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91.
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Coakley G; Mok CC; Hajeer AH; Ollier WE; Turner D; Sinnott PJ; Hutchinson IV; Panayi GS; Lanchbury JS 《Rheumatology (Oxford, England)》1998,37(9):988-991
OBJECTIVE: To examine whether promoter polymorphisms associated with
variation in interleukin-10 (IL-10) production are relevant to the
development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS:
DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The
promoter region between -533 and - 1120 was amplified by polymerase chain
reaction, and polymorphisms detected by restriction enzyme digest or
sequence-specific oligonucleotide probing. RESULTS: We found no significant
difference in allele or haplotype frequencies between the groups.
CONCLUSION: There is no association between FS or RA and these recently
identified IL-10 promoter polymorphisms. Other genetic or environmental
factors could explain the alterations in IL-10 levels seen in these
conditions.
相似文献
94.
OBJECTIVES: Growth Hormone (GH) promotes loss of body fat and causes insulin resistance. It is debated whether reduction of body fat mass during long term growth hormone (GH) administration improves carbohydrate metabolism. To answer this question we assessed carbohydrate handling and tissue specific function of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) during prolonged GH treatment of obese rats. METHODS: Body fat % estimated by DEXA scanning, plasma IGF-I, glucose and insulin were studied in 17 months old dietary induced obese rats treated for 4, 21 or 41 days (GH: 4 mg/kg/d or saline total n=90). Adipose tissue, muscle and liver samples were obtained after 21 days and expression and tyrosine phosphorylation of IR and IRS-1 proteins and the degree of IRS-1-Janus Kinase-2 (JAK2) interaction were analyzed by immunoprecipitation and immunoblotting. RESULTS: Forty-one days GH treatment caused the body fat to decline significantly to 20+/-3% (Mean+/-SEM), whereas it remained steady on 51+/-4% in the pair fed group. Insulin levels in response to OGTT were significantly elevated throughout the experiment. IR amount was elevated in adipose tissue but decreased in liver after GH treatment while IR phosphorylation was increased in muscle only. IRS-1 amount was elevated in adipose tissue and muscle while IRS-1 phosphorylation was increased only in liver. The association of IRS-1 with JAK-2 was increased in liver and muscle. CONCLUSIONS: An extensive reduction of fat mass did not improved signs of insulin resistance in GH treated old obese rats. The molecular events associated with GH treatment included tissue specific changes in the function of IR and IRS-1 suggesting the liver to be the primary site of insulin resistance. Furthermore, the association of IRS-1with JAK-2 in the course of GH signaling could present a mechanism for GH to directly induce insulin resistance. 相似文献
95.
Anders Bork Davidsen Marie Mardal Sys Stybe Johansen Petur Weihe Dalsgaard Kristian Linnet 《Drug testing and analysis》2020,12(7):987-993
The new psychoactive substance (NPS) 3‐HO‐PCP, a phencyclidine (PCP) analog, was detected in a law enforcement seizure and in forensic samples in Denmark. Compared with PCP, 3‐HO‐PCP is known to be a more potent dissociative NPS, but no toxicokinetic investigations of 3‐HO‐PCP are yet available. Therefore, 3‐HO‐PCP was quantified in in vivo samples, and the following were investigated: plasma protein binding, in vitro and in vivo metabolites, and metabolic targets. All samples were separated by liquid chromatography and analyzed by mass spectrometry. The unbound fraction in plasma was determined as 0.72 ± 0.09. After in vitro incubation with pooled human hepatocytes, four metabolites were identified: a piperidine‐hydroxyl‐and piperidine ring opened N‐dealkyl‐COOH metabolite, and O‐glucuronidated‐ and O‐sulfate‐conjugated metabolites. In vivo, depending on the sample and sample preparation, fewer metabolites were detected, as the O‐sulfate‐conjugated metabolite was not detected. The N‐dealkylated‐COOH metabolite was the main metabolite in the deconjugated urine sample. in vivo analytical targets in blood and brain samples were 3‐HO‐PCP and the O‐glucuronidated metabolite, with 3‐HO‐PCP having the highest relative signal intensity. The drug levels of 3‐HO‐PCP quantified in blood were 0.013 and 0.095 mg/kg in a living and a deceased subject, respectively. The 3‐HO‐PCP concentrations in deconjugated urine in a sample from a living subject and in post‐mortem brain were 7.8 and 0.16 mg/kg, respectively. The post mortem results showed a 1.5‐fold higher concentration of 3‐HO‐PCP in the brain tissue than in the post mortem blood sample. 相似文献
96.
Marco Gerlinger Sergio A Quezada Karl S Peggs Andrew JS Furness Rosalie Fisher Teresa Marafioti Vishvesh H Shende Nicholas McGranahan Andrew J Rowan Steven Hazell David Hamm Harlan S Robins Lisa Pickering Martin Gore David L Nicol James Larkin Charles Swanton 《The Journal of pathology》2013,231(4):424-432
The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
97.
Korsbek Lisa Vilholt-Johannesen Sofie Johansen Gry Krath Thomsen Rikke Johansen Merete Benedikte Rasmussen Klavs Serup 《Community mental health journal》2021,57(8):1435-1441
Community Mental Health Journal - The study reports the results of a qualitative study on the views and experiences of non-peer mental health providers on working together with peer colleagues in... 相似文献
98.
99.
Alterations in intervertebral disc composition,matrix homeostasis and biomechanical behavior in the UCD‐T2DM rat model of type 2 diabetes
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Aaron J. Fields Britta Berg‐Johansen Lionel N. Metz Stephanie Miller Brandan La Ellen C. Liebenberg Dezba G. Coughlin James L. Graham Kimber L. Stanhope Peter J. Havel Jeffrey C. Lotz 《Journal of orthopaedic research》2015,33(5):738-746
Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis, and biomechanical behavior. Coccygeal motion segments were harvested from 6‐month‐old lean Sprague‐Dawley rats, obese Sprague‐Dawley rats, and diabetic obese UCD‐T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end‐product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia‐inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress, and AGE/RAGE‐mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:738–746, 2015. 相似文献
100.
The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism 总被引:3,自引:0,他引:3
J S Johansen B J Riis C Hassager M Moen J Jacobson C Christiansen 《The Journal of clinical endocrinology and metabolism》1988,67(4):701-706
The effect on bone metabolism of an agonist analog of GnRH, nafarelin, was studied in 16 premenopausal women, who received 200 micrograms nafarelin/day for 6 months, and 9 premenopausal women, who received 400 micrograms nafarelin/day for 6 months, followed by a 6-month follow-up period. Bone mineral content in the forearm (measured by single photon absorptiometry) and in the spine (measured by dual photon absorptiometry) significantly decreased after 6 months of treatment with 400 micrograms nafarelin, but 6 months after termination of treatment all bone mineral measurements had returned to pretreatment levels. The bone mineral measurements in the 200 micrograms group did not change throughout the study. In both treatment groups the biochemical estimates of bone turnover increased significantly to postmenopausal levels. Withdrawal of treatment resulted in an abrupt decrease in the bone resorption parameters (fasting urinary hydroxyproline to creatinine and calcium to creatinine excretion ratios and serum phosphate), whereas there was a protracted fall in the bone formation parameters (plasma bone Gla protein and serum alkaline phosphatase) 6 months after termination of treatment. Our findings demonstrate that nafarelin in both doses increased biochemical indices of bone turnover, that 400 micrograms/day nafarelin resulted in a significant decrease in bone mineral content, and that these effects were reversible. 相似文献