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861.
A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43) 总被引:2,自引:0,他引:2
Eckman CB; Mehta ND; Crook R; Perez-tur J; Prihar G; Pfeiffer E; Graff- Radford N; Hinder P; Yager D; Zenk B; Refolo LM; Prada CM; Younkin SG; Hutton M; Hardy J 《Human molecular genetics》1997,6(12):2087-2089
We report a novel mutation in the amyloid precursor protein gene (APP
I716V) which probably leads to familial early onset Alzheimer's disease
with an onset age in the mid 50s. Cells transfected with cDNAs bearing this
mutation produce more A beta 1-42(43) than those transfected with wild-type
APP and this effect is additive with that of the previously reported APP
V717I mutation thus providing a novel approach for further increasing A
beta 1-42(43) in model systems.
相似文献
862.
Juul A; Scheike T; Pedersen AT; Main KM; Andersson AM; Pedersen LM; Skakkebaek NE 《Human reproduction (Oxford, England)》1997,12(10):2123-2128
Few studies exist on the physiological changes in the concentrations of
growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding
proteins (IGFBP) within the menstrual cycle, and some controversy remains.
We therefore decided to study the impact of endogenous sex steroids on the
GH-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women
(aged 18-40 years). Blood sampling and urinary collection was performed
every morning at 0800 h for 32 consecutive days. Every second day the
subjects were fasted overnight before blood sampling. Follicle stimulating
hormone, luteinizing hormone (LH), oestradiol, progesterone, IGF-I,
IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and
GH were determined in all samples, whereas insulin and IGFBP-1 were
determined in fasted samples only. Serum IGF-I concentrations showed some
fluctuation during the menstrual cycle, with significantly higher values in
the luteal phase compared to the proliferative phase (P < 0.001). Mean
individual variation in IGF-I concentrations throughout the menstrual cycle
was 13.2% (SD 4.3; range 0.1-18.3%). There were no cyclic changes in
IGFBP-3 serum concentrations and no differences in IGFBP-3 concentrations
between the luteal and the proliferative phases. Mean individual variation
in IGFBP- 3 concentrations throughout the menstrual cycle was 8.8% (SD 2.7;
range 3.2-14.1). IGFBP-1 concentrations were inversely associated with
insulin concentrations, and showed a significant pre-ovulatory increase
that returned to baseline at the day of the LH surge. Fasting insulin
concentrations showed large fluctuations throughout the menstrual cycle
without any distinct cyclic pattern. No cyclic changes in urinary GH
excretion during menstrual cycle were detected. We conclude that, although
IGF-I concentrations are dependent on the phase of the menstrual cycle, the
variation in IGF-I concentrations throughout the menstrual cycle is
relatively small. Therefore, the menstrual cycle does not need to be
considered when evaluating IGF-I or IGFBP-3 serum values in women suspected
to have GH deficiency.
相似文献
863.
S Neema LM Atuyambe E Otolok-Tanga C Twijukye A Kambugu L Thayer K McAdam 《African health sciences》2012,12(2):231-239
Background
Stigma has been associated with chronic health conditions such as HIV/AIDS, leprosy, tuberculosis, Mental illness and Epilepsy. Different forms of stigma have been identified: enacted stigma, perceived stigma, and self stigma. Stigma is increasingly regarded as a key driver of the HIV/AIDS epidemic and has a major impact on public health interventions.Objectives
The initiative was to provide activities in the clinic while patients waited to be seen by healthcare professionals. It was envisaged this would contribute to reduction of clinic based stigma felt by clients.Methods
This was a repeated cross-sectional survey (October–November 2005 and March–April 2007) that was conducted at the Infectious Diseases Institute clinic (IDC) at Mulago, the national referral hospital in Uganda. We utilized quantitative (survey) and qualitative (key informants, focus group discussions) methods to collect the data. Data were collected on stigma before the creativity initiative intervention was implemented, and a second phase survey was conducted to assess effectiveness of the interventions.Results
Clients who attended the IDC before the creativity intervention were about twice as likely to fear catching an infection as those who came after the intervention. The proportion that had fears to be seen by a friend or relative at the clinic decreased. Thus during the implementation of the Creativity intervention, HIV related stigma was reduced in this clinic setting.Conclusions
The creativity intervention helped to build self esteem and improved communication among those attending the clinic; there was observed ambiance at the clinic and clients became empowered, with creative, communication and networking skills. Improved knowledge and communication are key in addressing self stigma among HIV positive individuals. 相似文献864.
Wendy M. Gordon CPM LM MPH Safiya A. U. McCarter ND MSAOM Susan J. Myers CPM LM MPH 《Journal of Midwifery & Women's Health》2016,61(6):721-725
Creating a socially conscious educational environment is an imperative if health care practitioners are to have a significant impact on health inequities. The effects of practitioner bias, prejudice, and discrimination on health and health outcomes have been well documented in the literature. Individuals being trained to provide health care will be entering into an increasingly diverse world and must be equipped with the appropriate knowledge and skills in order to meet the needs of those seeking their care. Cultural competency training in medical education has evolved over the past 15 years since the Institute of Medicine's 2002 report, Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. As research on the effectiveness of this training has emerged, several authors have called for the integration of antiracism training into the cultural competency curriculum, but few have found effective ways of doing so. This article describes the approach of one midwifery program in order to inform clinical education programs across the spectrum of health care practitioners. 相似文献
865.
Saraswathi Vedam CNM RM MSN Lawrence Leeman MD MPH Melissa Cheyney PhD CPM LDM Timothy J. Fisher MD MS Susan Myers LM CPM MPH Lisa Kane Low CNM PhD Catherine Ruhl CNM MS 《Journal of Midwifery & Women's Health》2014,59(6):624-634
Women's heightened interest in choice of birthplace and increased rates of planned home birth in the United States have been well documented, yet there remains significant public and professional debate about the ethics of planned home birth in jurisdictions where care is not clearly integrated across birth settings. Simultaneously, the quality of interprofessional interactions is recognized as a predictor of health outcomes during obstetric events. When care is transferred across birth settings, confusion and conflict among providers with respect to roles and responsibilities can adversely affect both outcomes and the experience of care for women and newborns. This article reviews findings of recent North American studies that examine provider attitudes toward planned home birth, differing concepts of safety of birthplace as reported by women and providers, and sources of conflict among maternity care providers during transfer from home to hospital. Emerging evidence and clinical exemplars can inform the development of systems for seamless transfer of women and newborns from planned home births to hospital and improve experience and perceptions of safety among families and providers. Three successful models in the United States that have enhanced multidisciplinary cooperation and coordination of care across birth settings are described. Finally, best practice guidelines for roles, communication, and mutual accommodation among all participating providers when transfer occurs are introduced. Research, health professional education, and policy recommendations for incorporation of key components into existing health care systems in the United States are included. 相似文献
866.
自身免疫性肝炎患者自身抗体的测定及意义 总被引:2,自引:1,他引:2
目的:探讨自身抗体测定对诊断自身免疫性肝炎的临床意义.方法:采用间接免疫荧光法(IIF)检测47例自身免疫性肝炎患者、158例非自身免疫性肝炎患者及40例健康体检者体内抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗中性粒细胞胞质抗体(ANCA)、抗线粒体抗体(AMA)等自身抗体,ELISA法检测抗MPO抗体,并对结果进行回顾性分析.结果:ANA、SMA及ANCA检出率的比较,结果显示AIH中阳性率最高为SMA(66.0%, 31/47),而非AIH中则为6.3%(10/158),两组差异有非常显著性意义(P<0.01).经X2检验, SMA、AMA和MPO抗体检测在AIH与PBC中,均有非常显著性意义(P<0.01).AIH各型自身抗体检测结果表明,AIH-Ⅰ与ANA、SMA和ANCA相关,AIH-Ⅱ与LKM相关,而AIH=Ⅲ与SLA和ANCA相关.结论:血清自身抗体的检测对诊断、治疗和阻止自身免疫性肝炎的发展有着十分重要作用,对提高AIH在临床上同其他肝病鉴别诊断和治疗有着非常重要的意义. 相似文献
867.
Fanconi anemia genes act to suppress a cross-linker-inducible p53- independent apoptosis pathway in lymphoblastoid cell lines 总被引:5,自引:1,他引:5
Hypersensitivity to cross-linking agents such as mitomycin C (MMC) is characteristic of cells from patients suffering from the inherited bone marrow failure syndrome. Fanconi anemia (FA). Here, we link MMC hypersensitivity of Epstein-Barr virus (EBV)-immortalized FA lymphoblasts to a high susceptibility for apoptosis and p53 activation. In MMC-treated FA cells belonging to complementation group C (FA-C), apoptosis followed cell cycle arrest in the G2 phase. In stably transfected FA-C cells, plasmid-driven expression of the wild-type cytoplasmic FAC protein relieved MMC-dependent G2 arrest and suppressed p53 activation. However, in both FA and non-FA lymphoblasts, p53 seemed not to be instrumental in the induction of MMC-dependent apoptosis, since overexpression of a dominant-negative p53 mutant failed to affect cell survival. In addition, no differences in the level of Bcl-2 expression, an inhibitor of apoptosis, were detected between FA and non- FA cells either in the absence or presence of MMC. Our findings suggest that FAC and the other putative FA gene products may function in a yet to be identified p53-independent apoptosis pathway. 相似文献
868.
Abnormal assembly of membrane proteins in erythroid progenitors of patients with beta-thalassemia major 总被引:1,自引:1,他引:1
Aljurf M; Ma L; Angelucci E; Lucarelli G; Snyder LM; Kiefer CR; Yuan J; Schrier SL 《Blood》1996,87(5):2049-2056
The life threatening anemia in beta-thalassemia major (Cooley's anemia) is characterized by profound intramedullary lysis, the cause of which is incompletely understood. Using marrow obtained from beta thalassemia major patients undergoing allogeneic bone marrow transplantation in Pesaro Italy, it became possible to directly study the mechanism of the intramedullary hemolysis. Based on our previous studies, we hypothesized that the unmatched alpha globin chains would interfere with normal assembly of erythroid precursor membrane proteins. Patient and control erythroid precursors were reacted with monospecific polyclonal rabbit antibodies directed against spectrin, band 3, and band 4.1 and with a monoclonal anti-alpha globin chain antibody. Using laser confocal fluorescence microscopy, normal erythroid precursors show no alpha globin chain accumulation and exhibited uniformly smooth rim fluorescence of the three membrane proteins. In some thalassemic precursors, spectrin appeared to interact with large alpha globin accumulations, and in many of these cells the spectin appeared clumped and discontinuous. Band 4.1 interacted strongly with accumulations of alpha globin in thalassemic precursors to produce bizarrely clumped zones of abnormal band 4.1 distribution. Band 3 was incorporated smoothly into thalassemic erythroblast membranes. However, the proerythroblasts and basophilic erythroblasts were significantly deficient in band 3. Thus, accumulations of alpha globin in beta- thalassemia major colocalized with and disrupt band 4.1 and spectrin assembly into the membrane. The cause of deficient band 3 incorporation into thalassemic proerythroblast membranes remains unknown. These profound membrane alterations would likely contribute to the intramedullary lysis seen in Cooley's anemia. 相似文献
869.
Provan D; Bartlett-Pandite L; Zwicky C; Neuberg D; Maddocks A; Corradini P; Soiffer R; Ritz J; Nadler LM; Gribben JG 《Blood》1996,88(6):2228-2235
In chronic lymphocytic leukemia (CLL), clonal rearrangement of the immunoglobulin heavy chain locus (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. At the time of initial presentation, DNA from patients with CLL was polymerase chain reaction (PCR)-amplified using consensus Variable (VH) and Joining (JH) region primers using complementarity determining region III consensus region primers or a panel of VH family-specific framework region 1 (FR1) primers. The clonal product was directly sequenced and patient-specific probes constructed using N region nucleotide sequences. We amplified and sequenced the CDRIII region and designed patient specific oligonucleotide probes for the detection of MRD in 55 of 66 patients (84%, 90% Confidence Intervals (CI): 74% to 90%) with poor prognosis CLL referred for autologous and allogeneic bone marrow transplantation (BMT). To determine the clinical utility of this technique, PCR amplification was performed on patient samples at the time of and following autologous (21 patients) and allogeneic (10 patients) BMT in whom serial bone marrow samples obtained after BMT were available for analysis. We show that the persistence of MRD after BMT is associated with increased probability of relapse. In all cases that have relapsed to date, the IgH CDRII region was identical at the time of initial presentation and at relapse suggesting that clonal evolution of the IgH locus is unusual in this disease. The finding that a significant number of patients remain disease free and with no evidence of PCR-detectable MRD after BMT suggests that high-dose therapy may contribute to improved outcome in selected patients with CLL. 相似文献
870.
Inhibition of delayed-type contact hypersensitivity in mice deficient in both E-selectin and P-selectin 总被引:11,自引:1,他引:11
Leukocyte rolling and emigration in response to inflammatory stimuli appears to involve both E-selectin- and P-selectin-dependent adhesion, which suggests that these molecules have overlapping functions. To clarify their relative contributions in chronic inflammation, we examined delayed-type contact hypersensitivity (DTH) responses in P- selectin, E-selectin, and E-/P-selectin-deficient mice. Oxazolone- induced increases in ear thickness and ear weight were equivalent in wild-type mice and in P-selectin and E-selectin mutants, but were significantly reduced in E-/P-selectin mutants. The number and area of microabscesses on the ears of E-/P-deficient mice were decreased by 72% and 93%, and the number of leukocytes invading the subdermal ear tissue was reduced. T cells from E-/P-deficient mice transferred oxazolone reactivity into naive wild-type mice. However, when donor T cells from wild-type mice were transferred into E-/P-selectin-deficient mice, the DTH response was significantly impaired. These results show that leukocyte recruitment into a subacute inflammatory reaction can occur when either P-selectin or E-selectin is present, but is significantly reduced when both selectins are absent. Both P- and E-selectin are likely to play important roles in the development and maintenance of inflammatory diseases. 相似文献