Iatrogenic keratectasia after phototherapeutic keratectomy.
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Publications and source records attributed to K Ono.
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PURPOSE: To assess the luminal morphology of the extracranial internal carotid artery at three-dimensional (3D) computed tomographic (CT) angiography and how this factor affects measurement of maximum carotid arterial stenoses at conventional intraarterial digital subtraction angiography (DSA). MATERIALS AND METHODS: Prospectively, conventional intraarterial DSA and 3D CT angiography were performed in 42 carotid arteries in 21 patients with suspected carotid artery disease. The longest axis length-perpendicular axis length (L/P) ratios of the arterial lumen on the cross-sectional images at the most stenotic area and distal nonstenotic area were analyzed by acquiring multiplanar reconstruction (MPR) images at 3D CT angiography. The maximum stenosis was measured at each modality with North American Symptomatic Carotid Endarterectomy Trial criteria. RESULTS: The L/P ratios in the most stenotic areas ranged from 1.0 to 3.2 (mean, 1.5 +/- 0.5 [SD]). The mean difference in maximum percentage of stenosis between the two modalities for L/P ratios of 2.0 or greater was significantly greater than that for L/P ratios of less than 1.5 (P < .05). Three carotid arteries with 70%-99% stenosis, with grades determined only with 3D CT angiography, had L/P ratios of 2.0 or greater. CONCLUSION: On MPR images at 3D CT angiography, the lumen of extracranial internal carotid artery stenosis showed a wide range of shapes. When a carotid artery has a high L/P ratio, the luminal morphology of the carotid artery stenosis may affect the assessment of maximum stenosis of the internal carotid artery at conventional DSA.
PURPOSE: To assess the usefulness of intraarterial computed tomographic (CT) angiography in conjunction with digital subtraction angiography (DSA) by using a combined CT and angiographic unit in the preoperative evaluation of intracranial aneurysms. MATERIALS AND METHODS: Prospectively, 22 patients with or without subarachnoid hemorrhage underwent CT angiography in conjunction with DSA. Two radiologists independently evaluated DSA and CT angiographic images. Referring neurosurgeons were questioned as to how the additional information provided by CT angiography changed patient treatment. RESULTS: Intraarterial CT angiography was superior to DSA for use in aneurysm detection in three (12%) of 26 aneurysms and for delineation of aneurysm shape, neck, and location in more than half. In 14 (64%) of 22 patients, CT angiography demonstrated 18 additional findings: a very small aneurysm (n = 2), aneurysm shape and neck (n = 6), relationship of the aneurysm to adjacent arteries or bone structure (n = 8), and branches deriving from the aneurysm (n = 2). In four (27%) of 15 patients who underwent surgery or embolization, additional information obtained at CT angiography affected the treatment. CT angiography failed to clearly demonstrate an aneurysm adjacent to bone structures and small perforators, which were derived from the parent artery. CONCLUSION: Intraarterial CT angiography is useful for preoperative evaluation of intracranial aneurysms as a supplement to DSA.
Tristetraprolin (TTP) is a zinc finger protein that has been implicated in the control of tumor necrosis factor (TNF) mRNA stability. We show here that TTP protein has a suppressive effect on promoter elements from TNF-alpha and interleukin-8 and that lipopolysaccharide (LPS) stimulation can release this suppression. The release in LPS-stimulated cells was found to be primarily mediated by the p38 pathway because activation of p38 is sufficient to remove the suppressive effect of TTP. Indeed, TTP seems to be a direct substrate of p38 in vivo since it is an excellent substrate of p38 in vitro, and mutation of potential phosphorylation sites in TTP prevents release of the suppression imposed on TNF transcription. We found TTP protein to be present at low levels in the resting macrophage cell line RAW 264.7 and to be quickly induced after LPS stimulation. The kinetics of TTP induction suggests a potential role of TTP as an important player in switching off LPS-induced genes after induction. In conclusion, TTP plays an important role in maintaining gene quiescence, and this quenching effect on transcription can be released by p38 phosphorylation of TTP.
Although apoptosis has been observed in macrophages during the course of infections, the mechanism of apoptosis in activated macrophages is not fully understood. This study shows that pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (ZVAD) or t-butyloxycarbonyl-Asp-fluoromethylketone (Boc-D) caused the death of lipopolysaccharide (LPS)-activated macrophages and RAW 264.7 cells with apoptotic features. The apoptosis was also observed in lipoprotein-treated bacteria but not in CpG oligonucleotide- or flagellin-treated macrophages, indicating a difference of cellular responses downstream of different Toll-like receptors. Consistent with the induction of cell death by pan-caspase inhibitors, no activation of known caspases was detected in LPS-ZVAD-treated cells, suggesting an involvement of unknown proapoptotic caspases in the cell death. ZVAD inhibited the activation of extracellular signal-regulated kinase (ERK) and p38 but not of nuclear factor (NF)-kappa B induced by LPS, suggesting that the ZVAD-sensitive molecule lies upstream of the ERK and p38 pathways but downstream of the divergent site of NF-kappa B and mitogen-activated protein kinases. Our results demonstrate that apoptosis of macrophages induced by LPS+ZVAD is independent from the known proapoptotic caspases and suggest that activity of an unidentified ZVAD-sensitive molecule(s) is involved in the survival of LPS-activated macrophages.
Cholinergic actions on subfornical organ (SFO) neurons in rat slice preparations were studied by using whole cell voltage- and current-clamp recordings. In the voltage-clamp recordings, carbachol and muscarine decreased the frequency of GABAergic inhibitory postsynaptic currents (IPSCs) in a dose-dependent manner, with no effect on the amplitudes or the time constants of miniature IPSCs. Meanwhile, carbachol did not influence the amplitude of the outward currents induced by GABA. Furthermore, carbachol and muscarine also elicited inward currents in a TTX-containing solution. From the current-voltage relationship, the reversal potential was estimated to be -7.1 mV. These carbachol-induced responses were antagonized by atropine. In the current-clamp recordings, carbachol depolarized the membrane with increased frequency of action potentials. These observations suggest that acetylcholine suppresses GABA release through muscarinic receptors located on the presynaptic terminals. Acetylcholine also directly affects the postsynaptic membrane through muscarinic receptors, by opening nonselective cation channels. A combination of these presynaptic and postsynaptic actions may enhance activation of SFO neurons by acetylcholine.
Oligodendrocyte precursor cells (OPCs) originate in multiple restricted regions of the developing central nervous system (CNS). Here, we focus on morphological changes of oligodendrocyte lineage cells and their cellular dynamics including cell motility and proliferation. Morphological studies with molecular markers for OPCs suggest distinct spatiotemporal patterns of OPC migration in vivo, which are directly demonstrated by application of exogenous fluorescent markers to OPCs. Extensive proliferation of OPCs in the CNS parenchyma is also demonstrated by pulse labeling of the cells with bromodeoxyuridine. The results strongly suggest that oligodendrocyte lineage cells are highly motile and actively proliferate with an elongated morphology. These data provide insights into the potential molecular mechanisms of OPC dispersal throughout the CNS.
The molecular mechanisms that govern the coordinated programs of axonogenesis and cell body migration of the cerebellar granule cell are not well understood. In Pax6 mutant rats (rSey2/rSey2), granule cells in the external germinal layer (EGL) fail to form parallel fiber axons and to migrate tangentially along these fibers despite normal expression of differentiation markers. In culture, mutant cells sprout multiple neurites with enlarged growth cones, suggesting that the absence of Pax6 function perturbs cytoskeletal organization. Some of these alterations are cell-autonomous and rescuable by ectopic expression of Pax6 but not by co-culture with wild-type EGL cells. Cell-autonomous control of cytoskeletal dynamics by Pax6 is independent of the ROCK-mediated Rho small GTPase pathway. We propose that in addition to its roles during early patterning of the CNS, Pax6 is involved in a novel regulatory step of cytoskeletal organization during polarization and migration of CNS neurons.
Allixin, a phytoalexin isolated from garlic, was induced by irradiating fresh garlic cloves with sunlight or UV light. Induced allixin was analyzed by HPLC, and the accumulated amounts of allixin were 3.1-6.3 microg/g under experimental conditions.
Atheroma appears as a very low signal intensity area on 2-dimensional time-of-flight (TOF) magnetic resonance (MR) images, and its components have various signal intensities on spin-echo (SE) images. The present study investigated atheroma of the carotid arteries in 37 subjects with risk factors (63+/-10 years of age; 19 men) by magnetic resonance imaging (MRI). On 2-dimensional (2D) TOF images, the carotid arteries were clearly demonstrated in all cases and atheroma was detected in 23 patients. The most common location of atheroma was at the origin of the internal carotid artery. There was vascular remodeling in all patients with atheroma. 2D-TOF images showed 97% agreement with ultrasonography. SE images clearly demonstrated atheroma in all 23 patients with atheroma. All patients with atheroma showing high signal intensity on T1-weighted images had hyperlipidemia. These findings indicate that the 2D-TOF imaging method is useful for detecting atheroma and SE-images are useful for its characterization.
The presence of left atrial thrombus (LAT) is associated with an increased risk of embolic stroke. However, it has yet to be established definitively whether low-intensity warfarin therapy (INR: 1.5-2.0) can prevent LAT formation in patients with nonvalvular atrial fibrillation (NVAF). The present study analyzed the clinical and transesophageal echocardiography (TEE) features of 123 such patients to identify risk factors for LAT formation and the efficacy of prophylactic low-intensity warfarin therapy. Left atrial thrombi were found in 35 patients (28%) in whom systemic hypertension (49% vs 23%; p<0.01) and ischemic heart disease (17% vs 3%; p<0.01) were more frequent. Left ventricular ejection fraction (54+/-14% vs 60+/-11%; p<0.05), left ventricular end-diastolic dimension (51+/-7 mm vs 48+/-5 mm; p<0.05), spontaneous echo contrast (2.2+/-0.7 vs 1.4+/-0.9; p<0.01), left atrial diameter (50+/-6 mm vs 43+/-7 mm; p<0.01), left atrial appendage blood velocity (22.3+/-8.7 cm/s vs 37.2+/-21.5 cm/s; p<0.01) and the incidence of left ventricular hypertrophy (37% vs 15%; p<0.01) were also significantly different between the groups. Fourteen patients received continuous warfarin therapy (target INR: 1.5-2.0) and on the follow-up TEE study the left atrial thrombus resolved in 10 (71%). There were no thromboembolic events or major hemorrhagic complications in these patients, so it was concluded that low-intensity warfarin therapy is efficacious in treating LAT formation in patients with NVAF.
Although clinical evidence has suggested that dysregulated fatty acid metabolism is associated with atopic disorders, the molecular basis for such a correlation remains to be demonstrated. In the present study, we analyzed the fatty acid composition in peripheral blood cells of NC/Nga mice, a model for atopic dermatitis (AD). We found that arachidonic acid significantly accumulated in mice with the AD manifestation. In addition, the leucotriene B4-releasing ability upon calcium ionophore A23187 stimulation was potentiated in blood cells. An arachidonic acid accumulation was not apparent in the non-atopic BALB/c strain, but was still observed in healthy NC/Nga mice fed under specific pathogen-free conditions. These results indicate that a disturbed fatty acid metabolism in NC/Nga mice was not a trigger factor for their dermatitis development.
To identify which region of staphylococcal enterotoxin A (SEA) is responsible for the emetic activity, twelve synthetic peptides corresponding to the entire SEA amino acid sequence and their respective anti-peptide antibodies were prepared and tested. The anti-peptide antibodies were tested for neutralization of SEA-induced emesis in Suncus murinus (Shrew mouse). The results indicate that SEA-induced emesis was neutralized by the mixture of three anti-peptide antibodies to A-7 (corresponding to amino acid residues 121-140), A-8 (141-160) and A-9 (160-180). These findings suggest that the regions corresponding to residues 121-180 may be the epitopes responsible for the emetic activity of SEA.
Excitatory amino acid transporters play important roles in termination of glutamatergic neurotransmission and protection of neurons from the excitotoxicity of glutamate in the central nervous system. We herein report isolation of cDNA clones of two distinct excitatory amino acid transporters, GLT-1 and EAAC1, from canine brain cortex by PCR-based cloning, and characterization of these transporter subtypes. Canine GLT-1 and EAAC1 exhibited Na+-dependent glutamate transport with high affinities in a Xenopus oocyte expression system. Despite the similarity in transport kinetics and in the predicted primary structures, GLT-1, EAAC1, and the previously identified GLAST showed different sensitivities to several structural analogues of L-glutamate. In addition, transcripts of these transporter subtypes showed distinct regional distribution in the brain in RT-PCR analysis, suggesting that excitatory amino acid transporters have distinct physiological and pathophysiological roles in the brain.
Takagaki, M., Ono, K., Masunaga, S-I., Kinashi, Y., Oda, Y., Miyatake, S-I., Hashimoto, N., Powell, W., Sood, A. and Spielvogel, B. F. Boronated Dipeptide Borotrimethylglycylphenylalanine as a Potential Boron Carrier in Boron Neutron Capture Therapy for Malignant Brain Tumors. Radiat. Res. 156, 118-122 (2001).A boronated dipeptide, borotrimethylglycylphenylalanine (BGPA), was synthesized as a possible boron carrier for boron neutron capture therapy (BNCT) for malignant brain tumors. In vitro, at equal concentrations of (10)B in the extracellular medium, BGPA had the same effect in BNCT as p-boronophenylalanine (BPA). Boron analysis was carried out using prompt gamma-ray spectrometry and track-etch autoradiography. The tumor:blood and tumor:normal brain (10)B concentration ratios were 8.9 +/- 2.1 and 3.0 +/- 1.2, respectively, in rats bearing intracranial C6 gliosarcomas using alpha-particle track autoradiography. The IC(50), i.e. the dose capable of inhibiting the growth of C6 gliosarcoma cells by 50% after 3 days of incubation, was 5.9 x 10(-3) M BGPA, which is similar to that of 6.4 x 10(-3) M for BPA. The amide bond of BGPA is free from enzymatic attack, since it is protected from hydrolysis by the presence of a boron atom at the alpha-carbon position of glycine. These results suggest promise for the use of this agent for BNCT of malignant brain tumors. Further preclinical studies of BGPA are warranted, since BGPA has advantages over both BPA and BSH.
Strong depolarization pulses facilitate L-type Ca(2+) channels in various cell types including cardiac myocytes. The mechanisms underlying prepulse facilitation are controversial with respect to the requirements for channel subunits, cAMP-dependent protein kinase, and additional anchor proteins. The properties of voltage-dependent facilitation of the L-type Ca(2+) channel was studied in recombinant cardiac alpha(1) subunits with or without cardiac beta subunit, expressed in Chinese hamster fibroblast cells. The magnitude of voltage-dependent I(Ba) facilitation in the alpha(1) subunit channel is dependent on the duration of the prepulse as well as on the interval duration between prepulse and test pulse. The characteristics of this facilitation were not affected by coexpression of the beta subunit. These results indicate that cardiac alpha(1) subunits exhibit voltage-dependent facilitation because of their own intrinsic structure, independent of any other accessory subunit or additional regulatory proteins, and that cardiac beta subunits have no essential regulatory role at the onset or continuance of the voltage-dependent facilitation.
PURPOSE: To investigate the present state of blindness around the world. METHODS: The article reviews significant studies by WHO and literature on the topic. RESULTS: Current global estimates indicate that blindness affects close to 45 million people, with nine out of ten blind people living in developing countries. Two-thirds or more of all blindness is avoidable, in that the causes are preventable or treatable. Cataract is the major cause of blindness in the world and the number of cases is increasing. The second cause is glaucoma, and the third is trachoma. The extent of disability of blindness itself is very high compared to that of other illnesses. Also, in terms of the burden of diseases in society, blindness is a relatively huge problem in the developing world. CONCLUSIONS: Intervention should be focused on the factors that have the higheat possibility of change. Manpower development is the most important countermeasure. The aid required to support developing countries is what can make them stand on their own in long term ophthalmic care.
A 1-year-old infant with complete atrioventricular block was successfully treated with the pacemaker implantation using steroid-eluting epicardial pacing lead by the subxyphoid approach. Pacing threshold after implantation were measured frequently to use the function named "Capture management" of the generator (Medtronic: Kappa, Model 701). The postoperative pacing threshold were kept lower and stabilized after 5 weeks.