Search PubMed⌕ Search

Biomedical subjects

F Kern

Publications and source records attributed to F Kern.

At least 19 recordsLinked to original sources
PubMed1996

Delayed-type hypersensitivity-like mechanisms dominate late acute rejection episodes in renal allograft recipients.

Episodes of acute rejection (aRx) may occur in functional renal allografts even at a very late stage post-Tx. Histopathology in early and late aRx looks quite similar--however, there is a slower deterioration of graft function in late aRx, suggesting that pathogenetic immune mechanisms are different. In order to investigate this phenomenon we studied the gene expression pattern (IL-1beta, 2, 4, 8, 10, IFNgamma, TNFalpha, GrnA, IL-2R p55/p75) in PBMC and core biopsies from long-term renal allograft recipients with histologically proven late aRx and compared it with transplant and non-transplant controls using a semiquantitative RT-PCR technique. PBMC and graft-infiltrating cells of patients with late aRx showed an upregulation, especially of IFN-gamma, IL-4, IL-10, and TNFalpha transcripts. While IL-2 mRNA was only detected in PBMC of two patients with late aRx who were not on cyclosporine, upregulation of intragraft IL-2 mRNA allowed the best discrimination between aRx and the other groups (sensitivity: 83%, specificity: 93%). In contrast to several reports on early Rx we did not notice an elevation of granzyme A transcripts in comparison with the controls, suggesting that cell-mediated inflammatory processes (CD4+ T cell-mediated DTH) dominate the late aRx, while early aRx is characterized by the additional involvement of cytotoxic T cell response. This may explain the distinct clinical course. Additionally, in a pilot study we successfully treated late aRx in 10/12 patients with the anti-CD 4 mAb, 16H5. Our encouraging therapeutic results underline the pathogenetic role of CD4+ T cells and support our hypothesis on DTH-like mechanisms in late aRx.

Cytokines↗
PubMed1996

Ab initio calculations on (Z)-5-decenyl acetate, a component of the pheromone complex of Agrotis segetum (Lepidoptera: Noctuidae) and electrophysiological studies with chain elongated analogues.

Conformational analyses of (Z)-5-decenylacetate, a sex pheromone component of the turnip moth, Agrotis segetum, and double unsaturated pheromone analogues 4 and 5 have been performed by ab initio calculations using Gaussian 92. Two minima were found for a cisoid and a transoid conformer, differing for 0.03 kcal/mol only. Conformational energies of diene analogues (5Z,7E)-5,7-decadienyl acetate (4) and (3E,5Z)-3,5,-decadienyl acetate (5) were determined for conformers required to mimic spatial relationships of the cisoid conformation of the natural pheromone 2. Finally, single sensillum recording studies were carried out with chain elongated C11- to C16-pheromone analogues 6.

Acetates↗
PubMed1996

The enigma of CD57+CD28- T cell expansion--anergy or activation?

Expansion of a CD57+CD8+ T lymphocyte subset has been reported in HIV and human cytomegalovirus (HCMV) infection. Almost all of these T cells lack CD28 expression. While CD28- cells are often associated with anergy, some authors believe their expansion in HIV infection precipitates immunodeficiency. We studied 15 randomly chosen patients with immune activation and observed that CD57+CD28- T cell expansion may occur in various conditions and to the same degree as in HIV infection without resulting in immunodeficiency. Triple colour flow cytometry also revealed that the CD57 and CD28 antigens are coexpressed in only 3% of CD8+ T cells, irrespective of the underlying condition, so that almost all CD57+CD8+ cells are always CD28-. Analysis of Fas (CD95) expression with respect to CD28 expression on CD4+ and CD8+ T cells from 10 additional patients indicated no increased commitment to apoptosis in CD28- T cells. Semiquantitative polymerase chain reaction (PCR) comparing CD28+ and CD28-CD8+ T cells with respect to cytokine gene expression (tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1beta) in five renal transplant patients with expansion of the CD57+ subset detected no cytokine gene expression deficit in CD28- T cells. A direct association of increased proportions of CD57+CD28-CD8+ T cells with immunodeficiency/anergy is disputed.

CD28 Antigens↗
PubMed1995

Endothelium-modulated proliferation of medial smooth muscle cells: influence of angiotensin II and converting enzyme inhibition.

This study investigated the role of the endothelium and angiotensin II (Ang II) in regulating medial smooth muscle cell (SMC) proliferation. [3H]-thymidine incorporation into medial SMC of rat arteries was examined in vivo, using ballooned rat carotid arteries, as well as in vitro, using cultures of aortic tissue rings (organoids). In vivo, maximal medial [3H]-thymidine incorporation occurred within 3 days post-ballooning. In endothelium-denuded organoids, maximum medial DNA synthesis was achieved after 7 days of culture. [3H]-thymidine-labelling of SMC in intact organoids (with endothelium) increased minimally during culture, indicating that the endothelium provided protection with respect to medial proliferation under basal conditions (culture in the presence of 1% plasma-derived serum). Inclusion of 10(-7) M Ang II significantly elevated medial [3H]-thymidine incorporation above that in control cultures. The stimulatory effect of Ang II was much more pronounced in intact organoids that in endothelium-denuded organoids, indicating synergistic growth regulation by Ang II and endothelium-derived factors. When organoids were cultured in the combined presence of Ang II and the ACE inhibitor cilazaprilat, labelling indices of intact organoids were also significantly increased above control, but to a lower level than those obtained in the presence of Ang II alone. However, for endothelium-denuded organoids, medial [3H]-thymidine incorporation in the combined presence of Ang II and cilazaprilat was not significantly different from that in untreated controls. Thus, cilazaprilat exerts both endothelium-dependent and endothelium-independent negative regulatory effects on medial SMC proliferation.

Angiotensin II↗
PubMed1995

[Aspiration of petroleum by a "fire-eater"].

A 21-year-old man suffered from cough, dyspnoea and hemoptysis following accidental aspiration of petroleum. Chest x-ray and computerized tomography one day after the aspiration showed infiltrates in the lower fields. Fiberbronchoscopy revealed severe bronchitis without any signs of necrosis. Flunisolide inhalation (200 micrograms/d) and intravenous application of prednisolone (50 mg/d) and clindamycine (600 mg/d) improved pulmonary function within a few days. The infiltrates resolved over the following two weeks. This favourable result clearly shows that conservative treatment has a role in petroleum aspiration.

Administration, Topical↗
PubMed1994

Late acute rejection in long-term renal allograft recipients. Diagnostic and predictive value of circulating activated T cells.

Episodes of acute rejection can occur in functional renal grafts even at a very late stage after transplantation. They are not necessarily due to patient noncompliance. The incidence of late acute rejection is commonly underestimated because the diagnosis generally requires histopathology in order to rule out other origins of declining graft function, even more so, as the typical signs of acute rejection as seen in the early posttransplantation period (sudden and rapid increase of creatinine serum level, inflammatory signs) are missing. Histology revealed acute rejection in 157 of 412 renal allograft recipients suffering from progressive graft deterioration between the 2nd and 18th year after Tx. Late acute rejection was clearly associated with elevated levels of activated HLA-DR+ T cells in the peripheral blood. These cells were characterized by flow cytometry to be postmitotic activated effector-T cells belonging to the CD4+ and CD8+ "memory" T cell pool. The high sensitivity (97%) and specificity (88%) of flow cytometric analysis allows for the discrimination between late acute rejection and other causes of deteriorating graft function (infection, toxicity, arteriopathy, chronic rejection). Additionally, this immune monitoring can predict the success of antirejection therapy as early as a few days after initiation of treatment while conventional parameters do not reflect the therapeutic result until 1-3 weeks later. In addition to this, peripheral T cell activation also seems to identify a subgroup of patients with chronic rejection who would respond, at least partially, to steroid bolus therapy. As a result, this parameter is very useful for the clinical management of patients suffering from late deterioration of renal graft function.

Acute Disease↗
PubMed1994

ATP stimulates Ca2+ mobilization by a nucleotide receptor in glomerular endothelial cells.

The present study investigates ATP effects on Ca2+ mobilization in bovine glomerular endothelial cells (GEC) and the receptors mediating ATP response. Extracellular ATP stimulated a rise in inositol 1,4,5-trisphosphate and cytosolic free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. Extracellular Ca2+ depletion did not prevent [Ca2+]i rise. ATP effects were not mediated by P1, P2x, and P2t purinoceptors, since the P1 receptor agonist adenosine and the P2x receptor agonist [alpha,beta-CH2]ATP had no effect on inositol 1-monophosphate (IP) formation and Ca2+ mobilization and ATP does not activate P2t receptors. The P2y receptor antagonist reactive blue (10(-3) M) had little inhibitory effect on ATP (10(-5) M)-stimulated IP formation (15.6 +/- 4.2%) and Ca2+ rise (7.0 +/- 3.0%). According to the classification of purinoceptors, ATP is less potent than 2-methylthioadenosine 5'-triphosphate (2-MeS-ATP) in stimulating P2y receptors. In GEC, however, the rank order of potency in stimulating IP and [Ca2+]i rise was ATP > 2-MeS-ATP > ADP. The pyrimidine nucleotide UTP (10(-3) M) induced maximal IP formation (653 +/- 37%) and Ca2+ mobilization (591 +/- 22 nM) similar to ATP (IP 647 +/- 27%; [Ca2+]i 583 +/- 15 nM). At submaximal (10(-5) M) but not at maximal (10(-3) M) doses ATP and UTP effects were additive. ATP and UTP induced specific cross-desensitization. It is concluded that the purinergic nucleotide ATP and pyrimidine nucleotide UTP mediate their effects by a common nucleotide receptor. This receptor differs from P2z and P2y1 receptors, since by definition UTP does not activate these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1994

Discordant expression of LFA-1, VLA-4alpha, VLA-beta 1, CD45RO and CD28 on T-cell subsets: evidence for multiple subsets of 'memory' T cells.

Several adhesion molecules and CD45RO have been reported to be upregulated on the cell surface of 'memory' T cells. Using triple-color flow cytometry, we compared the levels of typical 'memory' cell markers on peripheral blood T-cell subpopulations in a number of kidney transplant recipients, patients with systemic lupus erythematosus, newborn infants and healthy donors. CD45RO, VLA-beta 1 (CD29), VLA-5 alpha (CD49e), LFA-1 (CD11a/18), and CD2 were found to be closely coregulated on CD4+ T cells, while regulation of VLA-2 alpha (Cd49b), VLA-4 alpha (CD49d) and CD44 was quite discordant. In CD8+ T cells, by contrast, multiple subsets of 'memory'-type cells were distinguished. Unlike TCR alpha/beta T cells, which expressed either high or low levels of LFA-1, TCR gamma/delta cells all expressed high levels of LFA-1 (CD11a/CD18). Examination of T cells from kidney graft fine-needle aspiration biopsies during rejection revealed intragraft accumulation of 'memory'-type T cells expressing high levels of CD2 and LFA-1 (CD11a/CD18). Regarding peripheral blood T-cell subsets, differences between patients and healthy controls were only of a quantitative nature.

Adult↗
PubMed1994

Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones.

We examined changes in cholesterol and bile acid metabolism produced by dietary cholesterol in gallstone subjects and matched controls. Healthy women were recruited and, after confirming the presence or absence of radiolucent gallstones, they were studied on regular diets and again on the same diet supplemented with five eggs daily for 15-18 d. Studies included plasma lipids, lipoproteins and apolipoproteins, dietary records, cholesterol absorption, cholesterol synthesis, plasma clearance of chylomicron remnants, biliary lipid composition, and secretion and bile acid kinetics. On low cholesterol, gallstone subjects absorbed a slightly lower fraction of dietary cholesterol, synthesized more cholesterol, and had smaller bile acid pools and faster fractional turnover rate (FTR) of bile acids. On high cholesterol, the fraction of cholesterol absorbed decreased in both groups and cholesterol synthesis decreased, especially in the gallstone group. Biliary cholesterol secretion increased in the gallstone group only. FTR of bile acids did not change in either group. Bile acid synthesis and pool tended to increase (P = NS) in the controls, but in gallstone subjects, synthesis and pool size decreased. We concluded that in gallstone subjects cholesterol and bile acid homeostasis is significantly altered, and that increasing dietary cholesterol increases biliary cholesterol secretion and decreases bile acid synthesis and pool, changes associated with cholesterol gallstone formation.

Adult↗
PubMed1993

Expression of soluble and insoluble fibronectin in rat aorta: effects of angiotensin II and endothelin-1.

This study has investigated the influence of the vasoconstrictor peptides angiotensin II (Ang II) and endothelin-1 (ET-1) on fibronectin expression by vascular smooth muscle cells (VSMC). In confluent, quiescent cultures of VSMC, Ang II and ET-1 elevated fibronectin mRNA levels in a time- and dose-dependent fashion. ET-1 and Ang II also induced a time-dependent expression of immunoreactive fibronectin in cultures of aortic organoids, and for both peptides the fibronectin immunoreactivity was most prominent within those medial smooth muscle cell layers close to the vessel lumen. Immunoprecipitation of biosynthetically labelled fibronectin elaborated by cultured VSMC revealed a predominant expression of soluble fibronectin in response to Ang II, whereas for ET-1 the newly synthesized fibronectin was predominantly incorporated into the extracellular matrix deposit of the cells. These findings indicate that Ang II and ET-1 may exert disparate effects on smooth muscle cell phenotype and migration.

Angiotensin II↗
PubMed1993

The renin-angiotensin system and extracellular matrix.

A hallmark of vascular disease is the inappropriate proliferative and synthetic behaviour of vascular smooth muscle cells. This phenotypically immature behaviour arises as a consequence of the myocytes undergoing phenotypic conversion and/or clonal proliferation of a "fetal" type of smooth muscle cell preexisting in the vessel wall. De-differentiation and initiation of proliferation is not only induced by endothelial desquamation and acute exposure of smooth muscle cells to platelet-derived mitogens, but also occurs in the uninjured blood vessel. Therefore normal components of the blood vessel are implicit in the pathological process. These include vasoconstrictor peptides, growth factor peptides and extracellular matrix molecules. In vitro and in vivo experimentation has indicated that while some of these compounds individually are only mild stimulators of smooth muscle proliferative metabolism, they may act synergistically to induce robust responses. Here we discuss the effects of the vasoconstrictor peptide angiotensin II, which can be locally generated within the vessel wall itself, on the expression of extracellular matrix molecules in vitro and in vivo. We focus on the angiotensin II-modulated expression of extracellular matrix glycoproteins, e.g. thrombospondin, tenascin, fibronectin and laminin.

Angiotensin II↗
PubMed1993

Peptide vasoconstrictors, vessel structure, and vascular smooth-muscle proliferation.

The peptide vasoconstrictors angiotensin II (Ang II) and endothelin-1 (ET-1), originally thought to derive exclusively from the plasma renin-angiotensin system and vascular endothelium, respectively, have been demonstrated to be produced independently of such sources. Local tissue angiotensin-generating systems are well documented, and endothelin production has been demonstrated for a variety of nonendothelial cells, including vascular smooth-muscle cells (VSMC). There is increasing evidence from in vitro studies that local production of these vasoconstrictor peptides may contribute to blood vessel homeostasis and the development of vascular pathologies. Results obtained from pharmaceutical intervention in humans and animals of these systems strongly support this hypothesis. In addition to their vasoconstrictor properties, Ang II and ET-1 act as potent biological effectors. In vitro, both vasoconstrictor peptides appear to modulate the activity of autocrine feedback loops in VSMC. The activity of these feedback loops in vivo may represent a central mechanism for regulation and phenotypic differentiation of this cell type. The best-recognized autocrine feedback loops of VSMC are constituted by platelet-derived growth factor and transforming growth factor-beta, both of which are influenced by the action of Ang II and ET-1. Because both vasoconstrictors (via their induction of autocrine growth modulators) may influence the composition of the extracellular matrix of VSMC, the effects of the peptide vasoconstrictors on the (auto-) regulated feedback loops are of long-term structural importance. Ang II and ET-1 promote the synthesis and secretion of the glycoproteins thrombospondin, fibronectin, and tenascin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Effects of endothelin-1 on vascular smooth muscle cell phenotypic differentiation.

Endothelin-1 (ET-1) produced by vascular endothelial cells has been proposed to act in a paracrine manner on adjacent smooth muscle cells (SMCs) in vivo, exerting a variety of short- and long-term effects. Although some of the in vitro ET-1-mediated effects are related to growth-promoting events, the physiological significance of these observations remains to be clarified. Reported discrepancies of the mitogenic potential of ET-1 may relate to differences in culturing conditions (submitogenic levels of serum in combination with ET-1). Because ET-1 has been implicated in proliferation of vascular SMCs (VSMCs) at sites of vascular injury, as well as pathological events during atherogenesis, a clarification of the mitogenic effects of ET-1 is important. This study demonstrates the possible autocrine role for ET-1 in the regulation of the vasculature, its influence on VSMC cell cycle, and autocrine and phenotypic regulation of VSMCs. Stimulation of quiescent VSMCs with a variety of peptides resulted in the secretion of biologically active ET-1 by VSMCs. In contrast to previous reports, long-term exposure (12-15 days) of VSMCs to ET-1 in nonmitogenic medium did not promote cycling of cells. On the contrary, ET-1 attenuated the cycling of VSMCs in the S and G2/M phases and interrupted progression through the cell cycle at late G1/early S phase. Subsequent to ET-1 exposure, VSMCs expressed increased levels of smooth muscle-specific alpha-actin. Therefore, autocrine-produced ET-1 may contribute to phenotypic differentiation of VSMCs.

Actins↗
PubMed1992

Expression of tenascin by vascular smooth muscle cells. Alterations in hypertensive rats and stimulation by angiotensin II.

The extracellular matrix glycoprotein tenascin is associated with remodeling events in many embryonic and pathologic tissues. The expression of tenascin has been investigated by immunohistochemistry in blood vessels of Wistar-Kyoto (normotensive) and spontaneously hypertensive rats. Weak tenascin staining was present throughout the tunica media of large and small arteries from normotensive animals; strong staining was only detectable at branching sites. In arteries from hypertensive animals, foci of strong tenascin staining were scattered throughout the tunica media. The expression of tenascin mRNA and protein by rat aortic smooth muscle cells cultured in serum-free medium was induced by the vasoconstrictor peptide angiotensin II. Transforming growth factor-beta and platelet-derived growth factor also stimulated tenascin mRNA expression. Vascular smooth muscle cells attached specifically to a substratum of tenascin, but remained rounded. Thus, increased focal tenascin expression by vascular smooth muscle cells is associated with hypertension, and may mediate angiotensin II-induced changes in vascular structure in hypertension.

Angiotensin II↗