Molecular matching in renal transplantation.
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Alleles↗
Biomedical subjects
J Hoyer
Publications and source records attributed to J Hoyer.
Differences in absorption of BAY u 3405 along the human gastrointestinal tract.
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Adult↗
Induction of cytokines in human peripheral blood and spleen cells by the Mycoplasma arthritidis-derived superantigen.
Recently, the mitogenic effects of the Mycoplasma arthritidis supernatant, MAS, and the induction of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) by MAS have been described. In the present series of experiments we investigated human peripheral blood mononuclear cells (PBM) and human spleen cells with respect to their production of these and other cytokines. In human spleen cell cultures and PBM, MAS induced the synthesis of interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Both interleukins were secreted faster and in higher amounts by PBM. IL-6 was also induced by MAS in PBM and human spleen cells. The amounts of IL-6 measured by ELISA were higher in PBM, whereas the biological activity of IL-6 was higher in spleen cell cultures. T-cell products such as IL-2, IL-4, and IFN-gamma were also induced by MAS in PBM and spleen cells. The kinetics of IFN-gamma and IL-4 induction were negatively correlated. In PBM we found low levels of IL-4 and high IFN-gamma induction, whereas in spleen cells high titers of IL-4 and low IFN-gamma titers were observed. Collectively, our results indicate that MAS induces different networks of cytokine interactions depending on the organ from which the cells are derived.
Antigens↗
The detection of human cytomegalovirus immediate early antigen in peripheral blood leucocytes.
Recently, Van der Bij et al. (1988) reported that active human cytomegalovirus (HCMV) infection could be diagnosed by the detection of HCMV immediate early antigen (IEA) directly in the peripheral blood leucocytes of renal transplant recipients. However, the indirect peroxidase technique used resulted in high background staining due to endogenous peroxidase activity and thus the detection of HCMV-IEA positive leucocytes, which are sometimes present in extremely low numbers, was not always reliable. In an attempt to solve this problem, we have evaluated the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique, immunogold-silver staining (IGSS), and several fixatives. Fixation with acetone: methanol 1:1 in conjunction with the APAAP technique proved to be the most successful method. In 155 blood samples obtained from 44 patients following renal transplantation and from three AIDS patients, the number of positive cells ranged between 1 and 700 out of 400,000 (median 2). In 23 samples from 11 patients (one AIDS patient) at least one positive cell was found. In this series there were no problems with the evaluation since strong positive signals were obtained without any background staining. We therefore recommend the use of this protocol for the rapid and reliable detection of HCMV-IEA in peripheral blood leucocytes.
Acquired Immunodeficiency Syndrome↗
Angiotensin II, vasopressin and GTP[gamma-S] inhibit inward-rectifying K+ channels in porcine cerebral capillary endothelial cells.
Cerebral capillaries from porcine brain were isolated, and endothelial cells were grown in primary culture. The whole-cell tight seal patch-clamp method was applied to freshly isolated single endothelial cells, and cells which were held in culture up to one week. With high K+ solution in the patch pipette and in the bath we observed inward-rectifying K+ currents, showing a time-dependent decay in part of the experiments. Ba2+ (1-10 mM) in the bath blocked this current, whereas outside tetraethylammonium (10 mM) decreased the peak current but increased the steady-state current. Addition of 1 microM of angiotensin II or of arginine-vasopressin to the extracellular side caused a time-dependent inhibition of the inward-rectifying K+ current in part of the experiments. Addition of 100 microM GTP[gamma-S] to the patch pipette blocked the K+ inward rectifier. In cell-attached membrane patches two types of single inward-rectifying K+ channels were observed, with single channel conductances of 7 and 35 pS. Cell-attached patches were also obtained at the antiluminal membrane of intact isolated cerebral capillaries. Only one type of K+ channel with g = 30 pS was recorded. In conclusion, inwardly rectifying K+ channels, which can be inhibited by extracellular angiotensin II and arginine-vasopressin, are present in cerebral capillary endothelial cells. The inhibition of this K+ conductance by GTP[gamma-S] indicates that G-proteins are involved in channel regulation. It is suggested that angiotensin II and vasopressin regulate K+ transport across the blood-brain barrier, mediating their effects via G-proteins.
Angiotensin II↗
Sodium-alanine cotransport in renal proximal tubule cells investigated by whole-cell current recording.
Sodium-alanine cotransport was investigated in single isolated proximal tubule cells from rabbit kidney with the whole-cell current recording technique. Addition of L-alanine at the extracellular side induced an inward-directed sodium current and a cell depolarization. The sodium-alanine cotransport current was stereospecific and sodium dependent. Competition experiments suggested a common cotransport system for L-alanine and L-phenylalanine. Sodium-alanine cotransport current followed simple Michaelis-Menten kinetics, with an apparent Km of 6.6 mM alanine and 11.6 mM sodium and a maximal cotransport current of 0.98 pA/pF at -60 mV clamp potential. Hill plots of cotransport current suggested a potential-independent coupling ratio of one sodium and one alanine. The apparent Km for sodium and the maximal cotransport current were potential dependent, whereas the apparent Km for L-alanine was not affected by transmembrane potential. The increase in Km for alanine with decreasing inward-directed sodium gradients suggested a simultaneous transport mechanism. These results are consistent with a cotransport model with potential-dependent binding or unbinding of sodium (high-field access channel) and a potential-dependent translocation step.
Alanine↗
Glomerular proteinuria as an early sign of renal-transplant rejection.
The introduction of cyclosporin gave rise to an additional problem in the surveillance of renal transplant patients, namely the differentiation between cyclosporin toxicity and acute transplant rejection. The development of assays for specific proteins in urine has produced a non-invasive solution to this problem. In 55 renal transplant patients the following proteins were determined daily in 24 h-urine samples: IgG, transferrin (TF), albumin, beta 2-microglobulin (beta 2-MG), retinol binding protein (RBP), alpha 1-microglobulin (alpha 1-MG) and alpha 1-antitrypsin (alpha 1-AT). All proteins were determined quantitatively using immunoluminometric assays and 10 microliters urine in dilutions from 1:1-1:100. The urinary protein excretion was related to the actual creatinine clearance as this index gave the best differentiation between normal and abnormal status. In 24 h-urine, intraindividual peaks of IgG, TF and albumin were seen regularly in acute rejection episodes. However, a peak in the "tubular" proteins (RBP, beta 2-MG, alpha 1-MG) could not be detected. After effective treatment of the rejection episode, the renal function improved and the protein excretion returned to prerejection episode levels. In bacterial infection of the urogenital tract, urinary alpha1-AT levels rose. They returned to normal after successful antibiotic treatment. In two cases of cyclosporin toxicity neither glomerular nor tubular proteins were excreted in abnormal amounts when compared with transplant patients without complications, the only changes being an increase in serum creatinine as a result of reduced renal function.
Cyclosporins↗
First results of the multicenter study of HTK protection for kidney transplants.
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Creatinine↗
[Diagnostic value of lymphocyte differentiation in the early phase following kidney transplantation].
In 50 patients who had a renal transplantation, treated with ciclosporin, regular monitoring of lymphocyte subpopulations was undertaken prospectively to assess its value with respect to cellular rejection, herpes virus infection, and ciclosporin overdosage. Herpes virus infection was characterized by inversion of the T4/T8 ratio below 1.0 (sensitivity 90%, specificity 88%), caused by proliferation of the T8 subpopulation, which--compared with the findings in patients with rejection crises--was significantly raised (P less than 0.001). But such rejection crises could not be predicted from the T4/T8 ratio. Ciclosporin had no effect on the ratio, total lymphocyte count in this group being higher (P less than 0.002) than in patients with rejection.
Creatinine↗
Membrane potential measurements in human oocytes.
Both maturation and fertilization of oocytes involve changes within the cell membrane as also in other cell structures. One method of documenting this phenomenon is the electrophysiological measurement of membrane potential (MP). Changes of MPs occurring coincidentally with the development of oocytes have been published previously for intervertebrates and vertebrates. In the present investigation MPs were measured in human oocytes at different stages of development. This was to prove whether the data published for animal models are also relevant in man. MPs were obtained from oocytes recovered for in vitro fertilization (IVF). This procedure produces not only the desired normal fertilized oocytes, but also immature cells, oocytes with failure of fertilization and pathologically fertilized oocytes. The results obtained show a good correlation of MP-changes during development and after fertilization with data published previously from a variety of species. In mouse and human oocytes, even absolute MP-values show a good correlation.
Cell Membrane↗
Regulation of alpha 2-adrenoceptor density in normotensive and hypertensive man.
We examined normotensive and hypertensive subjects in order to determine whether changes in platelet alpha 2-adrenoceptor density following alterations in plasma noradrenaline are related to changes in noradrenaline (NA) reactivity. Noradrenaline reactivity, plasma NA, alpha 2-adrenoceptor density, and adenylate cyclase activity were measured before and after a 24-h infusion of NA at a subpressor dose (0.02 micrograms/kg per min, n = 13), and also after application of drugs known to increase (nifedipine and furosemide) or decrease (clonidine) plasma NA. Measurements were obtained 60 min after nifedipine (20 mg in a single dose, n = 13), after 3 weeks on furosemide (30 mg twice a day, n = 8) and after 1 week on clonidine (150 micrograms three times a day, n = 5). Infusion of NA decreased alpha 2-adrenoceptor density (P less than 0.01) and NA reactivity (P less than 0.05). Nifedipine decreased alpha 2-adrenoceptor density and NA reactivity (P less than 0.01 for both) in patients with essential hypertension. The alterations in alpha 2-adrenoceptor densities were paralleled by a decreased adrenaline-induced inhibition of adenylate cyclase activity (P less than 0.01). Furosemide decreased alpha 2-adrenoceptor density (P less than 0.01), the fraction of high-affinity binding sites (P less than 0.01) and NA reactivity (P less than 0.05) in normotensive subjects. Following clonidine all three parameters, alpha 2-adrenoceptor density, the fraction of high affinity sites and NA reactivity, increased (P less than 0.05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenylyl Cyclases↗
Improvement of initial graft function after renal transplantation by fosfomycin.
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Adult↗
[Initial experiences with PTA of hemodialysis shunts].
Our experience of using PTA for stenoses of haemodialysis fistulae in 11 cases is described. PTA is the procedure of choice for re-establishing adequate shunt function. Intraluminal pressure measurements on the venous limb of well functioning Cimino shunts produced values of 7.5 to 44.5 mmHg, average 24.5 mmHg. These values are the basis for judging the success of a dilatation. Shunt angiography with DSA with a highly diluted non-ionic contrast medium injected via a remaining dialysis needle is an effective procedure with minimal discomfort to the patient.
Angioplasty, Balloon↗
Influence of immunosuppressive therapy with azathioprine and prednisolone on serum-immunoglobulin concentration in renal transplanted patients.
Serological diagnosis of infectious diseases are based on the assumption that a change in virus-specific antibody - titer reflects the response to a certain viral infection due to changes in the concentration of the respective virus - specific antibodies. On the other hand immunosuppressive medication interacts with that system responsible in producing antigen-specific antibodies. This study was outlined therefore to follow the variation of the concentration of serum immunoglobulins of classes IgG and IgM with regard to a better evaluation of virus-specific antibody titers especially for those viruses that remain persistent after a primary infection and an reactivate. The study followed ten patients after allogenic cadaver kidney transplantation under immunosuppressive medication with azathioprine and corticosteroids. Concentration of serum-IgG and -IgM protein was continuously measured for 6 months after transplantation along with measurement of virus-specific antibody-titers with enzyme immunoassay (Elisa) especially for cytomegalovirus. The results show a drastic decrease in serum immunoglobulins IgG and IgM - the lowest concentration being reached 25-50 days after transplantation. The concentration of IgG increased thereafter if no severe infectious diseases occurred during the post-transplant period. The concentration of IgM seems to react more sensitively upon infectious processes. In general, virus-specific antibody-titers (IgG) follow the sometimes drastic variation in the respective immunoglobulin class. It therefore reveals that antigen-specific antibody-titers in those patients should be controlled continuously during the time after transplantation for better evaluation of titer variations that eventually occur in correlation to the absolute concentration of the immunoglobulin class.
Adult↗
[Herpes simplex infection after kidney transplantation under immunosuppression by cyclosporin. Diagnostic and therapeutic experiences].
Incidence and course of herpes simplex infections was determined prospectively in 22 patients who had a kidney transplant and were treated with cyclosporin. In addition to clinical findings, serial studies were undertaken of throat washings for herpes simplex virus in cell culture, as well as of patient sera for herpes-specific IgG and IgM antibodies. There were 13 clinically manifest infections, 12 of them localized, while one had dissemination with necrotizing retinitis. Virus demonstration was successful in all cases in which virostatic drugs had not yet been used. Asymptomatic virus excretion was noted in three cases. Significant IgG titre rise occurred in six of the 13 cases, but a positive IgM titre in only two. Acyclovir proved to be an effective virostatic drug with few side effects. The outcome in the localized infections was favourable, but in the disseminated one residual defects remained.
Acyclovir↗
[Intravenous DSA following kidney transplantation].
Intravenous DSA is a simple angiographic technique in the follow-up of patients with renal transplants. It is of value in the post-operative anuric phase, for investigating renal function which is deteriorating and for demonstrating, or excluding, stenosis of the renal artery at the anastomosis during the development of hypertension. Changes in the peripheral arteries are not usually demonstrable. Reduced opacification of the parenchyma is observed during rejection and if there has been damage to the transplant, but is not seen if the transplant is functioning normally.
Adult↗
Differentiated lines of cells from rabbit renal medullary thick ascending limbs grown on amnion.
Previously we grew differentiated primary epithelial tissue cultures from rabbit renal medullary thick ascending limbs but were unable to subculture them into lines. Now, following the use of amnion as a support during the initial passages, two cell lines have grown from single fragments of medullary thick ascending limbs. Cells have now been in culture past 12 passages over more than 2 yr. On confluence they formed morphologically differentiated epithelial monolayers with polarization of the cells visible on electron microscopy. They had apical zonula occludens and microvilli, lateral cellular interdigitations, and basal membranes flat against the support. "Domes" often were visible when the epithelia formed on dishes, indicative of salt and water transport. Other functional differentiation in some passages of one line or the other included presence of Tamm-Horsfall protein (demonstrated by immunofluorescence) or transepithelial voltage oriented apical surface positive. Both the Tamm-Horsfall protein and the voltage are normally expressed by intact medullary thick ascending limbs and are characteristic of this particular nephron segment.
Amnion↗
[Modification of the incidence and course of CMV infections following kidney transplantation by passive immunization--initial experiences with a hyperimmunoglobulin].
In 45 recipients of a renal transplant the CMV-antibody titer was measured preoperatively (ELISA method). If possible, the donors were examined likewise. All seronegative recipients of grafts of a seropositive donor were immunized passively with a CMV-hyperimmunoglobulin for 6 months (2 ml/kg bw in 3 weeks intervals). 7 patients showed that constellation, and they were treated. 4 of them demonstrated neither serological nor clinical signs of a CMV-infection at any time. In 3 patients an infection was found serologically, but only 2 showed concomitant clinical symptoms. No serious complications (pneumonia etc.) were seen. One year later all patients are doing well with a functioning graft. For this reason we think the passive immunization of a seronegative recipient of a graft from a seropositive or unexamined donor to be advisable.
Adult↗