Showing papers by "University of Turin published in 2003"

Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer.

Abstract: Background Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established. Methods We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction. Results CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent ...

Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group

Abstract: The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.

ALPGEN, a generator for hard multiparton processes in hadronic collisions

Abstract: This paper presents a new event generator, ALPGEN, dedicated to the study of multiparton hard processes in hadronic collisions. The code performs, at the leading order in QCD and EW interactions, the calculation of the exact matrix elements for a large set of parton-level processes of interest in the study of the Tevatron and LHC data. The current version of the code describes the following final states: (W→f')Q+N jets (Q being a heavy quark, and f = l,q), with N ≤ 4;(Z/γ*→f)Q+N jets (f = l,ν), with N ≤ 4; W→f')+charm+N jets (f = l,q,N ≤ 5;W→f')+N jets (f = l,q and Z/γ*→f)+N jets (f = l,ν), with N ≤ 6; nW+mZ+lH+N jets, with n+m+l+N ≤ 8, N ≤ 3, including all 2-fermion decay modes of W and Z bosons, with spin correlations; Q+N jets, with t→bf' decays and relative spin correlations included where relevant, and N ≤ 6; QQ''+N jets, with Q and Q' heavy quarks (possibly equal) and N ≤ 4; HQ+N jets, with t→bf' decays and relative spin correlations included where relevant and N ≤ 4; N jets, with N ≤ 6. Parton-level events are generated, providing full information on their colour and flavour structure, enabling the evolution of the partons into fully hadronised final states.

A Smooth Model of Decision Making under Ambiguity

Abstract: We propose and axiomatize a model of preferences over acts such that the decision maker evaluates acts according to the expectation (over a set of probability measures) of an increasing transformation of an act's expected utility. This expectation is calculated using a subjective probability over the set of probability measures that the decision maker thinks are relevant given her subjective information. A key feature of our model is that it achieves a separation between ambiguity, identified as a characteristic of the decision maker's subjective information, and ambiguity attitude, a characteristic of the decision maker's tastes. We show that attitudes towards risk are characterized by the shape of the von Neumann-Morgenstern utility function, as usual, while attitudes towards ambiguity are characterized by the shape of the increasing transformation applied to expected utilities. We show that the negative exponential form of this transformation is the special case of constant ambiguity aversion. Ambiguity itself is defined behaviorally and is shown to be characterized by properties of the subjective set of measures. This characterization of ambiguity is formally related to the definitions of subjective ambiguity advanced by Epstein-Zhang (2001) and Ghirardato-Marinacci (2002). One advantage of this model is that the well-developed machinery for dealing with risk attitudes can be applied as well to ambiguity attitudes. The model is also distinct from many in the literature on ambiguity in that it allows smooth, rather than kinked, indifference curves. This leads to different behavior and improved tractability, while still sharing the main features (e.g., Ellsberg's Paradox, etc.). The Maxmin EU model (e.g., Gilboa and Schmeidler (1989)) with a given set of measures may be seen as an extreme case of our model with infinite ambiguity aversion. Two illustrative applications to portfolio choice are offered.

Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program

Abstract: Detection of minimal residual disease (MRD) has proven to provide independent prognostic information for treatment stratification in several types of leukemias such as childhood acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and acute promyelocytc leukemia. This report focuses on the accurate quantitative measurement of fusion gene (FG) transcripts as can be applied in 35-45% of ALL and acute myeloid leukemia, and in more than 90% of CML. A total of 26 European university laboratories from 10 countries have collaborated to establish a standardized protocol for TaqMan-based real-time quantitative PCR (RQ-PCR) analysis of the main leukemia-associated FGs within the Europe Against Cancer EAC) program. Four phases were scheduled: (1) training, (2) optimization, (3) sensitivity testing and (4) patient sample testing. During our program, three quality control rounds on a large series of coded RNA samples were performed including a balanced randomized assay, which enabled final validation of the EAC primer and probe sets. The expression level of the nine major FG transcripts in a large series of stored diagnostic leukemia samples (n = 278) was evaluated. After normalization, no statistically significant difference in expression level was observed between bone marrow and peripheral blood on paired samples at diagnosis. However, RQ-PCR revealed marked differences in FG expression between transcripts in leukemic samples at diagnosis that could account for differential assay sensitivity. The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels. This is likely to prove invaluable to the management of patients entered into multicenter therapeutic trials.

Diagnosis and Complications of Cushing’s Syndrome: A Consensus Statement

Abstract: In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.

The contribution of arbuscular mycorrhizal fungi in sustainable maintenance of plant health and soil fertility

Abstract: Beneficial plant–microbe interactions in the rhizosphere are primary determinants of plant health and soil fertility. Arbuscular mycorrhizas are the most important microbial symbioses for the majority of plants and, under conditions of P-limitation, influence plant community development, nutrient uptake, water relations and above-ground productivity. They also act as bioprotectants against pathogens and toxic stresses. This review discusses the mechanism by which these benefits are conferred through abiotic and biotic interactions in the rhizosphere. Attention is paid to the conservation of biodiversity in arbuscular mycorrhizal fungi (AMF). Examples are provided in which the ecology of AMF has been taken into account and has had an impact in landscape regeneration, horticulture, alleviation of desertification and in the bioremediation of contaminated soils. It is vital that soil scientists and agriculturalists pay due attention to the management of AMF in any schemes to increase, restore or maintain soil fertility.

Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using 'real-time' quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) - a Europe against cancer program

Abstract: Real-time quantitative RT-PCR (RQ-PCR) is a sensitive tool to monitor minimal residual disease (MRD) in leukemic patients through the amplification of a fusion gene (FG) transcript. In order to correct variations in RNA quality and quantity and to calculate the sensitivity of each measurement, a control gene (CG) transcript should be amplified in parallel to the FG transcript. To identify suitable CGs, a study group within the Europe Against Cancer (EAC) program initially focused on 14 potential CGs using a standardized RQ-PCR protocol. Based on the absence of pseudogenes and the level and stability of the CG expression, three genes were finally selected: Abelson (ABL), beta-2-microglobulin (B2M), and beta-glucuronidase (GUS). A multicenter prospective study on normal (n=126) and diagnostic leukemic (n=184) samples processed the same day has established reference values for the CG expression. A multicenter retrospective study on over 250 acute and chronic leukemia samples obtained at diagnosis and with an identified FG transcript confirmed that the three CGs had a stable expression in the different types of samples. However, only ABL gene transcript expression did not differ significantly between normal and leukemic samples at diagnosis. We therefore propose to use the ABL gene as CG for RQ-PCR-based diagnosis and MRD detection in leukemic patients. Overall, these data are not only eligible for quantification of fusion gene transcripts, but also for the quantification of aberrantly expressed genes.

Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis.

Abstract: Animal models indicate that the antimicrobial peptide hepcidin (HAMP; OMIM 606464) is probably a key regulator of iron absorption in mammals. Here we report the identification of two mutations (93delG and 166C→T) in HAMP on 19q13 in two families with a new type of juvenile hemochromatosis.

Conscious Expectation and Unconscious Conditioning in Analgesic, Motor, and Hormonal Placebo/Nocebo Responses

Abstract: The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms, although little is known about their role in different circumstances. In this study, we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure. We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone (GH) and cortisol did not have any effect on the secretion of these hormones. However, if a preconditioning was performed with sumatriptan, a 5-HT1B/1D agonist that stimulates GH and inhibits cortisol secretion, a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration, although opposite verbal suggestions were given. These findings indicate that verbally induced expectations have no effect on hormonal secretion, whereas they affect pain and motor performance. This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved, whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play, even though a conditioning procedure is performed.

The tobacco aquaporin NtAQP1 is a membrane CO2 pore with physiological functions

Abstract: Aquaporins, found in virtually all living organisms, are membrane-intrinsic proteins that form water-permeable complexes The mammalian aquaporin AQP1 has also shown CO2 permeability when expressed heterologously in Xenopus oocytes, although whether this is a biochemical curiosity or of physiological significance is a matter of debate Here we report that, in the same expression system, a CO2 permeability comparable to that of the human AQP1 is observed for the tobacco plasma membrane aquaporin NtAQP1 NtAQP1 facilitates CO2 membrane transport in the homologous plant system at the cellular level, and has a significant function in photosynthesis and in stomatal opening NtAQP1 overexpression heightens membrane permeability for CO2 and water, and increases leaf growth The results indicate that NtAQP1-related CO2 permeability is of physiological importance under conditions where the CO2 gradient across a membrane is small, as is the case between the atmosphere and the inside of a plant cell

Randomized Study of Adjuvant Chemotherapy for Completely Resected Stage I, II, or IIIA Non–Small-Cell Lung Cancer

Abstract: Background: Surgery is the primary treatment for patients with stage I, II, or IIIA non-small-cell lung cancer (NSCLC). However, long-term survival of NSCLC patients after surgery alone is largely unsatisfactory, and the role of adjuvant chemotherapy in patient survival has not yet been established. Methods: Between January 1994 and January 1999, 1209 patients with stage I, II, or IIIA NSCLC were randomly assigned to receive mitomycin C (8 mg/m 2 on day 1), vindesine (3 mg/m 2 on days 1 and 8), and cisplatin (100 mg/m 2 on day 1) every 3 weeks for three cycles (MVP group; n = 606) or no treatment (control group; n = 603) after complete resection. Randomization was stratified by investigational center, tumor size, lymph-node involvement, and the intention to perform radiotherapy. The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment. Survival curves were analyzed using the log-rank test. All statistical tests were two-sided. Results: After a median follow-up time of 64.5 months, there was no statistically significant difference between the two patient groups in overall survival (hazard ratio = 0.96, 95% confidence interval = 0.81 to 1.13; P = .589) or progression-free survival (hazard ratio = 0.89, 95% confidence interval = 0.76 to 1.03; P = .128). Only 69% of patients received the three planned cycles of MVP. Grades 3 and 4 neutropenia occurred in 16% and 12%, respectively, of patients in the MVP arm. Radiotherapy was completed by 65% of patients in the MVP arm and by 82% of patients in the control group. In the multivariable analysis, only disease stage and sex were associated with survival. Conclusion: This randomized trial failed to prospectively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC. Given the poor compliance with the MVP regimen used in this study, future studies should explore more effective treatments.

Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells.

Abstract: Angiogenic tumor vessels are promising targets for the activity and the selective delivery of cancer therapeutics. The bone marrow contributes different cell types to the tumor stroma, including hematopoietic cells and, as recently suggested, vascular endothelial cells (ECs). Thus, transplantation of genetically modified bone marrow progenitors may represent a vehicle for the transport of gene therapy to tumors. We transduced bone marrow progenitors with lentiviral vectors expressing genes from transcription-regulatory elements of Tie2/Tek gene. When tumors were grown in the transplanted mice, the new vector marked a distinct hematopoietic population that 'homed' to the tumor and closely interacted with vascular ECs at the tumor periphery. These Tie2-expressing mononuclear (TEM) cells had a distinguishable phenotype and were present selectively at angiogenic sites. Unexpectedly, we did not find bone marrow-derived ECs in tumor vessels when we transplanted bone marrow progenitors constitutively expressing a marker gene from the Tie2 or ubiquitously active promoters. By delivering a 'suicide' gene, we selectively eliminated the TEM cells and achieved substantial inhibition of angiogenesis and slower tumor growth without systemic toxicity. Thus, TEM cells may account for the proangiogenic activity of bone marrow-derived cells in tumors, may represent a new target for drug development and may provide the means for selective gene delivery and targeted inhibition of tumor angiogenesis.

Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function

Abstract: The motility and morphogenesis of endothelial cells is controlled by spatio-temporally regulated activation of integrin adhesion receptors, and integrin activation is stimulated by major determinants of vascular remodelling. In order for endothelial cells to be responsive to changes in activator gradients, the adhesiveness of these cells to the extracellular matrix must be dynamic, and negative regulators of integrins could be required. Here we show that during vascular development and experimental angiogenesis, endothelial cells generate autocrine chemorepulsive signals of class 3 semaphorins (SEMA3 proteins) that localize at nascent adhesive sites in spreading endothelial cells. Disrupting endogenous SEMA3 function in endothelial cells stimulates integrin-mediated adhesion and migration to extracellular matrices, whereas exogenous SEMA3 proteins antagonize integrin activation. Misexpression of dominant negative SEMA3 receptors in chick embryo endothelial cells locks integrins in an active conformation, and severely impairs vascular remodelling. Sema3a null mice show vascular defects as well. Thus during angiogenesis endothelial SEMA3 proteins endow the vascular system with the plasticity required for its reshaping by controlling integrin function.

Observation of a Narrow Meson State Decaying to Ds+π0 at a Mass of 2.32 GeV/c2

Abstract: We have observed a narrow state near 2.32 GeV/c(2) in the inclusive D(+)(s)pi(0) invariant mass distribution from e(+)e(-) annihilation data at energies near 10.6 GeV. The observed width is consistent with the experimental resolution. The small intrinsic width and the quantum numbers of the final state indicate that the decay violates isospin conservation. The state has natural spin-parity and the low mass suggests a J(P)=0(+) assignment. The data sample corresponds to an integrated luminosity of 91 fb(-1) recorded by the BABAR detector at the SLAC PEP-II asymmetric-energy e(+)e(-) storage ring.

Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation.

Abstract: These consensus guidelines have been compiled with input from the Scientific Advisors of the International Myeloma Foundation. Their production involved several steps including: A 3-day Scientific Advisors meeting, during which each specific area was presented and discussed (May 2002). Review of key literature, especially randomized study results, but also Medline, Internet, Cochrane database searches, and prior guidelines (Br J Haematol 115: 522-540, 2001). Feedback from patients participating in the International Myeloma Foundation, patient programs. These guidelines encompass both the published literature and expert opinions. Recommendations based upon expert opinions are identified as such. The intent is for the guidelines to be international in scope, plus provide recommendations for both clinical practice and research approaches. 'Consensus' reflects general, although not necessarily unanimous, agreement. Details are discussed as appropriate. For convenience, the recommendations are divided into: 1. Diagnostic criteria. 2. Staging and prognostic factors. 3. Frontline therapy. 4. High-dose therapy and transplant. 5. Maintenance therapy. 6. Supportive care and management of specific complications. 7. Novel therapies and new technologies.

Neural Stem Cells An Overview

Abstract: This review focuses on the nature and functional properties of stem cells of the adult mammalian central nervous system (CNS). It has recently been shown that cell turnover, including neurons, does occur in the mature CNS, thanks to the persistence of precursor cells that possess the functional characteristics of bona-fide neural stem cells (NSCs) within restricted brain areas. We discuss how the subventricular zone of the forebrain (SVZ) is the most active neurogenetic area and the richest source of NSCs. These NSCs ensure a life-long contribution of new neurons to the olfactory bulb and, when placed in culture, can be grown and extensively expanded for months, allowing the generation of stem cell lines, which maintain stable and constant functional properties. A survey of the differentiation potential of these NSCs, both in vitro and in vivo, outlines their extreme plasticity that seems to outstretch the brain boundaries, so that these neuroectodermal stem cells may give rise to cells that derive from developmentally distinct tissues. A critical discussion of the latest, controversial findings regarding this surprising phenomenon is provided.

Intrigue: Personalized recommendation of tourist attractions for desktop and hand held devices

Abstract: This paper presents INTRIGUE, a prototype tourist-information server that presents information about the area around Turin City, Italy, on desktop and hand held devices.This system recommends sightseeing destinations and itineraries by taking into account the preferences of heterogeneous tourist groups (such as families with children or the elderly) and explains the recommendations by addressing the group members' requirements. Moreover, the system provides an interactive agenda for scheduling the tour. The services offered by INTRIGUE rely on user modeling and adaptive hypermedia techniques; furthermore, XML-based technologies support the generation of the user interface and its adaptation to Web browsers and WAP minibrowsers.

Positional control of cell fate through joint integrin/receptor protein kinase signaling.

Abstract: Cells adhere to the extracellular matrix throughout most of their lifetime. This close, intimate contact with the matrix exerts an extraordinary control on the behavior of cells, determining whether they move or stay put, proliferate or remain quiescent, and even live or die. Attachment to the matrix not only enables cells to respond to soluble growth factors and cytokines but also determines the nature of the response. The integrins are a large family of receptors that attach cells to the matrix, organize their cytoskeleton, and cooperate with receptor protein tyrosine kinases to regulate cell fate. Research on integrin signaling is beginning to explain the complex and specific effects that the extracellular matrix exerts on cells.

Laparoscopic total mesorectal excision: a consecutive series of 100 patients.

Abstract: OBJECTIVE To analyze total mesorectal excision (TME) for rectal cancer by the laparoscopic approach during a prospective nonrandomized trial. SUMMARY BACKGROUND DATA Improved local control and survival rates in the treatment of rectal cancer have been reported after TME. METHODS The authors conducted a prospective consecutive series of 100 laparoscopic TMEs for low and mid-rectal tumors. All patients had a sphincter-saving procedure. Case selection, surgical technique, and clinical and oncologic results were reviewed. RESULTS The distal limit of rectal neoplasm was on average 6.1 (range 3-12) cm from the anal verge. The mean operative time was 250 (range 110-540) minutes. The conversion rate was 12%. Excluding the patient who stayed 104 days after a severe fistula and reoperation, the mean postoperative stay was 12.05 (range 5-53) days. The 30-day mortality was 2% and the overall postoperative morbidity was 36%, including 17 anastomotic leaks. Of 87 malignant cases, 70 (80.4%) had a minimum follow-up of 12 months, with a median follow-up of 45.7 (range 12-72) months. During this period 18.5% (13/70) died of cancer and 8.5% (6/70) are alive with metastatic disease. The port-site metastasis rate was 1.4% (1/70): a rectal cancer stage IV presented with a parietal recurrence at 17 months after surgery. The locoregional pelvic recurrence rate was 4.2% (3/70): three rectal cancers stage III at 19, 13, and 7 postoperative months. CONCLUSIONS Laparoscopic TME is a feasible but technically demanding procedure (12% conversion rate). This series confirms the safety of the procedure, while oncologic results are at present comparable to the open published series with the limitation of a short follow-up period. Further studies and possibly randomized series will be necessary to evaluate long-term clinical outcome in cancer patients.

Methadone maintenance at different dosages for opioid dependence.

Abstract: Background Methadone maintenance treatment (MMT) is a long term opiod replacement therapy, effective in the management of opiod dependence. Even if MMT at high dosage is recommended for reducing illicit opioid use and promoting longer retention in treatment, at present day "the organisation and regulation of the methadone maintenance treatment varies widely". Objectives To evaluate the efficacy of different dosages of MMT in modifying health and social outcomes and in promoting patients' familiar, occupational and relational functioning. Search methods We searched: - MEDLINE (OVID 1966-2001) - EMBASE (1988-2001) - ERIC (1988-2001) - Psychinfo (1947-2001) - Cochrane Controlled Trials Register (CCTR) (1947-2001) - Register of the Cochrane Drug and Alcohol Group (CDAG) (1947-2001) The CDAG search strategy was applied together with a specific MESH strategy. Further studies were searched through: · letters to the authors · check of references. Selection criteria Randomised Controlled Trials (RCT) and Controlled Prospective Studies (CPS) evaluating methadone maintenance at different dosages in the management of opioid dependence. Non-randomised trials were included when proper adjustment for confounding factors was performed at the analysis stage. Data collection and analysis Data Extraction was performed separately by two reviewers. Discrepancies were resolved by a third reviewer. Quality assessments of the methodology of studies were carried out using CDAG checklist. Main results 22 studies were excluded. 21 studies were included: 11 were RCTs (2279 participants) and 10 were CPSs (3715 participants). Outcomes: Retention rate - RCTs: High versus low doses at shorter follow-ups: RR=1.36 [1.13,1.63], and at longer ones: RR=1.62 [0.95,2.77]. Opioid use (self reported), times/w - RCTs: high versus low doses WMD= -2.00 [-4.77,0.77] high vs middle doses WMD= -1.89[-3.43, -0.35] Opioid abstinence, (urine based) at >3-4 w - RCTs: high versus low ones: RR=1.59 [1.16,2.18] high vs middle doses RR=1.51[0.63,3.61] Cocaine abstinence (urine based) at >3-4 w - RCTs: high versus low doses RR=1.81 [1.15,2.85] Overdose mortality - CPSs: high dose versus low dose at 6 years follow up: RR=0.29 [0.02-5.34] high dose vs middle dose at 6 years follow up: RR=0.38 [0.02-9.34] middle dose vs low dose at 6 years follow up: RR=0.57 [0.06-5.06] Authors' conclusions Methadone dosages ranging from 60 to 100 mg/day are more effective than lower dosages in retaining patients and in reducing use of heroin and cocaine during treatment. To find the optimal dose is a clinical ability, but clinician must consider these conclusions in treatment strategies.

Nephrin Expression Is Reduced in Human Diabetic Nephropathy Evidence for a Distinct Role for Glycated Albumin and Angiotensin II

Abstract: We studied the distribution of nephrin in renal biopsies from 17 patients with diabetes and nephrotic syndrome (7 type 1 and 10 type 2 diabetes), 6 patients with diabetes and microalbuminuria (1 type 1 and 5 type 2 diabetes), and 10 normal subjects. Nephrin expression was semiquantitatively evaluated by measuring immunofluorescence intensity by digital image analysis. We found an extensive reduction of nephrin staining in both type 1 (67 ± 9%; P P P

Modeling the early stages of vascular network assembly

Abstract: In vertebrates, networks of capillary vessels supply tissues with nutrients. Capillary patterns are closely mimicked by endothelial cells cultured on basement membrane proteins that allow single randomly dispersed cells to self-organize into vascular networks. Here we provide a model including chemoattraction as the fundamental mechanism for cell-to-cell communication in order to identify key parameters in the complexity of the formation of vascular patterns. By flanking biological experiments, theoretical insights and numerical simulations, we provide strong evidence that endothelial cell number and the range of activity of a chemoattractant factor regulate vascular network formation and size. We propose a mechanism linking the scale of formed endothelial structures to the range of cell-to-cell interaction mediated by the release of chemoattractants.