1 is one of the transcription regulators that belong to the PEBP2/AML family. The knockout mice, where the gene encoding PEBP2alphaA/AML3/CBFA1 was inactivated, showed no osteogenesis, indicating the critical role of this transcription factor in osteoblastic differentiation (Komori, Y. et al. Cell 89:755-764; 1997). The aim of this study is to examine the regulation of PEBP2alphaA/AML3/CBFA1 expression in skeletal (MC3T3E1, ROS17/2.8) and nonskeletal (C3H10T1/2, C2C12, NIH3T3) cell lines. The basal levels of PEBP2alphaA/AML3/CBFA1 were time dependent and were increased during culture in ROS17/2.8 by day 2, remaining similar during cultures in other types of cells. Treatment with a 100-ng/mL BMP4/7 heterodimer enhanced the expression of PEBP2alphaA/AML3/CBFA1 mRNA levels in MC3T3E1 and C2C12 cells, whereas BMP2 did not significantly alter PEBP2alphaA/AML3/CBFA1 mRNA levels in both skeletal and nonskeletal cells. The PEBP2alphaA/AML3/CBFA1 mRNA level in ROS17/2.8 cells was relatively high on day 2, and was not further enhanced by treatment with BMP4/7. In contrast to the reported type I collagen gene upregulation by the overexpression of Osf2/CBFA1, which differs from PEBP2alphaA/AML3/CBFA1 by containing a unique 87 amino acid sequence at its amino terminal end, overexpression of PEBP2alphaA/AML3/CBFA1 suppressed type I collagen mRNA levels in MC3T3E1, C2C12, and C3H10T1/2 cells and suppressed osteocalcin mRNA levels in ROS17/2.8 cells. The osteopontin mRNA level was enhanced by overexpression of PEBP2alphaA/AML3/CBFA1 in MC3T3E1, while the level was similar in ROS17/2.8 cells and was suppressed in C2C12 cells. These data indicate that PEBP2alphaA/AML3/CBFA1 is one of the targets of BMP4/7 and participates in the regulation of the expression of genes related to osteoblast phenotype. The overexpression study suggests that PEBP2alphaA/AML3/CBFA1 and Osf2/CBFA1 may have a different function in the regulation of the expression of the genes related to the osteoblast phenotype.

3T3 Cells↗
PubMed1998

Characterization and developmental regulation of proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta isoforms.

Protein tyrosine phosphatase zeta (PTPzeta/RPTPbeta) is a receptor-like protein tyrosine phosphatase specifically expressed in the brain. Alternative splicing produces three isoforms of this molecule: PTPzeta-A, the full-length form of PTPzeta; PTPzeta-B, the short form of PTPzeta; and PTPzeta-S, an extracellular variant. Here, we identified all these isoforms, including PTPzeta-B, as chondroitin sulfate proteoglycans, and characterized their carbohydrate modification and expression profiles in the rat brain. The level of PTPzeta-A expression was maintained during the prenatal period and decreased rapidly after birth. PTPzeta-S was expressed in a similar manner, although the postnatal decrease was gradual. In contrast, relatively constant amounts of PTPzeta-B were observed from embryonic day 13 (E13) through adulthood. PTPzeta-A and -S were constantly expressed only as proteoglycans during development, but a substantial amount of PTPzeta-B was detected in a non-proteoglycan form at E13-15. Moreover, PTPzeta-B did not contain LeX, HNK-1 carbohydrate, or keratan sulfate, although PTPzeta-A and -S were generally modified with these carbohydrates. L cells transfected with PTPzeta-A and -B cDNAs expressed these proteins as enzymatically active chondroitin sulfate proteoglycans. The PTPzeta-A and -B in L cells showed essentially similar localizations in cell cortical structures on immunofluorescence microscopy, although immature or processed forms of PTPzeta-A were accumulated additively in intracellular patchy structures. These results show that the three isoforms of PTPzeta are differentially regulated during development, and that the extracellular deleted region in PTPzeta-B is important for determination of carbohydrate modification.

Animals↗
PubMed1998

Long-term alcohol effects on hepatic phosphoglucomutase activities in relation to posttranslational modification of the protein.

ADP-ribosylation is a posttranslational protein modification catalyzed by two classes of enzymes: mono-ADP-ribosyltransferase and poly-ADP-ribose polymerases. We previously demonstrated that long-term alcohol intake remarkably enhanced an endogenous ADP-ribosylation of a 58 kDa protein in rat liver and also identified the 58 kDa protein as phosphoglucomutase (PGM). To assess biological significance of this phenomenon, we tested the effects of long-term alcohol intake on PGM activities in connection with posttranslational modification of the protein. ADP-ribosylation of PGM was mono- rather than poly-ADP-ribosylation. Also, nonenzymatic binding of ADP-ribose was excluded. It was of note that ADP-ribosylation of exogenous PGM was remarkably increased by adding rat liver plasma membranes, and that the extent of the increase was greater in alcohol-fed rats than in pair-fed controls. Furthermore, PGM activities were significantly increased after long-term alcohol intake concomitant with increased ADP-ribosyltransferase activities toward PGM. In view of the variety of roles of PGM in the liver, such as carbohydrate metabolism and Ca2+ homeostasis, it is tempting to speculate that increased ADP-ribosylation of PGM may play a role in long-term alcohol effects on hepatocytes.

ADP Ribose Transferases↗
PubMed1998

Clinical evaluation of serum prostate-specific antigen-alpha1-antichymotrypsin complex values in diagnosis of prostate cancer: a cooperative study.

BACKGROUND: We studied the clinical significance of serum prostate-specific antigen bound to alpha1-antichymotrypsin (PSA-ACT) values determined with a newly developed enzyme immunoassay. METHODS: Serum PSA-ACT values were determined in a total of 652 sera. Clinical utility for the diagnosis of prostate cancer was compared to that of Tandem-R PSA and gamma-seminoprotein (gamma-Sm). The new enzyme immunoassay is based on the use of the Stanford reference as an international standard for PSA assays. RESULTS: Serum PSA-ACT values ranged from less than 0.10 to 1.4 ng/mL in healthy males (n = 100) while values in patients with benign prostatic hyperplasia (n = 155) averaged 3.4 +/- 3.8 ng/mL (mean +/- SD). In patients with prostate cancer, serum PSA-ACT values increased significantly with progression of the clinical stage and there were statistically significant differences between benign prostatic hyperplasia and each stage of prostate cancer except for stage A. Using BPH levels as controls (4.8 ng/mL for PSA-ACT, 7.2 ng/mL for PSA, 3.8 ng/mL for gamma-Sm, and 2.4 ng/mL for the complexed/free PSA ratio of PSA-ACT/gamma-Sm), specificity was 80%. The sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57% for gamma-Sm, and 46% for the ratio between PSA-ACT/gamma-Sm. CONCLUSION: Although the determination of serum PSA-ACT showed essentially the same utility as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction of the clinical stage. The PSA-ACT assay may therefore replace PSA in the detection of prostate cancer.

Disease Progression↗
PubMed1998

Erythropoietin and Friend virus gp55 activate different JAK/STAT pathways through the erythropoietin receptor in erythroid cells.

Abnormal erythropoietin (EPO)-independent cell growth is induced after infection of erythroid progenitor cells with a polycythemic strain of Friend virus (FVp). Binding of its Env-related glycoprotein (gp55) to the EPO receptor (EPOR) mimics the activation of the EPOR with EPO. We investigated the gp55-EPOR signaling in erythroblastoid cells from mice infected with FVp and in cells of FVp-induced or gp55-transgenic-mouse-derived erythroleukemia cell lines, comparing it with the EPO-EPOR signaling in EPO-responsive erythroblastoid cells. While the Janus protein tyrosine kinase JAK2 and the transcription factor STAT5 became tyrosine phosphorylated with the EPO stimulation in EPO-responsive erythroblastoid cells from anemic mice, JAK1 and STAT5 were constitutively tyrosine phosphorylated in all of these FVp gp55-induced erythroblastoid or erythroleukemic cells. Moreover, this constitutively tyrosine-phosphorylated STAT5 was unable to bind to its specific DNA sequences and did not translocate to the nucleus. Nuclear translocation and DNA binding of this STAT5 species required EPO stimulation. These findings clearly indicate that the FVp gp55-EPOR signaling is distinct from the EPO-EPOR signaling and suggest that STAT5 may not play an essential role in the transmission of the cell growth signals in FVp gp55-induced erythroleukemia cells.

Animals↗
PubMed1998

Absorption of epirubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer.

As postoperative adjuvant therapy for superficial bladder cancer, intravesical instillation therapy is commonly conducted. In this case, from the view point of prevention of intraoperative dissemination, commencement of instillation therapy at an early postoperative period is preferred. However, increased drug permeability is suspected because of damage to the bladder mucosa during operation. Therefore, this study was conducted to investigate the plasma level of epirubicin (EPI) instilled immediately after transurethral operation. EPI (20 mg/40 ml or 50 mg/100 ml) was instilled immediately after a transurethral operation, and retained in the bladder for 1 h. Blood samples were obtained before instillation, as well as 30, 60, 120 and 240 min after instillation, and EPI levels were assayed. The mean EPI concentrations (ng/ml) among the 20-mg/40 ml group (n = 5) were < 2.5 and < 2.0 at 30 and 60 min, respectively, after which they were undetectable. The 50-mg/100 ml group (n = 5) recorded 5.0, 4.4 and < 3.0 after 30, 60 and 120 min, respectively, and after 240 min it was undetectable. Intravesical instillation of EPI immediately after a transurethral operation causes a small increase in the plasma level and it is thought to cause small systemic side effects.

Absorption↗
PubMed1998

Nutrient augmentation of Ca2+-dependent and Ca2+-independent pathways in stimulus-coupling to insulin secretion can be distinguished by their guanosine triphosphate requirements: studies on rat pancreatic islets.

To delineate the underlying mechanisms by which glucose augments both Ca2+-dependent and Ca2+-independent insulin release, the latter induced by the simultaneous activation of protein kinases A and C, we examined the effects of GTP depletion by mycophenolic acid (MPA), an inhibitor of GTP synthesis, on the augmentation of insulin release from rat pancreatic islets. MPA treatment reduced GTP content by 30-40% and completely abolished glucose-induced augmentation of Ca2+-independent insulin release. Thus, this pathway is extremely sensitive to a decrease in cellular GTP content. Complete inhibition was also observed in islets treated with MPA plus adenine, to maintain ATP levels, under which conditions GTP is selectively depleted. Provision of guanine, which increases the activity of a salvage pathway for GTP synthesis and normalizes GTP content, completely reversed the inhibitory effect of MPA. Neither glucose utilization nor glucose oxidation was affected by MPA. The augmentation of Ca2+-independent insulin release by several other metabolizable nutrients including alpha-ketoisocaproic acid (KIC) was also inhibited by MPA. In sharp contrast, augmentation of Ca2+-dependent insulin release by KIC was resistant to GTP depletion, indicating that nutrient-induced augmentation of the Ca2+-dependent- and Ca2+-independent secretory pathways can be differentiated by GTP dependency. We interpret these data in accord with current knowledge concerning the two known stimuli for exocytosis, Ca2+ and GTP (independently of Ca2+). We propose that both Ca2+-dependent and Ca2+-independent augmentation occurs via one metabolic pathway acting upon Ca2+- and upon GTP-stimulated exocytosis. Activation of PKA and PKC stimulates the GTP-sensitive exocytosis.

Adenosine Triphosphate↗
PubMed1998

Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro.

We have used homologous recombination in embryonic stem cells to generate mice with a targeted disruption of the osteopontin (Opn, or Spp1, for secreted phosphoprotein 1) gene. Mice homozygous for this disruption fail to express osteopontin (OPN) as assessed at both the mRNA and protein level, although an N-terminal fragment of OPN is detectable at extremely low levels in the bones of -/- animals. The Opn -/- mice are fertile, their litter size is normal, and they develop normally. The bones and teeth of animals not expressing OPN are morphologically normal at the level of light and electron microscopy, and the skeletal structure of young animals is normal as assessed by radiography. Ultrastructurally, proteinaceous structures normally rich in OPN, such as cement lines, persist in the bones of the Opn-/- animals. Osteoclastogenesis was assessed in vitro in cocultures with a feeder layer of calvarial osteoblast cells from wild-type mice. Spleen cells from Opn-/- mice cells formed osteoclasts 3- to 13-fold more frequently than did control Opn+/+ cells, while the extent of osteoclast development from Opn -/- bone marrow cells was about 2- to 4-fold more than from the corresponding wild-type cells. Osteoclast development occurred when Opn-/- spleen cells were differentiated in the presence of Opn-/-osteoblasts, indicating that endogenous OPN is not required for this process. These results suggest that OPN is not essential for normal mouse development and osteogenesis, but can modulate osteoclast differentiation.

Animals↗
PubMed1998

Establishment of two substrains, diabetes-prone and non-diabetic, from Long-Evans Tokushima Lean (LETL) rats.

Diabetes mellitus in Long-Evans Tokushima Lean (LETL) rats closely resembles type 1 diabetes in human beings, e.g., no gender differences in the incidence of diabetes and no T lymphopenia. Although the LETL rats have been established as an inbred strain, the incidence of diabetes is only approximately 20%. In the present study, we established two substrains, one a diabetes-prone (KDP) and the other a non-diabetic (KND) from the original inbred LETL rats. The features of KDP rats are a high incidence of diabetes (over all approximately 70%) without lymphopenia and 100% development of mild to severe insulitis at 120-220 days of age. In contrast, the KND substrain is characterized by the complete absence of diabetes incidence. Among 165 SSLP marker loci throughout all rat chromosomes, no loci showed variation among KDP and KND substrains and their parental LETL rats. In this regard, the genetic background of these two substrains, KDP and KND, appears to be uniform except for the major gene(s) that is responsible for the diabetes. In this context, these two substrains of LETL rats should serve as useful tools for research on the pathogenesis and for the genetic analysis of type 1 diabetes. In this report, we have not only established, but also characterized these two substrains, and provided their fundamental data.

Age of Onset↗
PubMed1998

Elongation of the epiphyseal trabecular bone in transgenic mice carrying a klotho gene locus mutation that leads to a syndrome resembling aging.

Bone diseases such as osteoporosis and osteoarthritis are regarded as age-associated diseases, and occur in a significantly increasing number of patients, but the underlying mechanisms of these age-associated bone diseases are not yet clear. We have established a transgenic mouse line by an insertion mutation. These mice exhibit many features related to precocious aging. Homozygote mutant mice, which lack expression of the newly identified targeted gene,klotho (kl), exhibit atherosclerosis, emphysema, hypogonadism and calcification of soft tissues, and die within 3-4 months. We describe here the radiological and histological characteristics of the skeletal abnormalities in the bones of the mice with a mutation in the kl gene locus. In heterozygous mice (+/kl), the skeletal patterns and structures remain normal and most features are similar to those in the wild-type, whereas histological examinations of homozygous mice (kl/kl) show abnormal elongation of the trabecular bone(s) in the epiphyses of long bones. As with their long bones, on radiographic examination the mid parts of the vertebral bones of these mice show less radiopacity compared with the wild-type, again resembling human vertebrae of osteoporotic patients. The elongation of the trabecular bones results in high radiopacity on both ends of each of the vertebrae, and in the epiphyses of the long bones. Cancellous bone volume in the epiphyses of the homozygote mice is three times that of the wild-type mice. The kl/kl mice are smaller than the wild-type litter mates and hence the size of their long bones is less than that of the wild-type litter mates. These observations, and the osteopenia in the vertebrae and long bones in these mice, suggest the presence of abnormality in bone metabolism, the elongation of the trabecular bone apparently resulting from the relatively low levels of bone resorption. Therefore, thekl/kl mutant mice could serve as an interesting tool to study the effects of the lack of the product of the new gene,klotho, on bone metabolism.

Aging↗
PubMed1998

Long-term patency of an aorta-aortic graft bypass in a patient with Takayasu arteritis.

A 39-year-old woman was diagnosed by means of angiography as Takayasu arteritis complicated with severe systemic hypertension due to atypical coarctation of the aorta. Aorta-aortic bypass graft surgery was carried out successfully and hypertension remarkably improved. An evaluation of the graft 23 years later confirmed an almost perfect condition with a very satisfactory clinical status. Extensive long-term follow-up studies have been conducted among young people after surgical repair of aortic coarctation showing encouraging results, however the situation seems to be different for the atypical coarctation in Takayasu patients, since not only the age at the time of intervention affects the outcome, but the different circumstances mainly related to the natural history of the disease. We evaluated the long-term outcome based on similar cases with particular consideration to the extremely rare coexistence of familiar hypercholesterolemia.

Adult↗
PubMed1998

Effects of pharmacokinetic modulating chemotherapy using oral UFT and continuous venous 5FU infusion on the prognosis of irradiated rectal carcinomas with p53 overexpression.

We previously found that patients with irradiated rectal carcinomas with p53 overexpression had poor prognoses after radical resection. In the present study, we attempted to improve the prognosis by the introduction of adjuvant chemotherapy. We administered pharmacokinetic modulating chemotherapy, based on the concept that the benefit of a continuous venous 5-fluorouracil (5FU) infusion can be potentiated by low-dose oral UFT, a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4. Forty-two of 107 patients examined between January 1992 and December 1997 with an irradiated rectal carcinoma (39%) showed positive immunohistochemical staining for p53. Among them, 14 patients received adjuvant chemotherapy (CT group). The percentage of highly malignant tumors in the CT group was higher than that in the no-chemotherapy (NCT) group (n=28). However, the rate of cumulative local recurrence in the CT group was 0%, while that in the NCT group was 28.6% (p=0.0392). The distant recurrence rate in the CT group was also significantly lower than that in the NCT group (7.1% vs. 42.9%, p=0.0376). The cumulative 3-year survival rate was 100% in the CT group and 64.3% in the NCT group (p=0.0245). These results suggested that the antitumor property of 5FU enhanced by pharmacokinetic modulation might have a lethal effect on rectal tumors with a loss of the p53-related apoptosis pathway. These preliminary findings are encouraging for the treatment of rectal cancers with possible poor prognosis.

Administration, Oral↗
PubMed1998

[The effects of midazolam on the memory of pain].

The purpose of this study was to evaluate the effects of low dose midazolam (MZ) on memories of spinal puncture. The low doses of MZ were administered to 70 patients (ASA 1-2), of whom 37 patients were premedicated with atropine sulfate 0.5 mg and pethidine hydrochloride i.m. (group P), and 33 patients received no premedication (group N). Double blind randomized trials were conducted with the doses of MZ (0, 0.03, 0.06 mg.kg-1), and MZ was administered i.v. to the patients just prior to spinal puncture. Subjective evaluation of pain was performed with pain score (PS) on postoperative phase, and objective evaluation of pain was performed with the reaction of spinal puncture. Short term memory was impaired mainly after administration of MZ. However, subjective memory of pain almost disappeared, but objective evaluation was not so good. We conclude that MZ induces impairment to recall of pain. However, it might maintain the response to the pain.

Adjuvants, Anesthesia↗
PubMed1998

[Increase in pulmonary vascular permeability caused by increased adhesiveness of polymorphonuclear leukocytes and superoxide].

We report that mechanical stimulation of human neutrophils results in their accumulation in isolated rat lungs and in an increase in pulmonary vascular permeability. To determine whether reactive oxygen species were involved in this increase and, if so, whether it is mediate by xanthine oxidase metabolites, we assessed the effect of stimulated and unstimulated neutrophils, and of a superoxide scavenger, superoxide dismutase (SOD), and a xanthine oxidase inhibitor, allopurinol (ALLO) on pulmonary vascular permeability in isolated perfused lungs from Sprague-Dawley rats. Pulmonary vascular permeability in isolated rat lungs was assessed using a filtration coefficient determined by gravimetry. To quantify neutrophil accumulation in the lung, we measured myeloperoxydase (MPO). Neutrophils were stimulated by gentle agitation in a glass container for 10 s and Mac-1 was subsequently upregulated on the surface of the neutrophils. In lungs that received stimulated neutrophils, the pulmonary vascular filtration coefficient was about 5 times higher than in lungs that received unstimulated neutrophils. An increase in filtration coefficient was almost completely blocked by pretreatment with SOD or ALLO. However, the accumulation of stimulated neutrophils was not, or only partly, blocked by SOD or ALLO, respectively. We conclude that the increase in pulmonary vascular permeability caused by mechanically stimulated neutrophils was partly mediated by reactive oxygen species generated via the xanthine oxidase system.

Animals↗