Search PubMed⌕ Search

Biomedical subjects

S Naito

Publications and source records attributed to S Naito.

At least 163 records · Page 9Linked to original sources

Significance of angiogenic factors in liver metastatic tumors originating from colorectal cancers.

We examined the expression of vascular endothelial growth factor (VEGF) and microvessel counts expressed by CD34 staining in 39 patients with primary and 44 patients with metastatic liver tumors of metastatic colorectal carcinoma, and 29 patients with nonmetastatic colorectal carcinoma as control in order to determine their value in the evaluation of prognosis and recurrence after hepatectomy. Microvessel counts in primary colorectal carcinomas of the metastatic group were significantly higher than those in control (P<0.05). Neither factor correlated with any clinicopathological feature of primary or metastatic liver carcinomas. Higher microvessel counts in metastatic liver tumors tended to be associated with a shorter disease-free interval to second recurrence in the remaining liver (P = 0.069) and were significantly associated with poor prognosis after hepatectomy (P<0.05). We conclude that microvessel count is an important marker of liver metastasis and prognosis in patients with colorectal carcinoma treated with hepatectomy.

Adult↗

Inducible nitric oxide synthase is expressed in granuloma pyogenicum.

It is known that granuloma pyogenicum (GP) grows rapidly but cherry angioma (CA) does not, although they show the same histological features of hyperplasia of the capillary vessels. Although some cytokines have been thought to be angiogenic factors, a nitric oxide (NO) synthase-dependent effector mechanism is reported to be involved in macrophage-derived angiogenesis in humans. Under the hypothesis that this mechanism is also involved in the more rapid growth of GP, we examined the expression of inducible NO synthase (iNOS) in GP as compared with that in CA. The expression of iNOS mRNA was detected in GP, but not in CA, by reverse transcription-polymerase chain reaction (RT-PCR) analysis. In situ hybridization (ISH) demonstrated iNOS mRNA expression in endothelial cells and to a lesser extent round cells and spindle cells in the myxomatous stroma in GP. Immunohistochemical study showed that iNOS protein was expressed in endothelial cells, infiltrating round cells and spindle cells in the stroma in GP. These results suggested that a NOS-dependent mechanism may be involved in angiogenesis and the rapid growth of GP.

Adult↗

Isolation of an Arabidopsis thaliana mutant in which accumulation of cucumber mosaic virus coat protein is delayed.

Cucumber mosaic virus (CMV) is known to systemically infect Arabidopsis thaliana ecotype Columbia plants. In order to identify the host factors involved in the multiplication of CMV, we isolated an A. thaliana mutant in which the accumulation of the coat protein (CP) of CMV in upper uninoculated leaves was delayed. Genetic analyses suggested that the phenotype of delayed accumulation of CMV CP in the mutant plants was caused by a single, nuclear and recessive mutation designated cum1-1, which was located on chromosome IV. The cum1-1 mutation did not affect the multiplication of tobacco mosaic virus, turnip crinkle virus or turnip yellow mosaic virus, which belong to different taxonomic groups from CMV. Accumulation of CMV CP in the inoculated leaves of cum1-1 plants was also delayed either when CMV virion or CMV virion RNA was inoculated. On the other hand, when cum1-1 and the wild-type Col-0 protoplasts were inoculated with CMV virion RNA by electroporation, the accumulations of CMV-related RNAs and the coat protein were similar. These results suggest that the cum1-1 mutation did not affect the uncoating of CMV virion and subsequent replication in an initially infected cell but affected the spreading of CMV within an infected leaf, possibly the cell-to-cell movement of CMV in a virus-specific manner.

Arabidopsis↗

Characterization of an Arabidopsis thaliana mutant that has a defect in ABA accumulation: ABA-dependent and ABA-independent accumulation of free amino acids during dehydration.

In an attempt to elucidate the physiological role of ABA in seed dormancy and the adaptive response to dehydration, we isolated an ABA-deficient mutant of Arabidopsis thaliana (L.) Heynh. which germinated in the presence of a gibberellin biosynthetic inhibitor. Genetic analysis showed this mutation is a new allele of a recently reported locus aba2, and therefore has been designated aba2-2. The levels of endogenous ABA in fresh and dehydrated tissues of the aba2-2 mutant were highly reduced compared to those of wild-type plants. As a consequence, aba2-2 plants wilt and produce seeds with reduced dormancy. Dark germinated seedlings of the aba2-2 mutant showed true leaves, which were not observed in those of the wild type, indicating that aba2-2 embryos grew precociously during seed maturation. In the dehydrated tissues of the wild-type plants, the levels of free proline, isoleucine and leucine were elevated to a content approximately 100-fold higher than those in fresh tissues. In contrast to the wild-type plants, dehydration-induced accumulation of proline was highly suppressed in the aba2-2 mutant plants while that of leucine and isoleucine accumulated. Furthermore, exogenous application of ABA to wild-type plants promoted accumulation of free proline, but not leucine nor isoleucine. These results suggest that dehydration-induced accumulation of free leucine and isoleucine is achieved independent of ABA.

Abscisic Acid↗

ND-2001 suppresses lung metastasis of human renal cancer cells in athymic mice.

Explants of highly metastatic human renal cell carcinoma SN12Cpm6 cells in athymic mice were treated with sodium D-glucaro-delta-lactam (sodium 5-amino-5-deoxy-D-glucosaccharic acid-delta-lactam; ND-2001). ND-2001 (50 micrograms/ml) caused 78% inhibition of lung metastasis of SN12Cpm6 cells (two of five animals remaining metastasis free). The in vitro tumor cell invasion assay showed that ND-2001 (100 micrograms/ml) suppressed the invasive activity of SN12Cpm6 cells to Matrigel matrix at an inhibition rate of 72%. These results suggest that ND-2001 may be a new anti-metastatic drug against human cancer cells.

Animals↗

Antiproliferative effect of calcitriol on human prostatic cancer cell lines: unrelated to the expression of major histocompatibility complex antigens or intercellular adhesion molecule-1 (ICAM-1).

BACKGROUND: In addition to its role in calcium and phosphorus metabolism, calcitriol (1,25-dihydroxyvitamin D3; 1,25-D3) demonstrates multiple effects on cell proliferation/differentiation by expressing major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1). It has recently been reported that 1,25-D3 inhibits the growth of prostatic cancer (PCa) cells. In this study we examined the effect of 1,25-D3 on both the growth and expression of HLA-ABC, HLA-DR and ICAM-1 antigens in PCa cells. METHODS: Four human PCa cell lines (PC-3, PPC-1, ALVA-41 and ALVA-101) were examined. The cell numbers were enumerated, and the effects of interferon-y (IFN-gamma) and 1,25-D3 on the expression of HLA-ABC, HLA-DR and ICAM-1 were quantitated by flow cytometry. RESULTS: A dose-dependent antiproliferative effect of 1,25-D3 was found in all PCa cells lines except ALVA-41.1,25-D3 was approximately 10 times as potent as its analogue 24,25-dihydroxyvitamin D3 in inhibiting the growth of PC-3 cells. Also, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-D3 receptor, indicating that the antiproliferative effect may require a receptor-ligand interaction. HLA-ABC was expressed in PC-3, ALVA-41 and ALVA-101, but not in PPC-1 cells, while HLA-DR was not expressed on any of the tested cells. IFN-gammacould enhance or induce HLA-ABC but not HLA-DR expression in the tested cells. ICAM-1 was expressed in all cells and slightly upregulated by IFN-gamma. CONCLUSION: In this study 1,25-D3 had an antiproliferative effect on 3 of the 4 examined PCa cell lines.

24,25-Dihydroxyvitamin D 3↗

Novel form of atrial tachycardia originating at the atrioventricular annulus.

We report two patients with reentrant atrial tachycardia that originated at the AV annulus. Atrial tachycardia originated in the posterior portion of mitral annulus in one patient (case 1) and the posterolateral portion of tricuspid annulus in one patient (case 2). Tachycardia was successfully eliminated by RF catheter ablation in both patients, with the catheter placed underneath the mitral valve in case 1 and on the tricuspid annulus in case 2. Spiky potentials were recorded in the diastolic phase of the atrium during tachycardia at the sites of successful ablation. Spiky potentials were also recorded after atrial electrogram during sinus rhythm, and showed decremental properties during atrial pacing. An accelerated atrial rhythm was observed during RF application, and tachycardia could not be induced after ablation in either patient. Tachycardia in these patients seemed to be due to reentrant tachycardia originating in the accessory AV node (Mahaim fiber) without ventricular connection.

Action Potentials↗

Simple electrocardiographic criteria for identifying the site of origin of focal right atrial tachycardia.

UNLABELLED: To construct an algorithm for identifying the precise site of origin of focal right atrial tachycardia (RAT), we analyzed the P wave configuration in 32 patients with RAT who underwent successful radiofrequency catheter ablation. The RA was divided into three areas in the left anterior oblique view: superolateral, inferolateral, and inferomedial. There were 17 RATs arising from the crista terminalis (CT-AT), 12 from the tricuspid annulus (TA-AT), and 3 from the septum away from the TA (Sep-AT). A negative P wave in lead aVR identified CT-AT with a sensitivity (sens) of 100% and a specificity (spec) of 93%. In CT-ATs, positive P waves in the inferior leads differentiated superolateral AT from inferolateral AT with a sens of 86% and a spec of 100%. In any type of AT with inferomedial or inferolateral foci, the P wave deflections in at least one of the inferior leads was negative, and negative P waves in leads V5 and V6 identified inferomedial AT with a sens of 92% and a spec of 100%. In ATs near the apex of Koch's triangle, the P wave duration in the inferior leads was shorter than during sinus rhythm. CONCLUSIONS: (1) the P wave configuration in lead aVR can easily differentiate CT-AT from TA-AT and Sep-AT; (2) the P wave configuration in the inferior leads helps to determine a superior versus inferior origin in any type of AT; (3) in inferior AT, the P wave polarity in leads V5 and V6 is useful in determining a lateral versus medial origin; (4) this algorithm can predict accurately the origin of AT.

Algorithms↗

Retrograde Purkinje potential activation during sinus rhythm following catheter ablation of idiopathic left ventricular tachycardia.

We describe two patients with idiopathic left ventricular tachycardia that were cured by radiofrequency catheter ablation. Tachycardia was inducible by ventricular stimulation and was verapamil sensitive. Two distinct presystolic potentials (P1 and P2) were recorded during tachycardia in the mid-septal or inferoapical area, but only one potential (P2) was recorded during sinus rhythm. After catheter ablation at this site, the P1 potential was noted after the QRS complex during sinus rhythm, while the P2 was still observed before the QRS complex. The P1 potential showed a decremental property during atrial or ventricular pacing. These data suggest that Purkinje tissue with decremental properties was responsible for the tachycardia mechanism, and that the reentry circuit involving this tissue is likely to be of considerable size.

Anti-Arrhythmia Agents↗

Verapamil-sensitive left anterior fascicular ventricular tachycardia: results of radiofrequency ablation in six patients.

INTRODUCTION: Verapamil-sensitive left ventricular tachycardia (VT) with a right bundle branch block (RBBB) configuration and left-axis deviation has been demonstrated to arise from the left posterior fascicle, and can be cured by catheter ablation guided by Purkinje potentials. Verapamil-sensitive VT with an RBBB configuration and right-axis deviation is rare, and may originate in the left anterior fascicle. METHODS AND RESULTS: Six patients (five men and one woman, mean age 54+/-15 years) with a history of sustained VT with an RBBB configuration and right-axis deviation underwent electrophysiologic study and radiofrequency (RF) ablation. VT was slowed and terminated by intravenous administration of verapamil in all six patients. Left ventricular endocardial mapping during VT identified the earliest ventricular activation in the anterolateral wall of the left ventricle in all patients. RF current delivered to this site suppressed the VT in three patients (ablation at the VT exit). The fused Purkinje potential was recorded at that site, and preceded the QRS complex by 35, 30, and 20 msec, with pace mapping showing an optimal match between the paced rhythm and the clinical VT. In the remaining three patients, RF catheter ablation at the site of the earliest ventricular activation was unsuccessful. In these three patients, Purkinje potential was recorded in the diastolic phase during VT at the mid-anterior left ventricular septum. The Purkinje potential preceded the QRS during VT by 66, 56, and 63 msec, and catheter ablation at these sites was successful (ablation at the zone of slow conduction). During 19 to 46 months of follow-up (mean 32+/-9 months), one patient in the group of ablation at the VT exit had sustained VT with a left bundle branch block configuration and an inferior axis, and one patient in the group of ablation at the zone of slow conduction experienced typical idiopathic VT with an RBBB configuration and left-axis deviation. CONCLUSION: Verapamil-sensitive VT with an RBBB configuration and right-axis deviation originates close to the anterior fascicle. RF catheter ablation can be performed successfully from the VT exit site or the zone of slow conduction where the Purkinje potential was recorded in the diastolic phase.

Adult↗

Selected slow pathway ablation in a patient with corrected transposition of the great arteries and atrioventricular nodal reentrant tachycardia.

We report the first known case of AV nodal reentrant tachycardia (AVNRT) associated with a corrected transposition of the great arteries to be treated successfully by ablation of the slow pathway. Triple AV nodal pathways were observed in the anterograde direction and two types of AVNRT were induced. Input of the fast pathway to the AV node was located at the anterior portion of the left-sided AV annulus, while the input of the intermediate and slow pathways was located at the anteroseptal portion of the right-sided AV annulus. Radiofrequency energy ablation at the right anteroseptal site eliminated the intermediate and slow pathways.

Atrioventricular Node↗

Isolation of an Arabidopsis thaliana mutant in which the multiplication of both cucumber mosaic virus and turnip crinkle virus is affected.

During the systemic infection of plants by viruses, host factors play an important role in supporting virus multiplication. To identify and characterize the host factors involved in this process, we isolated an Arabidopsis thaliana mutant named RB663, in which accumulation of the coat protein (CP) of cucumber mosaic virus (CMV) in upper uninoculated leaves was delayed. Genetic analyses suggested that the phenotype of delayed accumulation of CMV CP in RB663 plants was controlled by a monogenic, recessive mutation designated cum2-1, which is located on chromosome III and is distinct from the previously characterized cum1 mutation. Multiplication of CMV was delayed in inoculated leaves of RB663 plants, whereas the multiplication in RB663 protoplasts was similar to that in wild-type protoplasts. This suggests that the cum2-1 mutation affects the cell-to-cell movement of CMV rather than CMV replication within a single cell. In RB663 plants, the multiplication of turnip crinkle virus (TCV) was also delayed but that of tobacco mosaic virus was not affected. As observed with CMV, the multiplication of TCV was normal in protoplasts and delayed in inoculated leaves of RB663 plants compared to that in wild-type plants. Furthermore, the phenotype of delayed TCV multiplication cosegregated with the cum2-1 mutation as far as we examined. Therefore, the cum2-1 mutation is likely to affect the cell-to-cell movement of both CMV and TCV, implying a common aspect to the mechanisms of cell-to-cell movement in these two distinct viruses.

Arabidopsis↗

Ets-1 is an early response gene activated by ET-1 and PDGF-BB in vascular smooth muscle cells.

Ets-1 is a transcription factor that activates expression of matrix-degrading proteinases such as collagenase and stromelysin. To study the control of ets-1 gene expression in rat vascular smooth muscle cells (VSMC), cells were exposed to factors known to regulate VSMC migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB), endothelin-1 (ET-1), and phorbol 12-myristate 13-acetate (PMA) induced a dose-dependent expression of ets-1 mRNA. These effects were abrogated by inhibition of protein kinase C (PKC) by H-7 or chronic PMA treatment. Ets-1 mRNA was superinduced by PDGF-BB and ET-1 in the presence of cycloheximide. The chelation of intracellular Ca2+ by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester and the depletion of endoplasmic reticulum intracellular Ca2+ concentration ([Ca2+]i) by thapsigargin inhibited PDGF-BB- and ET-1-induced ets-1 mRNA, whereas ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid had no effect. However, [Ca2+]i release alone was not sufficient to increase ets-1 mRNA. Forskolin blocked ET-1-, PDGF-BB-, and PMA-induced ets-1 mRNA, as well as inositol phosphate formation, consistent with an effect through impairment of PKC activation. Inhibitors of ets-1 gene expression, such as H-7 and herbimycin A, inhibited the ET-1 induction of collagenase I mRNA. We propose that ets-1 may be an important element in the orchestration of matrix proteinase expression and of vascular remodeling after arterial injury.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Two different pathways of glomerular enlargement in adults with focal and segmental glomerulosclerosis: a morphometric study.

The renal biopsy specimens obtained from 15 adults with focal and segmental glomerulosclerosis (FSGS) and 15 adults with minimal change nephrotic syndrome (MCNS) were morphometrically analyzed using light and electron microscopy. Moreover, initial biopsy specimens obtained from 10 adults who were diagnosed as MCNS and developed FSGS, based on repeat biopsy findings ('MCNS'-FSGS), were also analyzed using electron microscopy. After comparing the actual values between the groups of FSGS and MCNS, the mean glomerular volume, the capillary volume per a glomerulus, the capillary filtration surface per a glomerulus, and the capillary diameter (Cap-D) were all larger in the FSGS group than in the MCNS group. In regard to the morphological values in the 'MCNS'-FSGS group, both values of the surface density of the capillary filtering surface and the capillary diameter at the first biopsy specimens as well as those in the FSGS group were higher than those in the MCNS group. When analyzing the structural parameters, in the FSGS series, we found a high association of the percentage of obsolescent glomeruli (%SG) with the mean glomerular volume, the capillary volume per a glomerulus, the capillary filtering surface per a glomerulus and the capillary length per a glomerulus, however we failed to demonstrate the correlation between the %SG and the Cap-D. Thus, the glomerular structure in the 'MCNS'-FSGS patients, even at the first renal biopsy, resembled that in FSGS, suggesting FSGS to be a distinct entity from MCNS. These data indicate that the enlargement of the capillary volume, resulting from the widening of the capillaries, was the initial structural event for adults with FSGS, while the elongation of the capillaries appeared to reflect some compensatory process for the decrease in the functioning nephron.

Adult↗

Induction of protection against tetanus toxin in mice by tetanus toxoid-liposome conjugate.

Tetanus toxoid (Ttd) was coupled to liposomes via glutaraldehyde. Intraperitoneal injection in BALB/c mice with Ttd-liposomes induced a substantial amount of anti-Ttd IgG antibody production and an extremely low level of anti-Ttd IgE antibody production. Mice immunized with Ttd-liposomes were successfully protected against a subsequent challenge with a lethal dose of tetanus toxin (Ttx). On the other hand, aluminum hydroxide-adsorbed Ttd (Ttd-alum) and plain Ttd solution induced the production of both IgG and IgE antibodies against Ttd. Moreover, secondary immunization with Ttd-liposomes in mice, in which anti-Ttd IgE antibody production was induced by Ttd-alum led to enhanced anti-Ttd IgG and a limited anti-Ttd IgE antibody production. When Ttd-liposome preparation was lyophilized, the efficacy of Ttd-liposomes was maintained for 6 months at 37 C, suggesting that this vaccine preparation would be stable without refrigeration. These results demonstrate the potential ability of Ttd-liposome conjugates to produce a tetanus vaccine which provides protection against (Ttx) while inducing the least amount of anti-Ttd IgE antibodies.

Animals↗

Induction of protection against oral infection with cytotoxin-producing Escherichia coli O157:H7 in mice by shiga-like toxin-liposome conjugate.

We have previously reported that purified Shiga-like toxins (SLT), SLT-I and SLT-II coupled with liposomes induced a substantial amount of anti-SLT-I and anti-SLT-II IgG antibody production, respectively, in mice. The levels of anti-SLT antibody in the sera of SLT-liposome-immune mice correlated well with the protection against subsequent challenge with SLT. In this study, mice were immunized intraperitoneally with the mixture of SLT-I-liposome and SLT-II-liposome and protection against oral infection with cytotoxin-producing Escherichia coli O157:H7 was evaluated. All of the mice that received immunization with the mixture of SLT-I-liposome and SLT-II-liposome were protected against subsequent intravenous challenge with 10 LD50 of either SLT-I or SLT-II. Eight weeks after primary immunization, mice were inoculated intragastrically with 10(9) CFU of E. coli O157:H7 strain 96-60. All SLT-liposome-immune mice tested survived without any apparent symptom while control mice died within 5 days. In addition, as shown by other antigen-liposome conjugates, SLT-liposome induced undetectable anti-SLT IgE antibody production while they induced substantial amounts of anti-SLT IgG antibodies. These results suggest that SLT-liposome conjugate may serve as a candidate vaccine that induces protection against cytotoxin-producing E. coli infection.

Animals↗