| 121. |
- Han, Shizhong, et al.
(författare)
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Evaluation of imputation-based association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE)
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:6, s. 1171-1180
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Tidskriftsartikel (refereegranskat)abstract
- We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an association between SLE susceptibility and ITGAM or ITGAM-ITGAX region. The primary objectives of this study are to assess whether single or multiple causal variants from the same gene or any nearby gene(s) are involved in SLE susceptibility and to confirm a robust ITGAM association across nine independent data sets (n = 8211). First, we confirmed our previously reported association of rs1143679 (risk allele 'A') with SLE in EAs (P = 1.0 x 10(-8)) and Hispanic-Americans (P = 2.9 x 10(-5)). Secondly, using a comprehensive imputation-based association test, we found that ITGAM is one of the major non-human leukocyte antigen susceptibility genes for SLE, and the strongest association for EA is the same coding variant rs1143679 (log(10)Bayes factor=20, P = 6.17 x 10(-24)). Thirdly, we determined the robustness of rs1143679 association with SLE across three additional case-control samples, including UK (P = 6.2 x 10(-8)), Colombian (P = 3.6 x 10(-7)), Mexican (P = 0.002), as well as two independent sets of trios from UK (P(TDT) = 1.4 x 10(-5)) and Mexico (P(TDT) = 0.015). A meta-analysis combing all independent data sets greatly reinforces the association (P(meta) = 7.1 x 10(-50), odds ratio = 1.83, 95% confidence interval = 1.69-1.98, n = 10 046). However, this ITGAM association was not observed in the Korean or Japanese samples, in which rs1143679 is monomorphic for the non-risk allele (G). Taken together along with our earlier findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM-SLE association, especially in European- and African-derived populations, but not in Asian populations.
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| 122. |
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| 123. |
- Harris, Valerie M., et al.
(författare)
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Klinefelters syndrome (47,XXY) is in excess among men with Sjogrens syndrome
- 2016
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Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 168, s. 25-29
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Tidskriftsartikel (refereegranskat)abstract
- Primary Sjogrens syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelters syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47)0(Y, p = 0.0012 by Fishers exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fishers exact test p = NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA. Published by Elsevier Inc.
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| 124. |
- Hering, Bernhard J., et al.
(författare)
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Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia
- 2016
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:7, s. 1230-1240
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA(1c) <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant. RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA(1c) level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
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| 125. |
- Joseph, Abigail, et al.
(författare)
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ABO Genotyping finds more A2 to B kidney transplant opportunities than lectin-based subtyping
- 2023
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 23:4, s. 512-519
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Tidskriftsartikel (refereegranskat)abstract
- ABO compatibility is important for kidney transplantation, with longer waitlist times for blood group B kidney transplant candidates. However, kidneys from non-A1 (eg, A2) subtype donors, which express less A antigen, can be safely transplanted into group B recipients. ABO subtyping is routinely performed using anti-A1 lectin, but DNA-based genotyping is also possible. Here, we compare lectin and genotyping testing. Lectin and genotype subtyping was performed on 554 group A deceased donor samples at 2 transplant laboratories. The findings were supported by 2 additional data sets of 210 group A living kidney donors and 124 samples with unclear lectin testing sent to a reference laboratory. In deceased donors, genotyping found 65% more A2 donors than lectin testing, most with weak lectin reactivity, a finding supported in living donors and samples sent for reference testing. DNA sequencing and flow cytometry showed that the discordances were because of several factors, including transfusion, small variability in A antigen levels, and rare ABO∗A2.06 and ABO∗A2.16 sequences. Although lectin testing is the current standard for transplantation subtyping, genotyping is accurate and could increase A2 kidney transplant opportunities for group B candidates, a difference that should reduce group B wait times and improve transplant equity.
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| 126. |
- Kaufman, DS, et al.
(författare)
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Technical note: Open-paleo-data implementation pilot-The PAGES 2k special issue
- 2018
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Ingår i: Climate of the Past. - 1814-9324 .- 1814-9332. ; 14, s. 593-600
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Tidskriftsartikel (refereegranskat)abstract
- Data stewardship is an essential element of the publication process. Knowing how to enact data polices that are described only in general terms can be difficult, however. Examples are needed to model the implementation of open-data polices in actual studies. Here we explain the procedure used to attain a high and consistent level of data stewardship across a special issue of the journal Climate of the Past. We discuss the challenges related to (1) determining which data are essential for public archival, (2) using data generated by others, and (3) understanding data citations. We anticipate that open-data sharing in paleo sciences will accelerate as the advantages become more evident and as practices that reduce data loss become the accepted convention.
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| 127. |
- Kaufman, M., et al.
(författare)
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CO observations of the interacting galaxy pair NGC 5394/95
- 2002
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 123:2 1754, s. 702-719
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Tidskriftsartikel (refereegranskat)abstract
- BIMA 12CO J = 1 → 0 observations are presented of the spiral galaxies NGC 5394 and NGC 5395 that have undergone a recent, grazing encounter. In NGC 5394 approximately 80% of the CO emission detected by BIMA is concentrated in the central 800 pc (FWHM) starburst region, and the rest is from a portion of the inner disk south and west of the central starburst. In an encounter simulation that reproduces some of the main features of this galaxy pair, a considerable amount of gas in NGC 5394 falls into the central region early in the collision. The observed total gas distribution in the disk of NGC 5394 is lopsided, with more H I, CO, and Hα emission coming from the western or southwestern side. The innermost western arm of NGC 5394 is seen in CO and Hα emission, but the eastern inner-disk arm, which is very bright in the optical continuum, is not detected in CO or Hα emission. The NGC 5394 starburst region is similar in radio continuum luminosity and size to the M82 starburst and has a CO luminosity ∼4 times greater. A CO position-velocity diagram of the NGC 5394 nucleus reveals two separate velocity features very close to the center. This may indicate a nuclear ring or the "twin peaks" of an ILR or some depletion of 12CO J = 1 → 0 at the nucleus. From a comparison of the radio continuum, Hα, 60 μm, and CO luminosities, we estimate that the average extinction A v of the starburst nucleus is 3-4 mag, the star formation rate is ∼6 M⊙ yr-1, and the conversion factor N(H 2)/ICO in the starburst is a factor of 3-4 below the standard value. Comparison of NGC 5394 with two other systems previously studied suggests that in prograde grazing encounters a central starburst may not develop until near the end of the ocular phase. Very little of the CO emission from NGC 5395 found in previous single-dish observations is detected in the BIMA data; thus molecular gas in NGC 5395 does not appear to be strongly concentrated in compressed ridges.
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| 128. |
- Kaufman, M., et al.
(författare)
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Observations of the Ocular Galaxy NGC 2535 and its Starburst Companion NGC 2536
- 1997
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 114, s. 2323-2349
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Tidskriftsartikel (refereegranskat)abstract
- H I, radio continuum, and 12CO J=1-->0 observations at resolutions of 12" to 33" (=2.9-8 kpc), and B, I, J, and K-band images, are presented of the galaxy NGC 2535 and its small starburst companion NGC 2536. NGC 2535 has an ocular (eye-shaped) structure with two long tidal arms indicative of a recent, close, nonmerging encounter. Our observations reveal widespread high velocity dispersions (30 km s-1) in the H I gas and five clouds with masses of ˜10^8 Msun in the tidal arms of NGC 2535. These clouds do not correspond to the most luminous blue knots or to major clumps in the old stellar population. Similar phenomena were found previously in other pairs (IC 2163/NGC 2207 and NGC 5774/5), suggesting that enhanced turbulence and massive gas clouds may be a general feature of interacting spiral galaxies during an early phase of post-encounter evolution. A search for 12CO J= 1-->O emission at 11 positions in NGC 2535 and one position in NGC 2536 yielded two clear detections, one at the center of NGC 2535 and the other on its tidal tail but close to the center of NGC 2535. Most of the massive H I clouds in NGC 2535 are not detected in CO emission. The virial masses of these clouds are significantly greater than their measured masses in gas, presumably because of the presence of old disk stars in the clouds. A form of the virial theorem that includes gas and stars is presented. NGC 2535 shows several unusual features, including an intrinsically oval shape to the disk, that are similar to those in the ocular galaxy IC 2163 studied previously. NGC 2535 also contains structures that are not seen in IC 2163. For example, there is an extended (R =48 kpc) H I envelope and a long, outer, elliptically-shaped H I arc in NGC 2535 that may be a gravitational wake produced by the passage of the companion within or close to the envelope. In the radio continuum, NGC 2535 exhibits a bar-like feature that leads the small stellar bar by 50°. The starburst companion, NGC 2536, lies in a 2 X 10^9 Msun clump of H I gas at the outer end of the tidal bridge from NGC 2535. Most of the gas in this clump is associated with the bridge. The H I emission on the anticompanion side of NGC 2536 has the same line-of-sight velocity and projected position as some of the bridge gas there. This observation is consistent with a previous model by Klaric in which NGC 2536 accretes gas from NGC 2535; we even find an H I feature that may represent bridge gas streaming towards NGC 2536. The failure to detect 12CO emission in NGC 2536 places an upper limit of 6 X H2 on its H2 mass if the standard value of the conversion factor between I_CO and N(H2) applies.
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| 129. |
- Kaufman, M., et al.
(författare)
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The Interacting Galaxies NGC 5394/5395: A Post-Ocular Galaxy and Its Ring/Spiral Companion
- 1999
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 118:4, s. 1577-1608
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Tidskriftsartikel (refereegranskat)abstract
- H I, radio continuum, Fabry-Perot Hα, and 12CO J = 1 → 0 observations and broadband optical and near infrared images are presented of the interacting spiral galaxies NGC 5395 and NGC 5394. Kinematically, there are three important, separate components to the H I gas associated with this galaxy pair: (1) the main disk of NGC 5395, (2) a long, northern tidal arm of NGC 5395 distinct in velocity from its main disk, and (3) the disk of NGC 5394. The H I northern tidal arm of NGC 5395 has a line of–sight velocity as much as 75–100 km s-1 greater than the main disk of NGC 5395 at the same projected location and thus is not in the same plane as the disk. The velocity field of the disk of NGC 5395 is asymmetric and distorted by large-scale and small-scale noncircular motions. In NGC 5395, the encounter appears to be exciting m = 1 and m = 0 modes in what had been a two-armed spiral. The dominant spiral arm of NGC 5395 forms a large ring or pseudo-ring of Hα, radio continuum, and H I emission, somewhat off center with respect to the nucleus. The H I trough in the center of NGC 5395 is not filled in by molecular gas. The Hα velocity contours exhibit an organized pattern of kinks in crossing the ring and also show streaming motions in a large stellar caustic feature. The eastern side of the ring is brighter in radio continuum and Hα; the western side is brighter in H I and contains massive (108 M☉) H I clouds not associated with the most luminous H II regions. The smaller galaxy NGC 5394 is in an immediate post-ocular phase, with a central starburst, an intrinsically oval disk, two long, fairly symmetric, open tidal arms with high arm-interarm contrast, and very bright inner spiral arms, disjoint from the outer tidal arms. Most of the gas in NGC 5394 is in molecular form and concentrated within 3.8 kpc of the center, so is suitable for fueling the starburst. Despite the presence of H I gas, two of the three optically bright inner spiral arms of NGC 5394 show no evidence of ongoing star formation.A galaxy encounter simulation reproduces some of the main features of this system with a collision that is prograde relative to NGC 5394 and retrograde at a high tilt angle relative to NGC 5395. The model finds that the inner spiral structure of NGC 5394 developed from an eye-shaped ("ocular") structure at slightly earlier times. NGC 5394 and the two ocular galaxies IC 2163 and NGC 2535, studied earlier, form an evolutionary sequence of structures resulting from prograde encounters and thus confirm the generic models of such collisions. The agreement between the model for NGC 5394/95 and the ring/spiral structures seen in NGC 5395 extends our understanding of collisional ring galaxies.
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| 130. |
- Kim, Jong Hyuk, et al.
(författare)
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Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion
- 2024
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Ingår i: Cancer Research Communications. - : American Association For Cancer Research (AACR). - 2767-9764. ; 4:6, s. 1467-1480
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Tidskriftsartikel (refereegranskat)abstract
- Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors.Significance: We demonstrate that hemangiosarcomas regulate molecular programs supporting hematopoietic expansion and differentiation, providing insights into their potential roles in creating a permissive stromal-immune environment for tumor progression.
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