Biomedical subjects

N Endo

Publications and source records attributed to N Endo.

At least 73 records · Page 4Linked to original sources

PubMed1998

Oxypurinol, a xanthine oxidase inhibitor and a superoxide scavenger, did not attenuate ischemic neuronal damage in gerbils.

The superoxide (O2.-) scavenging activity and neuroprotective effects of oxypurinol, a xanthine oxidase inhibitor, were compared with those of alpha-phenyl-N-tert-butyl nitrone (PBN). The rate constant for the reaction of oxypurinol with O2.- at pH 7.4 was 1.71 x 10(3) M(-1) s(-1) which was more than 100-fold that of PBN (1.65 x 10 M(-1) s(-1)). Oxypurinol inhibited the release of O2.- from stimulated neutrophils better than did PBN. However, oxypurinol did not attenuate the ischemic neuronal damage in gerbils, while PBN did. These results indicate that neither xanthine oxidase inhibiting activity nor O2.- scavenging activity correlates to the therapeutic efficacy of neuroprotective agents in ischemic-reperfusion injury.

Animals↗

PubMed1998

Immunohistochemistry of neuron-specific enolase in neurons of the medulla oblongata from human autopsies.

Neuron-specific enolase (NSE) is a glycolytic enzyme specifically expressed in neurons. NSE has been used as a marker for neuronal damage in brain injury. We studied the immunohistochemical localization of this enzyme in the medulla oblongata obtained from human forensic autopsy specimens. Neurons in the dorsal motor nucleus of vagal nerve expressed statistically significantly less NSE immunoreactivity in the cytoplasm than in the hypoglossal nucleus (XII), solitary nucleus, spinal trigeminal nucleus, and lateral cuneate nucleus. Cases of carbon monoxide intoxication by burning showed a higher incidence of NSE immunoreactivity in the cell nucleus of the XII than other cases, while there was no statistically significant correlation between NSE immunoreactivity in the cell nucleus and the Nissl amount. This indicates that the accumulation of NSE immunoreactivity in the cell nucleus might be a vital reaction rather than a postmortem artifact.

Adult↗

PubMed1998

Thujaplicin-copper chelates inhibit replication of human influenza viruses.

The effects of alpha-, beta- and gamma-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin-Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 microM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2 4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin-copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.

Animals↗

PubMed1998

[Inducibility of tumor necrosis factor alpha to peritoneal macrophages and lethality to mice of clinical isolates of Staphylococcus aureus].

When murine resident peritoneal macrophages were treated in vitro with overnight culture supernatants of clinical isolates of S. aureus (21 strains)(S. aureus-CS) for 4 hrs at 37 degrees C in a 5% CO2-air humidified incubator, TNF alpha induction from the treated cells was observed in 20/21 strains. The amount of TNF alpha dispersed from 88.4 to 1726.5 pg/ml but more or less amount of TNF alpha did not relate with the presence of TSST-1 and enterotoxin production of S. aureus. Recombinant protein A induced TNF alpha production by macrophages dose-dependently, but the relationship between the amount of protein A in each S. aureus CS and that of TNF alpha induced from macrophages treated with them were not satisfactory (r = 0.69). When each strain was injected (X10(9) bacterial cells) interperitonealy to mice, 13/21 strains indicated lethal activity. Relation between TNF alpha inducibility in vitro and lethal activity, however, was not found (r = 0.4). These results suggest that TNF alpha inducibility is the basic biological activity of S. aureus, although there is a difference in the induction amount and in component(s) to induce TNF alpha on each strain, and then because the strain is strong in TNF alpha inducibility, it does not necessarily follow that pathogenicity is strong.

Animals↗

PubMed1998

[Difference of host response in identical toxin-produced Staphylococcus aureus-injected mice].

Biological activities of two strains of Staphylococcus aureus (S. aureus), KU-1-06-37 and KU-1-12-44, which produce enterotoxin type C, TSST-1 and alpha-toxin were examined using Std:ddY strain mice. These two strains were found to be different in lethality, ratio of weight loss, induction of leukopenia, adhesion to surrounding organs and clearance period of bacterial cells from the liver, kidney and spleen within 24 hrs after intraperitoneal injection in the mice. All of them were weak or fast in KU-1-12-44 injected mice. Serum amyloid A on all the KU-1-06-37 and KU-1-12-44 injected mice rose within 5 hr to 18 hr. However, this concentration of KU-1-12-44 injected mice was about 40% lower compared with that of KU-1-06-37 injected mice at 21 hr. On the other hand, ability of bacterial adhesion to established cell lines, Vero and HeLa cells, was tested in vitro. Percentage adhesion of KU-1-06-37 was high to both cells, but that of KU-1-12-44 was high to Vero cells and was low to HeLa cells. Adhesion of KU-1-06-37 to HeLa cells that were treated with lipoteichoic acid was about 40% inhibition compared with untreated cells, although that of KU-1-12-44 to them was inhibited only 9%. As the results, identical toxin-produced KU-1-06-37 and KU-1-12-44 showed different biological activities in vivo and in vitro. Not only toxin production but also adhesion to cells or organs in mice may contribute to S. aureus virulence to the host.

Animals↗

PubMed1998

Beta-thujaplicin zinc chelate induces apoptosis in mouse high metastatic melanoma B16BL6 cells.

The cytotoxic effects of beta-thujaplicin and five kinds of metal chelates were examined on mouse melanoma B16BL6 cells by cell viability and lactate dehydrogenase (LDH) release assay. Beta-thujaplicin-zinc chelate and beta-thujaplicin-copper chelate had higher cytotoxic effects than beta-thujaplicin, and the 50% effective doses (ED50) of these metal chelates were 12.5 and 25 microM, respectively. In addition, the zinc chelate induced DNA ladder formation in B16BL6 cells, as shown by the DNA fragmentation assay, suggesting that cell death induced by the zinc chelate is apoptosis. The zinc chelate also had a cytotoxic effect and induced DNA fragmentation on other tumor cell lines: HeLa, Meth A, and B16F1 cells, but not on normal human diploid fibroblasts FS-4. These results suggest that beta-thujaplicin-zinc chelate induces apoptotic cell death in various tumor cell lines and is a potent antitumor agent for tumor cells including malignant melanomas.

Animals↗

PubMed1998

Effects of single and concurrent intermittent administration of human PTH (1-34) and incadronate on cancellous and cortical bone of femoral neck in ovariectomized rats.

The purpose of this study is to determine the efficacy of concurrent treatment with human parathyroid hormone, hPTH (1-34), and bisphosphonate (incadronate) in augmenting cortical and cancellous bone mass of femoral neck in ovariectomized (OVX) rats. Forty-eight 11-week-old female Sprague-Dawley rats were divided into eight groups (six animals in each group). The baseline control group was killed at the beginning of the experiment, at 11 weeks of age. An ovariectomy was performed in thirty rats and twelve rats were subjected to a sham surgery. OVX rats were untreated for the first four weeks of postsurgery to allow for the development of moderate osteopenia. These animals were then subjected to various treatments with either PTH, incadronate, or PTH+ incadronate for a period of 4 weeks. Right proximal femora (femoral necks) were used for bone histomorphometry. After OVX 8 weeks, there was a significant decrease in cancellous bone mass and cortical bone area of femoral neck in the OVX rats when compared to the sham control rats. In OVX rats treated with PTH alone or PTH+ incadronate were completely restored lost cancellous and cortical bone mass of femoral neck by increase bone formation. The bone formation parameters (OS/ BS, MS/BS) and bone turnover (BFR/BV) seen with PTH plus incadronate were similar to those seen with PTH treatment alone. This indicates that incadronate did not blunt the anabolic action of PTH when used concurrently. Our results suggest the followings: 1) the femoral neck of OVX rats is a suitable sample site for preclinical studies of the prevention of bone loss induced by estrogen depletion; 2) concurrent use of incadronate did not blunt the anabolic effect of PTH; 3) concurrent treatment showed the best results in restoring cancellous and cortical bone mass; and 4) it had additional benefits for bone strength independent of that achieved by the increase in bone mass.

Animals↗

PubMed1997

Rifampicin inhibits the toxicity of pre-aggregated amyloid peptides by binding to peptide fibrils and preventing amyloid-cell interaction.

Rifampicin and its analogues, p-benzoquinone and hydroquinone, inhibited the toxicity of preformed aggregates of human islet amyloid polypeptide, amylin, to rat pheochromocytoma PC12 cells, when preincubated with the aggregated peptide before addition to cell cultures. Immunofluorescence microscopy showed that they prevented the adhesion of amylin aggregates to the cell surface, and this effect was induced probably by their binding to peptide fibrils during preincubation. Other quinone derivatives, i.e., p-methoxyphenol, AA-861 and idebenone, failed to inhibit the toxicity and cell-surface adhesion of amylin aggregates. Rifampicin analogues also inhibited the toxicity of pre-aggregated amyloid beta1-42 peptides, suggesting a common toxic mechanism of different amyloid peptides and their therapeutic potential for several amyloidoses.

Amyloid↗

PubMed1997

Monocyte chemoattractant protein-2 can exert its effects through the MCP-1 receptor (CC CKR2B).

We studied the activities of the monocyte chemoattractant proteins MCP-1, MCP-2 and MCP-3 on human embryonic kidney 293-EBNA cells transfected with the MCP-1 receptor (CC CKR2B). At 4 nM, MCP-2 induced a Ca2+ influx which was as potent as that with MCP-1 at 4 nM, although the increase by MCP-2 became saturated at higher concentrations. In addition, all three MCPs showed dose-dependent inhibition of adenylyl cyclase activity stimulated by forskolin (IC50 values: 0.3 nM for MCP-1, 7 nM for MCP-2, and 1.5 nM for MCP-3). In conclusion, our data indicate that MCP-2 can exert its effects through the MCP-1 receptor, CC CKR2B.

Adenylyl Cyclase Inhibitors↗

PubMed1997

Magnetic resonance imaging of reticulo-endothelial system in patients with idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is characterized by accelerated platelet destruction in the reticulo-endothelial system (RES). We performed magnetic resonance imaging (MRI) to estimate the degree of activated RES. MRI was performed with a Gyroscan S-15 (1.5 tesla) in 7 healthy volunteers and 22 patients with ITP. The 22 patients included 19 who were at initial diagnosis or were nonresponders to the therapy (non-DX group), and 3 who were responders. For the non-DX group, the T1 relaxation time of the spleen was initially significantly shorter than for healthy volunteers, but normalized after responding to the therapy. The initially shorter T1 values of the spleen for ITP patients correlated with a low platelet count (P < 0.05). This condition may indicate foam cells or fatty components due to platelet destruction. There was no significant relationship between the sequestration in (111)In-scan and T1 values of the liver or spleen. However, MRI is a noninvasive method, and it may be a clinically useful tool in the evaluation of RES in patients with ITP.

Adolescent↗

PubMed1997

A morphometric comparison of trabecular structure of human ilium between microcomputed tomography and conventional histomorphometry.

Recently, an imaging technique using microcomputed tomography (micro-CT) has emerged as a method for nondestructively assessing the microarchitecture of unprocessed surgical bone biopsy specimens. Using micro-CT, two-dimensional (2D) axial images were obtained from undecalcified transiliac bone biopsies which were taken from 15 patients with various metabolic bone diseases. Total area, bone area, and bone perimeter were determined, from which the bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated semiautomatically and instantaneously. To evaluate the validity of this technique as a useful tool, the results were compared with those obtained from conventional histomorphometry. There were significant correlations between the two techniques for all parameters, with correlation coefficients ranging from 0.759 (Tb.N, P < 0.005) to 0.949 (BV/TV, P < 0.0001). Different resolutions seem to lead to major differences in perimeter values measured by the two methods. These factors may explain why the correlation coefficients of Tb.N and Tb.Th estimated from the perimeter and area is lower than that of BV/TV. Our results show that the micro-CT based on 2D images is a useful tool for imaging and nondestructively quantifying the microarchitecture of trabecular bone in unprocessed surgical bone specimens.

Adult↗

PubMed1997

Effects of intermittent administration of low dose human PTH(1-34) on cancellous and cortical bone of lumbar vertebral bodies in adult beagles.

This study assessed the effect of low dose human parathyroid hormone [hPTH(1-34)] administration on cancellous and cortical bone of lumbar vertebrae in intact male beagles. 16 19-20-month-old beagle dogs were randomized into four groups: in group 1, the vehicle control group, saline was injected daily; in group 2, the sequential group, 0.375 microg/kg of PTH was injected daily for 4 weeks, then off 8 weeks, and this sequence was once repeated for another 4 and 8 weeks; in group 3, the same dose of PTH was injected once per week for 24 weeks; and, in group 4, PTH was injected three times per week for 24 weeks. Histomorphometric assessment on cancelllous and cortical bone (both ventral and dorsal shell) and two-dimensional node-strut analysis were done on the fifth lumbar vertebral bodies after calcein double bone labeling. In intact adult beagles, on the group treated with 0.375 microg/kg per day three times per week (group 4): (1) had a higher mean value in cancellous bone formation parameters [osteoid surface (+74%), osteoid volume (twofold), mineral apposition rate (+21%), and bone formation rate (twofold)]; (2) exhibited no effect on cortical thickness and porosity in both the ventral and dorsal shell; and (3) showed a lower mean value of node to termini (0.11 +/- 0.02 vs. 0.22 +/- 0.09) and a higher mean value of cortex to node (0.18 +/- 0.06 vs. 0.08 +/- 0.02), but not in trabeculae to trabeculae node, than age-related controls. In conclusion, we found that a low dose of PTH administration: (1) stimulated cancellous bone formation; (2) improved connectivity of trabeculae joined to the cortex; (3) did not decrease cortical thickness; and (4) did not increase cortical porosity in both ventral and dorsal cortexal shell of the lumbar vertebrae during this dosage and period in intact male beagles.

Animals↗

PubMed1997

Vascularized iliac bone graft for avascular necrosis of the femoral head.

This is a followup study of 31 hips in 24 patients from 2 to 11 years after receiving a vascularized iliac bone graft for nontraumatic avascular necrosis of the femoral head. The clinical results according to the Merle d'Aubigne score were satisfactory in 24 (77%) of the hips, whereas the radiographic success rate for all hips was 58%. The extent of the lesion as shown on anteroposterior radiographs was predictive of the eventual outcome. Seven (39%) of 18 hips with a lateral type lesion had satisfactory results, whereas 11 (85%) of 13 hips with a medial type lesion had satisfactory results. All of the hips with a medial type lesion and a lateral head index of greater than 12% had satisfactory results. For the success of this procedure, the lateral buttress of the normal portion in the femoral head was necessary.

Adolescent↗

PubMed1997

[Isolation frequency and biological characteristics of the multiple-antibiotic resistant Pseudomonas aeruginosa isolated from clinical specimens].

Isolation frequency of multiple-antibiotic resistant Pseudomonas aeruginosa (MARPA) was 11.9% (fifty six strains) of a total of four-hundred seventy-one strains of P. aeruginosa isolated from clinical specimens at the Kyorin University Hospital from October 1994 to December 1996. Eighteen strains of MARPA and thirteen strains of antibiotic sensitive P. aeruginosa (ASPA) isolated from clinical specimens in internal medicine ward A were determined O serotype, and characterized with production of pyocyanin, pyoverdin, hemolysin, elastase, and caseinase. Sixteen strains (88.9%) of MARPA were identified as serotype C. The ability to produce pyocyanin, hemolysin, elastase, and caseinase was not detected in all MARPA. One side, thirteen strains of ASPA showed various serotypes, i.e., B: 5 strains (38.4%), G: 4 strains (30.8%), C: 2 strains (15.4%), E: 1 strain (7.7%) and unknown type: 1 strain (7.7%), and the production of both hemolysin and pyoverdin was observed in 13 strains (100%), pyocyanin in 8 strains (61.5%), elastase and caseinase in 9 strains (69.2%) of ASPAs, which suggests that ASPAs do maintain the synthetic ability of pathogenic factors and pigments, but MARPAs do not. These results indicate that from epidemiological points of view the current strains of MARPA spread from one clone within the internal medicine ward A with nosocomial outbreak by serotype C.

Ampicillin Resistance↗

PubMed1997

[Effects of Staphylococcus aureus protein A on the production of primary host defense factors against S. aureus infection].

In vitro examination was carried out to investigate the effects of protein A of Staphylococcus aureus (S. aureus) on the production of fibronectin (Fn) and the third component of complement (C3) by macrophages and that of CD11b, CD49e and H2O2 by granulocytes. Fn production of cultured murine peritoneal macrophages (M phi ) increased significantly (P < 0.01) by treatment for 4 hr at 37 degrees C with recombinant PA (rPA) and the supernatant of overnight culture of S. aureus Cowan I strain (CoCS) (p < 0.01), not that of Wood 46 strain (WoCS), in comparison with that of control. The activity of rPA was inhibited strongly in the presence of CYH (1.0 microgram/ml). The production of C3 by cultured M phi did not increased by treatment for 4 hr at 37 degrees C with rPA, CoCS and WoCS. In these cells treated with CoCS and WoCS, however, the production increased by cultivation in serum free medium for a further 20 hr at 37 degrees C after the treatment. But increase was not found in rPA treated cells. On the other hand, the production of Mac-1, VLA-5 and H2O2 by granulocytes did not increase by treatment with rPA and CoCS. These results show that rPA and PA in CoCS are major components which stimulates Fn synthesis and secretion by cultured M phi some component(s) contained in the supernatant of overnight culture of S. aureus increased the production C3 by cultured M phi , and the supernatant may not contain stimulators to induce production of CD49e, CD11b and H2O2. Increase of Fn production of M phi by PA stimulation may play an important role in the primary host defense against S. aureus infection.

Animals↗

PubMed1997

Assessment of nutritional status of postoperative patients with biliary atresia.

Some patients of biliary atresia (BA) suffer from chronic hepatic dysfunction and/or persistent jaundice. The adverse effects of chronic liver disease on nutrition and growth should be considered on BA patients. We studied 45 BA patients ranging in age from 0.5 to 38 years and divided them into 2 groups. Group A contains the patients whose total bilirubin > or = 2 mg/100 ml, and Group B contains the patients whose total bilirubin < 2 mg/100 ml. We measured height, weight, triceps skin fold (TSF), midarm circumference (MAC) and midarm muscle area (MAMA). Visceral protein kinetics was evaluated on the basis of serum albumin and prealbumin levels. Caloric and protein intake was calculated by collecting intake data for 3 days. The results of this study were; 1) The mean TSF in Group A (47th percentile) was not significantly different from that in Group B (53th percentile). 2) The mean MAMA was significantly lower (p < 0.01) in Group A (16.4th percentile) than in Group B (36.7th percentile) 3) The prealbumin level was significantly lower (p < 0.001) in Group A (mean 9.9 mg/100 ml) than in Group B (mean 18.8 mg/100 ml). The authors conclude that the evaluation of MAMA and prealbumin were very useful to characterize the low metabolic status of protein in the damaged liver. And repeated nutritional assessment was necessary to evaluate liver function and provide adequate nutrition in BA patients.

Adolescent↗

PubMed1996

Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate.

Alendronate (ALN), an aminobisphosphonate used in the treatment of osteoporosis, is a potent inhibitor of bone resorption. Its molecular target is still unknown. This study examines the effects of ALN on the activity of osteoclast protein-tyrosine phosphatase (PTP; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48), called PTPepsilon. Using osteoclast-like cells generated by coculturing mouse bone marrow cells with mouse calvaria osteoblasts, we found by molecular cloning and RNA blot hybridization that PTPepsilon is highly expressed in osteoclastic cells. A purified fusion protein of PTPepsilon expressed in bacteria was inhibited by ALN with an IC50 of 2 microM. Other PTP inhibitors--orthovanadate and phenylarsine oxide (PAO)-inhibited PTPepsilon with IC50 values of 0.3 microM and 18 microM, respectively. ALN and another bisphosphonate, etidronate, also inhibited the activities of other bacterially expressed PTPs such as PTPsigma and CD45 (also called leukocyte common antigen). The PTP inhibitors ALN, orthovanadate, and PAO suppressed in vitro formation of multinucleated osteoclasts from osteoclast precursors and in vitro bone resorption by isolated rat osteoclasts (pit formation) with estimated IC50 values of 10 microM, 3 microM, and 0.05 microM, respectively. These findings suggest that tyrosine phosphatase activity plays an important role in osteoclast formation and function and is a putative molecular target of bisphosphonate action.

Alendronate↗

PubMed1996

Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin. Its possible function as a hydroxyl radical scavenger.

Aggregation of physiologically produced soluble amyloid beta protein (Abeta) to insoluble, neurotoxic fibrils is a crucial step in the pathogenesis of Alzheimer's disease. Aggregation studies with synthetic Abeta1-40 peptide by the thioflavin T fluorescence assay and electron microscopy and cytotoxicity assays using rat pheochromocytoma PC12 cells showed that an antibiotic, rifampicin, and its derivatives, which possess a naphthohydroquinone or naphthoquinone structure, inhibited Abeta1-40 aggregation and neurotoxicity in a concentration-dependent manner. Hydroquinone, p-benzoquinone, and 1,4dihydroxynaphthalene, which represent partial structures of the aromatic chromophore of rifampicin derivatives, also inhibited A beta1 40 aggregation and neurotoxicity at comparable molar concentrations to rifampicin. Electron spin resonance spectrometric analysis revealed that the inhibitory activities of those agents correlated with their radical-scavenging ability on hydroxyl free radical, which was shown to be generated in cell-free incubation of Abeta1-40 peptide. These results suggest that at least one mechanism of rifampicin-mediated inhibition of A beta aggregation and neurotoxicity involves scavenging of free radicals and that rifampicin and/or appropriate hydroxyl radical scavengers may have therapeutic potential for Alzheimer's disease.

Alzheimer Disease↗