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Biomedical subjects

M Fujita

Publications and source records attributed to M Fujita.

At least 127 records · Page 7Linked to original sources

Doxazosin, an alpha1-adrenergic antihypertensive agent, decreases serum oxidized LDL.

Oxidized low-density lipoprotein (ox-LDL) is well known to play an important role in atherogenesis through the recruitment of monocytes into vessel walls and the deposition of cholesterol ester in the macrophages, which leads to the formation of lipid-rich plaque. It was assumed that only trace amounts of ox-LDL were present in plasma because the half-life of ox-LDL was only a few minutes. Recently, through the use of a monoclonal antibody against ox-LDL, a quantitative method to measure serum ox-LDL concentration has been developed. Metabolites of doxazosin, an alpha1-adrenergic antihypertensive agent, have been reported to inhibit oxidation of LDL in vitro. In this study, we investigated the in vivo effect of doxazosin on LDL oxidation using this new method to measure serum ox-LDL concentration. After the administration of doxazosin for 1 to 2 months, serum concentration of ox-LDL decreased significantly (P < .05). Although the reduction of ox-LDL concentration does not strictly indicate doxazosin's antiatherosclerotic effect, it may constitute one of doxazosin's additional weapons beside lowering blood pressure and serum lipid values in the prevention of atherosclerosis.

Adrenergic alpha-Antagonists↗

Analysis of the cell-dependent replication potentials of human immunodeficiency virus type 1 vif mutants.

Eleven in-frame vif gene mutants of HIV type 1 produced in non-permissive cells were examined for their replication potentials in various CD4-positive and -negative cell lines. Virus replication for each mutant was monitored by using several single- and multiple-cycle infectivity assays. Except for a mutant with wild-type phenotype, most mutants were severely defective for replication in all the cell lines as expected from the producer cell-dependent functioning of Vif so far reported. In contrast, two mutants, which have mutations in the hydrophilic or effector regions of Vif were found to have target cell-dependent replication potentials. These results demonstrate the presence of a novel category of the vif mutants important for elucidation of the Vif function.

Amino Acid Sequence↗

Heme oxygenase-1 (HO-1) protein induction in a mouse model of asthma.

BACKGROUND AND OBJECTIVE: Carbon monoxide (CO) is known to be present in measurable quantities in the exhalation of asthmatic patients. Corticosteroid treatment resulted in a decrease in exhaled CO levels in asthmatic patients, raising the possibility that an increase in exhaled CO concentration reflects inflammation of the asthmatic airway. Heme oxygenase-1 (HO-1) protein, also called HSP32, is the rate-limiting enzyme in the catabolism of heme to biliverdin, free iron and CO. However, it is unknown whether an expression of HO-1 within the lung tissue is related to allergic airway inflammation. We studied the expression of HO-1 in lung tissue and bronchoalveolar lavage cells in a mouse model of asthma. METHODS: Ovalbumin (OVA)-sensitized C57BL/6 mice were challenged with aerosolized OVA. HO-1 positive cells were identified by immunostaining in lung tissue and bronchoalveolar lavage fluid (BALF) after the challenge. RESULTS: HO-1 positive cell numbers increased in the subepithelium of the bronchi after OVA challenge. In cytospin preparations from BALF after OVA challenge, HO-1 was localized to alveolar macrophages. Inside the macrophages, HO-1 reactivity was expressed in the cytoplasm, and the perinuclear region in particular. CONCLUSION: The expression of HO-1 is increased within the lung tissue in allergic airway inflammation. Measurement of HO-1 activity may be clinically useful in the management of asthma.

Acetylcholine↗

Primary extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in the CNS.

Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type has been reported in various internal organs. Here a case is reported of MALT lymphoma developing in the cerebellopontine (CP) angle in a patient with Sjogren syndrome, and the concept of MALT lymphoma of the CNS is introduced. Pathologically, the tumor showed inflammatory features of reactive lymphocytic infiltration with follicle formation, but there were slightly atypical lymphocytes and plasmacytes with B-cell markers. These cells invaded reactive follicles, showing follicular colonization, and showed aberrant expression indicating their neoplastic nature. A review of the literature revealed eight cases of MALT lymphoma originating from the dura mater and one from the CP angle. The average age of patients was 50 years (range 28-66 years), and all patients were female. The tumors were slow to develop and the patients were cured after surgical removal and/or additional therapies. It is proposed that MALT lymphoma should be considered as a differential diagnosis of inflammatory pseudotumor of the CNS.

Adult↗

A study of the effect of color photostimulation from a cathode-ray tube (CRT) display on photosensitive patients: the effect of alternating red-cyan flicker stimulation.

PURPOSE: In an attempt to establish evidence for developing better guidelines for the production of animation programs that would not induce photosensitive seizures in Japan, we evaluated the effects of red flicker, alternating red/cyan (complementary color to red) flicker stimuli, and of contrast between the red and cyan frames from a cathode-ray tube (CRT) display in photosensitive patients. METHODS: We studied 35 photosensitive patients. They were exposed to seven types of flicker. The first three types were alternating red/cyan flicker (R/C) with the luminance of cyan set at three different levels, high, equal, and low luminance (65, 20, and 16 cd/m2, respectively) relative to the red (20 cd/m2). The following four types were red, cyan, yellow, and magenta flicker stimuli. EEGs were recorded while the patients watched these stimuli on a CRT display. RESULTS: Rates of photoparoxysmal response (PPR) provocation were 11.4, 13.7, and 14.0% with high-, no- and low-contrast R/C flicker, respectively, and 3.7% with red flicker. The differences between red and each of the other R/C flicker stimuli were all statistically significant (p<0.05, 0.01, 0.01). No significant differences were found between the effects by each of the three levels of contrast in alternating R/C flicker (p > 0.05). CONCLUSIONS: These findings suggest that alternating R/C flicker is more provocative than simple red flicker, and that contrast between frames of different colors may play some role in the effects of alternating flicker stimuli from a CRT display in photosensitive patients. Therefore, caution against the use of the combination of red and cyan, in addition to the red flicker stimulus, should be included in any guidelines drawn up to prevent photosensitive seizures.

Adolescent↗

Study on photo-pattern sensitivity in patients with electronic screen game-induced seizures (ESGS): effects of spatial resolution, brightness, and pattern movement.

PURPOSE: With the ever-increasing popularity of computers, electronic screen game-induced seizure (ESGS) is beginning to pose a serious social problem. To elucidate the pathophysiology of ESGS, with the ultimate goal of prevention, we have been studying photo-pattern sensitivity in detail with a pattern-stimulation test using a CRT (cathode ray tube) display. This method is referred to as the "CRT-pattern test." METHODS: We studied 17 patients brought to our department for evaluation of ESGS. EEG responses were recorded during exposure to various patterns consisting of three elements: spatial resolution, brightness perception, and pattern-movement recognition displayed on a CRT monitor. Photo-paroxysmal response (PPR) frequencies were compiled for each stimulation. RESULTS: PPR was induced by the CRT-pattern test in nine of the 17 cases. In four cases, PPR induction was obtained only after introducing CRT-pattern tests in addition to standard intermittent photic stimulation (IPS). The rate of PPR induction differed according to the type of pattern, spatial frequency, and pattern-reversal frequency. However, neither the clarity of the edges of a pattern nor changes in the brightness of a pattern element had any effect on the rate of PPR induction. With the exception of a few subjects, the stimulation caused by pattern movement was not effective in eliciting PPR. Six cases in whom spatial resolution was involved showed occipital dominance in PPR provocation, and three in whom brightness perception and pattern movement recognition was involved showed frontal dominance. CONCLUSIONS: The CRT-pattern test is useful for identifying patients with photosensitivity among patients considered to have incidental or nonphotosensitive seizures unresponsive to standard IPS. Patients with ESGS caused by photosensitivity can be divided into two groups: those with occipital dominance for PPR provocation, in whom spatial resolution is involved; and another group with frontal dominance, in whom brightness perception and pattern-movement recognition (or possibly perception of colors) are involved.

Adolescent↗

Enhanced external counterpulsation improved myocardial perfusion and coronary flow reserve in patients with chronic stable angina; evaluation by(13)N-ammonia positron emission tomography.

AIMS: The mechanism by which enhanced external counterpulsation therapy exerts its beneficial effects on chronic and symptomatic stable angina is largely unknown. To clarify the mechanism of action of enhanced external counterpulsation, we used(13)N-ammonia positron emission tomography to evaluate myocardial perfusion. METHODS AND RESULTS: This was not a randomized controlled study. Eleven patients (eight male, age: 61.6+/-9.7) with angina pectoris underwent enhanced external counterpulsation therapy for 35 1 h sessions. They underwent a treadmill exercise test and(13)N-ammonia positron emission tomography, both at rest and with dipyridamole, before and after enhanced external counterpulsation therapy. Neurohumoral factors and nitric oxide were also evaluated. Myocardial perfusion increased at rest after therapy (0.69+/-0.27 to 0.85+/-0.47 ml x min(-1) x g(-1), P<0.05). In ischaemic regions, particularly the anterior region, myocardial perfusion at rest and with dipyridamole and coronary flow reserve improved significantly after therapy (at rest: 0.71+/-0.26 to 0.86+/-0.31;P<0.05, with dipyridamole: 1.26+/-0.65 to 1.84+/-0.94;P<0.02, coronary flow reserve: 1.75+/-0.24 to 2.08+/-0.28;P<0.04). Exercise time was prolonged and the time to 1-mm ST depression improved markedly (P<0.01). After therapy, nitric oxide levels increased (P<0.02) and neurohumoral factors decreased. CONCLUSIONS: Enhanced external counterpulsation therapy improved myocardial perfusion at rest and with dipyridamole and was associated with an increased exercise tolerance with(13)N-ammonia positron emission tomography and increased nitric oxide levels. These results suggest that one of the enhanced external counterpulsation mechanisms is development and recruitment of collateral vessels.

Adult↗

Destruction of acetabular bone caused by early failure of a constrained acetabular component.

Use of a constrained acetabular component is 1 option for the treatment of dislocation after total hip arthroplasty. We report a case of a constrained acetabular component that resulted in postoperative early fixation loss and required revision 12 days after primary surgery. The superoposterior wall of the acetabulum was destroyed by the migrated acetabular component. Sharp ends of screws with a metal shell may have plowed up acetabular bone gradually after fixation loss of the component. This failure illustrates the potential risk of using a constrained acetabular component for total hip arthroplasty.

Acetabulum↗

Endoscopic screening for early esophageal cancer by iodine staining in patients with other current or prior primary cancers.

BACKGROUND: Although early diagnosis of esophageal carcinoma is an important determinant of outcome, early stage carcinomas are rarely detected on routine endoscopic examination. Iodine staining may be useful in the detection of early stage esophageal carcinoma, especially in high-risk populations. In a prior study, 29.2% (68/233) patients with superficial esophageal carcinoma (SEC) undergoing resection at our hospital had other nonesophageal primary carcinomas, suggesting that patients with nonesophageal primary cancers are at increased risk for the development of esophageal cancer. The aim of the current study was to determine whether endoscopic screening with iodine staining is useful for the detection of SEC in patients with a history of non-esophageal cancers. PATIENTS AND METHODS: In a prospective study, 331 patients with nonesophageal primary cancers were screened for esophageal cancer by endoscopic examination with iodine staining. All patients were men 55 years of age or older. RESULTS: Nine patients (2.7%) with SEC were identified. Among these patients, 7 with mucosal cancer were treated by endoscopic mucosal resection, and 2 with submucosal cancer were treated by surgical resection or radiation therapy. Five patients (1.5%) were found to have cancer confined to the epithelium or the lamina propria. These lesions were difficult to detect by conventional endoscopic screening and were cured by endoscopic mucosal resection. After exclusion of 51 patients with head and neck cancer, the incidence of SEC was still 2.1% (6/280), higher than reported in prior screening studies. CONCLUSIONS: All men with a history of nonesophageal primary cancers should undergo endoscopic screening for esophageal cancer. Endoscopic iodine staining in such patients may be useful in screening for early stage esophageal carcinoma.

Aged↗

Metachronous squamous cell carcinoma of the esophagus arising after endoscopic mucosal resection.

BACKGROUND: Endoscopic mucosal resection (EMR) is being used increasingly to treat early stage esophageal carcinoma. However, the preserved esophageal mucosa may be the source of new lesions. The aims of this study were to analyze the frequency of metachronous esophageal carcinoma after EMR and to determine whether minute iodine unstained areas often associated with squamous cell carcinoma develop into carcinoma. METHODS: Eighty-two patients with esophageal squamous cell carcinoma who underwent EMR were studied. Based on the iodine staining pattern at initial EMR, they were divided into those with uniform (group U) and scattered (group S) types of background mucosa. Patients were followed by endoscopy with iodine staining (group U: median 39 months, range 12 to 71 months; group S: median 38 months, range 14 to 68 months). RESULTS: In total, 12 (14.6%) of 82 patients were found to have metachronous esophageal carcinoma during follow-up, including 6 (37.5%) of 16 patients in group S. The cumulative proportion of metachronous carcinoma-free subjects was significantly lower in group S than group U (p = 0.0048). CONCLUSIONS: Primary esophageal carcinoma develops frequently in patients who have undergone EMR for esophageal squamous carcinoma. The high frequency of metachronous carcinoma may be attributed to field carcinogenesis. Careful long-term endoscopic observation is required for patients who undergo EMR for esophageal carcinoma, especially those with scattered-type iodine staining of the background mucosa.

Aged↗

Evaluation of the autonomic nervous system function in children with primary monosymptomatic nocturnal enuresis--power spectrum analysis of heart rate variability using 24-hour Holter electrocardiograms.

OBJECTIVE: The purpose of this study was to evaluate the circadian rhythm of the autonomic nervous system functions of children with primary monosymptomatic nocturnal enuresis. MATERIAL AND METHODS: The subjects were allocated to three groups--enuresis group (n = 72), normal control group (n = 26), post-treated and cured enuresis group (n = 13). In the three groups. we evaluated the autonomic nervous system function by the power spectrum analysis of heart rate variability (HRV) using 24-hour Holter electrocardiograms. Frequency components of the power spectra of HRV (% power) were divided into three factors; the very low frequency (VLF), the low frequency (LF) and the high frequency (HF) by computer analysis using Fast Fourier Transformation (FFT). RESULTS: In the three groups, the HF component reflecting parasympathetic activity was significantly higher, compared with the LF during sleep. The HF in the enuresis group was significantly higher, compared with the HF in the control group during sleep. The HF in the control group was significantly lower, compared with the LF during waking. However, the HF in the enuresis group was significantly higher, compared with the LF during waking. It showed more increased parasympathetic tone in the enuresis group, compared with that of the control group during sleep and waking. In the post-treated enuresis group, the HF during sleep and waking were significantly decreased, compared with those before treatment. CONCLUSION: These findings suggest the parasympathetic hyperfunction through 24 hours and abnormal circadian rhythm of autonomic nervous system functions in the enuresis group. The post-treated enuresis group showed normal autonomic nervous system functions.

Autonomic Nervous System↗

Lysophosphatidylcholine induces apoptosis in AR42J cells.

Phospholipase A2 (PLA2) has been suggested to play an important role in the pathogenesis of acute pancreatitis, in part through the PLA2-generated phospholipid by-products, most notably lysophosphatidylcholine (lyso-PC). The effects of lyso-PC on pancreatic acinar cells, other than the induction of necrosis, are poorly characterized. Here we examined the effects of lyso-PC on the induction of apoptosis in rat pancreatic AR42J cells. Lyso-PC induced apoptosis in a dose-dependent manner at 10 and 25 microM, but induced cell lysis at > or = 50 microM. Lyso-PC-induced (at 25 microM) apoptosis was not blocked by a protein kinase C inhibitor (staurosporine) or by inhibitors of caspases (acetyl-DEVD-aldehyde and benzoyloxycarbonyl-VAD-fluoromethylketone). Lyso-PC at 10 and 25 microM induced the expression of clusterin mRNA and wild-type p53. Apoptosis induction by lyso-PC (at 25 microM) was not inhibited by a specific antagonist of platelet-activating factor (PAF) receptor, suggesting that the action was independent of th

Animals↗

[11C]methionine positron emission tomography for the evaluation of pancreatic exocrine function in chronic pancreatitis.

Positron emission tomography (PET) can be used for the quantitative analysis of amino acid metabolism. The aim of this study was to investigate whether pancreatic exocrine function can be evaluated by [11C]methionine PET in chronic pancreatitis (CP) patients. Dynamic PET scan of the pancreas and liver was performed in eight healthy subjects and seven patients with CP after intravenous (i.v.) injection of [11C]methionine. Simultaneously, duodenal juice was collected with the background of continuous i.v. administration of secretin (125 ng/kg/h). The radioactivity ratio of the pancreas to that of the liver (PLR) was calculated by regions of interest (ROI) analysis. Amylase output and bicarbonate concentration were measured in the duodenal aspirates. The PLR of CP patients was significantly lower than that of healthy subjects at all time points after methionine injection. The PLRs at 4.5 minutes (PLR4.5) after methionine injection were positively correlated with the amylase output, mean bicarbonate concentration, and volume of duodenal aspirates (R = 0.74, 0.69, 0.46). It is concluded that [11C]methionine PET would be a noninvasive method for the evaluation of exocrine pancreatic function, which may represent total amino acids uptake of viable acinar cells in the pancreas.

Adult↗

Ascites of rat experimental model of severe acute pancreatitis induces lung injury.

The molecular mechanisms that lead from acute pancreatitis (AP) to multiple organ failure remain to be clarified. We previously reported that ascitic fluids from a rat model of severe acute pancreatitis (pancreatitis-associated ascitic fluids, PAAF) transcriptionally activated endothelial cells and leukocytes in vitro. To clarify the role of ascitic fluids on the development of multiple organ failure in AP, we examined the effects of PAAF on the prognosis and immunohistologic findings in cerulein pancreatitis, an experimental model of mild pancreatitis in vivo. Intraperitoneal injection of PAAF decreased the survival rates in a dose-dependent manner. Histologically, destruction of vessels, alveolar septal thickening, interstitial hypertrophy, and infiltration of inflammatory cells were prominent in the lung of PAAF-injected rats. Transcription factor, nuclear factor KB (NF-kappaB) was activated and the mRNA levels of tumor necrosis factor-alpha and interleukin-1beta were increased in the lung of the PAAF-injected rats. The permeability index assessed by Evans blue assay and the lung myeloperoxidase activity levels were significantly higher in the PAAF-injected rats than in controls. Inhibition of NF-kappaB ameliorated the histologic findings and improved the survival rates. Our results suggest that PAAF play a role in the pathogenesis of lung injury in severe AP, at least in part through the activation of NF-kappaB.

Acute Disease↗

Interactions and nuclear import of the N and P proteins of sonchus yellow net virus, a plant nucleorhabdovirus.

We have characterized the interaction and nuclear localization of the nucleocapsid (N) protein and phosphoprotein (P) of sonchus yellow net nucleorhabdovirus. Expression studies with plant and yeast cells revealed that both N and P are capable of independent nuclear import. Site-specific mutagenesis and deletion analyses demonstrated that N contains a carboxy-terminal bipartite nuclear localization signal (NLS) located between amino acids 465 and 481 and that P contains a karyophillic region between amino acids 40 and 124. The N NLS was fully capable of functioning outside of the context of the N protein and was able to direct the nuclear import of a synthetic protein fusion consisting of green fluorescent protein fused to glutathione S-transferase (GST). Expression and mapping studies suggested that the karyophillic domain in P is located within the N-binding domain. Coexpression of N and P drastically affected their localization patterns relative to those of individually expressed proteins and resulted in a shift of both proteins to a subnuclear region. Yeast two-hybrid and GST pulldown experiments verified the N-P and P-P interactions, and deletion analyses have identified the N and P interacting domains. N NLS mutants were not transported to the nucleus by import-competent P, presumably because N binding masks the P NLS. Taken together, our results support a model for independent entry of N and P into the nucleus followed by associations that mediate subnuclear localization.

Cell Nucleus↗