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Biomedical subjects

M Tsuji

Publications and source records attributed to M Tsuji.

At least 181 records · Page 10Linked to original sources

Inhibitory effect of heparin on red blood cell invasion by Theileria sergenti merozoites.

Theileria sergenti infection has been one of the most serious infectious diseases of cattle in Japan. A major component in the pathogenesis of T. sergenti is anaemia. The erythrocytic life-cycle, which is responsible for all of the clinical manifestations of T. sergenti infection, is initiated by invasion of bovine red blood cells (RBCs) by merozoites. Here we have focused on the effect of heparin, which has an inhibitory effect on RBC invasion by Plasmodium falciparum, and demonstrated for the first time that bovine RBC invasion by T. sergenti was inhibited by heparin. Further, analysis of this mechanism showed that bovine RBC agglutination, by purified T. sergenti merozoites, was inhibited by heparin and low molecular weight (LMW) heparin. Moreover, hemagglutination was inhibited by treatment of the merozoites with heparinase. These results suggest that merozoites have heparin-like molecules on their surface which may be one of the important factors for attachment to RBCs.

Animals↗

From discovery to eradication of schistosomiasis in Japan: 1847-1996.

Among the areas in Japan where schistosome infections have occurred for many years, three major areas were Katayama District, Kofu Basin and Chikugo River Basin and three minor areas were Numazu District, Tone River Basin and Obitsu River Bank. The presence of the disease had long been recognised in the Katayama Memoir written by Fujii (1847, in the Chinese Classics). The cause of this endemic disease had been studied by many researchers, and finally a new trematode, Schistosoma japonicum, was discovered by Katsurada in 1904 [Tokyo Iji Shinshi, Vol. 1371, pp. 13-32]. The route of percutaneous infection was proven by Fujinami & Nakamura (1909) [Kyoto Medical Journal, Vol. 6, pp. 224-252] using 17 calves. Miyairi & Suzuki (1913) [Tokyo Iji Shinshi, Vol. 1836, pp. 1961-1965] determined a small snail, Oncomelania nosophora, as being the intermediate host, and clarified the development of the schistosome in the snail. To kill schistosome eggs, human faecal matter ('night soil') was stored for 2 weeks or more before using as fertiliser. Control of the parasite used caustic lime and calcium cyanamide to kill eggs, cercariae and Oncomelania snails. Susceptible cows were replaced with horses, which were more resistant to infection as the animal of burden for agriculture. Ditches around the rice fields were cemented for destruction of snail habitats. For snail control, sodium pentachlorophenate (NaPCP) was sprayed extensively. Some wetlands were drained and reclaimed and in selected localities, the river bottom was dredged. Such projects were undertaken with government support and aided by community participation. Epidemiological surveys began in 1910, first at Kofu, and infected people were treated with sodium tartar emetic (Stibnal) after 1921. The total number of cases detected in Japan in 1920 was about 8000. This figure was reduced annually down to 438 by 1970. The last human case of new infection found in Japan was at Kofu in 1977. Although snails were eradicated in most areas by 1983, a limited number of uninfected snails remain at Kofu and Obitsu.

Animals↗

Antisense oligodeoxynucleotide to delta opioid receptors blocks cocaine-induced place preference in mice.

The effect of intracerebroventricular (i.c.v.) treatment with antisense oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on cocaine-induced place preference was examined in mice. Cocaine (10 mg/kg, s.c.) produced a significant place preference. I.c.v. treatment with A-oligo (0.001-1 microg/mouse) dose-dependently attenuated the cocaine (10 mg/kg, s.c.)-induced place preference, although mismatched oligodeoxynucleotide (1 microg/mouse, i.c.v.) was ineffective. In the present study, we found that the selective reduction in number and/or function of central delta opioid receptors by A-oligo suppresses the cocaine-induced place preference. These results suggest that the conditioned reward by cocaine may be partially mediated by central delta opioid receptors.

Animals↗

Antisense oligodeoxynucleotide to delta opioid receptors attenuates morphine dependence in mice.

The effect of intracerebroventricular (i.c.v.) treatment with antisense oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on the morphine-induced place preference and naloxone-precipitated jumping was examined in morphine-dependent mice. Morphine (5 mg/kg, s.c.) produced a significant place preference. I.c.v. pretreatment with A-oligo (0.01-1 microg/mouse) dose-dependently attenuated this morphine (5 mg/kg, s.c.)-induced place preference, while mismatched oligodeoxynucleotide (M-oligo; 1 microg/mouse, i.c.v.) was ineffective. Naloxone (3 mg/kg, s.c.) precipitated jumping in morphine-dependent mice. I.c.v. pretreatment with A-oligo (1 microg/mouse) attenuated this naloxone (3 mg/kg, s.c.)-precipitated jumping in morphine-dependent mice, while M-oligo (1 microg/mouse, i.c.v.) was ineffective. These data demonstrate that the selective reduction in supraspinal delta opioid receptor function caused by pretreatment with A-oligo attenuated the morphine-induced place preference and naloxone-precipitated jumping in morphine-dependent mice, suggesting that the rewarding effect of and physical dependence on morphine may be modulated by central delta opioid receptors.

Animals↗

Prognostic value of Ki-67 antigen and p53 protein in urinary bladder cancer: immunohistochemical analysis of radical cystectomy specimens.

OBJECTIVE: To investigate the role of tumour proliferation and p53 expression as a marker of survival in patients with urinary bladder cancer who undergo radical cystectomy. PATIENTS AND METHODS: Samples were obtained from 31 patients (29 men and two women, mean age 66.0 years, range 46-80) with transitional cell carcinoma of the bladder who underwent radical cystectomy. The 31 formalin-fixed radical cystectomy specimens were stained immunohistochemically for Ki-67 antigen and p53 protein using MIB1 and p53 antibodies, respectively, and the results correlated with tumour grade, stages and prognosis. RESULTS: The Ki-67 index was significantly greater in high-grade tumours and in those overexpressing p53 (> 20% positive nuclei). Patients whose tumour samples had a high Ki-67 index (> 32%) had a significantly worse prognosis than those with a lower index (P < 0.01). There was a similar correlation between Ki-67 index and prognosis in high-risk patients (grade 3 and pT3-4; P < 0.05). Although the associations between tumour grade, stage and p53 expression were not statistically significant, patients whose tumour samples overexpressed p53 had a lower survival rate (P < 0.05). No patients with tumours having a low Ki-67 and low p53 index (n = 14) died of urinary bladder cancer during the follow-up. CONCLUSION: These results suggest that immunohistochemical analyses for Ki-67 and p53 are useful prognostic indicators in patients with urinary bladder cancer who undergo radical cystectomy; the prognostic role of these markers was particularly important in high-risk (grade 3 and pT3-4) patients.

Aged↗

Symptomatic hypophyseal granular cell tumour: endocrinological and clinicopathological analysis.

We report a case of a hypophyseal granular cell tumour (GCT) presenting with visual failure and hyperprolactinaemia (serum prolactin level, 274 ng/ml; normal, < 10). Magnetic resonance images demonstrated an intrasellar mass with anterosuperior extension. As the patient had chronic renal failure (CRF) and hyperprolactinaemia is frequent in CRF patients, a firm preoperative diagnosis of prolactinoma could not be made. Transsphenoidal removal of the tumour resulted in improvement of both vision and serum prolactin. Histopathological analysis of the surgical specimen revealed GCT. A cell kinetic study, the first such report for this type of tumour, revealed a relatively high Ki-67 staining index of 3.2%. On electron microscopy, numerous intracytoplasmic granules with various electron densities were demonstrated. Moreover, cell-processes extending from the granule-rich cytoplasm contained intracytoplasmic filaments but few granules, suggesting that the filament-rich cells, which are occasionally seen in GCT tissues, are essentially identical to the granule-rich cells in origin.

Diagnosis, Differential↗

Early diagnosis of mucosal squamous cell carcinoma of the esophagus: including two interesting cases of superficial spreading-type and multicentric-type squamous cell carcinomas.

We reviewed 10 patients with esophageal mucosal carcinoma in order to improve the early diagnosis of the disease. Histologically seven of the 14 lesions were carcinomas in situ (epithelial cancer), and the other seven lesions were carcinomas confined to the mucosa other than epithelial cancer (muscularis mucosae cancer), all 14 lesions were squamous cell carcinomas (SCC). One of these seven mucosal SCC, which demonstrated an extensive spreading-type SCC in which the size of the SCC was 7 cm long while extending entirely around the esophageal lumen in circumferential spread, is described in detail, and multiple epithelial cancers existed separately in one case. Eleven lesions diagnosed before operation showed abnormal findings on conventional endoscopy regardless of the size and depth of transmural invasion. An additional lesion was visible with dye endoscopy as an unstained area, but it was not visible with radiography or conventional endoscopy. Dye endoscopy using Lugol solution is very important because it allows detection and evaluation of the extent of esophageal mucosal cancer.

Aged↗

Generalization of D-, L- and DL-chlorpheniramine and zolantidine to the discriminative stimulus effects of cocaine and methamphetamine.

We recently demonstrated that some H-antagonists have cocaine or methamphetamine-like discriminative stimulus effects. In the present study, the effects of optical isomers of chlorpheniramine (D-, L- and DL-forms) on the discriminative stimulus effects of cocaine and methamphetamine were examined in rats trained to discriminate between cocaine (10.0 mg/kg) or methamphetamine (1.0 mg/kg) and saline, to determine whether these effects of H1-antagonists are mediated by the blockade of H-receptors. In generalization tests with optical isomers of chlorpheniramine, the D-, L- and DL-forms all completely generalized to the discriminative stimulus effects of cocaine, but did not generalize to those of methamphetamine. Dose-generalization by the optical isomers of chlorpheniramine to the discriminative stimulus effects of cocaine did not correlate with the H-antagonistic potency of these drugs. These results suggest that all of the optical isomers of chlorpheniramine have cocaine-like discriminative stimulus effects, but that these effects are not mediated by H1-receptor blockade. On the other hand, the H2-antagonist, zolantidine, generalized to the discriminative stimulus effects of methamphetamine, but not to those of cocaine, suggesting that zolantidine may have methamphetamine-like discriminative stimulus effects. In the present study, GBR12909 (dopamine uptake inhibitor) completely generalized to the discriminative stimulus effects of cocaine, but not to those of methamphetamine, whereas apomorphine (dopamine receptor agonist) generalized more potently to the discriminative stimulus effects of methamphetamine than to those of cocaine. These findings imply that although the dopaminergic system plays an important role in the discriminative stimulus effects of both cocaine and methamphetamine, there may be differences between their effects.

Animals↗

Polyenylidene thiazolidinedione derivatives with retinoidal activities.

Several polyenylidene thiazolidine or 2-thioxo-4-thiazolidinone derivatives were synthesized and their retinoidal activities were examined in terms of the differentiation-inducing ability towards human promyelocytic leukemia HL-60 cells and inhibitory effect on interleukin (IL)-1 alpha-induced IL-6 production in MC3T3-E1 cells. Compounds containing a trimethylcyclohexenyl ring induced HL-60 cell differentiation with weaker activity than retinoic acid (1a) by one or two orders of magnitude. The thiazolidinedione derivatives (2, 5, 7) showed stronger activity than the corresponding 2-thioxo-4-thiazolidinone derivatives (3, 6, 8). The effects of a retinoid antagonist (LE540) and synergists (retinoid X receptor (RXR) agonists, HX600 or HX630) on the activities of thiazolidine derivatives indicate that these compounds elicit their activities through the nuclear retinoic acid receptors (RARs). All the thiazolidines examined also inhibited IL-1 alpha-induced IL-6 production with IC50 values of 10 nM order. The retinoidal activities of the thiazolidines are significant, considering that replacement of the carboxylic acid in retinoid structures with bioisosteric functional groups is generally ineffective, as seen in the structure-activity relationships of retinoidal benzoic acids.

Cell Differentiation↗

Phylogenetic analyses of Staphylococcus based on the 16S rDNA sequence and assignment of clinical isolates from animals.

The nucleotide sequences of the 16S rDNA in 17 strains of 16 taxa of the genus Staphylococcus were determined. The sequences were compared phylogenetically together with the gene sequences of 10 (including 7 other species) Staphylococcus species retrieved from the DNA Data Bank of Japan. Although the primary and secondary structures of most of Staphylococcus species were very similar (homology values 96.4% or more) except for S. caseolyticus MAFF 911387T (homology values 95.4% or less), the 23 staphylococcal species were divided into 10 groups based on similarity, evolutionary distance and phylogenetic tree analysis. Nucleotide stretches in several variable domains in the 16S rDNA sequences appeared to be specific for the bacterial groups or the species. By comparing such characteristics in the sequence and phylogenies of 5 staphylococcal clinical isolates from bovine mastitis, canine and feline pyoderma, and feline urogenital syndrome with the information obtained in this study, the species level of each organism was identified.

Animals↗

Effects of intraluminal or extraluminal endothelin on perfused rabbit basilar arteries.

The authors investigated selective intra- and extraluminal effects of endothelin (ET) on perfused basilar and extracranial arteries and also studied the interaction between ET and extraluminal oxyhemoglobin (oxyHb). The basilar, mesenteric, and femoral arteries were isolated from 23 Japanese White rabbits. After isolation of the intra- and extraluminal sides of the preparation, 3 x 10(-10) to 3 x 10(-8) mol/L of ET was administered intra- or extraluminally. After extraluminal pretreatment with 10(-5) mol/L oxyHb, 10(-5) mol/L N(G)-monomethyl-L-arginine (L-NMMA), or 10(-6) mol/L indomethacin, 10(-10) to 10(-8) mol/L of ET was administered intra- or extraluminally. Arterial contraction was evaluated by measuring the increase in the perfusion pressure gradient with a differential pressure gauge. Both intra- and extraluminal ET (10(-9) to 3 x 10(-8) mol/L) showed potent and dose-dependent vasoconstricting effects on basilar arteries (p < 0.01). The effect of ET on the basilar arteries was significantly greater than on the femoral or mesenteric arteries (both p < 0.01). The effect of intraluminal ET was enhanced by extraluminal oxyHb (p < 0.05) and L-NMMA (p < 0.01), but not by extraluminal indomethacin. Extraluminal oxyHb did not potentiate the contraction induced by extraluminal ET. These results indicate that the sensitivity of the basilar artery to intraluminal ET is greater than that of the femoral or mesenteric artery. Endothelin may act as a potent vasoconstrictor intra- as well as extraluminally under conditions such as subarachnoid hemorrhage in which oxyHb is present in the extraluminal space and endothelium-derived relaxing factors are inhibited.

Animals↗

Blood coagulability and fibrinolysis in streptozotocin-induced diabetic rats.

Changes in coagulation and fibrinolysis in the plasma (in vivo) and hepatocytes (ex vivo) were studied using hyperglycemic rats. Hyperglycemia was induced by intravenous injection of 50 mg/kg streptozotocin (STZ). Eight weeks after the injection, we observed increases in thrombin-antithrombin III complex and tissue type plasminogen activator activity, decreases in plasma levels of antithrombin III, plasminogen and alpha2-plasmin inhibitor, and significant shortening of activated partial thromboplastin time. In freshly isolated or cultured hepatocytes from STZ-induced hyperglycemic rats, concentrations of proteins related to coagulation were increased. An increase in alanine-aminotransferase leakage and decreases in the levels of amylase, triglycerides and phospholipids were observed in the culture medium of hepatocytes from STZ treated rats. In vivo study revealed that STZ-induced subchronic diabetes induced imbalance between coagulation and fibrinolysis, and ex vivo study in hepatocytes from STZ-treated rats showed membrane degeneration and reduction in amylase synthesis, while protein synthesis related to coagulation was not inhibited. These results suggest that, despite vulnerability of liver cells from STZ treated rats, coagulation activity in the liver is retained and rather enhanced in STZ-induced hyperglycemic rats, which may contribute to the promotion of atherosclerosis.

Animals↗

[The role of serum soluble interleukin 2 receptor (sIL-2R) levels in patients with renal cell carcinoma].

PURPOSE: The correlation between the serum soluble interleukin-2 receptor (SIL-2R) levels and clinical stage is demonstrable in a variety of non-Hodgkin lymphomas. The prognostic significance of sIL-2R levels in the serum of patients with renal cell carcinoma (RCC) was investigated. METHOD: sIL-2R were measured in patients with RCC (n=39) and normal control (n=6) by the enzyme immunoassay technique. Cases of RCC were classified according to the clinical stage, pathological grade and growth type. The IL-2R expression of RCC was evaluated by RT-PCR. RESULT: The serum sIL-2R levels of patients with RCC showed significantly higher values than those of controls (p < 0.05). The serum sIL-2R levels in RCC were closely associated with the stage, grade and growth type of disease. The patients with high serum sIL-2R level (> = 1,000 U/L) exhibited a significantly poorer prognosis than those with low serum sIL-2R level (<1,000 U/L). The band of IL-R was detected only by using the template from the mRNA extracted from a resected tumor tissue of the RCC but not from the RCC cell lines. CONCLUSION: It was suggested that the measurement of serum sIL-2R levels is useful for predicting the prognosis.

Adult↗

Quantitative and compositional changes in high density lipoprotein subclasses in patients with various genotypes of cholesteryl ester transfer protein deficiency.

High density lipoprotein (HDL) with and without apolipoprotein (apo) E was quantified and characterized in subjects with three genotypes of cholesteryl ester transfer protein (CETP) deficiency: the nonsense mutation in intron 14 (10 homozygotes and 5 heterozygotes); the missense mutation in the exon 15 (3 homozygotes and 9 heterozygotes); and the Int14A/D442G in 6 compound heterozygotes. ApoE-poor and apoE-rich HDL-cholesterol levels were elevated significantly in all genotypic groups with the decrease in CETP activity, indicating that both types of HDL-cholesterol can be a substrate for CETP. However, an unchanged or only slightly increased serum apoA-II level in each genotype indicated that the HDL particles with apoA-II are relatively resistant to CETP-mediated lipid transfer. Serum apoE-rich HDL level was considerably higher in the Int14A homozygotes than in the compound heterozygotes, in spite of similar apoE-poor HDL-cholesterol levels, which may indicate that apoE-rich HDL is a better substrate for CETP than apoE-poor HDL. Although the apoE-rich and apoE-poor HDL subclasses were similar in the accumulation of cholesteryl ester and depletion of triglyceride, the accumulation of free cholesterol was unique to apoE-rich HDL, indicating inhibited cholesterol esterification on this lipoprotein. Clinical laboratories should be aware of the discrepancy in HDL-cholesterol measurements that comes from the different recoveries of apoE-rich HDL using commercial reagents. In conclusion, CETP deficiency causes considerable quantitative and compositional changes in HDL subclasses, reflecting a significant physiological role for CETP in HDL metabolism.

Adult↗

Change in morphological and functional cytodifferentiation induced by seminal vesicle mesenchyme in cell suspensions of rat Dunning prostatic adenocarcinoma cells.

Previous experiments have shown that seminal vesicle mesenchyme (SVM) can induce small 0.5 mm fragments of the rat Dunning tumor (DT) to undergo secretory differentiation with a concomitant reduction in tumorigenesis. In the present experiments Dunning tumor epithelial cells (DTE) were purified from DT cell suspensions by Percoll gradient centrifugation and recombined with neonatal rat SVM. The resultant tissue recombinants (SVM + DTE) were grafted under the renal capsule of male athymic mice and grown for 2 months. Under these conditions SVM induced the DTE to exhibit a highly differentiated secretory phenotype by forming ducts lined with tall columnar epithelial cells or large clear cells with pale cytoplasm. Undifferentiated epithelial cells of the parental DT were rarely observed in these tissue recombinants. The loss of tumorigenicity in SVM + DTE recombinants was associated with a striking reduction of epithelial 3H-thymidine labeling index in SVM + DTE recombinants (DT = 8.31%; SVM + DTE recombinants = 1.10%). Differences in putative secretory proteins were also observed by SDS-PAGE in SVM + DTE recombinants in comparison with DT. Testosterone metabolism was examined in epithelial cells recovered from grafts of DT vs. SVM + DTE tissue recombinants by thin layer chromatography and revealed that the major metabolite produced by DTE was androstenedione, whereas in epithelium isolated from SVM + DTE tissue recombinants the major androgen metabolite was 5alpha-DHT. Thus, after induction by SVM the DTE metabolized androgens in a pattern similar to the normal rat dorsal prostate. The SVM-induced changes in DTE suggest the possibility that emerging or established carcinomas might be regulated at least in part by their connective tissue microenvironment.

Adenocarcinoma↗