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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 109 records · Page 6Linked to original sources

Fisetin induces transcription of NADPH:quinone oxidoreductase gene through an antioxidant responsive element-involved activation.

Induction of phase II enzymes such as NADPH:quinone oxidoreductase (QR) can reduce carcinogen-induced mutagenesis and tumor formation. In our search for novel dietary anticarcinogens, fisetin, a flavonol widely distributed in fruits and vegetables was found to induce QR activity in murine hepatoma 1c1c7 cells. The cells were treated with various concentrations of fisetin, and then were assessed for cell growth, QR activity, QR mRNA expression and transcription activation of the QR gene. The results showed that fisetin induced QR activity in time- and dose-dependent manner in the concentration range of 0.1 to 10 microM, and the activity induction was associated with QR mRNA expression as detected by reverse transcription-PCR. Furthermore, transfection studies using a human QR antioxidant/electrophile-response element (ARE/EpRE) reporter construct demonstrated that fisetin activated the ARE/EpRE. These results show that fisetin increases QR activity by transcriptional activation of the ARE/EpRE, suggesting a novel mechanism by which dietary fisetin may be implicated in cancer chemoprevention.

Animals↗

[Medical cost analysis of neoadjuvant chemotherapy for advanced tongue and oropharyngeal cancer].

We performed a medical cost analysis on the use of neoadjuvant chemotherapy (NAC) in multi-modal treatments for advanced tongue and oropharyngeal cancer. Twenty-two patients with stage III and IV squamous cell carcinoma of the tongue and oropharynx were enrolled in this study. Two courses of NAC with CDDP and 5-FU followed by radiotherapy were performed in 13 patients who showed a partial response or a complete response after the first course of NAC. The doses of radiation were 60 Gy for 4 patients (rad. group), and 72 Gy for 9 patients who received hyperfractionated radiotherapy with simultaneous Carboplatin (HF rad. group). Radical surgery was performed in 9 patients who did not respond to NAC (surg. group). The mean duration of hospital stay was 89.3 days for the rad. group, 92.0 days for the HF rad. group, and 113.3 days for the surg. group. The mean medical cost was 238,700 points for the rad. group, 264,846 points for the HF rad. group, and 459,468 points for the surg. group. The mean amounts and percentages of cost for NAC were 39,473 points and 16.1% for the rad. group, 44,802 points and 16.9% for the HF rad. group, and 23,451 points and 5.1% for the surg. group. The mean amounts of cost for NAC including examination costs and nursing costs for chemotherapy were 130,196 points and 54.5% for the rad. group, 150,046 points and 55.7% for the HF rad. group, and 113,839 points and 24.8% for the surg. group. The cost of NAC accounted for half of the total cost of chemo-radiation treatment for functional preservation. The duration of the hospital stay was prolonged by NAC, which accounted for a quarter of the total cost for the surg. group. Survival benefits are considered in the analysis of treatment cost-effectiveness for head and neck cancers. In the future, QOL, which is defined as the utility achieved as a result of multi-modal treatments, should also be analyzed along with survival benefits. Cost-utility analyses should include quality-adjusted life years, based upon the cost identification results of our analysis for NAC, to evaluate the efficacy of NAC in multi-modal treatments for head and neck cancers.

Antineoplastic Combined Chemotherapy Protocols↗

In vivo and in vitro effects of magnesium deficiency on hepatic haptoglobin mRNA levels.

We previously showed that haptoglobin (Hp) was increased in the plasma of dietary magnesium (Mg)-deficient rats. The present study was performed to examine the effects of dietary Mg-deficiency and Mg2+ deficit in culture medium on Hp mRNA levels in liver and isolated hepatocytes, respectively. The Hp mRNA level in the liver increased significantly from day 10 to day 30 in rats on a Mg-deficient diet (Mg; 0.001 per cent). In the cultured hepatocytes, lowering the Mg2+ level in the culture medium from 0.92 mM to 0.46 mM did not affect the Hp mRNA level of hepatocytes. When IL-1beta or IL-6 was added to the culture medium, the Hp mRNA level increased much more in the hepatocytes cultured in low Mg2+ medium (Mg2+; 0.46 mM) than in those cultured in the control Mg2+ medium (Mg2+; 0.92 mM). These results suggest that the increase in plasma Hp level during dietary Mg deficiency depends on the increase in Hp mRNA level in the liver, and that this increase in mRNA is not only directly correlated with a low Mg level in plasma, but also indirectly correlated with cytokines.

Animals↗

[Curative resection of advanced gastric cancer responding to preoperative chemotherapy--a case report].

A 56-year-old male was admitted for treatment of advanced gastric cancer. The patient was diagnosed as having an unresectable advanced gastric cancer because cancer cells had invaded the pancreas head and there were metastatic lymph nodes. The patient underwent preoperative chemotherapy (FLEP: intra-arterial infusion of CDDP, ETP and intravenous infusion of 5-FU, LV). The primary tumor and metastatic lymph nodes were reduced by three course of chemotherapy. The patient underwent curative resection and survived without recurrence for 14 months after operation. Preoperative chemotherapy using FLEP was performed in 15 patients with unresectable primary advanced gastric cancer. This therapy resulted in significantly higher survival times. In conclusion, FLEP has been shown to be effective for unresectable advanced gastric cancer.

Adenocarcinoma↗

[The effectiveness of ozonated water for hand washing before surgery].

Using an ozonated water-dispensing machine for sterilization of hands (Mediaqua MA-III; Core Medical Co., Ltd, Tokyo, Japan), we investigated the effectiveness of ozonated water as a disinfectant for hand washing before surgery. The effectiveness of this new hand-washing method, using 4 ppm of ozonated water, which is expected to have a short-term bactericidal effect, and 0.2% benzalkonium chloride/83% ethanol solution (Welpas), which is expected to have a long-term bactericidal effect, was compared with that of the conventional hand-washing method (Fürbringer's method using a scrubbing agent containing povidone-iodine). The results showed no significant differences in the numbers of live bacteria and exponential reduction rates in live bacteria. Thus, this new method for hand washing using ozonated water is an effective method for sterilization of the hands before surgery.

Benzalkonium Compounds↗

[Apical ballooning by transient left ventricular dysfunction (so-called "ampulla" cardiomyopathy) associated with therapy for acute pulmonary thromboembolism: a case report].

An 86-year-old-woman presented with apical ballooning left ventricular dysfunction associated with therapy for acute pulmonary thromboembolism. She was referred to our hospital for advanced treatment for her shock state due to acute pulmonary embolism with normal left ventricular(LV) function. Her condition was stabilized using a percutaneous cardiopulmonary support system. Suction embolectomy was successfully carried out after pulmonary arteriography. After the therapy, echocardiography revealed apical ballooning and hyperkinesis of the base(LV ejection fraction = 28%), although coronary arteriography showed no fixed stenosis. LV wall motion significantly improved on day 3(LV ejection fraction = 45%). Pulmonary embolism relapsed on day 5 in spite of anticoagulation treatment. She died of multiple organ failure on day 9. Autopsy findings indicated no sign of myocardial infarction or myocarditis, patchy appearance of myocardial contraction band necrosis and few migrated lymphocytes. The mechanism for the flow mis-matched LV dysfunction remains unknown. The probable explanations include non-ischemic stress such as catecholamine or neurogenic stress, and possibly ischemic stress or ischemia/reperfusion injury.

Aged↗

[Basic study about the development of the hybrid-artificial liver support system using human hepatoma cell lines (Hep G2, Huh 7): effects on liver functions by extracellular matrix (type I collagen) in monolayer culture].

The risk of xenozoonosis infections poses the greatest obstacles against the clinical application of hybrid-artificial liver support system (HALSS). To resolve this issue, we used human hepatoma cell lines (Hep G2, Huh 7) in a type I collagen-coated monolayer culture system, and analyzed liver specific functions such as ammonia removal and albumin synthesis capacity. Ammonia removal activity (nmol/10(6) nuclei/hour) and albumin synthesis activity (microgram/10(6) nuclei/day) were upregulated in both Hep G2 and Huh 7 by type I collagen-coated monolayer culture. In particular, Hep G2 cultured in type I collagen-coated monolayer demonstrated relatively high ammonia removal and albumin synthesis capacity. These results indicate the possibility of the application of human hepatocytes to HALSS.

Albumins↗

[Preparation of a manual for treatment of patients refusing blood transfusion].

We prepared a concise and simple manual for the treatment of a patient refusing blood transfusion. In this manual, we present the idea that our medical staff will respect the intention of adult patients but not the intention of juveniles below 18 years of age. If an unconscious adult patient is carrying a blood refusal card, we would regard the card as a document indemnifying the hospital from responsibility and we would treat the patient without blood transfusion. However, we would treat a juvenile patient below 18 years of age with blood transfusion if necessary, even if they and their parents refused blood transfusion. By following the manual, we can cope with the patient who refuses blood transfusion, promptly and precisely and we are rarely prosecuted by them. We respect the right of patients to make decisions regarding medical treatment and to resolve problems regarding medical expenses. We recommend that all medical institutions prepare a manual for the treatment of the patient refusing blood transfusion and officially announce the institution's policies on this matter.

Adult↗

[FLEP therapy for advanced and recurrent gastric cancer].

The FLEP regimen (5-FU, LV, ETP and CDDP) is a combination chemotherapy administered regionally and systemically for the control of both local and disseminated disease in intra- and extra-abdominal regions in patients with advanced and recurrent gastric cancer. Sixty-one patients with advanced and recurrent gastric cancer were entered into this study. The treatment regimen consisted of 5-FU at 370 mg/m2 (days 1 to 5, i.v. 24 h); LV at a dose of 30 mg (days 1 to 5, i.v. bolus); and ETP and CDDP each at 70 mg/m2 (days 7 and 21, ia 2 h). This regimen was repeated every four weeks. The overall response rate was 36.1% (22/61) and the 50% and median survival times were 10.23 and 11.80 months, respectively. The adverse events were Grade 3/4 leukocytopenia (18.0%), Grade 3/4 thrombocytopenia (4.9%), Grade 3 nausea and/or vomiting (3.3%) and Grade 3 stomatitis (1.6%). Of the 17 NAC patients, the six curability B patients showed a statistically higher survival rate than the curability C and unresected patients. Based on the encouraging response rate and the improvement in prognosis, we recommend the FLEP regimen for patients with primary gastric cancer. Neoadjuvant chemotherapy using the FLEP regimen should be performed with curative resection as an objective.

Adult↗

[Temporary placement of inferior vena cava filter prior to transcatheter arterial embolization (TAE) for hepatocellular carcinoma with IVC tumor thrombus--prevention of pulmonary tumor emboli after TAE].

A 66-year-old-man with a right huge hepatocellular carcinoma (HCC) extending into both the right portal vein and the right atrium underwent transcatheter arterial embolization (TAE) via the right hepatic artery. Prior to the TAE, a temporary inferior vena cava (IVC) filter was placed suprarenally for prevention of pulmonary tumor emboli. When we replaced the temporary IVC filter with a new one 7 days after the TAE, the filter which was pulled out of the IVC captured a fragment of the tumor thrombus. A histopathological specimen demonstrated only ghost cells. The patient has been followed at our outpatient clinic without any tumor thrombus or pulmonary infarction for 13 months after this procedure.

Aged↗

Clinical evaluation of physical fitness in male obese Japanese.

OBJECTIVE: To establish an effective exercise prescription, the exercise capacity of obese subjects was investigated. METHODS: In 71 male obese (body mass index: BMI > or = 26.4) Japanese, aged 26-77 years, the body composition and physical fitness such as aerobic exercise level, muscle strength and flexibility were determined and compared with those of age- and sex-matched 71 borderline (24.2 < or = BMI < 26.4) and 71 normal Japanese men (19.8 < or = BMI < 24.2). The relationship between body composition and other parameters was evaluated in obese subjects. RESULTS: In obese subjects, body weight, BMI, body fat percentage, waist hip ratio, and skinfold thickness were higher than those of borderline and normal subjects. Lower aerobic exercise level and weight bearing index (WBI) were noted in obese subjects. There was a negative correlation between waist hip ratio and aerobic exercise level (oxygen uptake at ventilatory threshold) (r = -0.509, P < 0.01) and also between waist hip ratio and WBI (r = -0.315, P < 0.01). CONCLUSIONS: Lower physical fitness is considered to be a general characteristic of male obese Japanese, and the accumulation of visceral adipose tissue might affect exercise capacity.

Adult↗

Transcriptional regulation of nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase in murine hepatoma cells by 6-(methylsufinyl)hexyl isothiocyanate, an active principle of wasabi (Eutrema wasabi Maxim).

Wasabi is a very popular pungent spice in Japan. This study examined the ability of 6-(methylsufinyl)hexyl isothiocyanate (6-MITC), an active principle of wasabi, to induce the cellular expression of nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase (QR) in Hepa 1c1c7 cells. The cells were treated with various concentrations of 6-MITC, and were then assessed for cell growth, QR activity and QR mRNA expression. The induction of QR activity and QR mRNA expression was time- and dose-responsive over a narrow range of 0.1-5 microM, with declining induction at higher concentrations due to cell toxicity. Furthermore, transfection studies demonstrated that the induction of transcription of the QR gene by 6-MITC involved an antioxidant/electrophile-responsive element (ARE/EpRE) activation. Our results suggest a novel mechanism by which dietary wasabi 6-MITC may be implicated in cancer chemoprevention.

Animals↗

The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome.

OBJECTIVE: To evaluate the clinical spectrum of anti-GAD-positive patients with stiff-person syndrome (SPS) and provide reproducible means of assessing stiffness. BACKGROUND: SPS can be difficult to diagnose. Delineation of the clinical spectrum in a well defined population will increase diagnostic sensitivity. METHODS: In 20 anti-GAD-positive patients with SPS (six men, 14 women), screened among 38 referred patients, the authors assessed symptoms and signs, degree of disability, associated conditions, and immunogenetic markers. Degree of bending, distribution of stiff areas, timed activities, and magnitude of heightened sensitivity were examined monthly for 4 months in five patients. RESULTS: Average age at symptom onset was 41.2 years. Time to diagnosis was delayed from 1 to 18 years (mean 6.2). Stiffness with superimposed episodic spasms and co-contractures of the abdominal and thoracic paraspinal muscles were characteristic. All had stiff gait and palpable stiffness in the paraspinal muscles. Stiffness was asymmetric or prominent in one leg in 15 patients (stiff-leg syndrome) and involved facial muscles in 13. In one patient spasms lasted for days (status spasticus). Twelve patients needed a cane and seven a walker due to truncal stiffness and frequent falls (average three to four per month). Distribution of stiffness and degree of heightened sensitivity were two reproducible indices of stiffness and spasms. Autoimmune diseases or autoantibodies were noted in 80% and an association of with DRss(1) 0301 allele in 70%. CONCLUSIONS: SPS is 1) frequently misdiagnosed due to multifaceted presentations and asymmetric signs, 2) disabling if untreated, and 3) associated with other autoimmune conditions.

Adult↗

High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate whether repetitive measurements of plasma levels of neurohumoral factors and cytokines before and after additional treatment are useful for predicting mortality in patients with congestive heart failure (CHF). BACKGROUND: Neurohumoral and immune activation play an important role in the pathophysiology of CHF. However, the effects of serial changes in these factors on the prognostic value remain unknown. METHODS: We measured plasma levels of neurohumoral factors and cytokines and left ventricular ejection fraction (LVEF) before and three months after optimized treatment for CHF in 102 consecutive patients with severe CHF (New York Heart Association class III to IV) on admission to our hospital. Physicians who were blind to the plasma neurohumoral factors until study completion treated patients using standard drugs. Patients were monitored for a mean follow-up period of 807 days. RESULTS: Plasma levels of neurohumoral factors, cytokines and LVEF were significantly improved three months after optimized treatment. Cardiac death occurred in 26 patients. Among 19 variables including LVEF, only a high level of brain natriuretic peptide (BNP) and interleukin-6 (IL-6) at three months after optimized treatment showed significant independent relationships by Cox proportional hazard analysis with a high mortality for patients with CHF. CONCLUSIONS: These findings indicate that high plasma BNP and IL-6 levels three months after optimized treatment are independent risk factors for mortality in patients with CHF, suggesting that sustained high plasma levels of BNP and IL-6 after additional standard treatment were independent risk factors for mortality in patients with CHF despite improvements in LVEF and symptoms.

Aged↗

Activation of oncogenic transcription factor AP-1 in T cells infected with human T cell leukemia virus type 1.

Human T cell leukemia virus type 1 (HTLV-1) Tax protein transforms primary human T cells in vitro. We previously showed that Tax induces the expression of various family members of the transcription factor AP-1 such as c-Jun, JunD, c-Fos, and Fra-1 at the mRNA level in T cells. In this study, we have examined the ability of Tax to activate transcription through the AP-1-binding site (AP-1 site). A transient transfection study showed that Tax can activate transcription through the AP-1-binding site in a human T cell line, whereas any combination of AP-1 proteins did so much less than Tax, indicating that the activation of the AP-1 site by Tax may require a mechanism other than the induction of AP-1 mRNA. Fresh peripheral blood leukemia cells of all surveyed ATL patients displayed constitutive AP-1 DNA-binding activity, whereas no normal individuals did. However, the HTLV-1 genes, including tax, are not significantly expressed in fresh leukemia cells from ATL patients. Our present results suggest that activation of AP-1 occurs through Tax-dependent and -independent mechanisms in HTLV-1-infected T cells, which may play some roles in dysregulated phenotypes of HTLV-1-infected cells.

Animals↗

Development of highly sensitive enzyme-linked immunosorbent assays for hepatocyte growth factor/scatter factor (HGF/SF): determination of HGF/SF in serum and urine from normal human subjects.

A sandwich enzyme-linked immunosorbent assay (ELISA) using rabbit anti-hepatocyte growth factor (HGF) IgG for human HGF, also known as the scatter factor, has previously been developed for determining increases in serum HGF levels in various liver diseases. The sensitivity limit of the ELISA is, however, approximately 0.2 ng/ml sample, and HGF concentrations in about 50% of normal subjects are not accurately measurable by this method, because the mean level of HGF in normal serum is close to the sensitivity limit. In the present study, chicken Fab' from egg yolk anti-HGF immunoglobulin Y and rabbit Fab' from rabbit anti-HGF IgG were conjugated with beta-D-galactosidase. With these conjugates as the second antibodies, we developed two sandwich ELISAs for human HGF and found that the sensitivities were about 20 pg/ml with the former conjugate and 2 pg/ml with the latter. The HGF concentration in sera from 138 normal subjects determined by the ELISA with the rabbit conjugate was 244+/-65 (SD) pg/ml serum, and it correlated very well with the number of leukocytes. Moreover, the ELISA with the rabbit conjugate permitted the determination of HGF levels in urine from normal subjects without first concentrating the sample. The determination of HGF in various biological fluids other than blood and urine by these ELISAs may aid the diagnosis and prognosis of various diseases.

Adult↗

Hydrophilicity of Polar and Apolar Domains of Amphiphiles.

The hydrophilicity of polar and apolar domains of various amphiphiles was systematically estimated for their homologues and analogues by measuring the molar adiabatic compressibility of an aqueous solution at infinite dilution. The homologues of protic alkyl H(CH(2))(n)-, perfluoroalkyl F(CF(2))(n)-, and alkylphenyl H(CH(2))(n)(C(6)H(5))- groups (n=0-10) were chosen to represent apolar hydrophobic domains. The polar hydrophilic domains tested were -SO(4)Na, -SO(3)Na, -COONH(4), -N(CH(3))(3)Br, N(C(m)H(2m+1))(4)Br (m=1-5), and -NH(CH(2))(n)SO(3) (n=3, 4) groups. Also tested were the tetraphenyl ionic compounds (C(6)H(5))(4)MX (M=B/X=Na, M=P/X=Cl, M=As/X=Cl) to study the effect of the ionic sign of the core atom across the tetraphenyl apolar shell, the polyethylene glycols H(OCH(2)CH(2))(m)OH (m=1-4) to study the role of apolar -CH(2)- units in the hydrophilic oxyethylene group, and the zwitterionic dimethylaminoalkylsulfonate (CH(3))(2)NH(CH(2))(n)SO(3) homologues to study the effect of intramolecular salt formation on the hydrophilicity of the zwitterion. The adiabatic compressibility of the solution was calculated from measurement of the sound velocity and density of solutions. The introduction of laboratory automation and the numerical control of the system improved the accuracies and efficiencies of the measurements a great deal. The range of the temperature scan was 0-40 degrees C with an effective accuracy of +/-0.001 degrees C and the concentration was automatically scanned down to far below the cmc of the surfactant. The hydrophilicity of various polar and apolar substances was estimated as the decrease of molar adiabatic compressibility of the aqueous solution with increased concentration of their homologues and analogues. The hydrophobic hydration of nonpolar substances was found to be very small at room temperature and was barely detected above 40 degrees C; however, it became large as the temperature was lowered and attained a maximum at 0 degrees C. The cationic charge of quaternary ammonium N(+)(C(n)H(2n+1))(4) was found to enhance the hydrophobic hydration of methylene groups located at a distance of 4 to 6 Å from the core nitrogen atom, while the terminal negative charge of the anionic surfactant R-SO(4)(-), R-SO(3)(-), or R-COO(-) was found to decrease the hydrophobic hydration of -CH(2)- units within the same range. The hydrophilicity of quaternary ammonium and the tetraphenyl ions should be synergistically given by both hydrophobic and ionic hydrations. The hydrophilicity of the perfluoromethylene unit -CF(2)- was found to have a value comparable to that of the protic methylene unit -CH(2)-. The hydrophobic hydration seems to offer a good measure of the hydrophilicity of apolar substances; however, it does not necessarily represent the "hydrophobicity" of the apolar segment when the "surface activity" of the amphiphile is concerned. Copyright 2000 Academic Press.

Journal Article↗

Effect of fatty acid Esters on permeation of ketoprofen through hairless rat skin.

Twelve medium to long chain fatty acid Esters (Esters), the total number of carbon atoms of which ranged from 17 to 34, were used to study the effect of the vehicle on the permeation of ketoprofen, and the effect was compared with the case of indomethacin. The solubility of ketoprofen was higher in Esters with a smaller number of carbon atoms. The permeation rate of ketoprofen from the Ester suspension through excised hairless rat skin was proportional to its solubility in the suspension, which was the same in the case of indomethacin. The diffusion constant and partition coefficient were calculated using the computer program MULTI(FILT). The diffusion constant decreased with increasing number of carbon atoms, and the partition coefficient was increased with increasing number of carbon atoms, in both cases of ketoprofen and indomethacin. Esters also penetrated the skin with the concentration of about 10 mg/g, independent of the number of carbon atoms. The Esters in the skin increase the diffusion rate of the drugs, especially in the case of Esters with a small number of carbon atoms. Also the drug solubility in the skin was improved, although the effect was similar for the range of Esters investigated in the present study. Then the permeation rate of ketoprofen and indomethacin increased.

Animals↗