We study spectra generated by Comptonization of soft photons by cold electrons radially free falling on to a black hole. We use a Monte Carlo method involving a fully relativistic description of ...Comptonization in the Kerr space-time. In agreement with previous studies, we find that Comptonization on the bulk motion of free fall gives rise to power-law spectra with the photon index of γ ≳ 3. In contrast to some previous studies, we find that these power-law spectra extend only to energies ≪mec2. We indicate several effects resulting in generic cut-offs of such spectra at several tens of keV, regardless of any specific values of physical parameters in the model. This inefficiency of producing photons with energies ≳100 keV rules out bulk motion Comptonization as a main radiative process in soft spectral states of black hole binaries. The normalization of the power law (below the cut-off) with respect to the peak of the blackbody emission of the surrounding disc is typically very low, except for models with an overlap between the disc and the plasma, in which case the spectra are very soft, γ ≳ 4.
Abstract
Contracting is an important part of running the business of private practice interventional radiology. A basic knowledge of contracting is vital for the practicing interventionalist to best ...position him or herself to excel in private practice. Exclusive contracts are common in interventional, diagnostic, and radiology practices. Such contracts, however, may significantly limit the practice of individual interventional radiologists and impede the growth of interventional procedures in communities at large. This article outlines the role of exclusive contracts in interventional practices, and describes the limitations of such contracts.
Strong clinical and experimental evidence shows that elevated levels of urokinase plasminogen activators (u-PA) and matrix metalloproteinases (MMPs) are associated with prostate cancer progression, ...metastasis and shortened survival in patients. MMP activities are regulated by specific tissue inhibitors of metalloproteinases (TIMPs). A nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract showed anticancer activity against a number of cancer cell lines. Our main objective was to study the effect of NM on the activity of u-PA, MMPs and their inhibitor TIMPs on human prostate cancer cell lines PC-3 and DU-145. Human prostate cancer cell lines PC-3 and DU-145 (ATCC) were grown in MEM media with 10% FBS and antibiotics in 24‑well tissue culture plates. At near confluence, the cells were treated with NM at 0-1000 µg/ml in triplicate at each concentration. Analysis of u-PA activity was carried out by fibrin zymography, MMPs by gelatinase zymography and TIMPs by reverse zymography. Both PC-3 and DU-145 prostate cancer cell lines demonstrated u-PA activity (subunits 1 and 2, corresponding to 35 and 33 kDa). Prostate cancer cell line PC-3 secretion of u-PA subunit 1 was decreased by 65% at NM 500 µg/ml and subunit 2 by 100% at NM 50 µg/ml. Prostate cancer cell line DU-145 secretion of u-PA subunit 1 was decreased by 97% at NM 500 µg/ml and subunit 2 by 100% at NM 100 µg/ml. Untreated PC-3 showed two bands for MMP-2 and MMP-9. NM inhibited their expression in a dose-dependent manner. The activity of MMP-2 and MMP-9 was significantly inhibited at 250 µg/ml with total inhibition at 500 µg/ml. DU-145 cells did not exhibit MMP activity. Activity of TIMPs was up-regulated in both prostate cancer cell lines in a dose-dependent manner. Minimum activity was expressed at 50 µg/ml NM and maximum at 1000 µg/ml. Correlation analyses revealed a positive correlation between u-PA and MMPs and a negative correlation between u-PA/MMPs and TIMPs. These results suggest NM as a potential anticancer agent since it targets invasive parameters of prostate cancer.
Invasion of surrounding tissues by malignant cells is a complex process mediated by the matrix degrading enzymes. In many solid tumors, the expression of MMPs, especially MMP-2 and MMP-9, is higher ...in stromal cells than in the tumor cells, suggesting stromal cells as the major source of these enzymes. Cytokines and signal transduction pathways, including those activated by phorbol 12-myristate 13-acetate (PMA), regulate the expression of MMPs. The aim of this study was to examine the pattern of MMP-2 and MMP-9 expression in human normal cells and in PMA-treated cells to determine if specific patterns of expression were associated with tissues of different origin. Epithelial, connective, and muscle tissues were selected since carcinomas, sarcomas, and adenosarcomas are derived from these tissue types, respectively. The cell lines were cultured in their recommended media and supplemented with 10% FBS and antibiotics in 24-well tissue culture plates. At near confluence, the cells were washed and fresh medium added. A parallel set of cultures was treated with PMA. After 24 h of incubation, media were collected and analyzed for MMP-2 and MMP-9 by gelatinase zymography. The results indicate that the normal cell expression of MMP-2 and MMP-9 depends on their primary tissue subtype. All cell lines, regardless of tissue origin, expressed MMP-2. PMA induced MMP-9 expression in glandular epithelia, supportive connective tissue, and muscle tissue cell lines. However, cell lines of endothelial origin and proper connective tissue were insensitive to PMA. These results suggest that MMP-2 and MMP-9 are differentially regulated and an understanding of this may open up avenues to use these enzymes as targets for therapy.
Brain tumors are highly aggressive tumors characterized by secretions of high levels of matrix metalloproteinase-2 and -9, leading to tumor growth, invasion and metastasis by digesting the basement ...membrane and extracellular matrix components. We previously demonstrated the effectiveness of a nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract in vitro: on activity of urokinase plasminogen activator, matrix metalloproteinases and TIMPs in various human glioblastoma (LN-18, T-98G and A-172) cell lines and on glioblastoma A-172 cell proliferation and Matrigel invasion.
Our main objective in this study was to investigate the effect of the NM in vivo on human glioblastoma U-87 MG cell line.
Athymic male nude mice inoculated with 3·10(6) U-87 MG cells subcutaneously and were fed a regular diet or a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed, the tumors were weighed and measured. The samples were studied histologically.
NM inhibited tumor weight and tumor burden by 53% (p = 0.015) and 48% (p = 0.010), respectively.
These results suggest the therapeutic potential of NM as an adjuvant in the treatment of glioblastoma.
Head and neck squamous cell carcinoma (HNSCC) and acute myeloid leukemia are the major causes of mortality and morbidity in Fanconi anemia (FA) patients. The objective of this study was to ...investigate the antineoplastic activity of a novel antineoplastic nutrient mixture (NM) (containing lysine, proline, ascorbic acid and green tea extract) in human FA-associated HNSCC (FA HNSCC) in vitro and in vivo. The human FA HNSCC cell line, OHSU-974 (Fanconi Anemia Research Fund), was cultured in RPMI medium supplemented with 20% FBS and antibiotics. At near confluence, cells were treated in triplicate with various concentrations of NM: 0, 50, 100, 250, 500 and 1,000 µg/ml. Cells were also treated with phorbol 12-myristate 13-acetate (PMA) to induce matrix metalloproteinase (MMP)-9 activity. Cell proliferation was detected by MTT assay, the secretion of MMPs by gelatinase zymo-graphy, cell invasion through Matrigel, cell migration by a scratch test and morphology by hematoxylin and eosin (H&E) staining. In vivo, athymic male nude mice (n=12) were inoculated with 3x106 OHSU‑974 cells subcutaneously and randomly divided into 2 groups: group A was fed a regular diet and group B a regular diet supplemented with 1% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighed and processed for histological analysis. NM inhibited the growth of OHSU-974 tumors by 47% and tumor burden by 50%. At lower concentrations, NM demonstrated no effect on proliferation, but at 1,000 µg/ml a 40% toxicity was observed. Zymography revealed the MMP-2 and PMA-induced MMP-9 secretion. NM suppressed the secretion of both MMPs in a dose-dependent manner, with a virtual inhibition at 500 µg/ml. NM inhibited OHSU-974 cell invasion through Matrigel in a dose-dependent manner with a complete block at 1,000 µg/ml. H&E staining showed no morphological changes below 500 µg/ml. These results suggest that NM has potential therapeutic use in the treatment of human FA HNSCC.
We present a general relativistic accretion disc model and its application to the soft-state X-ray spectra of black hole binaries. The model assumes a flat, optically thick disc around a rotating ...Kerr black hole. The disc locally radiates away the dissipated energy as a blackbody. Special and general relativistic effects influencing photons emitted by the disc are taken into account. The emerging spectrum, as seen by a distant observer, is parametrized by the black hole mass and spin, the accretion rate, the disc inclination angle and the inner disc radius. We fit the ASCA soft-state X-ray spectra of LMC X-1 and GRO J1655-40 by this model. We find that, having additional limits on the black hole mass and inclination angle from optical/UV observations, we can constrain the black hole spin from X-ray data. In LMC X-1 the constraint is weak, and we can only rule out the maximally rotating black hole. In GRO J1655-40 we can limit the spin much better, and we find 0.68 ⩽ a ⩽ 0.88. Accretion discs in both sources are radiation-pressure dominated. We do not find Compton reflection features in the spectra of any of these objects.
Although fully treatable in the early stages, once cervical cancer has metastasized, patient outcome is poor. The main objective of this study was to examine the effect of dietary supplementation ...with a nutrient mixture (NM) containing lysine, ascorbic acid, proline, green tea extract and other micronutrients on HeLa cell xenografts in nude female mice. Tumor growth was measured and immunohistochemical staining was evaluated for the following cancer markers: Ki67 (proliferation); matrix metalloproteinase (MMP)-2 and -9 (invasion/metastasis); vascular endothelial growth factor (VEGF) (angiogenesis); terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and B-cell lymphoma 2 (Bcl-2) (apoptosis); cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (inflammation); and glutathione S-transferase π (GSTπ) (a general cancer marker). Following housing for a week, 5/6-week-old female athymic nude mice (n=12) were inoculated subcutaneously with 3×106 HeLa cells in 0.2 ml phosphate-buffered saline and 0.1 ml Matrigel™ and randomly divided into two groups; control group mice were fed regular mouse chow and NM group mice the regular diet supplemented with 0.5% NM (w/w). After four weeks, the mice were sacrificed and their tumors were excised and processed for histology. The NM strongly inhibited the growth of HeLa xenografts in nude mice. The mean tumor weight was reduced to 59% (P=0.001) in the mice fed the NM compared with the tumor weight in the controlled diet mice. Ki67, MMP-2 and -9, VEGF, TUNEL, Bcl-2, COX-2, iNOS and GSTπ all showed a lower intensity and frequency of staining in the NM group compared with that in the control group. In conclusion, NM supplementation strongly inhibited tumor growth and cancer markers in female nude mice injected with HeLa xenografts.
We investigated the effects of a nutrient mixture (NM) consisting of ascorbic acid, quercetin, naringenin, hesperetin, tea catechins, lysine, proline, arginine and N-acetylcysteine on experimental in ...vivo and in vitro inflammation triggered by bacterial lipopolysaccharide (LPS). BALB/c mice (n=36) were administered NM (200 mg/kg BW) or ibuprofen (20 mg/kg BW) for two weeks. Blood plasma, collected three hours after a single intraperitoneal injection with LPS (1 mg/kg BW), was analyzed with 14 cytokine microarray. LPS inflammatory effects were analyzed in human U937 macrophages by cytokine release, cyclooxygenase (COX) enzymatic activity, COX protein expression (Western blot analysis), specific mRNA levels (RT-PCR), and nuclear factor kappabeta (NFkappabeta) activation (phosphorylated p65 immunoassay). Nutrient supplementation in mice altered the LPS-induced cytokine response in a manner similar to ibuprofen (r=0.4157, p=0.139). Cytokine response to LPS in cultured macrophages was similar to the in vivo study (r=0.718, p=0.023). NM inhibited COX-2 enzymatic activity, and COX-2 and pro-inflammatory cytokine protein expression levels were downregulated by NM at the transcription level complementing a blockade in NFkappabeta activation. NM demonstrated strong beneficial effects on the experimental inflammation by targeting multiple responsible mechanisms in the complex process involved in the inflammatory reaction to pathogens.