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991.
Hall JE Sullivan JP Richardson GS 《The Journal of clinical endocrinology and metabolism》2005,90(4):2050-2055
To determine the influence of sleep, sleep stage, and time of day on the dynamics of pulsatile LH secretion in the early follicular phase (EFP) of the menstrual cycle, 11 normal women underwent simultaneous polysomnographic monitoring of sleep and measurement of LH in frequent sampling studies during a 40-h protocol that consisted of one night of normal sleep and one night of sleep deprivation followed by an afternoon nap. The interpulse interval of LH was longer during sleep than wake whether it occurred at night or during the day (P < 0.002), implying a decrease in GnRH pulse frequency associated with sleep in the EFP. LH pulse amplitude was greater during sleep than wake (P < 0.001) and greater pulse amplitudes were associated with longer interpulse intervals during sleep (P < 0.005), but not wake. An interaction between sleep and time of day was observed for mean LH, with lower mean LH levels during sleep than wake at night (P < 0.02), but not during the day. Wakefulness was more likely to be associated with an LH pulse than were stages I/II, III/IV (slow wave), or rapid eye movement sleep (P < 0.005). In addition, the probability of wakefulness within the sleep episode increased 5-15 min before the onset of LH pulses (relative to randomly selected nonpulse LH; P < 0.05), suggesting that wakefulness was the primary event. In the absence of sleep, there was an effect of time of day on mean LH (P < 0.02) and LH pulse amplitude (P < 0.03), with greatest values seen during the evening. In conclusion, in the EFP, inhibition of LH pulse frequency is related to sleep rather than time of day. During periods of sleep, LH pulses occur most commonly in association with brief awakenings, suggesting that interruptions from sleep allow escape from the inhibitory effect of sleep on pulsatile GnRH secretion. A separate effect of time of day on LH pulse dynamics in the absence of sleep was also observed with evening augmentation of LH pulse amplitude and mean level; however, additional studies will be required to determine whether this represents a true circadian effect. 相似文献
992.
993.
An Improved Radioisotope Dilution Assay for Serum Vitamin B12 Using Hemoglobin-coated Charcoal 总被引:2,自引:0,他引:2
A radioisotope dilution assay for vitamin B12, using hemoglobin-coatedcharcoal, was modified in several respects, the most prominent of whichwas the use of cyanide extraction ofsera. With these modifications, the B12levels were significantly higher in serafrom normal subjects and patients withfolate deficiency, whereas sera frompatients with pernicious anemia andother B12-deficient states were onlyminimally affected. The use of cyanideextraction thus resulted in a clearerdifferentiation of B12-deficient serafrom other sera; all 23 patients withpernicious anemia had B12 levels below 140 pg/ml, whereas all of 85 normal and 218 folate-deficient subjectshad B12 levels above 156 pg/ml. Themicrobiologic assay with Euglenagracilis was similarly affected by cyanide extraction of sera. Thus, it appears that the use of cyanide resultsin more complete extraction of B12from serum proteins. Submitted on June 28, 1971 Revised on September 21, 1971 Accepted on September 23, 1971 相似文献
994.
Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo 下载免费PDF全文
Hochberg D Middeldorp JM Catalina M Sullivan JL Luzuriaga K Thorley-Lawson DA 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(1):239-244
Epstein-Barr virus (EBV) is a herpesvirus that establishes a lifelong, persistent infection. It was first discovered in the tumor Burkitt's lymphoma (BL). Despite intensive study, the role of EBV in BL remains enigmatic. One striking feature of the tumor is the unique pattern of viral latent protein expression, which is restricted to EBV-encoded nuclear antigen (EBNA) 1. EBNA1 is required to maintain the viral genome but is not recognized by cytotoxic T cells. Consequently, it was proposed that this expression pattern was used by latently infected B cells in vivo. This would be the site of long-term, persistent infection by the virus and, by implication, the progenitor of BL. We now know that EBV persists in memory B cells in the peripheral blood and that BL is a tumor of memory cells. However, a normal B cell expressing EBNA1 alone has been elusive. Here we show that most infected cells in the blood express no detectable latent mRNA or proteins. The exception is that when infected cells divide they express EBNA1 only. This is the first detection of the BL viral phenotype in a normal, infected B cell in vivo. It suggests that BL may be a tumor of a latently infected memory B cell that is stuck proliferating because it is a tumor and, therefore, constitutively expressing only EBNA1. 相似文献
995.
Sook‐Kwan Leang Simon Kwok Sheena G. Sullivan Sebastian Maurer‐Stroh Anne Kelso Ian G. Barr Aeron C. Hurt 《Influenza and other respiratory viruses》2014,8(2):135-139
Influenza viruses collected from regions of Asia, Africa and Oceania between 2009 and 2012 were tested for their susceptibility to two new neuraminidase inhibitors, peramivir and laninamivir. All viruses tested had normal laninamivir inhibition. However, 3·2% (19/599) of A(H1N1)pdm09 viruses had highly reduced peramivir inhibition (due to H275Y NA mutation) and <1% (6/1238) of influenza B viruses had reduced or highly reduced peramivir inhibition, with single occurrence of variants containing I221T, A245T, K360E, A395E, D432G and a combined G145R+Y142H mutation. These data demonstrate that despite an increase in H275Y variants in 2011, there was no marked change in the frequency of peramivir‐ or laninamivir‐resistant variants following the market release of the drugs in Japan in 2010. 相似文献
996.
Ethan A. Winkler Jesse D. Sengillo Abhay P. Sagare Zhen Zhao Qingyi Ma Edward Zuniga Yaoming Wang Zhihui Zhong John S. Sullivan John H. Griffin Don W. Cleveland Berislav V. Zlokovic 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(11):E1035-E1042
Humans with ALS and transgenic rodents expressing ALS-associated superoxide dismutase (SOD1) mutations develop spontaneous blood–spinal cord barrier (BSCB) breakdown, causing microvascular spinal-cord lesions. The role of BSCB breakdown in ALS disease pathogenesis in humans and mice remains, however, unclear, although chronic blood–brain barrier opening has been shown to facilitate accumulation of toxic blood-derived products in the central nervous system, resulting in secondary neurodegenerative changes. By repairing the BSCB and/or removing the BSCB-derived injurious stimuli, we now identify that accumulation of blood-derived neurotoxic hemoglobin and iron in the spinal cord leads to early motor-neuron degeneration in SOD1G93A mice at least in part through iron-dependent oxidant stress. Using spontaneous or warfarin-accelerated microvascular lesions, motor-neuron dysfunction and injury were found to be proportional to the degree of BSCB disruption at early disease stages in SOD1G93A mice. Early treatment with an activated protein C analog restored BSCB integrity that developed from spontaneous or warfarin-accelerated microvascular lesions in SOD1G93A mice and eliminated neurotoxic hemoglobin and iron deposits. Restoration of BSCB integrity delayed onset of motor-neuron impairment and degeneration. Early chelation of blood-derived iron and antioxidant treatment mitigated early motor-neuronal injury. Our data suggest that BSCB breakdown contributes to early motor-neuron degeneration in ALS mice and that restoring BSCB integrity during an early disease phase retards the disease process.The blood–brain barrier (BBB) and blood–spinal cord barrier (BSCB) prevent entry of toxic circulating molecules and cells into the central nervous system (CNS) (1). Amyotrophic lateral sclerosis (ALS) is the most prominent adult motor-neuron disorder resulting in progressive motor-neuron loss in the spinal cord, brainstem, and motor cortex (2). Most ALS cases are sporadic (90%) whereas 10% are familial ALS. Over twenty independent studies in postmortem human tissue and cerebrospinal fluid (CSF) sampling from living ALS patients have established that the BBB and BSCB are damaged in familial and sporadic ALS, as reviewed elsewhere (1, 3). This BBB and BSCB disruption has been shown by spinal-cord and/or motor-cortex accumulation of different plasma proteins (e.g., IgG, fibrin, thrombin), erythrocytes, erythrocyte-derived hemoglobin and iron-containing hemosiderin, elevated CSF/serum albumin ratios, and diminished expression or degradation of the BSCB tight-junction proteins (1, 3–5). Deposition of hemoglobin-derived iron within the CNS has also been shown in ALS patients (3, 6, 7). Because human postmortem studies reflect, however, end-stage disease, it has remained unclear as to which stage of disease is enhanced by BSCB disruption. Longitudinal CSF or BSCB imaging studies have yet to be performed in living ALS patients (3) to clarify whether spinal-cord vascular dysfunction contributes to early- or late-stage disease.Transgenic rodents expressing human ALS-associated Cu/Zn superoxide dismutase (SOD1) mutations that represent 20% of all familial cases also develop a spontaneous BBB/BSCB disruption (8–12) similar to vascular pathology reported in humans (1, 3–7). Mice with a chronic BBB disruption due to aberrant signal transduction between the central nervous system endothelial cells and pericytes or astrocytes and pericytes develop a chronic BBB opening accompanied by accumulation of toxic blood-derived products in the central nervous system and secondary functional and structural neuronal changes (13–15).To determine whether BSCB disruption contributes to fatal paralytic disease caused by expression of an ALS-causing mutant, we now report how perturbing the BSCB, repairing the BSCB, and/or removing the BSCB-derived injurious stimuli influence development of disease in SOD1G93A mice that develop a spontaneous BSCB breakdown (8, 9, 12). 相似文献
997.
Ayami Yoshimi Marry M. van den Heuvel-Eibrink Irith Baumann Stephan Schwarz Ingrid Simonitsch-Klupp Pascale de Paepe Vit Campr Gitte Birk Kerndrup Maureen O’Sullivan Rita Devito Roos Leguit Miguel Hernandez Michael Dworzak Barbara de Moerloose Jan Stary Henrik Hasle Owen P. Smith Marco Zecca Albert Catala Markus Schmugge Franco Locatelli Monika Führer Alexandra Fischer Anne Guderle Peter N?llke Brigitte Strahm Charlotte M. Niemeyer 《Haematologica》2014,99(4):656-663
Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: ) NCT00662090相似文献
998.
Jacek Debiec Regina Marie Sullivan 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(33):12222-12227
Emotional trauma is transmitted across generations. For example, children witnessing their parent expressing fear to specific sounds or images begin to express fear to those cues. Within normal range, this is adaptive, although pathological fear, such as occurs in posttraumatic stress disorder or specific phobias, is also socially transmitted to children and is thus of clinical concern. Here, using a rodent model, we report a mother-to-infant transfer of fear to a novel peppermint odor, which is dependent on the mother expressing fear to that smell in pups’ presence. Examination of pups’ neural activity using c-Fos early gene expression and 14C 2-deoxyglucose autoradiography during mother-to-infant fear transmission revealed lateral and basal amygdala nuclei activity, with a causal role highlighted by pharmacological inactivation of pups’ amygdala preventing the fear transmission. Maternal presence was not needed for fear transmission, because an elevation of pups’ corticosterone induced by the odor of the frightened mother along with a novel peppermint odor was sufficient to produce pups’ subsequent aversion to that odor. Disruption of axonal tracts from the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or blockade of pups’ alarm odor-induced corticosterone increase prevented transfer of fear. These memories are acquired at younger ages compared with amygdala-dependent odor-shock conditioning and are more enduring following minimal conditioning. Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups’ stress response paired with the cue to induce amygdala-dependent learning plasticity. Results are discussed within the context of caregiver emotional responses and adaptive vs. pathological fears social transmission.Children, including infants, use their parents’ emotions to guide their behavior and learn about safety and danger (1–4). The infant’s ability to regulate behavior in novel situations using the caregiver’s emotional expression is known as social referencing and occurs in humans and nonhuman primates (1). Although parental physical presence itself or particular cues indicating parental presence, such as voice, touch, or smell typically signal safety for the child, infants are especially responsive to the caregiver’s communication during threats (3–5). This social learning is critical for enhancing survival through an adaptation to the environment but also provides transmission of pathological fears, such as occurs in posttraumatic stress disorder (PTSD) or in specific phobias (3–7).Despite existing evidence that children are sensitive to parental fear and anxiety, the neurobiological mechanisms for the transmission of parental specific fear to the offspring have remained elusive (2–7). Animal studies investigating the impact of parental stress on the offspring focused on the history of parental trauma, quality of maternal care, and resultant overall behavioral alterations in the offspring (7, 8). However, to develop efficient survival strategies, progenies must learn about specific environmental threats triggering parental fear (9).Most of what we know about fear learning comes from studies using fear conditioning (FC) (10). In FC, a neutral sensory cue [conditioned stimulus (CS)] is paired with a noxious event [unconditioned stimulus (US)]. Animal studies indicate that the amygdala’s lateral and basal nuclei (LBA) play an important role in FC (10). However, FC in infant rats is naturally attenuated until postnatal day (PND) 10 due to low levels of the stress hormone corticosterone (CORT) during the stress hyporesponsive period (11–15). This fear suppression continues in older pups (until PND 16) in the mother’s presence due to social buffering (attenuation) of the shock-induced CORT increase (15).To study the intergenerational transmission of fear to specific triggers, we developed a mother-to-infant social fear learning paradigm. In social fear learning, an organism learns fear through an exposure to a conspecific expressing fear to a discrete CS. Social fear learning may thus serve as a model explaining how defense responses to specific triggers are transmitted between individuals. Social fear learning has been demonstrated in primates, including humans and in rodents, and involves the amygdala (16–19). 相似文献
999.
Retrospective echocardiographic review identified 58 consecutive infants and children with fixed subaortic stenosis. Mean (SD) age at diagnosis was 4.8 (3.6) years (range two days to 14.7 years), and diagnosis occurred in infancy in eight. Associated cardiac abnormalities were present in 41 (71%) whereas fixed subaortic stenosis was an isolated lesion in 17 (29%). Four types of fixed subaortic stenosis were identified: short segment (47 (81%)), long segment (7 (12%)), posterior displacement of the infundibular septum with additional discrete narrowing of the left ventricular outflow tract (3 (5%)), and redundant tissue arising from the membranous septum (1 (2%)). Echocardiographic studies had been performed before the diagnosis of fixed subaortic stenosis in nine patients, all with associated abnormalities. These were performed in infancy in each and showed a "normal" left ventricular outflow tract in six and posterior deviation of the infundibular septum in three. In 16 patients serial echocardiographic studies had been performed after the diagnosis of fixed subaortic stenosis but before surgery of the left ventricular outflow tract. Rapid evolution of short segment to long segment narrowing was seen in one patient, and tethering of the aortic valve or mitral valve developed in a further four patients. Aortic valve or mitral valve involvement was not seen before the age of three years but was common thereafter (10/40 patients, 25%). Fixed subaortic stenosis may be an "acquired" lesion with the potential for changes in form as well as progression in severity of left ventricular outflow tract obstruction. 相似文献
1000.
Pullen DJ; Sullivan MP; Falletta JM; Boyett JM; Humphrey GB; Starling KA; Land VJ; Dyment PG; Vats T; Duncan MH 《Blood》1982,60(5):1159-1168
In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24-49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC. 相似文献