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M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 73 records · Page 4Linked to original sources
PubMed2001

The effect of positive end-expiratory pressure and continuous positive airway pressure on the oxygenation and shunt fraction during one-lung ventilation with propofol anesthesia.

STUDY OBJECTIVE: To evaluate the effect of positive end-expiratory pressure (PEEP) and continuous positive airway pressure (CPAP) on the oxygenation and shunt fraction during one-lung ventilation (OLV). DESIGN: Prospective clinical study. SETTING: Inpatient thoracic surgery and anesthesia clinic at an University hospital. PATIENTS: 15 patients with esophageal cancer who were scheduled for radical surgery. INTERVENTIONS: Arterial oxygenation, shunt fraction, and hemodynamics were evaluated at 20 min after the start of operation, at 20 minutes after the initiation of OLV under zero end-expiratory pressure (ZEEP), 20 minutes after the application of 4 cm PEEP to the dependent lung, at 20 minutes after OLV under ZEEP, 20 minutes after the application of 4 cm CPAP to the nondependent lung, and again under ZEEP, and after the combined application of PEEP and CPAP to the dependent and nondependent lungs. MEASUREMENTS AND MAIN RESULTS: There were no significant changes in mean pulmonary artery pressure, mean arterial blood pressure, heart rate, mixed venous partial pressure of oxygen, or arterial and mixed venous saturation of oxygen (SVO(2)) during this study. Arterial partial pressure of oxygen (pO(2)) increased and shunt fraction values decreased significantly after the application of PEEP (pO(2); 197.8 +/- 32.9 mmHg, Qs/Qt; 22.9 +/- 5.6%), CPAP (pO(2); 212.6 +/- 15.9 mmHg, Qs/Qt; 22.8 +/- 5.9%), and combination of PEEP and CPAP (pO(2); 222.0 +/- 42.8 mmHg, Qs/Qt; 24.1 +/- 6.4%) compared with ZEEP (pO(2); 128.1 +/- 37.5 mmHg, Qs/Qt; 33.2 +/- 6.8% ). But there were no significant differences regarding oxygenation and shunt fraction during PEEP, CPAP, or the combination of PEEP and CPAP. CONCLUSIONS: The application of PEEP to the dependent lung, CPAP to the nondependent lung, and the combination of PEEP and CPAP, are useful for improving oxygenation and decreasing Qs/Qt.

Adult↗
PubMed2001

Three autopsied cases of cystic fibrosis in Japan.

The incidence of cystic fibrosis (CF) is very rare in Japanese, while it is frequent in Caucasians. Here we report on three Japanese cases of CF. One of the patients had consanguineous parents. All three patients initially developed meconium ileus, and hepatobiliary and pancreatic changes became more severe as age increased. The DeltaF508 mutation, the most frequent mutation associated with CF in Caucasians, was not found in these patients. To evaluate the relationship between the severity of hepatic lesions and a history of meconium ileus, we examined hepatic lesions in the present three cases, and we reviewed 22 Japanese autopsied cases of CF in the literature. No correlation was found between the incidence of biliary cirrhosis and a history of meconium ileus, because the cases with meconium ileus showed a high mortality during the neonatal period, before biliary cirrhosis developed. The high incidence of meconium ileus in Japanese CF patients may relate to a clinically severe phenotype and reflect a different genetic background between Caucasians and Japanese.

Adolescent↗
PubMed2001

Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma.

Normal alveolar capillary endothelium is quiescent in nature and displays anticoagulant thrombomodulin (TM) on its surface. The cytoplasms of these endothelial cells are ultrastructurally non-fenestrated type, and they barely express von Willebrand factor (vWf). Alveolar fibrosis is accompanied by a capillary endothelium reactive for vWf, and a loss of TM expression. In primary lung adenocarcinoma, neovascularization occurs in association with alveolar fibrosis. In order to study basic factors related to angiogenesis and phenotypic changes of the capillaries located in tumor-bearing alveolar walls, we examined 37 primary lung adenocarcinomas with electron microscopy and confocal laser scanning microscopy with antibodies for TM, vWf, vascular endothelial growth factor (VEGF), and its receptors (KDR and Flt-1), and proliferating markers (Ki-67/proliferating cell nuclear antigen). Tissues microdissected specifically from alveolar walls were used for reverse transcription-polymerase chain reaction (RT-PCR) to assess expressions of mRNA isoforms of VEGF and its receptors. New capillary branching was found by ultrastructural study in the alveolar walls in 12% of the patients. Nuclei of the capillary endothelial cells were reactive for proliferating cell markers. Endothelial fenestrae were developed in 65% of the patients, TM reactivity was lost in the alveolar capillaries, and their cell cytoplasms obtained a reactivity for vWf through a transitional mosaic-like distribution pattern of both antigens. Besides cytoplasmic VEGF expression in neoplastic cells, tumor-bearing alveolar walls showed significant expression of mRNA of VEGF165 and KDR. These findings imply that angiogenesis and phenotypic changes of the alveolar capillaries are closely related to a higher expression of tumor-associated VEGF165 and of KDR in the alveolar walls in primary lung adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Coronary flow reserve in angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors.

AIMS: Reduced coronary flow reserve has been reported in patients with traditional risk factors, in particular hyperlipidaemia, despite angiographically normal coronary arteries. However, it is recognized that traditional risk factors do not explain the presence of coronary atherosclerosis in a large proportion of patients. The aim of this study was to assess whether coronary flow reserve is preserved in the myocardium supplied by normal coronary arteries in patients with one-vessel coronary artery disease without traditional risk factors. METHODS AND RESULTS: Positron emission tomography using [13N]ammonia was performed at baseline and after intravenous dipyridamole administration (0.56 mg x dl(-1)over 4 min) in 30 subjects: six patients with ischaemia on effort, no myocardial infarction, and isolated left anterior descending coronary artery stenosis without traditional risk factors (coronary artery disease patients without risk factors, aged 59+/-13), five patients with ischaemia on effort, no myocardial infarction, and isolated left anterior descending coronary artery stenosis with multiple risk factors (coronary artery disease patients with risk factors, aged 69+/-7), 11 age-matched controls (aged 58+/-6), and eight healthy young volunteers (aged 34+/-4). Myocardial blood flow calculated in the myocardium supplied by normal coronary arteries in the coronary artery disease patients was compared with those of the two control groups. Coronary flow reserve was defined as the ratio of hyperaemic blood flow after dipyridamole infusion to baseline blood flow. Although coronary flow reserve in the coronary artery disease patients with risk factors was significantly lower than that in the age-matched controls (1.62+/-0.37, 2.58+/-0.71, P=0.0428), coronary flow reserve in the coronary artery disease patients without risk factors was similar to that in the age-matched controls (2.54+/-0.17 vs 2.58+/-0.71, P=ns). CONCLUSION: Coronary flow reserve is preserved in regions supplied by angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors.

Adult↗
PubMed2001

Aerogenous spread of primary lung adenocarcinoma induces ultrastructural remodeling of the alveolar capillary endothelium.

To determine whether pulmonary alveolar capillaries manifest ultrastructural remodeling at areas of neoplastic invasion of primary lung adenocarcinomas, we examined 17 well-differentiated adenocarcinomas of lung (2 bronchioloalveolar and 15 papillary adenocarcinomas) by electron microscopy. The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was demonstrated by immunohistochemical stainings. VEGF messenger RNA (mRNA) isoforms were detected by reverse-transcription polymerase chain reaction (RT-PCR) in alveolar walls microdissected from normal and tumor-associated tissues. Cytoplasm of neoplastic cells expressed VEGF protein in all patients. Endothelial cell nuclei of alveolar capillaries showed positive reaction for PCNA. Alveolar capillary lumina were distended like venules, and some intercellular junctions remained open. The cytoplasm of the capillary endothelial cells was enlarged and developed numerous organelles such as Weibel-Palade bodies and vesiculovacuolar organelles, in contrast to marked attenuation in their normal counterpart. Capillary sprouting occurred from proper alveolar capillaries in 2 patients. Cytoplasmic segments became extremely attenuated and developed diaphragm-like fenestrae in 65% of the patients. A relatively higher expression of diffusable isoforms of VEGF mRNA was seen in the tumor-bearing alveolar walls than in normal walls. Expression of KDR (one of the VEGF receptors) mRNA in tumor exceeded that in normal tissues. These results suggest that diffusable isoforms of VEGF mRNA released from the neoplastic cells are deeply involved in the induction of growth activity of alveolar capillary endothelial cells as much as in the characterization of tumor-associated microvessels in primary lung adenocarcinomas.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Neurological features in Gaucher's disease during enzyme replacement therapy.

UNLABELLED: This report describes two patients with Gaucher's disease who had unusual clinical symptoms during enzyme replacement therapy. One patient was a female with type 3 Gaucher's disease. She developed a pericardial effusion at 7 y of age, which contained many Gaucher cells despite enzyme replacement therapy. She died from neurological deterioration during enzyme replacement therapy, despite an improvement in her visceral manifestations. The other patient is a male with type 2 Gaucher's disease, who has achieved long-term survival after being supported by mechanical ventilation and enzyme replacement therapy. While on enzyme replacement therapy at the age of 4 y, he suffered a generalized cutaneous disease which was clinically diagnosed as ichthyosis. CONCLUSION: These cases suggest that ordinary enzyme replacement therapy is insufficient for some of the non-neurological manifestations of severe types of Gaucher's disease.

Atrophy↗
PubMed2001

Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors.

PURPOSE: Genetic alterations, including microsatellite instability (MSI), are ultimate steps toward malignant process. To investigate MSI in A-bomb survivors, leukaemic cells were analysed from 13 acute myelocytic leukaemia patients with a history of radiation exposure and also in 12 de novo patients. MATERIALS AND METHODS: To assess the microsatellite changes, a fluorescent system in 10 loci (BAT40, D3S643, D5S107, IRF1, MYC, D9S171, WT1, TP53, DM, D17S855) was used. RESULTS: MSI analysis revealed a high frequency of multiple microsatellite changes in the exposed patients (84.6%) compared with non-exposed patients (8.3%). There was a significant difference (p < 0.001) between the two groups. CONCLUSIONS: These analyses clearly demonstrate that leukaemic cells from heavily exposed patients contain a number of genetic instabilities that may strongly influence the development of leukaemia among people exposed to the Hiroshima A-bomb radiation.

Aged↗
PubMed2001

An Arabidopsis sigma factor (SIG2)-dependent expression of plastid-encoded tRNAs in chloroplasts.

A eubacteria-type RNA polymerase (PEP) plays crucial roles for chloroplast development in higher plants. The core subunits are encoded on plastid DNA (rpo genes) while the regulatory sigma factors are encoded on the nuclear DNA (SIG genes). However, the definite gene specificity of each sigma factor is unknown. We recently identified an Arabidopsis recessive pale-green mutant abc1 in which T-DNA is inserted in SIG2 (sigB). In this mutant, almost normal etioplasts were developed under dark conditions while the small chloroplasts with poor thylakoid membranes and stacked lamellar were developed under light conditions. The sig2-1 mutant was deficient in accumulating enough photosynthetic and photosynthesis-related proteins as well as chlorophyll. However, mRNAs of their structural genes were not significantly reduced. Further analyses revealed that several plastid-encoded tRNAs including trnE-UUC that has dual function for protein and ALA biosyntheses were drastically reduced in the sig2-1 mutant. In contrast, nucleus-encoded T7 phage-type RNA polymerase (NEP)-dependent gene transcripts were steadily accumulated in the mutant. These results indicate that progress of chloroplast development requires SIG2-dependent expression of plastid genes, particularly some of the tRNA genes.

Arabidopsis↗
PubMed2001

Increased frequency of alleles associated with elevated tumor necrosis factor-alpha levels in children with Kawasaki disease.

Genetic polymorphisms influence the magnitude of the cytokine response after an inflammatory stimulus. To determine whether such polymorphisms might play a role in Kawasaki disease (KD), we analyzed white and Japanese children with KD and control populations for two polymorphic loci in which the A allele is associated with high tumor necrosis factor-alpha secretion. The lymphotoxin-alpha+250 A/A genotype was overrepresented among white children with KD compared with controls (0.59 versus 0.36; p = 0.013). The tumor necrosis factor-alpha-308 A/G genotype was overrepresented among whites with KD who had coronary artery abnormalities compared with those with normal echocardiograms (0.36 versus 0.09; p = 0.044). No significant difference was seen at either locus between Japanese children with KD and Japanese controls. The increased frequency of the high secretor alleles in white children with KD suggests that these loci may be related to susceptibility to KD and to outcome after disease.

Alleles↗
PubMed2001

Role of relative myocardial perfusion reserve for evaluating stenosis severity in patients with single-vessel coronary artery disease using.

A statistically significant correlation was observed between the severity of anatomic stenosis and coronary flow reserve in experimental animals. A similar correlation in human coronary artery disease (CAD) was shown using positron emission tomography (PET) and pharmacologic vasodilator stress. The present study tested whether the concept of relative myocardial perfusion reserve (MPR) might be superior to absolute MPR in correlating coronary stenosis determined by quantitative coronary arteriography in patients with single vessel CAD using [13N]ammonia and PET. The study group comprised 21 patients (62 +/-10 years old; 15 men, 6 women) with normal left ventricular function who underwent angioplasty for isolated left anterior descending coronary artery stenosis. Absolute MPR, the ratio of dipyridamole-induced hyperemic blood flow to baseline blood flow by [13N]ammonia PET, and relative MPR, the ratio of MPR in regions supplied by stenosed coronary arteries to MPR in remote regions, were measured before and 3 months after angioplasty. The percent diameter stenosis was also quantified on coronary arteriograms just before the angioplasty and again at 3 months after. The study found that absolute MPR (r=0.755; p<0.0001) and relative MPR (r=0.814; p<0.0001) were inversely and nonlinearly correlated with the percent stenosis on angiography. The fitting curve of the correlation between relative MPR and coronary stenosis on angiography was identical to that observed in animal models. Therefore, relative MPR measured by [13N]ammonia PET more accurately and specifically describes stenosis severity in patients with CAD compared with absolute MPR, probably because of its independence from hemodynamic variations and the effects of coronary risk factors.

Adult↗
PubMed2001

[Characteristics of abnormal behavior induced by delta 9-tetrahydrocannabinol in rats].

delta 9-Tetrahydrocannabinol (THC), one of the active compounds of marihuana, is known to induce drug dependence and tolerance, and its action is weaker than those of other abused drugs in humans and animals. Acute effects of THC, "high", "irritable" and "cognitive deficits" are more important than the drug dependence and tolerance. For this reason, we examined characteristics of abnormal behavior such as catalepsy-like immobilization, aggressive behavior including irritable aggression and muricide, and spatial cognition impairment induced by acute and chronic treatments of THC in rats. The catalepsy-like immobilization is related to a decrease in catecholaminergic and serotonergic neurons in the nucleus accumbens and amygdaloid nucleus and thus serves as a useful model for amotivational syndrome, one of cannabis psychoses. In aggressive behavior, muricide was determined by the housing condition. Muricide was induced if the rat was placed under an isolated housing condition within the period of the effect of single injection of THC. The behavioral change resembles exacerbation and flashback in humans. Spatial cognition is impaired by the interaction between cannabinoid (CB1) and 5-HT2 receptor in the dorsal raphe-hippocampal serotonergic neurons. Thus the abnormal behavior induced by THC can be a useful model for investigating mental function in humans and new drugs for the treatment of mental disorders.

Animals↗
PubMed2001

Role of dopaminergic system in core part of nucleus accumbens in hyperlocomotion and rearing induced by MK-801 in rats: a behavioral and in vivo microdialysis study.

We investigated modification of the MK-801 effect on motor activity and extracellular amines concentration by 6-hydroxydopamine (6-OHDA)-induced lesion of core nucleus accumbens (cACC) of rats. In vivo microdialysis-HPLC showed that the concentrations (fmol/microl) of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and serotonin were 0.738 +/- 0.135, 155.34 +/- 41.01 and 0.334 +/- 0.024, respectively, in the cACC of intact rats. The DOPAC/DA ratio was 264.24 +/- 94.01. Unilateral lesion of the cACC with 6-OHDA (8 microg/microl) substantially reduced DA (-93%) and DOPAC (-97%) in desipramine (30 mg/kg, i.p.)-pretreated rats (6-OHDA+DMI rats) as compared to the 65% reduction rate of both amines in saline-pretreated rats (6-OHDA+saline rats). Moreover, DOPAC was reduced by 72% in 6-OHDA+DMI rats. MK-801 increased DOPAC (426-467%) and DOPAC/DA ratio (180-230%) in intact rats. On the other hand, MK-801 increased DA by 154% and 505% in 6-OHDA+saline and 6-OHDA+DMI rats, respectively. 6-OHDA reduced the effect of MK-801 on DOPAC and DOPAC/DA ratio. In the behavioral studies, MK-801 (0.01-0.3 mg/kg, i.p.) increased locomotor activity and rearing of intact rats. Bilateral 6-OHDA+DMI lesion of the cACC caused greater reduction in the effect of MK-801 (0.1 mg/kg) than that of the shell nucleus accumbens. These results suggest that increased extracellular DOPAC concentration (but not DA) and DOPAC/DA ratio in the cACC plays an important role in MK-801-hyperactivity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Characteristics of learning and memory impairment induced by delta9-tetrahydrocannabinol in rats.

We investigated the characteristics of delta9-tetrahydrocannabinol (THC)-induced impairment of learning and memory using an 8-arm radial maze task, a water maze, a visual discrimination task with 2 figures and a passive avoidance test in rats. THC (6 mg/kg, i.p.) impaired spatial memory in the standard task of the 8-arm radial maze. THC (4-6 mg/kg, i.p.) selectively impaired working memory in a reference and working memory task of the 8-arm radial maze. Even at a dose of 10 mg/kg, THC did not impair spatial memory in the water maze. In addition, THC at a dose of 6 mg/kg, which had inhibitory effects in the 8-arm radial maze, did not affect performance in the visual discrimination task. These results indicate that at low doses (2-6 mg/kg), THC may not produce visual function abnormalities. THC impaired retrieval (6 mg/kg, i.p.) as well as acquisition (10 mg/kg, i.p.) in the passive avoidance test. The consolidation process was also impaired by i.c.v. injection (100 microg), but not i.p. injection (6-10 mg/kg) of THC. These results suggest that THC-induced impairment of spatial memory is based on the selective impairment of working memory through its effects on acquisition and retrieval processes.

Animals↗
PubMed2001

Rat tripeptidyl peptidase I: molecular cloning, functional expression, tissue localization and enzymatic characterization.

We purified tripeptidyl peptidase I (TPP I) to homogeneity from a rat kidney lysosomal fraction and determined its physicochemical properties, including its molecular weight, substrate specificity and partial amino acid sequence. The molecular weight of the enzyme was calculated to be 280,000 and 290,000 by non-denaturing PAGE and gel filtration, respectively, and to be 43 000 and 46 000 on SDS-PAGE in the absence and presence of beta-ME, respectively. These findings suggest that the enzyme is composed of six identical subunits. The Km, Vmax, kcat and kcat/Km values of TPP I at optimal pH (pH 4.0) were 680 microM, 3.7 micromol x mg(-1) x min(-1), 33.1 s(-1) and 4.87 x 10(4) s(-1) x M(-1) for Ala-Ala-Phe-MCA, respectively. TPP I was significantly inhibited by PCMBS and HgCl2, and moderately by DFP. These findings also suggest that TPP I is an exotype serine peptidase that is regulated by SH reagent. TPP I released the tripeptide Arg-Val-Tyr from angiotensin III more rapidly than from Ala-Ala-Phe-MCA, and also released Gly-Asn-Leu from neuromedin B with the same velocity as from Ala-Ala-Phe-MCA. Angiotensin III and neuromedin B have recently been found to be good natural substrates for lysosomal TPP I. Furthermore, we determined the rat liver cDNA structure and deduced the amino acid sequence. The cDNA, designated as lambdaRTI-1, is composed of 2485 bp and encodes 563 amino acids in the coding region. By Northern blot analysis, the order for TPP I mRNA expression was kidney > or = liver > heart > brain > lung > spleen >> skeletal muscle and testis. In parallel experiments, the TPP I antigen was detected in various rat tissues by immunohistochemical staining.

Amino Acid Sequence↗
PubMed2001

Activation of Na+/H+ exchanger is associated with hyperinsulinemia in borderline hypertensive rats.

Activation of Na+/H+ exchanger (NHE) is known to be related to elevated blood pressure in hyperinsulinemia. To test whether there is the change in NHE activity in insulin resistance, we measured NHE activity of platelets in fructose-induced hyperinsulinemia in Wistar-Kyoto rats (WKY), in borderline hypertensive rats (BHR), and in spontaneously hypertensive rats (SHR). All rats were fed a 60% fructose diet for 4 weeks to induce hyperinsulinemia and hypertriglyceridemia. Intracellular pH (pHi) was measured with a pH-sensitive fluorescent dye 2'7'-bis (2-carboxyethyl)-5-carboxyfluorescein acetoxymethyl ester. NHE activity was evaluated by the recovery of pHi following addition of sodium propionate (Vmax). Measurement of intracellular calcium ([Ca2+]i) was performed using fura2/acetoxymethylester. Systolic blood pressure in fructose diet BHR elevated significantly greater than that in control diet BHR with the increase of both [Ca2+]i and Vmax. In WKY, there was no significant increase in systolic blood pressure and [Ca2+]i except Vmax in a fructose diet. Vmax in control diet SHR was greater than in control diet WKY and BHR, and we found no additional increase in Vmax with a fructose diet in SHR. In BHR, a high salt diet increased systolic blood pressure and Vmax to a similar degree as a fructose diet or a high salt combined with a fructose diet. Plasma insulin concentration correlated positively with Vmax in WKY and BHR, but not SHR. A fructose diet induces hyperinsulinemia and elevates blood pressure in BHR. Hyperinsulinemia appears to activate NHE in a different manner in SHR, and might be associated with an elevation in blood pressure in BHR.

Animals↗