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Biomedical subjects

Y Fujiwara

Publications and source records attributed to Y Fujiwara.

At least 271 records · Page 15Linked to original sources
PubMed1997

Serotonin1A receptor agonists induce Fos protein expression in the locus coeruleus of the conscious rat.

The azapirones, which are partial agonists of the serotonin (5-HT)1A receptor, possess anxiolytic activity. These agents may act at the pre- or postsynaptic 5-HT1A receptors, and involve the noradrenergic system. To determine whether these drugs activate noradrenergic neurons via 5-HT1A receptors, we have evaluated the expression of the immediate early gene c-fos in the locus coeruleus. Tandospirone and ipsapirone each induced expression of Fos protein in the noradrenergic neurons of the locus coeruleus of conscious rats. This effect was reversed by pretreatment with (+)-WAY100135, a specific 5-HT1A antagonist. These results clearly demonstrate that azapirones activate noradrenergic neurons via 5-HT1A receptors.

Animals↗
PubMed1997

Tolerance to cadmium cytotoxicity is induced by zinc through non-metallothionein mechanisms as well as metallothionein induction in cultured cells.

To investigate the relationship between metallothionein induction and zinc-induced tolerance to cadmium cytotoxicity at the cell level, Chang liver cells were pretreated with a wide range of concentrations of zinc sulfate and challenged with toxic levels of cadmium after removal of zinc. It was found that zinc-pretreated cells were significantly resistant even when the extracellular level of zinc was low and metallothionein was not induced by the metal. Pretreatment with zinc resulted in a lesser accumulation of cadmium and metallothionein after challenge with cadmium. In porcine kidney LLC-PK1 cells and bovine aortic smooth muscle cells pretreated with low levels of zinc, the intracellular accumulation of cadmium was significantly less and cadmium-induced decrease in intracellular zinc was significantly prevented without a change of metallothionein content; as the result, the toxic effect of cadmium was significantly diminished. It was therefore concluded that a tolerance to cadmium cytotoxicity is induced by zinc via non-metallothionein mechanisms such as decreasing intracellular cadmium as well as metallothionein induction at the cell level. The non-metallothionein mechanism was postulated to be particularly importatnt when the extracellular concentration of zinc is under the threshold for metallothionein induction.

Analysis of Variance↗
PubMed1997

Relationship between HLA-C locus and restenosis after coronary artery balloon angioplasty.

OBJECTIVES: To determine the relationship between human leukocyte antigen (HLA) loci and restenosis after percutaneous transluminal coronary angioplasty (PTCA). DESIGN AND SETTING: Cross-sectional study in patients treated by PTCA at Juntendo University Hospital, Tokyo, Japan. PATIENTS: A total of 65 patients (58 males and 7 females) with coronary artery stenosis who were consecutively selected between October 1994 and June 1995. MAIN OUTCOME MEASURES: Significant relationships between the restenosis and the HLA-Cw1. RESULTS: Among HLA-C locus, Cw1 was negatively related to restenosis (multivariate adjusted odds ratio, 0.19; 95% confidence interval, 0.06-0.63; P=.007). CONCLUSIONS: In HLA typing, Cw1 may be a useful marker for the prediction of restenosis after PTCA.

Aged↗
PubMed1997

Lead-induced alteration of heparan sulfate proteoglycans in cultured vascular endothelial cells.

We investigated the alterations of heparan sulfate proteoglycans produced by vascular endothelial cells after exposure to lead. Bovine aortic endothelial cells were cultured and metabolically labeled with [3H]glucosamine and [35S]sulfate in the presence of lead chloride at 10 microM. Radiolabeled HSPGs were separated by ion-exchange chromatography and either their hydrodynamic size or the length of heparan sulfate chains were characterized by gel filtration. It was found that lead markedly suppresses the incorporation of the radioactive precursors into HSPGs in the cell layer; the incorporation into chondroitin/dermatan sulfate proteoglycans was decreased by the metal only slightly. The suppression by lead occurred in the low molecular weight subclass of HSPGs rather than the high molecular weight subclass. However, the length of heparan sulfate chains was not changed by the metal. A sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]methionine-labeled proteoglycans after heparitinase digestion showed that there were slightly more HSPG core proteins without a change of the size in lead-treated cell layer. It was, therefore, suggested that vascular endothelial cell layer after exposure to lead has more HSPG core proteins with fewer heparan sulfate chains without a change in length.

Animals↗
PubMed1997

Group II phospholipase A2 as an autocrine growth factor mediating interleukin-1 action on mesangial cells.

The proliferation of mesangial cells plays a central role in the progression of glomerulonephritis. We studied the role of group II phospholipase A2 in interleukin-1-stimulated proliferation of mesangial cells. Cultured rat mesangial cells secreted 5.3 units group II phospholipase A2/24 h per 10(5) cells in response to stimulation of 200 U/ml of interleukin-1. Northern hybridization analysis showed that mRNA for group II phospholipase A2 was induced by exogenously added group II phospholipase A2 (15 U/ml) as well as interleukin-1. The pretreatment of quiescent mesangial cells with interleukin-1 augmented [3H]thymidine incorporation caused by platelet derived growth factor. Exogenous group II phospholipase A2 (5-36 U/ml) purified homogeneously from rat spleen also increased [3H]thymidine incorporation by platelet derived growth factor-stimulated mesangial cells in a dose dependent manner (36 U/ml phospholipase A2; 1.9-fold). The stimulatory effect of interleukin-1 on DNA synthesis of mesangial cells was specifically blunted by immunoglobulin raised against group II phospholipase A2. Group II phospholipase A2 (16 U/ml) amplified a platelet derived growth factor-stimulated increase in the mesangial cell number by 1.5-fold. Among the products of the phospholipase A2-catalyzed reaction, lysophospholipids including lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidic acid, but not fatty acids, mimicked the stimulatory effect of interleukin-1 and phospholipase A2. These results suggest that group II phospholipase A2 acts as a signaling molecule that mediates interleukin-1-induced growth of rat mesangial cells through yielding lysophospholipids.

Animals↗
PubMed1997

Inhibitory effect of lead on the repair of wounded monolayers of cultured vascular endothelial cells.

We investigated the effect of lead nitrate (0.5-5.0 microM) on the repair of wounded monolayer of cultured bovine aortic endothelial cells. It was morphologically found that lead decreases the appearance of the cells in the wounded area in a concentration-dependent manner without degenerative changes after a 48-h incubation. Although mercury weakly inhibited the repair with nonspecific cell damage, the other cations including bismuth, cobalt, manganese and nickel failed to affect the repair. The inhibition of endothelial repair caused by lead was observed even when stimulated by exogenous either basic or fibroblast growth factor. These results indicated that inhibition of the repair process of damaged endothelial cell layer is a component of lead-induced vascular lesions such as atherosclerosis.

Animals↗
PubMed1997

Thermodynamic studies of the hybridization properties of photolesions in DNA.

In order to gain insight into the mechanism of mutations induced by photolesions in DNA, the thermal melting curves of oligonucleotide duplexes containing the (6-4) photoproducts of TT and TC and the Dewar isomer were measured at varying concentrations, and the thermodynamic parameters were determined. The duplexes were designed to be used as models for template-primer systems. In the case of d(CAXYAGCACGAC) x d(GTCGTGCTN), in which XY = T(6-4)T, T(6-4)C, or T(Dewar)T and N = A, G, C, or T, the -deltaG degrees values were the largest when N = G, and the difference between N = G and N = C or T was 1.1, 0.8, and 0.5 kcal/mol at 25 degrees C for XY = T(6-4)T, T(6-4)C, and T(Dewar)T, respectively. These results provide evidence of base pair formation between the 3'-pyrimidone and the opposite guanine, which was proposed previously to explain the T --> C transition induced at the 3' side of the T(6-4)T photoproduct. This interaction was weakened by isomerization to the Dewar photoproduct, which would explain the lower mutation specificity. For d(CAXYAGCACGAC) x d(GTCGTGCTGN), no obvious differences were observed regarding the base opposite the 5'-pyrimidine of the photoproducts. In contrast to the tertiary structure, determined by NMR, of a duplex containing T(6-4)T in its center [Kim, J.-K., & Choi, B.-S. (1995) Eur. J. Biochem. 228, 849-854], base pair formation at the 5'-pyrimidine was not detected for any photoproduct used in this study, even when the base opposite the 3'-pyrimidone of T(6-4)T was changed to adenine.

Chromatography, High Pressure Liquid↗
PubMed1997

Significance of alpha-fetoprotein levels for detection of early recurrence of hepatocellular carcinoma after hepatic resection.

BACKGROUND: The recurrence of hepatocellular carcinoma (HCC) after surgery is common. The present study was conducted in order to clarify the significance of alpha-fetoprotein (AFP) in the detection of the early recurrence of HCC after surgery. METHODS: Fifty-eight patients who underwent a curative hepatic resection for HCC and whose preoperative AFP levels were >100 ng/ml, were selected for this study. RESULTS: In 26 cases, the postoperative AFP levels within 3 months after surgery did not decrease to <20 ng/ml (high AFP group). In the other 32 cases, the postoperative AFP levels within 3 months after surgery decreased to <20 ng/ml (low AFP group). No significant difference was observed in clinical or pathological backgrounds. The postoperative disease free rate in the low and high AFP groups was 84.2% and 18.4%, at 1 year, 61.2 and 4.6% at 3 years, respectively. The difference was statistically significant (P < 0.01). At the time of recurrence, the AFP levels increased in 25 (96.2%) of the patients who had early recurrence within 1 year after surgery as well as in 11 of 14 (78.5%) who had recurrence >1 year after surgery. The interval from surgery to recurrence significantly correlated with the doubling time of AFP at the time of recurrence in patients with early recurrence (within 1 year after hepatectomy) (r = 0.60, P < 0.01). In cases in which the preoperative AFP level was >100 ng/ml and the postoperative AFP level did not decrease to <20 ng/ml, early recurrence within 1 year after surgery would thus be strongly suspected. CONCLUSION: The measurement of the AFP levels after surgery is therefore considered to be important in the follow-up of hepatectomized patients, especially regarding the detection of early recurrence.

Aged↗
PubMed1997

Position-independent and high-level expression of human alpha-lactalbumin in the milk of transgenic rats carrying a 210-kb YAC DNA.

The level of expression of transgenes in transgenic animals varies among lines, and is often much lower than that of endogenous genes (position effects). In order to surmount position effects and establish a more efficient production system of transgenic animals producing pharmaceutical proteins in their milk, transgenic rats carrying 210-kb YAC DNA containing the human alpha-lactalbumin gene were produced. Three transgenic lines transmitted the transgene to the next generation. They had one copy of the alpha-lactalbumin gene and secreted human alpha-lactalbumin in their milk at concentrations of 2.0-4.3 mg/ml. No position effect was seen. The transgene was expressed specifically in the mammary gland of the transgenic rats. The 210-kb region is thought to contain all the DNA elements required for proper expression of the human alpha-lactalbumin gene. The YAC carrying the human alpha-lactalbumin gene is a potential vector for the expression of foreign genes in the mammary gland.

Animals↗
PubMed1997

The spread of methicillin-resistant Staphylococcus aureus in a rural community: will it become a common microorganism colonizing among the general population?

At Fujiwara Memorial Hospital (FMH), a community hospital with 140 beds located near a large agricultural area in Akita prefecture, the annual number of patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) has been increasing in recent years. To elucidate the current status of MRSA spread, the frequency of its isolation among a total of 10598 bacteriological specimens obtained from patients treated at FMH between July 1989 and December 1994 was evaluated. The frequency increased from 3.8% in 1990 to 9.6% in 1994, and of all the patients colonized with MRSA, outpatients accounted for 4.5% in 1990 and 34.9% in 1994. These outpatients included patients from long-term care facilities, those cared for at home with chronic diseases, and those who had been hospitalized in tertiary general hospitals. This remarkable increase in the percentage of outpatients colonized with MRSA may suggest the spread of MRSA in our community.

Ambulatory Care↗
PubMed1997

Salivary drug monitoring of irinotecan and its active metabolite in cancer patients.

To assess the clinical usefulness of salivary monitoring of irinotecan (CPT-11) and its active metabolite (SN-38), we examined the clinical pharmacological profile of both drugs in 9 patients with thoracic malignancies who received 60 mg/m2 CPT-11 (21 courses). Plasma and unstimulated whole saliva were collected over a 24-h period, and concentrations of CPT-11 and SN-38 were measured by high-performance liquid chromatography. Both CPT-11 and SN-38 were detectable in saliva, and the concentration-time curves in plasma and saliva showed a very similar pattern. A good correlation was observed between the saliva concentration (C3) and the plasma concentration (Cp) for both CPT-11 and SN-38 (r = 0.732, P < 0.0001 and r = 0.611, P < 0.0001, respectively). The area under the concentration-time curve calculated for saliva (AUCs) correlated with that generated for plasma (AUCp) for both CPT-11 and SN-38 (r = 0.531, P = 0.012 and r = 0.611, P = 0.0025, respectively). These results suggest that it may be feasible to use saliva instead of plasma for pharmacokinetics/pharmacodynamics studies of CPT-11.

Aged↗
PubMed1997

Genomic organization and chromosomal localization of the human casein gene family.

Five yeast artificial chromosome (YAC) clones containing the human casein gene family were isolated and characterized to study the control mechanisms for the expression of these genes. Partial restriction analysis in conjunction with the chromosomal fragmentation method and fluorescence in situ hybridization (FISH) analysis were performed to construct a detailed physical map of the casein gene family and to determine the chromosomal localization of these genes. The isolated YAC clones 748F3, 750D11, 882G11, 886B3 and 960D2 were 1.2 Mb, 860 kb, 800 kb, 1.5 Mb and 1.5 Mb in size, respectively. The clones 748F3, 882G11, 886B3 and 960D2 contained the entire casein gene family, while the kappa-casein gene was absent in 750D11. The human alphaS1-, beta- and kappa-casein genes were found to be closely linked and arranged in the order alphaS1-beta-kappa. The distance between alphaS1 and beta, and between alphaS1 and kappa was approximately 10 and 300 kb, respectively. The beta-casein gene was oriented in the opposite direction to the alphaS1- and kappa-casein genes. The casein gene family was localized to chromosome 4q21.1 by FISH analysis.

Caseins↗
PubMed1997

Basic fibroblast growth factor-induced glycosaminoglycan production in cultured vascular endothelial cells results from enhanced protein synthesis mediated by the lipoxygenase pathway.

To investigate the intracellular regulation of glycosaminoglycan (GAG) production induced by basic fibroblast growth factor (bFGF), bovine aortic endothelial cells were cultured with recombinant human bFGF in the presence of [3H]glucosamine or [35S]sulfate. It was shown that bFGF-induced incorporation of the radioactive precursors into GAGs was diminished by lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA) and esculetin, but not by a cyclooxygenase inhibitor indomethacin. A protein synthesis inhibitor cycloheximide also diminished the enhancement of the [3H]glucosamine incorporation by bFGF. On the other hand, the incorporation of [14C]leucine into the acid-insoluble fraction was strongly inhibited by NDGA but not by indomethacin in the presence or absence of bFGF. It was also shown that bFGF significantly increased the incorporation of [14C]xylose into GAGs. The present data suggested that bFGF may increase the number of GAG chains as a result of enhanced protein synthesis including xylosyl transferase through the lipoxygenase pathway of arachidonic acid metabolism in vascular endothelial cell layer.

Animals↗
PubMed1997

Nitric oxide stimulates prostaglandin synthesis in cultured rabbit gastric cells.

Both prostaglandins (PGs) and nitric oxide (NO) have cytoprotective and hyperemic effects in the stomach. However, the effect of NO on PG synthesis in gastric mucosal cells is unclear. We examined whether sodium nitroprusside (SNP), a releaser of NO, stimulates PG synthesis in cultured rabbit gastric mucus-producing cells. These cells did not release NO themselves. Co-incubation with SNP (2 x 10(-4), 5 x 10(-4), 10(-3) M) increased PGE2 synthesis, and SNP (10(-3) M) increased PGI2 synthesis in these cells. Hemoglobin, a scavenger of NO, (10(-5) M) eliminated the increase in PGE2 synthesis by SNP, but methylene blue, an inhibitor of soluble guanylate cyclase, (5 x 10(-5) M) did not affect the increase in PGE2 synthesis by SNP. 8-bromo guanosine 3':5'-cyclic monophosphate (8-bromo cGMP), a cGMP analogue, (10(-6), 10(-5), 10(-4), 10(-3) M) did not affect PGE2 synthesis. These findings suggest that NO increased PGE2 and PGI2 synthesis via a cGMP-independent pathway in cultured rabbit gastric cells.

Animals↗
PubMed1997

Alterations in serum levels of 1 alpha,25(OH)2 D3 and osteocalcin in patients with early diabetic nephropathy.

UNLABELLED: Serum levels of markers for bone remodeling and diabetic metabolic markers were measured in subjects with non-insulin-dependent diabetes mellitus (NIDDM) to investigate the relationship between early diabetic nephropathy and calcium/bone metabolism. 1 alpha,25(OH)2 D3 (Vit D), osteocalcin (OC), intact parathyroid hormone (PTH) and urine albumin excretion (UAE) were measured in all subjects. Serum levels of Vit D and OC were significantly decreased in diabetic subjects compared to age-matched, non-diabetic controls. In diabetic patients, a significant positive correlation was observed between intact PTH and OC. No significant correlation was found between levels of Vit D and OC. In early diabetic nephropathy without increased serum creatinine, Vit D decreased and OC increased with increasing UAE. Levels of hemoglobin Alc (HbAlc) and fructosamine (FRA) were not correlated with levels of Vit D or OC. Levels of Vit D were decreased and levels of OC were increased in diabetic subjects with proliferative retinopathy or with micro- or macro-albuminuria. CONCLUSIONS: Results of the present study indicate that changes in bone remodeling markers such as Vit D and OC levels are present in the early stages of diabetic nephropathy, and that circulating intact PTH is important in restoring the reduced OC levels in diabetic patients, probably as a reflection of bone remodeling.

Albuminuria↗
PubMed1997

Interleukin-8 stimulates leukocyte migration across a monolayer of cultured rabbit gastric epithelial cells. Effect associated with the impairment of gastric epithelial barrier function.

Acute Helicobacter pylori infection produces predominantly neutrophilic infiltration of the gastric mucosa. However, the precise mechanisms and mediators of neutrophil migration are not known. Interleukin-8 (IL-8), a potent chemotactic factor for neutrophils, is present at high concentration in the gastric mucosa of subjects with chronic gastritis caused by H. pylori infection. The aims of this study were to determine whether IL-8 stimulates polymorphonuclear leukocyte (PMN) migration across a cultured monolayer of rabbit gastric epithelial cells and whether PMN migration affects epithelial cell barrier function. Confluent gastric epithelial monolayers grown on the inserts were overlaid with PMNs and various amounts of IL-8 were administered into the well under the insert. Gastric epithelial barrier function was assessed by sodium back diffusion. IL-8 stimulated PMN migration across the monolayer in a dose- and time-dependent manner. PMN transmigration significantly increased sodium back diffusion. In conclusion, IL-8 induces PMN migration across a monolayer of cultured gastric epithelial cells. This IL-8 action is associated with impairment of gastric epithelial barrier function. Since H. pylori infection causes a local mucosal increase of IL-8, our present findings may explain the mechanism of H. pylori-induced PMN infiltration of the gastric glands and mucosal injury.

Animals↗
PubMed1997

Clinical characteristics of patients with the initial diagnosis of NIDDM with positivity for antibodies to glutamic acid decarboxylase.

UNLABELLED: The measurement of islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GAD-Ab) is clinically useful in evaluating patients with insulin-dependent diabetes mellitus (IDDM). Our objective was to correlate the clinical characteristics of patients with non-insulin-dependent diabetes mellitus (NIDDM) who exhibited positivity for GAD-Ab vs. patients who were negative for this enzyme. The serum level of GAD-Ab was measured by radiobinding assay (RBA) using pig brain GAD. The prevalence of GAD-Ab in the 181 patients was low; the 8 involved subjects (4.4%) were all females. The NIDDM patients who were GAD-Ab-positive were significantly younger, experienced diabetes onset at an early age, had a shorter duration of diabetes, a shorter interval between diabetes onset to initiation of insulin therapy, a lower body mass index (BMI), a lower serum C-peptide value, and required a higher dose of insulin. A higher proportion of the GAD-Ab-positive patients was receiving insulin therapy. CONCLUSIONS: Clinical characteristics of patients with NIDDM who were positive for GAD-Ab differed significantly from those of the patients negative for GAD-Ab. The profile of the GAD-Ab-positive patients with NIDDM resembled that of those with IDDM.

Adult↗