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Biomedical subjects

T Asano

Publications and source records attributed to T Asano.

At least 307 records · Page 17Linked to original sources
PubMed1997

Inhibition of growth and invasive activity of human pancreatic cancer cells by a farnesyltransferase inhibitor, manumycin.

The effects of manumycin, a competitive farnesyltransferase (FTase) inhibitor, on pancreatic cancer cell lines with or without K-ras mutation were studied. Manumycin inhibited the growth of human pancreatic cancer cells (SUIT-2, MIA PaCa-2, AsPC-1, BxPC-3) in a dose-dependent manner. The 50% inhibitory concentration (IC50) in cell lines with a mutant K-ras gene (SUIT-2, MIA PaCa-2, AsPC-1) was lower than that in BxPC-3 with a wild-type ras. Both mitogen-activated protein kinase activity after growth stimuli and the ability for chemotactic invasion were markedly more inhibited by manumycin in SUIT-2 than in BxPC-3. These results suggest that mutated Ras is more sensitive to manumycin than the wild type. Furthermore, tumor growth and liver metastasis in nude mice inoculated with manumycin-treated SUIT-2 cells were inhibited dose dependently. Inhibition of Ras activity might be a new anticancer strategy in pancreatic cancer in which Ras plays a role.

Alkyl and Aryl Transferases↗
PubMed1997

Assessment of energy status and fructose metabolism of liver in obstructive jaundice by 31P magnetic resonance spectroscopy.

The effect of cholestasis on hepatic energy status and fructose metabolism in jaundiced rats and patients was investigated using 31P magnetic resonance spectroscopy. Rats with obstructive jaundice (OJ group) were studied 7 days after bile duct ligation. Drainage rats were studied at 3 days (DR3 group) and 7 days (DR7 group) after the relief of 1 week obstruction of the common bile duct. In the bile duct ligated rat, the beta-adenosine triphosphate (ATP)/Pi (inorganic phosphate) ratio was significantly lower than in sham-operated controls. This ratio recovered rapidly in the DR3 and DR7 groups. The maximum increase in the phosphomonoester peak (PMEmax) after an intravenous bolus of fructose was significantly reduced in both the OJ and DR3 groups, and was accompanied by a decrease in hepatic fructokinase activity. The PMEmax and the fructokinase activity recovered in the DR7 group. In a clinical study, the beta-ATP/Pi ratio in six healthy volunteers was comparable to that of 15 patients with obstructive jaundice, regardless of their biliary drainage status. The PMEmax in all patients (serum bilirubin > or = 5 mg/dL), irrespective of biliary drainage, was significantly lower than in volunteers. Furthermore, the PMEmax in four of the eight patients with biliary drainage (serum bilirubin < 5 mg/dL) was lower than in volunteers. It is concluded that while energy status in jaundiced patients is well maintained, fructose phosphorylation is inhibited and recovery is delayed after the relief of obstruction compared with serum bilirubin. For the non-invasive evaluation of damaged liver function in jaundice, 31P magnetic resonance spectroscopy is a useful technique.

Adenosine Triphosphate↗
PubMed1997

Effects of basic fibroblast growth factor on human periodontal ligament cells.

In order to clarify the regulatory mechanisms of periodontal regeneration by basic fibroblast growth factor (bFGF), effects of bFGF on proliferation, alkaline phosphatase activity, calcified nodule formation and extracellular matrix synthesis of human periodontal ligament (PDL) cells were examined in this study. bFGF enhanced the proliferative responses of PDL cells in a dose-dependent manner. The maximum mitogenic effect of bFGF on PDL cells was observed at the concentration of 10 ng/ml. In contrast, bFGF inhibited the induction of alkaline phosphatase activity and the mineralized nodule formation by PDL cells. Moreover, employing the reverse transcription-polymerase chain reaction (RT-PCR) technique, we observed that the levels of laminin mRNA of human PDL cells was specifically upregulated by bFGF stimulation, but that of type I collagen mRNA was downregulated. On the other hand, the expression of type III collagen and fibronectin mRNA were not altered even when the cells were activated by bFGF. These results suggest that suppressing cytodifferentiation of PDL cells into mineralized tissue forming cells, bFGF may play a role in wound healing by inducing growth of immature PDL cells and that in turn accelerates periodontal regeneration.

Alkaline Phosphatase↗
PubMed1997

Roles of PI 3-kinase and Ras on insulin-stimulated glucose transport in 3T3-L1 adipocytes.

The dominant negative p85alpha regulatory subunit (delta p85alpha) of phosphatidylinositol (PI) 3-kinase or dominant negative Ras (N17Ras) was overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated gene transduction system. Functional expression of delta p85alpha and N17Ras was confirmed by marked inhibition of insulin-stimulated PI 3-kinase activity and mitogen-activated protein kinase activity, respectively. N17Ras expression did not affect glucose transport activity, whereas delta p85alpha expression inhibited insulin-stimulated glucose transport with impairment of GLUT-4 translocation, although inhibition of glucose transport activity was less remarkable than that of PI 3-kinase activity in delta p85alpha-expressing cells. Thus the Ras signaling pathway does not play a major part in either translocation or intrinsic activity of glucose transporters, but PI 3-kinase activation, via phosphotyrosyl proteins and heterodimeric PI 3-kinase, plays a pivotal role in insulin-stimulated glucose transport. However, a discrepancy was observed between PI 3-kinase activity and glucose transport activity, suggesting a possibility that a different pathway(s) is involved in insulin-stimulated intrinsic activity of glucose transporters.

3T3 Cells↗
PubMed1997

Direct stimulation of basal insulin secretion by physiological concentrations of leptin in pancreatic beta cells.

We examined a possible mechanism underlying the link between obesity and hyperinsulinemia, focusing on leptin, a peptide released from adipocytes which affects the satiety center in the brain. The leptin receptor isoforms, Ob-Ra and Ob-Rb, are present in the pancreatic beta cell line MIN6 and in rat pancreatic islets, based on RT-PCR. A 2 hr, but not a 30 min, incubation with 1 nM recombinant mouse leptin, the concentration observed in obese subjects, stimulated basal (at 5 mM glucose) insulin secretion by approximately 40% in both MIN6 and rat islets. Stimulatory effects were not observed without glucose or when the incubation medium containing 1 nM leptin had been preincubated with the immobilized leptin antibody. In contrast to the stimulatory effects on basal insulin secretion at 1 nM, the maximally stimulated insulin secretion at 25 mM glucose was not significantly changed by 1 nM leptin in isolated rat islets. In addition, 10 and 100 nM leptin exerted small but significant inhibitory effects on 16.7 mM glucose-stimulated insulin secretion. Thus, leptin acts directly on pancreatic beta cells, and stimulation of basal insulin secretion by physiological concentrations of leptin may account in part for the fasting hyperinsulinemia observed in obese subjects.

Animals↗
PubMed1997

Targeting of GLUT1-GLUT5 chimeric proteins in the polarized cell line Caco-2.

Caco-2, a human differentiated intestinal epithelial cell line, is a promising model for investigating the mechanism of polarized targeting of apical and basolateral membrane proteins. We stably transfected rat GLUT5 cDNA and rabbit GLUT1 cDNA into Caco-2 cells with an expression vector. Immunohistochemical study revealed that the GLUT5 protein expressed was localized at apical membranes and that the GLUT1 expressed was present primarily in the basolateral membranes of cells grown on permeable support. Next, to investigate the domain responsible for determining apical vs. basolateral sorting in glucose transporters, we prepared several GLUT1-GLUT5 chimeric cDNAs and transfected them into Caco-2 cells. A GLUT1 [N terminus approximately sixth transmembrane domain (TM6)]-GLUT5 [intracellular loop (IL) approximately C terminus] chimera was observed exclusively at the apical membrane, while GLUT1 (N terminus approximately IL)-GLUT5 (TM7 approximately C terminus) and GLUT1 (N terminus approximately TM12)-GLUT5 (C-terminal domain) chimeras were observed mainly at the basolateral membrane, a localization similar to that of GLUT1. Moreover, using a recombinant adenovirus expression system, we expressed a GLUT5 (N terminus approximately TM6)-GLUT1(IL)-GLUT5(TM7 approximately C-terminus) chimera, which was observed at the basolateral membrane. Based on these results, the C-terminal domain does not determine isoform-specific targeting of GLUT1 and GLUT5. Rather, it is the intracellular loop in glucose transporters that appears to play a pivotal role in apical-basolateral sorting signals in Caco-2 cells.

Animals↗
PubMed1997

Association of the gamma12 subunit of G proteins with actin filaments.

Recent studies have suggested an association between heterotrimeric G proteins, which play a major role in transmembrane signal transduction, and intracellular components. We therefore examined the subcellular localization of isoforms of G protein gamma subunits in Swiss 3T3 and C6 glioma cells, mainly containing the gamma5 and gamma12 subunits. Immunocytochemical double staining with phalloidin showed co-localization of the gamma12 subunit with actin filaments (F-actin), while the gamma5 co-localized with vinculin, suggesting an association with focal adhesion. Pretreatment of cells with Triton X-100 eliminated the gamma5 but not the gamma12 staining. Co-localization of gamma12 and F-actin was preserved when F-actin was disorganized with cytochalasin D or reorganized using fetal calf serum. Large amounts of gamma12 were recovered in the vimentin- and tubulin-free F-actin-rich fraction prepared from crude cytoskeleton preparations by double depolymerization-repolymerization. Co-localization of Gi2alpha, beta and gamma12 in the F-actin-rich fraction suggested the existence of gamma12 as a betagamma or heterotrimeric complex. Furthermore, purified betagamma12 was found to associate with F-actin in vitro more tightly than betagamma5. These results strongly suggest that the gamma12 subunit associates with F-actin in cells. The observed differential distribution of gamma12 and gamma5 implies functional differences for the two gamma subunits.

3T3 Cells↗
PubMed1997

SCID-bg mice as xenograft recipients.

SCID-bg (scid/scid, beige/beige) is a strain of double-mutant mice with impaired lymphoid development and reduced natural killer (NK) cell activity. The present study was undertaken to evaluate the usefulness of SCID-bg mice as xenograft recipients. Fetal guinea pig tissues (liver, thymus, spleen) were transplanted under the kidney capsule of the mice and their serum guinea pig IgG levels were measured weekly thereafter, C.B.-17-scid and anti-asialo GM1 antiserum-treated (NK-depleted) C.B.-17-scid (C.B.-17-scid-AGM1) mice that received the identical transplants were used as controls. Throughout the experimental period (1, 2, and 3 weeks after transplantation), the average serum guinea pig IgG concentrations was highest in C.B.-17-scid-AGM1 mice followed by SCID-bg mice and lowest in C.B.-17-scid mice without antiserum treatment, though we could not find any statistical significance among these groups. However, SCID-bg mice always showed the smallest within-group variance (individual difference) in the serum guinea pig IgG concentrations (P < 0.05, versus C.B.-17-scid-AGM1 mice at 1, 2, and 3 weeks and versus C.B.-17-scid mice at 2 weeks). The graft size was not significantly different among these three groups, but the spleen grafts in C.B.-17-scid mice contained fewer nucleate cells than the other two groups. These results indicate that the reduced NK cell activity by beige mutation is not crucial for the success of xenogenic transplantation, though SCID-bg mice may be useful as xenograft recipients with a consistent potential to retain the viability and function of engrafted tissues.

Animals↗
PubMed1997

Simple i.v. inoculation of HIV-1 to Thy/Liv SCID-hu mice induce reproducible HIV infection with narrowing of medulla in human thymic implant.

Human fetal thymus/liver engrafted SCID mice were constructed and studied for its susceptibility to HIVBRU infection by i.v. inoculation which seemed to represent an appropriate route of HIV infection in vivo. By the i.v. inoculation of HIV, the medulla in the engrafted thymus narrowed significantly when compared with that of the human thymic implant from virus-uninoculated mice. Further, immunohistochemical staining indicated the presence of HIV antigen predominantly in thymic epithelial cells in medulla of the engrafted thymus. Polymerase chain reaction (PCR) assays resulted in amplifications of HIV genome in the implanted grafts as well as in lymph nodes and PBMC. The virus infections to the implants were confirmed biologically by coculturing with PHA-stimulated human PBMC and the graft cells from the HIV-inoculated SCID-hu mice. Thus, the i.v. inoculation of HIV into Thy/Liv SCID-hu mice induce narrowing of medulla of the engrafted thymus and may become an efficient and useful tool for screening candidate anti-HIV agents.

Acquired Immunodeficiency Syndrome↗
PubMed1997

An improved canine model of subarachnoid hemorrhage using intrathecal indwelling catheters.

In the present study, the feasibility of intrathecal indwelling catheters in the preparation of a repeated subarachnoid hemorrhage (SAH) model in dogs, as well as chronic intrathecal administration of therapeutic agents against the ensuing cerebral vasospasm was examined. Briefly, through a small suboccipital incision, two catheters were introduced into the subarachnoid space so that their tips were positioned in the prepontine cistern. One was used to induce SAH by infusing autologous blood, and the other to administer pharmacological agents (saline and/or saline containing a dye in this study) by means of an osmotic pump. The occurrence of cerebral vasospasm was followed by angiography via the catheter placed in the vertebral artery. The obtained results show: i) the injected blood effectively formed a subarachnoid clot in the prepontine cistern, invariably leading to the occurrence of severe cerebral vasospasm of the basilar artery; ii) the fluid injected by the osmotic pump was evenly distributed in the cisterns around the brain stem; iii) on post mortem pathological examination, no injury of the brain or the major arteries ascribable to the placement of catheters was found. Therefore, the present model is considered to be useful for both the investigation of pathophysiology and therapy of cerebral vasospasm following SAH, to be more favorable from the standpoint of animal protection, and more convenient and reliable than those used until now.

Angiography↗
PubMed1997

Mental deterioration in childhood epilepsy.

Mental retardation is detected in 20-30% of children with epilepsy at hospitals specializing in treatment of childhood epilepsy. However, the incidence of mental deterioration in childhood epilepsy is not high. In this study, mental deterioration was found in 52 (1.8%) of the 2,880 children with epilepsy at Okayama University Hospital. The patients showing mental deterioration mostly suffered from specific epileptic syndromes, such as West syndrome, Lennox-Gastaut syndrome, severe myoclonic epilepsy in infancy and epilepsy with continuous spike-waves during slow wave sleep. These types of epilepsy show generalized electroencephalographic (EEG) abnormalities. It is presumed that mental deterioration is caused by the total effects of prolonged diffuse EEG abnormalities and the age of the patients. Antiepileptic drugs exert a relatively minor effect on mental deterioration.

Adolescent↗
PubMed1997

Childhood ischemic stroke caused by fibromuscular dysplasia of the intracranial artery--case report.

An 8-year-old girl presented with fibromuscular dysplasia of the intracranial vessels manifesting as ischemic stroke. Neuroimaging showed infarction of the right putamen and ipsilateral frontal white matter. Angiography revealed "string of beads" sign involving the terminal portion of the right internal carotid artery and the horizontal segment of the ipsilateral middle cerebral artery. She was treated conservatively. Magnetic resonance angiography at 2 months post ictus showed similar findings in the middle cerebral artery but improvement of the stenosis of the internal carotid artery. Her neurological deficits had almost resolved. Fibromuscular dysplasia should be part of the differential diagnosis of ischemia in children.

Brain Ischemia↗
PubMed1997

[Single photon emission computed tomography in the diagnosis of Alzheimer's disease].

Studies with single photon emission computed tomography (SPECT) have shown temporoparietal (TP) hypoperfusion in patients with Alzheimer's disease (AD). We evaluated the utility of this findings in the diagnosis of AD. SPECT images with 123I-iodoamphetamine were analyzed qualitatively by a rater without knowledge of the subject's clinical status. Sixty-seven of 302 consecutive patients were judged as having TP hypoperfusion by SPECT imaging. This perfusion pattern was observed in 44 of 51 patients with AD, in 5 with mixed dementia, 8 with cerebrovascular disease (including 5 with dementia), 4 with Parkinson's disease (including 2 with dementia), 1 with normal pressure hydrocephalus. 1 with slowly progressive aphasia. 1 with progressive autonomic failure, 2 with age associated memory impairment, and 1 with unclassified dementia. The sensitivity for AD was 86.3% (44 of 51 AD), and the specificity was 91.2% (229 of 251 non-AD). Next, we looked for differences in perfusion images between patients with AD and without AD. Some patients without AD had additional hypoperfusion beyond TP areas: deep gray matter hypoperfusion and diffuse frontal hypoperfusion, which could be used to differentiate them from the patients with AD. Other could not be distinguished from patients with AD by their perfusion pattern. Although patients with other cerebral disorders occasionally have TP hypoperfusion, this finding makes the diagnosis of AD very likely.

Adult↗
PubMed1997

[Nutritional status of patients with decubitus ulcers, and changes in the skin blood flow when the sacral region was compressed].

We studied the relationship between decubitus ulcers and changes in skin blood flow with respect to the presence or absence of a decompression medium. We also studied the relationship between decubitus ulcers and the results of biochemical tests that reflect nutritional status. Two groups of inpatients with decubitus ulcers in areas other than the sacral region were studied: One used cloth diapers and the other used paper diapers. Skin blood flow was measured with a laser Doppler blood flowmeter and a sheet of polyurethane (decompression medium) in the sacral region. Data were also obtained from patients with and without decubitus ulcers, and whose levels of albumin, total cholesterol, and triglyceride for three months were known. When the decompression medium was used, skin blood flow changed significantly after body position was changed in the patients who used paper diapers. Nutritional analyses showed significant differences in the levels of albumin and total cholesterol between patients with and without decubitus ulcers. The levels of albumin and total cholesterol were lower in the patients with decubitus ulcers than in those without decubitus ulcers. Because the cloth diapers acted as a compression factor, even an externally applied decompression medium did not suppress the reductions in skin blood flow.

Aged↗
PubMed1997

[Factors contributing to survival of elderly inpatients with chronic disease].

Clinical assessment and laboratory testing are important in predicting longevity and the outcomes of chronic diseases in the elderly. We therefore studied the prognostic utility of clinical and laboratory findings. A group of 168 elderly patients (70-97 years of age) with chronic diseases who were admitted to Kashiwazaki Kosei Hospital was studied. Data on 13 potentially prognostic factors were analyzed: dementia, being bedridden, anorexia, edema of the lower limbs, urinary incontinence, dyspnea fever, hepatic dysfunction, renal dysfunction, anemia, hypoalbuminemia, inflammation, and electrocardiographic abnormality. Kaplan-Meier survival curves were constructed, and either the log-rank or Wilcoxon method was used to look for significant differences in survival between patients with and without the factors listed above. Regression analysis was then done with the Coxproportional-hazards model to study the factors that contributed to the shortest survival. Patients lived longer if they were not bedridden, anorexic, incontinent of urine, hypoalbuminemic, or if they had no inflammation (p < 0.05): being bedridden, anorexia, urinary incontinence, hepatic dysfunction, hypoalbuminemia, inflammation, and electrocardiographic abnormalities. The survival curve obtained by using these factors as independent variables in the proportional-hazards model was similar to the Kaplan-Meier survival curve.

Aged↗
PubMed1997

[Pleural-origin malignant lymphoma in an elderly patient with chronic empyema and infection with the Epstein-Barr virus].

A 73-year-old woman with a long-standing history of right-sided chronic empyema complained of lumbago. An artificial pneumothorax had been induced to treat pulmonary tuberculosis about 40 years previously. The year after she began to complain of lumbago, a tumor mass over the right anterior chest wall had grown rapidly. Pathologic examination revealed that it was a malignant lymphoma (Non-Hodgkin's lymphoma, diffuse large cell, B cell type). Chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone, and then radiation therapy were given. The patient responded very well. The tumor mass on the surface of the chest wall disappeared completely. She was alive and well and there was no evidence of recurrence at the seven-month follow-up examination. Analysis with the polymerase chain reaction showed that the tumor contained DNA of the Epstein-Barr virus. The chronic empyema and local infection with the Epstein-Barr virus might have been a factor in the development of the malignant lymphoma.

Aged↗
PubMed1997

[Urinary neopterin levels in patients with genitourinary tract malignancies].

BACKGROUND: Neopterin is released from macrophages upon stimulation with gamma-interferon, secreted by activated T cell. Therefore it has been recognized as a useful indicator of the activation of the T cell-macrophage system. Increased neopterin levels are observed in patients with acute graft rejections, viral infections, auto-immune diseases and several malignancies. Urinary neopterin concentrations were determined in patients with genitourinary tract malignancies to evaluate the usefulness of neopterin as a tumor marker. METHODS: Urinary neopterin concentrations were determined by high-performance liquid chromatography in 90 patients with genitourinary tract malignancies and 28 patients with benign urological tumors and 34 healthy subjects. RESULTS: Increased urinary neopterin levels were observed in 52% of the patients with genitourinary tract malignancies and 7% with benign urological tumors. The positivity rate in patients with renal cell carcinoma (RCC), renal pelvic and ureteral tumor, bladder tumor (BT), prostatic carcinoma (PC) and testicular tumor was 68%, 80%, 47% and 30%, respectively. The difference in the urinary neopterin levels between low and high stages was highly significant (p < 0.0005) in patients with RCC (stage I-II vs. stage III-IV) and BT (T1S-1 VS. T2-4). The urinary neopterin levels were also correlated with the tumor grade in patients with RCC and PC. CONCLUSION: Our study suggests that urinary neopterin levels may supplement laboratory examinations for patients with genitourinary tract malignancies, providing useful information in evaluating the tumor stage and follow-up of the disease.

Adult↗