PubMed Health⌕ Search

Biomedical subjects

W Jelkmann

Publications and source records attributed to W Jelkmann.

At least 109 records · Page 6Linked to original sources
PubMed1991

Erythropoiesis and erythropoietin levels in renal transplant recipients.

Moderately increased blood levels of endogenous erythropoietin (Epo) usually induce complete restoration of renal anemia after successful kidney transplantation. With good graft function erythropoiesis is maintained by normal Epo serum levels. Persistent anemia can be related to iron deficiency, low excretory graft function, and high dosage of immunosuppressive agents leading to marrow suppression or nephrotoxicity. Acute early rejection is associated with a fall in serum Epo and abrogation of reticulocytosis. About 15% of recipients fail to exhibit the normal feedback regulation and develop a mostly transient posttransplant erythrocytosis. Both an increased sensitivity of erythrocytic progenitors to Epo and inappropriate Epo secretion by the native kidneys may account for this overshooting reaction.

Anemia↗
PubMed1991

Theophylline and magnesium inhibit the contraction elicited with ciclosporin and angiotensin II in mesangial cell cultures.

One serious side effect of ciclosporin (CS) therapy is its acute nephrotoxicity characterized by a marked decrease in glomerular filtration rate (GFR). A main determinant of GFR is the ultrafiltration coefficient which is thought to be regulated by the contractile state of the cells of the mesangium. CS enhances contractions of mesangial cells elicited with angiotensin II. By way of a lowered ultrafiltration coefficient this effect of CS may be partly responsible for its acute nephrotoxicity. We have therefore examined the effect of compounds that may attenuate the enhanced contractile response of the smooth-muscle-like mesangial cells. Prostaglandin E2 (10(-8)-10(-5) mol/l) and dibutyryl cyclic AMP (10(-4) mol/l) reduced the number of contracting cells from more than 50% to about 10%. The clinically used agent theophylline (10(-5) g/ml) decreased the number of contractions of CS-pretreated mesangial cells from 80.0 to 28.4% (p less than 0.001). Additionally, a marked decrease in the percentage of contractions (83.3 to 33.3%; p less than 0.001) was observed when the concentration of magnesium chloride was elevated from 0 to 2 mmol/l. The finding that the enhanced contractile response of CS-pretreated mesangial cells can be overcome by theophylline and/or high magnesium levels may be of clinical interest with a view to acute CS nephrotoxicity.

Angiotensin II↗
PubMed1991

Isolated serum-free perfused rat kidneys release immunoreactive erythropoietin in response to hypoxia.

The renal glycoprotein hormone erythropoietin (Epo) interacts with erythrocytic progenitors to stimulate their proliferation and differentiation in the bone marrow. The renal O2-sensing mechanism in the control of the synthesis of Epo is still poorly understood. Therefore, the capacity of isolated rat kidneys to produce Epo during hypoxic and anemic perfusion was studied. The kidneys were perfused at a constant perfusion pressure of 100 mm Hg with a substrate-enriched Krebs-Henseleit solution containing 60 g/liter BSA and freshly drawn human erythrocytes. Epo was measured by RIA. When the kidneys were perfused at an arterial pO2 of 720 or 150 mm Hg (hematocrit, 5%), Epo production was very low (0.1-0.2 U/g kidney within 3 h of perfusion). When the arterial pO2 was lowered to 35 or 20 mm Hg, Epo production increased to 0.4 and 0.9 U/g kidney, respectively. The release of Epo during hypoxic perfusion (pO2 35 and 20 mm Hg) was little affected by changes in the hematocrit, i.e. the O2-carrying capacity of the perfusion medium over a wide range (0-40%). These results indicate that the production of Epo in the isolated perfused kidney depends on the availability of O2 and can be modulated by changes in the arterial pO2.

Anemia↗
PubMed1990

Serum erythropoietin level: relationships to blood hemoglobin concentration and erythrocytic activity of the bone marrow.

The question as to whether the serum concentration of erythropoietin is relatively high for the degree of anemia in patients with erythrocytic hypoplasia has regained interest, since recombinant human-like erythropoietin has become available as a drug for replacement therapy. We have compared the concentration of serum immunoreactive erythropoietin in nonrenal anemic patients with erythrocytic hypoplasia (22 cases) or active erythropoiesis (82 cases). In both groups a negative correlation was determined between the blood hemoglobin concentration and the logarithm of the erythropoietin concentration. However, the two regression lines were not identical, and the serum erythropoietin concentration was significantly higher for the degree of anemia in the patients with erythrocytic hypoplasia. Additional measurements in four patients suffering from acute leukemia with marrow failure showed that the erythropoietin concentration decreased towards the values observed in anemic patients with active erythropoiesis when the erythron recovered in the early phase of complete remission. These data support the idea that, independent of the O2 offer, the proliferating erythrocytic progenitors by negative feedback lower the blood level of erythropoietin.

Adult↗
PubMed1990

Helium-neon laser irradiation inhibits the growth of kidney epithelial cells in culture.

We have investigated the in vitro action of helium-neon (He-Ne) laser light on the cell cycle and the growth of rat kidney epithelial cell cultures. Dose-response studies showed that repeated He-Ne irradiation (dose rate 40 mW/cm2) once a day in a dose range between 11.9 and 142 J/cm2 significantly inhibited cell growth, while daily irradiation with 4.7 J/cm2 had no effect. Microscopic examination of nuclear spreads revealed an increased number of cells in mitosis after a single irradiation with 142 J/cm2. These results support previous observations suggesting that laser light of low thermal energy interferes with cell cycling and may inhibit cell growth when irradiation is performed at doses of 11.9 J/cm2 or more.

Animals↗
PubMed1990

Dependence of serum erythropoietin level on erythropoiesis in leukemia.

The dependence of the serum erythropoietin (Epo) level on the blood hemoglobin concentration was compared in patients suffering from leukemia and ulcerative colitis. In leukemia, the level of immunoreactive and bioactive Epo was generally much higher than in ulcerative colitis at comparable degrees of anemia. The highest Epo values were found in patients with severe bone marrow insufficiency of erythropoiesis. These findings support the hypothesis that the plasma level of Epo depends not only on the hemoglobin concentration of the blood but is also influenced by the proliferative activity of the erythron.

Anemia↗
PubMed1990

Role of cytochrome P450 in the control of the production of erythropoietin.

Effects of agents affecting cytochrome P450 were studied on the production of erythropoietin (Epo) in cultures of the human hepatoma cell line HepG2. Epo was measured by radioimmunoassay of the culture media after 24 h of incubation. The addition of phenobarbital or 3-methylcholanthrene, which induce cytochrome P450, significantly enhanced the formation of Epo. Likewise, the thyroid hormones T3 and T4 stimulated the rate of the production of Epo. On the other hand, the formation of Epo was lowered following the addition of diethyldithiocarbamate or cysteamine chloride, which inhibit cytochrome P450. These findings support the idea that O2 sensitive hemoproteins of the microsomal mixed-functional oxidases play a role in the control of the synthesis of Epo.

Carcinoma, Hepatocellular↗
PubMed1990

A new potexvirus associated with strawberry mild yellow edge disease.

A physical map of cDNA clones prepared from dsRNA associated with the MY-18 source of strawberry mild yellow edge (SMYE) was constructed and 854 nucleotides adjacent to the 3' poly(A) tail were sequenced. The larger open reading frame product of Mr 25714 showed considerable amino acid homology to the coat protein cistrons of six potexviruses and two carlaviruses. A second product of Mr 11216 encoded completely within the coat protein cistron, but in a different frame, has similarities to two potexvirus polypeptides. The Mr 25714 ORF was fused to the Protein A gene in an expression vector and the fusion protein was purified by affinity chromatography and used to immunize a rabbit. The resulting polyclonal antiserum reacted strongly in immunoelectron microscopical tests with filamentous particles resembling those of potexviruses. Such particles were detected in the following SMYE sources: D-74 from Germany, two from the United Kingdom in Fragaria vesca 'Alpine' indicator plants and Oregon MY-18 in Rubus rosifolius. Among 27 potexvirus antisera tested for serological reactions none yielded strong decoration. Examination of ultrathin sections of R. rosifolius and F. vesca tissue infected with SMYE revealed aggregates of filamentous particles in phloem parenchyma cells. dsRNA from nine sources of SMYE collected from around the world reacted with the cDNA clones of this potexvirus in Northern hybridizations. It is concluded that the potexvirus is hitherto undescribed and the name strawberry mild yellow edge-associated potexvirus is proposed.

Amino Acid Sequence↗
PubMed1990

Modulation of the production of erythropoietin by cytokines: in vitro studies and their clinical implications.

The etiology of the anemia of chronic disorders is complex. Factors which clearly contribute to the suppression of erythropoiesis are (a) reduced iron availability and (b) stimulation of the synthesis of immunomodulatory peptides such as IL-1, TNF-alpha and IFN-gamma, which inhibit the proliferation of erythrocytic progenitors in the bone marrow. The question as to whether lack of EPO is of general importance in the pathogenesis of the anemia of chronic inflammatory and malignant diseases is still a subject of controversy. The present in vitro studies show that IL-1 and TNF-alpha, but not IFN-gamma significantly lower the pO2-dependent formation of EPO in HepG2 cultures. In addition, clinical examples are given of anomalously low or high EPO levels in association with diseases involving the immune system. It is proposed that monokines and related immunomodulatory peptides could play a role in the control of the production of EPO.

Erythropoietin↗
PubMed1990

Immunoreactive erythropoietin in the anemia of non-renal chronic diseases.

Knowledge of the endogenous blood level of erythropoietin (Epo) has gained recent interest in view of the advances in Epo replacement therapy in anemic patients. By radioimmunoassay, we have carried out comparative measurements of the serum Epo level in patients suffering from chronic enterocolitis or leukemia. In chronic enterocolitis, the Epo level showed an exponential increase with the degree of anemia (up to 250 U Epo/1 serum at 70 g hemoglobin/1 blood). Similarly anemic patients with leukemia and severe bone marrow insufficiency of erythropoiesis had much higher Epo levels (usually above 500 U/1). Our findings indicate that the level of Epo is not only dependent on the blood hemoglobin concentration but also on the type of anemia. In fact, additional in vitro studies showed that immunomodulatory peptides can significantly influence the production of Epo in the hepatoma cell culture HepG2.

Adult↗
PubMed1990

Erythropoietin production in the isolated perfused kidney.

In order to further investigate the dependency of the production of erythropoietin (Epo) on the renal O2 supply, experiments were carried out in the isolated perfused rat kidney (IPRK). The kidneys were perfused with a substrate enriched Krebs-Henseleit solution containing 60 g/l bovine serum albumin at a constant perfusion pressure of 100 mmHg. When the kidneys were perfused at an arterial pO2 of 720 or 150 mmHg (hematocrit 5%), Epo production measured by RIA was very low (0.1-0.2 U/g kidney after 3 h of perfusion). At a pO2 of 20 mmHg, Epo production increased markedly up to 0.9 U/g kidney. However, the production of Epo was little affected by changes in the hematocrit of the perfusion medium from zero to 40%, even if severe anemia was mimicked. These results indicate that Epo production in the IPRK is mainly under the control of the arterial pO2.

Anemia↗
PubMed1989

O2-supply to the kidneys and the production of erythropoietin.

The concentration of erythropoietin (Ep) in blood increases little following a reduction of the renal blood flow (rbf). In the present study we examined whether a reduction of rbf in rats induces a lowering of the renal venous PO2. In addition, the combined effects of reduced rbf and hypobaric hypoxia on the production of Ep were studied. To lower rbf, silver clips with stepwisely reduced inner diameters were applied on both renal arteries. The PO2 of renal venous blood decreased gradually to values below 10 mm Hg, when rbf was reduced from 80 to 10% of normal. Under these conditions plasma Ep increased only moderately from 20 +/- 6 to 69 +/- 24 mU/ml within 18-20 h. However, plasma Ep of rats exposed to hypobaric hypoxia (stimulated altitude of 6000 m for 18-20 h) was 431 +/- 68 mU/ml, when rbf was 100-80% of normal, compared to 931 +/- 91 mU/ml, when rbf was reduced to 40-10%. Thus, a reduction of the blood flow to the kidney appears to be no major stimulus for the production of Ep, even when the PO2 in the kidney becomes very low. However, plasma levels of Ep increase markedly, when the whole body O2 offer is lowered. These results support the view that Ep production is not only dependent on the PO2 in the kidney but also under the control of extrarenal O2 sensitive mechanisms. For example, the hypothalamic-hypophyseal system is thought to influence the production of Ep.

Animals↗
PubMed1989

Renal mesangium is a target for calcitonin gene-related peptide.

Rat calcitonin gene-related peptide (CGRP alpha; EC50, 1 nM) was shown to stimulate cAMP formation in cultured rat renal mesangial cells. CGRP concentration dependently (EC50, 1 nM) also inhibited contraction of mesangial cells by angiotensin II (10 nM). Angiotensin II (10 nM) caused a transient increase of the intracellular calcium concentration from 140 nM to 480 nM in the mesangial cells, but these calcium transients were not altered by CGRP. CGRP (10 nM) decreased vascular resistance in the isolated rat kidney perfused at constant pressure (100 mm Hg; P less than 0.01). The decreased vascular resistance was accompanied by a rise of the glomerular filtration fraction. CGRP, moreover, attenuated the effects of angiotensin II on renal vascular resistance and glomerular filtration (P less than 0.01). In conclusion, CGRP causes relaxation of renal mesangial cells and decreases renal vascular resistance. As a result CGRP raises glomerular filtration and the filtration fraction. The effect may be linked to cyclic AMP formation. Thus, regulation of renal vascular and glomerular function may represent a novel action of CGRP apart from its cardiovascular effects.

Angiotensin II↗