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11.
M D Brewer M N Burgess R J Dorgan R L Elliott P Mamalis B R Manger R A Webster 《Journal of medicinal chemistry》1989,32(9):2058-2062
A series of 1,2,3,4,6,7,8,12b-octahydropyrazino[2,1-alpha][2] benzazepine derivatives was prepared and the cestocidal activity of the compounds evaluated in an in vitro Taenia crassiceps screen. Many of these derivatives proved to be highly active, and 2-(cyclohexylcarbonyl)-4-oxo-1,2,3,4,6,7,8,12b- octahydropyrazino[2,1-alpha][2]benzazepine, epsiprantel (BAN) (22), was selected for further development. The structure-activity relationships are discussed. 相似文献
12.
Hormonal fluctuations associated with the menstrual cycle influence
appetite control and eating behaviour. Energy intake varies during the
reproductive cycle in humans and animals, with a periovulatory nadir and a
luteal phase peak. Patterns of macronutrient selection show less
consistency but a number of studies report carbohydrate cravings in the
premenstrual phase, particularly in women with premenstrual syndrome. The
cyclical nature of food cravings are frequently, but not invariably,
associated with depression. Fluctuations in appetite, cravings and energy
intake during the menstrual cycle may occur in parallel with cyclical
rhythms in serotonin, which can be accompanied by affective symptoms. The
premenstrual phase can be considered as a time when women are especially
vulnerable to overconsumption, food craving and depression; this is often
associated with low serotonin activity.
相似文献
13.
Production of interleukin 2 and interleukin 4 by immune CD4-CD8+ and their role in the generation of antigen-specific cytotoxic T cells 总被引:4,自引:0,他引:4
B Horvat J A Loukides L Anandan E Brewer P M Flood 《European journal of immunology》1991,21(8):1863-1871
In this report we investigated the production and role of interleukin (IL)2 and IL4 in the generation of antigen-specific cytotoxic T cells (CTL). We used as our model the ultraviolet-light-induced epithelial tumor 1591, a highly immunogenic regressor tumor which evokes a strong cell-mediated immune response leading to rejection. We show that IL2 and IL4 are differentially required for the development of optimal cytolytic activity to the 1591 tumor in primary and secondary in vitro splenic cultures. First, anti-IL2 receptor monoclonal antibody (mAb) significantly decreased specific cytotoxicity in both primary and secondary splenic mixed lymphocyte-tumor cell culture (MLTC) cultures, but anti-IL4 mAb inhibited the cytotoxic responses only secondary and not primary cultures. Second, when supernatants from MLTC were tested for lymphokine activity, primary cultures produced only IL2 while secondary cultures produced both IL2 and IL4. Splenic cells were then depleted of CD4+ cells by negative selection, or enriched for CD8+ cells by positive selection, and tested for lymphokine production and requirements. CD8+ cells could not generate significant CTL activity in primary cultures, but could in secondary MLTC. The addition of mAb to either IL2 or IL4 significantly inhibited the generation of CTL by CD8+ cells in these secondary MLTC.CD8+ cells were also found to produce both IL2 and IL4 in secondary MLTC by functional and Northern blot analysis. The production of IL2 and IL4 by CD8+ cells occurs during different phases of culture, with IL2 being produced early (days 1 and 2) and IL4 late (days 3-5). In addition, the requirement of CD8+ cells for both IL2 and IL4 is unique for that lymphokine. These results suggest that both IL2 and IL4 are both produced and required by CD8+ cells during secondary MLTC, and suggest an additional cellular source of IL4 production besides CD4+ T cells during antigen-specific CTL responses. 相似文献
14.
Telfer JF; Thomson AJ; Cameron IT; Greer IA; Norman JE 《Human reproduction (Oxford, England)》1997,12(10):2306-2312
Superoxide, an agent which attenuates the half-life of nitric oxide, is
metabolized and synthesized by superoxide dismutase (SOD) and xanthine
oxidase, respectively. Over the last few years much work has focused on the
role of nitric oxide in human parturition. The aim of this study was to
determine whether the onset of human parturition is associated with a
change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD),
manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the
uterus. Samples of myometrium, placenta, decidua and fetal membranes were
obtained from women before and after the onset of labour at term.
Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine
oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like
immunoreactivity was detected in syncytiotrophoblast cells, villous stromal
cells and endothelial cells of blood vessels in the placenta. In the
myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial
cells and to some vascular smooth muscle cells. In the fetal membranes we
observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion,
extravillous trophoblast and decidua. There was no difference in SOD enzyme
activity or staining intensity for SOD between different cell types before
and during labour. Xanthine oxidase immunoreactivity was identified in each
of the tissues examined and again there was no difference in immunostaining
in tissues obtained from women delivered before or after the onset of
labour. These results show that the pregnant uterus is capable of both
synthesizing and degrading superoxide and suggest that superoxide dismutase
and xanthine oxidase may play a role in the maintenance of uterine
quiescence during pregnancy, but not in the initiation of parturition.
相似文献
15.
Evaluation of intestinal parasite morphology in polyvinyl alcohol preservative: comparison of copper sulfate and mercuric chloride bases for use in Schaudinn fixative. 总被引:1,自引:2,他引:1 下载免费PDF全文
L S Garcia R Y Shimizu T C Brewer D A Bruckner 《Journal of clinical microbiology》1983,17(6):1092-1095
As a result of disposal problems inherent in the use of mercury compounds, many laboratories have considered using copper sulfate as a substitute for mercuric chloride in polyvinyl alcohol (PVA) preservative. The primary use for PVA-preserved specimens is the permanent stained smear, the most important technique for the identification of intestinal protozoa. A comparison of organism recovery and morphology was undertaken with PVA containing either copper sulfate or mercuric chloride base. Paired fecal specimens (417 pairs) were collected and examined with the Formalin-ether concentration and Trichrome stain techniques. Numbers of organisms recovered and helminth egg and protozoan morphology were assessed from the concentration sediment. Morphology, clarity of nuclear and cytoplasmic detail, overall color differences, and the ease or difficulty in detecting organisms in fecal debris were assessed from the permanent stained smear. No significant differences were found in the numbers and morphology of organisms seen in the concentration sediment. However, when the trichrome stain was used, the overall morphology of the intestinal protozoa preserved in PVA with copper sulfate was not equal to that seen with PVA with mercuric chloride. We do not recommend switching from mercuric chloride base to copper sulfate base unless that is the only option available for the preparation of permanent stained smears. 相似文献
16.
Hydrosalpinges adversely affect markers of endometrial receptivity 总被引:22,自引:10,他引:22
Meyer WR; Castelbaum AJ; Somkuti S; Sagoskin AW; Doyle M; Harris JE; Lessey BA 《Human reproduction (Oxford, England)》1997,12(7):1393-1398
While in-vitro fertilization (IVF) was initially developed in women with
tubal factor infertility, recent clinical studies have suggested that the
presence of hydrosalpinges lowers implantation and pregnancy rates. We
postulated that these hydrosalpinges cause impaired endometrial
receptivity. A total of 103 women with hydrosalpinges were prospectively
evaluated, and compared with 55 infertile and 44 fertile controls. All
women had endometrial biopsies during the window of implantation, analysed
by conventional histological criteria, and also stained for three integrin
markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha
vbeta3). Women with hydrosalpinges (cases) expressed significantly less of
the alpha vbeta3 integrin compared with controls. There was no difference
in expression of alpha1beta1 or alpha4beta1 among groups. A significantly
greater number of cases had out of phase histology and missing alpha vbeta3
(type I defects) and absent integrin expression despite normal histological
maturation (type II) defects, compared with controls. Of 20 women with
impaired endometrial receptivity who were also biopsied after hydrosalpinx
surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven
percent of type I and 57% of type II defects were corrected
postoperatively. Using markers of endometrial receptivity, this study
demonstrates that inflammatory hydrosalpinges have an adverse effect on
endometrial receptivity, which in some cases may be overcome by surgical
treatment of the hydrosalpinx.
相似文献
17.
Human visual cortex is organized into distinct visual field maps whose locations and properties provide important information about visual computations. There are two conflicting models of the organization and computational role of ventral occipital visual field maps. We report new functional MRI measurements that test these models. We also present the first coordinated measurements of visual field maps and stimulus responsivity to color, objects and faces in ventral occipital cortex. These measurements support a model that includes a hemifield map, hV4, adjacent to the central field representation of ventral V3. In addition, the measurements demonstrate a cluster of visual field maps in ventral occipital cortex (VO cluster) anterior to hV4. We describe the organization and stimulus responsivity of two new hemifield maps, VO-1 and VO-2, within this cluster. The maps and stimulus responsivity support a general organization of visual cortex based on clusters of maps that serve distinct computational functions. 相似文献
18.
Reorganization of human cortical maps caused by inherited photoreceptor abnormalities 总被引:3,自引:0,他引:3
We describe a compelling demonstration of large-scale developmental reorganization in the human visual pathways. The developmental reorganization was observed in rod monochromats, a rare group of congenitally colorblind individuals who virtually lack cone photoreceptor function. Normal controls had a cortical region, spanning several square centimeters, that responded to signals initiated in the all-cone foveola but was inactive under rod viewing conditions; in rod monochromats this cortical region responded powerfully to rod-initiated signals. The measurements trace a causal pathway that begins with a genetic anomaly that directly influences sensory cells and ultimately results in a substantial central reorganization. 相似文献
19.
Lee MH Gordon D Ott J Lu K Ose L Miettinen T Gylling H Stalenhoef AF Pandya A Hidaka H Brewer B Kojima H Sakuma N Pegoraro R Salen G Patel SB 《European journal of human genetics : EJHG》2001,9(5):375-384
Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM. 相似文献
20.
William Walker Craig W. Roberts James M. Brewer James Alexander 《European journal of immunology》1995,25(5):1426-1430
These studies describe the production of specific antibodies in human peripheral blood lymphocyte-reconstituted severe-combined immunodeficient (PBL-SCID) mice following vaccination with antigen from the protozoan parasite Toxoplasma gondii. To determine the effect of previous exposure of the lymphocyte donor to antigen, human-PBL-SCID animals were created by transferring peripheral blood lymphocytes from either a single T. gondii-seronegative or a single seropositive donor. These reconstituted animals were subsequently inoculated with T. gondii soluble tachyzoite antigen (STAg) entrapped within non-ionic surfactant vesicles as an immunological adjuvant. Animals were bled at pre-determined time points post-vaccination and the expression of human anti-STAg antibodies in the plasma determined by enzyme-linked immunosorbent assay. Human antibodies specific for STAg were readily inducible in both groups of reconstituted animals, although the pattern of isotype production differed markedly between groups. The response in animals reconstituted with lymphocytes from the T. gondii-seronegative donor consisted primarily of IgM and subsequently of IgG (predominantly IgG1). In animals reconstituted with lymphocytes from the seropositive donor, no parasite-specific IgM could be demonstrated. The detectable response to STAg consisted entirely of human antibodies of the IgG isotype (IgG1), indicative of a memory-type response. These results mimicked exactly the antibody responses that would be expected had the lymphocyte donors been directly challenged with either the antigen or the live infectious agent, demonstrating that the immune system within these animals is functional and reproducible with regard to both the primary and secondary responses of the human donors. 相似文献