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21.
Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults. 相似文献
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Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels. 相似文献
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Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-
myristate 13-acetate with activation of ERK mitogen-activated protein
kinases, synthesis of interleukin-2, and death, whereas phorbol ester-
resistant variants of this cell line do not exhibit these responses.
Additional aspects of the resistant phenotype were examined, using a
newly-established resistant cell line. Phorbol ester induced morphological
changes, ERK activation, calcium-dependent activation of the c-Jun
N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in
sensitive but not resistant cells. A series of protein kinase C activators
caused membrane translocation of protein kinase C's (PKCs) alpha, eta, and
theta in both cell lines. While PKC eta was expressed at higher levels in
sensitive than in resistant cells, overexpression of PKC eta did not
restore phorbol ester-induced ERK activation to resistant cells. In
sensitive cells, PKC activators had similar effects on cell viability and
ERK activation, but differed in their abilities to induce JNK activation
and interleukin-2 synthesis. PD 098059, an inhibitor of the mitogen
activated protein (MAP)/ERK kinase kinase MEK, partially inhibited ERK
activation and completely blocked phorbol ester-induced cell death in
sensitive cells. Thus MEK and/or ERK activation, but not JNK activation or
interleukin-2 synthesis, appears to be required for phorbol ester-induced
toxicity. Alterations in phorbol ester response pathways, rather than
altered expression of PKC isoforms, appear to confer phorbol ester
resistance to EL4 cells.
相似文献
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The present report describes psychobiological studies of behavior around the time of birth. An adaptive, ecological perspective is presented in which stimulation of the fetus and newborn is purported to instigate adaptive postpartum behavior. Studies describing the perinatal sensory environment are reviewed, with a consideration of emergent sensory function of the fetus. It is asserted that afferent input associated with parturition perturbs the fetus and neonate, producing a general arousal state that facilitates breathing, suckling, and early learning. The view developed herein is that perinatal sensory input induces and canalizes the newborn's behavior, thereby regulating adaptive postpartum function. Deviations in afferent input may alter ontogenetic trajectories and compromise developmental outcome by reducing availability of conditions necessary for adequate postpartum adaptation. 相似文献
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