Connective tissue activation

Connective tissue activating peptide-III (CTAP-III) isolated from human platelets is a potent mitogen for human connective tissue cells in culture in addition to stimulating glycosaminoglycan synthesis, glucose consumption, and lactate formation. The amino acid composition of apparently homogeneous CTAP-III was determined, confirming the presence of two disulfide links and providing a calculated molecular weight of 11,633 daltons. Comparison of the mitogenic activity of serum and plasma-serum suggests that CTAP-III is a major mitogenic component of human serum. Seventeen strains of human connective tissue cells (synovial, cartilage, dermal and thyroid) incorporated [ 3 H]-thymidine at up to 30 times control at levels under the influence of microgram quantities of CTAP-III and caused detectable increases in thymidine incorporation at levels as low as 10–29 ng/ml. Prostaglandin E 1 (0.01 Μg/ml) and dibutyryl cyclic AMP (25 Μg/ml) potentiated the glycosaminoglycan stimulating effect of CTAP-III, but not its mitogenic effect. Cycloheximide and actinomycin D blocked the biologic actions of CTAP-III. Cortisol and penicillamine had little effect on the mitogenic activity of CTAP-III, whereas antirheumatic agents such as acetylsalicylic acid and phenylbutazone opposed the mitogenic activity when added to cultures at clinically relevant concentrations. A weak antiheparin factor secreted by platelets, low affinity platelet factor 4 (LA-PF 4 ), was shown to be similar to CTAP-III in biologic actions, electrophoretic mobility, amino acid composition, and antigenic determinants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37739/1/1780220308_ftp.pd

Expansive components in H II regions

We study the presence of low intensity high velocity components, which we have termed wing features in the integrated Halpha emission line profiles of the HII region populations of the spiral barred galaxies NGC 1530, NGC 3359 and NGC 6951. We find that more than a third of the HII region line profiles in each galaxy show these components. The highest fraction is obtained in the galaxy whose line profiles show the best S:N, which suggests that wing features of this type may well exist in most, if not all, HII region line profiles. Applying selection criteria to the wing features, we obtain a sample of HII regions with clearly defined high velocity components in their profiles. Deconvolution of a representative sample of the line profiles eliminates any doubt that the wing features could possibly be due to instrumental effects. We present an analysis of the high velocity low intensity features fitting them with Gaussian functions; the emission measures, central velocities and velocity dispersions for the red and blue features take similar values. We interpret the features as signatures of expanding shells inside the HII regions. Up to a shell radius of R(shell)~0.2R(reg), the stellar winds from the central ionizing stars appear to satisfy the energy and momentum requirements for the formation and driving the shell. Several examples of the most luminous HII regions show that the shells appear to have larger radii; in these cases additional mechanisms may well be needed to explain the kinetic energies and momenta of the shells.Comment: 16 pages, 9 figures, accepted for publication in A&

Linear optical logical Bell state measurements with optimal loss-tolerance threshold

Quantum threshold theorems impose hard limits on the hardware capabilities to process quantum information. We derive tight and fundamental upper bounds to loss-tolerance thresholds in different linear-optical quantum information processing settings through an adversarial framework, taking into account the intrinsically probabilistic nature of linear optical Bell measurements. For logical Bell state measurements - ubiquitous operations in photonic quantum information - we demonstrate analytically that linear optics can achieve the fundamental loss threshold imposed by the no-cloning theorem even though, following the work of Lee et al., (Phys. Rev. A 100, 052303 (2019)), the constraint was widely assumed to be stricter. We spotlight the assumptions of the latter publication and find their bound holds for a logical Bell measurement built from adaptive physical linear-optical Bell measurements. We also give an explicit even stricter bound for non-adaptive Bell measurements.Comment: 17pages, 14 figure

Connective tissue activation. xxxv. detection of connective tissue activating peptide–iii isoforms in synovium from osteoarthritis and rheumatoid arthritis patients: patterns of interaction with other synovial cytokines in cell culture

Objective. To determine whether extracts of unincubated osteoarthritis (OA) and rheumatoid arthritis (RA) synovial tissue contain connective tissue activating peptide–III (CTAP-III) isoforms and prostaglandin E 2 (PGE 2 ), and whether such extracts have growth-promoting activity, and to determine whether binary combinations of CTAP-III with other cytokines reported to be present in synovial tissue lead to synergistic, additive, or inhibitory effects on growth. Methods. Acid–ethanol extracts of human synovium were examined for growth-promoting activity by measuring formation of 14 C-glycosaminoglycan ( 14 CGAG) and 3 H-DNA in synovial cell cultures; PGE 2 was measured by enzyme immunoassay, and CTAP-III isoforms were identified by Western blotting of extracted proteins separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Growth-promoting activity of CTAP-III and other cytokines was tested in synovial cultures treated with the agonists singly and in binary combination, by measuring changes in synthesis of 14 C-GAG and 3 H-DNA. Results. Platelet-derived CTAP-III and a cleavage isoform with the electrophoretic mobility of CTAP-III–des 1–15/neutrophil-activating peptide–2 (NAP-2) and PGE 2 were found in biologically active extracts of synovial samples from patients with RA and OA. Five growth factors (recombinant epidermal growth factor [rEGF], recombinant interleukin-1Β [rIL-1Β], basic fibroblast growth factor [bFGF], PGE 1 , and PGE 2 ) in binary combination with CTAP-III showed synergism in stimulating GAG synthesis; two (recombinant platelet-derived growth factor type BB [rPDGF-BB] and recombinant transforming growth factor Β [rTGFΒ]) had an additive effect. In combination with CTAP-III, rEGF and rPDGF-BB had a synergistic effect in promoting DNA synthesis, rTGFΒ and rbFGF had an additive effect, and rIL-1Β, PGE 1 , and PGE 2 were antagonistic. Conclusions. The results suggest that, in addition to endogenous factors, CTAP-III and other plateletderived cytokines may play roles in regulating synovial cell metabolism in RA and OA, and that combinations of growth factors may be more significant than single agents in amplification or suppression of important cell functions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37793/1/1780350712_ftp.pd

Connective tissue activation. xxxvi. the origin, variety, distribution, and biologic fate of connective tissue activating peptide–iii isoforms: characteristics in patients with rheumatic, renal, and arterial disease

Objective. To determine the origin, distribution, and biologic fate of platelet-derived connective tissue activating peptide–III (CTAP-III), to define the relative amounts of the antigen forms (CTAP-III, betathromboglobulin [Β-TG], neutrophil activating peptide–2 [NAP-2]) in plasma of normal persons and those with rheumatic or end-stage renal disease, and to define the isoforms of CTAP-III in platelets, plasma, transudates, and tissue deposits. Methods. CTAP-III in plasma was measured by enzyme-linked immunosorbent assay, and growth promoting activity of CTAP-III isoforms was tested in synovial and peritoneal cell cultures by measuring increased synthesis of 14 C-glycosaminoglycan ( 14 C-GAG) and 3 H-DNA. Isolated CTAP-III was characterized by Western blotting, microsequencing, and mass spectrometry. Results. CTAP-III was the primary isoform of this antigen family in normal platelets and platelet-rich plasma; Β-TG and NAP-2 accounted for 90%), and Β-TG was the most rare (0–1%). Deposition of CTAP-III in tissues, such as synovium, spleen, and kidney, is associated with partial processing to NAP-2–like isoforms and the potential to induce neutrophil and fibroblast activation in patients with rheumatic or end-stage renal disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37798/1/1780360816_ftp.pd

Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011.

Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. Since this occurs not only in the high risk but also in the standard/intermediate groups, the presently used risk stratification is suboptimal. The underlying mechanisms for treatment failure include presence of genetic changes causing insensitivity to the therapy administered. To identify relapse-associated aberrations we performed single nucleotide polymorphism array analyses of 307 uniformly treated, consecutive pediatric ALL cases accrued 1992-2011. Recurrent aberrations of 14 genes in patients who subsequently relapsed or had induction failure were detected. Of these, deletions/uniparental isodisomies of ADD3, ATP10A, EBF1, IKZF1, PAN3, RAG1, SPRED1, and TBL1XR1 were significantly more common in B-cell precursor ALL patients who relapsed compared with those remaining in complete remission. In univariate analyses, age (10 years), WBC counts (>100 × 109/l), t(9;22)(q34;q11), MLL rearrangements, near-haploidy, and deletions of ATP10A, IKZF1, SPRED1, and the pseudoautosomal 1 regions on Xp/Yp were significantly associated with decreased 10-year event-free survival, with IKZF1 abnormalities being an independent risk factor in multivariate analysis irrespective of risk group. High age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival. Thus, analyses of these genes provide clinically important information.Leukemia accepted article preview online, 4 July 2013; doi:10.1038/leu.2013.206

Review of united states data on neoplasms in rheumatoid arthritis

Relatively sparse literature developed during the past 30 years that sought to characterize the relationship of rheumatoid arthritis to neoplasms. The past decade has seen added concern over possible oncogenic effects of cytotoxic agents now used to manage some patients with rheumatoid arthritis. Acquisition of unambiguous data is complicated by the fact that the cumulative incidence of cancer in the general population exceeds 30 percent, and that most studies have insufficient patient numbers, duration follow-up, and attention to age, sex, race, or known etiologic agents. Thus, it is not surprising to find reports that cancer incidence is high, low, or unchanged in rheumatoid arthritis. Although equally ambiguous data were accumulated concerning potential neoplasm-inducing effects of cytotoxic drugs, concern is justified in relation to increased frequency of bladder cancer after cyclophosphamide and acute leukemia following alkylating agents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25802/1/0000365.pd

Testing Hydrodynamic Models of LMC X-4 with UV and X-ray Spectra

We compare the predictions of hydrodynamic models of the LMC X-4 X-ray binary system with observations of UV P Cygni lines with the GHRS and STIS spectrographs on the Hubble Space Telescope. The hydrodynamic model determines density and velocity fields of the stellar wind, wind-compressed disk, accretion stream, Keplerian accretion disk, and accretion disk wind. We use a Monte Carlo code to determine the UV P Cygni line profiles by simulating the radiative transfer of UV photons that originate on the star and are scattered in the wind. The qualitative orbital variation predicted is similar to that observed, although the model fails to reproduce the strong orbital asymmetry (the observed absorption is strongest for phi>0.5). The model predicts a mid-eclipse X-ray spectrum, due almost entirely to Compton scattering, with a factor 4 less flux than observed with ASCA. We discuss how the model may need to be altered to explain the spectral variability of the system.Comment: 11 figures, accepted by Ap

Detection of the 13CO(J=6-5) Transition in the Starburst Galaxy NGC 253

We report the detection of 13CO(J=6-5) emission from the nucleus of the starburst galaxy NGC 253 with the redshift (z) and Early Universe Spectrometer (ZEUS), a new submillimeter grating spectrometer. This is the first extragalactic detection of the 13CO(J=6-5) transition, which traces warm, dense molecular gas. We employ a multi-line LVG analysis and find ~ 35% - 60% of the molecular ISM is both warm (T ~ 110 K) and dense (n(H2) ~ 10^4 cm^-3). We analyze the potential heat sources, and conclude that UV and X-ray photons are unlikely to be energetically important. Instead, the molecular gas is most likely heated by an elevated density of cosmic rays or by the decay of supersonic turbulence through shocks. If the cosmic rays and turbulence are created by stellar feedback within the starburst, then our analysis suggests the starburst may be self-limiting.Comment: 4 pages, 2 figures, accepted by ApJ Letter

HI holes in galactic disks: Tracing the dark matter distribution

Multiple SN explosions in disk galaxies efficiently evacuate gas and form cavities with the sizes and shapes of the surrounding envelopes determined by the total amount of injected energy and by the initial gas distribution. Such cavities are seen as HI holes when observed in face-on galaxies. Gas hydrodynamics simulations are performed to obtain the quantitative characteristics of HI holes that could serve for the determination of the gas vertical scale height and the corresponding dark matter content and its distribution. Among these characteristics is the ratio of the maximum column density in the HI ring surrounding the hole to the background HI column density and the vertical expansion velocity of gas in the HI ring. We show that in some cases the extragalactic background ionizing radiation may produce HI holes in the outer regions of galaxies, and can account for the existence of HI holes in nearby face-on galaxies with the apparent lack of an underlying stellar population.Comment: 8 pages, 6 figures, accepted for publication in Astronomy & Astrophysic