Biomedical subjects

E Fujii

Publications and source records attributed to E Fujii.

At least 19 recordsLinked to original sources

PubMed2005

Collagenofibrotic glomerulonephropathy in a cynomolgus macaque (Macaca fascicularis).

Collagenofibrotic glomerulonephropathy (CFGN) is characterized by the deposition of type III collagen within the mesangial matrix and the absence of mesangial cell proliferation. A case of CFGN in a 2.7-year-old female cynomolgus macaque was investigated in the present study. Clinically, the animal was shown to have severe systemic edema along with hypoproteinemia. At necropsy, the kidneys were swollen and pale. The glomerular lesions were characterized by massive diffuse and global accumulation of fibrous materials in the mesangial areas. Neither mesangial cell proliferation nor changes in other organs were found. The fibrous materials were confirmed by the results of immunohistochemical and electron microscopic findings to consist mainly of randomly arranged, curve-shaped, twisted, and entwined type III collagen. This is the first case report of CFGN in nonhuman primates to date.

Animals↗

PubMed2003

Successful radiofrequency catheter ablation of "clockwise" and "counterclockwise" bundle branch re-entrant ventricular tachycardia in the absence of myocardial or valvar dysfunction without detecting bundle branch potentials.

A case is reported of a patient with only isolated conduction abnormalities of the His-Purkinje system with no identifiable myocardial or valvar dysfunction, leading to "clockwise" and "counterclockwise" bundle branch re-entrant ventricular tachycardias (BBRVTs). The electrophysiological study showed infra-Hisian conduction system disease and two different inducible wide QRS complex tachycardias. Neither right bundle branch nor left bundle branch potentials were recorded despite extensive catheter manipulation. However, these tachycardias were diagnosed as BBRVTs by using entrainment manoeuvres and comparing the HV intervals during both sinus rhythm and the tachycardias. These tachycardias were eliminated by catheter ablation of the right bundle branch, using the morphology of the local electrograms and anatomical findings.

Aged↗

PubMed2002

A lipid A analog ONO-4007 induces tolerance to plasma leakage in mice.

OBJECTIVE: The effects of pretreatment with ONO-4007, a lipid A analog, on cutaneous plasma leakage induced by ONO-4007, lipopolysaccharide (LPS) and inflammatory mediators were investigated. MATERIAL: Male ddY strain mice. TREATMENT: Mice were pretreated with ONO-4007 (up to 6 mg/kg i.p.), 0-24 h prior to plasma leakage study. METHODS: Plasma extravasation was determined by dye leakage. RESULTS: Systemic ONO-4007 (6 mg/kg i. p.) pretreatment for 2 to 12 h inhibited plasma extravasation in the mouse skin elicited by ONO-4007 and LPS. The inhibition was dose-dependent. Plasma leakage induced by platelet-activating factor (PAF), histamine and 5-hydroxytryptamine (5-HT) was also inhibited by ONO-4007 pretreatment. Plasma corticosterone levels increased 2 and 4 h after systemic ONO-4007 (6 mg/kg) administration and returned to the control level 24 h later. Adrenalectomy and metyrapone but not propranolol reversed the inhibition by ONO-4007 pretreatment of LPS-induced plasma leakage. CONCLUSIONS: A single injection of ONO-4007 in mice induced transient tolerance to plasma leakage elicited by LPS, ONO-4007 and inflammatory mediators. Endogenous corticosterone, at least in part, plays a role in the development of tolerance.

Adrenal Glands↗

PubMed2001

Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat: phosphorylation of Akt, activation of caspase-3-like protease.

Neuroprotective mechanisms of hypothermia have not been clearly established especially in the immature brain. To investigate the effect of hypothermia on cell death and cell survival signal pathways, we studied caspase-3-like activity and activation of Akt in a rat model of neonatal hypoxic-ischemic (H-I) brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1-h (n=32). During recovery, the body temperature was reduced to 30 degrees C for 24 h in 16 animals, but was kept at 37 degrees C in 16 animals. Post-ischemic hypothermia was shown to diminish the caspase-3-like activity compared to normothermia at 6 and 24 h after H-I. Phospho-Akt was increased during the early reperfusion period after H-I in the normothermia group, but hypothermia rather decreased this enhanced phosphorylation of Akt following H-I. These results indicated that hypothermia may have some depressant effects on both cell death and cell survival signal pathways, and that Akt conceivably may not play a major role in the neuroprotective effect of hypothermia in the immature brain.

Animals↗

PubMed2001

Fructose- 1,6-bisphosphate did not affect hippocampal neuronal damage caused by 10 min of complete umbilical cord occlusion in fetal sheep.

Fructose-1, 6-bisphosphate (FBP) has a neuroprotective effect in neonatal and adult rats. The purpose of this study was to examine the effects of FBP on hippocampal neuronal damage in fetal sheep asphyxiated by 10 min of complete umbilical cord occlusion. Thirteen fetal sheep at 124 days of gestation were surgically instrumented with catheters. Cardiorespiratory parameters were monitored, and biochemical analyses were performed with the blood samples. During the insult seven fetuses were given FBP (500 mg/kg) and six were given iso-osmotic saline, and hippocampal neuronal damage was examined histologically and scored. Cardiorespiratory changes were the same in both groups, and there was no neuroprotective effect of FBP in this study. However the decrease of serum total Ca level implied the Ca- chelating effect of FBP.

Animals↗

PubMed2001

Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia-ischemia.

The effects of hypothermia on caspase-3 activation were investigated in the newborn rat brain after hypoxia-ischemia (HI). Intense caspase-3 activation was observed in the control brains after HI, but this activation was significantly reduced by postischemic hypothermia. These findings suggest that the inhibition of caspase-3 activation may be an interventional point underlying the neuroprotective effect of hypothermia in neonates.

Animals↗

PubMed2001

Histocompatibility leukocyte antigen-G is not expressed by endometriosis or endometrial tissue.

OBJECTIVE: The immunological mechanisms that support persistence and proliferation of ectopic endometrial implants within the peritoneal cavity of women with endometriosis are unknown. Inhibition of natural killer (NK) and cytotoxic T-cell function has been proposed as a mechanism. We tested the hypothesis that expression of a nonclassical major histocompatibility antigen, HLA-G, might explain the local immunosuppression associated with ectopic endometrium. DESIGN: Nested case-control study of women with and without laparoscopic evidence of endometriosis. SETTING: Reproductive endocrinology clinic at a university hospital. PATIENT(S): Peritoneal fluid specimens from 10 women with revised AFS stage I-IV endometriosis and from 10 age-matched normal controls without laparoscopic evidence of endometriosis were tested for the presence of HLA-G protein. Endometriosis and normal endometrial biopsies from four patients were used to prepare stromal cell cultures directly evaluated for HLA-G protein. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The expression of HLA-G in peritoneal fluid, tissue, and cell cultures was determined by immunoblotting with a specific monoclonal antibody. RESULT(S): HLA-G protein was not detectable in peritoneal fluid specimens of endometriosis patients or controls. Moreover, ectopic and normal endometrial tissues and stromal cells did not express HLA-G. CONCLUSION(S): Immune cell inhibition in endometriosis must be mediated by factors other than HLA-G.

Amino Acid Sequence↗

PubMed2001

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)-induced microvascular permeability change in mouse skin.

Anti-inflammatory effects of cyclic AMP elevating agents were examined in a mouse model of lipopolysaccharide (LPS)-induced microvascular permeability change. Vascular permeability on the back skin was measured by the local accumulation of Pontamine sky blue (PSB) after subcutaneous injection of LPS (400 microg site-1) from Salmonella typhimurium. Dye leakage in the skin was significantly increased 2 h after injection of LPS. This LPS-induced dye leakage was suppressed by phosphodiesterase inhibitors, including pentoxifylline (160 mg kg-1), milrinone (5 - 10 mg kg-1), rolipram (0.5 - 10 mg kg-1) and zaprinast (5 - 10 mg kg-1). The dye leakage was also inhibited by beta-adrenoceptor agonists, including isoproterenol (0.5 - 5 mg kg-1) and salbutamol (0.05 - 5 mg kg-1), an adenylate cyclase activator, forskolin (5 mg kg-1), and a cell permeable cyclic AMP analogue, 8-bromo-cyclic AMP (8-Br-cAMP, 10 mg kg-1). LPS caused a transient increase in serum TNF-alpha level peaking at 1 h after the injection. This increase in serum TNF-alpha was completely blocked by a pretreatment with pentoxifylline (160 mg kg-1), milrinone (5 mg kg-1), rolipram (1 mg kg-1), zaprinast (10 mg kg-1), salbutamol (0.5 mg kg-1), forskolin (1 mg kg-1) and 8-Br-cAMP (10 mg kg-1). LPS caused an increase in serum IL-1alpha level peaking at 3 h after injection. This increase in serum IL-1alpha was not significantly suppressed by the cyclic AMP elevating agents. Our study suggests that cyclic AMP elevating agents attenuate LPS-induced microvascular permeability change by suppressing TNF-alpha up regulation.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2001

Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy.

BACKGROUND: The concurrent use of amiodarone and warfarin inhibits metabolism of S-warfarinby cytochrome P450 (CYP) 2C9, thereby increasing the anticoagulant effect of warfarin. Amiodarone primarily inhibits CYP1A2 and CYP3A4, and desethylamiodarone primarily inhibits CYP2C9. We investigate whether a relationship exists between the plasma concentration of desethylamiodarone and anticoagulation when amiodarone is administered to patients receiving warfarin therapy. METHODS AND RESULTS: The correlation between the plasma concentration of either amiodarone or desethylamiodarone, and prolongation of prothrombin time-international normalized ratio/dose of warfarin (Delta INR/Dose) on day 7 of amiodarone administration was studied in 25 patients (22-74 years old) with structural heart disease and refractory arrhythmias receiving stable warfarin therapy. RESULTS: No correlation was found between the plasma concentration of amiodarone and Delta INR/Dose, but a correlation was found between the plasma concentration of desethylamiodarone and Delta INR/Dose. CONCLUSIONS: It was suggested that inhibition of CYP2C9 by desethylamiodarone, the active metabolite of amiodarone, plays an important role in the interaction of warfarin and amiodarone.

Adult↗

PubMed2001

Regulation of uterine gamma-aminobutyric acid(A) receptor subunit expression throughout pregnancy.

Uterine contractions at parturition depend upon a variety of factors, including gamma-aminobutyric acid (GABA)-ergic stimulation. A new subunit of the GABA(A) receptor, pi, has recently been identified as being particularly abundant in the rat uterus. Reduced derivatives of progesterone, such as the 3alpha,5alpha-reduced derivative termed allopregnanolone, modulate GABA(A) receptor activity and neuronal inhibition by modulating the frequency and duration of GABA(A) channel opening. This modulation depends on the specific subunit composition of the GABA(A) receptor. In particular, assembly of recombinant pi and delta GABA(A) receptor subunits into a functional GABA(A) receptor have been reported to reduce sensitivity to allopregnanolone. As allopregnanolone works through the GABA(A) receptor to reduce uterine contraction, we hypothesized that incorporation of the pi-subunit into this receptor in the uterus might change the sensitivity of the GABA(A) receptor to allopregnanolone and modulate parturition. We therefore determined the expression of GABA(A) receptor subunit messenger RNAs (mRNAs) in rat uteri from various gestational ages and determined the physiological properties of the receptors. GABA(A) pi-subunit mRNA abundance was constant throughout gestation, but decreased at the onset of labor. Other GABA(A) subunits fluctuated differently during pregnancy: GABA(A) alpha(1)-subunit mRNA expression increased, whereas alpha(2)- and delta-subunit mRNA expression decreased during pregnancy, and beta(3)-subunit mRNA only appeared on postpartum day 1. We determined how allopregnanolone affected the binding of muscimol, a ligand for the GABA(A) receptor, to rat uterine GABA(A) receptors throughout pregnancy. Allopregnanolone caused the greatest increase in muscimol binding to uterine GABA(A) receptors at 19.5 days gestation and the least increase during labor, a time when pi and alpha(1) receptor subunit mRNA concentrations were low, and delta and alpha(2) receptor subunit mRNA concentrations were high. Thus, the subunit composition of the GABA(A) receptor differs in rat uteri throughout gestation. These changes may also affect the sensitivity of the GABA(A) receptor to allopregnanolone and thus contribute to the regulation of parturition.

3-Hydroxysteroid Dehydrogenases↗

PubMed2001

Risk factors for development of postoperative hypertension.

One hundred and eighty-nine patients who underwent digestive tract surgery were studied to investigate risk factors for the development of postoperative hypertension. We examined factors related to maximum postoperative systolic blood pressure and postoperative hypertensive urgency, a sign of postoperative hypertension. Data collected included blood pressure, age, sex, body mass index (BMI), medical history, total water balance and grade of surgical stress. Maximum postoperative systolic blood pressure and incidence of postoperative hypertensive urgency were the dependent variables. Mean preoperative systolic blood pressure, age and BMI were significantly related to maximum postoperative systolic blood pressure and postoperative hypertensive urgency. In addition, the grade of surgical stress was significantly related to maximum postoperative systolic blood pressure. In analyses of multiple variables, the adjusted odds ratio for postoperative hypertensive urgency was 1.16 for every 1 mmHg increase in mean preoperative systolic blood pressure, 1.05 for every 1 year increase in age and 0.82 for every 1 kg/m2 increase in BMI. These findings may have important clinical implications for the prevention of postoperative hypertension.

Adult↗

PubMed2001

[Proton magnetic resonance spectroscopy of the autistic brain].

To evaluate brain dysfunction in autism, proton magnetic resonance spectroscopy (1H-MRS) was performed for 29 autistic patients (5-15 y.o.) and 19 normal children (6-14 y.o.). We obtained magnetic resonance (MR) spectra of the left and right amygdaloid-hippocampal regions and the left cerebellar hemisphere with a STEAM sequence (TR = 5000 ms, TE = 18 ms). In addition to the evaluation of signal intensity ratios, the absolute concentration of three major metabolites (N-acetylaspartate [NAA], creatine/phosphocreatine [Cr] and choline-containing substances [Cho]) was quantified by an internal reference method using unsuppressed tissue water. Although no abnormal MR images were found in the three regions examined, the signal intensity and the concentration of NAA in the left amygdaloid-hippocampal region and the left cerebellar hemisphere were reduced significantly in autistic patients compared to normal children. We speculated that this decrease in NAA reflected neuronal loss, immaturity or hypofunction in these regions. The results of our study were in agreement with those of previous studies on autism, one by neuropathological methods and the other using a single photon emission computed tomography with 99mTc HMPAO. Disorders of the amygdaloid-hippocampal region and cerebellum are considered to play an important role in the characteristic cognitive and emotional dysfunction in autism. 1H-MRS is a valuable tool to clarify the pathophysiology of autism.

Adolescent↗

PubMed2000

Evaluation of iNOS-dependent and independent mechanisms of the microvascular permeability change induced by lipopolysaccharide.

1. Subcutaneous injection of lipopolysaccharide (LPS) increases plasma leakage in mouse skin. Pretreatment with LPS conditions mice tolerant to the LPS-induced plasma leakage. Nitric oxide (NO) has been suggested to be involved in these LPS effects. A specific role of inducible NO synthase (iNOS) was investigated in the LPS-induced plasma leakage using iNOS deficient mice. 2. Plasma leakage in mouse skin was measured by the local accumulation of Pontamine sky blue at the site of subcutaneous injection of LPS (Sal. typhimurium). LPS (100 - 400 microg site(-1)) produced a dose-related increase in dye leakage in both iNOS deficient and wild-type mice with about 40% less dye leakage in iNOS deficient mice. 3. Indomethacin (5 mg kg(-1)), N-[-2-cyclohexyloxy]-4-nitrophenyl methanesulphonamide (NS-398) (1 mg kg(-1)), diphenhydramine (10 mg kg(-1)) and anti-TNF-alpha antibody (dilution 1 : 400, 10 ml kg(-1)) inhibited the LPS-induced dye leakage in both iNOS deficient and wild-type mice, whereas N(G)-nitro-L-arginine methyl ester (L-NAME) (10 mg kg(-1)) or aminoguanidine (10 mg kg(-1)) inhibited that in wild-type but not in iNOS deficient mice. 4. Pretreatment with LPS (0.15 mg kg(-1) i.p.) 4 h before decreased the LPS-induced dye leakage in wild-type but not in iNOS deficient mice. LPS pretreatment increased serum corticosterone levels in both mice, while it increased the serum nitrate/nitrite levels in wild-type but not in iNOS deficient mice. 5. These studies indicate that an increase in vascular permeability induced by LPS is mediated by NO produced by iNOS, eicosanoids, histamine and TNF-alpha. The tolerance against LPS-induced vascular permeability change may be mediated by iNOS induction but not by an increased release of endogenous corticosteroids.

Animals↗

PubMed2000

Role of inflammatory mediators in lipid A analogue (ONO-4007)-induced vascular permeability change in mouse skin.

1. Endotoxin shock is accompanied by an increase in peripheral vascular permeability. It has been postulated that most biological activities of LPS are derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO-4007 in increasing vascular permeability and the possible mediators in mouse skin by a dye leakage method. 2. Subcutaneous injection of ONO-4007 (1 - 2 mg site(-1)) induced a dose-dependent increase in vascular permeability which was evident after 120 min. 3. ONO-4007-induced dye leakage was significantly attenuated by pretreatments with anti-tumour necrosis factor-alpha (TNF-alpha) and anti-interleukin-1alpha (IL-1alpha) antibodies, but not with indomethacin (5 mg kg(-1)) or diphenhydramine (10 mg kg(-1)). ONO-4007-induced dye leakage was significantly inhibited by a pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (10 mg kg(-1)) but not with aminoguanidine (50 mg kg(-1)). In inducible nitric oxide synthase (iNOS)-deficient mice, ONO-4007 significantly increased the dye leakage, while ONO-4007 dilated rat thoracic aortic rings pre-contracted with phenylephrine, and the L-NAME pretreatment inhibited the dilation. 4. Thus, TNF-alpha, IL-1alpha and constitutive NOSs-derived nitric oxide but not prostaglandins or histamine play a role in ONO-4007-induced increase in vascular permeability. Although ONO-4007 mimics LPS in increasing vascular permeability, mechanisms of permeability change elicited by ONO-4007 were not identical to those of LPS.

Animals↗

PubMed2000

Retreatment with interferon for chronic hepatitis C after transient response.

Approximately half of all patients with chronic hepatitis C show an initial biochemical response to interferon, but only 15% to 20% of patients achieve a sustained response. We studied the efficacy of retreatment with interferon for patients with chronic hepatitis C who showed transient biochemical responses to initial treatment. Thirty patients who relapsed were retreated 1 to 52 months (median 14) after the end of initial treatment, according to the previously used regimens. The responses were correlated with the pre-retreatment patient data. The liver histologic grades, compared with those found before the initial treatment, were better in eight (27%) patients but worse in six (20%), whereas the fibrosis stage was improved in five (17%) but worsened in eight (27%). All patients displayed end-of-retreatment biochemical responses. Of the 30 patients, 10 (33%) achieved sustained aminotransferase normalization and serum hepatitis C virus (HCV) RNA clearance, but the remaining 20 patients showed relapse within 1 year after cessation of retreatment. Univariate analysis associated the sustained response with low pre-retreatment viral loads (0.8 +/- 0.7 MEq/mL vs. 9.1 +/- 6.5 MEq/mL; p = 0.006), short treatment intervals (13 +/- 13 months vs. 22 +/- 14 months; p = 0.031), and low histologic grades (1.3 +/- 0.7 vs. 1.9 +/- 0.7; p = 0.039). However, multivariate analysis indicated that only the pre-retreatment viral load was predictive of the sustained response (p = 0.049). These findings suggest that transient responders to interferon are likely to respond to retreatment but the achievement of a sustained response depends on the HCV viral load before retreatment.

Adult↗

PubMed2000

Electrophysiological determinants of persistent dual atrioventricular nodal pathway physiology after slow pathway ablation in atrioventricular nodal reentrant tachycardia.

UNLABELLED: The purpose of this study was to examine the electrophysiological determinants of the elimination of recurrent atrioventricular nodal reentrant tachycardia (AVNRT) despite the persistence of dual AV nodal pathway physiology or single echo beats after ablation procedures. The study included 26 patients with common AVNRT who had undergone successful ablation treatment and no long-term recurrence of AVNRT. The slow pathway potential was targeted, and the endpoint of ablation was one echo during atrial extrastimulus testing (ET) with isoproterenol. Persistent dual pathways physiology or single echoes were present in 12 patients (group I) and absent in 16 (group II) after ablation. The number of anterograde AV nodal pathways and maximum AH interval (Max AH) during ET were measured before and after ablation, and ventriculoatrial conduction during ventricular pacing was examined. RESULTS: (1) multiple AV nodal pathways were more frequently observed in group I than in group II (50.0% vs 7%, P < 0.05); (2) Max AH decreased significantly after ablation in both groups (309 +/- 157 vs 171 +/- 53 ms in group II; P < 0.01, and 409 +/- 65 vs 274 +/- 86 ms in group I; P < 0.001); and (3) retrograde dual pathway conduction was more common in group I than in group II. These data suggest the presence of nonuniform conductive properties of the AV node in group I and that ablation targeting the slow pathway potential prevents recurrences of AVNRT by eliminating the pathway with the longest conduction time.

Adult↗

PubMed2000

Shortening of conduction time over arborized atrioventricular accessory pathway with Mahaim fibers physiology just before interruption during radiofrequency ablation.

A 21-year-old woman had paroxysmal wide QRS tachycardia with a left bundle branch block configuration and a retrograde conducted P wave just behind the QRS complex. An electrophysiological study revealed antidromic atrioventricular tachycardia involving an atrioventricular connection with decremental conduction as the anterograde limb and normal atrioventricular node as the retrograde limb. During constant pacing from the high right atrium (HRA) at the cycle length (CL) of 600 ms, the QRS configurations were not identical to those during the wide QRS tachycardia or constant pacing at the CL of less than 500 ms. The process by which this arborized atrioventricular accessory pathway with the Mahaim fibers physiology was interrupted by radiofrequency catheter ablation is described. Radiofrequency energy was delivered to the site recording a Mahaim potential at the tricuspid annulus during constant pacing from the HRA at the CL of 429 ms. The stimulus-QRS interval gradually shortened as it reached the power plateau without changing the preexcited QRS configuration. Shortening of the conduction time over the Mahiam pathway might have resulted in changing of the propagation from a slow to fast conduction zone or acceleration in response to thermal effect in a node-like structure on the atrial insertion site.

Adult↗

PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 11). Testicular toxicity of 2- or 4-week repeated or single-dose administration of a novel platinum complex.

A novel platinum complex, compound C, developed as an antitumor agent, was intravenously administered at 10 mg/kg/day to 6-week-old and 8-week-old rats. After 4 weeks of administration to the former, testicular enlargement was observed at a similar incidence as testicular atrophy and dilatation or atrophy of the seminiferous tubules was observed. Degeneration/necrosis of the seminiferous epithelium, decrease of seminiferous epithelium, formation of multinucleated giant cells, and vacuolar degeneration of Sertoli cells were also seen. These lesions were more marked in seminiferous tubules with atrophy than in those without atrophy. After 2-week administration to 8-week-old rats, slight initial-phase findings such as dilatation of seminiferous tubules and degeneration/necrosis of the seminiferous epithelium were noted in all rats. In rats administered 20 mg/kg/day, for which the administration period was shortened to 1 week due to marked weight loss, very slight initial lesions were similarly observed. However, these lesions were not easy to detect in these rats. Following single administration of a sublethal dose (80 mg/kg), testicular lesions were clearly observed 14 days after administration, but the incidence and grade of lesions were very low at 7 days. In conclusion, testicular toxicity of compound C can be clearly detected after 2-week administration, although the progression of lesions differed from the case with 4-week administration.

Animals↗