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S Heidenreich

Publications and source records attributed to S Heidenreich.

At least 37 records · Page 2Linked to original sources
PubMed1999

ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.

Adolescent↗
PubMed1999

Tyrosine phosphorylation in peripheral T cells of kidney transplant recipients: analyses of baseline levels and response to T cell receptor stimulation.

Impaired immunosurveillance in recipients of organ transplants has been attributed to alleviation of T cell functions. We analyzed the phosphorylation of tyrosine residues in T cells of peripheral blood, and after T cell receptor (TCR) stimulation. The TCR was stimulated by OKT3 monoclonal antibody (mAb) in non-separated heparinized blood specimens of patients (n=64) and healthy controls (n=25). After fixation and red cell lysis, lymphocytes were permeabilized by saponin. Subsequently, intracellular phosphotyrosine residues and surface CD3 antigen were stained simultaneously with specific mAbs. We analyzed transplant recipients and healthy donors for baseline levels of total cellular tyrosine phosphorylation and for increase in phosphotyrosine content following stimulation by OKT3. Phosphotyrosine levels were significantly lower in non-stimulated T cells of kidney transplant recipients compared to controls (p=0.004). There was a marked variability in the levels of tyrosine phosphorylation among transplanted patients (p=0.02). T cell receptor stimulation by OKT3 mAb in vitro led to a strong increase of tyrosine phosphorylation in all specimens of patients and healthy controls. In conclusion, we demonstrated decreased phosphotyrosine levels in T cells of kidney transplant recipients compared to healthy donors. However, increase in tyrosine phosphorylation was not impaired in all patients as a result of TCR stimulation.

Adult↗
PubMed1998

Transgenic hypertensive rats show a reduced angiotensin II induced [Ca2+]i response in glomerular mesangial cells.

The effects of angiotensin II (Ang II) induced changes of cytosolic free calcium concentration ([Ca2+]i) and growth response were investigated in transgenic TGR(mREN2)27 rats, a strain showing fulminant hypertension after the mouse Ren-2d renin gene has been integrated into its genome, in age-matched normotensive Sprague-Dawley rats (SD), in spontaneously hypertensive rats of the Münster strain (SHR), and in normotensive Wistar-Kyoto rats (WKY). In each strain the Ang II induced changes of [Ca2+]i were measured in cultured glomerular mesangial cells (MC) using the calcium-sensitive fluorescent dye, fura2. Resting [Ca2+]i was not significantly different between the strains tested. The Ang II induced [Ca2+]i rise was significantly less in MC from TGR(mREN2)27 compared to SD (peak level at 200 seconds: 161 +/- 15 nmol/L vs 217 +/- 43 nmol/L; mean +/- SEM; p<0.05). In the absence of external calcium, the Ang II induced [Ca2+]i increase was similar in MC from TGR(mREN2)27 and SD, indicating that the Ang II induced trans-plasma membrane calcium influx but not the calcium release is impaired in TGR(mREN2)27. The arginine vasopressin or endothelin induced [Ca2+]i increase were not significantly different in MC from TGR(mREN2)27 and SD. The Ang II or PDGF induced 3H-thymidine incorporation was not significantly different in MC from TGR(mREN2)27 and SD, indicating that the early growth response to Ang II is not impaired in TGR(mREN2)27. The Ang II induced peak [Ca2+]i increase was significantly enhanced in MC from SHR compared to WKY (215 +/- 30 nmol/L, n=17; vs 161 +/- 35 nmol/L, n=17; p<0.05). It is concluded that TGR(mREN2)27 show a selective defect in the cellular calcium response to Ang II.

Angiotensin II↗
PubMed1998

High rate of acute rejections in renal allograft recipients with thrombophilic risk factors.

Inherited and acquired thrombophilic disorders predispose patients for thromboembolic and probably other occlusive vascular events that occur when additional risk factors play in concert. Because acute rejections in renal transplant recipients may reflect vascular events, and an impairment of the fibrinolytic system in immunosuppressed patients has been previously described, the implications of genetic or acquired risk factors of thrombophilia for the occurrence of early acute rejections after kidney transplantation were evaluated. The following risk factors of thrombophilia were determined in 97 patients after cadaveric kidney transplantation: factor V Leiden mutation, protein S, protein C, and antithrombin deficiency. In a retrospective analysis, the prevalence of acute rejections, the histologic classification when rejection episodes had been confirmed by biopsy, and other vascular complications were evaluated. In 21 of the 97 patients, an inherited or acquired risk factor of thrombophilia was detected. Prevalence of acute rejections was 71% in the first 6 mo after transplantation in patients with a thrombophilic disorder and significantly higher compared with patients without thrombophilia (41%; P = 0.017). The distribution of classic risk factors associated with acute rejections, such as number of human leukocyte antigen mismatches or percentage of panel-reactive antibodies, was similar in patients with and without thrombophilia. In the eight patients with thrombophilia and histologically proven acute rejection, four patients had an acute vascular rejection, and in two patients a vascular involvement was suspected. Furthermore, prevalence of cerebral or coronary vascular disease, or venous thromboembolic complications, was significantly higher in patients with a thrombophilic clotting defect (67%) compared with patients with normal hemostasis parameters (28%; P < 0.002). It is concluded that renal allograft recipients with thrombophilia are at risk of developing an acute rejection or other vascular event. Although the determination of thrombotic risk factors was performed at least 3 mo after an acute rejection episode, it can be presumed that acute rejection episodes are associated with subsequent coagulatory abnormalities with further consequences for transplant survival. Thus, pretransplant evaluation of genetic and acquired risk factors of thrombophilia is recommended.

Acute Disease↗
PubMed1997

Regulation of human monocyte apoptosis by the CD14 molecule.

Bacterial products such as LPS have been shown to activate monocytes and to increase CD14 expression, while anti-inflammatory cytokines, i.e., IL-4, down-regulate CD14. Furthermore, activation of monocytes increases survival, whereas deactivation evokes apoptosis (programmed cell death, PCD). This correlation among activation, CD14 expression, and the lifespan of the cells prompted us to investigate the role of CD14 in monocyte apoptosis. The effects of LPS and IL-4 on the expression of CD14, indicated by binding of Leu M3 Ab, and PCD of monocytes were studied simultaneously and in a kinetic fashion by multiparameter flow cytometry. Monocyte PCD was determined by binding of FITC-conjugated annexin V, which indicates apoptotic cell death in early stages, and was confirmed using well-established detection methods, i.e., DNA electrophoresis, electron microscopy, or colorimetric DNA staining. The present study shows that the LPS-induced increase in CD14 expression rescued monocytes from apoptosis, whereas IL-4 treatment first down-regulated CD14 expression and consecutively evoked apoptosis. CD14-/annexin V- monocytes were not apoptotic as confirmed by DNA electrophoresis, whereas CD14-/ annexin V+ monocytes showed clear apoptotic features. Kinetic studies ruled out that monocytes first bound annexin V and later lost the CD14 Ag. Other molecules, such as HLA-A, -B, and -C Ags, were not down-regulated during apoptosis. Enzymatic removal of membrane-bound CD14 by phosphatidylinositol-specific phospholipase C evoked PCD similarly to IL-4. These results suggest that regulation of CD14 receptor expression is an early effector mechanism mediating life or death of monocytes. Down-regulation or removal of the receptor triggers apoptosis, whereas up-regulation promotes survival.

Annexin A5↗
PubMed1997

[Magnetic resonance tomography without and with gadolinium-DTPA for evaluating kidney transplants].

PURPOSE: To determine the value of MR imaging in differentiating the various causes of human renal allograft dysfunction. METHODS: A total of 123 human renal allografts (normal n = 20, acute rejection n = 57, acute tubular necrosis n = 14, interstitial fibrosis n = 11, chromic allograft glomerulopathy n = 11, cyclosporine nephrotoxicity n = 3, cortical necrosis n = 7) were investigated by means of MR imaging. Axial T1-weighted spin-echo images and coronal T1-weighted gradient-echo images were obtained before and after Gd-DTPA injection. Diagnostic parameters included corticomedullary contrast and allograft size and shape on the pre-contrast sequences. RESULTS: None of the diagnostic parameters used could differentiate among the various diagnostic groups. Diagnostic of cortical necrosis could be made only on post-contrast scans. Contrast-enhanced scans were superior to pre-contrast images in detection of focal allograft lesions. Otherwise, contrast-enhanced scans did not provide any more information than pre-contrast studies. Spin-echo and gradient-echo sequences displayed the same diagnostic value. CONCLUSIONS: MR imaging has a limited value in differentiating the various causes of renal allograft dysfunction.

Adult↗
PubMed1997

Induction of mesangial interleukin-6 synthesis by apoptotic U937 cells and monocytes.

Infiltration of the glomerular mesangium by monocytes and macrophages is a central pathologic feature in various forms of glomerulonephritis. Dependent on the presence and activity of local survival factors, monocytes may undergo apoptosis. Therefore, we looked for the interaction between cultured human mesangial cells (HMC) and intact, necrotic or apoptotic monocytic cells with different stages of programmed cell death (U937 cells and blood-derived human monocytes) and the possible evoked secretory responses of HMC. Interleukin-6 (IL-6) synthesis of HMC after a two hour co-culture with late apoptotic U937 cells was significantly increased (505 +/- 55 pg/ml) as compared to intact U937 cells (349 +/- 27 pg/ml; HMC alone, 319 +/- 62 pg/ml), and was further elevated after 20 hours (815 +/- 108 pg/ml). U937 cells alone, after incubation in HMC-conditioned medium or after coincubation with HMC, did not produce any detectable IL-6. A high mesangial IL-6 synthesis in response to apoptotic U937 cells was dependent on the cellular contact between HMC and U937 and could not be mimicked by apoptotic U937 culture supernatants. Radiolabeling studies indicated that HMC bound (16.6 +/- 2.4%) and ingested (12.5 +/- 1.9%) apoptotic U937 cells to a much higher amount as compared to intact U937 (5.3 +/- 2.0% binding; 5.0 +/- 1.1% phagocytosis). Binding and ingestion of monocytic cells undergoing apoptosis was confirmed by morphologic studies using electron microscopy. Incubation of HMC with a blocker of the CD36/ vitronectin receptor (VnR) dependent recognition mechanism of phagocytes for apoptotic leukocytes (RGDS peptide) did not alter binding, phagocytosis or IL-6 synthesis of HMC in response to apoptotic U937. Phospho-L-serine as an antagonist of the phosphatidylserine (PS) mediated recognition pathway for apoptotic cell disposal was able to reduce binding and IL-6 production by HMC but not phagocytosis. Thus, binding of apoptotic monocytic cells by HMC rather than ingestion may be the prerequisite for a stimulated secretory response. To elucidate whether binding and phagocytosis of particles in general might stimulate HMC to produce IL-6, we looked for mesangial IL-6 production after binding and ingestion of opsonized zymosan particles. In this case, IL-6 synthesis was markedly down-regulated. Furthermore, HMC proliferated after zymosan treatment, whereas after apoptotic cell uptake the mesangial cell number remained constant. In conclusion, apoptotic monocytic cells provoked an enhanced mesangial IL-6 synthesis by a PS-dependent recognition mechanism. This secretory response may have secondary implications for humoral or cellular processes within the mesangium.

Apoptosis↗
PubMed1997

Cellular protective action of angiotensin converting enzyme inhibitors.

In several studies organ protective effects of ACE inhibitors independent from their antihypertensive action have been demonstrated. The mechanisms of the protective effects of angiotensin converting enzyme (ACE) inhibitors on vasculature and kidney are largely unknown. In the present study the modulatory action of captopril on the angiotensin II (AngII), arginine vasopressin (AVP), and platelet derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2+]i) was investigated in cultured vascular smooth muscle cells (VSMC) and cultured glomerular mesangial cells (MC) from rats using the fluorescent dye technique. Resting [Ca2+]i in VSMC or MC was not significantly affected by captopril. The preincubation of VSMC with 1 mumol/l captopril significantly reduced the AngII-induced [Ca2+]i increase in VSMC from 90 +/- 10 nmol/l (n = 78; mean +/- SEM) to 51 +/- 16 nmol/l (n = 53; p < 0.05) and in MC from 102 +/- 42 nmol/l (n = 14) to 43 +/- 12 nmol/l (n = 7; p < 0.05). In the absence of extracellular calcium captopril produced no effect on AngII induced changes of [Ca2+]i. Captopril significantly attenuated the AVP-induced [Ca2+]i increase in VSMC and MC. The preincubation of MC with 1 mumol/l captopril for 40 min significantly reduced the PDGF-induced [Ca2+]i increase in MC from 127 +/- 31 nmol/l (n = 11) to 61 +/- 32 nmol/l (n = 5, p < 0.05). The present results may indicate that part of the protective effects of ACE inhibitors on vasculature and kidney may be promoted by inhibition of growth-factor induced changes of calcium homeostasis.

Angiotensin II↗
PubMed1997

Elemental mercurial poisoning.

A 39-year-old man injected 40 mL of elemental mercury in an attempted suicide 3 years before coming to our facility. No specific treatment regimen had been done since then. Chest x-ray films showed mercury deposits in the lungs, as well as around the injection site. The mercury concentration in his blood was at 96.3 micrograms (0.480 nmol/L), thus significantly elevated (given a reference range of up to 2 micrograms Hg/L), as was the renal mercury elimination. Despite mercurial deposits within the pulmonary circulation, the pulmonary function showed normal values, with no reduction of the diffusion capacity. There were signs of polyneuropathy. The patient was given sodium dimercaptopropanesulfate (Dimaval) for mercury complexation. This case report outlines the diagnosis and therapy for mercurial poisoning through metallic mercury.

Adult↗
PubMed1996

Apoptosis of monocytes cultured from long-term hemodialysis patients.

Monocyte apoptosis in vitro was studied in patients on long-term hemodialysis, CAPD, and in predialytic uremia to gain insight into the high susceptibility of these patients to infections. Monocytes from dialysis and control subjects were cultured for 24 to 120 hours in vitro to analyze the level and progression of DNA fragmentation as a hallmark of apoptosis. After an incubation time of 48 hours chromatin fragmentation of 48.5 +/- 7.7% was found in monocytes from dialysis patients, which significantly exceeded DNA fragmentation of control monocytes (23.1 +/- 9.1%; N = 12; P < 0.01). Over longer culture periods of up to 5 days, a continuous progression of apoptosis occurred with a similar slope of percent DNA fragmentation in the two studied groups. Monocyte viability was > 95% both in the dialysis and control group. Hemodialysis patients also showed elevated levels of monocyte apoptosis when programmed cell death was evaluated by transmission electron microscopy or DNA electrophoresis of cleaved chromatin. To test the functional relevance of monocyte apoptosis, a significant reduction of Candida growth inhibition by monocytes of dialysis patients was found with a strong linkage between percentage of DNA fragmentation and impaired microbicidal capacity. Monocytes obtained from patients after the hemodialysis session and from CAPD patients showed normal DNA fragmentation levels similar to controls. Differences of monocyte apoptosis between patients on cuprophane and high-flux polysulphone dialysis were not found. Uremic predialytic patients also exerted an increased monocyte DNA fragmentation of 44.2 +/- 1.5% (N = 7; P < 0.05 compared to controls). Enhanced apoptosis of uremic monocytes was accompanied by a reduced formation of TNF-alpha over 48 hours, revealing a significant negative correlation between chromatin fragmentation and monokine synthesis. Supplementation of monocyte cultures from dialysis patients with exogenous TNF-alpha turned increased apoptosis back to baseline levels, suggesting that inflammatory mediators may modulate monocyte senescence. In summary, the elevated degree of monocyte apoptosis in end-stage renal failure may contribute to the impaired cellular host defense seen in these patients.

Adult↗
PubMed1996

Diadenosine polyphosphates induce transplasma membrane calcium influx in cultured glomerular mesangial cells.

The effects of diadenosine tetraphosphate (AP4A) diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) on the cytosolic-free calcium concentration ([Ca2+]i) were evaluated in cultured rat glomerular mesangial cells (MCs) using the fluorescent dye technique. The addition of 10 mumol L-1 AP4A, AP5A or AP6A significantly increased [Ca2+]i in MCs by 57 +/- 9 nmol L-1 n = 17; P < 0.01), 76 +/- 27 nmol L-1 (n = 9; P < 0.01) or 65 +/- 12 nmol L-1 (n = 18; P < 0.01) respectively. In the absence of extracellular calcium, there was no significant change in [Ca2+]i in MCs after administration of diadenosine polyphosphates, indicating that these agents induce transplasma membrane Ca2+ influx. AP6A significantly enhanced the angiotensin II-induced changes in [Ca2+]i in MCs. The AP5A-induced transplasma membrane Ca2+ influx was inhibited by the P2 purinoceptor blockers suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), but was not affected by the adenosine A1 receptor blocker 8-cyclopentyl-1.3-dipro-pylzanthine (CPDPX). Adenosine triphosphate (ATP) and adenosine 5'-O-(3-thio)triphosphate (ATP-gamma S) increased [Ca2+]i in MCs, whereas alpha, beta-methylene ATP had no effect on [Ca2+]i in MCs. Measurements of diacylglycerol and phosphatidic acid showed that AP5A and AP6A also stimulated phospholipase C, but had no effect on phospholipase D. The inhibition of phosphatidylcholine-specific phospholipase C significantly reduced the AP5A-induced [Ca2+]i increase. In summary, diadenosine polyphosphates induce Ca2+ influx through P2 purinoceptors and may be involved in the local regulation of vascular resistance evoked by the Ca(2+)-dependent contractile response of mesangial cells.

Adenosine Triphosphate↗
PubMed1996

Predictive value of IgG subclass levels for infectious complications in renal transplant recipients.

Renal allograft recipients are at risk to acquire infectious disease complications primarily after an intensified immunosuppressive therapy. In this study, serum levels of IgG, IgA, IgM and IgG subclasses were compared between transplant patients after different anti-rejection regimen and evaluated as possible predictive markers for infectious implications. Thirty-six renal transplant recipients in the early posttransplantation period were allocated into three subgroups: group 1 consisted of 15 subjects with good primary graft function standing under a basal triple drug immunosuppression; patients of group 2 (n = 9) had a very early acute rejection episode which was treated by high steroid doses and patients of group 3 (n = 12) required antithymocyte globulin (ATG) therapy for acute rejection. Immune parameters were studied 5 weeks after transplantation, when basal triple drug immunosuppression was continued in all patients. Twenty-three age-matched patients under chronic hemodialysis were recruited as a control group. Total IgG serum levels were reduced in transplant patients compared to dialysis subjects, whereas IgA and IgM levels were not altered. IgG subclass analysis revealed, that IgG1 levels were similar in stable transplant compared to chronic hemodialysis patients, but were significantly reduced in rejection patients after steroid pulses or ATG therapy. IgG3 levels were significantly reduced in all transplant recipients compared to dialysis patients without differences between the transplant subgroups. IgG2 and IgG4 subclass levels were similar in all studied subjects. IgG subclass abnormalities were paralleled by a reduction of lymphocyte subsets in rejection patients of groups 2 and 3, which may be the basis for an altered Ig class switching. Seven out of 36 studied transplant patients had severe infections in the early posttransplantation period with four cases of viral infections. Patients with infections had significantly lower IgG1 levels and CD4 positive lymphocyte numbers but similar total IgG levels compared to patients without infections. So IgG1 levels may be of value to predict the occurrence of infectious complications in renal allograft recipients in the early posttransplantation period.

Antilymphocyte Serum↗
PubMed1996

Infection by Candida albicans inhibits apoptosis of human monocytes and monocytic U937 cells.

Infectious microorganisms can differently induce or inhibit apoptosis of immunocompetent effector and host cells. In this study we examined the influence of an infection by Candida albicans (C. albicans) on programmed cell death of monocytic U937 cells and human monocytes. Basal and tumor necrosis factor alpha (TNF-alpha)-induced DNA fragmentation of U937 cells was significantly inhibited by an infection with C. albicans. Enhanced apoptosis of U937 cells, induced by TNF-alpha, caused a diminished candidacidal activity of the effector cells, whereas inhibition of apoptosis by granulocyte-macrophage colony-stimulating factor (GM-CSF) was paralleled by an intensified host defense. Pretreatment of U937 cells or monocytes with the cyclooxygenase blocker indomethacin completely abolished the reduction of DNA fragmentation induced by the yeast. Studying the underlying mechanisms we found that C. albicans induced formation of prostaglandin E2 (PGE2) by U937. Exogenous administration of PGE2 down-regulated apoptosis of U937 or human monocytes to a similar extent as did fungal infection. Activation of protein kinase A by the cAMP analogue 8-bromo-cAMP inhibited U937 apoptosis, as did PGE2. On the other hand, rp-cAMP, a blocker of the cAMP-dependent signal transduction, restored and elevated DNA fragmentation levels down-regulated by C. albicans. U937 cells expressed the bcl-2 protein but the infection with fungi or PGE2 treatment did not increase proto-oncogene expression. Monocytic effector cells may therefore strengthen the defense against C. albicans by an autocrine feedback regulation via a PGE2-dependent, cAMP-transduced inhibition of apoptosis.

Apoptosis↗
PubMed1995

Effects of diadenosine polyphosphates, ATP and angiotensin II on membrane voltage and membrane conductances of rat mesangial cells.

Diadenosine polyphosphates have been shown to influence renal perfusion pressure. As mesangial cells may contribute to these effects we investigated the effects of diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) on membrane voltage (Vm) and membrane conductance (gm) in mesangial cells (MC) of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats in primary and long-term culture. We applied the patch-clamp technique in the fast-whole-cell configuration to measure Vm and gm. To compare the effects of diadenosine polyphosphates with hitherto known agonists we also tested adenosine 5&acute;-triphosphate (ATP) and angiotensin II (Ang II). As there was no significant difference in the Vm values in MC of WKY (-42 +/- 1 mV, n = 70) and SHR rats (-45 +/- 2 mV, n = 99) as well as in the agonist-induced changes of Vm, all data were pooled. The Vm of all the cells was -44 +/- 1 mV (n = 169) and gm was 15.9 +/- 1.8 nS (n = 141). Ion-exchange experiments showed the presence of a K+ and a non-selective cation conductance in resting MC whereas a Cl- conductance or a Na+-selective conductance could not be observed. Ap3A, Ap4A, Ap5A, AP6A and ATP each at a concentration of 5 micromol/l, led to a significant depolarization of Vm by 5 +/- 2 mV (n = 14), 7 +/- 1 mV (n = 25), 3 +/- 1 mV (n = 23), 2 +/- 1 mV (n = 16), and 14 +/- 2 mV (n = 23), respectively. For Ap4A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (EC50) as 6 micromol/l (n = 5-25), for ATP as 2 micromol/l (n = 9-37), and for Ang II as 8 nmol/l (n = 6-18). Ap4A 100 micromol/l increased gm significantly by 55 +/- 20% (n = 16), 100 micromol/l ATP by 135 +/- 60% (n = 18). The diadenosine polyphosphates examined were able to depolarize Vm (Ang II > ATP > Ap4A > Ap3A > Ap5A > Ap6A) by activation of a Cl- conductance and a non-selective cation conductance, as do ATP or Ang II.

Adenosine↗
PubMed1995

Prognostic value of serum erythropoietin levels in late acute rejection of renal transplants.

Since renal allograft rejection is frequently associated with a blunted erythropoiesis, we investigated erythropoietin (EPO) serum concentrations in 17 patients with acute rejection, eight patients with chronic rejection, and 18 transplant recipients with stable graft function. All rejection episodes were proven by biopsy. Erythropoietin serum levels were significantly reduced in patients with chronic rejection (6.2 +/- 3.4 mU/mL; P < 0.01) compared with individuals with acute rejection (35.6 +/- 33.9 mU/mL) or stable graft function (24.0 +/- 19.7 mU/mL). Suppressed EPO levels were associated with marked anemia in chronic rejection patients. In a subgroup of patients with acute rejection and bad responses to an intensified immunosuppressive regimen or with transplant failure, we found significantly suppressed EPO levels (11.6 +/- 6.1 mU/mL) compared with a subgroup of patients with a beneficial acute rejection outcome (57.0 +/- 34.2 mU/mL; P < 0.01). A correlation between histologic parameters of acute rejection and hormone levels showed that signs of moderate glomerulitis were associated with elevated EPO levels, whereas lesions of moderate tubulitis were associated with low values. We conclude that serum EPO may have prognostic value for rejection outcome in renal transplant recipients.

Acute Disease↗
PubMed1995

Regulation of rat mesangial cell growth by diadenosine phosphates.

The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A), were tested for growth stimulatory effects in rat mesangial cells (MC). Both AP5A and AP6A stimulated growth in micromolar concentrations. The growth stimulatory effect exceeded that of ATP, alpha,beta-methylene ATP, adenosine 5'-O-(3-thio)triphosphate and UTP. Both diadenosine phosphates potentiated the growth response to platelet-derived growth factor, but not to insulin-like growth factor-1. To further elucidate the site of action in the cell cycle, RNA and protein synthesis were assessed. AP5 and AP6A stimulated protein synthesis, but not RNA formation. Furthermore, both agents increased cytosolic free Ca2+ concentration. It is concluded that AP5A and AP6A may play a regulatory role in MC growth as progression factors and possibly modify MC proliferation in glomerular disease.

Adenosine↗