Hypoxic induction of interleukin-8 gene expression in human endothelial cells.

This is the published version. Copyright 1994 American Society for Clinical Investigation.Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis

The impact of age on post-operative outcomes of colorectal cancer patients undergoing surgical treatment

BACKGROUND: the purpose of study was to evaluate the impact of age on outcomes in colorectal cancer surgery. METHODS: patients on hospital database treated for colorectal cancer during the period 1995 – 2002 were divided into two groups: Group 1 – patients of 75 years or older (n = 154), and Group 2 – those younger than 75 years (n = 532). RESULTS: In Group 1, for colon cancers, proximal tumors were significantly more common (23% vs. 13.5%, p < 0.05), complicated cases were more frequent (46 % vs. 33%, p = 0.002), bowel obstruction more common at presentation (40% vs. 26.5%, p = 0.001), and more frequent emergency surgery required (24% vs. 14%, p = 0.003). Postoperative overall morbidity was higher in the elderly group, but with no differences in surgical complications rate. Overall 5 year survival was 39% vs. 55% (p = 0.0006) and cancer related 5 year survival was 44% vs. 62% (p = 0.0006). Multivariate Cox analysis showed that age was not an independent risk factor for postoperative mortality. CONCLUSION: Preoperative complications and co-morbidities, more advanced disease, and higher postoperative nonsurgical complication rates adversely affect postoperative outcomes after surgery for colorectal cancer in the elderly

Spin splitting in InGaSb/InAlSb 2DEG having high indium content

We formed a novel metamorphic InGaSb/InAlSb two-dimensional electron gas (2DEG) having high indium contents around 0.9 by molecular beam epitaxy (MBE), and investigated its spin splitting through magneto-resistance (MR) characteristics by using Hall-bar samples. We observed clear Shubnikov-de Haas (SdH) type MR oscillations with some peak splitting induced by the Zeeman-like spin splitting over B=1 T at 1.5K. An Estimated splitting energy, ΔE, was 9 meV at B=4 T for the Landau index, n=1. Moreover, we also observed no peak splitting, i.e. spin split vanishing around B=1 T. Additionally, we confirmed some SdH beat patterns due to the zero-field spin splitting less than B=1 T, and the splitting energy at B=0, ΔE_0, was estimated to be 4~6 meV from the SdH fast Fourier transform (FFT) analysis. We successfully demonstrated well fitting curves for the Landau plots of SdH peaks across B=1 T, thus the Zeeman-like splitting, the spin split vanishing, and the beat patterns due to the zero-field splitting can be connected, smoothly. The fitting curves were obtained by assuming not the Rashba effect but the Dresselhaus effect on the (001) surface with the confinement. Therefore, it suggests that the zero-field spin splitting in the present InGaSb/InAlSb 2DEG originates from the Dresselhaus effect

Hypoxic induction of interleukin-8 gene expression in human endothelial cells.

Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis

Pre-operative assessment of cancer in the elderly (PACE): A comprehensive assessment of underlying characteristics of elderly cancer patients prior to elective surgery

Background: Cancer is a disease that particularly affects the elderly and, although surgery is the first treatment choice, many elderly cancer patients do not receive standard surgery because they are considered unfit for treatment due to an inaccurate estimation of operative risk. Pre-operative Assessment of Cancer in the Elderly (PACE) was developed in order to address the need to provide detailed information about the functional reserve of the elderly cancer patient to aid individualised management. Methods: PACE incorporates a battery of validated instruments including the Comprehensive Geriatric Assessment (CGA), Brief Fatigue Inventory (BFI), Eastern Cooperative Oncotogy Group Performance Status (ECOG-PS), and American Society Anesthesiologists (ASA) grade. An international prospective study was conducted with 460 consecutive elderly cancer patients (216 breast, 146 GIT, 71 GUT, 27 other) receiving PACE prior to receiving elective surgery. Results: Three hundred and eighty four patients (83.4%) were observed to have at least one co-morbidity; the most common being hypertension (n = 246, 53.5%). More than two thirds of the patients had good functional and mental status according to PACE. After adjusting for age, sex and type of cancer, six of the seven items of PACE were found to be significantly associated with co-morbidities (according to the Satariano's Index of Comorbidities (SIC)). A multivariate analysis identified IADL, BFI and ASA to be the most important instruments in explaining SIC. Discussion: PACE has been effectively used to describe the functional capacity and health status in an international cohort of elderly cancer patients. The majority of PACE instruments have been found to be significantly associated with co-morbidities (SIC) and can distinguish between type and severity of cancer. PACE represents a useful tool. in evaluating onco-geriatric fitness for surgery