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Biomedical subjects

M Tsuji

Publications and source records attributed to M Tsuji.

At least 127 records · Page 7Linked to original sources

Evaluation of the histamine H1-antagonist-induced place preference in rats.

The place preferences by some histamine H1 antagonists, such as tripelennamine, optical isomers of chlorpheniramine (dl-, d- and l-forms) and pyrilamine, in rats were evaluated with the conditioned place preference paradigm. In the present study, tripelennamine and all of the optical isomers of chlorpheniramine, but not pyrilamine, produced a significant place preference. The degree of the place preference induced by optical isomers of chlorpheniramine (6.0 mg/kg) did not correlate with the H1-antagonistic potency of these drugs, suggesting that H1-antagonist-induced place preferences are not mediated by H1-receptor blockade. The tripelennamine (3.0 mg/kg)- and dl-chlorpheniramine (6.0 mg/kg)-induced place preferences were completely abolished by pretreatment with the dopamine D1-receptor antagonist SCH23390 (0.05 mg/kg). Furthermore, the doses of H1 antagonists that induced a place preference significantly reduced the levels of DOPAC, which may be mediated by inhibition of dopamine uptake, in the limbic forebrain (including the nucleus accumbens and olfactory tubercle). These results suggest that some H1 antagonists induce rewarding effects, which may be mediated by the activation of dopamine D1 receptors, followed by the inhibition of dopamine uptake.

Animals↗

Infectivity to hosts of the endogenous stages of chicken and murine Cryptosporidium.

Five groups of 4 mice each were inoculated with 10(6) Cryptosporidium muris oocysts. They were necropsied on days 2, 4, 6, 8 and 10. The stomach mucosa from each group were made into 10% suspension in physiological saline and were orally inoculated to 2 mice each. Recipients given suspension from infected mice on day 6, 8 and 10 shed oocysts from 6, 9 and 6, respectively. Similarly, White Leghorn received 10(6) Cryptosporidium sp. oocysts were killed daily between 1 and 6 days. Recipients given bursa of Fabricius or caecum of donor birds on days 4, 5 and 6 shed oocysts. The endogenous stages of murine and chicken Cryptosporidium were able to infect the appropriate host.

Animals↗

Preparation of antibodies directed to the Babesia ovata- or Theileria sergenti-parasitized erythrocytes.

To investigate the surface antigens of the bovine red blood cells (RBCs) parasitized by Babesia ovata or Theileria sergenti, attempts were made to produce monoclonal antibodies (mAbs) with BALB/c mice. Comparable numbers of hybridomas producing anti-piroplasm mAbs, as well as anti-bovine RBC mAbs, were obtained from the mice immunized with B. ovata- or T. sergenti-PRBCs. However, mAbs directed to the surface of parasitized RBCs (PRBCs) were obtained only from the mice immunized with B. ovata-PRBCs, but not from those immunized with T. sergenti-PRBCs. When serum samples from the immunized mice and the infected cattle were examined, antibodies recognizing B. ovata-PRBC surface were detected in the sera against B. ovata, but analogous antibodies were undetectable in the sera against T. sergenti, despite that the sera showed substantial antibody titers to T. sergenti piroplasms. The results suggest that significant antigenic modifications occur on the surface of B. ovata-PRBCs, but not on the surface of T. sergenti-PRBCs.

Animals↗

Rapid increase in circulating leptin in ventromedial hypothalamus-lesioned rats: role of hyperinsulinemia and implication for upregulation mechanism.

The mechanisms of marked increase in plasma leptin soon after ventromedial hypothalamus (VMH) lesions were investigated. Although rats did not gain body weight or parametrial fat-pad mass 24 h after the operation, the acute VMH-lesioned rats exhibited substantial five- and fourfold increases in plasma leptin levels compared with sham-operated control rats in fed (22.6 +/- 3.2 vs. 5.8 +/- 1.2 ng/ml) and fasted (8.8 +/- 2.0 vs. 2.3 +/- 0.3 ng/ml) states, respectively. Plasma insulin concentration was doubled in VMH-lesioned rats compared with sham-operated controls in both fed and fasting states. Northern blot analysis revealed that mRNA of ob gene was not increased in parametrial fat pad of animals 24 h after the creation of VMH lesions. However, leptin content in the fat pad was significantly increased in VMH-lesioned rats compared with sham-operated controls (32.2 +/- 4.7 vs. 17.4 +/- 2.3 ng/g wet tissue). The leptin content in parametrial fat pad was highly correlated with plasma leptin concentrations (r = 0.898, P < 0.001). To define the effect of hyperinsulinemia on their hyperleptinemia, a small dose of streptozotocin (STZ) (25 mg/kg body wt) was intravenously administered into rats 5 days before the creation of VMH lesions. Plasma insulin levels were not increased after VMH lesions in STZ-pretreated rats. Plasma leptin levels were halved in the absence of hyperinsulinemia, but still remained twofold higher than those in their sham-operated counterparts (9.9 +/- 1.3 vs. 4.8 +/- 0.7 ng/ml). These results indicate that the destruction of VMH rapidly promotes leptin production before obesity develops through an enhanced translational process in which hyperinsulinemia occurring after VMH lesioning plays an important role. The present study also suggests that there are other mechanisms that rapidly upregulate leptin production in adipocytes in VMH-lesioned rats in which the target organ of this hormone has been destroyed.

Animals↗

Biologic markers in prostatic intraepithelial neoplasia: immunohistochemical and cytogenetic analyses.

OBJECTIVE: We evaluated the biological properties of High-grade prostatic intraepithelial neoplasia (PIN) by immunohistochemistry and fluorescence in situ hybridization (FISH) analysis in relation to normal tissue and carcinoma lesions. MATERIALS AND METHODS: Immunohistochemical staining and FISH were performed on 23 formalin-fixed radical prostatectomy specimens taken from patients with PIN. Assays were performed using MIB-1, chromogranin A (CGA) and an anti-androgen receptor antibody (AR). A centromere probe for chromosome 8 was used to test for aneuploidy. RESULTS: The MIB-1 index of cancerous specimens (16.2 +/- 10.5%) was significantly higher than that of benign (1.9 +/- 1.6%, p < 0.0001) or PIN (4.0 +/- 4.5%, p < 0.0001) specimens. The percentage of CGA positive cells was significantly lower in normal tissue (1.2 +/- 1.8%) than in PIN (3.5 +/- 2.9%, p = 0.012) or carcinoma (5.4 +/- 4.9%, p = 0.005) lesions. Positive staining for AR was consistently observed in the nuclei of both benign and malignant epithelial cells, but positive cytoplasmic staining was also seen in PIN epithelial cells. No significant difference in FISH detected anomalies were found between PIN and carcinoma specimens. CONCLUSIONS: Our studies concerning proliferative activity, NE differentiation and chromosomal anomalies of prostatic specimens support the hypothesis that PIN is a biologically intermediate stage in the pathogenesis of prostatic carcinoma. The cellular distribution of AR was altered in PIN cells, but the role of AR in PIN is not yet clear.

Aged↗

Physical and functional association of the Src family kinases Fyn and Lyn with the collagen receptor glycoprotein VI-Fc receptor gamma chain complex on human platelets.

We have previously shown that uncharacterized glycoprotein VI (GPVI), which is constitutively associated and coexpressed with Fc receptor gamma chain (FcRgamma) in human platelets, is essential for collagen-stimulated tyrosine phosphorylation of FcRgamma, Syk, and phospholipase Cgamma2 (PLCgamma2), leading to platelet activation. Here we investigated involvement of the Src family in the proximal signals through the GPVI-FcRgamma complex, using the snake venom convulxin from Crotalus durissus terrificus, which specifically recognizes GPVI and activates platelets through cross-linking GPVI. Convulxin-coupled beads precipitated the GPVI-FcRgamma complex from platelet lysates. Collagen and convulxin induced tyrosine phosphorylation of FcRgamma, Syk, and PLCgamma2 and recruited tyrosine-phosphorylated Syk to the GPVI-FcRgamma complex. Using coprecipitation methods with convulxin-coupled beads and antibodies against FcRgamma and the Src family, we showed that Fyn and Lyn, but not Yes, Src, Fgr, Hck, and Lck, were physically associated with the GPVI-FcRgamma complex irrespective of stimulation. Furthermore, Fyn was rapidly activated by collagen or cross-linking GPVI. The Src family-specific inhibitor PP1 dose-dependently inhibited collagen- or convulxin-induced tyrosine phosphorylation of proteins including FcRgamma, Syk, and PLCgamma2, accompanied by a loss of aggregation and ATP release reaction. These results indicate that the Src family plays a critical role in platelet activation via the collagen receptor GPVI-FcRgamma complex.

Blood Platelets↗

Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice.

The effects of treatment with anxiogenic or anxiolytic agents and exposure to acute restraint stress on emotional behavior in mice were examined using an automatic hole-board apparatus. Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e., total locomotor activity, numbers and duration of rearing and head-dipping, and latency to the first head-dipping. The typical benzodiazepine anxiolytics diazepam (0.05-0.5 mg/kg, i.p.) and chlordiazepoxide (0.5-4 mg/kg, i.p.) dose-dependently increased the number and duration of head-dips at doses that did not produce sedation. In contrast with these anxiolytics, the typical anxiogenic drugs N-methyl-beta-carboline-3-carboxamide (FG7142, 0.125-10 mg/kg, i.p.) and methyl-beta-carboline-3-carboxylate (beta-CCM, 0.1-2 mg/kg, i.p.) decreased both the number and duration of head-dips, and increased the latency to head-dipping. Moreover, decreases in the number and duration of head-dips, and an increase in the latency to head-dipping, were also observed in animals that were exposed to acute restraint stress. These effects of acute restraint stress were suppressed by treatment with diazepam at a dose that alone did not produce significant behavioral effects (0.1 mg/kg, i.p.). In addition, non-benzodiazepine anxiolytic flesinoxan (0.1 mg/kg, i.p.), a 5-HT1A receptor agonist, also had an effect on the restraint stress-induced decrease in head-dipping behavior. The present study shows that the changes in several exploratory behaviors could be objectively measured using our automatic hole-board apparatus. Therefore, this system can serve as a useful tool for evaluating the changes in various emotional states of animals. Moreover, we also found that treatment with anxiolytics or anxiogenics and exposure to acute restraint stress affected head-dipping behavior. These results suggest that changes in head-dipping behavior in the hole-board test may reflect the anxiogenic and/or anxiolytic state of animals.

Animals↗

Premorbid personality traits of patients with organic (ICD-10 F0), schizophrenic (F2), mood (F3), and neurotic (F4) disorders according to the five-factor model of personality.

The present article aims to examine premorbid personality traits of psychiatric patients with various diagnoses by asking their close relatives to retrospectively rate the patients' usual self with a questionnaire designed for the five-factor model of personality, a rapidly emerging comprehensive theory of personality structure. Data for 140 patients and 84 controls were analyzed. Although psychiatric patients as a group were characterized by high neuroticism and low conscientiousness when compared with the healthy controls, there were only a few traits that distinguished a particular diagnostic group from either the normal control or from the rest of the patients: neurotic disorder patients had higher neuroticism scores than the normal controls; unipolar depressives had a higher conscientiousness score than the rest of the patient group. No salient premorbid trait was noted for patients with organic mental disorders, schizophrenic disorders or bipolar disorders.

Adult↗

Recombinant viruses expressing a human malaria antigen can elicit potentially protective immune CD8+ responses in mice.

Extensive studies on protective immunity to rodent malaria provided the basis for the current experiments in which mice were immunized with recombinant (re) influenza and vaccinia viruses expressing selected sequences of the circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum. Mice of different H-2 haplotypes immunized with re influenza viruses expressing the immunodominant B cell epitope of this CS protein produced high titers of antibodies to the parasite. A cytotoxic T lymphocyte epitope of the CS protein of P. falciparum, PF3, recognized by CD8+ T cells of H-2(k) mice, was expressed in a re vaccinia virus (VacPf) and a re influenza virus (FluPf). Immunization of mice with either FluPf or VacPf elicited a modest CS-specific CD8+ T cell response detected by interferon gamma secretion of individual immune cells. Priming of mice with FluPf, followed by a booster with VacPf, resulted in a striking enhancement of this T cell response. The reverse protocol, i.e., priming with VacPf followed by a booster with FluPf, failed to enhance the primary response. VacPf also greatly enhanced the primary response of mice injected with P. falciparum sporozoites or with a lipopeptide containing PF3. A booster with FluPf also amplified the response of lipopeptide- or sporozoite-primed mice but less than a VacPf booster did. Although mice are not susceptible to infection by P. falciparum sporozoites, we demonstrated that administration of two distinct immunogens expressing PF3 elicited activated, extravasating CS-specific T cells that protected against an intracerebral VacPf challenge.

Amino Acid Sequence↗

Living-related liver transplantation and neurological outcome in children with fulminant hepatic failure.

BACKGROUND: Fulminant hepatic failure (FHF) in children is associated with high mortality under medical management. Living-related liver transplantation (LRLT) is an accepted measure to treat the children with end-stage liver disease. Reversibility of hepatic encephalopathy is crucial for the quality of life among the survivors after transplantation. METHODS: A retrospective review was made of the records of children undergoing LRLT at this hospital between May 1992 and November 1996. RESULTS: Eleven children with FHF underwent emergency LRLT. The mean age was 5 years (range, 2 months to 15 years). The indication for transplantation was persistent or worsening hepatic encephalopathy and severe coagulopathy, despite repeated plasma exchanges or exchange transfusions. The cause of FHF was non-A, non-B hepatitis in seven children, hepatitis B in two children, herpes simplex virus hepatitis in one child, and fulminant Wilson's disease with intravascular hemolysis in one child. The grade of hepatic encephalopathy was II in four children, III in two, and IV in five. The actuarial survival rate was 73% after a mean follow-up of 28 months (range, 13-67 months). Short-term neurological morbidity was present in two children with grade IV encephalopathy who also showed brain edema on cranial computed tomography. Eight survivors exhibited no long-term neurological deficit; the mean intelligence or developmental quotient was 97 (range, 86-110) at the end of the follow-up period. CONCLUSIONS: LRLT is an effective option for the treatment of FHF in children. The long-term neurological status is satisfactory among survivors.

Brain Edema↗

In vivo phosphocreatine and ATP in piglet cerebral gray and white matter during seizures.

The creatine kinase (CK) reaction is thought to be important in coupling ATP metabolism and regulating ADP concentration in tissues with high and variable ATP turnover, including cerebral gray matter (GM). There is low phosphocreatine (PCr), low CK reaction rates, and high mitochondrial CK (MiCK) isoenzyme activity in GM compared to white matter (WM). To compare the CK reaction in GM and WM when ATP metabolism is high, CK reactants and reaction rates were measured in predominantly GM and WM slices in vivo in 2 and 14-day old piglets during pentylenetetrazole (PTZ) seizures using 31P nuclear magnetic resonance (NMR) 1-dimensional chemical shift imaging (CSI). Arterial pressure, temperature, and blood gasses were stable at both ages. Before seizures, the PCr/nucleoside triphosphate (NTP) ratio was higher in WM than GM at both ages with a developmental increase seen in WM. The CK reaction rate constant increased in both regions between 2 and 14 days. During seizures, PCr/NTP increased in GM at 14 days due to increased PCr while the ratio and PCr decreased in WM. The NTP was more stable in WM and GM at both ages. The CK reaction rate decreased in both regions more at 2 than at 14 days. Thus, brain ATP, deduced from NTP, is stable during seizures in the piglet. In GM stable ATP is associated with a unique increase in PCR concentration.

Adenosine Triphosphate↗

Increase in nitric oxide in the hypoxic-ischemic neonatal rat brain and suppression by 7-nitroindazole and aminoguanidine.

We measured the changes in nitric oxide (NO) metabolites in the brains of neonatal rats with hypoxic-ischemic damage. There were two peaks of NO metabolites in the lesioned side of the cortex without treatment: one during hypoxia and the other during the re-oxygenation period. Prehypoxic treatment with 7-nitroindazole, a selective neuronal NO synthase inhibitor, suppressed both peaks of NO metabolites, whereas prehypoxic treatment with aminoguanidine, a selective inducible NO synthase inhibitor, partially suppressed only the peak in the re-oxygenation period. These data suggest different roles of neuronal and inducible NO synthases in the pathogenesis of hypoxic-ischemic encephalopathy.

Animals↗

Primary small cell carcinoma of the esophagus: flow cytometric analysis and immunohistochemical staining for the p53 protein and proliferating cell nuclear antigen.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the clinical course and effects of histopathologic characteristics of specific tumors including DNA contents and immunohistochemical aspects in patients with small cell carcinoma of the esophagus. METHODS: Medical records of 4 patients who presented with small cell carcinoma of the esophagus were retrospectively reviewed. RESULTS: DNA aneuploidy was observed in 2 cases. Staining for the p53 product was positive in all cases. The average proliferating cell nuclear antigen (PCNA) labeling rate (LR) was 77.6% (64.0-90.8%). The estimated median survival was 42 days for all patients. Distant metastases were observed in 2 of the 4 patients. CONCLUSIONS: Higher PCNA LR of small cell carcinoma may be an unfavorable characteristic of biological behavior. Patients with disseminated disease should have symptomatically palliative operation combined with chemotherapy.

Aged↗

Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.

CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC.

Antigens, Neoplasm↗