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Biomedical subjects

T Shibasaki

Publications and source records attributed to T Shibasaki.

At least 73 records · Page 4Linked to original sources

Differentiating histologic malignancy of primary brain tumors: pentavalent technetium-99m-DMSA.

UNLABELLED: This study assessed pentavalent 99mTc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy. METHODS: SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq 99mTc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. RESULTS: Approximately 95% of both benign and malignant primary brain tumors were demonstrated by 99mTc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. The delayed uptake ratio, retention ratio and retention index were higher in the malignant tumors than the benign tumors. CONCLUSION: Technetium-99m(V)-DMSA washout from the tumor was highly dependent upon its histology and histologic malignancy. The delayed uptake ratio considerably reflected tumor histology and differentiated benign tumors from malignant tumors. The retention ratio and retention index significantly reflected tumor histology and histologic grade of primary brain tumors and clearly distinguished between benign and malignant tumors with statistically significant difference (p < 0.05). These results could suggest the clinical utility of 99mTc(V)-DMSA in imaging primary brain tumors and differentiating their histological malignancy grade noninvasively.

Adolescent↗

[Glucose metabolism and blood flow studies in 2 cases with juvenile Parkinson's disease].

Cerebral glucose metabolism at resting state and blood flows during resting state, during finger-movement, and during finger-brushing stimulation were measured in two cases with juvenile Parkinson's disease(Narabayashi) with PET. Major symptom was rigidity and hypokinesia in both cases. Glucose metabolism was reduced in frontal cortex and increased at striatum. In one case with it-pallidotomy 1 year before glucose metabolism was more reduced over entire it-hemisphere including striatum than the right without any additional symptoms after the surgery. Blood flow was increased during 2 tasks and focal increase patterns were different from those in normal volunteers. Classical glucose metabolism and blood flow studies are still useful in this disorder.

Adult↗

Aminoglycoside-induced viability in cultured PtK1 proximal tubular cell lines.

The cell viability after aminoglycoside administration was evaluated by the determination of adenosine triphosphate (ATP) level and trypan blue exclusion of cultured PtK1 tubular cells. The assay in tubular cells was performed using luciferin-luciferase determined by a chemiluminator. The data are expressed as relative light units per milligram tissue protein. The standard curve of ATP showed a linearity from 0.5 to 2.5 mg/ml ATP as determined by the chemiluminator. The incubation time was steady for ATP production during 90 min after addition of ligand. The optimal incubation time was 60 min. The ATP production in PtK1 cells showed linearity within 10(3) to 5 x 10(6) cells in 200 microliters buffer. Although the magnitude of ATP production in Ptk1 cells was correlated with the cell viability as defined by trypan blue exclusion, the reproducibility of the former was better than that of the latter. The cell viability after application of aminoglycoside showed a decrement in a dose-dependent fashion. Our ATP assay is an excellent tool for determining the cell viability of renal proximal tubules in cases with tubular damage after administration of aminoglycoside antibiotics.

Adenosine Triphosphate↗

[A case of primary antiphospholipid antibody syndrome with severe nephrotic syndrome showing remarkable endothelial cell damage in the capillary lumen].

A 25-year-old woman complained of anasarca and was admitted to Sakura National hospital on the presumptive diagnosis of nephrotic syndrome with 10.7 g of 24-hour urinary protein. At first, lupus nephritis with antiphospholipid antibody syndrome was suspected because of prolongation of APTT, existence of lupus anticoagulant and elevation of serum anticardiolipin antibody titer (IgM) in addition to positive ANA, lymphocytopenia and the biologically false positive test for syphilis (BFPTS). On day 28 of hospitalization, renal biopsy findings revealed severe endocapillary cell damage, such as swelling and proliferation of endothelial cells, fragmentation and double contour of the basement membrane walls, which were located only in the capillary lumens with a few thrombi. Immunofluorescent micrography revealed the absence of specific immunoglobulin or complement deposit. Therefore, the diagnosis of lupus nephritis was negated as these findings were suggestive of characteristic glomerulopathy due to primary antiphospholipid antibody syndrome. She was treated initially with oral prednisolone 60 mg and intravenous infusion of heparin 20,000 units daily. Moreover, cyclophosphamide 750 mg was administered intravenously as pulse therapy on day 13 as her serum level of CH50 had fallen suddenly, and hemodialysis was necessary because her renal function had deteriorated and she was suffering from cough and orthopnea with overhydratin. After the combined therapy, BFPTS disappeared and APTT returned to the normal range: dialysis treatment was not required further after the 4th hemodialysis. Thereafter, renal function improved and complete remission of nephrotic syndrome was obtained. This patient was a case of primary antiphospholipid antibody syndrome in which endothelial cell damage was located exclusively in the capillary lumens and pulse cyclophosphamide therapy in addition to prednisolone and anticoagulant was effective. We present this instructive case to promote understanding of the pathogenesis of primary antiphospholipid antibody syndrome.

Adult↗

Serum concentrations of free ubiquitin and multiubiquitin chains.

Ubiquitin, which can conjugate with cellular proteins, is classified into two forms: free ubiquitin and multiubiquitin chains. The latter is active as a signal for degradation of the targeted proteins. We found both forms in human serum and, using two immunoassays, quantitated them in sera from healthy subjects and patients with some diseases. Because of putative leakage of erythrocyte ubiquitin, hemolytic serum and serum obtained after long incubation (> 1-2 h) of blood at room temperature were excluded. Serum concentrations of multiubiquitin chains and free ubiquitin were substantially higher in rheumatoid arthritis and hemodialysis patients, respectively, than healthy subjects. Additionally, in acute viral hepatitis, serum multiubiquitin chain concentrations were increased in the acute phase, decreased in the recovery phase, and correlated with alanine and aspartate aminotransferase activities (r = 0.676 and 0.610, P < 0.0001 and < 0.001, respectively). Therefore, serum ubiquitin may have prognostic value.

Acute Disease↗

Technetium-99m(V)-DMSA and thallium-201 in brain tumor imaging: correlation with histology and malignant grade.

UNLABELLED: This study was performed to compare imaging ability between pentavalent 99mTc-DMSA and 201TlCl in primary and metastatic brain tumors and to evaluate the relationship between retention and histologic malignancy. METHODS: Patients with a brain tumor were selected by MRI and/or CT. Dynamic, early and delayed static SPECT images of the brain were obtained immediately, 30 min and 3 hr after intravenous administration of approximately 555 MBq 99mTc(V)-DMSA and 111 MBq 201Tl-Cl, respectively. Both studies were performed on separate days within a week. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. RESULTS: One-hundred six studies were performed on 100 patients and 118 lesions were demonstrated: 16 glioblastomas, 13 anaplastic astrocytomas (Grade III), 19 astrocytomas (Grade II), 29 meningiomas, 11 schwannomas and 14 metastases. Approximately 93% and 88%, respectively, of primary and metastatic brain tumors were demonstrated by 99mTc(V)-DMSA and 201TlCl. The early uptake ratios were closely related to the tumor vascularity, but had no statistically significant difference in the tumor histology or histologic malignancy on either radiopharmaceuticals. The delayed uptake ratio, retention ratio and retention index were higher in malignant tumors than benign ones on 99mTc(V)-DMSA, however, there was no statistically significant difference between benign and malignant tumors on 201TlCl. CONCLUSION: Technetium-99m(V)-DMSA washout from the tumor was highly dependent upon its histology and histologic malignancy. The delayed uptake ratio, retention ratio and retention index significantly reflected tumor histology and clearly distinguished between benign and malignant tumors with a statistically significant difference. There was no statistically significant difference in 201TlCl uptake or washout among the brain tumors. Technetium-99m-DMSA is superior to 201TlCl in imaging quality, sensitivity to brain tumors and specificity for differentiating benign tumors from malignant ones. These results could suggest the clinical utility of 99mTc(V)-DMSA in imaging primary and metastatic brain tumors and differentiating their histological malignancy grade noninvasively.

Brain Neoplasms↗

Increased pituitary growth hormone-releasing factor (GRF) receptor messenger ribonucleic acid expression in food-deprived rats.

In prolonged food-deprived rats, growth hormone (GH) secretion in response to exogenous GH-releasing factor (GRF) is enhanced both in vivo and in vitro. We tested the hypothesis that, in fasted rats, GRF receptors in the pituitary may be up-regulated. The expression of mRNA for the GRF receptor in the pituitary and GRF binding to the pituitary membrane were examined in adult male Wistar rats deprived of food for 72 h. The level of GRF receptor mRNA in the pituitary was significantly increased after 48 h food deprivation and was more than 3 times the level in control rats after 72 h food deprivation. GRF binding to the pituitary was significantly increased after 72 h food deprivation. The results of the present study provide evidence regarding changes in the GH axis in fasted rats, involving increased pituitary responsiveness to GRF and an increase in the pituitary membrane GRF receptor concentration.

Animals↗

Ability of ubiquitin radioimmunoassay to discriminate between monoubiquitin and multi-ubiquitin chains.

Free ubiquitin (mainly monoubiquitin) and multi-ubiquitin chains coexist in eukaryote cells and serve distinct cellular roles. However, any immunoassay systems established previously have not been proved to be applicable for measuring the former without cross-reactive responses with the latter. For this purpose, we developed a radioimmunoassay specific to monoubiquitin by employing antiserum US-1 against ubiquitin. In this assay, ubiquitin-protein conjugates, prepared by a reticulocyte lysate fraction II and fractionated on Moro Q and Superdex 200 columns, exhibited practically no cross-reactivity. The cross-reactivity of fractionated ubiquitin-lysozyme conjugates was also analyzed as a function of their multi-ubiquitin chain size. As a result, the larger the conjugates were found to be, the weaker were the cross-reactive responses they showed, and the multi-ubiquitin chains (n > approx. 20) were substantially unreactive in the radioimmunoassay. By using the radioimmunoassay, heat-shock-induced decrease in the level of cellular free (mono)ubiquitin was detected. In addition, the standard preparation of multi-ubiquitin chains was not cross-reactive in all other five radioimmunoassays employing distinct antibodies to ubiquitin (four antisera and a monoclonal antibody). These data suggest that radioimmunoassays employing ubiquitin antibodies raised by the general methods can discriminate between monoubiquitin and multi-ubiquitin chains and quantitate cellular free ubiquitin.

Animals↗

Neuropeptide Y reverses corticotropin-releasing hormone- and psychological stress-caused shortening of sodium pentobarbital-induced sleep in rats.

Intracerebroventricular injection of neuropeptide Y (NPY) prolonged sodium pentobarbital (PhNa)-induced sleep in rats. The prolongation of PbNa-induced sleep by NPY was blocked by naloxone. Both corticotropin-releasing hormone and psychological stress caused shortening of PbNa-induced sleep, and the shortening was reversed by NPY. These results suggest that NPY has a sedative action and that an opioid system in the brain mediates at least in part the action of NPY.

Animals↗

Intracerebroventricular administration of beta-endorphin increases the expression of c-fos and of corticotropin-releasing factor messenger ribonucleic acid in the paraventricular nucleus of the rat.

We evaluated the effects of intracerebroventricular (i.c.v.) administration of beta-endorphin and naloxone, an opioid antagonist, on the induction of c-fos and corticotropin-releasing factor (CRF) mRNA to clarify the effects of beta-endorphin on cellular activity and CRF gene expression in the paraventricular nucleus (PVN) of the rat using in situ hybridization. A significant induction of c-fos mRNA was noted in the PVN after i.c.v. injection of beta-endorphin, compared to control. This induction was inhibited by the administration of naloxone. A significant increase in CRF mRNA levels in the PVN was observed 120 min after the i.c.v. injection of beta-endorphin. This increase was partially, but significantly, inhibited by naloxone administration. In addition, i.c.v. administration of beta-endorphin increased plasma ACTH concentration in freely moving rats, which was inhibited by intravenous injection of CRF antiserum. These results suggest that the i.c.v. injection of beta-endorphin increases the neuronal activity and the biosynthesis of CRF in the PVN, and stimulates the secretion of ACTH by increasing CRF secretion. This effect on the PVN was mediated, at least in part, via the opioid receptor.

Animals↗

Effects of a hepato-protective agent and a hepato-secreting chelator on cadmium-induced nephrotoxicity in Syrian hamsters.

Cadmium (Cd)-induced nephropathy in male Syrian hamsters was treated with D/L-penicillamine (D/L-p) or neomynophagen C (NMC). The subcutaneous injection of CdCl(2), 3 mg/kg, three times a week led to marked renal damage, ie., increased proteinuria and the excretion of urinary N-acetyl-beta-D-glucosaminidase (NAG) as compared with the saline-injected controls. Cd-treated hamsters that were injected intraperitoneally with D/L-p, 0.1 mg/kg, five times a week, showed less renal damage, including a reduction in urinary protein from 3.60 + or - 0.42 to 1.77 + or - 0.7 mg/d. NMC-treated hamsters showed a reduced excretion of NAG (from 1.47 +/ - 0.34 to 0.91 + or - 0.68 u/d). The concentration of Cd in renal cortical tissue was reduced slightly (from 2.78 + or - 0.08 to 2.34 + or - 0.3 mg/g.prot) by NMC treatment, but not by D/L-p. The elevated malondialdehyde (MDA) in renal cortical tissue was unaffected by administering D/L-p or NMC. The concentration of glutathione (CSH) in the renal cortex was not elevated after administering Cd, but the ratio of the reduced to the oxidized GSH was elevated. The Cd induced liver dysfunction, as compared with untreated controls. The dysfunction was improved slightly by NMC administration, but not by that of D/L-p. Changes in renal morphology induced by Cd involving marked degeneration and necrosis of tubules as shown by light microscopy, were unaffected by treatment with D/L-p or NMC. We thus demonstrated the efficacy of D/L-p of NMC in treating the nephropathy induced by Cd in hamsters. The mechanism of therapeutic effect is not known.

Acetylglucosaminidase↗

The influence of aging on renal response to cadmium in Syrian hamsters.

To determine the renal effects of cadmium (Cd) in older animals, we administered subcutaneously a single dose of cadmium, 3.0 mg/kg/BW, to Syrian hamsters aged 16 wk ("young") and 60 wk ("old"). Marked morphologic changes in the kidney and renal dysfunction were observed, especially in the older animals. The concentration of MDA in the renal cortex was significantly increased only in young hamsters treated with cadmium. Concentrations of glutathione (GSH) in the renal cortex were increased in the old hamsters on d 6. Increased levels of renal MDA after cadmium treatment may induce the production of GSH in the kidney thus preventing renal damage. Aging can increase the susceptibility to the renal effects of cadmium.

Acetylglucosaminidase↗

Detection of Novel Proline 3-Hydroxylase Activities in Streptomyces and Bacillus spp. by Regio- and Stereospecific Hydroxylation of l-Proline.

During the screening of microbial proline hydroxylases, novel proline 3-hydroxylase activities, which hydroxylate free l-proline to free cis-3-hydroxy-l-proline, were detected in whole cells of Streptomyces sp. strain TH1 and Bacillus sp. strains TH2 and TH3 from 3,000 strains isolated from soil. The reaction product was purified from a reaction mixture of Streptomyces sp. strain TH1, and its chemical structure was identified as cis-3-hydroxy-l-proline by instrumental analyses. Proline 3-hydroxylase activity was also detected in Streptomyces canus ATCC 12647 which produces the 3-hydroxyproline-containing peptide antibiotic telomycin. Bacillus sp. strains TH2 and TH3 were found to accumulate cis-3-hydroxy-l-proline in culture media at 426 and 352 (mu)M, respectively. It was suggested that hydroxylation occurred in a highly regio- and stereospecific manner at position 3 of l-proline because no hydroxylation product other than cis-3-hydroxy-l-proline was observed. Proline 3-hydroxylases of these strains were first characterized on crude enzyme preparations. Since 2-oxoglutarate and ferrous ion were required for hydroxylation of l-proline, these 3-hydroxylases were thought to belong to a family of 2-oxoglutarate-related dioxygenases. The reaction was inhibited by Co(sup2+), Zn(sup2+), and Cu(sup2+). l-Ascorbic acid accelerated the reaction. The optimum pH and temperature were 7.5 and 35(deg)C, respectively.

Journal Article↗

Mizoribine reduces urinary protein excretion in rats given puromycin aminonucleoside.

Mizoribine (MZR), a purine nucleoside antibiotic, is an effective immunosuppressive agent that prevents rejection reactions after kidney transplantation in humans. The present study was performed to examine the effect of MZR on nephrosis produced in rats given puromycin aminonucleoside (PAN). Urinary protein excretion in rats injected with PAN and MZR (PAN + MZR rats) was shown to be reduced significantly in comparison with rats given only PAN (PAN rats). Although mild hypoproteinemia persisted during the experimental period in PAN + MZR rats, no loss of body weight or state of malnutrition was observed. The reduction of serum IgG and C3 was reversed by administration of MZR. Polyethyleinamine (PEI) staining of renal sections showed increased numbers of anionic sites in PAN + MZR rats in comparison with PAN rats, suggesting that MZR improved the permselectivity of the glomerular basement membrane (GBM). Moreover, the production of thromboxane B2 (TxB2) was significantly inhibited in PAN + MZR rats compared with PAN rats. No serious adverse effects of MZR were observed after a large dose of the agent. It is possible that restoration of the charge barrier of the GBM damaged by PAN, or reduction of TxB2 production by the glomeruli may underlie the reduction of protein excretion induced by administration of MZR.

Animals↗

Significance of serum lipase in patients undergoing hemodialysis.

Serum levels of lipase (Lp) during the end of the dialysis showed a significant increase after the administration of heparin in hemodialysis patients. However, serum Lp levels were not increased after the administration of the anti-coagulant nafamostat mesylate in hemodialysis patients. Serum levels of Lp were significantly correlated with serum levels of lipoprotein lipase (LPL), hepatic triglyceride lipase (H-TGL) and nonesterified fatty acid (NEFA) 20 min after the administration of heparin during maintenance hemodialysis. Lp activity did not appear with the NEFA ligand for determining the NEFA activity. Inhibitors of LPL and H-TGL reduced the measured Lp activity in vitro. The main mechanism of elevated measured serum Lp activity in hemodialysis patients was determined to be cross-reactivity with LPL or H-TGL. Furthermore, measurement of Lp may be a method for determining optimal coagulation time in patients with hemodialysis.

Adult↗

Intracerebroventricular administration of the growth hormone-releasing peptide KP-102 increases food intake in free-feeding rats.

Recent evidence suggests that growth hormone-releasing peptides (GHRPs) mimic an unidentified native GH-releasing hormone (GHRH)-amplifying hormone. GHRH has been shown to stimulate food intake acting on the central nervous system. The present studies were conducted to test the hypothesis that GHRPs may also potentiate the central effect of GHRH on feeding in free-feeding rats. Intracerebroventricular (ICV) administration of picomole doses of a newly developed GHRP, KP-102, or human GHRH stimulated feeding, but the phenomenon was not reproduced by systemic injection. A prior ICV injection of a GHRH antagonist completely prevented the increase of food intake evoked by GHRH, but this pretreatment did not influence the increase in food intake induced by KP-102. When maximally effective doses of GHRH and KP-102 were co-administered ICV, the amount of food intake increased significantly compared with after ICV injection of a maximum dose of either peptide alone. These findings suggest that GHRPs stimulate food intake via a specific receptor for GHRPs in the central nervous system and amplify the central effect of GHRH on feeding.

Animals↗