N7 and C8 coordinated purine complexes of [(NH3)5Os]. Crystal structures of 7-[9MeHyp(NH3)5Os]Cl3·H2O and 8-[1,3,7Me3Xan(NH3)5Os]Cl3·2H2O

Pentaammineosmium(III) coordinates to both the N7 and C8 positions of purine rings. The compound 7-[9MeHyp(NH₃)₅Os]Cl₃·H₂O crystallizes in the orthorhombic space group Pnma (No. 62) with the unit cell parameters: a=11.542(2), b=6.9841(8), c=21.960(3) Å and Z=4. The compound 8-[1,3,7Me₃Xan(NH₃)₅Os]Cl₃·2H₂O crystallizes in the monoclinic space group P2₁/c (No. 14) with the unit cell parameters: a=7.1228(X), b=14.613(1), c=19.667(1) Å, β=91.782(9)° and Z=4. The Os---C bond in the latter structure is 2.039(9) Å and the imidazolylidine ligand exerts a slight trans influence seen in the lengthening of the Os---N_ax distance (2.172(8) Å) by about 0.05 Å relative to the average of the equatorial Os---N_eq value of 2.123(8) Å. The spectroscopic, electrochemical and structural properties of these and additional N-bound purine complexes are compared with those of similar N7 and C8 ruthenium(III) species.     

The effects of crude and purified human gonadotropin on in vitro stimulated human lymphocyte cultures.

Crude human chorionic gonadotropin (hCG) was found to be several fold more immunosuppressive than purified hCG in human peripheral blood lymphocyte cultures stimulated by phytohemagglutinin, pokeweed, purified protein derivative and allogeneic cells in vitro. Immunosuppression by crude hCG was consistently noted at levels less than 1000 IU/ml and usually 80% inhibition was achieved with doses of 5000–10,000 IU/ml, whereas 40–50% inhibition or less was observed by purified hCG at 10,000 IU/ml. In two crude hCG preparations subjected to Sephadex G-100 chromatography, the fractions that inhibited lymphocyte cultures appeared in the eluate after the major peak of hCG activity. These data indicate that inhibitory substance(s) other than hCG are responsible for most of the immunosuppressive properties of first trimester pregnancy urine. Both crude and purified hCG were stimulatory to human lymphocytes when used alone without mitogens when cultured in fetal calf serum.     

ADAMTS9, a novel member of the ADAM-TS/ metallospondin gene family

ADAM-TS/metallospondin genes encode a new family of proteins with structural homology to the ADAM metalloprotease-disintegrin family. However, unlike other ADAMs, these proteins contain thrombospondin type 1 (TSP1) repeats at the carboxy-terminal end and are secreted proteins instead of being membrane bound. Members of the ADAM-TS family have been implicated in the cleavage of proteoglycans, the control of organ shape during development, and the inhibition of angiogenesis. We have cloned a new member of the ADAM-TS/metallospondin family designated here as ADAMTS9. This protein has a metalloprotease domain, a disintegrin-like domain, one internal TSP1 motif, and three carboxy-terminal TSP1-like submotifs. In contrast to other ADAM-TS family members, ADAMTS9 is expressed in all fetal tissues examined as well as some adult tissues. Using FISH and radiation hybrid analysis, we have localized ADAMTS9 to chromosome 3p14.2-p14.3, an area known to be lost in hereditary renal tumors.     

SMAD3 Is Associated with the Total Burden of Radiographic Osteoarthritis: The Chingford Study

Background

A newly-described syndrome called Aneurysm-Osteoarthritis Syndrome (AOS) was recently reported. AOS presents with early onset osteoarthritis (OA) in multiple joints, together with aneurysms in major arteries, and is caused by rare mutations in SMAD3. Because of the similarity of AOS to idiopathic generalized OA (GOA), we hypothesized that SMAD3 is also associated with GOA and tested the hypothesis in a population-based cohort.

Methods

Study participants were derived from the Chingford study. Kellgren-Lawrence (KL) grades and the individual features of osteophytes and joint space narrowing (JSN) were scored from radiographs of hands, knees, hips, and lumbar spines. The total KL score, osteophyte score, and JSN score were calculated and used as indicators of the total burden of radiographic OA. Forty-one common SNPs within SMAD3 were genotyped using the Illumina HumanHap610Q array. Linear regression modelling was used to test the association between the total KL score, osteophyte score, and JSN score and each of the 41 SNPs, with adjustment for patient age and BMI. Permutation testing was used to control the false positive rate.

Results

A total of 609 individuals were included in the analysis. All were Caucasian females with a mean age of 60.9±5.8. We found that rs3825977, with a minor allele (T) frequency of 20%, in the last intron of SMAD3, was significantly associated with total KL score (β = 0.14, P_permutation = 0.002). This association was stronger for the total JSN score (β = 0.19, P_permutation = 0.002) than for total osteophyte score (β = 0.11, P_permutation = 0.02). The T allele is associated with a 1.47-fold increased odds for people with 5 or more joints to be affected by radiographic OA (P_permutation = 0.046).

Conclusion

We found that SMAD3 is significantly associated with the total burden of radiographic OA. Further studies are required to reveal the mechanism of the association.     

Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations

Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR) =?1.07 (95%CI 0.94 -1.21; p?=?0.28). For rs7775228 the meta-analysis resulted in OR?=?0.94 (95%CI 0.81-1.09; p?=?0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r(2)?=?0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r(2)<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.     

Patient Adipose Stem Cell-Derived Adipocytes Reveal Genetic Variation that Predicts Antidiabetic Drug Response

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