-
[show abstract]
[hide abstract]
ABSTRACT: Among the family of herpes viruses, only cytomegalovirus (CMV) and, to a lesser extent, human herpes virus 8 (HHV-8) are of relevance in transfusion medicine. Due to neutropism, herpes simplex viruses (HSV) types 1 and 2 are considered to be of minor relevance. However, several reports gave evidence that a HSV DNAemia might occur and HSV could therefore be transmissible by blood products. The aim of our study was to collect data about prevalence of HSV antibodies among blood donors and to clarify whether HSV DNAemia is possible. HSV antibody states of 653 blood donors were investigated. Blood specimens of 46 patients with primary and recurrent HSV infection were tested for HSV-1 and HSV-2 DNA using TaqMan polymerase chain reaction. In 505 of the 653 blood donors HSV antibodies were detectable, most of which were HSV-1 antibodies. HSV DNA was detected in plasma, but not in peripheral blood mononuclear cells (PBMCs) of seven rather seriously ill patients with primary herpes genitalis. No HSV viraemia was detectable in otherwise healthy patients with recurrent herpes labialis. Thus, HSV DNAemia is possible, but seems to be limited to primary infections and could not be detected in the recurrent infection. Therefore, blood donors with primary herpes infection should be deferred from donation. Blood donors with recurrent HSV infection are probably not at risk of transmitting HSV, but further studies are necessary to prove this hypothesis. Detection of HSV DNA in PBMCs as described formerly could not be confirmed by this study.
Transfusion Medicine 09/2009; 20(1):38-47. · 1.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Deficiencies in early complement components are associated with the development of systemic lupus erythematosus (SLE) and therefore early complement components have been proposed to influence B lymphocyte activation and tolerance induction. A defect in apoptosis is a potential mechanism for breaking of peripheral B cell tolerance, and we hypothesized that the lack of the early complement component C4 could initiate autoimmunity through a defect in peripheral B lymphocyte apoptosis. Previous studies have shown that injection of a high dose of soluble antigen, during an established primary immune response, induces massive apoptotic death in germinal centre B cells. Here, we tested if the antigen-induced apoptosis within germinal centres is influenced by early complement components by comparing complement C4-deficient mice with C57BL/6 wild-type mice. We demonstrate that after the application of a high dose of soluble antigen in wild-type mice, antibody levels declined temporarily but were restored almost completely after a week. However, after antigen-induced apoptosis, B cell memory was severely limited. Interestingly, no difference was observed between wild-type and complement C4-deficient animals in the number of apoptotic cells, restoration of antibody levels and memory response.
Clinical & Experimental Immunology 11/2007; 150(1):132-9. · 3.36 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Spleen cells of various mouse strains (e.g. BALB/c, C3H, and CBA) reacted towards MAS (a mitogen derived from supernatants of cultured Mycoplasma arthritidis) with a marked lymphoproliferative response. This reactivity was T-cell-dependent. It was reduced by 90% after removal of macrophages by passage of the spleen cells through Sephadex G-10 columns. Addition of 2-mercaptoethanol (2-ME) to macrophage-depleted CBA spleen cells completely restored the response to MAS. Spleen cells of C57BL/6 and C57BL/10 mice were unreactive to MAS, even in the presence of macrophages, and this non-reactivity was controlled by the I-region of H-2. Other mouse strains that, similarly to C57BL/6, lack the expression of I-E on the cell surface (that is, mice of the haplotype H-2f, H-2q, and H-2s) were also non-responsive to MAS. However, the addition of 2-ME to spleen cells of non-responder mice resulted in high lymphoproliferative responses to MAS, which were as high as those of CBA spleen cells. The reaction of C57BL/6 spleen cells to MAS in the presence of 2-ME again was T-cell-dependent, as shown by data with spleen cells of homozygous nude mice and spleen cells treated by anti-thy-1 and C. A macrophage dependency of this response was also evident. When C57BL/6 spleen cells were vigorously freed of accessory cells by the use of nylon wool columns, the MAS response could no longer be restored by 2-ME.
Scandinavian Journal of Immunology 06/2006; 20(2):133 - 139. · 2.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hepatitis delta virus (HDV) RNA editing controls the formation of hepatitis-delta-antigen-S and -L and therefore indirectly regulates HDV replication. Editing is thought to be catalysed by the adenosine deaminase acting on RNA1 (ADAR1) of which two different forms exist, interferon (IFN)-alpha-inducible ADAR1-L and constitutively expressed ADAR1-S. ADAR1-L is hypothesized to be a part of the innate cellular immune system, responsible for deaminating adenosines in viral dsRNAs. We examined the influence of both forms on HDV RNA editing in IFN-alpha-stimulated and unstimulated hepatoma cells. For gene silencing, an antisense oligodeoxyribonucleotide against a common sequence of both forms of ADAR1 and another one specific for ADAR1-L alone were used. IFN-alpha treatment of host cells led to approximately twofold increase of RNA editing compared with unstimulated controls. If ADAR1-L expression was inhibited, this substantial increase in editing could no longer be observed. In unstimulated cells, ADAR1-L suppression had only minor effects on editing. Inhibition of both forms of ADAR1 simultaneously led to a substantial decrease of edited RNA independently of IFN-alpha-stimulation. In conclusion, the two forms of ADAR1 are responsible almost alone for HDV editing. In unstimulated cells, ADAR1-S is the main editing activity. The increase of edited RNA under IFN-alpha-stimulation is because of induction of ADAR1-L, showing for the first time that this IFN-inducible protein is involved in the base modification of replicating HDV RNA. Thus, induction of ADAR1-L may at least partially cause the antiviral effect of IFN-alpha in natural immune response to HDV as well as in case of therapeutic administration of IFN.
Journal of Viral Hepatitis 04/2006; 13(3):150-7. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The transfusion of natural killer (NK) lymphocytes into patients suffering from malignant diseases is an approach of current interest in the field of immunotherapy. Little is known about the organ distribution, survival, and clearance of donor immune effector cells in cellular therapy, and no reports exist on these important parameters considering NK cells in particular or any other type of allogeneic lymphocytes in humans. In the context of a clinical Phase I/II study we examined the distribution of transfused allogeneic NK cells in patients suffering from renal cell carcinoma. The NK cells were ex vivo cultivated and activated before transfusion. To assess the circulation of the transfused cells in the peripheral blood, we used a nested PCR technique to detect HLA DRB1 alleles of the NK cell donors. Post-transfusion, all patients showed evidence of circulating donor cells for up to 3 days. After 7 days, all donor cells were cleared from the blood to undetectable levels. To assess organ distribution, (111)In-labeled NK cells were injected and monitored by whole-body scintiscans. A distribution to the whole body, with preference for liver, spleen, and bone marrow, was observed after a short initial uptake in the lungs. No activity was observed in lymphatic nodes. A total of 2/4 evaluable metastases showed a clear accumulation of transfused NK cells. The half-life corrected activity in all body compartments remained almost constant over the 6-day observation period in concordance with the absence of any excretion of radioactivity. This may indicate an extended survival of the transfused cells, despite their foreign nature, in the host organism.
Stem Cells and Development 07/2004; 13(3):307-14. · 4.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Autologous bone marrow or peripheral blood stem cell transplantation are well-recognized treatments for certain malignant hematological diseases. Therapy-induced pancytopenia and immunodeficiency that lead to increased rates of bleeding complications and higher susceptibility to bacterial, viral, and fungal infections often occur following transplantation. Infections during or shortly after transplantation are more likely to be associated with the severe depression of mononuclear cells and neutrophil granulocytes, whereas post-engraftment infections in the long term are probably due to numerical and functional impairment of primarily CD4+ T-helper-cells and B-lymphocytes. A prompt and sustained engraftment of the hematopoiesis and a complete and functionally intact recovery of the immune system are necessary for a good patient outcome. The quality of reconstitution depends upon several factors, including the underlying disease, the intensity of prior therapy, and the graft source. The faster hematopoietic engraftment as well as the larger mononuclear cell inoculum transfused to recipients of blood stem cell products might be superior to bone marrow transplantation with respect to lymphohematopoietic reconstitution. In this review, data published more recently on immune reconstitution after autologous stem cell transplantation are discussed, and laboratory parameters useful for monitoring states of deficiency of cellular and humoral immunity are evaluated.Zusammenfassung: Die autologe Knochenmark- und Blutstammzelltransplantation sind anerkannte Behandlungsformen für bestimmte maligne hämatologische Erkrankungen geworden. Eine therapiebedingte Panzytopenie und Immundefizienz, die zu einer erhöhten Rate an Blutungskomplikationen und zu einer gesteigerten Anfälligkeit gegenüber bakteriellen, viralen und fungalen Infektionen führt, tritt häufig nach Transplantationen auf. Infektionen während und kurz nach Transplantation sind meistens mit einer ausgeprägten Reduktion mononukleärer Zellen und neutrophiler Granulozyten assoziiert, während Infektionen in Postrekonstitutionsphase wahrscheinlich eher in Folge einer numerischen und funktionellen Beeinträchtigung der CD4+ T-Helferzellen und B-Lymphozyten auftreten. Ein schnelles und anhaltendes Anwachsen der Hämatopoese und eine komplette und funktionell intakte Erholung des Immunsystems sind für einen guten Therapieerfolg notwendig. Die Qualität der Rekonstitution ist von der zugrunde liegenden Erkrankung, der Intensität der zuvor erfolgten Therapie und von der Stammzellquelle abhängig. Wegen des schnelleren hämatopoetischen Anwachsens als auch aufgrund des höheren Gehaltes an transfundierten mononukleären Zellen kann die Verwendung von Blutstammzellprodukten der Transplantation von Knochenmark in Hinblick auf die lymphohämatopoetische Rekonstitution überlegen sein. In diesem Übersichtsartikel werden kürzlich publizierte Ergebnisse zur immunologischen Rekonstitution nach autologer Stammzelltransplantation diskutiert und Laborparameter zur Überwachung von zellulären und humoralen Immundefizienzen dargestellt.
Laboratoriums Medizin 10/2002; 26(7‐8):399 - 407.
-
[show abstract]
[hide abstract]
ABSTRACT: The use of long-term automated erythrocytapheresis via an arterio-venous fistula for the prevention of recurrent ischaemic stroke in a child with sickle-cell disease (SCD) has not been described previously. We report the successful use of this technique in a 13-year-old boy. A procedure was performed every 36 +/- 6 days, transfusing six units of donor packed red blood cells (RBCs) and discarding 1318 +/- 174 mL of exchanged erythrocytes (Hct 60%). After transfusion of 85 units over 17 months, there is no evidence for iron-overload, red cell alloimmunization, transfusion-transmitted infections, or other complications. Until now, no cerebrovascular ischaemia has been observed.
Transfusion Medicine 03/2002; 12(1):75-7. · 1.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The counting of colony-forming units granulocyte-macrophage (CFU-GM) and burst-forming units erythrocyte (BFU-E) provides substantial in vitro information about the graft quality after peripheral stem cell transplantation (PBSCT). By using different techniques for culturing and scoring, high inter- and intralaboratory coefficients of variation (CV) are frequently reported. We minimized the imprecision by using flow cytometry-based incorporation of constant numbers of CD34(+) cells per culture dish instead of the formerly used mononuclear cells. Our results show acceptable CVs for CFU-GM (12.3%) and for BFU-E (13.3%) based on this seeding technique, which contributes to fulfilling the demands of a quality assurance system in stem cell laboratories.
Journal of Hematotherapy & Stem Cell Research 01/2002; 10(6):881-5.
-
[show abstract]
[hide abstract]
ABSTRACT: Chronic renal failure is associated with a T-cell-dependent immune defect. In the past, various studies have focused on the insufficient immune response to vaccination of hemodialysis patients. An impaired vaccination response rate has been reported for vaccines against hepatitis B, influenza, tetanus, diphtheria, and others. However, no data exist on the long-term success of vaccination against tetanus and diphtheria in these patients. The aim of the present study is to investigate seroresponse to tetanus and diphtheria vaccination over a 5-year period. Antibody levels were determined by enzyme immunoassay. Antidiphtheria antibody levels of 31 hemodialysis patients were determined 5 years after vaccination. After 5 years, 10 of 31 patients (32%) had a protective antibody level against diphtheria (>/=0.1 IU/mL), whereas 12 months after vaccination, 26 of 71 patients (37%) were protected. Also, mean antibody levels significantly decreased. Furthermore, antitetanus antibody levels of 21 patients simultaneously vaccinated against tetanus and diphtheria were investigated. After 5 years, 15 of 21 patients (71%) were protected compared with 46 of 71 patients (65%) in the hemodialysis collective studied after 12 months. In the interval between 1 and 5 years after vaccination, significantly more patients in the initial nonresponder group had died than in the responder group; therefore, the overall protection rate observed in vaccinated patients increased. Our results provide evidence that during a 5-year period, antibody persistence against tetanus toxoid is better than that against diphtheria toxoid. Therefore, detection of individual antibody concentrations may be indicated to decide on revaccination.
American Journal of Kidney Diseases 12/2001; 38(6):1264-70. · 5.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The effects of surgery, surgical stress, and anesthesia compromise the optimal function of the immune system. Recent studies demonstrate the influence of anesthesia on the immune response by modulation of neural-immune interactions. To evaluate the immunologic effects of general anesthesia with the hypnotic agent propofol and the opioid fentanyl, two drugs used frequently in anesthesia, we studied 30 patients undergoing elective orthopedic surgery before and during narcosis. We found a significant enhancement of interferon-gamma (IFN-gamma) and soluble interleukin-2 receptor (sIL-2R) release in lipopolysaccharide (LPS)-stimulated whole blood cultures after induction of anesthesia. Similar results were observed in cultures stimulated with polyclonal T cell activators, such as staphylococcal enterotoxin B (SEB) and phytohemagglutinin (PHA). IL-1beta and IL-8 release was not affected, but the anti-inflammatory cytokine IL-10 decreased after skin incision. Serum prolactin significantly increased immediately after induction of anesthesia, whereas serum cortisol levels declined. Our results point to enhanced proinflammatory T lymphocyte and natural killer (NK) cell activity, probably caused by prolactin and cortisol modulation in the serum. This may disturb the balance of human proinflammatory and anti-inflammatory pathways during surgery and general anesthesia.
Journal of Interferon & Cytokine Research 11/2001; 21(10):793-6. · 3.06 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of this work was to develop a novel and highly sensitive RT-PCR method that is suitable for HCV RNA screening of blood donations according to the criteria released by the Paul Ehrlich Institute, the federal licensing agency of Germany, for routine HCV NAT.
RNA was prepared from plasma pools of up to 20 single blood donations using an automated nucleic acid isolation system (NucliSens Extractor, Organon Teknika). For reverse transcription, amplification, and simultaneous detection of PCR products, a novel approach based on the TaqMan technology was developed. Glyceraldehyde-3-phosphate dehydrogenase messenger RNA, which is detectable in human plasma, was coamplified in each reaction as an internal positive control.
The HCV genotypes and subtypes 1a, 1b, 2a, 2b, 2c, 2i, 3a, 4, and 5a were detected in parallel with comparable amplification efficiency. The 95-percent detection limit related to the WHO HCV RNA standard preparation was calculated to be 389 IU per mL of plasma of the single blood donation. Total CVs (%) were <4. The screening of up to 180 blood donations took 5 hours; as a rule, the blood components could be released on the day of donation.
The TaqMan HCV RT-PCR is an almost completely automated, highly sensitive, specific, and rapid method that is reliable for HCV RNA screening of blood donations. It allows a closed-tube HCV RNA detection without risk of contamination by PCR products.
Transfusion 10/2001; 41(9):1100-6. · 3.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent evidence suggests that neurodegeneration may be involved in the pathophysiology of major depression. The astroglial peptide S-100B was shown to be increased in many diseases causing neuronal cell damage or degeneration.
S-100B plasma levels were determined in 28 patients with major depression and 28 matched healthy controls using an immunofluorometric sandwich assay.
Patients suffering from melancholic depression showed significantly increased S-100B levels compared to healthy controls while non-melancholic patients demonstrated normal levels.
Medication of patients varied. The differentiation between melancholic and non-melancholic patients was performed clinically without using a standardized instrument.
Neurodegeneration or axonal remodeling may be involved in the pathogenesis of melancholic depression.
Journal of Affective Disorders 10/2001; 66(1):89-93. · 3.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chronic haemodialysis patients show various clinical signs of immunodeficiency and there is growing evidence that a dysregulated monocyte cytokine production is heavily involved in this deficiency. The production of monokines in vitro has been proposed to correlate closely with the in vivo immune status and to be of high clinical relevance in cuprophane haemodialysis. Even though it is well known that the biocompatibility of dialyser membranes has a significant impact on immune functions, little is known about the influence of the ultrafiltration flow rate (UFR). The aim of this study was to investigate the potential long-term effects of UFR on the production of interleukin-10 (IL-10), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in an intra-individual study design.
In 11 patients previously treated with polysulphone haemodiafiltration, UFR was reduced from 40-46 ml/min to 24-28 ml/min, then to 7-10 ml/min before it was reinstated at 40-46 ml/min for periods of 4 weeks each. Monokine secretion into culture supernatants and mRNA expression (assessed using a novel Taqman PCR technique), were determined in a whole blood assay after lipopolysaccharide stimulation.
Reduction of UFR led to a significant increase in IL-10 secretion and mRNA expression (P=0.012, P=0.001). Conversely, a substantial (but not complete) decrease was observed when UFR returned to initial levels. In contrast, supernatant concentrations of IL-1beta (P=0.04) and IL-6 (P=0.003), and mRNA expression of both monokines (P<0.001, P<0.001) decreased significantly when UFR was reduced. Calculation of the IL-1beta/IL-10 ratio also revealed a decrease when UFR was reduced, with an increase again being observed when the initial degree of UFR was reinstated (P<0.001).
These results indicate a significant impact of UFR on the production of monokines at both the transcriptional and the protein level. We suggest that middle molecule removal has to be considered as a possible pathophysiological mechanism to explain our findings. Since monokine production in vitro was shown to be closely correlated with the in vivo immune status in patients on cuprophane haemodialysis, further investigations are necessary to clarify the impact of UFR on the immunocompetence of patients under polysulphone haemodiafiltration.
Nephrology Dialysis Transplantation 09/2001; 16(9):1830-7. · 3.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: S100B, a calcium-binding protein produced by astroglial cells, is a marker of astroglial cellular integrity. It has been shown to be increased in acute brain damage and neurodegeneration. A recent study showed increased S100B levels in medicated acutely psychotic patients with schizophrenia. The study presented here included 26 drug-free patients with acute schizophrenia and 26 matched healthy controls. S100B blood concentrations were determined using a quantitative immunoassay upon admission and after 6 weeks of neuroleptic treatment. The PANSS was used to investigate psychopathology. Unmedicated schizophrenic patients showed significantly increased S100B levels compared to matched healthy controls. After 6 weeks of treatment, 11 patients showed normal S100B levels while in 15 patients the levels remained increased. These patients showed significantly higher PANSS negative scores upon admission and after 6 weeks of treatment. Schizophrenic patients display a loss of astroglial integrity which is not caused by neuroleptic medication. Continuously increased S100B levels are associated with negative symptomatology.
Molecular Psychiatry 08/2001; 6(4):445-9. · 13.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: For the better understanding of engraftment properties after autologous peripheral blood stem cell transplantation (PBSCT), hematopoietic recovery, immune reconstitution and functional capacity of cytokine production in different lymphocyte populations were examined. In a prospective study, we examined 24 patients suffering from different malignancies after autologous PBSCT. The examination intervals were 1, 3, 6 and 12 months after PBSCT. T cells, B cells and NK cells were analyzed using flow cytometry. The expression and kinetics of cytokines in T lymphocytes were evaluated in 10 patients by intracellular staining of cytokines after PMA/ionomycin stimulation. We observed rapid hematopoietic engraftment proceeding to stable long-term reconstitution. For CD3(+) lymphocytes, a consistent reconstitution associated with an increase in CD3(+)CD8(+) cytotoxic T cells was observed, whereas the CD3(+)CD4(+) helper/inducer T cells remained low (< 200/microl). Impaired B lymphopoiesis with severe depression (<1%) was detected 1 month after PBSCT but recovered thereafter (12.8% after 3 months). The percentages of cytokine-producing T cells and the mean fluorescence intensity (MFI) shifts suggested an insufficient capacity for producing IFNgamma, in particular for CD3(+)CD4(+) T cells, compared to healthy volunteers early after PBSCT. Rapid hematopoietic recovery and partly impaired immune reconstitution, especially regarding the regeneration of B lymphocytes and T helper cells, was observed. The CD4(+) subpopulation remained low throughout the period of examination, whereas the B cells showed a delayed recovery after 3 months. Cytokine production proved to be sufficient after in vitro stimulation in T cell populations with the exception of IFNgamma synthesis.
Bone Marrow Transplantation 08/2001; 28(3):251-7. · 3.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There is evidence that patients with major depression (MD) also suffer an inflammatory immune reaction. However, the results remain ambiguous. This could be due to the psychiatrically heterogeneous patient samples investigated in many published studies. Since melancholic depression is psychopathologically and possibly etiologically different from non-melancholic MD, we focused on investigating immune parameters in these two subgroups.
43 in-patients suffering from acute major depression were diagnosed, sub-classified according to DSM IV criteria, and compared to 43 matched healthy controls. Cell counts were determined by morphology, and acute phase proteins [c-reactive protein (CRP), alpha(2)-macroglobulin (A2M), haptoglobin (HP)] were measured by laser nephelometry. Cytokine production (IL-1beta) upon mitogen stimulation was measured by ELISA in a whole blood assay.
Non-melancholic patients showed increased monocyte counts and A2M serum concentrations in the acute stage of disease and after 2 and 4 weeks of treatment. Melancholic patients demonstrated a decreased monocyte count upon admission and after 4 weeks of treatment. HP levels and IL-1beta production were unchanged in all studied subjects.
Medication of the patients varied. The differentiation between melancholic and non-melancholic depression was performed clinically and was not performed using any standardized instrument.
Melancholic and non-melancholic patients show different immune patterns. This differentiation might clarify immunological findings in MD and point towards etiological factors that are involved in the development of various subtypes of MD.
Journal of Affective Disorders 04/2001; 63(1-3):93-102. · 3.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The load of Epstein-Barr virus (EBV) in peripheral blood mononuclear cells of transplant recipients represents a predictive parameter for posttransplant lymphoproliferative disorders (PTLD). The aim of our work was to develop a rapid and reliable PCR protocol for the quantification of cell-associated EBV DNA in transplant recipients. In contrast to previous studies, a protocol that facilitated quantification independent of photometric nucleic acid analysis was established. We took advantage of the real-time PCR technology which allows for single-tube coamplification of EBV and genomic C-reactive protein (CRP) DNA. EBV copy numbers were normalized by division by the amount of CRP DNA, with the quotient representing the actual amount of amplifiable genomic DNA per reaction. Coamplification of CRP DNA did not result in a diminished detection limit for EBV. By using the protocol without normalization, EBV copy numbers in 4 out of 10 PTLD patients were within the normal range determined with data for 114 transplant recipients that served as controls. After normalization, however, all of the PTLD patients had a higher viral load than the control population, indicating an increased sensitivity of the assay. Moreover, EBV copy numbers obtained for one patient by conventional quantification and suggestive of relapsing PTLD were within normal range after normalization. We conclude that normalization of PCR signals to coamplified genomic DNA allows a more accurate quantification of cell-bound EBV.
Journal of Clinical Microbiology 03/2001; 39(2):564-9. · 4.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The acute immunological rejection and long time survival of kidney allografts are correlated with the human leukocyte antigen (HLA) match status between donor and recipient. HLA-A, -B and -DR have all turned out to be relevant HLA loci in several studies. The role of HLA-C has not been studied before now.
In 104 consecutive patient/donor pairs from our transplantation unit, we retrospectively analysed whether acute graft rejection is influenced by HLA-C match status between donor and recipient. For typing HLA-C alleles, we used an allele-specific PCR protocol in combination with serology.
By analysing groups of donor/recipient pairs with a homogeneous distribution of HLA-B mismatches in order to exclude an effect of the linkage disequilibrium between HLA-B/C, HLA-C mismatch turned out to be significantly correlated with acute transplant rejection in pairs with one additional mismatch on the B locus (P=0.004). Additional parameters that may hypothetically influence acute rejection episodes (HLA-A or DR mismatch, time of cold and warm ischaemia, previous transplantations, pre-existing HLA antibodies) were also analysed but cannot explain this finding.
HLA-C matching of all kidney donors and recipients seems to be an option to reduce the probability of acute rejection episodes. Further studies of greater patient cohorts analysing organ rejection and organ survival are warranted.
Nephrology Dialysis Transplantation 03/2001; 16(2):355-60. · 3.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Compensation for acute blood loss requires cardiovascular integrity. In older people, asymptomatic cardiovascular impairment is common. In these subjects, even moderate blood loss is often treated by external volume replacement although its benefits are not clear. We investigated the effect of 450 ml of blood loss on the microcirculation and compensatory mechanisms in healthy older blood donors. Red blood cell count, plasma viscosity and protein concentration were measured. Plasma volume replacement was calculated using haematocrit. We measured microcirculation tissue perfusion by laser Doppler fluxmetry prior to, during and after blood donation. Blood loss was immediately accompanied by a median rapid water shift of 208 ml (interquartile range 134-298 ml). Haemodilution led to a decrease in haematocrit, protein and plasma viscosity. We observed no changes in cutaneous microcirculation. Moderate blood loss is tolerated in older cardiovascularly asymptomatic patients without having an impact on microcirculation. This may reduce the need for external volume replacement.
Anaesthesia 03/2001; 56(2):103-7. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The search for immune patterns in major depression has thus far resulted in ambiguous findings, probably because patient samples are psychiatrically heterogeneous. We therefore focused on a detailed classification of subtypes of major depression, comparing patients with melancholic and non-melancholic major depression. Inpatients suffering from acute major depression were diagnosed and subclassified according to DSM IV criteria. Cell counts were determined by FACS analysis and morphology. Cytokine production (IL-2, IFN-gamma, IL-10) upon mitogen stimulation was measured by ELISA in a whole blood assay. Non-melancholic patients showed increased counts of leukocytes, lymphocytes and NK-cells in the acute stage of disease and after two and four weeks of treatment. Their lymphokine production was unchanged compared to that of healthy controls. Melancholic patients on the other hand demonstrated normal cell counts but a decreased production of IL-2, IFN-gamma and IL-10 during the acute stage of disease followed by a normalization with clinical improvement. Melancholic and non-melancholic patients showed different immune patterns. Classifying melancholic and non-melancholic patients is helpful towards the identification of immune characteristics typical for these diseases.
European Archives of Psychiatry and Clinical Neuroscience 02/2001; 251(2):90-7. · 3.49 Impact Factor
