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Summary
Objective: Our objective was to test the hypothesis, that pregnancy-related diseases are going along with changes in cytokine mRNA-expression at the placental site, either as a part of a pathological process or in connection with regulatory mechanisms induced by disturbances at the feto-maternal interface resulting from previous pathological changes – in the sense of counterregulation. Material and methods: The cytokines chosen for this investigation are known to 1.) be expressed in the human placental tissue, 2.) to be involved in immunological processes and 3.) the regulation of growth and differentiation processes of different cell types of the placenta or decidua, 4.) to play a role in the angiogenesis at the feto-placental interface and 5.) to be involved in pathological processes in other human diseases. 32 samples derived from term human placentas were examined for messenger RNA levels of interleukin 1 alpha (Il-1α), tumor necrosis factor-alpha (TNF-α), platelet derived growth factor-A chain (PDGF-A), platelet derived growth factor-B chain (PDGF-B), and platelet derived growth factor receptor (PDGF-R) using a semiquantitative reverse transcriptase (RT) polymerase chain reaction (PCR) protocol. To calibrate samples in our procedure, β-actin mRNA (messanger ribonucleid acid) known as a "house keeping" gene was proven to be constantly expressed. The sample-groups consisted of normal pregnancies (n = 8), gestational hypertension (GH, n = 7), intrauterine growth retardation (IUGR, n = 6), gestational diabetes mellitus (GDM, n = 5), and gemini (n = 3 × 2). Results: Throughout the 32 samples, a significant correlation between PDGF-A and PDGF-R expression, PDGF-A and TNF-alpha expression was stated (p = 0.007). Compared with the pattern of expression in normal placentas, placentas of growth retarded pregnancies had higher Il-1α mRNA (p = 0.016), PDGF-A (p = 0.029) and PDGF-B (p = 0.001) levels. The samples of the gestational hypertension group and placentas of patients with gestational diabetes displayed a significantly stronger PDGF-R mRNA signal (p = 0.0029 and p = 0.008). Conclusions: Though these marked differences in cytokine mRNA levels between clinical groups were statistically proven, clear correlation of these differences with clinical data was not found.

Muller, H.: Proliferation of conventional armament and weapons of mass destruction: the security risks. - S.5-12. ... Gere, F.: La contre-proliferation: les options politiques de l'Europe occidentale. - S.19-24. Wikinson, P.: The changing international terrorist threat. - S.25-37. Baron Crespo, E.: Le terrorisme comme instrument des "rogue states" et "non state actors": la response politique de l'Europe occidentale. - S.39-42. Rocard, M.: Terrorisme et proliferation: Mythe ou realite? - S.43-55

Purpose of the studyDetermination of HIV‐1 coreceptor tropism is a major prerequisite before starting treatment with a CCR5‐antagonist. While most of the patients currently under treatment with maraviroc are probably infected with HIV‐1 subtype B viruses, recently published data show differences in the distribution of coreceptor tropism in different HIV‐1 subtypes.MethodsIn a Germany‐wide project within the HIV‐GRADE society, V3‐loop sequences of 2466 isolates were analysed with geno2pheno for coreceptor tropism using a FPR cut‐off of 10%. HIV‐1 subtype was determined by using the COMET HIV subtyping tool. Sequences consisted of at least the V3 loop fragment. The ratio of CCR5 vs CXCR4 tropic viruses was calculated for each subtype. A normalized mean for all analyzed subtypes was calculated to extrapolate the overall ratio of coreceptor usage distribution. From this the expected distribution in the particular subtype was calculated and compared to the observed one. Statistical analysis was performed using the chi2 test.Summary of ResultsMost samples were classified as HIV‐1 subtype B (79%, n=1952). Other subtypes present in at least 23 samples were A1 (9.5%, n=234), C (4.8%, n=118), CRF01_AE (2.2%, n=55), G (1.6%, n=39), D (1.1%, n=27), F (0.9%, n=23). The calculated normalized mean distribution over all subtypes was 71% CCR5‐ vs. 29% CXCR4‐tropic viruses. No significant difference compared to the mean distribution could be observed for HIV‐1 subtypes B (71/29%), C (76/24%) and F (70/30%). Higher rates of CXCR4 tropic virus were detected in subtypes D (52/48%, p=0.01) and CRF01_AE (49/51%, p=0.001), while in HIV‐1 subtypes A1 (22/78%, p=0.02) and G (13/87%, p=0.02), a higher rate of CCR5‐tropic virus was observed.ConclusionsOur analysis shows a different distribution of CCR5 and CXCR4 tropic virus in some subtypes. In contrast to other publications, we could not observe a statistically significant difference in subtype C compared to the overall mean distribution, while we could confirm a higher rate of CXCR4‐tropic virus in subtype D, as previously described. Without further data on treatment success of patients with non‐B subtypes under treatment with maraviroc, it remains unclear if subtype‐specific differences in the distribution of tropism are biased by differences in clinical variables before test or if there is a bias in the tropism interpretation system. In the latter case, individual interpretation cut‐offs for different subtypes may be necessary.