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Biomedical subjects

C Blais

Publications and source records attributed to C Blais.

At least 37 records · Page 2Linked to original sources

Kallikrein-kininogen system activation and bradykinin (B2) receptors in indomethacin induced enterocolitis in genetically susceptible Lewis rats.

BACKGROUND: The plasma kallikrein-kinin (K-K) system is activated in acute and chronic relapsing intestinal inflammation induced in Lewis rats by intramural injection of exogenous bacterial components. AIMS: To determine whether this effect is model specific, K-K system activation was investigated in a modified indomethacin induced enterocolitis model, as well as bradykinin 2 (B2) receptor distribution in the normal and acutely inflamed intestine. METHODS: Lewis rats injected with daily sublethal doses of indomethacin for two days developed acute (two days) and chronic (14 days) intestinal inflammation. Plasma prekallikrein (amidolytic), high molecular weight kininogen (HK, coagulant) and cleavage of HK (western blot) were assayed to detect K-K activation. RESULTS: Liver and spleen weights were significantly higher, and body weights and haematocrit values were significantly lower in the indomethacin group than in the control group. During both acute and chronic phases, rats displayed K-K system activation manifested by a significant decrease in plasma prekallikrein and HK functional levels, and by HK cleavage. Plasma T kininogen (a major acute phase protein) was significantly elevated. B2 receptors were identified in both normal and inflammatory intestine with more prominent specific immunohistochemical staining in the acutely inflamed tissue. CONCLUSIONS: K-K system activation occurs in association with both acute and chronic phases of intestinal injury, regardless of the triggering agent, suggesting that activation of this system is integrally involved in intestinal inflammation in genetically susceptible hosts. Localisation of B2 receptors across intestinal layers provides a structural basis for the kinin function in the intestine.

Acute Disease↗

Zidovudine potentiates local and systemic inflammatory responses in the rat.

The effect of chronic treatment with zidovudine (AZT) on the inflammatory response was examined in the rat. AZT was administered orally for 36 days. On day 35, inflammation was induced by hindpaw injection of 1% carrageenan lambda. Paw edema over a 24-hour period was used as a marker of the local inflammatory reaction. On day 36, quantification of immunoreactive T-kininogen and alpha 1-inhibitor-3 in liver and serum was used to assess the systemic inflammatory response. Albumin was selected as a protein whose concentration is modified only slightly or not at all during the acute-phase response. Animals treated with AZT transiently exhibited significantly greater (18%) paw edema 3 hours after carrageenan injection. AZT treatment alone induced a 1.8-fold increase in serum T-kininogen concentration, but it had no effect on albumin and alpha 1-inhibitor-3. In rats with inflamed paws, AZT administration led to a significant increase in liver (3.4-fold) and serum (1.8-fold) immunoreactive T-kininogen content. Dot blot analysis of total RNA isolated from liver correlated with the protein measurements. Our results indicate that chronic treatment with AZT potentiates the nonspecific local and the systemic inflammatory responses in the rat.

Acute-Phase Proteins↗

Involvement of a 3beta-hydroxysteroid dehydrogenase activity in ecdysteroid biosynthesis.

Ecdysteroid biosynthesis was analyzed in vitro using dissociated Y-organ cells from the shore crab Carcinus maenas. 3-Dehydroecdysone (3DE) was detected as a minor secretory product, in addition to the formerly identified end-products 25-deoxyecdysone and ecdysone (E). In conversion studies, 3DE was formed from tritiated 5beta-ketodiol (2,22,25-trideoxyecdysone), 2,22-deoxyecdysone and 2-deoxyecdysone but not from E. Further experiments were performed in order to understand the interconversions between 3-oxo and 3beta-OH compounds in the crab Y-organ. The enzyme involved in 3beta-dehydrogenation was not ecdysone oxidase, a soluble enzyme found in peripheral tissues of many arthropods but it presented strong similarities with 3beta-hydroxysteroid dehydrogenase enzymes from vertebrates: it was membrane-bound and NAD+-dependent. Moreover, a NADH-dependent 3beta-reduction of several 3-oxo-ecdysteroids was obtained using the same microsomal fraction (100,000 x g pellet) of Y-organs, indicating that the reaction might be reversible. As this activity was specific of molting glands, we hypothesize that there is at least one 3beta-hydroxysteroid dehydrogenase enzyme involved in the biosynthetic pathway of ecdysteroids.

3-Hydroxysteroid Dehydrogenases↗

Involvement of endogenous kinins in the pathogenesis of peptidoglycan-induced arthritis in the Lewis rat.

OBJECTIVE: To investigate the pathophysiologic roles of endogenous bradykinin (BK) and des-Arg9-BK on local and systemic inflammatory responses in a rat model of acute arthritis induced by peptidoglycan-polysaccharide (PG-APS). METHODS: Female Lewis rats were injected intraperitoneally with PG-APS. Selective antagonists of B1 (Lys-[Leu8]-des-Arg9-BK) and B2 (Hoe 140) receptors were infused at 500 microg/kg and 5 mg/kg per day for 6 days, starting 3 days before induction of inflammation, with subcutaneous micro-osmotic pumps. The local inflammatory response was assessed by paw edema, joint swelling, and tissue content of BK and des-Arg9-BK. These peptides were measured by highly sensitive and specific chemiluminescent enzyme immunoassays. Systemic inflammatory reaction was evaluated by the hepatic concentration of the type 2 acute-phase protein T-kininogen. RESULTS: PG-APS induced significant paw edema and joint swelling 24-72 hours after intraperitoneal injection. The maximal responses to PG-APS observed at 72 hours were significantly reduced (31-38%) by the combination of both B1 and B2 receptor antagonists at 5 mg/kg per day. PG-APS induced a significant increase of BK (up to 5.3-fold) and des-Arg9-BK (up to 4.1-fold) 72 hours after challenge. Liver T-kininogen content was increased by 5.3-, 7.7-, and 5.8-fold at 24, 48, and 72 hours, respectively, after PG-APS injection. At 24 hours, Hoe 140 and Lys-[Leu8]-des-Arg9-BK increased liver T-kininogen content by 43% and 45%, respectively, but they had no effect at 72 hours. CONCLUSION: The results indicate that endogenous kinins are involved in local and systemic acute inflammatory responses, through both B1 and B2 kinin receptors, in the model of PG-APS-induced arthritis.

Acute Disease↗

Contribution of angiotensin-converting enzyme to the cardiac metabolism of bradykinin: an interspecies study.

The role of angiotensin-converting enzyme (ACE) in the metabolism of bradykinin (BK) has been studied in several tissues. However, and contrary to angiotensin I, the metabolism of BK at the cardiac level has not been investigated. In this study, we define the participation of ACE in the carboxy-terminal degradation of BK in heart membranes of the dog, human, rabbit, and rat. The calculation of the kinetic parameters characterizing the metabolism of BK and the generated des-Arg9-BK can be summarized as follows: the half-life (t1/2) of BK [dog (218 +/- 32 s) > human (143 +/- 9 s) = rat (150 +/- 4 s) > rabbit (22 +/- 2 s)] and of des-Arg9-BK [dog (1,042 +/- 40 s) > human (891 +/- 87 s) > rat (621 +/- 65 s) > rabbit (89 +/- 8 s)] both showed significant differences according to species. Enalaprilat, an ACE inhibitor, significantly prevented the rapid degradation of BK and des-Arg9-BK in all species studied, whereas retrothiorphan, a neutral endopeptidase inhibitor, and losartan, an angiotensin II type I receptor antagonist, did not affect this metabolism. The relative importance of ACE in the cardiac metabolism of BK was species related: dog (68.4 +/- 3.2%) = human (72.2 +/- 2.0%) > rabbit (47.7 +/- 5.0%) = rat (45.3 +/- 3.9%). ACE participation in the metabolism of des-Arg9-BK was as follows: rabbit (57.0 +/- 4.0%) > dog (39.9 +/- 8.8%) = human (25.4 +/- 5.5%) = rat (36.0 +/- 7.0%). The participation of cardiac kininase I (carboxypeptidase M) in the transformation of BK into des-Arg9-BK was minor: human (2.6 +/- 0.1%) > dog (0.9 +/- 0.1%) = rabbit (1.0 +/- 0.1%) = rat (1.0 +/- 0.1%). These results demonstrate that ACE is the major BK-degrading enzyme in cardiac membranes. However, the metabolism of exogenous BK by heart membranes is species dependent. Our observations could explain some discrepancies regarding the contribution of kinins in the cardioprotective effects of ACE inhibitors.

Amino Acid Sequence↗

Digoxigenin-labeled peptides for the immunological quantification of intracellular signaling proteins: application to the MAP kinase kinase isoform MEK2.

Two competitive enzyme immunoassays using digoxigenin-labeled peptides have been developed for the quantification of the protein kinase MEK2 in cell extracts. Rabbit polyclonal antibodies directed against either the amino-terminal or proline-rich amino acid sequences of MEK2 were used for the immunoconcentration of the protein. Anti-digoxigenin Fab fragments labeled with horseradish peroxidase allowed the detection of the immune complexes. Amino-terminal and proline-rich enzyme immunoassays exhibited a sensitivity level of 63 and 71 fmol/mL, respectively, and displayed a half-maximal saturation value of 1320 and 1780 fmol/mL. The intra- and inter-assay coefficients of variation for both assays assessed at three different concentrations of MEK2 were lower than 6% and 12%, respectively. The amount of MEK2 measured by the two methods demonstrated an excellent correlation with the expression level of the protein detected by immunoblot analyses when tested on different cell lysates.

Animals↗

Evidence for the involvement of 3-oxo-delta 4 intermediates in ecdysteroid biosynthesis.

Although the involvement of 3-oxo-delta 4 compounds as intermediates in arthropod ecdysteroid biosynthesis has been postulated for a long time, it has not yet been directly demonstrated. In the present study, 3-oxo-delta 4-steroids have been synthesized and incubated in vitro with dissociated moulting gland cells from the crab Carcinus maenas. The tritiated compounds were converted into 3-dehydroecdysone, ecdysone and/or 25-deoxyecdysone, i.e. final ecdysteroids. This means that the 3-oxo-delta 4 compounds had undergone a 5 beta-reduction, to give the 5 beta-conformation of ecdysteroids. Our results suggest that the 3-oxo-delta 4-steroid 4,7-cholestadien-14 alpha-ol-3,6-dione may be an intermediate in the biosynthetic pathway. The 5 beta-reduction reaction involves a cytosolic enzyme which requires NADPH as electron donor and seems specific for 3-oxo-delta 4 substrates. This reaction was the most active in crab Y-organs, as compared with other tissues. The characteristics of the 5 beta-reductase (subcellular localization, substrate and cofactor requirements) appear similar to those of the vertebrate 3-oxo-delta 4-steroid 5 beta-reductase involved in steroid hormone catabolism and bile acid biosynthesis.

Animals↗

Bradykinin decreases T-kininogen synthesis in a rat hepatoma cell line: evidence of bradykinin B2-type receptors.

Using the rat H4-II-E-C3 hepatoma cell line, we investigated the presence of [125I][Tyr8]BK binding sites and the direct modulation of T-kininogen synthesis, an acute phase protein of inflammation, by bradykinin (BK) analogues. H4-II-E-C3 membrane preparations exhibited [125I][Tyr8]BK binding sites with a Kd of 4 nM and a Bmax of 120 fmol/mg of protein. Des-Arg9-BK showed no affinity (Ki > 10(-4) M) for these sites. The B2 metabolism-resistant and selective agonist [Phe8 psi (CH2-NH)Arg9]BK decreased the T-kininogen concentration in H4-II-E-C3 medium by 23% (p < 0.05). This effect was reversed by coincubation with the B2 antagonist HOE140. The B1 agonist Sar[D-Phe8]des-Arg9-BK and the B1 antagonist Lys[Leu8]des-Arg9-BK did not modify T-kininogen concentrations. The interaction between cytokines and kinins in the modulation of T-kininogen synthesis was also studied. Preincubation of hepatoma cells for 1 h with interleukin-1 alpha (IL-1 alpha) alone reduced T-kininogen concentrations by 37%, and this effect was blocked by co-addition of HOE140. Preincubation with interleukin-6 (IL-6) increased T-kininogen levels by threefold. Coincubation in the presence of the B2 agonist decreased this augmentation by 24%. The latter effect was reversed by co-addition of HOE140. None of the cytokines tested induced a response to the B1 agonist or antagonist under the experimental conditions studied. Overall, these results support the presence of a functional B2 receptor on H4-II-E-C3 cells that modulates T-kininogen synthesis. We suggest that the receptor is involved in vivo in a retroaction loop between kinins and T-kininogen production during inflammation. We speculate that BK could be a mediator in the modulation of acute phase protein synthesis by the cytokines IL-1 alpha and IL-6.

Acute-Phase Reaction↗

Chloramphenicol and the inflammatory response in the rat. Upregulation of the gene for T2-kininogen in liver.

Recent observations have indicated that cytokine and glucocorticoid mediators of the inflammatory response in mammals interfere with mitochondrial respiratory capacity of cultured cells. Here, we report studies on the effect of the antibiotic chloramphenicol (CAP), a potent mitochondrial protein synthesis and respiratory inhibitor, on the inflammatory response in the rat. CAP was injected daily (i.p.) at doses of 30, 100 and 300 mg kg-1 during a period of 10 days. Acute inflammation was induced on day 10 by s.c. injection of carrageenan into the hindpaws. Paw edema reaction and liver and serum expression of the acute phase protein T-kininogen were used as markers of the local and systemic inflammatory response, respectively. Albumin was selected as a liver protein whose expression is little or not affected in inflamed rats. We found that the swelling process induced locally by carrageenan injection was significantly altered in rats treated with CAP at the dose level of 300 mg kg-1. The inhibitory effect of CAP was transient, extending up to 3 hr after carrageenan injection. CAP was observed also to alter the mitochondrial respiratory capacity of liver cells, reducing cytochrome C oxidase activity up to 50%. In contrast, liver immunoreactive T-kininogen content and the T2-kininogen mRNA steady-state level were found to increase in a dose-related manner in CAP-treated animals. These values were slightly different from those recorded in control rats inflamed with carrageenan. No significant increase of T-kininogen serum content was seen at all dose levels of CAP injected. Among inflamed animals, those exposed long-term to CAP had elevated liver and serum T-kininogen content and t2-kininogen mRNA steady-state levels. Expression of the gene for albumin was not affected in rats treated or not with CAP. The present observations indicate that CAP influences both local and systemic inflammatory responses in the rat.

Animals↗

Preoperative ultrasound diagnosis of a gastric duplication cyst with ectopic pancreas in a child.

Duplication cysts of the antral and duodenal regions are rare, and small ones are difficult to diagnose preoperatively. The authors present the case of a 4-year-old boy with recurrent bouts of upper gastrointestinal hemorrhage over the previous 2 years. At first, gastroscopy was diagnostic for antral ulcerations, which healed with medical treatment. Chronic blood loss persisted and was associated with abdominal pain. A barium study showed antral deformity, with a suspected mass, which prompted a selective ultrasound examination, during which a 1-cm duplication cyst was detected. Of special interest is the change in shape and content of that cyst, demonstrated sonographically over a 2-month period. In children, high-resolution ultrasonography can be an important step in evaluation of the gastrointestinal tract. Here it showed a small but surgically significant lesion.

Child, Preschool↗

Reliability of frontal chest x-ray in diagnosing pulmonary opacities in children.

RATIONALE AND OBJECTIVES: The World Health Organization recommends that the routine investigation of children with suspected pneumonia should not include lateral chest x-rays. However, the reliability of the frontal view alone in the diagnosis of pulmonary opacities has not been reported. METHODS: The authors studied prospectively 373 consecutive chest x-rays of children, ranging in age from 0 to 17 years, who were examined for suspected pneumonia. One radiologist interpreted the frontal view, and the diagnoses were compared with those of three radiologists who interpreted both frontal and lateral x-rays. RESULTS: William's index for rater reliability was 0.98 for all ages (95% confidence interval: 0.94, 1.00). Thus, a radiologist using only a frontal view would agree with members of an independent group using both frontal and lateral views as often as an isolated member of that group would agree with the other group members. CONCLUSIONS: Detecting a definite pulmonary opacity on the frontal view alone predicts its presence on frontal-lateral views. However, the interpretation of bronchial thickening and peribronchial alveolar confluences as opacities is a problem remaining on either frontal or frontal-lateral views.

Child↗

The radiologic report: a realistic approach.

The radiologic report records all of the important steps taken in the practice of radiology and should be evaluated with special interest. The literature reflects the subjectivity inherent to a field left to personal interpretation, and few prospective studies of radiologic reporting are available. To determine the characteristics of the ideal radiologic report, the authors held workshops with two groups of radiologists and residents in radiology. The following items (in order of priority) were considered of prime importance by the participants and are discussed here: expression of an opinion and presentation of a workable differential diagnosis; an answer to the referring physician's question; a list of the limitations of the examination, if any; open-ended recommendations to the referring physician; integration of the findings with the clinical context; a synthesis of the findings obtained with various imaging modalities, when pertinent; and a complete description of the findings. The radiologic report has been compared to a scientific paper, and this comparison suggests the format for bringing these items together. The resulting realistic blueprint for the ideal radiologic report can be tailored to fit every imaging situation. Moreover, it can be a useful tool for evaluating the whole imaging process.

Humans↗

Biliary pseudolithiasis in a child associated with 2 days of ceftriaxone therapy.

Ceftriaxone, a third-generation cephalosporin, is known to induce reversible precipitations in the gallbladder of children. In general, radiologic signs and symptoms will develop after 9-11 days of treatment. The authors report a case where 48 h of therapy were sufficient to develop a biliary pseudolithiasis. Clinicians and radiologists should be aware of this complication which mimics true cholelithiasis.

Ceftriaxone↗

Short-term response to dietary counseling of hyperlipidemic outpatients of a lipid clinic.

OBJECTIVE: To evaluate the efficacy of a limited dietary intervention delivered by dietitians in a single counseling session on plasma lipid levels in free-living subjects with hyperlipidemia. DESIGN: A 2-month, nonrandomized comparative study of dietary counseling efficacy in subjects with hyperlipidemia. Dietary instruction was conducted in a lipid clinic by dietitians. Subjects were instructed to follow a diet low in saturated fat and cholesterol (National Education Cholesterol Program step 1 or 2 diets) for 2 months with concomitant energy restriction for weight reduction when necessary. Another group of patients who did not receive dietary counseling during the same period served as a control. SUBJECTS: Ambulatory patients were recruited from the Lipid Clinic of the Montreal Clinical Research Institute. INTERVENTION: Dietary counseling was provided to 104 subjects with hypercholesterolemia and 113 subjects with hypertriglyceridemia. They were compared with 72 subjects with hypercholesterolemia and 80 subjects with hypertriglyceridemia who did not receive dietary counseling. RESULTS: In the hypercholesterolemic group, significant reductions in plasma cholesterol (mean +/- standard deviation = -5.7 +/- 11.7%) and low-density lipoprotein cholesterol (LDL-C) (-7.3 +/- 14.2%) and no changes in plasma very-low-density lipoprotein cholesterol (VLDL-C) or high-density lipoprotein cholesterol (HDL-C) were observed after dietary counseling. The LDL-C response to diet was normally distributed, and 20% of the individuals with hypercholesterolemia reached LDL-C levels below 4.1 mmol/L. In patients with hypercholesterolemia and no clinical evidence of familial hypercholesterolemia, (n = 76) the reductions in plasma cholesterol (-6.6 +/- 10.8%) and LDL-C (-8.2 +/- 14%) were more pronounced. Among the latter patients, 27.6% reached LDL-C levels below 4.1 mmol/L. In subjects with hypertriglyceridemia, the reductions in plasma cholesterol (-4.8 +/- 12.8%), triglycerides (-20.7 +/- 33%), and VLDL-C (-19.5 +/- 29%) were associated with an increase in LDL-C (+8.5 +/- 25.7%) and HDL-C (+5.5 +/- 18%). Of the subjects with hypertriglyceridemia, 20% had triglyceride levels below 2.3 mmol/L after treatment. No significant changes were observed in the control groups during the same period. CONCLUSIONS: Dietary counseling of subjects with hypercholesterolemia or hypertriglyceridemia was associated with beneficial changes in plasma lipid levels after 2 months of dietary intervention. However, longer and more controlled dietary interventions are necessary for most patients to achieve lipid goals.

Adult↗

Concept mapping of movement-related knowledge.

Concept mapping was developed by Novak and Gowin in 1984 as a technique to examine an individual's knowledge-base in a given domain. In the motor domain, however, with a heavy emphasis on automated and tacit knowledge there may not be a base of information which can be verbally reported. 52 subjects with similar academic backgrounds were asked to explain all they knew about the concept of movement, and these reports were transcribed and assessed by four judges. Subjects also completed a pattern-recognition task related to procedural knowledge for movement. Over-all, the judges were able to identify a clear hierarchy in the levels of movement-related knowledge, suggesting that this technique may be useful in research on movement. However, this declarative knowledge appeared to be distinct from associated procedural knowledge, supporting Anderson's (1982) theory and the need for several tools to provide a more complete reflection of the knowledge base in a particular domain.

Acceleration↗

[Antegrade puncture of the superficial femoral artery: a pilot project].

Antegrade puncture of the femoral artery is often the first step in angioplasty or thrombolysis of the lower limb. Because of presumed complications, mostly from anecdotal literature, the common femoral artery is the preferred site of entry. From there, selective catheterization of the superficial femoral artery can be performed. This two-step procedure is sometimes long and difficult for both the patient and the radiologist. To improve the ease and the rapidity of this procedure, the author performed direct antegrade puncture of the superficial femoral artery during 25 consecutive antegrade approaches. The only local complication was hematoma, which developed in two patients but disappeared spontaneously. Aggravating factors were the size of the catheters used and fibrinolytic therapy in one of the affected patients. The results of this pilot study suggest strongly that direct antegrade puncture of the superficial femoral artery is safer than might be expected from the literature, which deals primarily with retrograde puncture. This approach must now be systematically compared with the "classic" common femoral artery approach.

Aged↗