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Biomedical subjects

M Tsuji

Publications and source records attributed to M Tsuji.

At least 163 records · Page 9Linked to original sources
PubMed1998

Potent retinoid synergists with a diphenylamine skeleton.

4-[N-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)amino]benzoic acid (5) exhibited weak retinoidal and retinoid synergistic activities in HL-60 cell differentiation assay. N-Alkylation of 5 caused decrease or loss of differentiation-inducing activity, but enhanced the synergistic activity with a synthetic retinoid Am80 (2), as reflected in the potent synergistic EC50 (SEC50) values of DA023 (11, 1.6 x 10(-10) M) and DA113 (14, 1.4 x 10(-10) M) in the presence of 1.0 x 10(-10) M Am80 (2).

Cell Differentiation↗
PubMed1998

A method for analysis of cell to cell transmission of Theileria sergenti piroplasms.

We tried to develop an experimental system for quantifying piroplasm transmission in Theileria sergenti infection using a SCID mouse model, of which red blood cells (RBC) had been substituted with bovine (Bo). A mouse hybridoma cell producing antibody against Holstein RBC was established for distinguishing Holstein RBC from Japanese Black RBC by a immuno-staining method. T. sergenti piroplasms in RBC were stained by 4',6-diamidino-2-phenylindole. With the aid of these techniques the piroplasm transmission from one to another race of Bo-RBCs could successfully be quantified in SCID mice.

Animals↗
PubMed1998

Antigenic and genetic diversities of Babesia ovata in persistently infected cattle.

Exploring the antigenic and genetic diversities of Babesia ovata, we obtained several field isolates from grazing cattle in the Okushiri island, Japan. Parasite isolation was greatly facilitated by using bovine red blood cell-substituted SCID mice (Bo-RBC-SCID mice), into which the blood samples of the cattle were inoculated. Isolates from different individuals within a herd of cattle were compared in immunoblot analysis with an anti-B. ovata serum and also in Southern blot analysis with a probe for the small subunit ribosomal RNA gene. In both analyses, the isolates exhibited banding patterns that were significantly different from each other. We were also able to obtain a series of parasite isolates from a single cow in different seasons of a nine months period, including winter when active vector ticks were not in the field environment. Different seasonal isolates showed different banding patterns in both immunoblot and Southern blot analyses. By contrast, these analyses detected little difference among the parasites that had been passed various times in Bo-RBC-SCID mice, where no specific immune responses should be generated. These results indicate that individual animals within a herd of cattle were infected with antigenically and genetically diversified populations of B. ovata, and that the parasites could persistently infect a single animal with dynamic change in their predominant subpopulations.

Animals↗
PubMed1998

Antagonism of central CRF systems mediates stress-induced changes in noradrenaline and serotonin turnover in rat brain regions.

The present study was conducted to test the hypothesis that central corticotropin-releasing factor (CRF) systems mediate the changes in the dynamics of brain noradrenergic and serotonergic systems induced by electric footshock stress. Serum corticosterone concentrations were determined fluorometrically and brain monoamine contents (noradrenaline, serotonin and their metabolites) in five brain regions in rats were measured by high-performance liquid chromatography with electrochemical detection 10 and 40 min after exposure to electric footshock stress for 1 hour. Intracerebroventricular administration of a CRF antagonist, alpha-helical CRF (100 micrograms), had no effect on serum corticosterone concentrations in either normal or stressed animals. However, electric footshock stress-induced increases in noradrenaline turnover were significantly reduced by the administration of alpha-helical CRF9-41, in the amygdala and septum at both time points after exposure to electric footshock stress. In contrast, electric footshock stress-induced increases in serotonin turnover in all of the brain regions were further elevated by the administration of alpha-helical CRF 9-41, in almost all of the brain regions examined. These results suggest that central CRF neuronal systems are involved in mediating the electric footshock stress-induced changes in the dynamics of brain noradrenergic and serotonergic systems in rats.

Animals↗
PubMed1998

Candida guilliermondii infection in SCID mice in association with the acceleration of the elimination of transfused human red blood cells.

An acceleration of the elimination of transfused human (Hu) red blood cells (RBC) was found in C.B-17 scid (SCID) mice that were kept in our facility. Yeast like organisms were isolated from their tap water just as a pure culture and the two isolates SW5 and SW6 were assigned to be Candida guilliermondii by analysing their generic small subunit ribosomal RNA sequences. To test whether the isolates are infectious in mice, we inoculated SCID and BALB/c mice orally with SW5 and observed them for 63 and 48 days, respectively. The yeasts were frequently recovered from oral swabs, feces and their tap water throughout the experiment. Although none of the mice developed clinical signs or histopathological changes, a positive sero-conversion was confirmed in 4 of 5 SW5-inoculated BALB/c mice. Moreover, a significant acceleration of Hu-RBC elimination in all of the SW5-infected SCID mice was demonstrated. We believe this to be the first report of an inapparent but significant outbreak of C. guilliermondii infection in mice.

Animals↗
PubMed1998

Familial hypercholesterolemia with cholesteryl ester transfer protein deficiency.

A 21-year-old male was clinically diagnosed with familial hypercholesterolemia (FH) by the manifestations of hypercholesterolemia, tendon xanthoma and family history of premature coronary heart disease. Low density lipoprotein receptor gene was analyzed in attempt to determine a possible point mutation. The normal sequence was partially preserved, and the patient was genetically diagnosed as a heterozygote of FH. In addition, screening for two cholesteryl ester transfer protein (CETP) gene mutations common to Japanese revealed the patient to be a heterozygote of CETP deficiency. A complication of two influential mutations for atherosclerotic ailments was genetically ascertained.

Adult↗
PubMed1998

Management of continuous anastomosis of pancreatic duct and jejunal mucosa after pancreaticoduodenectomy: historical study of 300 patients.

BACKGROUND: Pancreaticojejunostomy is the most problematic anastomosis in the reconstruction after pancreaticoduodenectomy. In the past, much of the morbidity and mortality associated with this operation was related to problems with this anastomosis. Recent data, however, suggest that the use of duct-to-mucosa sutures has led to a marked drop in both morbidity and mortality associated with pancreaticojejunostomy. METHODS: Among the 300 patients who underwent pancreaticoduodenectomy, including pylorus-preserving pancreaticoduodenectomy, 87 patients underwent traditional pancreaticojejunostomy by invagination of the end of the pancreas into the bowel (group B). Recently three-layer anastomosis was created in 213 patients. The outer layer was created between the pancreatic capsule and the serosa of jejunum. The middle layer was created between the pancreatic parenchyma and the seromuscular wall of jejunum. The inner layer was placed between the pancreatic duct and a small opening in the antimesenteric border of the jejunal mucosa. Among the 213 patients, the inner anastomosis was created with interrupted absorbable sutures (group A1) in 93 patients and continuous absorbable sutures (group A2) in 120 patients. RESULTS: The three groups were similar with respect to age, gender, and primary disease. In the anastomosis, the incidence of leakage in group A2 (4.2%) was significantly less than in groups B (17.2%, p < 0.01) and A1 (11.8%, p < 0.05). The operative mortality rates were 3.2% in group A1, 1.7% in group A2, and 5.7% in group B. CONCLUSIONS: We recommend continuous anastomosis of the pancreatic duct and jejunal mucosa as a safe procedure after pancreaticoduodenectomy.

Adolescent↗
PubMed1997

A novel association of Fc receptor gamma-chain with glycoprotein VI and their co-expression as a collagen receptor in human platelets.

The mechanism by which occupancy of collagen receptors is coupled to platelet activation has been uncertain. Our group previously demonstrated that glycoprotein (GP) VI, an uncharacterized platelet membrane protein, is specifically required for collagen-platelet interaction leading to activation of protein-tyrosine kinase Syk. Since collagen stimulation of platelets has recently been found to induce tyrosine phosphorylation of Fc receptor (FcR) gamma-chain, a signal-generating subunit of FcR, we further investigated the relationships between FcR gamma-chain and GPVI in human platelets. Our present study revealed the following. FcR gamma-chain was physically and stably associated with GPVI in human platelets; both FcR gamma-chain and GPVI were proportionally absent in GPVI-deficient platelets; GPVI cross-linking or collagen stimulation of platelets resulted in tyrosine phosphorylation of GPVI-associated FcR gamma-chain accompanied by Syk association and activation. These findings strongly suggest that the associated complex of GPVI and FcR gamma-chain is a collagen receptor featuring the signaling through immune receptors.

Blood Platelets↗
PubMed1997

The role of delta-opioid receptors in the discriminative stimulus properties of a low dose of methamphetamine.

The effects of selective mu-, delta- and kappa-opioid receptor agonists and antagonists on the discriminative stimulus properties of methamphetamine were examined in rats that had been trained to discriminate between methamphetamine (0.4 mg/kg) and saline. Methamphetamine produced a dose-related increase in methamphetamine-appropriate responses in all of the rats. In generalization tests, neither morphine (a mu-opioid receptor agonist: 0.3-10 mg/kg) nor 3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexo]benzeneacetamide (U50,488H: a kappa-opioid receptor agonist: 1.0-8.0 mg/kg) generalized to the discriminative stimulus properties of methamphetamine. A newly synthesized non-peptide selective delta-opioid receptor agonist 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha- octahydroquinolino(2,3,3,-g)isoquinoline (TAN-67: 32 mg/kg) partially generalized (70% methamphetamine-appropriate responses) to the discriminative stimulus properties of methamphetamine. In combination tests, pretreatment with the mu- and kappa-opioid receptor antagonists, beta-funaltrexamine (9.0 mg/kg) and nor-binaltorphimine (10 mg/kg), respectively, had little or no influence on the discriminative stimulus properties of methamphetamine. In contrast, pretreatment with naltrindole (a non-selective delta-opioid receptor antagonist: 3.0 mg/kg) or naltriben (a selective delta2-opioid receptor antagonist: 1.0 mg/kg), but not with 7-benzylidenenaltrexone (a selective delta1-opioid receptor antagonist: 0.5 and 1.0 mg/kg), significantly attenuated the discriminative stimulus properties of methamphetamine. However, naltrindole (3.0 mg/kg) did not significantly attenuate the discriminative stimulus properties of methamphetamine at a higher training dose (1.0 mg/kg). Our findings may have some bearing on the relative importance of the role of delta-opioid (especially delta2-opioid) receptors in the discriminative stimulus properties of a low dose of methamphetamine.

Animals↗
PubMed1997

Genetic modifiers of Leprfa associated with variability in insulin production and susceptibility to NIDDM.

In an attempt to identify the genetic basis for susceptibility to non-insulin-dependent diabetes mellitus within the context of obesity, we generated 401 genetically obese Leprfa/Leprfa F2 WKY13M intercross rats that demonstrated wide variation in multiple phenotypic measures related to diabetes, including plasma glucose concentration, percentage of glycosylated hemoglobin, plasma insulin concentration, and pancreatic islet morphology. Using selective genotyping genome scanning approaches, we have identified three quantitative trait loci (QTLs) on Chr. 1 (LOD 7.1 for pancreatic morpholology), Chr. 12 (LOD 5.1 for body mass index and LOD 3.4 for plasma glucose concentration), and Chr. 16 (P < 0.001 for genotype effect on plasma glucose concentration). The obese F2 progeny demonstrated sexual dimorphism for these traits, with increased diabetes susceptibility in the males appearing at approximately 6 weeks of age, as sexual maturation occurred. For each of the QTLs, the linked phenotypes demonstrated sexual dimorphism (more severe affection in males). The QTL on Chr. 1 maps to a region vicinal to that previously linked to adiposity in studies of diabetes susceptibility in the nonobese Goto-Kakizaki rat, which is genetically closely related to the Wistar counterstrain we employed. Several candidate genes, including tubby (tub), multigenic obesity 1 (Mob1), adult obesity and diabetes (Ad), and insulin-like growth factor-2 (Igf2), map to murine regions homologous to the QTL region identified on rat Chr. 1.

Alleles↗
PubMed1997

Differential effects of mu-, delta- and kappa-opioid receptor agonists on the discriminative stimulus properties of cocaine in rats.

The effects of selective mu-, delta- and kappa-opioid receptor agonists on the discriminative stimulus properties of cocaine were examined in rats trained to discriminate between cocaine (10 mg/kg) and saline. Cocaine produced a dose-related increase in cocaine-appropriate responses in all of the rats. In generalization tests, neither morphine (mu-opioid receptor agonist) nor N-methyl-N-7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-11-4-benzofu ranacetamide (U50,488H: kappa-opioid receptor agonist) generalized to the discriminative stimulus properties of cocaine. On the other hand, the newly synthesized non-peptide selective delta-opioid receptor agonist 2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydro-quinolino(2,3,3,-g)isoquinoline (TAN-67) partially generalized (56.7% cocaine-appropriate responses) to the discriminative stimulus properties of cocaine. Intracerebroventricular (i.c.v.) administration of [D-Ala2]deltorphin II (peptide delta 2-opioid receptor agonist) completely generalized, while neither [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO: mu-opioid receptor agonist) nor [D-Pen2,D-Pen5]enkephalin (DPDPE; delta 1-opioid receptor agonist) generalized to the discriminative stimulus properties of cocaine. These results suggest that the discriminative stimulus properties of cocaine may be partially mediated by delta-opioid (especially delta 2-opioid) receptors. In combination tests, pretreatment with morphine (3.0 mg/kg) and TAN-67 (3.0 and 10 mg/kg) significantly potentiated the discriminative stimulus properties cocaine. In contrast, pretreatment with U50,488H (2.0 and 4.0 mg/kg) scarcely shifted the discriminative stimulus properties of cocaine. Furthermore, the potentiating effect of 3.0 mg/kg morphine on the discriminative stimulus properties of cocaine was attenuated by 2.0 mg/kg U50,488H. In contrast, the potentiating effect of 10 mg/kg TAN-67 on the discriminative stimulus properties of cocaine was not reversed by either 2.0 or 4.0 mg/kg U50,488H. These results suggest that mu-, delta- and kappa-opioid receptor agonists modulate the discriminative stimulus properties of cocaine through different mechanisms, perhaps through different effects on the dopaminergic system.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1997

Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell-mediated protective immunity against malaria.

The immunogenicity of a recombinant replication defective adenovirus expressing a major malaria Ag, the circumsporozoite (CS) protein (AdPyCS), was determined using a rodent malaria model. A single immunizing dose of this construct induced a large number of CS-specific CD8+ and CD4+ T cells in the spleens of these animals, particularly when given by the s.c. or i.m. route. A single dose of AdPyCS also induced high titers of Abs to Plasmodium yoelii sporozoites in mice. No other form of presentation of the CS protein given as a single immunizing dose, i.e., irradiated sporozoites, recombinant vaccinia, or influenza virus, etc., elicits comparably high numbers of CS-specific CD8+ T cells. The high concentration of CS-specific CD8+ T cells in the spleen was relatively short-lived, decreasing to half of its original value by 4 wk and to one-third at 8 wk after AdPyCS inoculation. The decrease in splenic CS-specific CD4+ T cells was even more rapid. Most importantly, a single dose of inoculation of AdPyCS into mice rendered them highly resistant to sporozoite challenge, resulting in a 93% inhibition of liver stage development of the parasites. This protective effect was primarily mediated by CD8+ T cells, as shown by depletion of this T cell population, while depletion of the CD4+ T cell population had only a minor effect on anti-plasmodial activity. Moreover, the inoculation of mice with AdPyCS induces sterile immunity in a significant proportion of mice, preventing the occurrence of parasitemia.

Amino Acid Sequence↗
PubMed1997

Lipopolysaccharide-induced biphasic inositol 1,4,5-trisphosphate response and tyrosine phosphorylation of 140-kilodalton protein in mouse peritoneal macrophages.

We previously showed that a relatively high dose of LPS induced the selective translocation of protein kinase C-beta (PKC-beta) in LPS-responsive mouse macrophages. This result suggested that phosphatidylinositol-specific phospholipase C (PLC) might be activated in the upstream of PKC-beta. Stimulation of C3H/HeN mouse macrophages by LPS induced the characteristic phosphatidylinositol-1,4,5-trisphosphate (IP3) response, that is, a biphasic response consisting of a rapid increase occurring within the first 1 min, and another increase beginning at around 1 min after stimulation. Only the first response was disappeared when cells were treated with a platelet-activating factor receptor antagonist. LPS-inducible TNF-alpha gene activation, however, was not suppressed by the same antagonist, but suppressed by PKC inhibitors. LPS-stimulated macrophage lysates showed tyrosine phosphorylation of some proteins, and the strongest phosphorylation was observed at molecular mass of 140 kDa. The phosphorylation of this protein started at 40 s after LPS stimulation and continued to increase. Anti-PLC-gamma2 Ab seemed to recognize the same protein as the tyrosine-phosphorylated 140-kDa protein. A low dose of LPS (1 ng/ml) could not induce the tyrosine phosphorylation of this protein. Furthermore, LPS induced only the first phase change, but not the second phase increase in LPS-hyporesponsive C3H/HeJ mouse macrophages. These results indicate that the first phase rapid IP3 change, which is also seen in HeJ macrophages, is mediated via a platelet-activating factor receptor, and is not responsible for TNF-alpha production, while the second phase change mediated by a molecule other than CD14 is responsible for PKC-beta translocation and TNF-alpha production. The results also suggest that the later IP3 change is considered to be mediated through a gamma2 type of phosphatidylinositol-specific PLC.

Animals↗
PubMed1997

Involvement of dopamine-dependent and -independent mechanisms in the rewarding effects mediated by delta opioid receptor subtypes in mice.

The rewarding effects of the delta 1 opioid receptor agonist [D-Pen2, Pen5]enkephalin (DPDPE) and the delta 2 opioid receptor agonist [D-Ala2]deltorphin II (DELT) on the activity of mesolimbic and nigrostriatal dopamine (DA) neurons were examined in mice. Both DPDPE (15 nmol, i.c.v.) and DELT (5 nmol, i.c.v.) produced a significant place preference in mice. The DPDPE (15 mol, i.c.v.)-induced place preference was abolished by 7-benzylidenenaltrexone (BNTX; 0.5 mg/kg, s.c.), a delta1 opioid receptor antagonist, but not by naltriben (NTB; 0.5 mg/kg, s.c.), a delta 2 opioid receptor antagonist. In contrast, the DELT (5 nmol, i.c.v.)-induced place preference was antagonized by NTB, but not BNTX. I.c.v.. injection of DPDPE, but not DELT, at a dose that produced a significant place preference produced a significant elevation of DA turnover in the mouse limbic forebrain, and this effect of DPDPE was antagonized by BNTX but not by NTB. In addition, i.c.v. injection of DPDPE or DELT not affect DA turnover in the mouse striatum. These results suggest that the rewarding effects produced by the activation of central delta 1, but not delta 2, opioid receptors may be caused through the enhancement of the mesolimbic DA neurotransmission, and confirm our previous hypothesis that the DA-dependent and -independent mechanisms may exist in the rewarding effects produced by the activation of central delta opioid receptor subtypes.

Analgesics↗
PubMed1997

Primary leiomyosarcoma arising in the lesser sac: report of a case.

We describe herein a very rare case of leiomyosarcoma arising in the lesser sac. A 58-year-old man with a psychiatric disorder was admitted to our department for the investigation of epigastralgia and nausea which he had been suffering since the previous month. A laparotomy revealed that the abdominal mass, found on physical examination, was a primary lesser omental tumor, histological examinations of which confirmed a diagnosis of leiomyosarcoma. The tumor cells showed a DNA diploid pattern. Leiomyosarcoma of the lesser sac is extremely unusual and it is important that it be distinguished from an extraluminal tumor of the abdomen.

DNA, Neoplasm↗
PubMed1997

Hepatocellular carcinoma presenting as extrahepatic mass on computed tomography.

The authors describe an extremely rare case of extrahepatic hepatocellular carcinoma. The patient was a 70-year-old man who was examined by a local doctor because of abdominal discomfort. Barium meal examination demonstrated a defect occupying the lesser curvature of the stomach from the middle of the corpus to the fornix. On an abdominal computed tomography (CT) scan, the lesion, 10 cm in diameter, touched the lower surface of the caudate lobe of the liver. Under laparotomy, the tumor was found between the caudate lobe of the liver and posterior wall of the gastric corpus. As the tumor appeared to be connected with the caudate lobe by a pedicle, only the tumor was resected. Histological examination showed the tumor to be hepatocellular carcinoma of Edmondson's grade III-IV, pedunculated type.

Aged↗
PubMed1997

Interactions between H1-antagonists and opioids: a drug discrimination study.

We previously demonstrated that combination of opioids, pentazocine and dihydrocodeine, with the histamine H1-receptor antagonists tripelennamine and chlorpheniramine could enhance their rewarding effects in rats. In the present study, the effects of combined treatment with opioids and H1-antagonists on discriminative stimulus effects were examined in rats trained to discriminate between cocaine (10 mg/kg) or morphine (3.0 mg/kg) and saline, since it is believed that discriminative stimulus effects of abused drugs are related to their rewarding effects. Tripelennamine and chlorpheniramine, but not pentazocine or dihydrocodeine, generalized to the discriminative stimulus effects of cocaine. Pentazocine (3.0 mg/kg) and dihydrocodeine (5.6 mg/kg) significantly potentiated the cocaine-like discriminative stimulus effects of low doses of tripelennamine and chlorpheniramine, respectively. On the other hand, pentazocine and dihydrocodeine, but not tripelennamine or chlorpheniramine, generalized to the discriminative stimulus effects of morphine. Neither 1.0 or 3.0 mg/kg tripelennamine nor chlorpheniramine affected the morphine-like discriminative stimulus effects of pentazocine and dihydrocodeine, respectively. These results suggest that the potentiation of the cocaine-like discriminative stimulus effects of H1-antagonists by opioids may be involved in the enhanced rewarding effects of combinations of opioids and H1-antagonists.

Analgesics, Opioid↗