[Importance of ANCAs in the pathogenesis of chronic inflammatory bowel diseases].
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Antibodies, Antineutrophil Cytoplasmic↗
Biomedical subjects
V Gross
Publications and source records attributed to V Gross.
Focal white-matter lesions in brain of patients with inflammatory bowel disease.
Inflammatory bowel diseases are often associated with extra-intestinal manifestations, such as arthritis and iritis/uveitis. Using magnetic-resonance imaging we found hyperintense focal white-matter lesions in the brain in 20 of 48 (42%) patients with Crohn's disease, in 11 of 24 (46%) patients with ulcerative colitis, but in only 8 of 50 (16%) healthy age-matched controls (relative risk [95% CI] vs controls 2.6 [1.3-5.3] and 2.9 [1.3-6.2], respectively). These findings may represent another extra-intestinal manifestation of inflammatory bowel disease.
Adult↗
Regulation of interleukin-8 production in a human colon epithelial cell line (HT-29).
BACKGROUND/AIMS: Interleukin (IL) 8 is a major neutrophil-activating cytokine synthesized by intestinal epithelial cell lines. The aim of this study was to improve the understanding of the regulation of IL-8 synthesis by investigating the roles of protein kinase C (PKC), protein kinase A (PKA), and protein tyrosine kinase (PTK) in the induction of IL-8. METHODS: HT-29 cells were stimulated with IL-1 beta or tumor necrosis factor alpha (TNF-alpha) together with activators or inhibitors of PKC and PKA or with inhibitors of PTK. The presence of IL-8 protein was detected by enzyme-linked immunosorbent assay and that of IL-8 messenger RNA by Northern blotting and in situ hybridization. RESULTS: TNF-alpha and IL-1 beta dose-dependently induced IL-8 production in HT-29 cells. Activation of PKC by phorbol myristate acetate also stimulated IL-8 production; however, the effects of IL-1 beta or TNF-alpha did not require PKC, as shown by the PKC inhibitor staurosporin or PKC depletion. Stimulation of PKA by forskolin or inhibition by H89 or H7 had no influence on the synthesis of IL-8. However, induction of IL-8 by IL-1 beta or TNF-alpha was reduced by the PTK inhibitors herbimycin (by 79% or 89%, respectively) and genistein (by > 95%). CONCLUSIONS: The synthesis of IL-8 is stimulated in HT-29 cells by IL-1 beta or TNF-alpha. This stimulation is independent from PKC or PKA but depends on protein tyrosine phosphorylation.
Cell Line↗
Control of renal medullary blood flow by vasopressin V1 and V2 receptors.
Experiments were performed in anesthetized renal-denervated rats to determine the contribution of renal medullary vasopressin V1 and V2 receptor stimulation in the regulation of renal medullary blood flow. Renal medullary interstitial infusion of the selective V1 agonist [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1) significantly decreased outer medullary blood flow by 15% and inner medullary blood flow by 35%, as measured with implanted optical fibers for laser-Doppler flowmetry. Medullary interstitial infusion of equimolar doses of arginine vasopressin (AVP) also decreased outer medullary blood flow by 15% but decreased inner medullary blood flow by only 17%, a decrease significantly less than that during the infusion of the V1 agonist. These results were confirmed in videomicroscopy experiments on the exposed papilla, which demonstrated that the V1 agonist and AVP decreased descending and ascending vasa recta capillary red blood cell velocity and calculated blood flow, with greater decreases during infusion of the V1 agonist. In further laser-Doppler flowmetry studies, stimulation of V2 receptors by medullary interstitial infusion of 1-desamino-8-D-arginine vasopressin (2 ng.kg-1.min-1) or AVP in rats pretreated with the vasopressin V1 receptor antagonist d(CH2)5[Tyr(Me)2,Ala-NH2]AVP increased renal medullary blood flow by 16 +/- 3 and 27 +/- 8%, respectively. The present experiments indicate that vasopressin V1 receptor stimulation serves to decrease renal medullary blood flow while V2 receptor stimulation appears to increase renal medullary blood flow; however, the net effect of AVP is to decrease renal medullary blood flow.
Animals↗
Effect of captopril and angiotensin II receptor blockade on pressure natriuresis in transgenic TGR(mRen-2)27 rats.
The pressure-natriuresis curve of transgenic rats harboring an extra mouse renin gene [TGR(mRen-2)27] is shifted rightward compared with controls; however, whether intrarenal angiotensin II effects are responsible for the rightward shift is unknown. To clarify this issue we infused the converting enzyme inhibitor captopril or the angiotensin II receptor blocker CV 11974 into transgenic and normotensive Sprague-Dawley Hannover control rats. We eliminated any other neural or endocrine regulatory differences between transgenic and control rats by renal denervation and infusion of vasopressin, aldosterone, corticosterone, and norepinephrine in sufficient quantities to occupy all receptors. Sodium excretion increased from 3.4 +/- 1.2 to 10.1 +/- 0.5 mumol/min per gram kidney weight in transgenic rats when renal perfusion pressure was increased from 158 to 201 mm Hg. Captopril (4 mg/kg) and CV 11974 (0.1 mg/kg) shifted the pressure-natriuresis curve of transgenic rats leftward, so that sodium excretion was threefold higher at similar renal perfusion pressures (150 to 160 mm Hg). Similarly, fractional sodium and water excretion curves were shifted leftward, so that values for transgenic and control rats were no longer different. Over the pressure range, renal blood flow in transgenic rats ranged from 3.1 +/- 0.7 to 4.4 +/- 0.5 mL/min per gram kidney weight and increased (P < .05) with both captopril and CV 11974 to ranges from 4.8 +/- 0.9 to 6.8 +/- 0.6 or from 4.5 +/- 0.7 to 6.9 +/- 1.0 mL/min per gram kidney weight, respectively. Glomerular filtration rate in transgenic rats, on the other hand, was not increased. Transgenic kidneys showed severe hypertension-induced nephrosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗
Comparison between high dose 5-aminosalicylic acid and 6-methylprednisolone in active Crohn's ileocolitis. A multicenter randomized double-blind study. German 5-ASA Study Group.
BACKGROUND: The value of 5-aminosalicylic acid (5-ASA) in Crohn's disease (CD) is still under discussion. In a previous study 2 g 5-ASA per day were inferior to a standard glucocorticoid treatment with 6-methylprednisolone (6-MPred) (Can J Gastroenterol 1990; 4: 446-51). In the present study we tested whether in active CD response rates to 4.5 g 5-ASA/day were not different from those to 6-MPred. METHODS: Multicenter randomized double-blind double-dummy trial. 34 patients with active CD (CDAI > 150) were included. 17 patients were in the 5-ASA group (Salofalk, 4.5 g/day), 17 patients in the 6-MPred group (Urbason, initial dose 48 mg/day, weekly tapering). Duration of treatment was 8 weeks. Main outcome measure was remission of CD (CDAI < 150) and decrease of at least 60 points. RESULTS: Both groups were comparable with respect to demographic and clinical parameters. The median CDAI decrease in the 5-ASA group was 85, in the 6-MPred group 122 (p = 0.7437). The median AUC of the CDAI in the 5-ASA group was 1027, in the 6-MPred group 950 (p = 0.137). The median AUC of the CDAI per treatment day was 22.94 in the 5-ASA group, and 17.33 in the 6-MPred group (p = 0.0555). On an intention-to-treat basis remission rates after 8 weeks were 40.0% in the 5-ASA group and 56.3% in the 6-MPred group (p = 0.5867). CONCLUSIONS: Response rates to 5-ASA or 6-MPred were not significantly different although there was a trend towards a higher efficacy of 6-MPred. 5-ASA may be considered as alternative treatment in patients with activer CD who are intolerant to or refuse glucocorticoids.
Adult↗
[Crohn disease: prevention and drug therapy].
In view of a high recurrence rate of Crohn's disease after surgical resection prophylaxis is desirable. The value of various medical therapies to maintain remission after surgery has thus far only partially been established in clinical trials. Therefore, no clear guidelines are presently available. In patients with complete resection and a low risk of recurrence prophylactic treatment seems not to be necessary. In patients with a high risk of recurrence prophylactic treatment is recommended. This recommendation is supported by some clinical trials, although major trials are still ongoing. 5-Aminosalicylic acid in a daily dose of ca. 2-3 g is the primary choice for prophylaxis of recurrence. It reduces the risk of recurrence presumably by about 50%. In patients with a complicated course of the disease who have undergone several previous resections immunosuppressive treatment with azathioprine (1-2 mg/kg body weight/day) is recommended to avoid further recurrences. Conventional corticosteroids are not effective for postoperative prophylaxis. Ongoing studies evaluate the non-systemic steroid budesonide as prophylactic treatment. There is no specific nutritional therapy to prevent recurrences; however, patients are advised to avoid nutrients which they do not tolerate. When patients have a clinical relapse systemic or topical corticosteroids are the treatment of choice. In moderately active disease and in patients who refuse to take corticosteroids high dose 5-aminosalicylic acid (at least 4 g/day) may be used alternatively. In patients with chronic complicated disease azathioprine is recommended.
Aminosalicylic Acids↗
A zona biochemical change and spontaneous cortical granule loss in eggs that fail to fertilize in in vitro fertilization.
OBJECTIVE: To determine the extent of biochemical changes in the zona pellucida (ZP) and cortical granule release in eggs failing to fertilize in IVF. DESIGN: After insemination, unactivated eggs without two pronuclei (PN) were studied by high resolution microscopy and fluorescent probes to determine cortical granule density and meiotic stage. After ZP isolation, proteins from individual ZPs were biotinylated, electrophoresed, and visualized by western blots with avidin-chemiluminescence. Controls included mouse unfertilized and fertilized eggs and human germinal vesicle stage oocytes and > or = 3PN eggs. SETTING: University medical center and hospital tertiary care IVF-ET program. RESULTS: Many of the unfertilized eggs were in metaphase and had relatively low cortical granule densities indicative of cortical granule loss. Approximately one half of the ZPs showed evidence of biochemical hardening with a modification of a 90 to 100 x 10(3) molecular (weight) ratio (M(r)) ZP protein. The 3PN eggs had few cortical granules and their ZPs had a pronounced 90 to 100 x 10(3) M(r) modification that was not detected in germinal vesicle stage ZP controls. CONCLUSION: The observed changes in ZP biochemistry and cortical granule quantitation demonstrate that failed fertilization is frequently associated with spontaneous cytoplasmic, but not nuclear, activation. In affected eggs, these changes could prevent fertilization in routine IVF and in cases of reinsemination. The relationship of changes in the ZP and cortical granules to infertility and in vitro culture requires further investigation. The 90 to 100 x 10(3) M(r) ZP protein modification can be detected biochemically with 1/10 of a human ZP.
Animals↗
Treatment of active Crohn's ileocolitis with oral pH-modified budesonide. Germany Budesonide Study Group.
Budesonide is a topical steroid which after intestinal absorption is rapidly degraded into inactive metabolites in the liver. Its systemic bioavailability is only 10-15%. In the present open trial the efficiency and safety of oral pH-modified release budesonide were assessed in patients with active Crohn's ileocolitis. This report describes the results of the first 30 of 78 patients. After 6 weeks of treatment with 3 x 3 mg budesonide/day 67% of the patients were in clinical remission. Typical steroid-related side effects were observed in only one patient. Budesonide therefore seems to be suited as an alternative for classical steroids in patients with Crohn's ileocolitis. Its clinical efficacy is comparable with classical steroids but it's rate of steroid-related side effects is lower.
Administration, Oral↗
[Multiple gastric wall abscesses--a rare differential endosonographic diagnosis of submucous stomach tumors].
We report a rare case of a 52 year old patient with multiple gastric wall abscesses. In 1987 a selective proximal vagotomy was performed. Because of non-specific gastric symptoms in 1993 an endoscopy and an endoscopic ultrasound was performed at another hospital which resulted in the likely diagnosis of multiple leiomyomas. Three months later a control endosonography showed three well demarcated submucosal tumors, partly echo-genic, but with an inhomogeneous echo-pattern. A laparotomy and histological examination of the submucosal gastric tumors revealed multiple gastric abscesses with granulomas after selective proximal vagotomy. Difficulties in the differential diagnosis of submucosal gastric tumors arising from this case are demonstrated and discussed.
Abscess↗
[Diagnosis of round liver lesions].
Ultrasound and computed tomography are dominant in the diagnosis of liver lesions. Angiography, magnetic resonance imaging, and scintigraphic procedures complete the spectrum. Ultrasound and computed tomography are able to detect focal liver lesions and to distinguish between hypoechoic, anechoic and hyperechoic lesions. We differentiate in addition between liver lesions found accidentally or in patients suffering from a known tumor. For a definite diagnosis of a haemangioma a computerized tomography with rapid contrast bolus or MRI should be performed. If there is suspicion of an adenoma or a focal nodal hyperplasia a hepatobiliary sequence scintigraphy should be performed. In the following the essential procedures for the differential diagnosis of liver lesions based on there sonomorphological appearance is presented.
Adenoma, Liver Cell↗
High interleukin-6 concentrations in hepatic ascites.
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Ascitic Fluid↗
Rapid assay of lactoferrin in keratoconjunctivitis sicca.
We compared measurement of lactoferrin concentration by the LactoCard solid phase ELISA assay with the LactoPlate radial immunodiffusion assay in tears of normal patients and those with keratoconjunctivitis sicca. The LactoCard, a new lactoferrin assay, allows rapid determination of tear lactoferrin concentration in 10-15 min, a notable improvement over the 3 days required of the LactoPlate. There was no statistically significant difference between the accuracy of the two assays in normal patients nor in those patients with a diagnosis of keratoconjunctivitis sicca. Both assays showed a significant decrease in tear lactoferrin concentration in patients with severe keratoconjunctivitis sicca when compared to normal patients. The LactoCard is a rapid and reliable means of measuring tear lactoferrin concentration in a clinical setting.
Adult↗
Clinical significance of sonographic findings in outpatient clinics.
In the literature substantial controversy exists about the clinical significance of abdominal screening procedures. Therefore, the aim of our prospective study was to determine the clinical relevance and the differences of sonographic findings in both symptomatic and asymptomatic screening outpatients. We therefore systematically analyzed the sonographic findings in 200 consecutive patients of a medical outpatient unit. The patients were divided into 2 subgroups: group I consisted of 128 patients without specific clinical symptoms in the abdomen (screening group); group II included 72 patients with abdominal symptoms and therefore well-defined sonographic requests. The consequences drawn from the sonographic results were analyzed separately for both patient groups. All findings were subdivided into relevant, prospectively relevant or not relevant, depending on their individual influence on the patients' course. In all cases the entire abdomen and basal parts of the thorax were examined. In the 1st group (n = 128/93 findings) 6 findings (6.5%) were relevant, 24 (26%) prospectively relevant and 63 not relevant (67.5%). In contrast, the 2nd group (n = 72/68 findings) contained 13 relevant (19%), 27 prospectively relevant (40%) and 28 not relevant sonographic findings (41%). The differences between group I and II were statistically significant for the relevant findings (2p < 0.05) and the not relevant findings (2p < 0.01). In conclusion, abdominal ultrasonography provides--even for the screening of the outpatient population--in up to 30% additional clinically acute or prospectively relevant information. Therefore, it completes the physical examination adding a substantial amount of clinical information to the medical record of outpatients.
Abdomen↗
Abnormal pressure-natriuresis in transgenic renin gene rats.
OBJECTIVE: Pressure-diuresis-natriuresis relationships were compared in rats made transgenic by implantation of the mouse salivary gland renin gene [TGR(mRen-2)27 rats] and Sprague-Dawley/Hannover rats to determine whether resetting of renal function contributes to the development of hypertension in these rats. METHODS: Differences in the neural and hormonal background were minimized by denervating the kidney and holding plasma vasopressin, aldosterone, cortisol and norepinephrine levels constant by intravenous infusion. RESULTS: In Hannover rats (n = 9), urine flow and sodium excretion increased from 26.4 +/- 6.2 to 86.8 +/- 8.6 microliters/min per g kidney weight and from 5.1 +/- 0.8 to 15.3 +/- 1.0 mumol/min per g kidney weight as renal perfusion pressure (RPP) was increased from 107 to 153 mmHg. The renal blood flow (RBF) and glomerular filtration rate (GFR) were well-autoregulated and averaged 6.6 and 1.5 ml/min per g kidney weight throughout the range of pressures studied. In TGR (n = 10), urine flow and sodium excretion increased from 30.0 +/- 6.1 to 59.7 +/- 7.2 microliters/min per g kidney weight and from 3.8 +/- 0.9 to 8.5 +/- 1.3 mumol/min per g kidney weight in response to an elevation in RPP from 170 to 212 mmHg. The RBF and GFR were about 20% lower in TGR than in Hannover rats and averaged 4.1 and 1.0 ml/min per g kidney weight, respectively. CONCLUSION: The results show that the pressure-diuresis-natriuresis relationship is shifted to higher pressure levels in TGR and that this is associated with enhanced tubular reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Free radicals in inflammatory bowel diseases pathophysiology and therapeutic implications.
Inflammatory bowel diseases are characterized by the accumulation of granulocytes and monocytes/macrophages at the site of inflammation. Activation of these cells leads to the release of degradative enzymes, e.g., proteinases and glycosidases, and the production of reactive oxygen metabolites. This has been shown both in animal models of experimental intestinal injury, and in human inflammatory bowel disease. Scavenging of oxygen radicals protected tissue from damage in experimental inflammation models. Human studies with specific oxygen radical scavengers are rare, preliminary results appear promising. The fact that the aminosalicylates used in the treatment of inflammatory bowel disease are potent antioxidants underscores the important role of reactive oxygen metabolites in this setting.
Aminosalicylic Acids↗
[The metabolic and endocrine functions of the cytokines].
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Amino Acids↗
Retinoic acid inhibits interleukin-1-induced cytokine synthesis in human monocytes.
Retinoids are pluripotent morphogens whose effects on gene expression are mediated through specific intracellular receptors. They have certain anti-inflammatory effects in vivo, the basis of which is not clearly understood. To characterize mechanisms involved with potential anti-inflammatory actions of retinoids, we studied the effects of retinoic acid (RA) on cytokine production in human peripheral blood monocytes. RA differentially modulated the expression of interleukin-1 beta (IL-1 beta), IL-6, and IL-8 mRNAs depending on the inducing stimulus. While phorbol myristate acetate-induced IL-1 beta and IL-8 mRNA expression was increased by RA (IL-6 could not be induced by this pathway in monocytes), IL-1 beta-induced expression of IL-1 beta and IL-8 was markedly reduced and IL-6 gene expression was almost completely suppressed. Lipopolysaccharide (LPS)-induced cytokine synthesis was only slightly reduced and this required a longer preincubation (> 72 h) of monocytes with RA. IL-1-induced de novo synthesis of IL-6 protein and secretion of biologically active IL-6 were also inhibited by RA. The inhibition pattern of RA was different from that of dexamethasone, which inhibited both IL-1 and LPS effects. In summary, our data show that RA regulates monocyte cytokine expression selectively in response to the particular stimuli. Inhibition of IL-1 beta-induced cytokine expression provides a mechanism that can explain some of the anti-inflammatory effects of RA.
Base Sequence↗