The muscular membrane and calcium activation of the contractile system of a lamellibranch smooth muscle (ABRM)

1. Thin bundles of fresh ABRM treated by EDTA solution or Triton x-100 0.1% can be brought like glycerol-extracted fibres through contraction-relaxation cycles by changing the free Ca2+ level of the bathing medium for 10-6 M to 10-9 M. The kinetics of isometric force development and relaxation has been studied in the two conditions i.e ionic strength 0.06 pH 6.5 and ionic strength 0.28, pH 7.0 which are known to induce the catch-state in glycerol extracted fibres. When the low Ca-2+ solution (10-9M) is substituted for the high Ca-2+ solution (10-6M) immediately after the maximal force has been developed, relaxation occurs at a higher rate at ionic strength 0928 and pH 6.5. In this last condition, no tension redevelops after a quick release applied during the slow relaxation. 2. During the plateau, in presence of Ca-2+ 10-6 M. a quick release applied at any time is followed by a large redevelopment of tension at ionic strength 0.06 and pH 6.5. At ionic strength 0.28 and pH 7.0, the tension redevelops only during the decreased from 10-6 to 10-9 M without any change in the time course of the tension maintained. 3. These results suggest that in EDTA and Triton X-100 treated fibres of Abrm, the catch-state is spontaneously induced after the activation of the contractile mechanism under the same conditions of ionic strengh and pH as in glycerol extracted fibres. However, in the EDTA and Triton treated fibres, the presence of a high free Ca-2+ level is not necessary to maintain the tension in the catch-state induced at ionic strength 0.28 and pH 7.0.     

Role for macrophage migration inhibitory factor in acute respiratory distress syndrome

The critical role of macrophage migration inhibitory factor (MIF) in mediating inflammatory lung injury in acute respiratory distress syndrome (ARDS) has been raised recently. The present study has identified enhanced MIF protein expression in alveolar capillary endothelium and infiltrating macrophages in lung tissues from ARDS patients. The possibility that MIF up-regulates its synthesis in an autocrine fashion in ARDS was tested using cultured endothelial cells stimulated with MIF and a murine model of lipopolysaccharide (LPS)-induced acute lung injury. MIF induced significant MIF and tumour necrosis factor (TNF)-alpha synthesis in cultured endothelial cells and the effect was blocked by neutralizing anti-MIF antibody. A similar blocking effect was observed when MIF-stimulated endothelial cells were pretreated with neutralizing anti-TNF-alpha antibody or glucocorticoid, supporting the notion that MIF induced TNF-alpha production via an amplifying pro-inflammatory loop. Treatment with anti-MIF or glucocorticoid effectively attenuated pulmonary pathology and the synthesis of MIF or TNF-alpha in mice with LPS-induced acute lung injury. Mildly augmented expression of aquaporin 1 (AQP1) was also detected in alveolar capillary endothelium in ARDS. In vitro studies revealed that both MIF and TNF-alpha induced a small increase of AQP1 synthesis in cultured endothelial cells. These findings suggest that MIF plays a crucial pathological role leading to alveolar inflammation in ARDS. Anti-MIF and early glucocorticoid therapy may represent a novel therapeutic approach for reducing alveolar inflammation in ARDS.     

Ruptured abdominal aortic aneurysm: Impact of comorbidity and postoperative complications on outcome

Ruptured abdominal aortic aneurysm (AAA) remains a common and highly lethal problem. This study evaluates the morbidity and mortality rates and aims to identify which clinical variables could predict the outcome. We reviewed the records of 112 patients (97 men and 15 women) operated on for ruptured infrarenal AAA within the past 12 years (April 1, 1980, to March 31, 1992). Forty-seven clinical variables were collected and correlated with outcome by univariate and multivariate analysis. Mean age was 72.4 years (range 51 to 89 years). Only 12.5% were known to have an AAA before rupture. Preoperative systolic pressure <90 mm Hg was present in 84 patients (75%) and 11 patients (9.8%) experienced cardiac arrest before surgery. The in-hospital mortality rate was 49.1% (55/112). Two preoperative variables were associated with increased mortality: systolic pressure <90 mm Hg and cardiac arrest (p = 0.04 andp= 0.009, respectively). Preoperative comorbidity had no impact on outcome. Massive blood loss (5000 ml) was an intraoperative factor predictive of increased mortality (p = 0.0007). After multivariate analysis, only the following five postoperative variables were associated with increased mortality: cardiac event, renal failure requiring dialysis, coagulopathy, bleeding, and multisystem organ failure (allp <0.05). We did not identify a preoperative factor that predicts certain death and allows us to deny a patient a chance at survival. The occurrence of multisystem organ failure is associated with no survivors and raises the ethical issue of withholding treatment for these patients in the postoperative course. We favor selective screening and aggressive elective repair to improve survival by operating before rupture occurs.Presented at the Fifteenth Annual Meeting of the Canadian Society for Vascular Surgery, Vancouver, B.C., September 10–12, 1993, and at the Fourth Annual Winter Meeting of the Peripheral Vascular Surgery Society, Breckenridge, Colo., January 21–23, 1994.     

Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up.

BACKGROUND & AIMS: Collagenous colitis (CC) is a well-described entity causing chronic diarrhea and characteristic histologic findings. Several treatment options have been suggested, but no controlled data are available. We conducted a placebo-controlled trial to show the clinical and histologic effects of budesonide in CC. METHODS: Twenty-eight patients were randomly assigned to receive placebo (n = 14) or budesonide 9 mg daily (n = 14) for 8 weeks. Patients were evaluated clinically, and blinded biopsy specimens were analyzed from fixed locations at weeks 0 and 8. Clinical response was defined as a decrease of at least 50% in the disease activity score (number of bowel movements in the last 7 days). At week 8, nonresponders received open-label budesonide for the next 8-week period; responders discontinued treatment and were followed up. RESULTS: Three patients discontinued the study prematurely. Intention-to-treat analysis showed clinical response in 8 of 14 patients in the budesonide group compared with 3 of 14 responders for placebo (P = 0.05) after 8 weeks of blinded therapy, together with improved stool consistency. Histologically, there was no change in the mean thickness of the collagen band but a significant decrease of the lamina propria infiltrate in the budesonide group (P < 0.001). CONCLUSIONS: Budesonide is efficacious in inducing short-term clinical response in CC with significant reduction of the histologic infiltrate in the lamina propria.     

Specificity and regioselectivity of the conjugation of estradiol, estrone, and their catecholestrogen and methoxyestrogen metabolites by human uridine diphospho-glucuronosyltransferases expressed in endometrium

Uridine diphospho-glucuronosyltransferases (UGTs) inactivate and facilitate the excretion of estrogens to glucuronides (-G), the most abundant circulating estrogen conjugates. The identity of the conjugated estrogens formed by all known overexpressed UGTs (n = 16) was analyzed by comparison with retention time and mass fragmentation of authentic standards by HPLC tandem mass spectrometry methods. Six UGTs, namely 1A1, 1A3, 1A8, 1A9, 1A10, and 2B7, were found to glucuronidate estradiol (E(2)) and estrone (E(1)), their hydroxyls (OH), and their methoxy derivatives (MeO). Addition of glucuronic acid was catalyzed by specific UGTs at positions 2, 3, and 4 of the estrogens, whereas only E(2) was conjugated at position 17 by UGT2B7. Kinetic parameters indicate that the conjugation of E(2) at position 3 was predominantly catalyzed by 1A1, 1A3, and 1A8 and by 1A8 for E(1). Conjugation of 2-OHE(1)/E(2) and 2- and 4-MeOE(1)/E(2) was selective at position 3, mostly catalyzed by 1A1 and 1A8. Of all UGTs, UGT2B7 demonstrated the highest catalytic activities for estrogens and at least 10- to 50-fold higher activity for the conjugation of genotoxic 4-hydroxycatecholestrogens at position 4, compared with the conjugation of E(2), E(1), and 2-hydroxycatecholestrogens. Its presence was further shown in the endometrium by RT-PCR and immunohistochemistry, localizing in the same cells expressing CYP1B1, involved locally in the formation of 4-hydroxycatecholestrogens. Data show that several UGT enzymes detected in the endometrium are involved in the glucuronidation of E(2) and its 2-OH, 4-OH, and 2-MeO metabolites that exert various biological effects in the tissue.     

The Peculiar Epidemiology of Dracunculiasis in Chad

Dracunculiasis was rediscovered in Chad in 2010 after an apparent absence of 10 years. In April 2012 active village-based surveillance was initiated to determine where, when, and how transmission of the disease was occurring, and to implement interventions to interrupt it. The current epidemiologic pattern of the disease in Chad is unlike that seen previously in Chad or other endemic countries, i.e., no clustering of cases by village or association with a common water source, the average number of worms per person was small, and a large number of dogs were found to be infected. Molecular sequencing suggests these infections were all caused by Dracunculus medinensis. It appears that the infection in dogs is serving as the major driving force sustaining transmission in Chad, that an aberrant life cycle involving a paratenic host common to people and dogs is occurring, and that the cases in humans are sporadic and incidental.     

Preparation and Evaluation at the Delta Opioid Receptor of a Series of Linear Leu-Enkephalin Analogues Obtained by Systematic Replacement of the Amides

相似文献   

Characteristics of Radioimmunoassays for the α- and β-Subunits of Human Luteinizing Hormone

Abstract

The binding characteristics and specificities of the National Hormone and Pituitary Program (NHPP) kits for the radioimmunoassay of the alpha- and beta-subunits of human luteinizing hormone (hLH-α and hLH-β) were studied, as well as the specificities of the anti-hLH and anti-human follicle stimulating hormone (anti-hFSH) antisera distributed by the same organization. The affinity constants of the anti-hLH-α and anti-hLH-β antisera were calculated at 157 ± 8.4 nM^?1 and 109 ± 7.4 nM^?1, respectively. Both antisera were highly specific with regard to the other subunit. However, in the homologous hLH-α RIA, native hLH cross-reacted at 21.9%, hFSH at 17.5% and hTSH at 7.9%. The alpha-subunit of the human chorionic gonadotropin, hCG-α, was equipotent with the hLH-α standard in this assay. In the homologous hLH-β RIA, hLH showed a cross-reactivity of 14.7% while the cross-reactivities of hCG-β, hFSH and hTSH were 3.5%, 1.2% and 0.6%, respectively. The anti-hFSH antiserum was highly specific, while the anti-hLH antiserum showed non parallel competition curves. With this knowledge of the specificity of each antiserum, corrections can be properly made for the assays of hLH, hLH-α and hLH-β while the hFSH RIA can be used without correction for the presence of the three other components.