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1.
BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease. 相似文献
2.
Axillary lymphadenectomy in breast conservation surgery is associated with substantial morbidity in either seroma formation or infection. Seroma formation in the axilla requiring aspiration occurs in up to 42 per cent of patients treated without drainage. Prolonged outpatient suction drainage reduces but does not eliminate the incidence of seroma formation, while increasing cost, discomfort, and possibly infection rates. We studied the efficacy of overnight closed suction drainage in patients undergoing breast conservation surgery. Fifty consecutive patients undergoing a standard axillary dissection for breast cancer were studied. The axilla was drained with a 7-French closed suction drain. All drains were removed within 23 hours of surgery and prior to discharge from the outpatient surgical center. Patients were examined by the operating surgeon 7 to 10 days after surgery. One patient (2%) experienced a seroma postoperatively. No infections were observed in all 50 patients, and the remaining 49 patients did not experience visible or symptomatic seromas. The number of lymph nodes removed ranged between 5 and 33 with a mean of 15.5 +/- 0.6. Nine out of 50 (18%) patients had metastatic breast cancer to the axillary lymph nodes. Patients undergoing breast conservation surgery benefit from overnight closed suction drainage of the axilla. This short-term method reduces the incidence and the inherent morbidity of axillary seroma formation. 相似文献
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CD Wroe 《Canadian Metallurgical Quarterly》1997,51(7):463-465
Cardiac dysrhythmias in septic patients often reflect hypovolaemia, hypokalaemia or endocarditis as cardiac manifestation of the infection, but may be indicative for underlying cardiac pathology previously undiagnosed. We report on the case of a patient with severe peritonitis, on whom transoesophageal echocardiography (TEE) had been performed intraoperatively due to progressive circulatory instability. TEE revealed first diagnosis of asymmetric hypertrophic cardiomyopathy, which complicated the features of septic syndrome. Further perioperative treatment to support the circulation was successfully adjusted on the grounds of this diagnosis. 相似文献
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Discrimination of simple visual attributes can improve significantly with practice. We have trained human observers to perform peripherally presented tasks involving the localization of short line segments and examined the specificity of the learning for the visual location, orientation, and geometric arrangement of the trained stimulus. Several weeks of training resulted in dramatic threshold reductions. The learning was specific for the orientation and location of the trained stimulus, indicating the involvement of the earliest cortical stages in the visual pathway where the orientation and location of stimuli are mapped with highest resolution. Furthermore, improvement was also specific for both the configuration of the trained stimulus and the attribute of the stimulus that was under scrutiny during training. This degree of specificity suggests that the learning cannot be achieved by cortical recruitment alone, as proposed in current models, but is likely to involve a refinement of lateral interactions within the cortex and possibly a gating of lower level changes by attentional mechanisms. 相似文献
8.
MS Ali PP Sayeski LB Dirksen DJ Hayzer MB Marrero KE Bernstein 《Canadian Metallurgical Quarterly》1997,272(37):23382-23388
Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors. 相似文献
9.
WI Bensinger KS Schiffman L Holmberg FR Appelbaum R Maziarz P Montgomery E Ellis S Rivkin P Weiden K Lilleby S Rowley S Petersdorf JP Klarnet W Nichols A Hertler R McCroskey CH Weaver CD Buckner 《Canadian Metallurgical Quarterly》1997,19(12):1183-1189
The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens. 相似文献
10.
CD Hébert MR Elwell GS Travlos E Zeiger JE French JR Bucher 《Canadian Metallurgical Quarterly》1993,20(3):348-359
1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献