Genetic evidence of multiple transmissions of HIV type 1 subtype F within Romania from adult blood donors to children

We studied the phylogeny of HIV-1 subtype F viruses from children and adults in Romania in order to (1) clarify whether the Romanian subtype F epidemic was caused by one or several virus introductions and (2) gain insight into the route of spread of the HIV-1 subtype F virus among children and adults in Romania. env (V3), gag (p17/half p24), and pol (prot/half RT) sequences were obtained from three districts in Romania: Tirgu Mures (n = 9, children), Craiova (n = 15, children), and Bucharest (n = 13, adults). Of 37 HIV V3 sequences from Romania, 35 belonged to the genetic subtype F in the neighbor-joining tree, whereas 2 sequences from adults clustered with subtypes A and C. Within the subtype F cluster, no bootstrap-supported subclusters were observed according to geographic area in Romania. Two of the adult V3 sequences that clustered with the children were obtained from individuals who tested HIV seropositive in 1989 and 1990, showing that the subtype F virus was present among adults when the HIV epidemic began among children in Romania. The HIV-1 subtype F viruses obtained from children showed a mean pairwise V3 nucleotide distance of 7.9% and maximum distances of between 18 and 19%; both are higher than previously described. The mean V3 distances (overall, synonymous, and nonsynonymous) were significantly higher for adults than for children. One V3 sequence from the Democratic Republic of Congo clustered within the Romanian sequences, suggesting that the subtype F virus in Romania may originate from this area. Our data also suggest that HIV-1 subtype F was present among Romanian adults before it appeared in 1989 among institutionalized children. The juvenile population was most likely infected with the HIV-1 subtype F virus on more than one occasion, presumably through HIV-contaminated blood (products) obtained from adults.     

ImmunoGlobulin galaxy (IGGalaxy) for simple determination and quantitation of immunoglobulin heavy chain rearrangements from NGS

Background

Toxic shock syndrome (TSS) is caused by an overwhelming host-mediated response to bacterial superantigens produced mainly by Staphylococcus aureus and Streptococcus pyogenes. TSS is characterized by aberrant activation of T cells and excessive release of pro-inflammatory cytokines ultimately resulting in capillary leak, septic shock, multiple organ dysfunction and high mortality rates. No therapeutic or vaccine has been approved by the U.S. Food and Drug Administration for TSS, and novel therapeutic strategies to improve clinical outcome are needed. Mesenchymal stromal (stem) cells (MSCs) are stromal cells capable of self-renewal and differentiation. Moreover, MSCs have immunomodulatory properties, including profound effects on activities of T cells and macrophages in specific contexts. Based on the critical role of host-derived immune mediators in TSS, we hypothesized that MSCs could modulate the host-derived proinflammatory response triggered by Staphylococcal enterotoxin B (SEB) and improve survival in experimental TSS.

Methods

Effects of MSCs on proinflammatory cytokines in peripheral blood were measured in wild-type C57BL/6 mice injected with 50 μg of SEB. Effects of MSCs on survival were monitored in fatal experimental TSS induced by consecutive doses of D-galactosamine (10 mg) and SEB (10 μg) in HLA-DR4 transgenic mice.

Results

Despite significantly decreasing serum levels of IL-2, IL-6 and TNF induced by SEB in wild-type mice, human MSCs failed to improve survival in experimental TSS in HLA-DR4 transgenic mice. Similarly, a previously described downstream mediator of human MSCs, TNF-stimulated gene 6 (TSG-6), did not significantly improve survival in experimental TSS. Furthermore, murine MSCs, whether unstimulated or pre-treated with IFNγ, failed to improve survival in experimental TSS.

Conclusions

Our results suggest that the immunomodulatory effects of MSCs are insufficient to rescue mice from experimental TSS, and that mediators other than IL-2, IL-6 and TNF are likely to play critical mechanistic roles in the pathogenesis of experimental TSS.     

Contact allergies to topical corticosteroids: 10 cases of contact dermatitis

Patients who noticed worsening of their skin disease after using topical corticosteroid preparations were patch tested both with the commercial preparation and the corticosteroid itself. Between 1987 and 1989, 10 cases of contact dermatitis due to topical corticosteroids were detected in this way. The corticosteroids wee amcinonide (2 patients), hydrocortisone butyrate, clobetasol propionate (2), betamethasone valerate (2), prednicarbate and fluocortolone (2). Patch tests with the commercial preparations and the corticosteroids themselves elicited reactions almost identical in time course and severity. Individual sensitivity seems to be more important for test results than test conditions. 9 of the 10 patients underwent further patch testing with a corticosteroid series. In 2 patients, a true cross-reaction between budesonide and hydrocortisone butyrate was found. All 9 patients showed further sensitivities to other corticosteroids. Most of the cross or concomitant reactions could be categorized into recently defined corticosteroid classes. To improve our understanding of corticosteroid sensitization, and to help the patient avoid reactions to other topical corticosteroids, a corticosteroid series should be patch tested in every case of corticosteroid sensitivity.     

Sjögren-Lupus erythematodesÜberlappungssyndrom

Zusammenfassung Patienten mit ph?notypischer Sj?gren-Syndrom (SS)-Lupus erythematodes(LE)-überlappung stellen eine immungenetisch, serologisch und klinisch einheitliche Krankheitsgruppe dar mit polyzyklisch-anul?ren, erythematosquam?sen Hautl?sionen, zirkulierenden SSA(Ro)-Antik?rpern und hoher Pr?valenz des immungenetischen Ph?notyps HLA-DR3. Die Sicca-Symptomatologie des SS kann der LE-Symptomatik zeitlich folgen oder vorangehen. Neben Hautver?nderungen wie beim subakuten kutanen LE (SCLE) kommt es zu vaskulitischen, purpuriformen und Sweet-Syndrom-artigen Hautl?sionen. Die ?lteren, vornehmlich weiblichen Patienten zeigen ein erh?htes Risiko pulmonaler und neurologischer Komplikationen. Demgegenüber kommt es selten zu einer Nierenbeteiligung. Eine 81j?hrige, anti-SSA(Ro)-, HLA-DR3-positive Frau mit 30j?hriger Anamnese eines kutanen LE wird vorgestellt, bei der erst Jahre sp?ter neben den Hautver?nderungen eines SCLE eine Sicca-Symptomatik, vaskulitische und Sweet-Syndrom-artige Hautver?nderungen auftraten. Wenngleich diskutiert werden kann, ob es sich bei der ph?notypischen SS-LE-überlappung um ein eigenst?ndiges Krankheitsbild oder um einen LE mit sekund?rem SS bzw. ein prim?res SS mit Hautmanifestationen handelt, scheint das SS-LE-überlappungssyndrom hinreichend gut charakterisiert, um es als eine Krankheitsentit?t mit eigenen Implikationen für die Therapie und Prognose anzuerkennen. Die Stellung des SS/LE-überlappungssyndroms im Spektrum der anti-SSA(Ro)-, HLA-DR3-positiven Erkrankungen, und die enge immunologische Verwandtschaft zum SS und zum anti-SSA(Ro)-positiven LE werden diskutiert. Eingegangen am 5. April 1994 Angenommen am 24. August 1994     

Increased extracellular matrix density decreases MCF10A breast cell acinus formation in 3D culture conditions

The extracellular matrix (ECM) contributes to the generation and dynamic of normal breast tissue, in particular to the generation of polarized acinar and ductal structures. In vitro 3D culture conditions, including variations in the composition of the ECM, have been shown to directly influence the formation and organization of acinus‐like and duct‐like structures. Furthermore, the density of the ECM appears to also play a role in the normal mammary tissue and tumour formation. Here we show that the density of the ECM directly influences the number, organization and function of breast acini. Briefly, non‐malignant human breast MCF10A cells were incubated in increasing densities of a Matrigel®–collagen I matrix. Elastic moduli near and distant to the acinus structures were measured by atomic force microscopy, and the number of acinus structures was determined. Immunochemistry was used to investigate the expression levels of E‐cadherin, laminin, matrix metalloproteinase‐14 and ß‐casein in MCF10A cells. The modulus of the ECM was significantly increased near the acinus structures and the number of acinus structures decreased with the increase in Matrigel–collagen I density. As evaluated by the expression of laminin, the organization of the acinus structures present was altered as the density of the ECM increased. Increases in both E‐cadherin and MMP14 expression by MCF10A cells as ECM density increased were also observed. In contrast, MCF10A cells expressed lower ß‐casein levels as the ECM density increased. Taken together, these observations highlight the key role of ECM density in modulating the number, organization and function of breast acini. Copyright © 2013 John Wiley & Sons, Ltd.     

Cardiorespiratory fitness and body mass index values in 9-year-old rural Norwegian children

Aim: To describe cardiorespiratory fitness and body mass index (BMI) values in a representative population of 9-year-old Norwegian children in two rural communities and compare present values with previous findings.
Methods: Two hundred and fifty-nine 9-year-old children were invited, and 256 participated in this study. Maximal oxygen uptake was directly measured during a continuous progressive treadmill protocol. Body mass and height were also measured.
Results: The mean ± SD relative maximal oxygen uptake was 52.8 ± 6.5 for boys and 46.9 ± 7.2 mL/kg/min for girls. Eight percent of the boys and 16.8% of the girls were classified as overweight, and 1.6% of the boys and 6.9% of the girls as obese. Mean age, body mass, height and Ponderal index were not significantly different between sexes. Girls had a higher BMI than boys (p = 0.05).
Conclusion: Compared to earlier Norwegian studies, children's BMI values seem to have increased substantially. This increase is most pronounced in girls. When assessing these differences using the PI, this increase is less marked. Comparing maximal oxygen uptake data with that in earlier Nordic studies, there is no evidence that fitness has declined among 9-year olds. However, the limitations of the few earlier studies make reliable comparisons difficult.