Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 649 records · Page 36Linked to original sources

PubMed1999

Growth hormone/insulin-like growth factor 1 axis alterations contribute to disturbed protein metabolism in cirrhosis patients after hepatectomy.

BACKGROUND/AIM: Liver cirrhosis is accompanied by a fall in whole-body protein turnover and alterations of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, the influence of liver cirrhosis on the GH/IGF-1 axis in the perioperative period, and the contribution of the GH/IGF-1 axis alteration in cirrhosis to postoperative nitrogen metabolism are not known. METHODS: Plasma GH, IGF-1 and IGF binding protein 3 (IGF-BP3) levels were measured sequentially in patients undergoing hepatectomy with or without cirrhosis. Postoperative nitrogen excretion and whole-body protein turnover rate were also determined. RESULTS: Preoperative plasma IGF-1 level showed a negative correlation with indocyanine green retention rate. Cirrhosis patients undergoing hepatectomy had low IGF-1 and IGF-BP3 levels, despite extremely high GH levels in the perioperative period. Perioperative IGF-1 levels were lower in patients with postoperative complications than in those without complications. Postoperative nitrogen excretion was higher and whole-body protein turnover rate was lower in patients with cirrhosis than in those without cirrhosis. The post-operative IGF-1 level showed a positive correlation with whole-body protein turnover rate. CONCLUSIONS: Postoperative hepatic IGF-1 production may be severely disturbed in patients with cirrhosis, and the impaired IGF-1 production contributes to the suppressed postoperative protein metabolism in cirrhosis. It may be appropriate to increase plasma IGF-1 level in patients with cirrhosis to enhance postoperative protein metabolism and improve the postoperative outcome.

Aged↗

PubMed1999

Tolerance of NK and LAK activity for HLA class I-deficient targets in a TAP1-deficient patient (bare lymphocyte syndrome type I).

NK cells recognize target cells that lack HLA class I molecules and lyse them, according to the 'missing self' hypothesis. It was previously reported that a TAP2-deficient patient with an HLA class I-deficiency, had a normal number of NK cells but that the lymphocytes of this patient had lost their NK activity against K562 cells. In this study, we investigated the HLA class I-recognizing NK receptor expressions and the NK and LAK activities of the lymphocytes of a TAP1-deficient patient. The patient had a normal number of NK cells. Although the lymphocytes showed LAK activity against class I expressing targets following IL-2, IL-12 and IL-15 stimulation for 3 days, neither NK nor LAK activity against targets lacking class I molecules was induced. The NK cells of the patient expressed class I-recognizing NK receptors, although the percentages of such cells were low. However, no differences were observed in the expression levels of inhibitory and activating NK receptors between lymphocytes of the patient and those of healthy controls, suggesting that the modulation of the NK receptor expression is not primarily responsible for this tolerance. These results also suggest that the lymphocytes of the patient are defective in the recognition of class I-deficient target cells in order to promote the induction of self tolerance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Risk factors for vertebral fractures in renal osteodystrophy.

We determined the prevalence of vertebral fractures in hemodialysis (HD) patients, investigated whether low bone mineral density (BMD) is predictive of vertebral fracture, and evaluated the effect of serum intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) levels on vertebral fracture. One hundred eighty-seven male HD patients were assessed for vertebral fractures, and lumbar-spine and total-body BMD were measured by dual-energy x-ray absorptiometory. Thirty-nine patients (20.9%) had vertebral fractures. Each standard deviation (SD) decrease in lumbar-spine BMD increased the age-adjusted odds ratio of vertebral fracture 2.0 times (95% confidence interval [CI], 1.4 to 2.0) and 1.6 times (95% CI, 1.1 to 1.6) for total-body BMD. The area under the receiver operating characteristic curve for lumbar-spine BMD was significantly greater than that for total-body BMD (P < 0.05). Patients with serum iPTH levels in the lowest tertile had a 2.4-fold greater risk for vertebral fracture than those in the middle tertile and a 1.6-fold greater risk than those in the highest tertile (P < 0.05). When the two criteria of lowest tertile of serum iPTH level and highest tertile of serum ALP level were combined, the prevalence of vertebral fractures was the greatest. Similarly, when the lowest tertile of serum iPTH level and lowest tertile of serum ALP level were combined, the prevalence was the second greatest among the combined groups according to tertiles of serum iPTH and ALP levels. We conclude that low lumbar-spine BMD might be a sensitive predictor of vertebral fracture in HD patients, and patients with relatively low iPTH levels would have a greater risk for vertebral fracture than those with hyperparathyroidism.

Absorptiometry, Photon↗

PubMed1999

Effects of the benzodiazepine antagonist flumazenil on conditioned fear stress in rats.

1. The authors investigated the effect of the benzodiazepine receptor antagonist flumazenil on freezing behavior induced by conditioned fear stress and used a time-sampling procedure. 2. Rats were individually subjected to 5 min of inescapable electric footshock in a shock chamber. Twenty-four hours after the footshock, the rats were again placed in the shock chamber and observed for 5 min without shocks: this procedure is termed conditioned fear stress. 3. Subcutaneous administration of flumazenil (10 mg/kg) 30 min before conditioned fear stress reduced conditioned freezing, while flumazenil (1-10 mg/kg) 30 min before footshock did not. This indicates that flumazenil reduced the expression of conditioned fear, suggesting an anxiolytic effect of flumazenil. 4. This effect may be attributable to antagonism by flumazenil to endogenous inverse agonist-like ligands for benzodiazepine receptors. It is suggested that endogenous inverse agonist-like ligands for benzodiazepine receptors are involved in the expression of conditioned fear stress.

Animals↗

PubMed1999

Toxicological studies on procyanidin B-2 for external application as a hair growing agent.

Procyanidin B-2 [epicatechin-(4beta --> 8)-epicatechin] is one of condensed tannin that exists widely in plants. We have reported previously that procyanidin B-2 possesses hair epithelial cell growth-promoting activity and stimulates anagen induction in hair cycle progression. To evaluate the safety of topical procyanidin B-2 as a hair growing agent, we examined the mutagenicity, acute subcutaneous injection, primary irritation, skin sensitization, and eye irritation of this compound. Mutagenicity tests using bacteria showed procyanidin B-2 to be non-mutagenic. Chromosomal aberration tests using CHL cells indicated that procyanidin B-2 caused polyploidy but no structural aberrations. In micronucleus tests for mutagenicity using mice, procyanidin B-2 was negative. Acute subcutaneous injection study using rats revealed no symptoms of significant injury. The lethal dose of procyanidin B-2 is greater than 2000 mg/kg (subcutaneous injection). Primary irritation tests using rabbits indicated that procyanidin B-2 containing preparation shows no primary irritation. In the guinea pig maximization test, there was no evidence of sensitization to procyanidin B-2. In primary ocular irritation tests using rabbits, procyanidin B-2 containing preparation and vehicle showed slight irritation of conjunctivae which is assumed to be caused by ethanol. It is suggested that topical procyanidin B-2 is safe and acceptable from the series of toxicological tests.

Administration, Topical↗

PubMed1999

Toxicity study of a rubber antioxidant, mixture of 2-mercaptomethylbenzimidazoles, by repeated oral administration to rats.

2-Mercaptobenzimidazole (2-MBI), a rubber antioxidant, is known to exhibit potent antithyroid toxicity in rats and is a candidate as an environmental endocrine disrupter. 2-Mercaptomethylbenzimidazoles (a 1:1 mixture of 4-methyl and 5-methyl isomers, MMBIs), are also employed industrially as rubber antioxidants and are suspected to exert antithyroid toxicity such as 2-MBI. In this investigation, acute and subacute oral toxicity studies of MMBIs in Wistar rats were conducted. The clinical signs of acute oral toxicity were observed including decreased spontaneous movement, a paralytic gait, salivation and lacrimation, and adoption of prone and lateral positions. The LD50 was estimated to be 330 mg/kg. In the subacute oral toxicity study, male and female rats were treated with MMBIs by gavage at doses of 0 (corn oil), 4, 20 and 100 mg/kg for 28 consecutive days followed by a 2-week recovery period for the control and highest dose groups. Body weight and food consumption, clinical signs, organ weights, clinical biochemistry and haematological parameters including clotting times and micronuclei induction in bone marrow erythropoeitic cells, and histopathology were examined. Relative organ weights of lung, liver and kidney, and serum cholesterol and phospholipid significantly increased in male rats treated with MMBIs at doses of 20 and 100 mg/kg. Male rats administered 100 mg/kg MMBIs exhibited a 1.8-fold increase in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Female rats administered 100 mg MMBIs/kg exhibited significant increases of liver and kidney but not thyroid weights, and serum cholesterol level. The antithyroid toxicity of MMBIs in rats was estimated to be one-tenth that of 2-MBI. No-observed-effect levels for male and female rats were found to be 4 and 20 mg/kg, respectively, in this subacute oral toxicity study.

Animals↗

PubMed1999

Late expression of red cell membrane protein 4.2 in normal human erythroid maturation with seven isoforms of the protein 4.2 gene.

The expression of protein 4.2 in normal human erythroid cells was studied utilizing erythroblasts from bone marrow and erythroid cells cultured by the two-phase liquid culture method from burst-forming unit erythroid (BFU-E) in peripheral blood. As opposed to spectrin, which was expressed in erythroid progenitors or very early erythroblasts, protein 4.2 was first detected in late erythroblasts with a morphology nearly identical to orthochromatic erythroblasts. Among the various major membrane proteins, the expression of protein 4.2 was the latest. At the gene level, protein 4.2 gene mRNA was expressed in early erythroblasts. During normal erythroid maturation, the expression of seven different protein 4.2 gene products was observed by Southern blot analysis. These seven gene products appeared to be derived from protein 4.2 gene in the presence or absence of skipping of the 90 bp in exon 1, exon 3, and/or exon 5, as judged by deduction from the protein 4.2 sequence. Therefore, it can be speculated that protein 4.2 is expressed after the cytoskeletal network has been constructed and assembled with integral proteins in the membrane lipid bilayer.

Blood Proteins↗

PubMed1999

Relationship between molecular mass and duration of activity of polyethylene glycol conjugated granulocyte colony-stimulating factor mutein.

Proteins conjugated with polyethylene glycol (PEG) have increased in vivo activity compared to native proteins. We examined the activity of a variety of PEG conjugates prepared with a recombinant mutein of granulocyte colony-stimulating factor (nartograstim [NTG], KW-2228). The total PEG mass was varied by the number and size of the PEG molecules conjugated. In vitro activity, determined using a proliferation assay with G-NFS-60 cells, demonstrated an inverse relationship between PEG mass and concentration required for half-maximal proliferation. In vivo activity was examined by injecting compounds subcutaneously into normal mice and determining neutrophil counts at various times. Initial experiments in C57BL/6J mice indicated that neutrophil levels were significantly elevated 5 days after a single injection of 25 micrograms/mouse of each PEG-NTG preparation. More detailed experiments were performed with several of the preparations in C3H/HeJ mice lacking endotoxin receptors. The results demonstrated that the time after injection at which neutrophil numbers reached a maximum increased with increasing size of PEG. Similar results were obtained with purified preparations containing 1, 2, or 3 units of 20-kDa PEG per molecule of NTG, showing that increasing the extent of PEGylation also increases in vivo activity. Dose-response studies with the 20-kDa PEG-NTG demonstrated a plateau at doses > 2.7 micrograms/mouse at day 3. The plateau dose increased to 8.4 micrograms/mouse at day 5, and no plateau was evident at the highest dose tested (50 micrograms/mL) at days 7 and 10. These results demonstrate that elevated neutrophil levels can be maintained for extended periods following single administration of high-molecular-weight PEG-NTG.

Animals↗

PubMed1999

Imaging the pyramidal tract in patients with brain tumors.

The clinical usefulness of diffusion-weighted magnetic resonance imaging (DWI) of the pyramidal tract was evaluated in patients with brain tumors. Five normal volunteers and seven patients with glioma (n = 4) or meningioma (n = 3) near the pyramidal tract underwent coronal echo planar DWI. Greyscale DWIs in each of the three orthogonal diffusion gradients were transformed into graduations, color-coded as red, green or blue, respectively, and then composited to form a combined color image. The entire pyramidal tract was visualized on a single fiber mapping image by combining the upper half of the image slice including the primary motor cortex, the corona radiata and the internal capsule with the lower half of the image slice including the internal capsule, the cerebral peduncle and the ventral brain stem. Fiber mapping images demonstrated the pyramidal tract as a distinct band indicating nerve fiber integrity in all volunteers. The entire pyramidal tract from the primary motor subcortex to the ventral brain stem could be traced. Fiber mapping images showed the ipsilateral pyramidal tract as either discontinuous due to impaired anisotropy or compressed due to mass effect in patients with brain tumors. These findings corresponded well with the pre- and postoperative motor functions. Fiber mapping images are useful for evaluating the white matter neuronal tracts and can provide indications for determining surgical strategy.

Adult↗

PubMed1999

Cholinergic-drug induced sicca syndrome in Parkinson's disease: a case report and a review of the literature.

A 67-year-old woman developed severe sicca manifestations after initial treatment of Parkinson's disease with an anti-cholinergic drug, which prompted us to look for the presence of Sjögren's syndrome. The results of sialography, labial salivary gland biopsy, Rose-Bengal test as well as the presence of antinuclear antibody were consistent with the diagnosis of Sjögren's syndrome. The sicca symptoms diminished by cessation of the anti-cholinergic drug, and the parkinsonian features were controlled by levodopa. We suggest that Sjögren's syndrome should be considered, if patients with Parkinson's disease complain severe xerostomia.

Aged↗

PubMed1999

Prophylactic treatment with growth hormone and insulin-like growth factor I improve systemic bacterial clearance and survival in a murine model of burn-induced gut-derived sepsis.

The purpose of this investigation was to evaluate the effects of GH and IGF-I administration in a murine model of burn-induced gut-derived sepsis. BALB/C mice were treated with 4.8 mg/kg/day of GH, 24 mg/kg/day of IGF-I or saline for 4 days. They were then administered 10(10) E. coli by gavage and subjected to 20% full thickness flame burn. All mice received allogeneic blood transfusion 5 days before burn injury to induce mild immunosuppression. Seventy-three mice were observed for survival and 51 mice were sacrificed at 4 and 20 h postburn. Blood, mesenteric lymph nodes (MLN), spleen and liver were harvested aseptically, and viable bacterial counts in the organs were determined. The small intestine was harvested for the evaluation of villus height and mitoses in the crypts. GH and IGF-I groups showed a significantly better survival than the control group. GH and IGF-I groups had significantly greater villus height and mitoses/crypt than the control group. Translocation of bacteria was not significantly different among groups, however, the relation between the numbers of viable bacteria in MLN and blood suggests that both GH and IGF-I reduced systemic spread of translocated bacteria. It is concluded that GH and IGF-I had positive effects on outcome in this model of burn-induced gut-derived sepsis. It appears that GH and IGF-I may have immune-enhancing effects and that administration of these agents may be useful for burn injury.

Animals↗

PubMed1999

Fluorescence property of oxazole yellow-linked oligonucleotide. Triple helix formation and photocleavage of double-stranded DNA in the presence of spermine.

Oxazole yellow is an intercalator that shows enhanced fluorescence upon binding to DNA. We prepared an oxazole yellow-linked oligonucleotide that can form triple helix with interleukin 2 receptor alpha chain promoter. The oxazole yellow-linked oligonucleotide showed linear increase of fluorescence by the triple helix formation with double-stranded DNA and also induced photocleavage of the targeted DNA in the presence of spermine upon visible illumination. Cleavage site of one strand was 7 or 8 bases away from the site of intercalation whereas the other strand was cleaved at the intercalated site.

Benzoxazoles↗

PubMed1999

Localization of indium-111 in human malignant tumor xenografts and control by chelators.

The kinetics of soluble indium-111 ((111)In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of (111)In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. (111)In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of (111)In-chloride. Secondly, the effect of edetate calcium disodium (CaNa2EDTA) on radioactivity in (111)In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa2EDTA significantly reduced (111)In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa2EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with (111)In-chloride was investigated. In one group of mice CaNa2EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of (111)In-chloride (postadministration), the localization of (111)In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa2EDTA administered intraperitoneally at 12 and 1 h before injection of (111)In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa3DTPA had a more powerful effect than CaNa2EDTA. In conclusion, (111)In-activity in tumors consists of intracellular and extracellular components, and the extracellular (111)In may be cleared by chelators. Pre- and postadministration of CaNa3DTPA could remove (111)In-nonspecific localization in tumors when (111)In is released from the radiolabeled agents.

Animals↗

PubMed1999

Yttrium-90-labeled human macroaggregated albumin for internal radiotherapy: combined use with DTPA.

The aim of this study was to investigate the possibility of yttrium-90-labeled human macroaggregated albumin (90Y-MAA) as an internal radiotherapeutic agent for whole-lung irradiation in combination with diethylenetriamine pentaacetic acid (DTPA). The influence of trisodium calcium DTPA (CaNa3DTPA) on the radioactivity of 90Y-MAA in serum was investigated in vitro. The effect of CaNa3DTPA on the biodistribution of radioactivity in normal mice intraveneously injected with 90Y-MAA was examined. CaNa3DTPA could deprive in vitro radioactivity of 90Y-MAA in 48-h incubation. Most of the radioactivity (>90% injected dose per lung) was observed at murine lung after injection of 90Y-MAA. Pulmonary radioactivity was cleared within 72 h postinjection, whereas the radioactivities in the bone, liver, kidneys, and spleen increased with a peak at 48 h. CaNa3DTPA-treatment reduced the in vivo radioactivities in bone, liver, and kidneys without influence on the radioactivity of lung. In conclusion, combined use of CaNa3DTPA enables 90Y-MAA to be used as a radiopharmaceutical for internal irradiation against whole lung.

Albumins↗

PubMed1999

Enhanced microbial adaptation to p-nitrophenol using activated sludge retained in porous carrier particles and simultaneous removal of nitrite released from degradation of p-nitrophenol.

In order to examine the microbial degradation of p-nitrophenol (PNP) by a mixed culture system and simultaneous removal of nitrite released via the degradation, an activated sludge retained in porous carrier particles and a suspension culture as a control were acclimated to artificial sewage containing PNP as the sole carbon source. The adaptation of microbes retained in porous carrier particles to PNP was faster than that of suspended microbes by more than 20 d. After microbial adaptation to PNP, it was degraded completely without significant accumulation of intermediate metabolites. The PNP degradation activity of the retained microbes was more than 2 times higher than that of the suspended microbes. By increasing the retained microbial concentration, nitrite released from the degraded PNP was removed by denitrification. This research demonstrates that using microbes retained in porous carrier particles is not only effective for reduction of acclimation time but also enables simultaneous removal of the nitrogen compounds resulting from the degradation of nitroaromatics.

Journal Article↗

PubMed1999

Improvement of isoamyl acetate productivity in sake yeast by isolating mutants resistant to econazole.

Sake yeast strains were improved so as to produce larger amounts of isoamyl acetate than the parental strain by isolating econazole-resistant mutants. Econazole, an imidazole antimycotic, directly interacts with unsaturated fatty acids in the yeast cell membrane, where it also inhibits the synthesis of ergosterol and decreases the ratio of unsaturated to saturated fatty acids. In contrast, alcohol acetyltransferase (AATase), which catalyzes the synthesis of isoamyl acetate, is inhibited by unsaturated fatty acids. Fifty econazole-resistant mutants were isolated from a sake yeast, Kyokai no. 701, several of which produced approximately 1.4 to 2.4 times more isoamyl acetate and an almost equal amount of isoamyl alcohol compared with the parental strain. The AATase activities of the mutants in koji extract were 1.2 to 1.4 times higher, and the unsaturated to saturated fatty acid ratios were lower, than in the parental strain.

Journal Article↗

PubMed1999

TPA-enhanced motility and invasion in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1: selective role of PKC-alpha and its inhibition by a combination of PDBu-induced PKC downregulation and antisense oligonucleotides treatment.

We previously found that 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced invasiveness was associated with augmentation of cell motility but not that of metalloproteinase activity in a highly metastatic variant (L-10) of the human colon adenocarcinoma cell line RCM-1 and that this enhancement was possibly mediated by protein kinase C (PKC). In this study, we first intended to determine the specific isoforms of PKC involved in this TPA-enhanced L-10 cell motility that leads to invasion, and then investigated the way to inhibit the enhanced motility and invasion by using antisense oligodeoxynucleotides (ODN) targeting the isoform. An activator of conventional PKC isoforms (cPKC), thymeleatoxin, enhanced L-10 cell motility and invasion like TPA, and an inhibitor of cPKC, Go-6976, efficiently inhibited TPA-enhanced motility and invasion. TPA treatment induced a shift of PKC-alpha, but not other isoforms, from the cytosol to the membrane fraction, indicating the activation of the isoform. During the assay period, only activation but not downregulation of PKC-alpha occurred with the low concentration of TPA used in our assays. Antisense ODNs specific for PKC-alpha efficiently reduced its expression at the protein levels and inhibited L-10 cell motility in the absence of TPA. With TPA treatment, however, the remaining PKC-alpha was sufficient for activation leading to enhanced invasion. Only a combination of depletion of PKC by prolonged stimulation with a high concentration of phorbol 12,13 dibutyrate (PDBu) and treatment with antisense ODNs effectively inhibited L-10 cell invasion even in the presence of TPA. These results suggested that downregulation of PKC isoforms by treatment with antisense ODNs alone is insufficient to suppress the isoform-mediated cellular events in the presence of PKC activators, and thus that some additional treatments are necessary for the successful downregulation of them.

Adenocarcinoma↗

PubMed1999

Cell surface expression of HLA-E molecules on PBMC from a TAP1-deficient patient.

It was recently revealed from studies on TAP-deficient cell lines that HLA-E molecules are associated with nonamer peptides derived from certain HLA class I leader sequences and are expressed on the cell surface in a TAP-dependent manner. We have previously reported a homozygous TAP1 gene mutation in a HLA class I-deficient patient. In the present report, we demonstrate HLA-E molecule expression on the surface of the peripheral blood mononuclear cells (PBMC) of the TAP1-deficient patient. The HLA-E expression level on the monocytes of the patient was as high as that in healthy donors, whereas the HLA-E expression level on the lymphocytes of the patient was slightly lower. On the other hand, HLA-E expression was not detected on KMW-B2 cells, an Epstein-Barr virus (EBV)-transformed B-cell line derived from the lymphocytes of the TAP1-deficient patient. These data suggest the existence of TAP-dependent and -independent pathways for the surface expression of HLA-E molecules.

ATP Binding Cassette Transporter, Subfamily B, Mem↗