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Biomedical subjects

H Fukui

Publications and source records attributed to H Fukui.

At least 109 records · Page 6Linked to original sources
PubMed2000

Assessment of efficiency and safety of adenovirus mediated gene transfer into normal and damaged murine livers.

BACKGROUND: When recombinant adenoviruses are infused directly into the circulation, transgene expression is almost completely restricted to the liver. AIMS: Efficiency and safety of adenovirus mediated gene transfer into damaged livers were examined in mice with liver cirrhosis or fulminant hepatitis. METHODS: Liver cirrhosis and fulminant hepatitis were induced by intraperitoneal administration of thioacetamide and D-galactosamine followed by lipopolysaccharide, respectively. Mice were infused with adenoviruses carrying the Escherichia coli beta-galactosidase gene, lacZ gene, into the tail vein. Transduction efficiency of the lacZ gene was estimated histochemically by X-gal staining and quantitatively using a chemiluminescent assay. Activation of adenovirus specific T cells and development of neutralising antibodies against adenovirus were also examined. RESULTS: Histochemical evaluation revealed that approximately 40%, 80%, and 40% of cells in normal, cirrhotic, and fulminant hepatitis livers, respectively, were stained blue using X-gal staining. Quantitative analyses revealed that levels of lacZ expression in cirrhotic livers were approximately 2.5-fold and sixfold greater than those in normal and fulminant hepatitis livers, respectively. Although transgene expression in fulminant hepatitis livers was significantly lower than that in normal livers, marked levels of transgene expression were achieved even in fulminant hepatitis livers. Significant adverse effects of adenoviruses were not observed in damaged livers. There were no significant differences in cellular or humoral immune responses to adenoviruses among animals with normal, cirrhotic, and fulminant hepatitis livers. CONCLUSIONS: Our results suggest that gene therapy with adenoviruses may be used efficiently and safely, even in patients with severe liver disease.

Adenoviridae↗
PubMed2000

Effect of endothelin-1 (1-31) on human mesangial cell proliferation.

It was previously found that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs (1-31). In the present study, human plasma concentrations of ET-1 (1-31) and ET-1 were examined and the effect of synthetic ET-1 (1-31) on the proliferation of cultured human mesangial cells (HMCs) was investigated. The proliferative effect of ET-1 (1-31) was evaluated from the [3H]-thymidine uptake. The activity of extracellular signal-regulated kinase (ERK) and DNA binding activity of activator protein-1 were determined by using an in-gel kinase assay and gel mobility shift assay, respectively. Immunoreactive ET-1 (1-31) was detectable in plasma, but the level was slightly lower than that of ET-1. ET-1 (1-31) increased [3H]-thymidine incorporation in HMCs to a degree similar to that induced by ET-1. ET-1 (1-31) also activated ERK1/2. Inhibition of protein kinase C and ERK kinase caused a reduction of ET-1 (1-31)-induced ERK1/2 activation. The ERK1/2 activation was followed by an increase in transcription factor activator protein-1 DNA binding activity. These findings suggest that ET-1 (1-31) is a bioactive peptide in humans and ET-1 (1-31) itself stimulates HMC proliferation.

Adult↗
PubMed2000

NMR determination of the absolute configuration of an alpha-exo-methylene-gamma-lactone.

Both the enantiomers of the axially chiral reagent, 2'-methoxy-1,1'-binaphthalene-2-carbohydroximoyl chloride (MBCC), were used to convert igalan, an alpha-exo-methylene-gamma-lactone, to yield 4,5-dihydroisoxazoles. The absolute configuration of igalan was determined to be (3aR,5R,6R,7aR)-6-ethenylhexahydro-6-methyl-3-methylen e-5-(1-methylethenyl)-2(3H)-benzofuranone (IUPAC name) on the basis of NOE correlations in these derivatives. The absolute configurations of other alpha-exo-methylene-gamma-lactones can be determined by the same method.

Lactones↗
PubMed2000

A new chlorinated red naphthoquinone from roots of Sesamum indicum.

A new chlorinated red naphthoquinone pigment having antifungal activity, named chlorosesamone, was isolated from the roots of Sesamum indicum. Its structure was characterized as 2-chloro-5,8-dihydroxy-3-(3methyl-2-butenyl)- 1,4-na phthoquinone on the basis of spectral evidence.

Chlorides↗
PubMed2000

Usefulness and safety of theophylline injection form (Theodrip) for the treatment of acute asthma.

The effects of the speed of intravenous infusion on the pharmacokinetics of theophylline were studied in 9 healthy volunteers (Ex I). Subjects were intravenously administered either six 4.8 mg/kg theophylline (Theodrip, Nikken Chemicals Co., Ltd., Japan) or three matching placebo injections (4.8 ml/kg physiological saline) for 30 min (Step I) or for 15 min (Step II). In Steps I and II, Cmax was 10.8 +/- 1.1 and 10.8 +/- 0.8 micrograms/ml, respectively. These Cmaxs were concentrations yielding therapeutic effects in patients with acute asthma. Next, comparative pharmacokinetics between theophylline (Theodrip) and aminophylline were examined by a crossover method in 16 healthy volunteers (Ex II). The 90% confidence limits of the differences of mean values were within 80-120% and were 92.8-100.1% for Cmax, 99.7-105.3% for t1/2 and 100.2-104.4% for AUC. Thus, we concluded that the pharmacokinetics of the plasma theophylline after intravenous administration of Theodrip (theophylline at 4.8 mg/kg) were bioequivalent to those of aminophylline (6.0 mg/kg) for 30 min. In Ex I and II, no subjects had adverse effects and in Ex I no influence on ECG was seen. In addition, the convenience of Theodrip was compared with that of ampules of aminophylline among nurse volunteers (Ex III). The times required for set-up of Theodrip were significantly shorter than those of aminophylline ampules. On the other hand, the adverse reactions to aminophylline resulting from hypersensitivity reactions to its ethylenediamine component have been reported. Theodrip consists of 200 mg theophylline and 200 ml physiological saline in a plastic bag. Therefore, Theodrip, which does not contain ethylenediamine, is expected to have less adverse effects and be easier to handle than aminophylline.

Acute Disease↗
PubMed2000

A novel mutation of the KAL1 gene in monozygotic twins with Kallmann syndrome.

OBJECTIVE: Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism and anosmia. The KAL1 gene is responsible for the X-linked form of Kallmann syndrome. In this study we describe monozygotic twins with Kallmann syndrome due to the same mutation in the KAL1 gene. DESIGN: We studied male monozygotic twins with Kallmann syndrome. METHODS: We analyzed the KAL1 gene using the PCR-direct sequencing method. The twins' mother was examined for the identified mutation. RESULTS: We identified a 14 bp deletion from codon 419 in exon 9 (Pro419del14) in both KAL1 genes of the twins. This was a novel mutation in the KAL1 gene and was responsible for Kallmann syndrome. As Pro419del14 was not detected in the mother of the twins, Pro419del14 was a germline mutation originating from them. These monozygotic twins showed different LH and FSH responses to LH-RH stimulation and different phenotypes such as complications, physiques and psychiatric characters. CONCLUSIONS: We report an identical KAL1 gene mutation in the monozygotic twins with Kallmann syndrome. As these monozygotic twins showed different phenotypes in some respects, we suggest that factors other than mutations in the KAL1gene affect the symptomatic features of Kallmann syndrome.

Adult↗
PubMed2000

Microscopic polyangiitis that presented liver dysfunction prior to noted renal manifestations.

In microscopic polyangiitis (MPA), renal manifestations are very common as first symptoms. Here, we report a case of MPA which presented liver dysfunction prior to noted renal manifestations. A 58-year-old woman was hospitalized because of a fever for 8 weeks. A laboratory examination revealed marked elevation of alkaline phosphatase and gamma-glutamyl transpeptidase, while blood urea nitrogen and creatinine levels remained normal. Although apparent renal dysfunction developed in this case soon after hospitalization, physicians should be aware of the variety of clinical manifestations in MPA. Moreover, antineutrophil cytoplasmic autoantibodies were found to be helpful for diagnosing MPA.

Female↗
PubMed2000

Electrochemotherapy with bleomycin against colorectal carcinoma in a mouse model: evaluations of the dose and administration route of the drug and the electric field intensity.

Effectiveness of electrochemotherapy against colorectal carcinoma (CRC) was evaluated in a mouse model. When mice with a subcutaneously established CRC tumor were administered intratumorally, intravenously or intraperitoneally with bleomycin (BLM) ranging from 1/50 to 1/2 of the 50% lethal dose, significant suppression of tumor development and even some cures were observed. When various electric field intensities ranging from 500 to 2,000 V/cm were applied for electrochemotherapy with BLM, all treatment protocols were similarly effective. Furthermore, when electrochemotherapy with the lowest dose of BLM and the lowest electric field intensity was repeated, complete cures of CRC were achieved in all animals.

Animals↗
PubMed2000

Electrochemotherapy can eradicate established colorectal carcinoma and leaves a systemic protective memory in mice.

Mice bearing subcutaneously established colorectal carcinoma (CRC) were given intratumoral, intravenous or intraperitoneal injection of various doses of bleomycin (BLM), followed by the delivery of direct current, square wave electric pulses to the tumor. Approximately 50% of animals treated with electrochemotherapy with BLM had completely eradicated established CRC tumors. Importantly, it was shown that CRC-specific cytotoxic T lymphocytes were elicited in the spleens of cured animals, resulting in the protection of the rechallenge with CRC. These results indicate that electrochemotherapy with BLM is promising for the treatment of metastatic CRC as well as the original lesion.

Animals↗
PubMed2000

Interfacial oxidations of pure titanium and titanium alloys with investments.

External oxides of a commercially pure titanium (cpTi), Ti6Al4V alloy, and an experimental beta-type titanium alloy (Ti 53.4 wt%, Nb 29 wt%, Ta 13 wt%, and Zr 4.6 wt%) were characterized after heating to 600, 900, 1150, and 1400 degrees C in contact with three types of investments (alumina cement, magnesia cement, and phosphate-bonded) in air. XRD studies demonstrated that MgO, Li2TiO3 and/or Li2Ti3O7 were formed through reactions with the metal and the constituents in the magnesia cement-investment after heating to 900, 1150, and 1400 degrees C. Except for these conditions, TiO2 (rutile) was only formed on cpTi. For titanium alloys, the other components apart from Ti also formed simple and complex oxides such as Al2O3 and Al2TiO5 on Ti6Al4V, and Zr0.25Ti0.75Nb2O7 on the beta-type titanium alloy. However, no oxides containing V or Ta were formed. These results suggest that the constituents of titanium alloys reacted with the investment oxides and atmospheric oxygen to form external oxides due to the free energy of oxide formation and the concentration of each element on the metal surface.

Alloys↗
PubMed2000

[Effect of radiotherapy for inoperable remnant and recurrent gastric cancer--focusing of improvement in quality of life].

We investigated six cases of inoperable remnant and recurrent gastric cancer treated with radiotherapy with regard to quality of life (QOL). The radiation dose was from 22 to 70 Gy, with a mean dose of 46 +/- 18 Gy. Four cases could be evaluated. Two were PR and two were NC. No patients could ingest food before radiotherapy, but two became able to eat whole gruel, one half gruel and three water. The mean survival time was 5.5 months and prognosis was not improved. Subjective symptoms such as food passage disturbance were decreased by radiotherapy and QOL was improved. Radiotherapy for patients with inoperable gastric cancer seemed to be effective in improving QOL.

Aged↗
PubMed2000

Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis: relation to severity of liver disturbance.

BACKGROUND: Endotoxin plays an important role in the initiation and aggravation of alcoholic liver disease. In this study, we evaluated plasma endotoxin levels and serum concentrations of cytokines and lipopolysaccharide binding protein (LBP) during the acute and recovery phase of patients with alcoholic hepatitis; we also explored the prognostic factors associated with a fatal outcome. METHODS: Fourteen patients, consisting of eight patients with alcoholic hepatitis (AH), five cirrhotics with superimposed AH (LC+AH), and one patient with severe alcoholic hepatitis (SAH), were studied. Among these, two with LC+AH died of hepatic failure. RESULTS: Plasma endotoxin levels in the acute phase were higher in patients with AH (184.4 +/- 159.4 pg/ml) and LC+AH (206.9 +/- 174.9 pg/ml) than in healthy subjects (10.4 +/- 5.5 pg/ml, p < 0.001). In particular, in one patient with SAH and one of two nonsurvivors, plasma endotoxin levels were markedly high relative to the other cases. In most survivors, plasma endotoxin levels decreased in the recovery phase, whereas they further increased at the terminal stage in one of two nonsurvivors. Serum interleukin (IL)-6 and IL-8 levels in the acute phase were significantly higher in patients with AH and LC+AH as compared with healthy subjects. These levels were especially high in nonsurvivors and in one patient with SAH. IL-10 increased in two nonsurvivors, one patient with SAH, and one with LC+AH. In the recovery phase, these cytokine levels in survivors tended to decrease, but in nonsurvivors, IL-6 remained high, and IL-8 and IL-10 further increased. Tumor necrosis factor-alpha levels were below the detection limit throughout the course in all patients. Serum lipopolysaccharide binding protein (LBP) generally was elevated in the acute phase and decreased in the recovery phase in all survivors, but in one of the nonsurvivors, LBP was elevated markedly at the terminal stage. In the acute phase, plasma endotoxin levels were correlated positively with white blood cell counts, neutrophil counts, and serum IL-8. IL-8 was correlated positively with neutrophil counts and negatively with serum cholinesterase, hepaplastin test, and serum albumin levels. IL-6 was correlated positively with white blood cell and neutrophil counts, C-reactive protein, and serum total bilirubin and negatively with hepaplastin test and serum total protein levels. Serum LBP was correlated positively with white blood cell and neutrophil counts. CONCLUSIONS: Endotoxemia and related elevation of IL-8 may play an important role in the activation and migration of neutrophils in patients with alcoholic hepatitis. Marked elevation of inflammatory cytokines, IL-6 and IL-8, are related to severity and poor prognosis of alcoholic hepatitis. Serum LBP may serve as an index of inflammatory reaction in alcoholics.

Acute-Phase Proteins↗
PubMed2000

Relationship between cyclooxygenase-2 expression and K-ras gene mutation in colorectal adenomas.

BACKGROUND AND AIMS: Cyclooxygenase (COX)-2 has a trophic effect on gastrointestinal epithelial cells and is associated with the progression of colorectal adenomas. Mutation of the K-ras gene is also associated with the progression of colorectal adenomas and has recently been suggested to play an important role in the induction of COX-2. In the present study, we investigated the relationship between COX-2 expression and K-ras mutation in colorectal adenomas. METHODS: Twenty-nine colorectal adenomas were obtained from specimens resected by the use of surgery or endoscopic mucosal resection and analyzed clinicopathologically. Immunohistochemistry was performed to analyze COX-2 expression in the adenoma specimens. The K-ras codon 12 mutations were detected by using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: An increase of COX-2-positive cells in adenoma was observed in 11 (37.9%) lesions, 10 (90.9%) of which had a K-ras gene mutation, suggesting a significant correlation between COX-2 expression and K-ras gene mutation in colorectal adenomas. Morphologically, COX-2-positive adenomas (13.8 +/- 2.6 mm) were significantly larger than COX-2-negative ones (5.8 +/- 0.9 mm). In addition, the increase of COX-2-positive cells in the lesion was observed more frequently in tubulovillous (63.6%) than in tubular (36.4%) adenoma. CONCLUSIONS: Cycloxygenase-2 expression in colorectal adenoma cells is strongly correlated with K-ras gene mutation, suggesting that COX-2 and mutated K-ras are connectively associated with the progression of colorectal adenoma.

Adenoma↗