Behavioral and endocrine effects of endotoxin in wild-type mice and mice deficient in interleukin 1: sickness behavior or adaptive response?
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Biomedical subjects
Publications and source records attributed to Y Endo.
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We examined the suppression of virus expression by cleaveage of the HIV-1 RNA gene using a mammalian tRNA 3' processing endoribonuclease and an External Guide Sequence Oligozyme (EGS) in vivo. We constructed an EGS expression vector that used the tRNA(met) promoter as an expression cassette for EGS. The EGS expression vector was targeted to the upstream region of gag, region. The EGS expression vector was co-transfected into COS cells with the HIV-1 gene plasmid vector. As compared with the EGS non-expressing cells and the EGS expressing cells, the EGS expressing cells with the targeted gag start codon had a clearly decreased amount of the HIV-1 gag p24 protein. The EGS expressing cells with the targeted gag start codon showed effective suppression of HIV-1 gene expression. Thus, these studies describe novel gene targeting agents for the inhibition of gene expression and antiviral activity.
Two new leukocyte removal filters, Nipro CF-1 and CF-2 (Nipo Medical Industries, Osaka, Japan), were evaluated. These non-woven polyester filters, which are gravity flow devices that require no priming and no rinsing after use, were developed for preparing 400 ml of whole blood or red cell concentrates from 400 ml of whole blood. A flow cytometric technique was developed to measure extremely low white blood cell (WBC) counts. To evaluate the efficiency of these filters, leukocyte counts were measured by three techniques: 1) electronic, 2) visual, and 3) flow cytometry. Flow cytometric counting was done using a Coulter EPICS-C cytometer (Coulter Corp., Hialeah, FL). Nipro CF-1 removed 99.97 +/- 0.01% (mean +/- SD, n = 14) of leukocytes measured by flow cytometry, and CF-1 recovered 90.7 +/- 4.47% (n = 21) of red blood cells. After filtration through CF-2, more than a 6 log10 (> 99.9999%) depletion of WBCs was detected in six samples, a 6 log10 (99.9999%) depletion of WBCs was detected in two samples, a 5 log10 (99.999%) depletion was detected in five samples, and a 4 log10 (99.99%) depletion was detected in one sample. CF-1, in which size and priming volume was smaller than other commercial leukocyte removal filters, accomplished a 3 log10 reduction in WBC count, compared with other commercial filters. CF-2 achieved a 4-6 log10 depletion of WBCs assayed by flow cytometry.
Bilateral breast tumors, a malignant phyllodes tumor in the right breast and an invasive lobular carcinoma in the left breast, occurred in a 47-year-old woman with 46XX/46XY mosaic karyotype in her peripheral blood lymphocytes and intersex external genitalia. Postmortem examination revealed bilateral ovotestis. Three of the patient's sisters also had breast cancer. In situ hybridization with a Y-specific probe revealed Y-chromosome-specific signal in both tumors, suggesting that the clonal origin of tumors in this patient was Y-containing cells. Androgen-receptor polymorphism also revealed a monoallelic X chromosome pattern in the recurrent phyllodes tumor tissue taken at autopsy, in addition to loss of heterozygosity demonstrated at locus TP53. The slippage of the CA repeats in the tumor was also shown at the loci of D5S82 and D11S527. The mechanistic basis for the occurrence of bilateral malignant tumors of the breast, XX/XY mosaicism, and familial clustering of breast cancer is still unknown. The present study, however, suggests that the sex chromosome abnormality may have modified the cancer phenotype in a manner similar to breast cancer in Klinefelter's syndrome (though phenotypically male) and the Y chromosome may have promoted cell growth.
PROBLEM: The effect of epidermal growth factor (EGF) on the acid-solubilized zona pellucida (ZP)-induced acrosome reaction was investigated in mouse sperm. METHOD: Mouse epididymal sperm were capacitated in modified Krebs-Ringer bicarbonate buffer (m-KRB) for 120 min and further treated with acid-solubilized ZP(4 zona/microliters) for an additional 60 min to induce the acrosome reaction. The chlortetracycline fluorescence assay was used to monitor the acrosome reaction. The acrosome reacted sperm featured the acrosome reacted (AR) pattern, which demonstrates the lack of fluorescence on the head and bright midpiece. RESULTS: EGF caused an early increase in the AR pattern in response to the acid-solubilized ZP in a dose-dependent manner. The EGF-dependent stimulation of the ZP-induced acrosome reaction was inhibited by an inhibitor of protein tyrosine kinases, genistein or activators of Ca++ and phospholipid-dependent protein kinase (protein kinase C). Furthermore, the stimulatory effect of EGF was not attenuated when sperm were capacitated in the presence of islet-activating protein, an inactivator of inhibitory guanine nucleotide-binding regulatory protein (Gi protein). CONCLUSION: EGF stimulates the ZP-induced acrosome reaction in a manner that is independent of the Gi protein. The EGF action is regulated by protein tyrosine kinase and protein kinase C.
Renal vasoconstrictor action of angiotensin II (Ang II) is exaggerated in the spontaneously hypertensive rat (SHR) before development of hypertension. We have recently demonstrated that in the rabbit afferent arteriole (Af-Art) activation of the AT2 receptor causes vasodilation, which modulates the vasoconstrictor action of Ang II mediated by the AT1 receptor. In this study, we tested the hypothesis that vasoconstrictor action of Ang II is exaggerated in SHR Af-Arts due to an impaired function of the AT2 receptor before development of hypertension. Af-Arts were microdissected from the superficial cortex of 4- to 5-week-old SHR or age-matched Wistar Kyoto rats (WKY), and perfused at 60 mm Hg in vitro. Ang II (10(-11) to 10(-8) M) decreased the luminal diameter of Af-Arts of both strains in a dose-dependent manner. However, the constriction was stronger in SHR; at 10(-10) M, the diameter decreased by 34 +/- 4% in SHR (n = 6) compared to 18 +/- 3% in WKY (n = 6; p < 0.01). Pretreatment with PD123319 (PD), an AT2 receptor antagonist, significantly augmented Ang II-induced constriction in WKY but not SHR Af-Arts; at 10(-10) M, the diameter now decreased by 41 +/- 5 and 37 +/- 1% in SHR (n = 6) and WKY (n = 6), respectively. Thus, blockade of the AT2 receptor abolished the difference in Ang II action on Af-Arts between strains. Moreover, with the AT1 receptor blockade Ang II caused dose-dependent dilation of preconstricted Af-Arts only in WKY (27 +/- 5% at 10(-8) M, n = 5), and the dilation was abolished by simultaneous treatment with PD. In contrast, no such dilation was observed in SHR Af-Arts. These results suggest that activation of the AT2 receptor modulates AT1 receptor vasoconstriction in WKY Af-Arts, while impaired modulatory function of AT2 receptor may play a role in the exaggerated vasoconstrictor action of Ang II on the Af-Art of prehypertensive SHR.
We report an Rh(D)-negative man with myelodysplastic syndrome who produced six anti-erythrocyte alloantibodies (anti-D, -C, -E, -Dia, -Jka and -S) in succession. Three of these antibodies (anti-E, -Jka and -S) were not noted until delayed hemolytic transfusion reactions occurred. Treatment with cortico-steroids was effective in preventing both further formations of antibodies and other transfusion reactions. It was very difficult to find blood compatible with the patient, but repetitive blood transfusions were required for his progressive anemia and thrombocytopenia. Several problems concerning the transfusion of blood in such a case are discussed.
A 28-year-old woman developed central pontine myelinolysis (CPM) following severe hyponatremia. Radiological examinations demonstrated a characteristic pontine lesion of CPM. Her neurological symptoms (drowsiness, emotional lability, dysarthria, dysphagia, and quadriparesis) were improved dramatically by treatment with thyrotropin-releasing hormone (TRH) and rehabilitation. However, results of repeat computed tomographic (CT) scans of the brain remained unchanged. This case therefore suggests that TRH may be beneficial for the treatment of CPM, and that CT findings appear to be a limited prognostic indicator for CPM.
Feline immunodeficiency virus (FIV) was first isolated in 1987 from a cat with an acquired immunodeficiency syndrome (AIDS)-like disease. Since then, FIV has been subject of intensive research. Perturbation in cytokine production observed in human immunodeficiency virus infection (HIV) is paralleled in the FIV-infected cat. Interferon gamma (IFN-gamma) is a type 1 lymphokine that exert protective effects during infection through upregulation of cellular immunity and phagocytic functions. The present study was carried out to examine the expression of IFN-gamma in a feline T-lymphoid cell line (Fel-039) infected with FIV as well as the viral replication in these cells after addition of recombinant-type feline IFN (rIFn). We found a marked inhibition of IFN-gamma release in Fel-039 cells infected with FIV which might be pivotal for high viral replication. Infection of Fel-039 cells with FIV resulted in an increase of the reverse transcriptase (RT) activity in the culture supernatant. When the cells were cultured in the presence of rIFN a significant dose-dependent inhibition of RT activity of FIV was detected without cytotoxicity. On the basis of these in vitro results, we suggest that IFN therapies aimed at restoring depleted level of this important cytokine in FIV infected T-cells make this compound a promising candidate for development of suitable drugs for AIDS treatment.
BACKGROUND: We have reported that only psychological stress, but not physical stress, induces a significant elevation of body temperature following repeated exposures, however, we did not evaluate the effects of psychological stress in an acute case. In this study, we evaluated hormonal and physiological changes caused by an acute exposure to psychological stress in rats, compared to physical stress. MATERIAL AND METHODS: Adult male Wistar rats, weighing 300-400 g, were exposed to foot shock or non-foot shock stress induced by the communication box for 1 h. The rats in the foot shock group received the electrical shock directly, and the rats in the non-foot shock group could escape from the electrical shock, but received various emotional stimuli from other foot-shocked rats in the communication box. Before, during and after the exposure to each stress, we measured body temperature and motor activity by means of the telemetry system, and also measured plasma corticosterone level by radioimmunoassay. RESULTS: Non-foot shocked rats showed a significant elevation of body temperature (from 37.18 +/- 0.13 degrees C at baseline to the peak, 38.71 +/- 0.10 degrees C), in association with a slight but significant increase in motor activity, and a temporal elevation of plasma corticosterone (from 22.1 +/- 1.6 microg/dl at baseline to 29.5 +/- 2.7 microg/dl). These changes were at a lower magnitude compared to foot shocked rats. CONCLUSION: It is concluded that psychological stress, generated by the communication box, could have lower influences as an acute stress than physical stress.
It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). The administration of 3'-MeDAB in combination with 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) delayed the appearance of oval cells and the formation of hyperplastic nodules, which were observed in the liver from 3 and 5 weeks, respectively, after the onset of 3'-MeDAB feeding, and also delayed the transient increase of serum alpha-fetoprotein level, which transiently peaked at 5 weeks, and completely suppressed the transient increase of tissue thymidylate synthetase activity, but not thymidine kinase, which were induced by 3'-MeDAB at 5 weeks, and finally reduced markedly the incidence of hepatocarcinomas. These results indicate that the suppression of de novo synthesis in pyrimidine metabolism prevents hepatocarcinogenesis.
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We investigated the synergistic efficacy of CDDP and UFT, an oral anticancer derivative of 5-fluorouracil, on DNA synthesis of 3'-MeDAB-induced hepatocarcinomas in rats. Chronic treatment with CDDP slightly reduced tissue activities of thymidylate synthetase and thymidine kinase in the hepatocarcinomas, and, moreover, simultaneous administration of a low dose of UFT with CDDP markedly suppressed both enzyme activities, i.e., UFT and CDDP showed a potent synergism on DNA synthesis in hepatocarcinomas.
To elucidate the degree of malignancy or the host-killing ability of rat ascites hepatoma AH66F, AH66 and AH130, the chick embryo-polymerase chain reaction system was used to measure the metastasis of these hepatoma cells. When inoculated into the chorioallantoic membrane vein of 10-day fertilized chicken eggs, AH66F cells metastasized in the lung and liver in an inoculum size-dependent manner up to 10(6) cells, but AH66 and AH130 cells only a little even at 10(6) cells. The adhesion of AH66F cells, but not other hepatoma cells, to rat mesentery-derived mesothelial cells was inhibited by protein kinase C inhibitors NA-382 and H-7, but not by other protein kinase inhibitors, and the life-span of rats inoculated with AH66F cells was also prolonged by treatment with Na-382. AH66F cells, pretreated with protein kinase inhibitors were inoculated into the fertile eggs and micrometastasis was assayed. Metastasis of AH66F cells in the chick embryo was clearly decreased by treatment with NA-382. The chick embryo-polymerase chain reaction system is a sensitive method to measure the metastatic ability of mammalian tumor cells, and the high metastatic ability of AH66F cells is probably related to their adhesion to target cells mediated by the protein kinase C pathway.