摘要:

Abstract.CD4+T‐lymphocytes induce and regulate allergic inflammatory responses to common environmental aeroallergens derived fromDermatophagoidesspp. (house dust mite, HDM), which cause clinical symptoms in approximately 10% of the population. Definition of the molecular structure of HDM proteins combined with the ability to isolate monoclonal populations of human CD4+T‐cells representative of the ‘interleukin‐4 (IL‐4) dominant functional pheno‐type, which support immunoglobulin E (IgE) synthesis, has allowed T‐cell recognition of HDM to be examined in detail. The results of these investigations demonstrated extensive heterogeneity in both the antigen and HLA class II restriction specificity of the HDM reactive T‐cell repertoire. Furthermore, long‐lived clones of T‐cells with oligoclonality in T‐cell antigen receptor (TcR) usage, driven by chronic stimulation with HDM, have been identified in human peripheral blood. The presentation of specific peptides and superantigens under conditions that induce T‐cell non‐responsiveness has provided anin vitromodel for analysing the mechanisms of CD4+T‐cell targeted immunotherapy.’ It appears that the mechanisms underlying T‐cell anergy are accompanied by a transient downregulation of TcR and CD28 and mediated by a shift in the cytokine profile from that of the ‘IL‐4 dominant’ to the ‘interferon‐γ (IFN‐γ) dominant’ functional phenotype of CD4+T‐cells. In parallel, using a murine model, it has been demonstrated that administration of an immunodominant peptide via the mucosal surfaces of the respiratory and alimentary tracts may tolerize an established response to intact HDM proteins. The potential application of these models in the development

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00729.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Soluble secondary bile acids in the colon are supposed to be cytotoxic for normal colonic cells, resulting in an increased compensatory proliferation of colonic crypt cells, which is associated with an increased risk for colonic cancer. We developed a sensitive method to determine cytotoxicity of bile acids in the HT‐29 colon cancer cell line, using a tetrazolium‐based colorimetric assay. Only in vital cells, tetrazo‐lium‐salts are converted into formazan, which can be measured easily. Chenodeoxycholic acid and deoxy‐cholic acid (DCA) were cytotoxic in concentrations above 100 μM, which is in the physiological range for soluble DCA in faeces. Conjugation of bile acids diminished cytotoxicity 7–10 fold. In this concentration range, no effect of calcium or calciumphosphate was demonstrated, suggesting that the effect of calcium on colonic proliferation is not mediated by a precipitation of soluble bile acids in the large bowel. Finally, we could demonstrate a significant correlation between the cytotoxicity of the aqueous phase of faeces and the soluble DCA c

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00730.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The aminoterminal propeptide of type III procollagen (PIIINP) in serum is employed as a direct marker of fibrillogenesis. The balance between local fibrillogenesis and serum PIIINP is governed by the transport and possible degradation en route from tissue to circulation. In conscious pigs, we investigated the transport of PIIINP from the knee cavity into the circulation after intra‐articular injection of radiola‐belled PIIINP followed by sequential sampling of thoracic duct lymph, serum and urine. Clearance from the joint space was evaluated by external detection of131I‐HSA, used as co‐tracer. Lymph samples were gel filtrated to assess possible lymphatic degradation of the intact PIIINP.125I‐PIIINP and131I‐HSA were found in thoracic duct lymph within 20 min of the intra‐articular injection. Both isotopes had a biphasic appearance, with the first peak after 60 min and a larger peak after 150 min. During the 6 h observational period 18% of the injected PIIINP was found in the lymph. Gel chromatography of lymph showed the fast formation of a small fraction with a lower MW than that of PIIINP, which suggests that some degradation of PIIINP may occur through the lymphatics. The half‐life of the joint clearance of HSA by bulk flow was assessed to be 8.3 h. The clearance of PIIINP from the joint was estimated to be equal to that of HSA, which indicates that PIIINP leaves the joint space by bulk flow as has been proposed for HSA. Whereas the fractional amount of PIIINP in lymph and blood was lower than that of HSA, in urine the fractional amount of PIIINP was substantially higher than that of HSA. This may be the outcome of a more rapid irreversible degradation of PIIINP than of HSA.We conclude that I) PIIINP is cleared from the joint space by bulk flow; 2) degradation of PIIINP en route to the circulation cannot be excluded, but is less than 10%, and 3) after disappearing from the joint, PIIINP is distributed in body compartments in a ratio different from that of HSA. Our observations suggest that serum PIIINP may be used as a marker of fibrillogenesis in n

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00731.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Understanding the effect of fibrinolysis on platelet function is of clinical importance. Plasmin is recognized to affect platelet adhesive function by reducing the interaction of platelet glycoprotein (GP) lb with von Willebrand factor (vWF) bound to the subendothelium. This platelet function is commonly exploredin vitroby the ristocetin‐induced agglutination test. Our previous study demonstrated a plasmin‐induced redistribution of GP Ib molecules from the platelet surface to the linings of the surface‐connected canalicular system (SCCS), a critical mechanism for understanding plasmin‐induced GP Ib dysfunction. Here, we demonstrate that neutralization of plasmin by its inhibitors, aprotinin or tripeptide Val‐Phe‐Lys‐CH2CI, permits a time dependent recovery (within 30 min) of ristocetin‐induced agglutination in the platelets which were stimulated by plasmin at<1 CUml‐1. This functional recovery was accompanied with a restoration of a normal amount of GP Ib on the platelet surface, as measured by the binding of both monoclonal anti‐GP Ib antibody SZ 2 and125I‐labelled vWF to the platelets. Cytochalasin D did not inhibit this recovery, suggesting that this process may be due to passive actin depolymerization. These findings were further confirmed by immunoelectron microscopic study. Utilizing the platelets pre‐labelled with anti‐GP Jb antibody prior to plasmin stimulation, it was demonstrated that the observed recovery is due to a reverse translocation from the SCCS to the plasma membrane of the same GP Ib molecules which were present initially at the cell surface. It is concluded that plasmin‐induced GP Ib dysfunction can be reversed by plasmin neutralization and GP Ib reverse translocation plays an important role in the restoration of pl

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00732.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The effect of oral chronic administration of ursodeoxycholic acid has been examined in rats with cholestasis induced by ethinyl estradiol. Ursodeoxycholic acid at the dose of 25 mg kg‐1per day during 4 days, did not improve the decrease in basal bile flow and bile acid secretion induced by ethinyl estradiol alone. In contrast, when ursodeoxycholic acid was given at the same dose during 10 days, basal bile flow was significantly improved and basal bile acid secretion was restored to control values. When ursodeoxycholic acid was given at the dose of 500 mg kg‐1per day, basal bile flow and bile acid output were not further improved. However, bile flow and bile acid output under taurocholate infusion were restored to control values. Bile of rats treated with ursodeoxycholic acid was enriched with this bile acid. These results show a significant improvement of ethinyl estradiol‐induced cholestasis in rats after chronic administration of ursodeoxycholic acid and support the use of this bile acid in intrahepatic cholestasis i

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00733.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Platelet‐rich plasma was obtained from patients with untreated heterozygous familial hypercholesterolaemia (FH), from FH patients treated with cholestyramine and from control subjects. Responsiveness of platelets to the aggregation inhibitors adenosine, its analogue N‐ethylcarboxamidoadeno‐sine (NECA) and prostaglandin 12was decreased in FH. Patients on cholestyramine therapy showed normal responsiveness to adenosine and NECA. There were only minor changes in the binding of [3H]NECA to high‐affinity binding sites on platelet membranes from untreated FH or cholestyramine‐treated FH patients. The initial rate of cyclic AMP formation in response to a high concentration of NECA was severely decreased in platelets from FH patients. By contrast, the rate of cyclic AMP formation in response to forskolin or a high concentration of prostaglandin 12 was unchanged. These data point to a defect in the coupling of the platelet A2adenosine receptor to adenylyl cyclase in untreated FH

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00734.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.To obtain insight in the effect of TNF on the synthesis of acute phase proteins like CRP, αl‐antitrypsine, αl‐acidglycoprotein, C3 and C4 and the immunoglobulins (IgG‐M‐A), nine cancer patients who were treated with an isolated limb perfusion (ILP) with high dose recombinant TNF‐α (rTNF‐α) were investigated during a 7–day period after the end of the perfusion. Resorption of rTNF‐α from out of these limbs into the circulation after the ILP induced within 30 min to 6 h in all patients elevated serum levels of IL‐6. At the same time C‐reactive protein became detectable in serum. The highest serum levels were obtained at 48 h after ILP. The serum levels of the other acute phase proteins (α l–acidglycoprotein, αl‐antitrypsine, C3, C4), rose more slowly and the highest serum levels were found at the third day. All investigated proteins declined after they had reached their peak levels. Levels of α1‐‐acidglycoprotein and a,‐anti‐trypsin α1‐‐acid declined slower than both complement component. In regard to the immunoglobulin levels a nearly continuous increase in the serum level of specifically IgM was observed. This study clearly shows the interrelationship between TNF‐α and IL‐6 in regard to the synthesis of the different acute phase proteins; and

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00735.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.We evaluated the effect of periodical treatment with LDL‐apheresis by adsorption to dextran sulfate (Liposorber LA‐15) on several aspects related to LDL and Lipoprotein(a) metabolisms, in three homozygous familial hypercholesterolaemic patients with LDL receptor deficiency. The dextran sulfate columns retained apolipoprotein B‐containing particles with high affinity and capacity, in such a way that the treatment of a volume of plasma equivalent to three times the patient plasma volume resulted in an 85% decrease of circulating LDL‐cholesterol and Lipoprotein(a). The continuous treatment with LDL‐apheresis was highly beneficial for these patients since an average plasma concentration lower than 200 mg dl‐′ for LDL‐cholesterol, and lower than 25 mg dl‐′ for Lipoprotein(a) could be achieved by treating the patients once a week. After each apheresis treatment, plasma concentrations of these metabolites progressively returned to the pretreatment, steady‐state, levels. The analysis of the rates of return allowed us to estimate the fractional catabolic rates. FCRs of LDL‐cholesterol were 0–052, 0.049 and 0.047 pools day‐1, and those of apolipoprotein B, 0.065, 0.045 and 0.050 pools day‐1in the three subjects, respectively. These values are much lower than those in normolipidaemic individuals as observed by others, and are in accordance with the LDL‐receptor deficiency condition of our patients. Two of them had highly elevated Lipo‐protein(a) plasma concentrations, and their FCRs of Lipoprotein(a) were calculated to be 0.112 and 0.066 pools day‐1. These values were significantly higher than the respective FCR of LDL‐cholesterol and apolipoprotein B, which demonstrates that Lipopro‐tein(a) and LDL were not metabolically homogeneous in these patients. Values of‐ktfor Lipoprotein(a), LDL‐cholesterol and apolipoprotein B correlated during the first days inmediately after each apheresis session, suggesting that production of Lipoprotein(a) in these individuals was associated to that of apolipoprotein B. It is proposed that elevated Lipoprotein(a) plasma levels in familial hypercholesterolaemia are mainly a consequence of a high production rate rath

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00736.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Intestinal absorption of cholesterol, campes‐terol, campestanol, stigmasterol and sitosterol were measured in 10 healthy subjects by an intestinal perfusion technique over a 50 cm segment of the upper jejunum using sitostanol as non‐absorbable marker. Cholesterol absorption was highest and averaged 33%, whereas the absorption rate of sitosterol averaged 4.2% and of stigmasterol 4.8%. Higher absorption rates were found for campesterol (9.6%). Canipestanol, the 5a saturated derivative of campesterol, showed the highest absorption rate (12.5%) of all plant sterols. A positive correlation between the absorption rate of cholesterol and campesterol was established. In addition, there was a negative correlation between the ratio of sitosterol to cholesterol and the mass of cholesterol absorption. These results are in agreement with previous observations in animal studies, namely, that increasing the length of the side‐chain of cholesterol decreases the absorbability of the sterol. Surprisingly, campestanol, the 5α saturated derivate of campesterol, was shown to have higher absorbability compared with its unsaturated compound. This finding is in contrast to previous assumptions, that hydrogenisa‐tion of the nucleus double bond of a sterol causes a decrease of absorbability, as has been demonstrated for cholesterol/cholestanol and sitosterol/si

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00737.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin‐6, as well as acute phase reactants a‐l‐antitrypsin and C‐reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF‐α), neopterin, interleukin 2–receptor and granu‐locyte‐macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin‐2 and interleukin‐1 levels. In addition, interleukin‐6, TNF‐α and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontane

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00738.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY