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Biomedical subjects

K Fujii

Publications and source records attributed to K Fujii.

At least 379 records · Page 21Linked to original sources

Conversion of gamma-glutamylcysteinylethyl ester to glutathione in rat hepatocytes.

The conversion of gamma-glutamylcysteinylethyl ester (gamma-GCE) to glutathione in a reduced form (GSH) was examined using isolated rat hepatocytes pretreated with diethylmaleate, a GSH-depletor. Incubation of hepatocytes with 0.1 and 5.0 mM gamma-GCE (gamma-GCE-hepatocytes) over a 30-min period resulted in time-dependent increases in intracellular GSH and nonprotein-SH (NP-SH) concentrations. Hepatocytes incubated with 5.0 mM but not 0.1 mM GSH over a period of 30 min showed a time-dependent increase in intracellular GSH concentration. In the gamma-GCE-hepatocytes pretreated with bis-(p-nitrophenyl)phosphate (BNPP), a non-specific esterase inhibitor, an enhancement of intracellular GSH concentration was markedly reduced. gamma-GCE concentration in the gamma-GCE-hepatocytes with BNPP pretreatment was significantly higher than that in the cells without BNPP pretreatment, although there was no difference in the total amount of intracellular NP-SH, i.e., gamma-GCE, GSH, gamma-glutamylcysteine, cysteine ethyl ester, and cysteine between both gamma-GCE-hepatocytes. The present results indicate that gamma-GCE is transported into liver cells more easily than GSH itself, resulting in its conversion to GSH via esterase and glutathione synthetase within the cells.

Animals↗

Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute anterior wall myocardial infarction.

BACKGROUND: Epicardial coronary flow is occasionally reduced even after coronary intervention despite the absence of vessel obstruction in patients with acute myocardial infarction. Our aim was to clarify the cause and outcomes of radiocontrast slow filling in patients with reperfused acute anterior myocardial infarction by assessing microvascular damage with the use of myocardial contrast echocardiography (MCE) and functional outcomes. METHODS AND RESULTS: We carefully reviewed the cineangiograms of 86 patients who achieved coronary revascularization within 12 hours of the onset and underwent MCE before and soon after recanalization with the intracoronary injection of sonicated microbubbles. Antegrade coronary flow after recanalization was graded by two observers based on Thrombolysis in Myocardial Infarction (TIMI) trial flow grades. Left ventricular ejection fraction was measured on the day of infarction and 1 month later. TIMI grade 2 was observed in 18 patients (21%), and the other 68 patients manifested TIMI grade 3 after recanalization. All patients with TIMI 2 showed substantial MCE no reflow, whereas only 11 patients (16%) with TIMI 3 showed MCE no reflow. Functional improvement was worse in patients with TIMI 2 than in those with TIMI 3 (TIMI 2, 38 +/- 8% versus 40 +/- 8%, P = NS [acute versus late]; TIMI 3, 44 +/- 13% versus 55 +/- 13%, P < .001). Among patients with TIMI 3, significant functional improvement was observed only in patients with MCE reflow (MCE reflow, 46 +/- 13% versus 57 +/- 12%, P < .001; MCE no reflow, 35 +/- 11% versus 45 +/- 12%, P = NS). CONCLUSIONS: Despite no obstructive lesion of the vessel, TIMI 2 is caused by advanced microvascular damage and is a highly specific, although not sensitive, predictor of poor functional outcomes in patients with acute myocardial infarction. TIMI 3 does not necessarily indicate myocardial salvage, and detection of MCE no reflow in these patients is particularly useful for the prediction of functional outcome.

Adult↗

Expression of c-fos gene inhibits proteoglycan synthesis in transfected chondrocyte.

The effect of expression of c-fos gene on proteoglycan synthesis, one of the important markers of cartilage metabolism, was examined by introducing the c-fos DNA into HCS 2/8 chondrocytes. The [35S]sulfate incorporation into proteoglycan was decreased in the c-fos transfectants expressing exogenous c-fos mRNA, when compared to a control transfectant. A significant increase in transcription of MMP-3 with the suppressed transcription of aggrecan and TIMP-1 were also observed in the c-fos transfectants. Moreover, analysis of the effect of AP-1 proteins on the collagenase and TIMP-1 promoters in gastric carcinoma KKLS cells revealed that c-Fos combined with any of the Jun-related proteins failed to stimulate the TIMP-1 promoter, though collagenase promoter was effectively activated by any Fos/Jun-related protein heterocomplex. These findings indicate that the c-fos expression may govern the cartilage metabolism and hence may play an important role in the pathogenesis of joint destruction in arthritis.

Base Sequence↗

Ligand activation of overexpressed epidermal growth factor receptor results in colony dissociation and disturbed E-cadherin function in HSC-1 human cutaneous squamous carcinoma cells.

Various types of tumors show aberrant expression and overexpression of epidermal growth factor (EGF) receptor and the degree of receptor expression correlates with a malignant phenotype in many epithelial tumors. However, in vitro evidence supporting the advantageous role of receptor overexpression is deficient. In this study, we compared the effects of exogenous EGF on the cell colony morphology in monolayer and collagen gel culture between HSC-1 squamous carcinoma cells overexpressing EGF receptor and their revertant subline cells. These cells formed coherent cell colonies under routine culture conditions, but addition of EGF induced dissociation of cell colonies within 24 h in the parent HSC-1 cells, though not in the subline cells. Since the colony dissociation apparently involved loss of cell-cell adhesion, we also studied the effects of EGF on E-cadherin expression and its function. Cell aggregation assays showed that EGF reduced E-cadherin function dose-dependently in the parent cells, but not in the subline cells. However, immunoblotting analysis and ELISA showed the absence of downregulation or degradation of E-cadherin. Instead, EGF tyrosine phosphorylated cadherin/catenin complex components including beta-catenin and increased the detergent solubility of E-cadherin in the parent cells. These results suggest that EGF modified the functional association between E-cadherin and actin filament through tyrosine phosphorylation of the cadherin/catenin complex and thereby made the adhesion molecule incompetent. Our results indicate that the ligand activation of overexpressed EGF receptor impairs E-cadherin-mediated cell-cell adhesion and causes dissociation of the squamous carcinoma cell colonies, which facilitates tumor cell invasion in vivo. This might be relevant to the advantageous role of EGF receptor overexpression in malignant phenotype of epithelial tumor cells.

Cadherins↗

K-ras and p53 mutations in stage I gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct.

BACKGROUND: An anomalous junction of the pancreaticobiliary duct (AJPBD) was thought to be an important risk factor for gallbladder carcinoma in Japan. In this report, we compared K-ras and p53 mutations in Stage I gallbladder carcinomas (GC) of patients with AJPBD with those in patients without AJPBD: METHODS: We examined 6 GC of patients with AJPBD and 20 GC of patients without AJPBD: Immunohistochemistry was performed for p53 protein. K-ras and p53 mutations were examined using genomic DNA extracted from the cancer regions. The methods of polymerase chain reaction (PCR) single strand conformation polymorphism analysis were performed for mutations in exons 5-8 of p53. The methods of PCR restriction fragment length polymorphism were performed for mutation in codon 12 of K-ras. RESULTS: p53 positivity was 67% in GC of patients with AJPBD and 65% in GC of patients without AJPBD: p53 mutations were found in exons 7 and 8 in GC of patients with AJPBD and in exons 5, 6, and 7 in GC of patients without AJPBD: The incidence of K-ras mutation in GC of patients with AJPBD (50%) was greater than that in patients without AJPBD (6%) (P < 0.05). CONCLUSIONS: These results suggest that K-ras mutation may be important in the early stage of carcinogenesis of the gallbladder mucosa with AJPBD, and that p53 mutations may also contribute to the early stage of carcinogenesis of the gallbladder mucosa, regardless of AJPBD:

Adenocarcinoma↗

Clinical implications of the 'no reflow' phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction.

BACKGROUND: Recent studies demonstrated that the "no reflow" phenomenon after coronary reflow implies the presence of advanced myocardial damage. In this study, we verified the prognostic value of the detection of this phenomenon by studying complications, left ventricular morphology, and in-hospital survival after acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 126 patients with a first anterior AMI. All patients received coronary reflow within 24 hours of onset of symptoms and underwent myocardial contrast echocardiography (MCE) before and shortly after coronary reflow with an intracoronary injection of sonicated microbubbles. From contrast reperfusion patterns, patients were divided into two subsets: those with MCE no reflow (47 patients, 37%) and those with MCE reflow (79 patients). There was no difference in the frequency of arrhythmia or coronary events between the two subsets. Pericardial effusion and early congestive heart failure were observed more frequently in patients with MCE no reflow than in those with MCE reflow (26% versus 4%, P < .05; 45% versus 15%, P < .05, respectively). Congestive heart failure tended to be prolonged in those with MCE no reflow, and 3 patients (7%) of this subset died of pump failure. Left ventricular end-diastolic volume progressively increased in the convalescent stage in patients with MCE no reflow (early versus late, 145 +/- 43 versus 169 +/- 60 mL, P < .001), whereas it decreased in those with MCE reflow (154 +/- 42 versus 144 +/- 44 mL, P < .01). CONCLUSIONS: The substantial size of the MCE no reflow phenomenon at coronary reflow conveys useful information about an outcome of coronary intervention and left ventricular remodeling in individual patients with anterior wall AMI, although these are suggestive results in a limited number of patients.

Adult↗

Significance of proliferating cell nuclear antigen (PCNA) expression in gastric cancer in relation to lymph node metastasis.

Proliferating cell nuclear antigen (PCNA) in gastric cancer was evaluated in relation to lymph node metastasis. A total of 125 gastric cancer patients who underwent gastrectomy were studied immunohistochemically. The PCNA-positive rate of the primary lesion with lymph node metastasis (47.6%) was significantly higher than those in those without metastasis (24.3%, P < 0.0001). The PCNA-positive rate of early gastric cancer was significantly higher in lesions with lymph node metastasis (36.9%) than in lesions without lymph node metastasis (14.7%). However, there was no significant difference between lesions with and without lymph node metastasis in advanced gastric cancer. In addition, the PCNA-positive rate in metastatic lesions (44.6%) was significantly higher than that in the primary lesion (40.0%, P = 0.001). It is concluded that gastric cancer with higher tumor growth activity has a higher rate of lymph node metastasis. Cancer cells in the metastatic foci of lymph node have a higher proliferating activity than that in the primary lesion.

Female↗

Expression of cripto in human gall bladder lesions.

The expression of cripto, a member of the epidermal growth factor (EGF) family, was examined by immunohistochemistry in benign lesions and carcinomas of the gall bladder. Cripto expression was detected in 6 (67 percent) of 9 hyperplasias, 4 (58 percent) of 7 adenomas, and 89 (68 percent) of 132 adenocarcinomas of the gall bladder. The degree of cripto expression was not correlated with depth of tumour invasion, tumour stage or patient prognosis. The incidence of cases with cripto expression was significantly higher in papillary and well-differentiated adenocarcinomas (positive 73 percent; strongly positive 38 percent) than in moderately and poorly differentiated adenocarcinomas (positive 54 percent; strongly positive 17 percent) (P < 0.05). These results suggest that cripto expression may not relate to progression in gall bladder carcinomas, but may be associated with tumour differentiation.

Adenocarcinoma↗

Effects of the addition of hyaluronate segments with different chain lengths on the viscoelasticity of hyaluronic acid solutions.

The effects of the addition of sodium hyaluronate segments (sHA) with different chain lengths on the viscoelasticity of high molecular weight sodium hyaluronate (HA) aqueous solutions were studied. The additive effects of sHA depended on the chain length of sHA. Shorter sHA decreased storage (G') and loss (G") moduli, whereas longer sHA increased both moduli. In physiological saline, the effects of the addition of sHA depended on the chain length of sHA, as in aqueous solutions, except that shorter segments did not decrease both moduli. The effects of the addition of monosaccharides, i.e., N-acetyl glucosamine (GlcNAc) and sodium glucuronate (GlcANa), were also studied. Although GlcNAc increased G' and G", GlcANa decreased both moduli. A shift factor "A," which depended on chain-length effects, a sugar effect, and a salt effect, was developed to explain these additive effects quantitatively.

Carbohydrate Sequence↗

A source of haemorrhage in adult patients with moyamoya disease: the significance of tributaries from the choroidal artery.

This study concerns 19 patients over 16 years of age with Moyamoya disease. Ten cases of intracranial haemorrhage, as the initial haemorrhagic event in patients aged from 21 to 55 (haemorrhagic group) and 9 cases of ischaemic events in 18- to 53-year-old patients (ischaemic group) were included. All haemorrhages were associated with intraventricular haemorrhages (IVH); and all but one case of thalamic haemorrhage were thought to be primary IVH (2 cases of small paraventricular haemorrhage; 2 of small haemorrhages in the splenium; 5 with no intracerebral haematoma). In the 9 patients of the ischaemic group, there were 2 cases of transient ischaemic attacks and 7 of cerebral infarction. Angiographic evaluations demonstrated that the abnormal basal vessel formation and the collateral supplies from the external carotid arteries were poorly developed in both groups. In contrast, the collateral circulation via the choroidal and posterior pericallosal arteries was well demonstrated. Furthermore, marked enlargement of the choroidal arteries and the medullary arteries derived from them was seen more frequently in the haemorrhagic group. These findings suggested that the haemodynamic load in the vessels supplying the walls of the posterior parts of the ventricles and the periventricular region was increased, especially in the haemorrhagic group. Those vessels were considered to be important sites of IVH in adult patients with Moyamoya disease.

Adult↗

Hepatic Fas antigen expression before and after interferon therapy in patients with chronic hepatitis C.

To assess the relationship between hepatitis C virus infection and Fas antigen expression on hepatocytes, we examined changes in hepatic Fas antigen expression in the presence or absence of active hepatitis C virus infection. Twenty patients with chronic hepatitis C infection were treated with interferon and underwent pre- and posttreatment liver biopsies. Patients were classified according to the absence (group A; n = 9) or the presence (group B; n = 11) of hepatitis C virus RNA (HCV-RNA) in the liver after interferon therapy. An immunohistochemical assay showed Fas antigen staining in hepatocytes membranes and cytoplasm with expression concentrated mainly in periportal areas. The percentage of Fas-positive cells in the liver before treatment was not different between group A (39.5+/-19.1%) and group B (32.5+/-15.6%). Hepatic Fas expression was reduced significantly after treatment (24.3+/-10.6%) compared with the pretreatment values in group A (p < 0.05) but not in group B (25.9+/-16.9%). There was no significant difference between the two groups in the degree of histologic improvement. These results suggest that hepatic Fas expression is associated with persistent infection of hepatitis C virus.

Adult↗

Benign fibrous histiocytoma of the femur: review of three cases.

OBJECTIVE: Benign fibrous histiocytoma is a tumor with histologic features similar to those of xanthofibromas, which include fibrous cortical defects and nonossifying fibromas, but with different clinical features. This study investigated the findings of benign fibrous histiocytoma on various imaging modalities. It emphasized the importance of clinical and imaging features as well as histologic findings in establishing the diagnosis. DESIGN: We reviewed three cases of benign fibrous histiocytoma of the femur that had been diagnosed histologically as (fibro)xanthoma during a retrospective analysis of 187 primary benign and malignant bone lesions. PATIENTS: All the patients were middle-aged women with various knee complaints. RESULTS AND CONCLUSIONS: Radiologically, the lesions were all lytic with well-defined geographic margins and sclerotic rims. The tumors arose within the medullary cavity in the distal metaphysis of the femur and involved the epiphysis. CT showed lytic destruction with well-defined marginal sclerosis. T1-weighted MR images showed that the lesions had predominantly the same signal intensity as that of skeletal muscle. The lesions were hypovascular on angiography. Bone scintigraphy showed moderately increased uptake. It was concluded that multiple images as well as clinical features can be useful in differentiating benign fibrous histiocytoma from fibroxanthoma, giant cell tumor, and other fibrohistiocytic tumors of bone.

Aged↗

Lithium side effects in relation to brain lithium concentration measured by lithium-7 magnetic resonance spectroscopy.

1. The relationship between lithium (Li) side effects and brain Li concentration was examined in 17 patients with bipolar disorder treated with Li and other psychotropic drugs. 2. Brain Li concentration was measured by Li-7 magnetic resonance spectroscopy (MRS). Side effects were assessed using the UCLA General Side Effect Rating Scale For Lithium Treatment (GSE). 3. There was no correlation between the total GSE score and the brain, serum, or erythrocyte Li concentrations. Patients with hand tremor had significantly higher brain Li level (0.51 + or - 0.27 mM) than those without apparent tremor (0.36 + or - 0.20 mM), but no significant difference in serum Li level was seen. As far as the patients had hand tremor, they rarely had brain Li concentration less than the therapeutic range (1 of 15 measurement). On the other hand, they often had brain Li levels less than the therapeutic range when they did not have apparent tremor (13 of 52 measurements). 4. This preliminary study suggests that hand tremor is associated with the brain Li concentration.

Adult↗

Mild hyperglycemia and insulin treatment in experimental cerebral ischemia in rats.

We investigated the effects of mild hyperglycemia and insulin treatment on the metabolism of the ischemic brain in spontaneously hypertensive rats with acute hyperglycemia (n = 9), acute hyperglycemia treated with insulin during ischemia (n = 10), and normoglycemia (n = 10). Cerebral blood flow was measured by the H2 clearance method. Cerebral ischemia induced by occlusion of the bilateral carotid arteries. Cerebral glycolytic metabolites were measured enzymatically. Blood glucose levels were significantly higher in hyperglycemic animals (11.8 to 13.7 mM/l) than in normoglycemic animals (6.0 mM/l). At 60 min of ischemia, the blood flow to the parietal cortex was decreased to 3% of the resting value in all groups. Blood glucose levels at 60 min of ischemia in the hyperglycemic rats were 1.9--3 times higher than the treated hyperglycemic rats and normo-glycemic rats. Glucose concentrations were significantly and positively correlated with the ATP level (p < .0001) but not with the lactate levels in the ischemic brain. Our results suggest that mild hyperglycemia may preserve glucose metabolism in the presence of ischemic insult.

Analysis of Variance↗

Temporal changes in regional end-diastolic wall thickness early after reperfusion in acute anterior myocardial infarction: relation to myocardial viability and vascular damage.

We investigated early temporal changes in end-diastolic wall thickness (EDWT) of the infarcted myocardium in 46 patients with reperfused anterior acute myocardial infarction in relation to myocardial viability. Two-dimensional echocardiography was performed on days 1 and 2 of acute myocardial infarction, and the EDWT of the anterior segment was measured in the short-axis view. Patients were divided into three groups on the basis of day 1 to day 2 ratio of EDWT: the ratio < or = 0.85 as group A (n = 13), >0.85 but < or = 1.15 as group B (n = 23), and >1.15 as group C (n = 1 0). Left ventricular functional improvement was significantly better in group B than in groups A and C. Substantial size of "no reflow" phenomenon was observed only in groups A (n = 9, 69%) and C (n = 6, 60%). The frequency of transient ST re-elevation after reperfusion was the highest in group C (70%), and left ventricular expansion was observed at day 2 only in group A. We conclude that changes in the EDWT of the infarct segment early after reperfusion, either decreases or increases, are related to irreversibly damaged myocardium. A decrease in EDWT and concomitant ventricular expansion may be related to impaired myocardial perfusion. An increase in EDWT after reperfusion may be caused by accelerated myocardial and microvascular damage after reperfusion.

Adult↗

Myocardial integrated ultrasonic backscatter in patients with old myocardial infarction: comparison with radionuclide evaluation.

The purpose of our study was to clarify whether the abnormalities in integrated backscatter may be used to assess myocardial viability in patients with old myocardial infarction by comparing these integrated backscatter parameters with conventional radionuclide and echocardiographic estimates of myocardial viability. Two myocardial integrated backscatter parameters, the magnitude of cyclic variation in integrated backscatter and the myocardial integrated backscatter calibrated with the power of Doppler signals from the blood along the same ultrasound beam (calibrated myocardial integrated backscatter), were measured in 21 normal persons and 33 patients with old anteroseptal myocardial infarction. Calibrated myocardial integrated backscatter was higher and the magnitude of cyclic variation in integrated backscatter was lower in the infarct septum compared with the septum of normal subjects. Percent thallium uptake, as assessed in scintigraphic images taken at rest or after reinjection, correlated well with the calibrated myocardial integrated backscatter (r = -0.72, p < 0.01) and more weakly but significantly with the magnitude of cyclic variation in integrated backscatter (r = 0.55, p < 0.05) in 16 of 33 patients. The measurement of calibrated myocardial integrated backscatter, in addition to the magnitude of cyclic variation of integrated backscatter, may likely be valuable in the noninvasive assessment of myocardial viability.

Adult↗