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1.
We attempted to determine the effects of the combination of a 5-alpha reductase inhibitor and an antiandrogen on rat ventral prostate and seminal vesicle weight. We also attempted to determine whether the prostatic cell death gene TRPM-2 would be expressed using this combination of drugs. Adult male Sprague-Dawley rats were randomly assigned to 7 groups of 15 animals. Four groups served as controls: an intact group sacrificed at the initiation of the trial (group 1), a castrate control group (group 2), an intact control group (group 3), and a group treated with the combination of an LHRH agonist plus antiandrogen (group 7). Three other groups were treated with daily subcutaneous injections of 5 alpha reductase inhibitor (group 5), a nonsteroidal pure antiandrogen (group 4) or both (group 6). After 5 days of treatment 5 animals in each group were sacrificed and prostatic tissue was assayed for the androgen repressed prostatic cell death gene TRPM-2. At 30 days (35 days for group 7) the remaining animals were sacrificed and their ventral prostates, seminal vesicles, and testes (except group 3) were weighed. The combination group (group 6) had a significantly lower prostate weight than either of the monotherapy groups (4, 5), or intact control groups, was equivalent to group 7 but was significantly heavier than the castrate group 2. The seminal vesicle weights of the combination group 6 were significantly lower than the monotherapy groups (4, 5), intact control group, castrate group (3) and was equivalent to group 7. Only castration was able to induce expression of the cell death gene TRPM-2. In this model, the combination of 5 alpha reductase inhibitor and an antiandrogen is as effective a mode of androgen ablation as combination therapy of LHRH agonist plus antiandrogen. Clinically, this combination may translate into adequate androgen blockade without impotence or other side effects of testosterone deprivation. Clinical trials appear warranted to assess this hypothesis. 相似文献
2.
Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones 下载免费PDF全文
Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4+ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio 0.1 and 1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P<0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H2-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H1- and H3-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H2-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma. 相似文献
3.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
4.
M. Fleshner D. Bellgrau L.R. Watkins M.L. Laudenslager S.F. Maier 《Journal of neuroimmunology》1995,56(1):45-52
Exposure to aversive events or Stressors modulates various aspects of immune function. We have previously reported that exposure to an acute Stressor, inescapable tail shock (IS), resulted in a shift in T cell subpopulations in rat mesenteric lymph nodes but not in cervical lymph nodes (Fleshner et al. (1992) J. Neuroimmunol. 41, 131–142). The mesenteric ratio was increased immediately after exposure to IS and was due primarily to an increase in the percent of CD4+ cells. The present experiments were designed to determine the relationship between the IS-associated phenotypic shift and its significance in the function of CD4+ T cells. The function assessed was the in vitro proliferative response to alloantigens coded for by the Major Histocompatibility Complex (MHC). Using the mixed lymphocyte reaction (MLR), we report that exposure to IS resulted in a decrease in the MLR response of cells from both cervical and mesenteric lymph nodes. Depletion of macrophages (nylon wool adherent cells) eliminated the IS-induced reduction and co-culture of macrophages (irradiation-insensitive cells) from shocked rats produced the suppression. One interpretation of these data is that exposure to IS resulted in the activation of macrophages and the release of a suppressive factor which reduced the MLR response of peripheral lymph node lymphocytes. 相似文献
5.
Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. 总被引:4,自引:0,他引:4
Dietary intake of tomatoes and tomato products containing lycopene, an antioxidant carotenoid, has been shown in recent studies to reduce the risk of cancer. This study was conducted to investigate the serum and prostate tissue lycopene and other major carotenoid concentrations in cancer patients and their controls. Serum lipid and protein oxidation was also measured. Twelve prostate cancer patients and 12 age-matched subjects were used in the study. Significantly lower serum and tissue lycopene levels (44%, p = 0.04; 78%, p = 0.050, respectively) were observed in the cancer patients than in their controls. Serum and tissue beta-carotene and other major carotenoids did not differ between the two groups (p = 0.395 and p = 0.280, respectively). Although there was no difference (p = 0.760) in serum lipid peroxidation between cancer patients and their controls (7.09 +/- 0.74 and 6.81 +/- 0.56 mumol/l, respectively), serum protein thiol levels were significantly lower among the cancer patients (p = 0.026). This study demonstrates that the status of lycopene but not other carotenoids in prostate cancer patients is different from controls. The role of dietary lycopene in preventing oxidative damage of biomolecules and thereby reducing the risk of prostate cancer needs to be evaluated in future studies. 相似文献
6.
HABIB BOUKERCHE MARIE-HéLèNE RUCHAUD-SPARAGANO CHRISTINE R OUEN JEAN BROCH IER CéCILE KAPLAN & JOHN LOUIS MCGREGOR 《British journal of haematology》1996,92(2):442-451
P-selectin (also called CD62, GMP-140, PADGEM, CD62P) is a recently described member of a family of vascular adhesion receptors expressed by activated platelets and endothelial cells that are involved in leucocyte cell adhesion. The aim of this study was to characterize a new monoclonal antibody (LYP7) directed against activated human blood platelets that inhibits ristocetin-induced platelet aggregation. Immunoadsorbent affinity chromatography and immunoprecipitation studies showed that LYP7 (IgG1) bound a surface-labelled glycoprotein (GP) which changed its apparent molecular mass (Mr) on reduction from 138 kD (situated below GPIIb) to 148 kD (above GPIIbα). LYP7 and S12, a monoclonal antibody directed against P-selectin immunoprecipitated the same band. Using ELISA assay, purified P-selectin was shown to bind LYP7 and S12 monoclonal antibodies. Binding sites of 125I-labelled LYP7, which was greatly increased on thrombin-stimulated (2 U/ml) washed platelets (10825±2886, mean ±SD) (Kd=1.5±0.5 nm ) compared to resting platelets (2801±1278, mean ±SD) (Kd=1.5±0.6 nm ), was found to be normal on thrombin-stimulated platelets taken from a patient with grey platelet syndrome or a patient with Glanzmann thrombasthenia. LYP7 (IgG1, F(ab′)2 or Fab fragments) inhibited ristocetin-induced platelet aggregation of platelets in a dose-dependent fashion without affecting the binding of von Willebrand (vWf ) factor. However, agglutination of formaldehyde-fixed platelets induced by ristocetin was not affected by monoclonal antibody LYP7. In addition, the binding of thrombin-activated platelets to neutrophils was inhibited by monoclonal antibody LYP7. These results strongly suggest that P-selectin, by promoting cell–cell contact, may play an active role in platelet–platelet interactions. 相似文献
7.
Hanzel Jurij Almradi Ahmed Istl Alexandra C. Yang Mei Lucy Fleshner Katherine A. Parker Claire E. Guizzetti Leonardo Ma Christopher Singh Siddharth Jairath Vipul 《Digestive diseases and sciences》2022,67(2):646-660
Digestive Diseases and Sciences - Postoperative complication rates in patients with inflammatory bowel disease (IBD) receiving preoperative biologics have been analyzed without considering the... 相似文献
8.
Samuel J Bowers Sophie Lambert Shannon He Christopher A Lowry Monika Fleshner Kenneth P Wright Jr Fred W Turek Martha H Vitaterna 《Sleep》2021,44(6)
Study ObjectivesSleep deprivation induces systemic inflammation that may contribute to stress vulnerability and other pathologies. We tested the hypothesis that immunization with heat-killed Mycobacterium vaccae NCTC 11659 (MV), an environmental bacterium with immunoregulatory and anti-inflammatory properties, prevents the negative impacts of 5 days of sleep disruption on stress-induced changes in sleep, behavior, and physiology in mice.MethodsIn a 2 × 2 × 2 experimental design, male C57BL/6N mice were given injections of either MV or vehicle on days –17, –10, and –3. On days 1–5, mice were exposed to intermittent sleep disruption, whereby sleep was disrupted for 20 h per day. Immediately following sleep disruption, mice were exposed to 1-h social defeat stress or novel cage (control) conditions. Object location memory (OLM) testing was conducted 24 h after social defeat, and tissues were collected 6 days later to measure inflammatory markers. Sleep was recorded using electroencephalography (EEG) and electromyography (EMG) throughout the experiment.ResultsIn vehicle-treated mice, only the combination of sleep disruption followed by social defeat (double hit): (1) increased brief arousals and NREM beta (15–30 Hz) EEG power in sleep immediately post-social defeat compared to baseline; (2) induced an increase in the proportion of rapid-eye-movement (REM) sleep and number of state shifts for at least 5 days post-social defeat; and (3) induced hyperlocomotion and lack of habituation in the OLM task. Immunization with MV prevented most of these sleep and behavioral changes.ConclusionsImmunization with MV ameliorates a stress-induced sleep and behavioral phenotype that shares features with human posttraumatic stress disorder. 相似文献
9.
B-chronic lymphocytic leukemia (CLL) patients frequently suffer from moderate to severe hypogammaglobulinemia. This complication is a serious cause of morbidity and mortality in this disorder. There is recent evidence that natural killer (NK) cells modulate B-cell immunoglobin (Ig) synthesis/secretion. The authors therefore evaluated the circulating NK cells from B-CLL patients on their ability to regulate mitogen-induced B-cell Ig synthesis. Blood, NK cells (CD16+, CD3-) from three B-CLL patients with hypogammaglobulinemia were able to clearly down-regulate the pokeweed mitogen (PWM)-induced-B-cell Ig secretion. In contrast, CD16+, CD3- cells from age-sex-matched controls or B-CLL patients with normal Ig were either nonregulatory or enhanced mitogen-induced B-cell Ig secretion. An alternative explanation for hypogammaglobulinemia in B-CLL patients is the immunomodulation of B- cell Ig production/secretion by CD16+, CD3- blood cells. 相似文献
10.