Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells

BACKGROUND: Human multipotent mesenchymal stromal cells (MSCs) are promising candidates for a growing spectrum of regenerative and immunomodulatory cellular therapies. Translation of auspicious experimental results into clinical applications has been limited by the dependence of MSC propagation from fetal bovine serum (FBS). STUDY DESIGN AND METHODS: The capacity of human platelet lysate (HPL) to replace FBS for clinical-scale MSC propagation was analyzed. RESULTS: HPL could be efficiently produced from buffy coats. Multiplex analyses allowed a distinct HPL growth factor profile to be delineated. With a previously established two-step clinical-scale procedure, HPL was reproducibly more efficient than FBS in supporting MSC outgrowth. With only 3 x 10(5) primary culture-derived MSCs, a mean of 4.36 x 10(8) HPL-MSCs (range, 3.01 x 10(8)-5.40 x 10(8)) was obtained within a single secondary 11- to 13-day culture step. Although morphologically distinct, HPL-MSCs and FBS-MSCs did not differ significantly in terms of immunophenotype, differentiation potential in vitro, and lack of tumorigenicity in nude mice in vivo. CONCLUSIONS: Replacing FBS with HPL prevents bovine prion, viral, and zoonose contamination of the stem cell product. This new efficient FBS-free two-step procedure for clinical-scale MSC propagation may represent a major step toward challenging new stem cell therapies.     

2-Acylamino-5-chlorobenzophenones with enhanced selectivity towards malaria parasites

Previously we described a series of 5-acylaminobenzophenones with considerable antimalarial activity. Unfortunately, most compounds also displayed high cytotoxicity resulting in low selectivity towards malaria parasites. Through the replacement of the 5-acylamino moiety by simple chlorine and further modifications of the 2-acylamino residue we could obtain inhibitors with improved selectivity towards malaria parasites combined with an acceptable reduction of antimalarial activity.     

Identification of 14 new alleles at the fucosyltransferase 1, 2, and 3 loci in Styrian blood donors, Austria

BACKGROUND: Genes for fucosyltransferases 1 (FUT1:H), 2 (FUT2:Secretor), and 3 (FUT3:Lewis) encode enzymes crucial for ABH and Lewis blood group antigen synthesis. They are highly polymorphic and ethnically and geographically specific.
STUDY DESIGN AND METHODS: Genetic variations and allele frequencies of FUT1, FUT2, and FUT3 encoding regions and flanking sequences were analyzed in 100 Styrian blood donors by systematic sequencing. Haplotypes were verified with sequence-specific primers. To identify discrepancies, serologically determined ABO and Lewis blood groups were correlated to respective genotypes.
RESULTS: Two novel FUT1 alleles were defined by 9C>T (silent) and 991C>A (P331T) mutations, the latter located in the catalytic domain of the enzyme. Five new alleles of FUT2 were found: three were characterized by new variants and two resulted from new combinations of known polymorphisms. The new 412G>A (G138S) mutation also is located in the catalytic domain. A new nonsecretor allele, based on the presence of 428G>A (nonsense), was found. Another FUT2 allele may have resulted from an intragenic crossover event. FUT3 analysis revealed seven novel alleles, partly based on the new mutations 41G>A (R14H), 1060C>G (R354G), 735G>C (silent), and 882C>T (silent). While 41G>A is placed in the cytoplasmic domain and functional, 1060C>G is placed in the catalytic domain.
CONCLUSION: Multiple common and sporadic sequence variations including 14 new alleles at FUT1, FUT2, and FUT3 loci were identified. Four novel mutations result in amino acid substitution in the protein. Three of them are predicted to have adverse effects on the enzyme activity. A novel nonsecretor allele was found.     

Acute midbrain syndrome as an adverse reaction to tetanus immunization

An acute midbrain syndrome III/IV developed twice after tetanus immunization. The occurrence of nearly identical episodes was remarkable, as well as the relatively rapid return to normal consciousness and neurological status after deep coma. Special emphasis is placed upon the chronological relationship of the coma to the immunization and upon immunological tests (tetanus antibody titres) performed to confirm the diagnosis.     

Parasitism and chromosome dynamics in protozoan parasites: is there a connection?

Genomic plasticity is a hallmark of many protozoan parasites, including Plasmodium spp, Trypanosoma spp, Leishmania ssp and Giardia lamblia. Strikingly, there is a common theme regarding the structural basis of this karyotype variability. Chromosomes are compartmentalized into conserved central domains and polymorphic chromosome ends. Since antigen-encoding genes frequently reside in telomere-proximal domains, it is tempting to speculate that the genetic flexibility of chromosome ends has been recruited as a tool in immune evasion strategies by some parasitic protozoa.     

Extensor tendon rupture due to Coccidioides immitis. Report of a case

In a 60-year-old man, extensor tendon rupture was associated with coccidioidal tenosynovitis. Dissemination of Coccidioides immitis to the tenosynovium in the wrist is an unusual complication following pulmonary coccidioidomycosis.     

Mechanisms of action and clinical importance of C3-nephritic-factor (author's transl)

The C3-nephritic-factor is an autoantibody specific against C3-convertases. This IgG-immunoglobulin is particularly found in patients suffering from membranoproliferative glomerulonephritis and causes a complement-activation under elimination of physiological regulator mechanisms. The clinical importance of this factor is discussed.     

Willingness to pay for hypothetical malaria vaccines in rural Burkina Faso

AIMS: This study aims to set priorities for anti-disease malaria vaccines by determining community preference in a hyperendemic area. METHODS: A bidding game technique was used to elucidate willingness to pay in rural Burkina Faso and 2,326 adults were interviewed. RESULTS: It is shown that there are significant differences between community preference for an anti-disease vaccine aimed at reducing pathology in pregnant women, and for a vaccine directed against childhood malaria. While the target population was willing to pay CFAfr 2101 for a vaccine against maternal malaria, its members were prepared to pay only CFAfr 1433 for a vaccine against childhood malaria. CONCLUSIONS: Whilst it is increasingly likely that anti-disease malaria vaccines will become available in the foreseeable future, lessons from the past suggest that a lack of acceptance and support from the intended recipients may lead to less than optimal compliance, and hence efficacy. For the planning of vaccine development and application strategies, it is therefore highly important to take community views into account. Here it is argued that such information could help researchers and funding agencies to set priorities for future vaccine research.     

Serum levels of the soluble receptor for tumor necrosis factor in patients with renal disease

Tumor necrosis factor- (TNF-) has been found to be elevated in patients during hemodialysis and is thought to mediate some of the immune and metabolic dysfunctions in these patients. It has been speculated that infusions of soluble TNF receptor (sTNF-R) may prevent some of the cytotoxic effects of TNF. However, little is still known about preexisting serum TNF-R levels in patients with chronic renal failure, with or without hemodialysis. Therefore we analyzed serum samples of sTNF-R in 26 patients with chronic renal failure (group I), 6I hemodialysis patients (group II), 9 renal transplant recipients with acute renal failure requiring posttransplant dialysis (group III), 13 renal transplant patients with rejection and moderate kidney dysfunction (group IV), and 21 renal transplant recipients with borderline kidney dysfunction and diverse infectious complications (group V). Control groups consisted of 34 blood donors and diseased controls (11 renal transplant recipients with normal kidney function without complications). All patient groups showed significantly higher sTNF-R levels compared to the control groups. In groups I, IV, and V comparable levels were observed. In group I there was a clear correlation between sTNF-R levels and serum creatinine. The highest sTNF-R serum levels were seen in groups II and III, but there was no correlation with creatinine. In the posttransplant cases (group III and diseased controls) there was a decrease in sTNF-R with improvement of kidney function. These data strongly suggest that sTNF-R serum levels are dependent on kidney function.Abbreviations TNF tumor necrosis factor - TNF-R tumor necrosis factor receptor - sTNF-R soluble tumor necrosis factor receptor - RTX renal transplantation - ELISA enzyme-linked immunosorbent assay Correspondence to: G. Halwachs