Endothelial progenitor cells as a biological marker of peripheral artery disease.

The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.

Characteristics of Consecutive Esophageal Motility Diagnoses After a Decade of Change

BACKGROUND AND AIMS Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) measures concomitantly bolus transit and pressure changes allowing determination of the functional impact of esophageal motility abnormalities. Ten years ago our laboratory reported MII-EM results in 350 consecutive patients. Since then high-resolution impedance manometry (HRIM) became available and the definitions of ineffective esophageal motility (IEM) and nutcracker esophagus were revised. The aim of this study was to assess the impact of these developments on esophageal function testing. METHODS From August 2012 through May 2013, HRIM was performed in 350 patients referred for esophageal function testing. Each patient received 10 liquid and 10 viscous swallows. While taking advantage of the new technology and revised criteria, HRIM findings were classified according to the conventional criteria to allow more appropriate comparison with our earlier analysis. RESULTS Compared with the study performed 10 years ago, the prevalence of normal manometry (36% vs. 35%), achalasia (7% vs. 8%), scleroderma (1% vs. 1%), hypertensive lower esophageal sphincter (LES) (7% vs. 7%), and hypotensive LES (1% vs. 2%) remained the same, whereas the prevalence of distal esophageal spasm (9% vs. 3%), nutcracker esophagus (9% vs. 3%), and poorly relaxing LES (10% vs. 3%) decreased and the prevalence of IEM increased (20% vs. 31%) significantly. Compared with the early study, normal liquid bolus transit was significantly different in patients with hypertensive LES (96% vs. 57%) and poorly relaxing LES (55% vs. 100%). CONCLUSIONS This study brings to light the increase in prevalence of IEM. In addition, it suggests that the hypertensive LES and poorly relaxing LES may each affect bolus transit in about half of these patients.

Clinical and economic outcomes of serious postoperative infections following resection of common respiratory and gastrointestinal solid tumors

Unlike infections occurring during periods of chemotherapy-induced neutropenia, postoperative infections in patients with solid malignancy remain largely understudied. The purpose of this population-based study was to evaluate the clinical and economic burden, as well as the relationship of hospital surgical volume and outcomes associated with serious postoperative infection (SPI) – i.e., bacteremia/sepsis, pneumonia, and wound infection – following resection of common solid tumors.^ From the Texas Discharge Data Research File, we identified all Texas residents who underwent resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum between 2002 and 2006. From their billing records, we identified ICD-9 codes indicating SPI and also subsequent SPI-related readmissions occurring within 30 days of surgery. Random-effects logistic regression was used to calculate the impact of SPI on mortality, as well as the association between surgical volume and SPI, adjusting for case-mix, hospital characteristics, and clustering of multiple surgical admissions within the same patient and patients within the same hospital. Excess bed days and costs were calculated by subtracting values for patients without infections from those with infections computed using multilevel mixed-effects generalized linear model by fitting a gamma distribution to the data using log link.^ Serious postoperative infection occurred following 9.4% of the 37,582 eligible tumor resections and was independently associated with an 11-fold increase in the odds of in-hospital mortality (95% Confidence Interval [95% CI], 6.7-18.5, P < 0.001). Patients with SPI required 6.3 additional hospital days (95% CI, 6.1 - 6.5) at an incremental cost of $16,396 (95% CI, $15,927–$16,875). There was a significant trend toward lower overall rates of SPI with higher surgical volume (P=0.037). ^ Due to the substantial morbidity, mortality, and excess costs associated with SPI following solid tumor resections and given that, under current reimbursement practices, most of this heavy burden is borne by acute care providers, it is imperative for hospitals to identify more effective prophylactic measures, so that these potentially preventable infections and their associated expenditures can be averted. Additional volume-outcomes research is also needed to identify infection prevention processes that can be transferred from higher- to lower-volume providers.^

Assessment of cancer incidence in Titus County, Texas, 1977--1984

The purpose of this study was to determine the incidence of cancer in Titus County, Texas, through the identification of all cases of cancer that occurred in residents of the county during the period from 1977 to 1984. Data gathered from Texas Cancer Registry, hospital records, and death certificates were analyzed with regard to anatomic site, race, sex, age, city of residence, and place of birth. Adjustment of incidence rates by sex and race allowed comparisons with U.S. rates provided by the Surveillance, Epidemiology, and End Results Program (SEER).^ Seven hundred sixty-six (766) cancer cases were identified for the eight year period during 171,536 person-years of observation. In whites, statistically significant standardized incidence ratios (SIR) were found for leukemia (males SIR = 2.70 and females SIR = 2.26), melanoma (males SIR = 1.90 and females SIR = 2.25), lung (males SIR = 1.45) and for multiple myeloma (both sexes combined SIR = 1.86). In blacks, significant excess numbers of cases were found for Hodgkin's disease (males SIR = 8.33 and females SIR = 13.3) and for esophagus and bone considering both sexes together (SIR = 2.68 and 12.54, respectively). Rates for blacks were based on a small population and therefore unstable. A statistically significant excess number of cases for all sites combined was found in Mount Pleasant residents (age-adjusted incidence rate = 563.6 per 100,000 per year).^ A review of possible environmental risk factors in the area: hazardous waste disposal site, lignite deposits, and petrochemical and poultry industries are presented. A need for further epidemiological and environmental studies to identify etiological factors that could be responsible for the excess number of leukemia cases are recommended. For melanoma, a public health educational program to teach the population methods of protection from sun exposure is also suggested. ^

The association of previous induced abortion with the subsequent pregnancy complication of placenta previa

Placenta previa is alleged to be more common among women with a history of prior induced abortion. To investigate further whether there is a relationship between previous induced abortion and subsequent pregnancy complication of placenta previa, a matched case-comparison study was conducted comparing the reproductive histories of 256 women with placenta previa matched on age, date of delivery, and hospital with those of 256 women having normal deliveries and cesarean section deliveries without placental complications.^ Women with placenta previa had a twofold increase in the odds of having had one previous induced abortion (odds ratio 2.25) over women with no placental complications. Women with placenta previa and two or more previous induced abortions had a sevenfold increase in odds.^ The significant association of placenta previa and previous induced abortion remained after including gravida status, previous dilatation and curettage (D&C) status, previous spontaneous abortion, and race in a conditional logistic regression model. There is interaction between high gravidity and previous spontaneous abortion. Dilatation and curettage is associated with placenta previa primarily because women with abortion histories have also had a dilatation and curettage.^ Women who are seeking abortion and wish to have children later should be informed that there may be a longterm effect of developing placental complications in subsequent pregnancies. Women who have had at least one induced abortion or any dilatation and curettage procedure should be monitored carefully during any subsequent pregnancy for the risk of the complication of placenta previa. This knowledge should alert the physician or nurse-midwife to treat those women with a history of previous induced abortions as potential high risk pregnancies and could perhaps reduce maternal and fetal morbidity rates. ^

Static GPS measurements and elevation model in the vicinity of the EDML deep-drilling site

Interpretation of ice-core records requires accurate knowledge of the past and present surface topography and stress-strain fields. The European Project for Ice Coring in Antarctica (EPICA) drilling site (0.0684° E and 75.0025° S, 2891.7 m) in Dronning Maud Land, Antarctica, is located in the immediate vicinity of a transient and splitting ice divide. A digital elevation model is determined from the combination of kinematic GPS measurements with the GLAS12 data sets from the ICESat satellite. Based on a network of stakes, surveyed with static GPS, the velocity field around the EDML drilling site is calculated. The annual mean velocity magnitude of 12 survey points amounts to 0.74 m/a. Flow directions mainly vary according to their distance from the ice divide. Surface strain rates are determined from a pentagon-shaped stake network with one center point, close to the drilling site. The strain field is characterised by along flow compression, lateral dilatation, and vertical layer thinning.

Sedimentation and mineral analysis on sediment cores from the Lena Delta

Core and outcrop analysis from Lena mouth deposits have been used to reconstruct the Late Quaternary sedimentation history of the Lena Delta. Sediment properties (heavy mineral composition, grain size characteristics, organic carbon content) and age determinations (14C AMS and IR-OSL) are applied to discriminate the main sedimentary units of the three major geomorphic terraces, which form the delta. The development of the terraces is controlled by complex interactions among the following four factors: (1) Channel migration. According to the distribution of 14C and IR-OSL age determinations of Lena mouth sediments, the major river runoff direction shifted from the west during marine isotope stages 5-3 (third terrace deposits) towards the northwest during marine isotope stage 2 and transition to stage 1 (second terrace), to the northeast and east during the Holocene (first terrace deposits). (2) Eustasy. Sea level rise from Last Glacial lowstand to the modern sea level position, reached at 6-5 ka BP, resulted in back-filling and flooding of the palaeovalleys. (3) Neotectonics. The extension of the Arctic Mid-Ocean Ridge into the Laptev Sea shelf acted as a halfgraben, showing dilatation movements with different subsidence rates. From the continent side, differential neotectonics with uplift and transpression in the Siberian coast ridges are active. Both likely have influenced river behavior by providing sites for preservation, with uplift, in particular, allowing accumulation of deposits in the second terrace in the western sector. The actual delta setting comprises only the eastern sector of the Lena Delta. (4) Peat formation. Polygenetic formation of ice-rich peaty sand (''Ice Complex'') was most extensive (7-11 m in thickness) in the southern part of the delta area between 43 and 14 ka BP (third terrace deposits). In recent times, alluvial peat (5-6 m in thickness) is accumulated on top of the deltaic sequences in the eastern sector (first terrace).

Global Scale Impacts

Global scale impacts modify the physical or thermal state of a substantial fraction of a target asteroid. Specific effects include accretion, family formation, reshaping, mixing and layering, shock and frictional heating, fragmentation, material compaction, dilatation, stripping of mantle and crust, and seismic degradation. Deciphering the complicated record of global scale impacts, in asteroids and meteorites, will lead us to understand the original planet-forming process and its resultant populations, and their evolution in time as collisions became faster and fewer. We provide a brief overview of these ideas, and an introduction to models.

Investigación sobre las causas que pudieron originar el hundimiento de la cubierta del tercer depósito del Canal de Isabel II en 1905

En la presente investigación se analiza la causa del hundimiento del cuarto compartimento del Tercer Depósito del Canal de Isabel II el 8 de abril de 1905, uno de los más graves de la historia de la construcción en España: fallecieron 30 personas y quedaron heridas otras 60. El Proyecto y Construcción de esta estructura era de D. José Eugenio Ribera, una de las grandes figuras de la ingeniería civil en nuestro país, cuya carrera pudo haber quedado truncada como consecuencia del siniestro. Dado el tiempo transcurrido desde la ocurrencia de este accidente, la investigación ha partido de la recopilación de la información relativa al Proyecto y a la propia construcción de la estructura, para revisar a continuación la información disponible sobre el hundimiento. De la construcción de la cubierta es interesante destacar la atrevida configuración estructural, cubriéndose una inmensa superficie de 74.000 m2 mediante una sucesión de bóvedas de hormigón armado de tan sólo 5 cm de espesor y un rebajamiento de 1/10 para salvar una luz de 6 m, que apoyaban en pórticos del mismo material, con pilares también muy esbeltos: 0,25 m de lado para 8 m de altura. Y todo ello en una época en la que la tecnología y conocimiento de las estructuras con este "nuevo" material se basaban en buena medida en el desarrollo de patentes. En cuanto a la información sobre el hundimiento, llama la atención en primer lugar la relevancia de los técnicos, peritos y letrados que intervinieron en el juicio y en el procedimiento administrativo posterior, poniéndose de manifiesto la trascendencia que el accidente tuvo en su momento y que, sin embargo, no ha trascendido hasta nuestros días. Ejemplo de ello es el papel de Echegaray -primera figura intelectual de la época- como perito en la defensa de Ribera, de D. Melquiades Álvarez -futuro presidente del Congreso- como abogado defensor, el General Marvá -uno de los máximos exponentes del papel de los ingenieros militares en la introducción del hormigón armado en nuestro país-, que presidiría la Comisión encargada del peritaje por parte del juzgado, o las opiniones de reconocidas personalidades internacionales del "nuevo" material como el Dr. von Emperger o Hennebique. Pero lo más relevante de dicha información es la falta de uniformidad sobre lo que pudo ocasionar el hundimiento: fallos en los materiales, durante la construcción, defectos en el diseño de la estructura, la realización de unas pruebas de carga cuando se concluyó ésta, etc. Pero la que durante el juicio y en los Informes posteriores se impuso como causa del fallo de la estructura fue su dilatación como consecuencia de las altas temperaturas que se produjeron aquella primavera. Y ello a pesar de que el hundimiento ocurrió a las 7 de la mañana... Con base en esta información se ha analizado el comportamiento estructural de la cubierta, permitiendo evaluar el papel que diversos factores pudieron tener en el inicio del hundimiento y en su extensión a toda la superficie construida, concluyéndose así cuáles fueron las causas del siniestro. De los resultados obtenidos se presta especial atención a las enseñanzas que se desprenden de la ocurrencia del hundimiento, enfatizándose en la relevancia de la historia -y en particular de los casos históricos de error- para la formación continua que debe existir en la Ingeniería. En el caso del hundimiento del Tercer Depósito algunas de estas "enseñanzas" son de plena actualidad, tales como la importancia de los detalles constructivos en la "robustez" de la estructuras, el diseño de estructuras "integrales" o la vigilancia del proceso constructivo. Por último, la investigación ha servido para recuperar, una vez más, la figura de D. José Eugenio Ribera, cuyo papel en la introducción del hormigón armado en España fue decisivo. En la obra del Tercer Depósito se arriesgó demasiado, y provocó un desastre que aceleró la transición hacia una nueva etapa en el hormigón estructural al abrigo de un mayor conocimiento científico y de las primeras normativas. También en esta etapa sería protagonista. This dissertation analyses the cause of the collapse of the 4th compartment of the 3th Reservoir of Canal de Isabel II in Madrid. It happened in 1905, on April 8th, being one of the most disastrous accidents occurred in the history of Spanish construction: 30 people died and 60 were injured. The design and construction supervision were carried out by D. José Eugenio Ribera, one of the main figures in Civil Engineering of our country, whose career could have been destroyed as a result of this accident. Since it occurred more than 100 years ago, the investigation started by compiling information about the structure`s design and construction, followed by reviewing the available information about the accident. With regard to the construction, it is interesting to point out its daring structural configuration. It covered a huge area of 74.000 m2 with a series of reinforced concrete vaults with a thickness of not more than 5 cm, a 6 m span and a rise of 1/10th. In turn, these vaults were supported by frames composed of very slender 0,25 m x 0,25 m columns with a height of 8 m. It is noteworthy that this took place in a time when the technology and knowledge about this "new" material was largely based on patents. In relation to the information about the collapse, its significance is shown by the important experts and lawyers that were involved in the trial and the subsequent administrative procedure. For example, Echegaray -the most important intellectual of that time- defended Ribera, Melquiades Álvarez –the future president of the Congress- was his lawyer, and General Marvá -who represented the important role of the military engineers in the introduction of reinforced concrete in our country-, led the Commission that was put in charge by the judge of the root cause analysis. In addition, the matter caught the interest of renowned foreigners like Dr. von Emperger or Hennebique and their opinions had a great influence. Nonetheless, this structural failure is unknown to most of today’s engineers. However, what is most surprising are the different causes that were claimed to lie at the root of the disaster: material defects, construction flaws, errors in the design, load tests performed after the structure was finished, etc. The final cause that was put forth during the trial and in the following reports was attributed to the dilatation of the roof due to the high temperatures that spring, albeit the collapse occurred at 7 AM... Based on this information the structural behaviour of the roof has been analysed, which allowed identifying the causes that could have provoked the initial failure and those that could have led to the global collapse. Lessons have been learned from these results, which points out the relevance of history -and in particular, of examples gone wrong- for the continuous education that should exist in engineering. In the case of the 3th Reservoir some of these lessons are still relevant during the present time, like the importance of detailing in "robustness", the design of "integral" structures or the due consideration of construction methods. Finally, the investigation has revived, once again, the figure of D. José Eugenio Ribera, whose role in the introduction of reinforced concrete in Spain was crucial. With the construction of the 3th Reservoir he took too much risk and caused a disaster that accelerated the transition to a new era in structural concrete based on greater scientific knowledge and the first codes. In this new period he would also play a major role.

Transient cardiac expression of constitutively active Gαq leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways

Cardiac hypertrophy and dilatation can result from stimulation of signal transduction pathways mediated by heterotrimeric G proteins, especially Gq, whose α subunit activates phospholipase Cβ (PLCβ). We now report that transient, modest expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the Gq α subunit (HAα*q) in hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after the initiating stimulus becomes undetectable. At 2 weeks, HAα*q protein is expressed at less than 50% of endogenous αq/11, and the transgenic hearts are essentially normal morphologically. Although HAα*q protein declines at 4 weeks and is undetectable by 10 weeks, the animals develop cardiac hypertrophy and dilatation and die between 8 and 30 weeks in heart failure. As the pathology develops, endogenous αq/11 rises (2.9-fold in atria; 1.8-fold in ventricles). At 2 weeks, basal PLC activity is increased 9- to 10-fold in atria but not ventricles. By 10 weeks, it is elevated in both, presumably because of the rise in endogenous αq/11. We conclude that the pathological changes initiated by early, transient HAα*q expression are maintained in part by compensatory changes in signal transduction and other pathways. Cyclosporin A (CsA) prevents hypertrophy caused by activation of calcineurin [Molkentin, J. D., Lu, J.-R., Antos, C. L., Markham, B., Richardson, J., Robbins, J., Grant, S. R. & Olson, E. N. (1998) Cell 93, 215–228]. Because HAα*q acts upstream of calcineurin, we hypothesized that HAα*q might initiate additional pathways leading to hypertrophy and dilatation. Treating HAα*q mice with CsA diminished some, but not all, aspects of the hypertrophic phenotype, suggesting that multiple pathways are involved.

Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A

Natriuretic peptides, produced in the heart, bind to the natriuretic peptide receptor A (NPRA) and cause vasodilation and natriuresis important in the regulation of blood pressure. We here report that mice lacking a functional Npr1 gene coding for NPRA have elevated blood pressures and hearts exhibiting marked hypertrophy with interstitial fibrosis resembling that seen in human hypertensive heart disease. Echocardiographic evaluation of the mice demonstrated a compensated state of systemic hypertension in which cardiac hypertrophy and dilatation are evident but with no reduction in ventricular performance. Nevertheless, sudden death, with morphologic evidence indicative in some animals of congestive heart failure and in others of aortic dissection, occurred in all 15 male mice lacking Npr1 before 6 months of age, and in one of 16 females in our study. Thus complete absence of NPRA causes hypertension in mice and leads to cardiac hypertrophy and, particularly in males, lethal vascular events similar to those seen in untreated human hypertensive patients.

Lipotoxic heart disease in obese rats: Implications for human obesity

To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of ceramide, a mediator of apoptosis, were 2–3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids.

Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to βadrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein–kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein–kinin system could be involved in the development or progression of cardiovascular diseases.

Sequence and expression of the murine Hoxd-3 homeobox gene.

Murine Hoxd-3 (Hox 4.1) genomic DNA and cDNA and Hoxa-3 (Hox 1.5) cDNA were cloned and sequenced. The homeodomains of Hoxd-3 and Hoxa-3 and regions before and after the homeodomain are highly conserved. Both Hoxa-3 and Hoxa-3 proteins have a proline-rich region that contains consensus amino acid sequences for binding to Src homology 3 domains of some signal transduction proteins. Northern blot analysis of RNA from 8- to 11-day-old mouse embryos revealed a 4.3-kb species of Hoxd-3 RNA, whereas a less abundant 3.0-kb species of Hoxd-3 RNA was found in RNA from 9- to 11-day-old embryos. Two species of Hoxd-3 poly(A)+ RNA, 4.3 and 6.0 kb in length, were found in poly(A)+ RNA from adult mouse kidney, but not in RNA from other adult tissues tested. Hoxd-3 mRNA was detected by in situ hybridization in 12-, 14-, and 17-day-old mouse embryos in the posterior half of the myelencephalon, spinal cord, dorsal root ganglia, first cervical vertebra, thyroid gland, kidney tubules, esophagus, stomach, and intestines.

Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells.

Tumor-derived adhesion factor (TAF) was previously identified as a cell adhesion molecule secreted by human bladder carcinoma cell line EJ-1. To elucidate the physiological function of TAF, we examined its distribution in human normal and tumor tissues. Immunochemical staining with an anti-TAF monoclonal antibody showed that TAF was specifically accumulated in small blood vessels and capillaries within and adjacent to tumor nests, but not in those in normal tissues. Tumor blood vessel-specific staining of TAF was observed in various human cancers, such as esophagus, brain, lung, and stomach cancers. Double immunofluorescent staining showed apparent colocalization of TAF and type IV collagen in the vascular basement membrane. In vitro experiments demonstrated that TAF preferentially bound to type IV collagen among various extracellular matrix components tested. In cell culture experiments, TAF promoted adhesion of human umbilical vein endothelial cells to type IV collagen substrate and induced their morphological change. Furthermore, when the endothelial cells were induced to form capillary tube-like structures by type I collagen, TAF and type IV collagen were exclusively detected on the tubular structures. The capillary tube formation in vitro was prevented by heparin, which inhibited the binding of TAF to the endothelial cells. These results strongly suggest that TAF contributes to the organization of new capillary vessels in tumor tissues by modulating the interaction of endothelial cells with type IV collagen.