Initial clinical application of cone-beam CT scan in pulmonary imaging.
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Aged↗
Biomedical subjects
H Takagi
Publications and source records attributed to H Takagi.
Angiotensin II-stimulated vascular endothelial growth factor expression in bovine retinal pericytes.
PURPOSE: Angiotensin II (AII) has been shown to play a role in many vascular diseases. In the study described, the effect of AII on vascular endothelial growth factor (VEGF) expression and related intracellular signaling mechanism was investigated in bovine retinal microcapillary pericytes. METHODS: Cultured bovine retinal microvascular endothelial cells and pericytes were prepared. VEGF expression was determined by Northern blot analysis and immunoprecipitation assay. Cell proliferation was assessed by DNA content growth assay. Reporter gene studies were performed to identify the AII responsible transcription-activating region of VEGF gene. RESULTS: Angiotensin II induced a significant increase in VEGF mRNA in a time- and dose-dependent manner. Angiotensin II type I receptor antagonist inhibited this effect. Angiotensin II activates the transcription of VEGF gene without changing the mRNA half-life, and the AII responsible region was found in the 5'-flanking region of the VEGF gene. Angiotensin II also increased the expression of c-fos and c-jun mRNA, and antisense oligonucleotides against c-Fos blocked the AII-induced VEGF mRNA expression. The conditioned media of AII-stimulated pericyte cultures had a growth-promoting effect on endothelial cells, and this effect was inhibited almost completely by VEGF neutralizing antibody. CONCLUSIONS: These findings suggest that AII might induce angiogenic activity through a paracrine function of VEGF in retinal microvascular cells.
Angiotensin II↗
[Neuronal cytokine involvement in synaptic plasticity].
Hippocampal long-term potentiation (LTP) is one of the best-studied models of learning and memory at the molecular level. In the hippocampal CA1 region, at least three different LTPs were reported: early phase LTP (E-LTP), late phase LTP (L-LTP) and anoxic LTP (A-LTP). E-LTP is induced by the activation of postsynaptically silent synapses. Unlike the E-LTP, L-LTP is dependent on protein synthesis and may be due to an increase in the number of sites of synapse. Unlike the E- and L-LTP, A-LTP is induced by presynaptic K+ channel modulations and is a crucial trigger for neuronal cell death. Interleukin-1 beta (IL-1 beta), which is produced under the anoxic conditions, plays an important role in A-LTP induction, and brain-derived neurotrophic factor (BDNF) plays a crucial role in L-LTP induction. IL-1 beta antagonist and or BDNF improve the cerebral anoxia-induced inhibition of E-LTP. These results suggested that the new synaptic sites, products of the BDNF induced L-LTP, will play an important role in synaptic plasticity (ex. E-LTP) instead of the synaptic sites of death neurons (induced by A-LTP). The neuronal cytokine system regulates these LTP expressions co-operatively and may play a crucial role to keep the brain system in the steady-state condition.
Animals↗
Sequential chemoimmunotherapy with cisplatin, interferon-beta and interleukin-2 inhibits the growth of B16-F1 melanoma in syngeneic mice.
Sequential combinations of chemotherapy with biological response modifiers has recently been evaluated as systemic treatment for patients with advanced melanoma. The response rates of the chemoimmunotherapy were reported to be higher than conventional treatment using chemotherapy or biological agents alone. To investigate the effectiveness of such chemoimmunotherapy, we evaluated the antitumour effect of sequential chemoimmunotherapy in vivo using a B16 mouse melanoma system. In this sequential regimen, administration of cisplatin (CDDP) was followed by interferon-beta (IFNbeta) and interleukin-2 (IL-2). This combination therapy synergistically inhibited the growth of B16-F1 melanoma and prolonged the survival of mice bearing B16-F1. In contrast, this therapy did not show any antitumour effect on B16-F10 melanoma. The exact mechanism of the antitumour effect is not clear, but the following results were noted: no synergistic effect of this therapy was detected in nude mice, neutralizing anti-IFNgamma antibody significantly blocked the antitumour effect of this therapy, and the number of apoptotic melanoma cells was significantly increased in melanoma tissues removed from mice treated with this therapy. These results demonstrated the potent immunological antitumour effect of this sequential chemoimmunotherapy.
Animals↗
Genetic association between rheumatoid arthritis and estrogen receptor microsatellite polymorphism.
OBJECTIVE: To investigate estrogen receptor (ER) microsatellite allele frequencies in patients with rheumatoid arthritis (RA), and possible associations of ER microsatellites with osteoporosis and disease progression. METHODS: We typed 144 Japanese females with RA and 200 healthy postmenopausal Japanese controls for ER microsatellites by polymerase chain reaction methods using fluorescent labeled primer and semiautomatic genotyping. Bone mineral density (BMD) of patients was measured in the spine by dual energy x-ray absorptiometry, and recent radiographs of the hands and wrists were scored according to the method described by Sharp, et al. RESULTS: The ER genotype was classified according to number of dinucleotide (thymine-adenine, TA) repeats between 10 and 27. The frequency of allele 14 (14 repeats of TA) was significantly increased in patients versus controls. No association of ER microsatellites with osteoporosis or radiographic progression in the RA patients was noted. CONCLUSION: These results suggest that a genetic variation at the ER locus may be associated with other pathogenetic factors in patients with rheumatoid arthritis, but not with BMD and disease aggressiveness.
Adult↗
[Role of vascular endothelial growth factor in microvascular abnormalities in diabetic retinopathy].
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Capillaries↗
[A case of acute respiratory distress syndrome induced by fulminant influenza A (H3 N2) pneumonia].
We report a rare case of acute respiratory distress syndrome (ARDS) induced by Influenza A (H3 N2) without secondary microbiological infection. A 69-year-old woman was admitted to our hospital because of cough and severe dyspnea. We diagnosed ARDS, because of the severe respiratory failure resistant to high-dose oxygen, the diffuse bilateral infiltrates without cardiomegaly on chest radiography, and the normal pulmonary artery wedge pressure. This patient was treated with high doses of methylprednisolone, antibiotics, globulins, urinastatin, neutrophilic elastase inhibitor, nitric oxide inhalation, and extracorporeal membrane oxygenation, but died on the thirteenth hospital day. Our final diagnosis was ARDS induced by fulminant influenza (A/Hong Kong/68 (H3 N2)) virus pneumonia, because the antibody titers of H3 N2 influenza of paired sera showed a 128-fold increase.
Acute Disease↗
[A 90-day repeated dose oral toxicity study of magnesium chloride in F344 rats].
In order to examine the toxicity of magnesium chloride hexahydrate, four groups of 10 male and 10 female F344 rats received the compound by dietary supplementation at 2.5, 0.5, 0.1 or 0% for 90 days. No treatment-related death was observed during the study. Transient soft stool and sustained increase in water consumption were observed both in males and females of the 2.5% group and slight reduction in body weight gain was noted in the high-dose males. There were no toxic changes in food consumption, organ weights, hematology and biochemistry, and histopathological examinations in any treated-groups. Based on these results, the no-observed-adverse-effect-level was estimated to be 0.5%, and 2.5% is considered to be appropriate as highest dose for a 2-year carcinogenicity study.
Administration, Oral↗
Microbial alkaline proteases: from a bioindustrial viewpoint.
Alkaline proteases are of considerable interest in view of their activity and stability at alkaline pH. This review describes the proteases that can resist extreme alkaline environments produced by a wide range of alkalophilic microorganisms. Different isolation methods are discussed which enable the screening and selection of promising organisms for industrial production. Further, strain improvement using mutagenesis and/or recombinant DNA technology can be applied to augment the efficiency of the producer strain to a commercial status. The various nutritional and environmental parameters affecting the production of alkaline proteases are delineated. The purification and properties of these proteases is discussed, and the use of alkaline proteases in diverse industrial applications is highlighted.
Journal Article↗
Overproduction of L-cysteine and L-cystine by expression of genes for feedback inhibition-insensitive serine acetyltransferase from Arabidopsis thaliana in Escherichia coli.
Two cDNAs encoding feedback inhibition-insensitive serine acetyltransferases of Arabidopsis thaliana were expressed in the chromosomal serine acetyltransferase-deficient and L-cysteine non-utilizing Escherichia coli strain JM39-8. The transformants produced 1600 to 1700 mg l(-1) of L-cysteine and L-cystine from glucose. The amount of these amino acids produced per cell was 30 to 60% higher than that of an E. coli strain carrying mutant serine acetyltransferase less sensitive to feedback inhibition.
Acetyltransferases↗
Tumor-promoting activity of 2,6-dimethylaniline in a two-stage nasal carcinogenesis model in N-bis(2-hydroxypropyl)nitrosamine-treated rats.
The potential promotion activity on nasal carcinogenesis of 2,6-dimethylaniline (DMA), an alpha2-adrenergic agonist metabolite of xylazine which is used for food-producing animals as a sedative agent, was examined. Male F344 rats received diet containing 0 or 3000 ppm DMA for 52 weeks after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Histopathological assessment showed the incidence of carcinomas in the DHPN+DMA group (33%) to be significantly elevated as compared with that for the DHPN-alone group (5%). Incidences and/or multiplicity of epithelial hyperplasias and dysplastic foci were also increased in the DHPN+DMA group. These lesions were exclusively observed in the olfactory mucosa. The lowest plasma levels of DMA in tumor- and dysplastic foci-bearing rats were 0.05 and 0.20 microg/ml, respectively. These results indicate that DHPN acts as an appropriate initiator for nasal carcinogenesis and that DMA exerts a tumor-promoting effect on the olfactory mucosa in the rat nasal cavity.
Adenoma↗
PCR random mutagenesis into Escherichia coli serine acetyltransferase: isolation of the mutant enzymes that cause overproduction of L-cysteine and L-cystine due to the desensitization to feedback inhibition.
PCR random mutagenesis in the cysE gene encoding Escherichia coli serine acetyltransferase was employed to isolate the mutant enzymes that, due to a much less feedback inhibition by L-cysteine, cause overproduction of L-cysteine and L-cystine in the recombinant strains. The L-cysteine auxotrophic and non-utilizing E. coli strain was transformed with plasmids having the altered cysE genes. Then, several transformants overproducing L-cysteine were selected by detecting the halo formation of the L-cysteine auxotroph. The production test of amino acids and analysis of the catalytic property on the mutant enzymes suggest that the carboxy-terminal region of serine acetyltransferase plays an important role in the desensitization to feedback inhibition and the high level production of L-cysteine and L-cystine.
Acetyltransferases↗
Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells.
Recent studies have shown that the angiopoietin-Tie2 system is a predominant regulator of vascular integrity. In this study, we investigated the effect of two known angiogenic stimuli, hypoxia and vascular endothelial growth factor (VEGF), on these molecules. VEGF induced both a time- and concentration-dependent increase in angiopoietin-2 (Ang2) mRNA expression in bovine microvascular endothelial cells. This up-regulation was derived primarily from an increased transcription rate as evidenced by nuclear run-on assay and mRNA decay study. The increased Ang2 expression upon VEGF treatment was almost totally abolished by inhibition of tyrosine kinase or mitogen-activated protein kinase and partially by suppression of protein kinase C. Hypoxia also directly increased Ang2 mRNA expression. In contrast, Ang1 and Tie2 responded to neither of these stimuli. The enhanced Ang2 expression following VEGF stimulation and hypoxia was accompanied by de novo protein synthesis as detected by immunoprecipitation. In a mouse model of ischemia-induced retinal neovascularization, Ang2 mRNA was up-regulated in the ischemic inner retinal layer, and remarkable expression was observed in neovascular vessels. These data suggest that both hypoxia- and VEGF-induced neovascularization might be facilitated by selective induction of Ang2, which deteriorates the integrity of preexisting vasculature.
Angiopoietin-2↗
Inhibition of focus formation of transformed cloned cells by contact with non-transformed BALB/c 3T3 A31-1-1 cells.
When transformed cells were co-cultured with various densities of non-transformed BALB/c 3T3 A31-1-1 cells, the number of transformed cell foci decreased as the density of the A31-1-1 cells was increased. Under the condition of separate co-cultivation in which transformed cloned cells could not make contact with A31-1-1 cells, no inhibitory effect was induced. We examined with a dye-transfer assay the formation of heterologous gap-junctional intercellular communication (GJIC), links between the transformed cells and A31-1-1 cells before and after focus formation. Heterologous GJIC was observed almost always before, but almost never after, focus formation. Using time-lapse photography to record the fate of transformed cloned cells that did not form foci in the co-cultivation, it was noted that most of them were living, but did not proliferate. These results suggested that focus formation of transformed cloned cells was inhibited by contact with non-transformed A31-1-1 cells.
3T3 Cells↗
Presence of molecular chaperones, heat shock cognate (Hsc) 70 and heat shock proteins (Hsp) 40, in the postsynaptic structures of rat brain.
The synaptic localization of molecular chaperones, heat shock cognate protein 70 (Hsc70) and Hsp40, was investigated immunohistochemically in the normal rat brain. Postsynaptic density (PSD) fractions contained a constitutive form of HSP70, heat shock cognate protein 70 (Hsc70 or p73) but not inducible form of HSP70 (p72). The immunoreactivities of Hsc70 (p73) were distributed throughout the rat brain, in neuronal somata, dendrites and axons. Their immunoreactivity in neurons was localized in the cytoplasmic matrix, dendrites, and spines at the electron microscopic level. Presynaptic terminals, but less frequently than postsynaptic staining, were also reactive. Postsynaptic areas immediately beneath the synaptic contact or PSDs were immunoreactive for Hsc70. The Hsp40 was highly concentrated in PSD fractions. The staining of Hsp40 immunoreactivity was punctate and distributed widely in the brain. Hsp40 immunoreactivity was localized in dendritic spines, especially in the subsynaptic web, with weak staining of PSDs at the electron microscopic level. Double immunofluorescent staining and confocal microscopy revealed that Hsc70 and Hsp40 were co-localized on somata and neuronal processes of cultured cerebral neurons, on which synaptophysin immunoreactive spots were scattered. These results suggest that Hsp40 and Hsc70 are co-localized at postsynaptic sites and postsynaptic chaperone activity may be mediated by these two heat shock proteins.
Animals↗
Predictability of dielectric properties for ischemic injury of the skeletal muscle before reperfusion.
OBJECTIVE: The purpose of this study is to assess whether or not dielectric properties could predict the severity of ischemic injury of the skeletal muscle before reperfusion to prevent the myonephropathic metabolic syndrome (MNMS). METHODS: Japanese White rabbits were anesthetized and their hind limbs were subjected to 0, 2, 4, and 6 h of ischemia and then 10 h of reperfusion (n = 4, 5, 6, and 6). Dielectric properties of the gastrocnemius muscle were measured and tan delta(m) and D were calculated from them. To assess ischemic injury, we also measured (a) creatine phosphate kinase (CPK) and aldolase, (b) spectrophotometric assay of triphenyltetrazolium chloride assay, and (c) histological evaluation by H & E staining, 10 h after reperfusion. RESULTS: The tan delta(m) increased and D decreased significantly compared with those in preischemia (P < 0.01). The tan delta(m) value just before reperfusion significantly correlated positively with the maximum value of CPK (CPK(max)) or the maximum value of aldolase (ALD(max)) (r = 0.73, 0.69) and negatively with %TTC (r = 0.66). The D value just prior to reperfusion significantly correlated negatively with CPK(max) and ALD(max) (r = 0.81, 0.86) and positively with %TTC (r = 0.79) after reperfusion, respectively. Histologically, skeletal muscle necrosis was detected in 11 out of 12 skeletal muscles with tan delta(m) values which were 3.70 or more and 11 out of 14 muscles with D values which were 1.47 or less. CONCLUSION: The severity of skeletal muscle ischemic injury can be evaluated before reperfusion by measuring the dielectric properties during ischemia.
Animals↗
Phase II trial of 5-fluorouracil and low-dose cisplatin in patients with squamous cell carcinoma of the esophagus.
A phase II study was conducted to determine the clinical efficacy and toxicity of 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) in patients with squamous cell carcinoma of the esophagus. Chemotherapy consisted of 5-FU at a dose of 330 mg/m2 per day, given as a 24-h infusion on days 1-7, and CDDP at a dose of 6 mg/m2 per day, given as a 2-h infusion on days 1-5. Either two or four cycles of chemotherapy were administered to 20 patients with stage III advanced esophageal carcinoma. All 20 patients were then assessed for response and toxicity. An objective response was demonstrated by 11 of the 20 patients, with one complete response (CR) and ten partial responses (PR), bringing the response rate to 55%, with a 95% confidence interval of 27% to 83%. Surgical resection of the tumor was performed in all 20 patients. One patient was found to have a grade 3 histological CR. The median survival of all the patients was 20.5 months, with a range of 4.5 to 48.0 months. Neutropenia and thrombocytopenia developed in five (25%) and two (10%) patients, respectively, and the nonhematologic toxicities were insignificant. The findings of this phase II study indicate that preoperative treatment using 5-FU and low-dose CDDP chemotherapy for patients with advanced esophageal carcinoma appears to achieve a high response rate after short-term administration without affecting the quality of sophisticated lymph node dissection.
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