Umbilical cord blood transplantation: acceptance of umbilical cord blood donation by pregnant patients

BACKGROUND/OBJECTIVE: Umbilical cord blood is an alternative source for allogeneic transplantation of hematopoietic stem cells from related and unrelated donors. It can easily be collected, cryopreserved and stored in cord blood banks for later use. In Switzerland, cord blood banks for related and unrelated stem cell transplantation are being established. The aim of the study was to evaluate previous knowledge of the possible medical use of cord blood and acceptance of cord blood banking in pregnant women. METHODS: We performed a prospective open study using a structured, anonymous questionnaire at the University of Basel Women's Hospital pregnancy outpatient clinic. After concise information on the use of cord blood for transplantation, questions were asked concerning previous knowledge of the use of placenta and cord blood in general, concerning the attitude to donation of cord blood for transplantation, and the respondent's willingness to donate cord blood of her own child. Women of different ethnic background were compared. RESULTS: From 300 questionnaires handed out to pregnant women of different ethnic background attending our outpatient clinic, 250 (83%) were returned, and 245 could be evaluated for final analysis. Only 40% indicated that they did know what usually happens to the placenta after birth. In contrast, the vast majority (95%) supported the idea of umbilical cord blood for banking and later use for stem cell transplantation. Similarly, 93% stated that they would agree to donate the cord blood from their own child for this purpose, while no statistically significant differences could be identified either between women with or without previous knowledge or of different ethnic background. CONCLUSIONS: This study shows the high acceptance of umbilical cord blood donation for banking and stem cell transplantation purposes in pregnant women, irrespective of previous knowledge. As there are no major differences between women of different ethnic background, a high degree of diversity of HLA-types of donated cord blood samples can be expected and may offset the underrepresentation of ethnic minorities in bone marrow donor registries.     

Xenoantibodies to pig endothelium are expressed in germline configuration and share a conserved immunoglobulin VH gene structure with antibodies to common infectious agents

BACKGROUND: The rejection of pig xenografts in humans is initiated by preformed antibodies that may be related to the natural antibodies that formulate a first line of defense against infectious agents. Immunoglobulin gene variable domains encoding the antibodies that react with similar epitopes expressed on xenoantigens and bacteria may share structurally similar antigen-binding site configurations. METHODS: We sequenced the VH immunoglobulin genes and germline progenitors of two rat monoclonal antibodies that recognize pig xenoantigens. Nucleic and amino acid sequences of these xenoantibodies were compared with immunoglobulin genes encoding antibodies that react with bacteria or viruses. RESULTS AND CONCLUSIONS: VH genes encoding rat anti-pig xenoantibodies are expressed in germline configuration and share structural similarities, including identical amino acids in key antigenic contact sites that define antibody canonical structural groups, with antibodies to infectious agents.     

Major histocompatibility complex class I-restricted T cells are required for all but the end stages of diabetes development in nonobese diabetic mice and use a prevalent T cell receptor alpha chain gene rearrangement

Nonobese diabetic (NOD) mice develop insulin-dependent diabetes mellitus due to autoimmune T lymphocyte-mediated destruction of pancreatic beta cells. Although both major histocompatibility complex class I-restricted CD8(+) and class II-restricted CD4(+) T cell subsets are required, the specific role each subset plays in the pathogenic process is still unclear. Here we show that class I-dependent T cells are required for all but the terminal stages of autoimmune diabetes development. To characterize the diabetogenic CD8(+) T cells responsible, we isolated and propagated in vitro CD8(+) T cells from the earliest insulitic lesions of NOD mice. They were cytotoxic to NOD islet cells, restricted to H-2Kd, and showed a diverse T cell receptor beta chain repertoire. In contrast, their alpha chain repertoire was more restricted, with a recurrent amino acid sequence motif in the complementarity-determining region 3 loop and a prevalence of Valpha17 family members frequently joined to the Jalpha42 gene segment. These results suggest that a number of the CD8(+) T cells participating in the initial phase of autoimmune beta cell destruction recognize a common structural component of Kd/peptide complexes on pancreatic beta cells, possibly a single peptide.     

Human Herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report

We examined cerebral spinal fluid (CSF) from multiple sclerosis (MS) patients and patients with other neurological diseases (OND) for antibody specific for Human Herpesvirus-6 (HHV-6) and for HHV-6 DNA detectable by PCR. CSF from MS patients had a higher frequency of IgG antibody to HHV-6 late antigens (39.4%) compared with CSF from OND (7.4%). In contrast, the frequency of detectable IgG antibody in CSF from MS patients specific for Epstein-Barr Virus (EBV) (12.1%) and Human Cytomegalovirus (HCMV) (6.1%) was much lower. Two of 12 MS CSFs (16.7%) also contained HHV-6 DNA detected by PCR. None of four OND CSF were positive for HHV-6 DNA. Plasma from 16 patients with MS, eight with OND and 72 healthy donors were tested for antibodies by ELISA to HHV-6 early (p41/38) and late (gp110) proteins. Although no differences in anti-gp110 IgG antibody were detected between MS patients, patients with other neurological diseases, and normals, IgG antibody to early protein p41/38 was detected in > 68% of the plasma from MS patients, 12.5% from OND patients and 27.8% of the controls. IgM antibody to p41/38 was present in > 56% of MS patients, 12.5% of OND patients, and 19% of controls. These data suggest that more than half of the MS patients had active, ongoing HHV-6 infections. HHV-6 was also isolated from peripheral blood mononuclear cells (PBMC) from 3/5 MS patients who were in relapse or had progressive disease and was identified as HHV-6 Variant B. These preliminary results support the hypothesis that HHV-6 may be a co-factor in the pathogenesis of some cases of MS.     

NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin

Cyclic AMP is a major second messenger that inhibits the brush border Na+/H+ exchanger NHE3. We have previously shown that either of two related regulatory proteins, E3KARP or NHERF, is necessary for the cAMP-dependent inhibition of NHE3. In the present study, we characterized the interaction between NHE3 and E3KARP using in vitro binding assays. We found that NHE3 directly binds to E3KARP and that the entirety of the second PSD-95/Dlg/ZO-1 (PDZ) domain plus the carboxyl-terminal domain of E3KARP are required to bind NHE3. E3KARP binds an internal region within the NHE3 C-terminal cytoplasmic tail, defining a new mode of PDZ domain interaction. Analyses of cellular distribution of NHE3 and E3KARP expressed in PS120 fibroblasts show that NHE3 and E3KARP are co-localized on the plasma membrane, but not in a distinct juxtanuclear compartment in which NHE3 is predominantly expressed. The distributions of NHE3 and E3KARP were not affected by treatment with 8-bromo-cAMP. As shown earlier for the human homolog of NHERF, we also found that the cytoskeletal protein ezrin binds to the carboxyl-terminal domain of E3KARP. These results are consistent with the possibility that E3KARP and NHERF may function as scaffold proteins that bind to both NHE3 and ezrin. Since ezrin is a protein kinase A anchoring protein, we suggest that the scaffolding function of E3KARP binding to both ezrin and NHE3 localizes cAMP-dependent protein kinase in the vicinity of the cytoplasmic domain of NHE3, which is phosphorylated by elevated cAMP.     

The left ventricular contractility of the rat heart is modulated by changes in flow and alpha 1-adrenoceptor stimulation

Myocardial contractility depends on several mechanisms such as coronary perfusion pressure (CPP) and flow as well as on alpha 1-adrenoceptor stimulation. Both effects occur during the sympathetic stimulation mediated by norepinephrine. Norepinephrine increases force development in the heart and produces vasoconstriction increasing arterial pressure and, in turn, CPP. The contribution of each of these factors to the increase in myocardial performance needs to be clarified. Thus, in the present study we used two protocols: in the first we measured mean arterial pressure, left ventricular pressure and rate of rise of left ventricular pressure development in anesthetized rats (N = 10) submitted to phenylephrine (PE) stimulation before and after propranolol plus atropine treatment. These observations showed that in vivo alpha 1-adrenergic stimulation increases left ventricular developed pressure (P < 0.05) together with arterial blood pressure (P < 0.05). In the second protocol, we measured left ventricular isovolumic systolic pressure (ISP) and CPP in Langendorff constant flow-perfused hearts. The hearts (N = 7) were perfused with increasing flow rates under control conditions and PE or PE + nitroprusside (NP). Both CPP and ISP increased (P < 0.01) as a function of flow. CPP changes were not affected by drug treatment but ISP increased (P < 0.01). The largest ISP increase was obtained with PE + NP treatment (P < 0.01). The results suggest that both mechanisms, i.e., direct stimulation of myocardial alpha 1-adrenoceptors and increased flow, increased cardiac performance acting simultaneously and synergistically.     

Monte Carlo simulation of steps behavior on Si(111) surface during sublimation

Investigation of steps behavior on vicinal (111) surface during sublimation was carried out using 3D-model of diamond-like crystal. Step width periodic variations predicted by Schwoebel were found by modeling. Diamond-like crystal structure results in the asymmetry in atom fluxes to the upper or lower terraces, with the sign of asymmetry depending on the step structure. The essential effect of vacancies created on terraces on migration length of atoms was revealed.     

Secretory immunoglobulins A from human milk possess affinity to oligonucleotides and nucleic acids

Dreams provide access to underlying personality structure, defensive and adaptive functions, and they elucidate the psychological forces that lead to overt symptomatic behavior. Two hundred three dreams of 39 personality disordered patients were factor analyzed and compared with Hall and Van de Castle's normative data (Hall C, Van de Castle RI [1966] The content analysis of dreams. New York: Appleton-Century-Crofts). Results included a five-factor solution that sheds light on some core issues of the dreamers. Comparisons between the groups resulted in the personality-disordered group demonstrating more estrangement in their dreams, fewer interactions, and more emotionality. In their interactions, they demonstrated a lower ratio of aggressive interactions yet a higher tendency to view themselves as the aggressor. Results are related to theoretical literature on personality and defensive styles, mostly from a psychodynamic perspective.