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81.
Evidence for direct action of human biosynthetic (recombinant) GM-CSF on erythroid progenitors in serum-free culture 总被引:1,自引:0,他引:1
The biologic activity of human biosynthetic granulocyte-monocyte colony stimulating factor (GM-CSF) was investigated in serum-free culture of erythroid progenitors derived from adult peripheral blood. The morphology of erythroid bursts and the cloning efficiency of BFU-E under serum-free conditions were similar to those observed in dishes with fetal bovine serum (FBS). For these experiments, progenitor cells were partially purified by Ficoll-Paque density centrifugation, adherence to a plastic surface, and complement-mediated cytotoxicity of Leu-1+ elements. For some studies, blastlike cells were harvested directly from 6-day-old semisolid cultures. In serum-free culture of the light-density cell fraction, biosynthetic erythropoietin (Ep) was sufficient for formation of pure and mixed erythroid colonies whereas GM-CSF was required for granulocyte-monocytic colonies. When adherent and Leu-1+ cells were removed, or when in vitro differentiated blast cells were used as a source of progenitors, neither Ep or GM-CSF alone induced colony formation. In dishes supplemented with both growth factors, erythroid bursts were detected. Although the presence of GM- CSF alone did not induce formation of any colony or clusters, BFU-E were recorded when Ep was added 8 days later, suggesting that BFU-E could be maintained. Terminal maturation of the resulting erythroid bursts was delayed by 8 days. These results provide evidence that GM- CSF acts directly on early erythroid progenitors. Furthermore, they suggest that both Ep and GM-CSF are necessary to start the differentiation process. 相似文献
82.
Blanca Lizaola Alan Bonder Elliot B. Tapper Nezam Afdhal 《Current hepatitis reports》2016,15(4):220-229
Chronic hepatitis B represents a major public health burden. One quarter of patients with chronic hepatitis B will progress to cirrhosis without treatment. According to the current hepatitis B guidelines, treatment is based upon alanine aminotransferase (ALT) elevation and hepatitis B virus (HBV) DNA levels, along with liver fibrosis staging. Liver biopsy still represents the gold standard for the diagnosis and staging of liver fibrosis. However, this method has several limitations like invasiveness, sampling variations, pain, time commitments, and bleeding. In response to this concern, in the last decade, a large amount of noninvasive methods have emerged offering promising diagnostic capabilities. These techniques include serum markers of fibrosis and radiological tests. In the present review, we discuss the performance characteristics and advantages of using noninvasive methods to diagnose and stage liver fibrosis in patients with chronic hepatitis B and its utility in clinical practice. 相似文献
83.
Community‐Based Palliative Care and Advance Care Planning Documentation: Evidence from a Multispecialty Group 下载免费PDF全文
84.
85.
Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions 总被引:2,自引:0,他引:2
Mills IH; Park GR; Manara AR; Merriman RJ 《QJM : monthly journal of the Association of Physicians》1998,91(7):493-503
We have previously shown that eating disorders are a compulsive behaviour
disease, characterized by frequent recall of anorexic thoughts. Evidence
suggests that memory is a neocortical neuronal network, excitation of which
involves the hippocampus, with recall occurring by re-excitement of the
same specific network. Excitement of the hippocampus by glutamate-NMDA
receptors, leading to long-term potentiation (LTP), can be blocked by
ketamine. Continuous block of LTP prevents new memory formation but does
not affect previous memories. Opioid antagonists prevent loss of
consciousness with ketamine but do not prevent the block of LTP. We used
infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily
nalmefene as opioid antagonist to treat 15 patients with a long history of
eating disorder, all of whom were chronic and resistant to several other
forms of treatment. Nine (responders) showed prolonged remission when
treated with two to nine ketamine infusions at intervals of 5 days to 3
weeks. Clinical response was associated with a significant decrease in
Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after
ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients
(non-responders) the score was: before ketamine, 42.8 +/- 3.7; after
ketamine, 44.8 +/- 3.1. There was no significant response to at least five
ketamine treatments, perhaps because the compulsive drive was
re-established too soon after the infusion, or because the dose of opioid
antagonist, nalmefene, was too low.
相似文献
86.
Cuello C; Palladinetti P; Tedla N; Di Girolamo N; Lloyd AR; McCluskey PJ; Wakefield D 《Rheumatology (Oxford, England)》1998,37(7):779-783
OBJECTIVE: To investigate the expression and source of chemokines in minor
salivary gland biopsies (MSGs) in patients with Sjogren's syndrome (SS).
METHODS: Immunohistochemical analysis was used to determine the pattern of
chemokine expression in MSGs from patients with (n=6) and without (n=5) SS,
as well as to examine the phenotype of both resident and infiltrating cells
expressing chemokines. RESULTS: Significant differences in the number of
infiltrating mononuclear (MN) cells in patients with and without SS were
noted. Ductal epithelial cells of SS biopsies expressed significantly
increased levels of macrophage inflammatory protein (MIP)-1alpha,
MIP-1beta, interleukin-8 (IL-8) and RANTES (Regulated upon Activation,
Normal T cell Expressed and Secreted). Biopsies from patients with SS
showed that MIP-1beta was expressed by 51% of infiltrating cells, while 41%
expressed MIP-1alpha, whereas 22 and 7% expressed RANTES and IL-8,
respectively. CONCLUSION: Chemokines expressed by ductal epithelial cells
may attract circulating leucocytes, in particular CD4+ T cells, towards the
site of inflammation, thereby orchestrating the influx of MN cells
characteristically seen in MSGs in SS. Chemokines may be induced directly
by a putative triggering agent for SS, or secondary to the release of
pro-inflammatory cytokines produced by epithelial cells. These findings
further implicate epithelial cells as playing a major role in the
pathogenesis of SS and implicate chemokines in the leucocyte recruitment in
this setting.
相似文献
87.
Background
Wilson disease is rare, found in 3 of 100,000 people (0.03%). Ceruloplasmin is often ordered to evaluate liver enzyme elevations. Because Wilson disease often presents before middle-age, the American Association for the Study of Liver Disease recommends screening patients between the ages of 3 and 55 years with liver abnormalities of uncertain cause. We evaluate guideline adherence and the clinical and economic impact of current clinical use of ceruloplasmin.Methods
We reviewed all ceruloplasmin measurements at a clinical laboratory that serves a large primary care network, specialty clinics, and a 600-bed tertiary referral center between January 1, 2003, and December 12, 2011.Results
Ceruloplasmin was measured 5325 times in 5023 unique patients, resulting in 8 (0.16%) new Wilson disease diagnoses. Ceruloplasmin's positive predictive value was 8.4% (95% confidence interval, 7.7-9.3) and false-positive rate was 98.1% (95% confidence interval, 96.2-99.1). A total of 1109 ceruloplasmin levels (20.8%) were ordered in the 1066 patients aged more than 55 years (none with Wilson disease). A “shotgun” approach to liver disease diagnosis was found: Ceruloplasmin was ordered on the same day as hepatitis B (81.0%), hepatitis C (76.0%), autoimmune hepatitis (75.1%), and hemochromatosis (73.1%). Of 424 positive ceruloplasmin results, 91% were not pursued further.Conclusions
Guideline adherence restricts ceruloplasmin use to a population with a higher pre-test probability of Wilson disease: patients with chronic liver disease aged 3 to 55 years who have been tested for common causes of liver disease. The majority of the serum ceruloplasmin was measured in patients not indicated by the guidelines, resulting in poor test performance and wasted healthcare resources. Our data on ceruloplasmin use could serve as a touchstone for broader discussions on rational clinical decision making. 相似文献88.
TG Bird L Boutler A Cole S Lorenzini WY Lu T Hay R Ridgway M Williams B Knight S Gordon Keylock D Wjotacha T Jamieson JP Iredale AR Clarke OJ Sansom SJ Forbes 《Lancet》2013
Insufficient regeneration of the adult liver is believed to cause failure to recover from severe liver disease. An undifferentiated cell population with stem-cell-like qualities known as hepatic progenitor cells (HPCs) is hypothesised to have a central role in regeneration of the adult liver during massive or chronic liver disease. Stem cells in other organ systems are believed to reside in a specialised microenvironment or niche that supports their maintenance and function. The existence of a hepatic stem cell niche might provide a means of therapeutically manipulating endogenous HPCs in vivo as a regenerative therapy.To investigate the physiological potential of HPCs to regenerate the mammalian liver, we have established a novel model of hepatocellular injury and HPC activation using genetic manipulation of hepatocytes. After hepatocyte senescence and death in this model (AhCre Mdm2flox), HPCs expand and bring about the complete regeneration of the liver parenchyma.We demonstrate that a stereotypical niche, consisting partly of macrophages, exists in both animal models and correlating human disease. Using cell tracking, we show active recruitment of extrahepatic macrophages into this niche during injury. In health, intravenous injection of macrophages results in macrophage engraftment to the liver niche, with subsequent HPC activation and changes to liver structure and function.Within the niche, macrophages use paracrine signalling to control both HPC proliferation and cell fate via TWEAK (tumour-necrosis-factor-like weak inducer of apoptosis) and the Wnt signalling pathway, respectively. After hepatocellular injury, macrophages ingest hepatocyte debris, and release Wnt which promotes HPC differentiation into hepatocytes. TWEAK is vital for HPC proliferation in the AhCre Mdm2flox model of regeneration. Here, the absence of TWEAK signalling results in liver failure and mortality.This work has demonstrated for the first time the ability of a solid organ to fully regenerate in the adult mammal from progenitor cells, and additionally highlights mechanisms by which this process can be modulated by either small molecule or cell therapy.FundingUniversity of Edinburgh. 相似文献
89.
90.
Complementary medicine: use and attitudes among GPs 总被引:9,自引:0,他引:9
BACKGROUND: Information about use and attitudes of GPs towards
complementary medicine is required in order to inform the debate about its
place within mainstream medicine. There is evidence that public use of
complementary medicine is particularly high in the South-West of England.
OBJECTIVE: This study aimed to determine the use of, and attitudes towards,
complementary medicine among GPs. METHODS: A questionnaire survey was
performed of all primary care physicians working in the health service in
Devon and Cornwall. RESULTS: Replies were received from 461 GPs, a response
rate of 47%. A total of 314 GPs (68%, range 32-85%) had been involved in
complementary medicine in some way during the previous week. One or other
form of complementary medicine was practised by 74 of the respondents
(16%), the two most common being homoeopathy (5.9%) and acupuncture (4.3%).
In addition, 115 of the respondents (25%) had referred at least one patient
to a complementary therapist in the previous week, and 253 (55%) had
endorsed or recommended treatment with complementary medicine.
Chiropractic, acupuncture and osteopathy were rated as the three most
effective therapies, and the majority of respondents believed that these
three therapies should be funded by the health service. A total of 176
(38%) of respondents reported adverse effects, most commonly after
manipulation. CONCLUSION: Over two-thirds of the GPs in Devon and Cornwall
who responded to the survey had been involved with complementary medicine
in some way during the previous week. This figure is higher than the
national average. The majority of respondents believed that acupuncture,
chiropractic and osteopathy were effective and should be funded by the NHS.
相似文献