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71.
That most patients with chronic myelogenous leukemia (CML) have either very low levels or no leukocyte alkaline phosphatase activity (LAP) is an established fact. In view of our new findings7 that normal mature human polymorphonuclear leukocytes (PMN) contain two types of granules, azurophils (1/3) and specifics (2/3), and that alkaline phosphatase is present only in specific granules, we undertook the present studies to determine whether these neoplastic PMN lack a specific granule population or simply lack the enzyme. The cellular buffy coats of five patients with CML (Ph1 plus, LAP minus) were fixed in glutaraldehyde, incubated for peroxidase to identify the azurophil population, and examined by electron microscopy. It was found that the specific granule population was present in all mature PMN. Counts of both azurophil and specific granules per cell were slightly lower than normal but were within an 80%-90% overlap of the normal range. We therefore conclude that the low level of LAP in patients with CML reflects a deficiency of the enzyme rather than a missing granule population. Although the mature PMN appeared relatively normal (with few exceptions), circulating myeloblasts and promyelocytes revealed several abnormalities, the most notable being the presence of large bundles of cytoplasmic microfilaments. The blood of two patients in the terminal phase of disease was reexamined. Most of their cells were immature, with aberrations similar to those in myeloblasts and promyelocytes in the chronic phase of the disorder. In addition, however, we discovered three adnormal populations of mature PMN: (1) PMN containing both populations of granules but lacking peroxidase, (2) PMN lacking specific granules, and (3) PMN lacking azurophil granules. Our findings emphasize the value of electron microscopy and cytochemistry in detecting abnormalities of maturation in the cytoplasm of leukemic PMN. 相似文献
72.
RS McLeod BG Wolff AH Steinhart PW Carryer K O'Rourke DF Andrews JE Blair JR Cangemi Z Cohen JB Cullen RG Chaytor GR Greenberg NM Jaffer KN Jeejeebhoy RL MacCarty RL Ready LH Weiland 《Gastroenterology》1997,113(6):1823-1827
BACKGROUND & AIMS: The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn's disease postoperatively and the long-term outcome. METHODS: A randomized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn's disease postoperatively. Patients in the control group were examined endoscopically/radiologically before entry into and annually during the trial. Findings were classified as minimal or severe. RESULTS: There were 76 patients (49 men and 37 women; mean age, 37.1 +/- 13.2 years). Fifty (61.7%) had terminal ileal resections. Overall, 55 endoscopic/radiological recurrences were observed in 51 patients (67.1%). Expressed actuarially, the recurrence rate was 27.5% at 1 year (95% confidence interval [CI], 15.8%-37.6%), 60.8% at 2 years (95% CI, 46%-71.3%), and 77.3% at 3 years (95% CI, 62.7%-86.3%). Nineteen (37%) were symptomatic and 12 (24%) were initially asymptomatic but later became symptomatic (mean, 13.0 +/- 8.8 months), whereas 20 (39%) remained asymptomatic (mean, 16.9 +/- 17.4 months). Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease (23 of 32 vs. 8 of 19, respectively; P = 0.0437). CONCLUSIONS: This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported. Furthermore, many of these patients, especially with minimal disease, will remain asymptomatic. (Gastroenterology 1997 Dec;113(6):1823-7) 相似文献
73.
Pieter-Jan DF Guns Jan Hendrickx Tim Van Assche Paul Fransen Hidde Bult 《British journal of pharmacology》2010,159(2):326-336
Background and purpose:
P2Y nucleotide receptors are involved in the regulation of vascular tone, smooth muscle cell (SMC) proliferation and inflammatory responses. The present study investigated whether they are involved in atherosclerosis.Experimental approach:
mRNA of P2Y receptors was quantified (RT-PCR) in atherosclerotic and plaque-free aorta segments of apolipoprotein E-deficient (apoE–/–) mice. Macrophage activation was assessed in J774 macrophages, and effects of non-selective purinoceptor antagonists on atherosclerosis were evaluated in cholesterol-fed apoE–/– mice.Key results:
P2Y6 receptor mRNA was consistently elevated in segments with atherosclerosis, whereas P2Y2 receptor expression remained unchanged. Expression of P2Y1 or P2Y4 receptor mRNA was low or undetectable, and not influenced by atherosclerosis. P2Y6 mRNA expression was higher in cultured J774 macrophages than in cultured aortic SMCs. Furthermore, immunohistochemical staining of plaques demonstrated P2Y6-positive macrophages, but few SMCs, suggesting that macrophage recruitment accounted for the increase in P2Y6 receptor mRNA during atherosclerosis. In contrast to ATP, the P2Y6-selective agonist UDP increased mRNA expression and activity of inducible nitric oxide synthase and interleukin-6 in J774 macrophages; this effect was blocked by suramin (100–300 µM) or pyridoxal-phosphate-6-azophenyl-2′-4′-disulphonic acid (PPADS, 10–30 µM). Finally, 4-week treatment of cholesterol-fed apoE–/– mice with suramin or PPADS (50 and 25 mg·kg−1·day−1 respectively) reduced plaque size, without changing plaque composition (relative SMC and macrophage content) or cell replication.Conclusions and implications:
These results suggest involvement of nucleotide receptors, particularly P2Y6 receptors, during atherosclerosis, and warrant further research with selective purinoceptor antagonists or P2Y6 receptor-deficient mice. 相似文献74.
Adam Bryant Catalina A Palma Vivek Jayaswal Yee Wa Yang Mark Lutherborrow David DF Ma 《Molecular cancer》2012,11(1):1-9
Background
Semaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumours, indicating a role for plexinB1 in the pathogenesis of prostate cancer.Results
Two specific mutations found in prostate cancer enhance RhoD binding and one other mutation results in loss of inhibition of Rac-dependent Pak1 phosphorylation and lamellipodia formation and in impairment of trafficking of plexinB1 to the membrane. None of the three characterised mutations affect PDZRhoGEF binding, RhoA activity, the interaction of plexinB1with the oncogenes ErbB2 or c-Met or ErbB2 phosphorylation. The mutations have the net effect of increasing cell motility by blocking plexinB1-mediated inhibition of Rac while enhancing the interaction with RhoD, an anti-migratory factor.Conclusions
PlexinB1 mutations block plexinB1-mediated signalling pathways that inhibit cell motility. 相似文献75.
Abdominal computed tomography (CT) scans of 55 patients who had ingested Gastrografin (meglumine diatrizoate and diatrizoate sodium) diluted to 2% with tap water and flavored with a commercial fruit juice base were reviewed. Twenty patients (36%) demonstrated intraluminal precipitation of Gastrografin shown by focal areas of markedly increased attenuation within the gastric lumen or trapped within gastric folds. Beam-hardening artifact produced by precipitation was observed, which limited the diagnostic value of some examinations. In vitro CT scans of the same Gastrografin solution titrated with hydrochloric acid or sodium hydroxide showed that by raising the pH of the solution, precipitation was virtually eliminated. Fifty-one CT scans of the abdomen using a buffered Gastrografin solution demonstrated precipitation in only five patients. Properly buffered dilute oral Gastrografin solutions should significantly decrease the prevalence of precipitation during abdominal CT examinations. 相似文献
76.
Synergism of atenoloi and nitrendipine on hemodynamic amelioration and organ protection in hypertensive rats 下载免费PDF全文
OBJECTIVE: This study was designed to investigate the possible synergism of atenolol and nitrendipine on blood pressure (BP) and blood pressure variability (BPV) reductions, baroreflex sensitivity (BRS) amelioration, and organ protection in hypertensive rats. METHOD: The dose was 20 mg/kg for atenolol, 10 mg/kg for nitrendipine and 20 + 10 mg/kg for the combination of these two drugs. In an acute study, a single dose was given via a catheter previously inserted into the stomach in spontaneously hypertensive rats (SHR). 相似文献
77.
78.
79.
Yi-Ming W Shu H Miao CY Shen FM Jiang YY Su DF 《第二军医大学学报》2005,26(10):1119-1119
Anesthesia inhibits arterial baroreflex functions such as baroreflex sensitivity (BRS). The main objective of the present study was to determine the time course of BRS recovery from anesthesia and to determine whether BRS recovery is synchronous with the recovery of consciousness and blood pressure (BP). Experiments were performed in male Sprague-Dawley rats using different commonly used anesthetics at routine doses through intraperitoneal administration: (1) diazepam/ketamine, 相似文献
80.
Dietary energy restriction was previously shown to be effective in
preventing a wide range of experimentally induced cancers. Studies were
conducted to assess the influence on pancreatic carcinogenesis of dietary
energy restrictions (reduced fat and carbohydrate) of 10%, 20% or 40% in
comparison with control in Syrian hamsters treated with N-
nitrosobis(2-oxopropyl)amine (BOP). Two carcinogenesis studies were
conducted. One used a single treatment with 20 mg BOP/kg body weight and
followed hamsters for 102 weeks following treatment, and the other used
three weekly treatments of 20 mg BOP/kg body weight and followed hamsters
for 45 weeks after treatment. Hamsters were fed control or energy
restricted diet beginning the week following the last BOP treatment.
Pancreatic carcinomas were induced in 9-18% of the hamsters in the first
experiment and in 59-66% of the animals in the second. Dietary energy
restriction did not influence carcinoma incidence in either study, and in
the second experiment the multiplicity of tumors was higher in the 40%
energy restriction (ER) group than in control hamsters. Plasma
corticosterone was suppressed by BOP treatment, particularly in the 20% and
40% ER hamsters in the second experiment, and diet or BOP treatment did not
significantly alter plasma cortisol. Pancreatic protein kinase Czeta
measured by Western blot was highest in the cytosol and particulate
fractions of the 40% ER hamsters in the first experiment. These results
indicate that dietary energy restriction is not effective in the prevention
of BOP induced pancreatic carcinogenesis in the Syrian hamster.
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