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J D Seebach

Publications and source records attributed to J D Seebach.

At least 19 recordsLinked to original sources

Deadly carousel or difficult interpretation of new diagnostic tools for Whipple's disease: case report and review of the literature.

Whipple's disease is a rare systemic disorder classically presenting with weight loss, arthralgias, and diarrhea, which was first described in 1907. The causative bacterium Tropheryma whipplei, is a fastidious organism not growing on conventional media. Before the introduction of polymerase chain reaction (PCR)-based methods, the diagnostic gold standard was histological detection of diastase-resistant periodic acid Schiff (PAS)-positive macrophages or electron microscopy. As in the present case, contradictory results between the former and new diagnostic methods may obscure the correct diagnosis. We critically summarize the performance of the different diagnostic methods and discuss their impact on the clinical management of patients with suspected Whipple's disease.

Aged↗

Levels of anti-A/B antibodies after ABO-incompatible hematopoietic stem cell transplantation.

In contrast to solid organ transplantation, ABO incompatibility is generally not associated with survival differences in hematopoietic stem cell transplantation. Therefore, patients receiving ABO-incompatible stem cell transplantation can be analyzed to study the mechanism of tolerance induction after antigen-mismatched transplantation. The goal of this study was to analyze the levels of anti-A/B antibodies after ABO-incompatible transplantation. Host-derived antidonor antibodies disappeared rapidly after transplantation and did not reappear in the further posttransplant course. Donor-derived antihost antibodies did not significantly increase and compatible anti-A/B antibodies remained positive after hematopoietic stem cell transplantation. Thus, there is no evidence for stimulation of donor B lymphocytes to produce antirecipient antibodies suggesting a potential B cell tolerance.

ABO Blood-Group System↗

Isotype-specific detection of ABO blood group antibodies using a novel flow cytometric method.

Several methods to detect anti-A/B antibodies based on haemagglutination and haemolysis have been described. These methods measure predominantly anti-A/B immunoglobulin (Ig)M, whereas anti-A/B IgG and IgG subclasses are less well examined. We established a flow cytometry method (ABO-fluorescence-activated cell sorting; ABO-FACS) to quantify binding of anti-A/B IgM, IgG and IgG subclasses to human A or B red blood cells. Anti-A/B IgM were present in the majority of 120 blood donors, as expected from blood group typing. The sensitivity and specificity of anti-A/B IgM to predict the blood group was 93% and 96% respectively. Anti-A/B IgG was found in 34/38 blood group O samples (89%). Anti-B IgG in blood group A or anti-A IgG in blood group B was present in 4/28 (14%) and 1/28 (4%) samples, respectively, and absent in 26 AB sera. IgG2 was the predominant IgG subclass. The correlation of anti-A/B IgM and IgG in the ABO-FACS with haemagglutination titres was 0.870 and 0.783, respectively (n = 240; P < 0.001) whereas the comparison of ABO-FACS with ABO-enzyme-linked immunosorbent assay was less significant. In conclusion, ABO-FACS is a valid method to quantify anti-A/B IgM, IgG and IgG subclasses. It opens the possibility of isotype-specific monitoring of anti-A/B antibodies levels after ABO-incompatible solid organ and stem cell transplantation.

ABO Blood-Group System↗

Aerococcus urinae endocarditis: case report and review of the literature.

Aerococcus urinae is a rare cause of urinary tract infections, mainly in elderly men with underlying urinary tract pathologies. In addition, it has been described as a pathogen in balanitis, soft tissue infections, septicemia and endocarditis. To date ten cases of A. urinae endocarditis have been reported in the literature with a high rate of mortality (7/10) and morbidity, as two out of three survivors suffered from neurovascular complications. Here we present the case of an additional patient who was successfully treated with surgical valve replacement and antibiotic therapy consisting of ceftriaxone and netilmicin for 6 weeks. Furthermore, we review all reported cases of A. urinae endocarditis with emphasis on predisposing factors and therapeutic options.

Aged↗

Consequences of ABO incompatibility in allogeneic hematopoietic stem cell transplantation.

Aside from causing hemolytic reactions the ABO blood group system does not have an impact on outcome after allogeneic bone marrow or peripheral blood stem cell transplantation (SCT). However, only a few studies have addressed the effect of ABO incompatibility on the incidence of GVHD, time to engraftment, relapse and survival. Therefore, we performed a retrospective two-center analysis of 562 consecutive patients receiving allogeneic SCT, including 361 ABO-identical, 98 minor, 86 major and 17 bidirectional ABO-incompatible SCT. In multivariate analysis adjusted for potential confounders survival was significantly associated with ABO incompatibility (P = 0.006). Compared to ABO-identical SCT, bidirectional ABO incompatibility increased the risk significantly (RR, 2.8; 95% CI, 1.5-5.1; P = 0.0009), whereas survival of patients with minor (RR, 1.2; 95% CI, 0.9-1.7; P = 0.27), or major ABO-incompatible SCT (RR, 1.3; 95% CI, 0.9-1.8; P= 0.18) was not significantly different. RBC engraftment was delayed in major ABO-incompatible SCT (RR, 0.66; 95% CI, 0.51-0.85; P = 0.001). The incidence of acute GVHD (grade I-IV) was higher in minor ABO-incompatible SCT as compared to ABO identity (RR, 2.8; 95% CI, 1.3-5.9, P = 0.009). This difference was limited to mild GVHD; in moderate-to-severe GVHD (grade II-IV) no significant difference was found among the groups (P = 0.53). The relapse rate was not influenced by ABO incompatibility (P = 0.78). In conclusion, these results suggest that ABO incompatibility represents a risk factor not only for post-transplant hemolysis, but also for survival and the rate of mild GVHD after allogeneic SCT.

ABO Blood-Group System↗

HLA-G inhibits rolling adhesion of activated human NK cells on porcine endothelial cells.

Human NK cells adhere to and lyse porcine endothelial cells (pEC) and therefore may contribute to the cell-mediated rejection of vascularized pig-to-human xenografts. Since MHC class I molecules inhibit the cytotoxic activity of NK cells, the expression of HLA genes in pEC has been proposed as a potential solution to overcome NK cell-mediated xenogeneic cytotoxicity. HLA-G, a minimally polymorphic HLA class I molecule that can inhibit a wide range of NK cells, is an especially attractive candidate for this purpose. In this study we tested whether the expression of HLA-G on pEC inhibits the molecular mechanisms that lead to adhesion of human NK cells to pEC and subsequent xenogeneic NK cytotoxicity. To this end two immortalized pEC lines (2A2 and PED) were stably transfected with HLA-G1. Rolling adhesion of activated human NK cells to pEC monolayers and xenogeneic cytotoxicity against pEC mediated by polyclonal human NK lines as well as NK clones were inhibited by the expression of HLA-G. The adhesion was partially reversed by masking HLA-G on pEC with anti-HLA mAbs or by masking the HLA-G-specific inhibitory receptor ILT-2 on NK cells with the mAb HP-F1. The inhibition of NK cytotoxicity by HLA-G was only partially mediated by ILT-2, indicating a role for other unknown NK receptors. In conclusion, transgenic expression of HLA-G may be useful to prevent human NK cell responses to porcine xenografts, but is probably not sufficient on its own. Moreover, the blocking of rolling adhesion by HLA-G provides evidence for a novel biological function of HLA molecules.

Animals↗

Polyclonal proliferation of large granular lymphocytes during cytomegalovirus primary infection in a human immunodeficiency virus-infected patient receiving antiretroviral therapy.

We report the first case of a patient infected with HIV in whom polyclonal CD8+/CD57- T lymphocyte large granular lymphocyte (LGL) proliferation was observed in association with cytomegalovirus primary infection. Because the differential diagnosis of an increased number of LGLs includes both monoclonal LGL leukemia and polyclonal proliferation of LGL, patients in whom LGL proliferation is detected always need close hematological and clinical observation to determine whether therapeutic intervention is necessary.

AIDS-Related Opportunistic Infections↗

Inhibition of human NK cell-mediated cytotoxicity by exposure to ammonium chloride.

Ammonium-chloride-containing solutions (AC) are routinely used to lyse red blood cells during preparation of PBMC. Although exposure to AC has been described to affect the ultrastructural appearance of large granular lymphocytes and to temporarily inhibit cytolytic activity of PBMC preparations, the cellular basis of this phenomenon has not been studied. Here, the inhibitory effect of AC on human CTL and NK-mediated cytotoxicity has been analyzed in 4-h 51Cr-release assays. The results show that NK killing of K562 leukemia cells and xenogeneic endothelial cells is inhibited by AC exposure. The effect is dose-dependent and reversible, because recovery of cytotoxicity is observed within 15 h of re-culturing. AC does not reduce the viability of NK cells and the inhibitory effect is not mediated by the exhaustive release of granzymes upon AC treatment. In contrast, antigen-specific CTL killing of EBV-transformed B-lymphoblastoid cell lines and xenogeneic PHA lymphoblasts was less sensitive to AC and data are presented suggesting that FasL-induced apoptosis is not inhibited by AC. In conclusion, perforin-mediated NK killing is AC-sensitive whereas CTL killing and FasL-mediated killing appear to be AC-resistant. Therefore, AC represents a powerful tool to study different mechanisms of cell-mediated cytotoxicity and may be helpful in assessing antigen-specific CTL cytotoxicity without the influence of NK cell-mediated background killing.

Ammonium Chloride↗

Immortalized bone-marrow derived pig endothelial cells.

Primary cultures of porcine endothelial cells (EC) can only be maintained for a limited number of passages. To facilitate studies of xenogeneic human anti-pig immune responses in vitro, pig microvascular bone-marrow (BM) and macrovascular aortic EC were obtained from our herd of partially inbred miniature swine, homozygous for the major histocompatibility locus, and immortalized with a modified SV40 large T vector. The resulting BM-derived (2A2) and aortic (PEDSV.15) immortalized EC lines showed unlimited growth and EC phenotype as indicated by expression of von Willebrand Factor (vWF) and low density lipoprotein (LDL) receptors as well as by formation of typical cobblestone monolayers. Ultrastructural studies revealed morphological similarities in primary and immortalized EC. Flow cytometry analysis demonstrated constitutive SLA class I expression by all lines whereas SLA class II was only expressed after stimulation with porcine IFNgamma. Furthermore, pig CD34 mRNA was detected by Northern blot analysis in primary and immortalized aortic EC but not in 2A2. Both EC lines expressed a number of myeloid markers, adhesion molecules and xenoantigens, the latter being determined by binding of human natural antibodies. Gene transfer into the porcine EC lines was successfully performed by electroporation or calcium-phosphate transfection, as well as by adenoviral infection. Finally, the functional similarity between primary and immortalized EC was demonstrated in adhesion and cytotoxicity assays. Together, these results suggest that 2A2 and PEDSV. 15 represent valuable tools to study both human cellular and humoral immune responses in vitro against pig EC derived from microvascular and large vessels.

Animals↗

Graft-versus-host disease and survival after ABO-incompatible allogeneic bone marrow transplantation: a single-centre experience.

The effect of ABO-incompatibility on graft versus host disease (GVHD) and survival was evaluated in 173 consecutive patients receiving allogeneic bone marrow transplantation (BMT). Thirty-four percent of the patients developed GVHD and univariate analysis suggested a higher incidence of GVHD in minor ABO-incompatibility than in ABO-identity (14/30, 47% versus 37/112, 33%; P = 0.02). However, using logistic regression adjusted for potential confounders, the GVHD risk did not differ significantly. During a mean follow-up time of 59 months, the mortality was 37% and survival was significantly dependent on ABO-compatibility (P = 0.004). In particular, patients with bidirectional ABO-incompatibility had an excess mortality rate (RR, 7.6; 95% CI, 2.5-23.2; P = 0.0004). Taken together, these results suggest that ABO-incompatibility may represent a risk factor in allogeneic BMT.

ABO Blood-Group System↗

Acral necrosis of the fingers as initial manifestation of cutaneous polyarteritis nodosa--a case report.

Cutaneous polyarteritis nodosa (CPN) is a well-known entity showing subcutaneous tender nodules, livedo reticularis, and ulcerations as predominant features; arthralgia, myalgia, peripheral neuropathy, and general symptoms such as fever and malaise may also be present. Although the localization of the disease is not specific, the characteristic primary lesions are painful subcutaneous nodules on the lower extremities. Here we report the case of a 33-year-old man with blue-colored distal phalanges and necrosis of several fingertips on both hands as the initial manifestation of CPN.

Adult↗

[Ant venoms: a rare cause of allergic reactions in Switzerland].

In Switzerland, unlike other countries, allergic reactions to ants are a rare phenomenon when compared to the well known allergies to bee and wasp venom. In this report we present a series of case reports and a review of the different types of allergy to ants. Due to increased travel and heterogeneity of the population, we have observed several patients with sensitisation or allergy to the venom of imported fire ants (Solenopsis), a species of ant found in the Americas. Furthermore, allergic reactions to bites of the mound-building wood ant (Formica rufa), whose habitat is Central and Northern Europe, have been documented. Whereas reactions to fire ants can be life-threatening, reactions to mound-building wood ants have led to marked local reactions and in 2 cases to dyspnoea and wheezing. These reactions could be due either to primary sensitisation to ant venom or cross-reactivity in the presence of an allergy to wasp venom. Evaluation of patients presenting with a potential ant venom allergy includes a detailed personal history, skin testing and determination of specific IgE. However, to date only extracts from fire ants are commercially available for diagnostic tests. In the light of our observations we assume cross-reactivity between the venoms of fire ants and mound-building wood ants, and it therefore seems appropriate to use fire ant diagnostics in determining sensitisation to mound-building wood ants. In patients with severe fire ant-venom allergy we recommend desensitisation by immunotherapy, whereas in patients presenting with minor allergic reactions, e.g. after bites by mound-building wood ants, we provide the patients with emergency medication. Since current knowledge of ant allergies in Europe is limited, further studies are warranted.

Animals↗

Porcine aortic endothelial cells transfected with HLA-G are partially protected from xenogeneic human NK cytotoxicity.

In this study we tested whether the expression of HLA-G protects porcine endothelial cells (PEC) from the lysis mediated by human natural killer (NK) cells. Because HLA-E is not present in PEC, this model provides an ideal tool to study the direct role of HLA-G in NK inhibition. Immortalized porcine aortic endothelial cells (PED) were stably transfected with a vector coding for the HLA-G1 protein and surface expression was demonstrated by flow cytometry analysis. Although the adhesion of human NK cells to PED was not compromised by HLA-G, the expression of HLA-G partially protected PED from the lysis mediated by polyclonal NK lines derived from different donors. A decrease of the surface expression of HLA-G on PED corresponded to a loss of the capacity of PED to inhibit NK cytotoxicity, indicating that the surface density of HLA-G molecules must exceed a certain threshold to protect target cells. In summary, these data show that HLA-G, independent from the presence of HLA-E, can only partially and inefficiently protect PED from human NK cell-mediated cytotoxicity. Because ILT-2/LIR-1 expression did not correlate with HLA-G mediated inhibition, we hypothesize that other yet unidentified receptors expressed by peripheral blood NK cells are involved in the recognition of HLA-G.

Animals↗

Age-related expression of the cellular prion protein in human peripheral blood leukocytes.

BACKGROUND AND OBJECTIVE: Creutzfeldt-Jakob disease typically affects older patients, yet victims of new-variant Creutzfeldt-Jakob disease (nvCJD) are unusually young. Because the cellular prion protein PrP(C) is required for disease development, we investigated age-dependent variability in cell surface PrP(C) expression on various subclasses of human peripheral blood leukocytes (PBL) as a possible susceptibility factor. DESIGN AND METHODS: Three age groups of healthy individuals (mean ages: 6, 33 and 68) were studied by two-color FACS analysis of PBL with fluorescent monoclonal antibodies to PrP(C) and to the lineage markers CD3, CD19, CD4, and CD8. For each subclass marker, surface PrP(C) levels were expressed as mean fluorescence intensity ratios (MFIR) by dividing the geometric mean of the fluorescence of each test antibody by the geometric mean of its isotype-matched control antibody. PrP(C) expression levels in each age and lineage group were compared using appropriate non-parametric tests. RESULTS: We found significant age-related differences in PrP(C) expression on lymphocytes (p=0. 0004). The elderly expressed significantly higher levels than children (p=0.0006) and adults (p=0.0009). PrP(C) expression was also significantly higher in CD3(+) compared to CD19(+ )(p=0.0004) and in CD8(+) compared to CD4(+ )lymphocytes (p=0.0044). INTERPRETATION AND CONCLUSIONS: If PrP(C) expression on PBL were a significant susceptibility factor for nvCJD, young persons would display higher levels. Instead, the elderly expressed the highest amounts of PrP(C) on PBL. This argues against the hypothesis that variability in cell surface expression of PrP(C) in PBL contributes to the exquisite susceptibility of the young to nvCJD.

Adolescent↗

Human CD4+ T cells mediate rejection of porcine xenografts.

It has previously been demonstrated that xenograft rejection in rodents is dependent on CD4+ T cells. However, because of the lack of an appropriate in vivo model, little is known about the cellular basis of human T cell-mediated rejection of xenografts. In this study, we have evaluated the ability of human T cells to mediate rejection of porcine skin grafts in a novel in vivo experimental system using immunodeficient mice as recipients. Recombinase-activating gene-1-deficient mice (R-) lacking mature B and T cells were grafted with porcine skin and received human lymphocytes stimulated in vitro with irradiated porcine PBMC. Skin grafts on mice given either unseparated, activated human lymphocytes, or NK cell-depleted lymphocyte populations were rejected within 18 days after adoptive cell transfer. In contrast, skin grafts on mice given T cell-depleted human lymphocytes or saline showed no gross or histologic evidence of rejection up to 100 days after adoptive transfer. Purified CD4+ T cells were also able to mediate rejection of porcine skin grafts. These data suggest that human CD4+ T cells are sufficient to induce rejection of porcine xenografts. Thus, strategies directed toward CD4+ T cells may effectively prevent cellular rejection of porcine xenografts in humans.

Animals↗