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Biomedical subjects

N Endo

Publications and source records attributed to N Endo.

At least 91 records · Page 5Linked to original sources

Maintaining bone mass by bisphosphonate incadronate disodium (YM175) sequential treatment after discontinuation of intermittent human parathyroid hormone (1-34) administration in ovariectomized rats.

Intermittent treatment with human parathyroid hormone (1-34) [hPTH(1-34)] stimulates bone formation and increases cancellous bone mass in ovariectomized (OVX) rats. But PTH-induced cancellous bone rapidly disappears upon cessation of treatment. The fate of cortical bone treated by PTH has not been well characterized. Incadronate disodium (disodium cycloheptylaminomethylenedisphosphonate monohydrate, YM175) was expected to be antiresorptive without inhibiting bone formation. The purposes of this study were to determine (1) whether PTH treatment increases new cancellous and cortical bone mass and bone formation, (2) whether the new bone could be maintained by YM175 sequential treatment, and (3) whether the maintenance effect is persistent after YM175 withdrawal. Eighty-eight 11-week-old Sprague-Dawley rats were divided into sham operation and OVX groups. The OVX rats were treated for 8 weeks with the subcutaneous intermittent injection of 30 micrograms/kg of hPTH(1-34) three times a week beginning 4 weeks after surgery, then PTH treatment was withdrawn and YM175 (10 micrograms/kg) was injected subcutaneously three times a week for 4 weeks. YM175 treatment was withdrawn for the last 8 weeks of the protocol. The results of microstructural assessment in proximal tibial metaphysis and bone mineral density in distal and proximal femur demonstrated that PTH treatment for 8 weeks restored bone mass to the sham control level. However, after cessation of PTH treatment, the PTH-induced tibial cancellous bone mass showed a decrease at 4 weeks and almost totally disappeared after 12 weeks. Conversely, YM175 treatment maintained the PTH-induced tibial cancellous bone mass, and the bone continued to be maintained after 8 weeks of withdrawal of the YM175. Cortical bone was not lost during PTH treatment. YM175 maintained the PTH-induced new tibial cancellous bone in OVX rats by suppressing remodeling.

Animals↗

Human protein tyrosine phosphatase-sigma: alternative splicing and inhibition by bisphosphonates.

Two forms of the transmembrane human protein tyrosine phosphatase (PTP sigma), generated by alternative splicing, were identified by cDNA cloning and Northern hybridization with selective cDNA probes. The larger form of PTP sigma is expressed in various human tissues, human osteosarcoma, and rat tibia. The hPTP sigma cDNA codes for a protein of 1911 amino acid residues and is composed of a cytoplasmic region with two PTP domains and an extracellular region that can be organized into three tandem repeats of immunoglobulin-like domains and eight tandem repeats of fibronectin type III-like domains. In the brain, the major transcript of PTP sigma is an alternatively spliced mRNA, in which the coding region for the fibronectin type III-like domains number four to seven are spliced out, thus coding for a protein of 1502 amino acid residues similar to the rat PTP sigma and rat PTP-NE3. Using in situ hybridization, we assigned hPTP sigma to chromosome 6, arm 6q and band 6q15. The bacterial-expressed hPTP sigma exhibits PTPase activity that was inhibited by orthovanadate (IC50 = 0.02 microM) and by two bisphosphonates used for the treatment of bone diseases, alendronate (ALN) (IC50 = 0.5 microM) and etidronate (IC50 = 0.2 microM). In quiescent calvaria osteoblasts, micromolar concentrations of vanadate, ALN and etidronate stimulate cellular proliferation. These findings show tissue-specific alternative splicing of PTP sigma and suggest that PTPs are putative targets of bisphosphonate action.

Alternative Splicing↗

Effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on rat bone: inhibition of bone formation at the endosteal surface of vertebra and tibia.

The effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on bone was evaluated by histomorphometry using Sprague-Dawley rats. rh G-CSF was injected at doses of 0, 50, 150, and 450 microg/kg for 6 weeks. In vivo double fluorochrome labeling was performed before sacrifice. No significant change in body weight was observed. Bone mineral density (BMD) of lumbar vertebrae and femora was significantly decreased in G-CSF-treated groups. In the lumbar vertebra, osteoid surface, osteoid thickness, trabecular thickness, and labeled surface in G-CSF-treated groups were also significantly lower. In addition, osteoclast number and osteoclast surface were significantly higher in the G-CSF-treated groups. The endocortical surface at the mid-tibia showed lower labeled surface and mineral apposition rate in G-CSF-treated groups, without significant changes at the periosteal surface. Furthermore, numerous granulocytes fully occupied the bone marrow area. We conclude that proliferating granulocytes in the bone marrow may inhibit bone-forming cells from contacting the bone surface, resulting in reduction of bone formation; and increased osteoclastic bone resorption induced by G-CSF treatment contributed to the reduction of BMD.

Animals↗

Lantibiotic nisin Z fermentative production by Lactococcus lactis IO-1: relationship between production of the lantibiotic and lactate and cell growth.

The influence of several parameters on the fermentative production of nisin Z by Lactococcus lactis IO-1 was studied. Considerable attention has been focused on the relationship between the primary metabolite production of bacteriocin and lactate and cell growth, which has so far not been clarified in detail. Production of nisin Z was optimal at 30 degrees C and in the pH range 5.0-5.5. The addition of Ca2+ to the medium showed a stimulating effect on the production of nisin Z. A maximum activity of 3150 IU/ml was obtained during pH-controlled batch fermentation in the medium supplemented with 0.1 M CaCl2. It was about three times higher than that obtained under the optimal conditions for cell growth and lactic acid production.

Anti-Bacterial Agents↗

Current status of 21 patients who have survived more than 20 years since undergoing surgery for biliary atresia.

Between 1952 and 1993, 289 patients with biliary atresia underwent surgery at the authors' institution. Twenty-two of them survived more than 20 years; one has since died of hepatic failure (at age 28 years). Of the 21 current survivors (age range, 20 to 39 years), 13 underwent hepatic portoenterostomy; the others had hepaticoenterostomy. None of these patients has undergone liver transplantation. Sixteen patients have led near-normal lives. This includes three married women, one of whom has given birth to a healthy baby boy. Of the six patients who had portal hypertension, three underwent both splenectomy and proximal splenorenal shunting in or before 1985. None of these patients has required additional treatment for portal hypertension. The quality of life of one patient has been severely affected by an unrelated condition (Turner's syndrome). A 22-year-old man was diagnosed as having intrahepatic stones 3 years ago. In another 22-year-old man, hepatic dysfunction developed after frequent episodes of cholangitis. He is now being considered for liver transplantation. The majority of the long-term survivors have good quality of life. However, a few continue to suffer from complications including recurrent cholangitis. Close long-term postoperative follow-up is required for patients with biliary atresia.

Adult↗

Human osteosarcoma (OST) induces mouse reactive bone formation in xenograft system.

To distinguish the origin of bone-forming cells in the osteosarcoma (OST) tumor inoculated into nude mice, we have developed a novel in situ hybridization technique. The system used digoxygenin (DIG) labeled DNA probes that encoded human specific repetitive gene, Alu, and mouse specific repetitive gene, mouse L1 (m-L1). The chondrogenic and osteogenic cells in the tumor had strongly positive signals for m-L1 probe without any signals for Alu probe. The expression of bone matrix proteins was also examined by in situ hybridization. The bone-forming cells were positive for mRNAs of mouse osteonectin, osteopontin, and osteocalcin relating to calcification during bone formation, while these were negative for human mRNAs of these bone matrix proteins. The OST cells in the tumor expressed the human bone morphogenetic proteins (BMPs) mRNAs by RT-PCR. These data indicated that the mouse cells, not the human sarcoma cells, are responsible for cartilage and bone formation in the OST tumor inoculated into nude mice, and we speculated that BMPs, at least in part, could play an important role in this ossification.

Animals↗

Bone particles disturb new bone formation on the interface of the titanium implant after reaming of the marrow cavity.

Histomorphometric studies were conducted in rats to determine whether bone particles would disturb new bone formation on the interface of titanium implants inserted after reaming of the marrow cavity. In eighty 10-week-old female Wistar rats, smooth-surfaced titanium alloy implants were inserted bilaterally into the marrow cavity after reaming in the distal femur. There were three experimental groups: in the irrigated femora, sterile saline was flushed through the medullary canal; in the particle femora, autologous bone particles were inserted into the intramedullary cavity; and in the reamed femora, the implant was inserted without procedures after reaming. The rats were sacrificed at one, two, four or eight weeks postoperatively, and Villanueva bone staining was applied for histomorphometric studies. The bone volume of new bone on the interface of the implant in the irrigated femora was greater than that in the particle or the reamed femora throughout the study period. The results suggest that clearance of bone particles by irrigation after reaming of the marrow cavity significantly facilitates new bone formation on the interface of implants by one week. The findings also suggest the potential clinical application of total canal irrigation prior to insertion of cementless femoral components as well as cemented prosthesis.

Absorptiometry, Photon↗

Cloning and structural analysis of the melanin biosynthesis gene SCD1 encoding scytalone dehydratase in Colletotrichum lagenarium.

Appressoria of the phytopathogenic fungus Colletotrichum lagenarium contain melanin, which has been implicated as an important factor in the penetration of host plants. A cDNA clone containing the melanin biosynthetic gene encoding scytalone dehydratase (SCD1) from C. lagenarium was identified by hybridization with a heterologous cDNA probe from Magnaporthe grisea. The cDNA clone was used to identify a cosmid containing SCD1 in a genomic library of C. lagenarium, and the nucleotide sequence was determined for both the cDNA and genomic clones. The SCD1 gene contained one open reading frame composed of 188 codons and two deduced introns of 57 and 67 nucleotides. The deduced amino acid sequence of the N-terminal region of SCD1 showed high similarity to the amino acid sequence of scytalone dehydratase from Cochliobolus miyabeanus. A plasmid containing the SCD1 gene transformed the melanin-deficient mutant 9201Y (Scd-) to the wild phenotype but did not complement the conditional scytalone dehydratase-deficient mutant C. lagenarium 8015. Genomic DNA analysis indicated that the SCD1 gene is a single locus in C. lagenarium. Transcripts of the SCD1 gene were detected 2 h after the start of conidial germination.

Amino Acid Sequence↗

Potent allelochemical falcalindiol from Glehnia littoralis F. Schm.

A potent allelochemical in Glehnia littoralis F. Schm. was investigated. Falcalindiol was isolated from G. littoralis; 859.9 mg/kg of fresh root and 62.5 mg/kg of fresh aerial parts. Its structure was elucidated by spectroscopic methods, and the antimicrobial activities of falcalindiol were evaluated by the paper disk method against several microorganisms. The plant growth inhibition of falcalindiol was also investigated.

Antifungal Agents↗

Antimicrobial benzopyrans from the receptacle of sunflower.

The antimicrobial substances in sunflower (Helianthus annuus) were investigated. Two antifungal benzopyran derivatives, 6-acetyl-2,2-dimethyl-1,2-benzopyran (1) and 6-acetyl-7-hydroxy-2,2-dimethyl-1,2-benzopyran (2), were isolated from the ethanol extract of sunflower receptacles. The antimicrobial activities of isolated compounds 1 and 2 and their related compounds (precocenes) were evaluated by the paper disk method, using Pyricularia oryzae as the test fungus.

Anti-Infective Agents↗

Full active baculovirus-expressed human monocyte chemoattractant protein 1 with the intact N-terminus.

The Sf-9 insect cells infected with a recombinant baculovirus integrated with a cDNA encoding human monocyte chemoattractant protein-1 (MCP-1) produced three different MCP-1s, which were isolated by reverse-phase HPLC as 13kDa, 14kDa, and 15kDa bands on SDS-PAGE. The heterogeneity between these MCP-1s was ascribed to the different degree of O-glycosylation with Gal beta 1-3GalNAc beta 1-Ser/Thr, while the 13kDa was regarded as carbohydrate-free. The integrity of the N-termius was confirmed by the amino acid sequence analysis. Each MCP-1 isolated showed equipotent monocyte chemotactic activity, which was rather higher than that of the E. coli-derived one.

Amino Acid Sequence↗

Hypoaminotransferasemia in patients undergoing long-term hemodialysis: clinical and biochemical appraisal.

BACKGROUND & AIMS: It has been reported that patients with chronic renal failure have low serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as a result of vitamin B6 deficiency. Chronic hepatitis C is common among patients undergoing hemodialysis, and low aminotransferase levels cause diagnostic problems. The aim of this study was to determine the cause of hypoaminotransferasemia. METHODS: Serum levels of vitamin B6 and its coenzyme were reassessed in relation to AST and ALT levels in patients undergoing long-term hemodialysis using high-performance liquid chromatography. RESULTS: The mean (+/- SD) serum AST and ALT levels in 304 patients negative for hepatitis B surface antigen and anti-hepatitis C virus were 9.2 +/- 2.4 and 7.4 +/- 1.7 IU/L, respectively. In 556 normal adults, they were 22.7 +/- 5.4 and 18.0 +/- 4.0 IU/L, respectively (P < 0.001). Mean serum vitamin B6 and pyridoxal-5'-phosphate levels in patients undergoing dialysis were not reduced compared with the control, although occasionally patients had low levels. The AST and ALT assay reagents in Japan do not contain added pyridoxal-5'-phosphate; addition of pyridoxal-5'-phosphate (0.1 mmol/L) to the reagent significantly increased measurements to similar extents in both groups. CONCLUSIONS: Serum AST and ALT levels in patients undergoing dialysis are very low, but they are not a result of vitamin B6 deficiency. The upper normal limits of AST and ALT levels in patients undergoing dialysis should be reduced considerably, and these levels should be interpreted with caution in the diagnosis of liver disease.

Adult↗

Discrepancy of response of hPTH administration and its withdrawal between trabecular and cortical bone sites in OVX rats.

We demonstrated the differences of response between trabecular and cortical bone sites in the rat induced by OVX and hPTH(1-34) administration [subcutaneous injection, 30 micrograms/kg, 3 times/week, for 12 weeks] and its withdrawal [for 8 weeks]. We observed that hPTH(1-34) administration in OVX rats partially prevented OVX-induced cancellous bone loss in the proximal tiabial metaphysis and added cortical bone in the tibial shaft. After cessation of hPTH treatment, bone loss was observed both in trabecular and cortical bone; however, it was more dramatic on endocortical surfaces.

Animals↗

The effect of a synthetic 7-thiaprostaglandin E1 derivative, TEI-6122, on monocyte chemoattractant protein-1 induced chemotaxis in THP-1 cells.

1 The ability of various prostaglandins (PGs) to inhibit monocyte chemotaxis induced by monocyte chemoattractant protein-1 (MCP-1) was investigated with a human monocytic leukaemia cell line, THP-1. Moreover, to investigate the mechanism of the inhibitory action of PGs the involvement of either intracellular adenosine 3': 5'-cyclic monosphosphate (cyclic AMP) accumulation or intracellular Ca2+ mobilization was studied. 2 TEI-6122, a synthetic 7-thia-PGE1 derivative, inhibited chemotaxis of THP-1 cells induced by MCP-1 with an IC50 of 1.5 pM. Its inhibitory activity was 1000 fold more than that of PGE1 and PGE2 (IC50 = 2.8 nM and 0.9 nM, respectively), which were more potent than other PGs such as PGA1, PGA2, PGF2 alpha and PGI2 (IC50 > or = 1 microM). 3 With respect to the effect on intracellular cyclic AMP accumulation in THP-1 cells, TEI-6122 was as potent as PGE1 and PGE2, which were approximately 100 to 1000 fold more potent than the other PGs such as PGA1, PGA2 and PGI2. The minimum concentration of TEI-6122 required to increase intracellular cyclic AMP accumulation in THP-1 cells was 1 nM. 4 TEI-6122 and PGE1 (4 microM) transiently increased intracellular calcium levels in THP-1 cells. When added prior to MCP-1, both PGs partially suppressed the increased in Ca2+ caused by this cytokine. There were no significant differences between the activity of TEI-6122 and PGE1 in either respect. 5 It is concluded that TEI-6122, a synthetic 7-thia-PGE1 derivative is a much more potent inhibitor of MCP-1-induced THP-1 cell chemotaxis than PGEI and PGE2 which are the best inhibitors among the natural PGs tested, while neither intracellular cyclic AMP accumulation nor effects on Ca2+ mobilization account for the extremely potent inhibitory activity of TEI-6122. Thus, either a novel PGE2 receptor (EPreceptor) or a novel intracellular signal transduction system may be involved in the extremely potent chemotaxis inhibitory activity of TEI-6122.

Alprostadil↗

Rifampicin prevents the aggregation and neurotoxicity of amyloid beta protein in vitro.

The aggregation and cerebral deposition of amyloid beta protein (A beta), which is a major component of senile plaques in Alzheimer's disease (AD) brains, is believed to be involved in the pathogenesis of AD. Inhibition of A beta aggregation would seem to be a promising strategy for the treatment of AD. Here, we show that rifampicin, which is an antibiotic widely used in the treatment of tuberculosis and leprosy, inhibited the aggregation and fibril formation of synthetic A beta 1-40 peptide in a dose-dependent manner at reasonable concentrations. Furthermore, rifampicin was found to prevent A beta 1-40-induced neurotoxicity on rat pheochromocytoma PC12 cells. Rifampicin may have therapeutic potential as an agent for inhibiting the initial step of amyloid formation in AD.

Adrenal Gland Neoplasms↗

NER, a new member of the gene family encoding the human steroid hormone nuclear receptor.

NER, a new member of the steroid hormone nuclear receptor (NR)-encoding gene family, was isolated from a human osteosarcoma SAOS/B10 cell line cDNA library. NER codes for a polypeptide of 461 amino acids which contains the conserved sequences of the DNA-binding and ligand-binding domains of typical steroid hormone NR. It has highest homology with the retinoic acid receptors: 55% at the DNA-binding domain and 38-40% at the ligand-binding domain. A single transcript of 2.3 kb was detected in all cells and tissues tested. Although no ligand was identified for NER-I, its wide distribution may indicate that this novel steroid hormone NR may play a basic role in cell function.

Amino Acid Sequence↗

cDNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor.

A novel human G-protein-coupled seven-transmembrane-type receptor gene, 24-1, has been cloned from THP-1 cells. The 24-1 was 56% and 34% identical to the macrophage inflammatory protein-1 alpha (MIP-1 alpha) receptor and the interleukin-8 (IL-8) receptors at the amino acid level, respectively. To examine the ligand specificity of the receptor, we have established a stable transfectant of this gene with human kidney 293 cells. Monocyte chemoattractant protein-1 (MCP-1) induced a rapid increase of Ca++ influx in the 24-1-transfectant, while other C-C chemokines tested did not. This indicates that the 24-1 encodes the human MCP-1 receptor.

Amino Acid Sequence↗