Prediction of transition to chronic atrial fibrillation in patients with paroxysmal atrial fibrillation.
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Age Factors↗
Biomedical subjects
H Sakamoto
Publications and source records attributed to H Sakamoto.
Crystallization and preliminary X-ray diffraction studies on the water soluble form of rat heme oxygenase-1 in complex with heme.
The water-soluble portion of rat heme oxygenase-1 which lacks 22 hydrophobic amino-acid residues at the C-terminus was expressed in E. coli and crystallized in the form of a complex with heme by the vapor-diffusion method using polyethylene glycol 4000 as the precipitant. The crystals belong to the tetragonal space group P41212 or P43212, with unit-cell dimensions of a = b = 56.7, c = 186. 7 A. The crystal contains one heme-heme oxygenase-1 complex in an asymmetric unit and diffracts X-rays beyond 3.0 A resolution with a conventional X-ray source.
Animals↗
A Janus kinase inhibitor, JAB, is an interferon-gamma-inducible gene and confers resistance to interferons.
It has been shown that interferons (IFNs) exert their signals through receptor-associated Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). However, molecular mechanism of regulation of IFN signaling has not been fully understood. We have reported novel cytokine-inducible SH2 protein (CIS) and JAK binding protein (JAB) family genes that can potentially modulate cytokine signaling. Here we report that JAB is strongly induced by IFN-gamma but not by IFN-beta in mouse myeloid leukemia M1 cells and NIH-3T3 fibroblasts. NIH-3T3 cells ectopically expressing JAB but not CIS3 lost responsiveness to the antiviral effect of IFN-beta and IFN-gamma. M1 leukemic cells stably expressing JAB were also resistant to IFN-gamma and IFN-beta-induced growth arrest. In both NIH-3T3 and M1 transformants expressing JAB, IFN-gamma did not induce tyrosine phosphorylation and DNA binding activity of STAT1. Moreover, IFN-gamma-induced activation of JAK1 and JAK2 and IFN-beta-induced JAK1 and Tyk2 activation were inhibited in NIH-3T3 JAB transformants. These results suggest that JAB inhibits IFN signaling by blocking JAK activity. We also found that IFN-resistant clones derived from LoVo cells and Daudi cells expressed high levels of JAB without stimulation. In IFN-resistant Daudi cells, IFN-induced STAT1 and JAK phosphorylation was partially reduced. Therefore, overexpression of JAB could be, at least in part, a mechanism of IFN resistance.
3T3 Cells↗
Production of parathyroid hormone-related peptide by synovial fibroblasts in human osteoarthritis.
Synovial fibroblasts from patients with osteoarthritis in culture produced parathyroid hormone-related peptide (PTHrP) on treatment with phorbol ester (TPA) in a dose- and time-dependent manner. The levels of PTHrP immunoreactivity in the conditioned medium of synovial fibroblast cultures were measured using specific PTHrP antibody. The maximum production was obtained at a concentration of 10(-8) M and 24 h after TPA treatment. But sensitivity to TPA of synovial fibroblasts differed among four patients from slight to marked. PTHrP production was also induced with inflammatory cytokines, such as 1 ng/ml of IL-1alpha, IL-1beta, IL-6 and TNF-alpha, and 10(-6) M prostaglandin E2, after 24 h treatment. The expression of PTHrP was confirmed by reverse-transcriptase polymerase chain reaction. Since the synovial fibroblasts isolated from osteoarthritic patients produce high levels of IL-6 and IL-8, typical cytokines produced in synovial fibroblasts, production of PTHrP may provide new insight into the pathophysiology of joint disorder.
Cells, Cultured↗
Colocalization of heparin and receptor binding sites on keratinocyte growth factor.
Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. FGFs are also known as heparin-binding growth factors because they bind to heparin and their physical and biological properties are modulated by heparin. Consistent with a role as a paracrine effector, KGF is produced by cells of mesenchymal origin but is active primarily, if not exclusively, on epithelial cells. KGF is involved in a variety of physiological processes, including proliferation, differentiation, wound healing, and cytoprotection. To identify regions in KGF that contribute to heparin and tyrosine kinase receptor interactions, nine peptides spanning defined motifs in the predicted structure of KGF were synthesized, and their heparin and receptor binding properties were analyzed. Peptides at the amino and carboxyl termini bound heparin, and one peptide showed relative binding comparable to that of KGF. Competitive binding studies showed that this peptide along with two other overlapping peptides specifically displaced KGF bound to the KGF receptor. These three peptides were also selectively recognized by a neutralizing monoclonal antibody against KGF, though only in the presence of heparin. Together, these data suggest that the sites for heparin and receptor binding both reside in the amino and carboxyl termini of KGF, which are spatially juxtaposed in the predicted three-dimensional structure of this molecule.
Amino Acid Sequence↗
Development of a three-electrode-lens drift tube for time-of-flight mass spectrometry.
A three-electrode-lens drift tube for time-of-flight mass spectrometry (TOF-MS) has been developed for utilizing a detector to observe photon-stimulated desorption (PSD). In spite of a small detection area, the detector has a high detection efficiency and durability to reactive gas atmosphere at high pressure. The TOF-MS performance of the drift tube was examined for PSD using single-bunch-mode synchrotron radiation on a dichlorosilane (SiH(2)Cl(2))-saturated Si(001) surface. The measured acceleration and focusing-voltage dependences of the time of flight, intensity and full width at half-maximum for the peak of H(+) and Cl(+) PSD ions are discussed in terms of the numerical calculations of ion trajectories and focusing characteristic of the drift tube.
Journal Article↗
Suppression of leukotriene formation in RBL-2H3 cells that overexpressed phospholipid hydroperoxide glutathione peroxidase.
The overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) by RBL-2H3 cells was used as the basis for an investigation of the effects of PHGPx on the formation of leukotrienes. The rates of production of leukotriene C4 (LTC4) and leukotriene B4 (LTB4) in cells that overexpressed PHGPx were 8 times lower than those in a control line of cells. The reduction in rates of production of leukotrienes apparently resulted from the increase in the PHGPx activity since control rates of formation of leukotrienes could be achieved in PHGPx-overexpressing cells upon inhibition of PHGPx activity by diethyl malate. The conversion of radioactively labeled arachidonic acid to intermediates in the lipoxygenase pathway, such as 5-hydroxyeicosatetraenoic acid (5-HETE), LTC4, and LTB4, was strongly inhibited in PHGPx-overexpressing cells that had been prelabeled with [14C]arachidonic acid. PHGPx apparently inactivated the 5-lipoxygenase that catalyzed the conversion of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) since 5-HPETE is a common precursor of 5-HETE, LTC4, and LTB4. The rates of formation of LTC4 and LTB4 in PHGPx-overexpressing cells returned to control rates upon the addition of a small amount of 12-HPETE. Flow cytometric analysis revealed that the rapid burst of formation of lipid hydroperoxides induced by A23187 was suppressed in PHGPx-overexpressing cells as compared with the control lines of cells. Subcellular fractionation analysis showed that the amount of PHGPx associated with nuclear fractions from PHGPx-overexpressing cells was 3.5 times higher than that from the control line of cells. These results indicate that PHGPx might be involved in inactivation of 5-lipoxygenase via reductions in levels of the fatty acid hydroperoxides that are required for the full activation of 5-lipoxygenase. Thus, in addition to its role as an antioxidant enzyme, PHGPx appears to have a novel function as a modulator of the production of leukotrienes.
Animals↗
Clinical role of soluble adhesion molecules during immunotherapy for perennial allergic rhinitis.
BACKGROUND: Soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) have recently been identified in serum samples from atopic patients, but their clinical significance in the treatment of allergic diseases remains to be established. OBJECTIVE: To study the clinical roles of serum sICAM-1 and sVCAM-1 during immunotherapy for perennial allergic rhinitis. DESIGN: Our study included 30 nonatopic volunteers and 60 patients with perennial allergic rhinitis due to Dermatophagoides farinae. The 60 patients had been treated for variable periods (7.3+/-3.0 years [mean+/-SD]) with immunotherapy using a standardized D. farinae antigen. Serum samples were collected from each patient before and after immunotherapy to determine sICAM-1 and sVCAM-1 with sandwich enzyme-linked immunosorbent assays. RESULTS: Serum levels of sICAM-1 in the patients before immunotherapy were higher than those in the nonatopic volunteers (P<.001). The levels of sICAM-1 in the patients' serum samples were decreased significantly after immunotherapy (P<.001), and the percentage of the decrease in the sICAM-1 levels was significantly correlated with the duration of immunotherapy (P=.04) and with the percentage of the decrease in symptom scores (P<.001). The levels of sVCAM-1 in the serum samples from the patients with severe symptoms were significantly higher before immunotherapy than those in the nonatopic volunteers (P=.002) and were significantly decreased after immunotherapy (P=.05). However, the percentage of the decrease in the sVCAM-1 levels was not correlated with the duration of immunotherapy (P=.89) or with the percentage of the decrease in symptom scores (P=.89). CONCLUSION: Decrease in serum sICAM-1 levels during immunotherapy is probably involved in the working mechanisms of immunotherapy, but modulation of serum sVCAM-1 levels is not likely related to the clinical effect of immunotherapy.
Adult↗
Effects of platelet release products on neutrophilic Fc gamma receptors.
Large and small macromolecular activators of phagocytosis from platelets (I-MAPP and s-MAPP, respectively), which function via the neutrophilic Fc gamma receptors (Fc gammaR) were refined from platelet release products by gel filtration and affinity chromatography with the use of an anti transferrin antibody column and the mechanism of phagocytosis activation was investigated. Flow cytometry revealed that 1-MAPP and s-MAPP did not increase the expression of neutrophilic Fc gammaRII (CD32) and Fc gammaRIII (CD16) antigens, whereas rosette formation of neutrophils with rabbit IgG-sensitized sheep erythrocytes (EA) in the presence of anti Fc gammaR antibodies suggested that both MAPPs increase the binding ability of Fc gammaRII. On the other hand, the enhancing effect of I-MAPP and s-MAPP on neutrophilic phagocytosis disappeared with the increase in phagocytosis by the phosphate-buffered saline control neutrophils when they were centrifuged with EA before incubation for phagocytosis. The enhanced phagocytosis, both by the two MAPPs and centrifugation, was canceled by treatment of the neutrophils with anti-CD32 Fab. The phagocytosis activatory effects of MAPP on neutrophils were canceled by anti-CD71 monoclonal antibody but not by transferrin.
Adult↗
Clinical significance of ventricular size in shunted-hydrocephalic children.
For maintaining the intracranial buffering capacity against shunt obstruction, we tried to seek the most suitable size of the lateral ventricles in hydrocephalic children. Thirty-seven shunted-hydrocephalic children who required emergent revision of the shunt were analyzed. At the time of shunt obstruction, the lateral ventricle remained small (0.35 or less than 0.35 on the Evans' index) in 13 patients (Slit-like group), but it enlarged (more than 0.35 on the Evans' index) in 24 patients (Dilated group). The mean age in the Slit-like group was significantly older than in the Dilated group and there was no patient younger than 3 years in the Slit-like group. Compared with the Dilated group, the Slit-like group showed significantly rapid deterioration into lethargy after shunt obstruction. Also, at the time of obstruction CT scans showed a significantly higher rate of narrowing of the ambient cistern. While the shunt was working well before shunt obstruction, the Evans' index was less than 0.33 in all patients of the Slit-like group. In conclusion, because small ventricles after shunt strongly suggest the presence of ventricular tautness, the lateral ventricular size should be maintained at more than 0.33 on the Evans' index in shunted children at an age of 3 or more than 3 years.
Adolescent↗
Relatively high F-18 fluorodeoxyglucose uptake in paranasal sinus aspergillosis: a PET study.
We report a case of maxillary sinus (MS) aspergillosis studied by positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and by 67Ga-citrate (Ga) single photon emission computed tomography (SPECT). The FDG uptake existed in the lesion and along the inflammatory edematous mucous membrane of the MS. Ga uptake occurred not only in the lesion and in the mucous membrane but also in the MS. Relative quantification, the standardized uptake value (SUV) of the lesion showed relatively high FDG uptake (3.7). But in other reports, many malignant head and neck tumors had a SUV below 3.7. It was thought to be difficult to differentiate between aspergillosis and malignant head and neck tumors by FDG-PET.
Aged↗
Ultrastructural and permeability features of microvessels in the olfactory bulbs of SAM mice.
The ultrastructural features of microvessels showing increased permeability to intravenously injected horseradish peroxidase (HRP) were examined in the olfactory bulbs of senescence-accelerated prone mice (SAMP8), which showed age-related deficits in learning and memory, and senescence-accelerated resistant mice (SAMR1), which did not show the age-related deficits. HRP was visualized with tetramethyl benzidine (TMB) and diaminobenzidine (DAB) for light and electron microscopic examination, respectively. In the olfactory bulbs of 13-month-old SAMP8 mice, the staining reaction with TMB for HRP appeared in the neuropil of central area (granule cell layer and subependymal layer), in the pia mater and in the vascular wall. Some vessels located in the central area showed several changes observed at the ultrastructural level. The cytoplasm of the endothelial cells, especially in the arterioles, was segmentally thickened and contained numerous vesicles and vacuoles, some of which were HRP positive. The endothelial cell surface was occasionally undulated with microvillous protrusions. Membranous inclusions within the basal lamina, suggesting the cellular (presumably pericytal) degeneration, were frequently observed, especially in venules. The collagen deposits were occasionally observed in the subendothelial space of some vessels. Perivascular cells with vacuolated inclusions or lipid-like droplets were present around some vessels in the central area of the olfactory bulbs of aged SAMP8 mice. On the other hand, in the microvessels located in the areas negative for HRP-TMB reaction, except the vessel walls, the cytoplasm of the endothelial cells with smooth luminal surface was flattened and some vesicles located there contained HRP-DAB reaction product. Weak staining reaction with TMB for HRP appeared also in the central area of the olfactory bulbs of 3-month-old SAMP8 mice and 3- and 13-month-old SAMR1 mice. The cytoplasm of the endothelial cells in the olfactory bulbs of these mice was focally thickened and contained some cytoplasmic vesicles. Occasionally, the endothelial cell surface was moderately undulated with few microvillous protrusions. Membranous inclusions within the basal lamina were not observed in these animals. These findings indicate that the endothelial cells and pericytes in some vessels located in the central area of the olfactory bulb of aged SAMP8 mice, which show staining reaction with TMB for HRP, are ultrastructurally changed, suggesting their altered functions.
Age Factors↗
Goblet cell carcinoid of the appendix endoscopically diagnosed and examined with p53 immunostaining.
We report a case of a 62-year-old woman with goblet cell carcinoid of the appendix. She was admitted to our hospital in September 1994 after the discovery of liver tumors. After admission, a tumor in the right kidney and multiple tumors in the liver were found. She was diagnosed with renal cell cancer and metastasis to the liver and underwent excision of the kidney and enucleation of the largest liver tumor. Histological examination revealed that the liver tumor was a metastatic carcinoid tumor. As carcinoid tumors have frequently been found in the appendix, endoscopic examination was performed and a lesion was found in the appendix by colonoscopy. As predicted, the biopsy specimen was a carcinoid tumor, and she underwent an appendectomy. Histologically, the tumor was a goblet cell carcinoid. Goblet cell carcinoid is a rather rare neoplasm that has the histologic features of both carcinoids and adenocarcinoma. Forty-two cases of goblet cell carcinoid of the appendix have been reported thus far in Japan. However, few were diagnosed via endoscopic examination before surgical operation. We also carried out an immunohistochemical study with anti p53 antibody on the goblet cell carcinoid tumor of the appendix. Most tumor cells were strongly positive, while in three benign carcinoid tumors investigated simultaneously they were negative. These findings suggest that goblet cell carcinoid has an aggressive phenotype compared with benign carcinoid tumors.
Appendiceal Neoplasms↗
An additional variant of the persistent primitive trigeminal artery: accessory meningeal artery--antero-superior cerebellar artery anastomosis associated with moyamoya disease.
Persistent embryological carotid-basilar anastomoses are rare. There has been no report on persistent anastomosis between the accessory meningeal artery and the antero-superior cerebellar artery. We describe a 3-year-old boy with moyamoya disease manifesting such a congenital vascular anomaly, namely, a large anastomosis between the accessory meningeal artery and the antero-superior cerebellar artery associated with marked hypoplasia of the basilar artery. This persistent vascular anomaly is considered embryologically as an additional variant of the persistent primitive trigeminal artery, i.e., a "stapedo-trigemino-cerebellar" variant.
Basilar Artery↗
Anxiolytic-like effects of perospirone, a novel serotonin-2 and dopamine-2 antagonist (SDA)-type antipsychotic agent.
We examined the anxiolytic potential of perospirone, a novel serotonin-2 and dopamine-2 antagonist (SDA)-type antipsychotic agent, and compared its effects with those of the standard anxiolytic diazepam and the conventional antipsychotic haloperidol by using conditioned defensive burying (CDB) and social interaction (SI) tests in rats. The tests were conducted 1 h after oral administration of the drug. Diazepam inhibited CDB specifically directed toward a probe previously associated with brief electric shock and increased the time spent in SI by pairs of naive rats in a brightly illuminated novel environment. Perospirone mimicked the effects of diazepam by dose dependently suppressing CDB and facilitating SI. In contrast, haloperidol failed to inhibit CDB or increase SI. These results suggested that, unlike the conventional antipsychotic haloperidol, perospirone exerts anxiolytic-like effects in animal models with different motivational and emotional states. A braoder efficacy of perospirone for the treatment of anxiety and related symptoms in schizophrenia is discussed.
Aggression↗
Effect of acyclovir on bronchoconstriction and urinary leukotriene E4 excretion in aspirin-induced asthma.
BACKGROUND: Acyclovir (9-[2-hydroxyethoxymethyl] guanine), an inhibitor of the DNA polymerase of the herpes virus, has been reported to exhibit pharmacologic activity other than antiviral activity, including antiasthmatic effects. OBJECTIVE: This study was designed to investigate the protective effect of acyclovir on airway responsiveness to the sulpyrine provocation test and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary leukotriene E4 (u-LTE4 ), a marker of cysteinyl leukotriene (LT) overproduction that participates in the pathogenesis of aspirin-induced asthma. METHODS: We assessed the effects of pretreatment with acyclovir on bronchoconstriction precipitated by inhalation of sulpyrine in 16 adult patients with mild or moderate aspirin-induced asthma; those who were in stable clinical condition and were hyperresponsive to the sulpyrine provocation test were allocated to this study. A double-blind, randomized, cross-over design was used. u-LTE4 was measured by a combined reverse-phase HPLC enzyme immunoassay. RESULTS: Acyclovir protects against aspirin-induced attacks of asthma through mechanisms unrelated to its bronchodilator property but related to the improvement of bronchial hypersensitivity to sulpyrine; protection was nearly complete in all patients (P <.0001). By contrast, after acyclovir, the maximum level of u-LTE4 in patients was significantly lower than that in control subjects (P <. 01). CONCLUSION: Our results suggest that acyclovir is not only an antiviral drug but also an inhibitor of analgesic-induced bronchoconstriction, probably acting by inhibiting the release of cysteinyl LTs.
Acyclovir↗
Antihypertensive agents prevent nephrosclerosis and left ventricular hypertrophy induced in rats by prolonged inhibition of nitric oxide synthesis.
We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n = 10-12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 +/- 0.65 v 0.05 +/- 0.02 mg/day/100 g in control), and the area of the left ventricular wall (83.3 +/- 3.0 v 69.8 +/- 1.8 mm2 in control). Nephrosclerosis and myocardial interstitial fibrosis were documented histologically. The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 +/- 1.8 mm2), the albuminuria (0.05 +/- 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in rats produced nephrosclerosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of calcium channels in preventing hypertensive tissue injury.
Amlodipine↗
Cromolyn sodium prevents bronchoconstriction and urinary LTE4 excretion in aspirin-induced asthma.
BACKGROUND: Inhalation of cromolyn sodium protects against sulpyrine-induced bronchoconstriction and prevents urinary leukotriene E4 (u-LTE4) excretion in aspirin-induced asthma. OBJECTIVE: This study was designed to investigate the protective effect of cromolyn sodium on airway responsiveness to the sulpyrine provocation test, and to investigate whether this protective activity is associated with a reduction in aspirin-induced urinary excretion of LTE4, a marker of the cysteinyl leukotriene overproduction that participates in the pathogenesis of aspirin-induced asthma. METHODS: We evaluated the effects of pretreatment with cromolyn sodium on bronchoconstriction precipitated by inhalation of sulpyrine in ten adult patients with mild aspirin-induced asthma. Those who were in stable clinical condition and were hyperresponsive to sulpyrine provocation test were allocated to this study. Urinary leukotriene E4 was measured using combined reverse phase high performance liquid chromatography (rp-HPLC)/enzyme immunoassay. RESULTS: Inhaled cromolyn sodium protects against aspirin-induced attacks of asthma through mechanisms not related to the bronchodilator property, but related to the improvement of the bronchial hypersensitivity, almost completely in all patients (P < .001). By contrast, after cromolyn sodium the maximum level of u-LTE4 was significantly lower than control (P < .05). CONCLUSION: Our results suggest for the first time that inhaled cromolyn sodium is one of the most useful inhibitors of aspirin-induced bronchoconstriction, probably acting by inhibiting the release of cysteinyl leukotrienes, and possibly other chemical mediators, by bronchial inflammatory cells.
Administration, Inhalation↗