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Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour.
Anastasios Matzavinos Mark A J Chaplain Vladimir A Kuznetsov 《Mathematical medicine and biology》2004,21(1):1-34
In this paper a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. In particular, attention is focused upon the attack of tumour cells by so-called tumour-infiltrating cytotoxic lymphocytes (TICLs), in a small, multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. At this stage the immune cells and the tumour cells are considered to be in a state of dynamic equilibrium--cancer dormancy--a phenomenon which has been observed in primary tumours, micrometastases and residual disease after ablation of the primary tumour. Nonetheless, the precise biochemical and cellular mechanisms by which TICLs control cancer dormancy are still poorly understood from a biological and immunological point of view. Therefore we focus on the analysis of the spatio-temporal dynamics of tumour cells, immune cells and chemokines in an immunogenic tumour. The lymphocytes are assumed to migrate into the growing solid tumour and interact with the tumour cells in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation (sometimes even the death) of the lymphocytes. The migration of the TICLs is determined by a combination of random motility and chemotaxis in response to the presence of chemokines. The resulting system of four nonlinear partial differential equations (TICLs, tumour cells, complexes and chemokines) is analysed and numerical simulations are presented. We consider two different tumour geometries--multi-layered cell growth and multi-cellular spheroid growth. The numerical simulations demonstrate the existence of cell distributions that are quasi-stationary in time and heterogeneous in space. A linear stability analysis of the underlying (spatially homogeneous) ordinary differential equation (ODE) kinetics coupled with a numerical investigation of the ODE system reveals the existence of a stable limit cycle. This is verified further when a subsequent bifurcation analysis is undertaken using a numerical continuation package. These results then explain the complex heterogeneous spatio-temporal dynamics observed in the partial differential equation (PDE) system. Our approach may lead to a deeper understanding of the phenomenon of cancer dormancy and may be helpful in the future development of more effective anti-cancer vaccines. 相似文献
3.
Dietmar Winkler Matth?us Willeit Rainer Wolf Mara Stamenkovic Johannes Tauscher Edda Pjrek Anastasios Konstantinidis Shird Schindler Christian Barnas Siegfried Kasper 《European neuropsychopharmacology》2003,13(2):129-134
The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials. 相似文献
4.
Sofia I. Andrikoula Haris S. Vasiliadis Anastasios V. Tokis Paraskevi Kosta Anna Batistatou Anastasios D. Georgoulis 《Arthroscopy》2007
Intra-articular ganglia are rare and mostly incidental findings on magnetic resonance imaging (MRI) and arthroscopy. We present 4 cases of intra-articular ganglion cysts associated with the anterior cruciate ligament (ACL) in 3 patients. The most commonly occurring symptoms were pain aggravated after stressing activities and limited knee range of motion. In 1 patient, ganglion cysts appeared in both knees with a time difference of 1 year. An MRI revealed typical signs of ganglion cysts in the substance of the ACL. Arthroscopy was performed for further evaluation and treatment. Histologic examination of the tissue removed revealed the presence of features consistent with ganglion cysts. Therefore, in the case of chronic knee discomfort with nonspecific clinical signs and symptoms and without a clear cause, an intra-articular ganglion cyst should be considered as causing pathology. An MRI is the most sensitive and specific method for diagnosis. However, the relatively slow progression of symptoms may delay the patient’s decision to seek medical attention. Delayed diagnosis makes arthroscopic total resection of the ganglion technically demanding or not possible at all, and extensive debridement of the ACL may be required. 相似文献
5.
Theodore H. Xenakis Konstantinos N. Malizos Alexandros E. Beris Marios Vekris Anastasios D. Georgoulis Panayotis N. Soucacos 《Microsurgery》1994,15(7):479-484
Reconstruction of large bony defects of long bones was performed using vascularised fibular grafts in four patients at the Department of Orthopaedic Surgery of the University of Ioannina Medical School. Indications for grafting procedures in this small series had been the loss of bone due to the extensive resection of avascular and necrotic bone from septic pseudoarthrosis in three patients and congenital pseudarthrosis secondary to neurofibromatosis in a child. Primary skeletal union with graft hypertrophy occurred in three of the patients. The fourth patient had an asymptomatic nonunion at the proximal end of the graft. The result in each patient was the presence of a well-aligned limb that had normal or nearly normal motion and acceptable length. © 1994 Wiley-Liss, Inc. 相似文献
6.
Ioannis Alexiou Anastasios Germenis Athanasios Ziogas Katerina Theodoridou Lazaros I Sakkas 《BMC musculoskeletal disorders》2007,8(1):37
Background
Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis (RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. 相似文献7.
Anastasios Dondos Evgenia Pierri Labros Skartsis Christos Economou 《Macromolecular chemistry and physics.》1988,189(7):1685-1692
A relation is proposed which yields the occupied volume by macromolecular chains in solution. The experimental verification of the model is carried out by a viscometric study of the ternary system polymer A/polymer B/solvent. More precisely the viscometric study permits the determination of the critical concentration c** corresponding to the incipient overlap of spherical coils. 相似文献
8.
Evaluation of a microsphere-based flow cytometric assay for diagnosis of celiac disease 总被引:2,自引:0,他引:2
Yiannaki EE Zintzaras E Analatos A Theodoridou C Dalekos GN Germenis AE 《Journal of immunoassay & immunochemistry》2004,25(4):345-357
The multiplexed particle-based flow cytometric technology proposes a new approach for the diagnosis of autoimmune diseases combining the advantages of conventional methods with the ability to quantitatively determine multiple autoantibodies in the same sample, simultaneously and rapidly. Recently, a commercial kit (FIDIS Celiac, Biomedical Diagnostics, Mane la Vallé, France) was introduced for the simultaneous detection of IgA anti-tissue transglutaminase (anti-tTG), IgG, and IgA anti-gliadin antibodies (AGA). This study was undertaken to evaluate and compare the FIDIS Celiac kit with standardized commercial ELISAs (QUANTA Lite, INOVA Diagnostics Inc., San Diego, CA). A disease group consisted of 21 samples from untreated patients with biopsy confirmed celiac disease (CD), and two control groups of historical sera (207 from regular blood donors and 181 from chronically infected hepatitis patients) were studied. All control sera were negative for IgA anti-endomysial antibodies (EmA) and had an IgA concentration above the lower normal limit. Concerning the reproducibility, intra- and inter-assay coefficients of variation (CVs) ranging between 2% and 12%, and between 3% and 21%, respectively, were observed. Regarding the diagnostic quality, each assay was compared to the disease diagnosis using the McNemar test and the kappa (K) parameter, while ROC analysis was applied. Generally, the performance of FIDIS assay was proved almost equally adequate to that of ELISA in the detection of IgA anti-tTG antibodies, IgA and IgG AGA. However, the performance of FIDIS assay was found surmounting that of ELISA among hepatitis patients, possibly due to the avoidance of debris and unbound cross contaminants and, hence, the "noise" of such materials in samples under analysis. Taking our results together with the simplicity and the high throughput of FIDIS assay, its overall performance in the diagnosis of CD seems better than that of ELISA. 相似文献
9.
10.
Aidonopoulos AP Papavramidis ST Zaraboukas TG Habib HW Pothoulakis IG 《Obesity surgery》1994,4(1):8-12
Morbidly obese patients constitute a high risk group for the development of gallbladder disease. In our series 70 consecutive
patients underwent vertical gastroplasty in an effort to manage morbid obesity. The mean age was 37 years (range 20-60), and
the mean excess body weight was 92 kg (range 52-265). Six patients (8.5%) had undergone cholecystectomy before bariatric surgery
because of symptomatic cholelithiasis. The remaining 64 patients underwent cholecystectomy at the time of vertical gastroplasty.
Ninety-seven percent of the removed gallbladders had gross or histologic abnormalities, including cholelithiasis 18.5% (13
patients), and cholesterolosis 31% (22 patients). Histologically, chronic cholecystitis was present in all patients with cholelithiasis
and cholesterolosis. Chronic cholecystitis alone was found in 27 patients (38.5%) and only two patients (3%) had normal findings.
The mean excess body weight of the patients with cholesterolosis (96 kg) was not significantly greater than that of patients
with cholelithiasis (89 kg) or chronic cholecystitis (88 kg). Our findings suggest that cholecystectomy should be performed
in all morbidly obese patients concomitant with vertical gastroplasty. 相似文献