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Biomedical subjects

R Tsuji

Publications and source records attributed to R Tsuji.

At least 19 recordsLinked to original sources

Interleukin-18 stimulates hematopoietic cytokine and growth factor formation and augments circulating granulocytes in mice.

Because interleukin-18 (IL-18) is similar to IL-1 and is known to be involved in the hematopoietic progenitor cell growth, the effect of IL-18 on circulating cell populations was examined. Repeated administration of IL-18 induced significant amounts of neutrophilia in mice. In parallel, high levels of interferon-gamma (IFN-gamma), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were detected in the serum of these mice. Interestingly, the cytokine profiles as well as the cell populations in circulation altered around 2 weeks after the beginning of IL-18 administration. A weak but definite eosinophilia was observed concurrently with the appearance of serum IL-5. Consistent with these observations, IL-18 induced secretion of IFN-gamma, GM-CSF, and IL-6 from splenocytes in culture. IL-18 also induced low levels of IL-5 in the splenocyte culture, which was inhibited by IL-12. However, markedly high levels of IL-5 were secreted into the culture medium when splenocytes from IFN-gamma-deficient mice were stimulated by IL-18. CD4(+) T cells strongly responded to IL-18 to secrete IL-5 and GM-CSF. IL-18 stimulated secretion of IL-6 and expression of G-CSF mRNA in splenic adherent cells. Expression of IL-18 receptors was detected in CD4(+) T cells and splenic adherent cells (macrophages). These results show that IL-18 stimulates CD4(+) T cells and macrophages to secrete IL-5, GM-CSF, IL-6, and granulocyte-colony stimulating factor in the absence of IL-12, which in turn induces hematopoietic cell proliferation causing neutrophilia and eosinophilia in mice.

Animals↗

Tissue factor pathway inhibitor as a universal anticoagulant for use in clinical laboratory tests.

Tissue factor pathway inhibitor (TFPI) is a protease inhibitor of extrinsic coagulation. The present study investigates the possibility of utilizing TFPI as a universal anticoagulant in clinical laboratory tests. The optimal concentration of TFPI for use in clinical laboratory tests was found to be 1 microl TFPI/ml blood (100 mmol TFPI/ml blood); the subsequent analyses were conducted at this concentration. In hematological tests, complete blood cell count and differential white blood cell count were done with an automatic blood analyzer. The results except for platelet and white blood cell counts were similar for ethylenediaminetetraacetic acid (EDTA)-treated and TFPI-treated samples. The effects of TFPI on platelet count were more pronounced when blood samples were stored at 4 degrees C than at room temperature. The effects of TFPI on cell morphology were evaluated by spreading blood samples into thin films and applying a Giemsa stain. The results showed that TFPI did not alter the morphology of blood cells. An automatic biochemical analyzer performed seventeen basic biochemical tests on serum samples and TFPI-treated plasma samples. The results of seventeen tests were comparable between TFPI-treated samples and EDTA-treated samples. The prothrombin time for TFPI-treated plasma samples was longer than that for citrated plasma samples. Nonetheless, in activated partial thromboplastin time tests, the addition of the reagent caused turbidity and partial coagulation, thus demonstrating that TFPI is not suitable for this assay. These findings suggest that although some tests cannot be performed with TFPI, this compound may be useful as a universal anticoagulant in the future.

Anticoagulants↗

Postoperative oblique sagittal MR imaging of microvascular decompression for hemifacial spasm.

Pre-operative and postoperative oblique sagittal gradient-echo magnetic resonance (MR) imaging was used to evaluate micro-vascular decompression of the facial nerves in 26 patients with hemifacial spasm. The pre-operative MR images were divided into two groups as follows: 22 images in Group I, clear imaging of a high-intensity line and/or spot at the root exit zone (REZ) of the facial nerve; and 4 in Group II, and unreliable image around the REZ. Surgery found that the causative vessel was the vertebral artery (VA) in 9 cases and the anterior inferior cerebellar artery (AICA) or the posterior inferior cerebellar artery (PICA) in 13 cases in Group I, and the AICA or the PICA in the 4 cases in Group II. Postoperative MR imaging showed clear decompression as the high-intensity line and/or spot completely separated from the REZ by a low- and/or iso- intensity area in 9 cases of VA compression repositioned to the petrous dura matter, in 11 cases of PICA or AICA compression treated by shredded Teflon pledgets in Group I and in 3 cases in Group II. Postoperative MR imaging showed an incomplete separation of any high-intensity line and/or spot in the REZ in 2 cases of PICA or AICA compression in Group I and in one in Group II. The outcome was excellent in 22 of 23 cases with clear decompression, and in 1 of 3 cases of unclear decompression. Hemifacial spasm persisted in 3 cases. Oblique sagittal gradient-echo MR imaging is a useful method for postoperative follow-up which can demonstrate changes around the REZ of the facial nerve if hemifacial spasm recurs.

Arteries↗

Prediction of vertebral artery compression in patients with hemifacial spasm using oblique sagittal MR imaging.

To discriminate between the various compressing vessels of the facial nerves in patients with hemifacial spasm, pre-operative oblique sagittal gradient-echo MR imaging was performed. Forty-two patients underwent pre-operative MR imaging and microvascular decompression. The MR images were divided according to findings into three groups as follows: Group A, a thick and/or long high-intensity line along the root exit zone (REZ) of the facial nerve; Group B, a thin and/or short high-intensity line along the REZ; and Group C, an unreliable image around the REZ. Fifteen images were classified as Group A, 19 as Group B, and 8 as Group C. In Group A, vertebral artery (VA) compression was confirmed intra-operatively in 12 cases and posterior inferior cerebellar artery (PICA) or anterior inferior cerebellar artery (AICA) compression in 3. In Group B, PICA or AICA compression was confirmed intra-operatively in all cases. In Group C, PICA or AICA compression was confirmed intra-operatively in 7 cases and no compression in one. In all cases of VA compression of the facial nerve, the oblique sagittal gradient-echo images demonstrated a thick and/or long high intensity line along the REZ. Oblique sagittal gradient-echo MR imaging is a useful preoperative planning aid, which can predict the possibility of VA compression prior to microvascular decompression for hemifacial spasm.

Facial Nerve↗

Increased expression of vascular endothelial growth factor is associated with tumor progression in hepatocellular carcinoma.

Vascular endothelial growth factor is a potent direct-acting angiogenic factor. Early in hepatocarcinogenesis, hepatocellular carcinomas do not show hypervascularity; at later stages, they require abundant arterial blood flow. We investigated the role of vascular endothelial growth factor in hepatocellular carcinoma arterialization. We studied 51 patients with hepatocellular carcinoma. All patients had undergone hepatic arteriography. Vascular endothelial growth factor expression was investigated by immunohistochemistry (n = 51) and in situ hybridization (n = 13), and the changes in vascular endothelial growth factor expression were evaluated in relation to tumor differentiation and changes in tumor vascularity. The expression of vascular endothelial growth factor isoforms in hepatocellular carcinomas was also analyzed by reverse transcriptase-polymerase chain reaction (n = 10). Vascular endothelial growth factor expression was detected in hepatoma cells and hepatic stellate cells, and increased vascular endothelial growth factor expression was associated with tumor dedifferentiation. Vascular endothelial growth factor expression in hypervascular hepatocellular carcinomas was greater than in those not showing hypervascularity. The major vascular endothelial growth factor isoforms expressed in hepatocellular carcinoma were 121 and 165. These findings indicate that vascular endothelial growth factors 121 and 165 play a critical role in the process of angiogenesis in hepatocellular carcinomas.

Aged↗

Surgical treatment of discrete subaortic stenosis in an adult.

We report on an adult patient with discrete-type subaortic stenosis. A 48-year-old man who had progressed asymptomatically since childhood despite heart murmur was transferred to our hospital. The patient was diagnosed as having severe aortic stenosis with a pressure gradient of 100 mmHg across the aortic valve, associated with a grade II aortic regurgitation. A conventional aortic valve replacement was scheduled. During surgery, the aortic valve was found to be tricuspid but incompetent as a result of shrinking and thickening of the left coronary cusp. A circumferential fibromuscular ridge was observed under the cusps, which corresponded to Kelly's type II discrete subaortic stenosis. Because of the small subaortic area and deformity of the cusp, we performed aortic valve replacement after excision of all cusps and the fibromuscular ridge. Early corrective surgery is recommended for discrete subaortic stenosis to prevention regurgitation progression.

Aortic Valve Stenosis↗

Visual recovery following immediate decompression of traumatic retrobulbar hemorrhage via transcranial approach.

A 17-year-old boy presented with retrobulbar hemorrhage manifesting as right proptosis, periorbital swelling, and blindness after suffering a midfacial trauma. Immediate decompression by removal of the retrobulbar hemorrhage via the transcranial approach was performed. The proptosis was resolved and visual acuity and eye movement were restored. Retrobulbar hemorrhage is a serious injury which may lead to blindness. However, recovery from blindness can be achieved with adequate management including neurosurgical decompression in the early stage.

Adolescent↗

Relaxing effect of interleukin-1 on rat cultured Ito cells.

Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were isolated from the livers of male Wistar rats and cultured for 24 hours. Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and intensity of fluorescence of cGMP were examined using a confocal laser microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta were observed over 12 hours, and the area of the same Ito cell was compared before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L-arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence of iNOS was observed, and fluorescent intensity of cGMP increased after addition of IL-1beta. Intracellular cGMP concentration increased dose-dependently after addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated group compared with the untreated group. Relaxation of Ito cells by IL-1beta treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and relaxes the cells via cGMP.

Animals↗

Coordinated expression of integrin alpha6beta1 and laminin in hepatocellular carcinoma.

The interaction between tumor cells and laminin mediated by laminin-binding integrins is critical for tumor invasion and metastasis. The aim of this study was to clarify the altered expression of laminin-binding integrins with the change of laminin deposition in hepatocellular carcinoma (HCC) in comparison with cirrhotic or normal liver by immunohistochemistry. In HCC, hepatoma cells and sinusoidal endothelial cells expressed integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta1. Integrins alpha1beta1 and alpha6beta1 were detected in a continuous pattern along the sinusoids in accordance with laminin assembly. Integrins alpha2beta1 and alpha3beta1 were detected in a discontinuous pattern at these sites. Integrin alpha6beta4 was not detected. In cirrhotic liver, although integrins alpha1beta1 and alpha6beta1 as well as laminin were detected in a continuous pattern along the sinusoids, integrins alpha2beta1, alpha3beta1, and alpha6beta4 were not detected. In normal liver, although integrin alpha1beta1 was detected in a continuous pattern along the sinusoids, neither integrins alpha2beta1, alpha3beta1, alpha6beta1, alpha6beta4, nor laminin were detected. We have clarified that, of laminin-binding integrins, the localization of integrin alpha6beta1 shows the best correspondence with the localization of laminin. These results suggest that of laminin-binding integrins, integrin alpha6beta1 is very important for cell-laminin interactions in HCC.

Adult↗

Basic fibroblast growth factor regulates proliferation and motility of human hepatoma cells by an autocrine mechanism.

BACKGROUND/AIMS: Basic fibroblast growth factor has mitogenic and angiogenic properties. In this study, we aimed to evaluate the role of fibroblast growth factor in the development and progression of human hepatocellular carcinoma. METHODS: The expression of basic fibroblast growth factor, fibroblast growth factor receptor-1, and a receptor isoform was investigated by in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction, Western blot analysis and confocal laser-scanning microscopy. The influence of exogenous basic fibroblast growth factor on DNA synthesis and motility of human hepatoma cells were also evaluated. RESULTS: Basic fibroblast growth factor and fibroblast growth factor receptor-1 messenger RNAs were present mainly in tumor cells and less so in hepatocytes from noncancerous liver tissue. Immunoreactive products of basic fibroblast growth factor and fibroblast growth factor receptor-1 were observed in tumor cells. The isoform IIIc was expressed in hepatocellular carcinoma tissue and hepatoma cell lines. Exogenous basic fibroblast growth factor stimulated DNA synthesis and motility of hepatoma cells. The effect was more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. Fibroblast growth factor-1 expression on hepatoma cells was also more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. The stimulated motility on basic fibroblast growth factor was suppressed by an anti-fibroblast growth factor receptor-1 antibody. CONCLUSIONS: Basic fibroblast growth factor may play an important role in the development and progression of hepatocellular carcinoma via an autocrine mechanism involving fibroblast growth factor and its receptor.

Adult↗

Therapeutic effects of restricted diet and exercise in obese patients with fatty liver.

BACKGROUND/AIMS: The incidence of obese patients with fatty liver has recently increased in Japan as well as in the United States and Europe. Fatty liver may occasionally progress to liver cirrhosis. In this study, we have compared the effects of restricted diet and exercise versus no treatment in obese patients with fatty liver. METHODS: Twenty-five obese patients with fatty liver were divided into treated and control groups. Fifteen obese patients followed a program of restricted diet (ideal weight x 25 Cal x kg(-1)) and exercise (walking or jogging) for a trial period of 3 months. No changes in diet or lifestyle were made by the other 10 patients during the same trial period. Blood biochemical tests and liver histology were compared in all patients before and after the trial. RESULTS: In the treated group, weight, blood biochemical data such as aminotransferase, albumin, cholinesterase, total cholesterol and fasting blood glucose values, and steatosis were significantly decreased after the trial. In the control group, there were no significant differences in the clinical and histological findings before and after the trial. CONCLUSIONS: These results indicate that restricted diet and exercise therapy, such as walking and jogging, are useful means of improving blood biochemical data and histological findings in liver tissues related to fatty liver.

Adolescent↗

Mechanism of prolongation of pentobarbital-induced sleeping time by empenthrin in mice.

The effect of empenthrin, a synthetic pyrethroid, on pentobarbital (PTB)-induced sleeping time was examined in mice and rats. In mice, pretreatment with empenthrin prolonged PTB-induced sleeping time in a dose-dependent manner. The maximum effect on PTB-sleeping time was noted when mice were pretreated orally with empenthrin 2-4 h before PTB injection. However, empenthrin did not change the sleeping time induced by diethyl ether which is hardly metabolized in liver. Empenthrin inhibited the clearance of serum PTB in mic, but did not change the PTB concentration in serum at which animals recovered from sleeping. To examine the effect of PTB on metabolic enzymes in mouse liver, PTB was incubated aerobically with a hepatic microsomal fraction in the presence of NADPH at 37 degrees C. Empenthrin inhibited the vitro metabolism of PTB dose-dependently. In rats, empenthrin neither changed the PTB sleeping time, nor inhibited the clearance of serum PTB. No inhibitory effect of empenthrin was observed on the in vitro metabolism of PTB using rat hepatic microsomal fraction. These findings indicate that empenthrin prolongs PTB-sleeping time in mice through an inhibition of the PTB-metabolizing enzyme(s) in the liver , an effect that does not occur in rats. Also, there is a clear species-specificity in the inhibitory effect of empenthrin on the PTB-metabolizing enzyme(s).

Animals↗

Effect of pyrethroids on pentobarbital-induced sleeping time in relation to the chemical structure.

The effect of pyrethroids on pentobarbital-induced sleeping time was examined in mice. Pentobarbital-induced sleeping time was defined as the time interval from loss of righting reflex to reappearance of righting reflex. Mice were administered pyrethroids orally 2 h before the intraperitoneal injection of pentobarbital at a dose of 45 mg/kg. Pyrethroids with a cyano group on the alcohol moiety, such as cyphenothrin, cypermethrin, fenvalerate and fenpropathrin shortened the pentobarbital-induced sleeping time, while pyrethroids with an ethynyl group on the acid moiety, such as prallethrin, furamethrin and empenthrin, prolonged sleeping time. Pyrethroids with neither a cyano nor an ethynyl group had no effect on sleeping time. We, thus, found a clear relationship between the chemical structure of pyrethroids and their effect on pentobarbital-induced sleeping time.

Administration, Oral↗

A patient with chronic hepatitis C and a history of abuse of analeptic drugs, who showed hallucination and delusion with interferon administration.

We experienced a case of chronic hepatitis type C accompanied with hallucination and delusion induced by interferon (IFN) therapy positive. The case was a 47-year-old male, whose laboratory data showed positive for anti-Hepatitis C Virus (HCV) and elevated transaminase level. He was treated with 6 MU/day of natural-type IFN-alpha (HLBI). Sleeplessness and delusions of persecution developed about 2 months after the start of IFN therapy. The interview of the psychiatrist disclosed that the patient had a history of addiction to drugs, and these psychiatric symptoms were diagnosed as being of "the flashback phenomenon." These side effects were improved after the administration of psychotropics and it was suggested that we had to take care of the development of flashback phenomenon during the treatment of IFN in cases of chronic hepatitis with a history of addiction to drugs.

Delusions↗

Human heart-type cytoplasmic fatty acid-binding protein as an indicator of acute myocardial infarction.

Human heart-type cytoplasmic fatty acid-binding protein (HH-FABPc) has been proposed as an early biochemical indicator of acute myocardial infarction (AMI). However, skeletal muscles also contain HH-FABPc identical to that found in the heart. Before HH-FABPc can be clinically employed as an indicator of AMI, its content in various tissues other than the heart must be known. Accordingly, we measured the HH-FABPc content of various human muscles and organs, using a sandwich enzyme-linked immunosorbent assay (ELISA) for HH-FABPc. HH-FABPc was abundant in the ventricles (0.46 mg/g wet weight and 1.5% of the cytoplasmic protein in the left ventricle), while the atria contained slightly less HH-FABPc (0.25 mg/g wet weight and 0.7% of the cytoplasmic protein in the left atrium). Of the skeletal muscles tested, the diaphragm contained about one-quarter of the HH-FABPc content of the heart, but other skeletal muscles contained very low levels of this protein. Other than the muscles, the kidneys contained less than one-tenth of the HH-FABPc in the heart, and negligible amounts were found in the liver and small intestine. The distribution of HH-FABPc in the heart and skeletal muscles was comparable to that of cardiac-specific creatine kinase (CK-MB) activity, and was inverse to the distribution of myoglobin. The plasma myoglobin/HH-FABPc ratio, determined in patients with AMI and those without AMI, closely reflected that in the heart and skeletal muscles. These findings indicate that HH-FABPc may be useful as a specific indicator of AMI, and the plasma myoglobin/HH-FABPc ratio could provide valuable information for the diagnosis of AMI.

Adult↗

Pyrethroids, nerve poisons: how their risks to human health should be assessed.

The extensive worldwide efforts of structural modification of natural pyrethrins for better performances have resulted in successful development of a wide variety of synthetic pyrethroids with tremendously high efficacy, knock-down activity or vapor action, and/or with acceptable environmental stability and safety. Currently these pyrethroids including their preferentially manufactured stereoisomers are widely used in agriculture, and for public health as well as household insect control. The detailed toxicology and metabolism studies intended to attain human risk assessment have revealed that with voltage-dependent sodium channel as target site pyrethroids induce pronounced repetitive activity characterized grossly by tremor, hypersensitivity, choleoathetosis, and salivation. In addition, so-called cyano-pyrethroids cause transient skin paresthesia in workers. With regard to tumorigenicity, mutagenicity, teratogenicity and developmental toxicity, no significant findings have been reported. Pyrethroids are eliminated from the animals quite rapidly and completely, undergoing oxidation and ester hydrolysis followed by various conjugations, with low tissue residues. Thus, overall, sound scientific bases exist for human risk assessment under the present usage conditions.

Animals↗

A case of acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg with remission of liver damage after long-term treatment with interferon.

The patient was a 47-year-old female with chronic hepatitis B having antibody to HBe antigen (HBeAg). She was admitted to our hospital in March, 1994, because of acute exacerbation of chronic hepatitis B. Laboratory data revealed the elevated serum transaminase and DNA-polymerase levels, and decreased prothrombin activity. The histological examination of the liver showed chronic active hepatitis with severe hepatic necrosis. Point mutation of the precore region of HBV-DNA (pre-C mutant) was observed in clones from this case by polymerase chain reaction method. The patient was treated with recombinant interferon alpha-2a 9 MU daily for 2 weeks and thereafter 3 times weekly for 6 months. After interferon therapy, the pre-C mutant disappeared with the improvement of transaminase levels and prothrombin activity. These findings suggest the possibility that long-term treatment with interferon therapy is effective for the acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg.

Chronic Disease↗