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21.
M. M. Weber P. Luppa D. Engelhardt 《Journal of molecular medicine (Berlin, Germany)》1989,67(14):707-712
Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.Abbreviations CV
coefficient of variation
- MV
mean value
- SEM
standard error of the mean
- f
female
- m
male
- K
ketoconazole
- ACTH
adrenocorticotropic hormone
- DHEA
dehydroepiandrosterone
- DHEAS
dehydroepiandrosterone sulfate
- A
androstenedione
- T
testosterone
- F
cortisol
- P
progesterone
- H
hirsutism
- C
Cushing's disease
- EAS
ectopic ACTH syndrome
- ATU
adrenal tumor 相似文献
22.
23.
This paper describes the tragic case of a young woman who died of cancer of
the colon after successfully donating eggs to her younger sister. Although
there is no direct link between her operation and the subsequent
development of bowel carcinoma, this case imparts a feeling of unease when
seen in conjunction with other cases reported during the last few years. It
is a reminder that little is known of the long-term consequences of some
aspects of assisted conception. Women undergoing ovarian stimulation for
themselves or a matched recipient have the right to be advised, in an
agreed format, that there is some concern about unproven potential risks
from the stimulatory drugs. The safety of egg donors must assume priority
over all other considerations, including lack of donors or any moral
position. The recent decision by the Human Fertilisation and Embryology
Authority (HFEA) to withdraw any form of payment or recompense to egg
donors does not seem to us to be based on a balance of scientific advances,
patient needs and the ethics of gamete supply. They state that the
intention to withdraw payments was implicit in the 1990 Human Fertilisation
and Embryology (HFE) Act. However the Act was based on the Warnock report
made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility
drugs had not yet caused any unease. The Act provided the HFEA with
discretionary powers to issue directions so that the future policies would
be consistent with any emerging new medical evidence. It is imperative that
the HFEA provide convincing evidence on how the current policy of payment
to donors harms society, donors or recipients, and how in the UK the new
policy will improve medical practice in assisted conception. Successful
pilot studies must precede the implementation of any new policy. Failure to
do this could cause irreversible harm to the practice of assisted
conception using donor gametes, which will ultimately be against the basic
aims of the 1990 HFE Act.
相似文献
24.
25.
Guimezanes A Barrett-Wilt GA Gulden-Thompson P Shabanowitz J Engelhard VH Hunt DF Schmitt-Verhulst AM Engelhardt VH 《European journal of immunology》2001,31(2):421-432
We studied the molecular basis for CD8 independence of in vivo generated (BM3.3) versus CD8 dependence of in vitro sensitized (KB5.C20/Des) alloreactive H-2K(b)-specific cytotoxic T lymphocytes (CTL). Using microcapillary high-performance liquid chromatography fractionation of H-2K(b) eluates, mass spectrometry and CTL reconstitution assays, we determined that BM3.3 and KB5.C20 recognize, respectively, a single peptide (pBM1) expressed on 8,000 H-2K(b) molecules per allogeneic cell, and three distinct peptides (pKB1, 2, 3), each expressed on around 200 H-2K(b) molecules per allogeneic cell. CD8 (in)dependence was intrinsic to the respective TCR/H-2K(b)-peptide interactions. KB5.C20 and BM3.3 TCR illustrate the correlation that appears to exist between CD8 dependence/low affinity and in vitro sensitization as opposed to low dependency on CD8 and high TCR affinity observed after in vivo sensitization. The results suggest that CD8-dependent alloreactive CTL obtained in vitro with high frequency correspond to low-affinity TCR from the MHC-biased TCR repertoire unpurged by negative selection and have implications for cellular immunotherapeutic approaches. 相似文献
26.
Madan Jagasia Jennifer Giglia Wichai Chinratanalab Sheri Dixon Heidi Chen Haydar Frangoul Brian Engelhardt Stacey Goodman John Greer Adetola Kassim David Morgan Katherine Ruffner Friedrich Schuening 《Biology of blood and marrow transplantation》2007,13(10):1207-1215
Chronic graft-versus-host disease (cGVHD), a common complication after stem cell transplant (SCT), has an impact on morbidity and survival. Previous classification of cGVHD has not been reproducible or prognostic for nonrelapse mortality (NRM). Recently the National Institutes of Health (NIH) consensus criteria were proposed, but the ability of this classification to predict outcome of various subtypes of cGVHD is unknown. Patients (N = 110) undergoing an SCT for a hematologic malignancy and surviving until day 100 posttransplant from 2001 to 2003 were studied. The overall survival (OS) using a landmark analysis at day 100 was 44% versus 66% (no GVHD vs. GVHD, P = .026). The OS of patients with various types of GVHD as proposed by the NIH criteria were significantly different (P < .0001). In a univariate analyses, this was more apparent when patients with any acute features of GVHD were compared to classic cGVHD (3-year OS 46% vs. 68%, P = .033). The 3-year NRM for the entire cohort was 21%, and was not affected by presence or absence of GVHD or subtypes of GVHD. In a multivariable analysis, extensive cGVHD (hazard ratio [HR] 0.35, P = .015) and having any acute feature of GVHD after day 100 (HR 3.36, P = .0144) were significant independent predictors of survival. The OS with different NIH subtypes of GVHD after day 100 from SCT varies, and is superior for patients with classic cGVHD. 相似文献
27.
The authors approach the societal problem of the just distribution of health care resources by exploring one example-- the allocation of intensive care unit (ICU) beds between present patients and those awaiting admission--within the context of not expending a disproportionate share of resources for marginal benefit. They propose the metaphor of the societal "insurance policy" under which decisions regarding the investment of resources to meet various possible contingencies are made in advance. They then analyze several cases to demonstrate how various economic and moral options of the "insurance policy" could be applied in ICUs. 相似文献
28.
Lymphocytes infiltrating the CNS during inflammation display a distinctive phenotype and bind to VCAM-1 but not to MAdCAM-1 总被引:3,自引:0,他引:3
Engelhardt Britta; Conley Frances K.; Kilshaw Peter J.; Butcher Eugene C. 《International immunology》1995,7(3):481-491
The nature of inflammatory lymphocytes recruited to the CNShas been studied in a model of chronic inflammation. Injectionof killed Corynebacterlum parvum into the cortex of the mousebrain produces a circumscribed inflammatory cellular infiltratearound the injection site, and recruited mononuclear inflammatorycells (IC) can be isolated for flow cytometric analysis. Themajority of IC were T cells. In comparison with the predominantnaive population of mesenteric lymph node T cells, IC T cellsexpress much higher levels of CD44, LFA-1 and ICAM-1, and lowerlevels of CD45RB, features commonly associated with memory (previouslyactivated) cells. In addition, in contrast to the L-selectin+6-integrinlow phenotype of naive lymph node T cells, IC T cellslacked L-selectin and were 6-integrin–. Mac-1, recentlyproposed as another marker of memory T cell differentation,was not displayed by IC T cells, suggesting that Mac-1 expressionmay be heterogeneous among memory T cell subsets. A subset ofmesenteric lymph node (MLN) T cells, probably representing activatedT cells undergoing the naive to memory transition, but not ofIC T cells, expressed high levels of 6-, ß7- and E-integrin.IC and MLN naive T cells expressed comparable levels of 4-integrin,but IC T cells stain poorly with anti-ß7 mAbs andwith mAb DATK 32, specific for the 4ß7 heterodimericlymphocyte homing receptor for the mucosal addressin MAdCAM-1,suggesting that these inflammatory cells express more 4ß1than 4ß7. Consistent with this, in in vitro adhesionassays, brain IC bound better than MLN cells to the 4ß1integrin ligand VCAM-1 and the LFA-1 ligand ICAM-1 but adheredvery poorly to the 4ß7 ligand MAdCAM-1. These findingsare consistent with and extend previous immunohistological studiesof T cells in murine experimental autoimmune encephalomyelitis,and demonstrate a distinctive phenotype for lymphocytes beingpresent in the chronically inflamed brain. 相似文献
29.
Altered calcium homeostasis has been demonstrated in human spinal cord motor axon terminals of ALS patients, in spinal motor neurons of mutant SOD transgenic mice and following injection of ALS immunoglobulins. In all three paradigms oculomotor neurons are relatively spared. To explore mechanisms of selective resistance, we applied similar calcium localization techniques to terminals of oculomotor neurons in the two animal models. In both cases large vacuoles, which connect with the extracellular space, accumulated the majority of intracellular calcium, while terminals of vulnerable neurons (e.g. innervating interosseus muscle), which possess no such vacuoles, displayed evenly distributed calcium. These relatively unique membrane enveloped structures may permit neurons to control their cytoplasmic Ca2+ concentration and contribute to selective resistance. 相似文献
30.
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR 总被引:8,自引:0,他引:8
Yang Yiping; Devor Daniel C.; Engelhardt John F.; Ernst Stephen A.; Strong Theresa V.; Collins Francis S.; Cohn Jonathan A.; Frizzell Raymond A.; Wilson James M. 《Human molecular genetics》1993,2(8):1253-1261
Cystic fibrosis (CF) is caused by mutations in the gene encodinga chloride channel called the CF transmembrane conductance regulator(CFTR). A single mutation in this gene, deletion of three nucleotidesthat leads to the absence of phenylalanine 508 (i.e., F508),is found on 70% of all CF chromosomes. To explore the molecularmechanism(s) responsible for defective chloride transport inpatients with CF, we have studied the processing, localization,and function of wild type (W.T.), F508 and G551D CFTR (a GDmissense mutation at position 551) in retrovirus transducedL cells. Cell transduced with W.T. CFTR expressed a 170 kd CFTRprotein that was endoglycosidase H (Endo H) resistant, localizedto the plasma membrane, and generated a cAMP-mediated anionconductance (GCl) when stimulated with standard concentrationsof forskolin (5 µM), cpt cAMP (400 µM) and IBMX(100 µM). The G551D CFTR was indistinguishable from W.T.CFTR with respect to post-translational processing and localization,but it did not produce a cAMP-activated GCI in response to thestandard stimulation cocktail. However, raising the IBMX concentrationto 4 mM produced Gc, in G551D expressing cells. Cells transducedwith F508 CFTR expressed an Endo H sensitive CFTR protein (140kd) that was found in a cytosolic, perinuclear location. Thesecells did not respond to the standard cocktail, but 20% of cellsincreased GCI when the cocktail contained 4 mM IBMX. Incubationof cells at 26°C for 48 hours prior to analysis elicitedresponses in F508 expressing cells at low IBMX concentrations,but had no effect on the responses of cells expressing W.T.or G551D CFTR. The response of F508 to 26°C was associatedwith plasma membrane localization of CFTR protein. These resultssuggest that there are two mechanisms whereby CFTR mutationslead to loss of cAMP-responsive GCI. First, shown by G551D CFTR,the protein can be processed and targeted to the plasma membranecorrectly, but lack full responsiveness to stimulation by cAMP.Second, as examplified by F508 CFTR, a partially functionalprotein which is not targeted to its correct cellular locationcan also lead to loss of the cAMP, responsive GCI. 相似文献