Soft-x-ray-emission studies of YNi2B2C and LaNi2B2C: Observation of the B 2p and C 2p partial density of states.
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Journal Article↗
Biomedical subjects
H Takagi
Publications and source records attributed to H Takagi.
Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins.
The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P < 0.006) or hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-microns section averaged 47% +/- 4% (P < 0.001) and 37% +/- 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66%, respectively. No retinal toxicity was observed by light microscopy. These data demonstrate VEGF's causal role in retinal angiogenesis and prove the potential of VEGF inhibition as a specific therapy for ischemic retinal disease.
Animals↗
Fertirelin and buserelin compared by LH release, milk progesterone and subsequent reproductive performance in dairy cows treated for follicular cysts.
This field study compared the efficacy of a single injection of 200 microg fertirelin with that of 20 microg buserelin in shortening the recovery period of 68 laotating Holstein-Friesian cows with ovarian follicular cysts 65 d post partum or later. Differential diagnosis was based not only on palpation per rectum but also on skim milk progesterone profiles ( or= 1.0 ng/ml) 1 wk after treatment, was evidenced in 75% of the fertirelin group and 72% of the buserelin group. A 74% conception rate was achieved in fertirelin-treated cows, with a mean interval of 71 d from treatment to conception. In the buserelin-treated cows, 65% conceived and the treatment-to-conception interval was 63 d. Differences were insignificant. At the doses used the two GnRH analogs were deemed equally effective in managing particularly stubborn follicular cysts.
Journal Article↗
Application of inferior vena cava graft to split liver transplantation of pig.
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Animals↗
Dissociative recombination of HD+ with an ultracold electron beam in a cooler ring.
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Journal Article↗
Overexpression of DNA methyltransferase in myoblast cells accelerates myotube formation.
We overexpressed mouse DNA methyltransferase in murine C2C12 myoblast cells and tested the isolated clones for their ability to differentiate. Significant numbers of the clones showed distinct myotubes 24 h after the isolated transformants had been induced to differentiate, whereas the parent C2C12 cells did not form myotubes at this time point. Transfection of the vacant vector or the plasmid containing the reverse-oriented DNA methyltransferase cDNA did not provide significant numbers of transformants with the accelerated differentiation phenotype, suggesting that the effect is caused by the expression of DNA methyltransferase. The expressions of skeletal muscle myosin and creatine kinase in clones that showed the accelerated differentiation-phenotype were also induced about 24 h earlier and at higher levels relative to the parent C2C12 or the control cells, indicating that the entire process of myogenesis had been accelerated. All the methyltransferase-transfected clones, regardless of their phenotypes, demonstrated about threefold higher DNA methyltransferase activity and higher methylation levels than those of the clones transfected with vector alone or the reverse-oriented plasmid. At the early stage of transfection of the sense-oriented plasmid, high de novo methylation activities were detected. We consider it likely that this high de novo methylation activity is the reason for the high methylation levels and the accelerated myotube formation of the clones transfected with the sense-oriented plasmid. In some transformants which showed the accelerated differentiation phenotype, MyoD1 was already fully expressed under the growth conditions while, in control cells, MyoD1 was expressed at low levels. This elevated level of MyoD1 transcription could account for the accelerated myotube formation observed in the transformants. The methylation state of the HpaII sites in exon 1 through exon 2 of the MyoD1 gene and the expression of the MyoD1 transcript are positively correlated.
Animals↗
A new animal model of cerebral infarction: magnetic embolization with carbonyl iron particles.
A new animal model of cerebral infarction was developed by magnetic embolization with carbonyl iron particles. An electromagnet was placed upon the lateral portion outside the orbit of Mongolian gerbils and charged with a current intensity of 2 A, 3 V (400 G) for 10 min. By intracardiac injection of iron particles at the beginning of the electric charge, infarction was selectively produced in the cerebral cortex. Two days after the operation, microhemorrhaging was seen in the necrotic region. Multiple scattered infarctions accompanied with microhemorrhagic signs closely resembled embolic infarction encountered in the human brain.
Animals↗
Expression of E-selectin on endothelial cells of small veins in human colorectal cancer.
E-selectin is an adhesion molecule of endothelial cells that binds to cancer cells mediated by sialyl Lewis A (sLea) or sialyl Lewis X (sLe(x)). It is suspected to be involved in hematogenous metastasis of tumors. Therefore, it is worth examining E-selectin expression in human colorectal cancer and its hepatic metastasis. In the present study, E-selectin was clearly revealed on the endothelial cells of small vessels adjacent to cancer nests both in primary and in metastatic nests in immunohistochemistry. In these tissues, E-selectin was observed on the endothelial cells lining the lumen of small vessels. Its expression adjacent to cancer nests appears to be induced through some stimuli by cancer cells, since its degree of expression is inversely correlated to the distance of the blood vessels from the cancer nests (p < 0.001). Endothelial cells adjacent to the metastatic lesion expressed E-selectin more extensively than those adjacent to the primary foci. This is also in line with the finding on serum E-selectin levels which were significantly elevated in the metastatic group as compared with the non-metastatic group. The serum E-selectin level may provide useful information in the diagnosis for hepatic metastasis of colorectal cancer, although the results are still tentative.
Aged↗
Muon Spin Relaxation and Magnetic Susceptibility Measurements in the Haldane System Y2-xCax)Ba(Ni1-yMgy)O5.
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Journal Article↗
Hypoxic regulation of vascular endothelial growth factor in retinal cells.
BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic protein and vasopermeability factor whose intraocular concentrations are closely correlated with active neovascularization in patients with diabetes mellitus, central retinal vein occlusion, retinopathy of prematurity, and rubeosis iridis. OBJECTIVE: To determine whether hypoxia could induce expression of VEGF in retinal cells, which then promotes retinal endothelial cell proliferation. METHODS: Retinal pigment epithelial cells, pericytes, and microvascular endothelial cells were exposed to hypoxic conditions in vitro, and RNA expression of VEGF was evaluated by Northern blot analysis. The VEGF-specific proliferative potential of the medium was measured by means of retinal endothelial cell growth assays and VEGF-neutralizing VEGF receptor IgG chimeric protein. RESULTS: The VEGF RNA levels increased within 4 hours and reached elevations of threefold to 30-fold after 18 hours of hypoxia (0% to 5% oxygen, 5% carbon dioxide, 90% to 95% nitrogen) in all cell types (.01 < P < .03). Stimulation was dependent on oxygen concentration. The VEGF RNA levels were normalized by reinstitution of normoxia for 24 hours (P < .004). Medium conditioned by hypoxic retinal pericytes and retinal pigment epithelial cells stimulated retinal endothelial cell growth by 20% (P = .04), and this stimulation was entirely inhibited by VEGF-neutralizing receptor chimeric protein (P = .02). CONCLUSION: Hypoxia increases VEGF expression in retinal cells, which promotes retinal endothelial cell proliferation, suggesting that VEGF plays a major role in mediating intraocular neovascularization resulting from ischemic retinal diseases.
Animals↗
Anti-neutrophil antibody attenuates the severity of acute lung injury in rats with experimental acute pancreatitis.
OBJECTIVE: To examine the role of activated neutrophils in microvascular injury after severe acute pancreatitis. We used the polyclonal anti-rat neutrophil antibody (PoAb) to deplete peripheral neutrophil counts and the anti-rat monoclonal antibody (MoAb) CD18 to block neutrophil adherence functions. DESIGN: Prospective, controlled trial. SETTING: Laboratory. PARTICIPANTS: Anesthetized male Wistar breeder rats, in which necrotizing pancreatitis was induced by injecting necrotizing agents into the pancreatic duct. INTERVENTIONS: Treatment groups received an infusion of PoAb, 8 mL/kg, before induction of pancreatitis or MoAb CD18, 2 mg/kg, after induction of pancreatitis. Control animals received 2 mL of rabbit serum or 1 mL of saline solution. MAIN OUTCOME MEASURES: Survival rate, white blood cell count, levels of serum amylase and lipase, myeloperoxidase activity in the lung, lipid peroxide levels in the pancreas, and results of histological studies. RESULTS: The survival rate of rats treated either with PoAb before or MoAb CD18 after induction of sepsis improved significantly (P < .01). Histologically and according to the levels of neutrophil myeloperoxidase in their lungs, rats treated with the antibodies 24 hours after inducing pancreatitis improved significantly (P < .05). Moreover, the serum lipase concentrations and lipid peroxide levels in the pancreas of these rats decreased significantly (P < .05). CONCLUSIONS: Both the depletion of peripheral neutrophils by PoAb and blocking of neutrophil adherence functions by MoAb CD18 may help to prevent acute lung injury caused by severe acute pancreatitis in this model.
Acute Disease↗
Dopamine compensates for deterioration of hepatic hemodynamics and metabolism during occlusion and reperfusion of the hepatic artery.
OBJECTIVE: To investigate the effects of temporary hepatic arterial occlusion and dopamine on hepatic hemodynamics and metabolism. DESIGN: Experimental animal study in a dog model. The proper hepatic artery was occluded for 60 minutes; then, it was reperfused for 60 minutes. Hepatic hemodynamic and oxygen metabolic values, lactate uptake ratios, and blood glucose levels were determined repeatedly throughout the experiment. Data are given as mean +/- SE. INTERVENTION: In another group, dopamine hydrochloride, 10 micrograms/kg per minute, was infused intravenously throughout the experiment, and the same variables were recorded. RESULTS: Portal vein blood flow continuously decreased during occlusion, and it decreased even further after declamping of the hepatic artery; this led to a disturbance of oxygen and lactate metabolism in the control group. Dopamine increased the portal vein blood flow from 84.9% +/- 3.9% to 100.9% +/- 3.6% of the preocclusion levels after 60-minute occlusion and from 79.0% +/- 3.6% to 93.6% +/- 5.1% of the preocclusion levels after 60-minute reperfusion (P < .05, respectively). Dopamine also enhanced the hepatic oxygen uptake ratio from 112.8% +/- 12.0% to 150.7% +/- 11.6% of the preocclusion levels after 60-minute reperfusion (P < .05, respectively). These factors contributed to acceleration of the hepatic oxygen consumption and lactate uptake ratio in the group of dogs that were infused with dopamine. CONCLUSIONS: Temporary occlusion of the hepatic artery causes deterioration of hepatic hemodynamics and metabolism. Administration of dopamine is an effective way to support hepatic function during occlusion of the hepatic artery.
Analysis of Variance↗
Lymph node metastases in carcinoma of the head of the pancreas region.
Histopathological examination of lymph node metastatic involvement in 139 specimens obtained from patients who underwent pancreatoduodenectomy or total pancreatectomy combined with wide resection of lymph nodes was performed, to clarify the critical areas of lymph node dissection in patients with carcinoma of the head of the pancreas region. Perigastric lymph node involvement in patients with carcinoma of the head of the pancreas was 14 per cent, in those with carcinoma of the distal bile duct 0 per cent and in those with carcinoma of the papilla of Vater 4 per cent. Para-aortic lymph node involvement in patients with carcinoma of the head of the pancreas, the distal bile duct and the papilla of Vater was 26, 9 and 0 per cent, respectively. On the basis of these results, pylorus-preserving pancreatoduodenectomy is indicated in almost all patients with carcinoma of the distal bile duct and the papilla of Vater. In patients with carcinoma of the head of the pancreas, however, wide dissection of lymph nodes, including para-aortic lymph nodes, should be carried out because of the relatively high incidence of para-aortic lymph node involvement.
Carcinoma, Ductal, Breast↗
Intracaval ultrasonography in the diagnosis of tumour involvement of the vena cava.
A retrospective study of 34 consecutive patients with possible tumour involvement of the vena cava was performed to assess the usefulness of intracaval ultrasonography. Twenty-five of the 34 patients were operated and resection carried out in 23, including seven with combined resection of the vena cava. The sonographic criterion for vena cava invasion was obliteration of the echogenic ring of the vena cava wall or intracaval tumour mass. The sensitivity, specificity and overall accuracy of intracaval endovascular ultrasonography in the diagnosis of tumour involvement of the vena cava were 100, 96 and 97 per cent respectively. The respective values were 91, 61 and 71 per cent for computed tomography and 82, 67 and 72 per cent for cavography. Ultrasonography is a useful technique that can precisely evaluate the vena cava for possible tumour invasion, especially when the presence or extent of tumour involvement is not definitely established by conventional imaging techniques.
Adult↗
Preoperative intra-aortic ultrasonography to determine resectability in advanced oesophageal cancer.
This study was designed to evaluate the effectiveness of intra-aortic ultrasonography in the preoperative diagnosis of aortic wall invasion by oesophageal cancer. Twenty-four patients with advanced oesophageal cancer underwent the procedure, and aortic invasion was found in seven. In three of these seven patients, the invasion was diagnosed to be limited to the aortic adventitia, enabling preoperative prediction of the resectability of the tumour. The contact angle of the tumour in relation to the descending aorta was more than 90 degrees in six patients, and aortic invasion to all layers was visualized in four by intra-aortic ultrasonography. On the other hand, aortic invasion to the adventitia was found in three of 14 patients in whom the contact angle was less than 90 degrees. Intra-aortic ultrasonography provides important information to help determine the resectability of advanced oesophageal cancer.
Adult↗
Bone-bonding behavior under load-bearing conditions of an alumina ceramic implant incorporating beads coated with glass-ceramic containing apatite and wollastonite.
Alumina ceramic with a porous surface coated with glass-ceramic containing apatite and wollastonite (AW-GC) was implanted in a state of press-fit under load-bearing conditions in the femoral condylus of the mongrel dog and compared with a non-glass-ceramic-coated alumina ceramic. A trapezoid alumina ceramic implant (7 x 10 x 5 mm) with a lateral recess (0.9 mm deep) coated with alumina ceramic beads (mean diameter, 750 microns) in a single layer was prepared. The alumina ceramic beads were bonded to the alumina ceramic substratum using an identical alumina binder. The thickness of coating was 10-50 microns (mean, 30 microns). The surface of the beads and the substratum of the alumina implant were coated with AW-GC. A pull-out test and histologic examination were performed at 4, 8, and 24 weeks after implantation. The interfacial shear load was significantly increased from 8 to 24 weeks in both groups. The shear load of the glass-ceramic-coated implant was significantly greater than that of the noncoated implant at every stage. The interface shear load of the noncoated implant was 12.13 +/- 2.76 kg at 4 weeks, 13.92 +/- 4.18 kg at 8 weeks, and 24.17 +/- 5.17 kg at 24 weeks after implantation. The interface shear load of the glass-ceramic-coated implant was 17.96 +/- 2.81 kg at 4 weeks, 24.92 +/- 9.87 kg at 8 weeks, and 34.83 +/- 4.12 kg at 24 weeks after implantation. Histologic examination showed more ingrown bone tissue in the glass-ceramic-coated implants. It is suggested that AW-GC stimulated the bone ingrowth.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Decreased levels of alpha 1(I) procollagen mRNA in dermal fibroblasts grown on fibrin gels and in response to fibrinopeptide B.
We have investigated human neonatal fibroblast synthetic activity in response to fibrin substrates and components of fibrin formation and degradation. Greater than threefold downregulation of procollagen mRNA levels was seen 24 hours after fibroblasts were grown on fibrin gels as compared to tissue culture plastic. This downregulation occurred in both reptilase-generated fibrin (retention of fibrinopeptide B) and thrombin-generated fibrin (loss of both fibrinopeptide A and B). However, fibroblasts grown on fibrin retained their capacity to respond to the stimulatory action of transforming growth factor (TGF)-beta 1. Fibroblasts seeded on reptilase-generated fibrin displayed an abnormal morphology manifested by dendritic appearance and cell rounding, while fibroblast attachment was enhanced by 30% on thrombin-generated fibrin substrate (P < 0.02). Fibrinopeptides A and B, which are generated during fibrin formation, increased and decreased procollagen mRNA levels, respectively. Tissue plasminogen activator (t-PA) increased procollagen mRNA and TGF-beta 1 levels as early as 6 hours after cells were grown on tissue culture plastic, but this stimulation did not occur in cells cultured on a fibrin substrate. We conclude that alpha 1(I) procollagen mRNA levels in cultures of human dermal fibroblasts are consistently down-regulated by a fibrin substrate and are directly and profoundly influenced by complex interactions between components involved in the formation and removal of fibrin.
Blotting, Northern↗
Establishment and characterization of human gastric and colonic xenograft lines resistant to CPT-11 (a new derivative of camptothecin).
CPT-11-resistant human gastric and colonic xenograft lines were established by direct intratumoral injection of CPT-11 into subcutaneous SC-1-NU and CC-2-NU tumors in nude mice once a week for 10 months. The resistance of these xenograft lines to CPT-11 was confirmed by growth inhibition rate, to be 36.3% and 45.4%, respectively, compared to each parent cell line. DNA topoisomerase I activity of the nuclear extracts of SC-1-NU/CPT-11 and CC-2-NU/CPT-11, as assayed by relaxation of supercoiled DNA Col-E1, was significantly less than those of the parent lines. The cellular levels of topoisomerase I in those resistant lines measured by Western blot analysis were 0.57- and 0.79-fold lower than those of the parental lines, respectively. However, the activity of DNA topoisomerase II of those resistant cell lines assayed by decatenation of kinetoplast DNA was higher than that of the parental lines and the cellular levels of topoisomerase II in the resistant lines measured by Western blot analysis were 10.8- and 8.1-fold higher than those of the parent lines. Intracellular accumulation of CPT-11 in CPT-11-resistant tumors was not changed as compared to that of the parental lines, but hydrolysis of CPT-11 to more active SN-38 was reduced in the resistant tumors.
Animals↗