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Background. Acquired calcified aortic valve stenosis is the most common valve disease in adulthood. In the etiopathogenesis of this complex pathology, the importance of inflammation is mentioned, in which non-infectious influences represented by the biological effects of metal pollutants may participate. The main goal of the study was to determine the concentration of 21 metals and trace elements—aluminium (Al), barium (Ba), cadmium (Cd), calcium (Ca), chrome (Cr), cobalt (Co), copper (Cu), gold (Au), lead (Pb), magnesium (Mg), mercury (Hg), molybdenum (Mo), nickel (Ni), phosphorus (P), selenium (Se), strontium (Sr), sulfur (S), tin (Sn), titanium (Ti), vanadium (V) and zinc (Zn)—in the tissue of calcified aortic valves and to compare them with the concentrations of the same elements in the tissue of healthy aortic valves in the control group. Material and methods. The study group consisted of 49 patients (25 men, mean age: 74) with acquired, severe, calcified aortic valve stenosis with indicated heart surgery. The control group included 34 deceased (20 men, median age: 53) with no evidence of heart disease. Calcified valves were explanted during cardiac surgery and deep frozen. Similarly, the valves of the control group were removed. All valves were lyophilized and analyzed by inductively coupled plasma mass spectrometry. The concentrations of selected elements were compared by means of standard statistical methods. Results. Calcified aortic valves contained significantly higher (p < 0.05) concentrations of Ba, Ca, Co, Cr, Mg, P, Pb, Se, Sn, Sr and Zn and—in contrast—lower concentrations of Cd, Cu, Mo, S and V than valves of the control group. Significant positive correlations of concentrations between the pairs Ca-P, Cu-S and Se-S and strong negative correlations between the elements Mg-Se, P-S and Ca-S were found in the affected valves. Conclusion. Aortic valve calcification is associated with increased tissue accumulation of the majority of the analyzed elements, including metal pollutants. Some exposure factors may increase their accumulation in the valve tissue. A relationship between exposure to environmental burden and the aortic valve calcification process cannot be ruled out. Advances in histochemical and imaging techniques allowing imaging of metal pollutants directly in valve tissue may represent an important future perspective.

Autoři předkladaji kazuistiku 59lete ženy dosetřovane pro recentně zjistěnou pancytopenii během hospitalizace pro oboustrannou intersticialni pneumonii bez zjistěneho vyvolavajiciho agens. Soucasně byly přitomny systemove symptomy nechutenstvi a vahový ubytek. Primarni hematologicke onemocněni bylo vylouceno. Poměrně překvapivý byl pozitivni serologický screening na HIV-1,2. Absolutni pocet CD4+ lymfocytů byl 8/µl. Prokazana nakaza lidským virem imunodeficience (HIV) byla tedy již ve stadiu AIDS a prodělanou intersticialni pneumonii nutno zpětně hodnotit jako onemocněni indikativni pro AIDS.

Bernard-Soulier syndrome (BSS) is a rare inherited disorder characterized by unusually large platelets, low platelet count, and prolonged bleeding time. BSS is usually inherited in an autosomal recessive (AR) mode of inheritance due to a deficiency of the GPIb-IX-V complex also known as the von Willebrand factor (VWF) receptor. We investigated a family with macrothrombocytopenia, a mild bleeding tendency, slightly lowered platelet aggregation tests, and suspected autosomal dominant (AD) inheritance. We have detected a heterozygous GP1BA likely pathogenic variant, causing monoallelic BSS. A germline GP1BA gene variant (NM_000173:c.98G > A:p.C33Y), segregating with the macrothrombocytopenia, was detected by whole-exome sequencing. In silico analysis of the protein structure of the novel GPIbα variant revealed a potential structural defect, which could impact proper protein folding and subsequent binding to VWF. Flow cytometry, immunoblot, and electron microscopy demonstrated further differences between p.C33Y GP1BA carriers and healthy controls. Here, we provide a detailed insight into its clinical presentation and phenotype. Moreover, the here described case first presents an mBSS patient with two previous ischemic strokes.

The authors present a case report of 59-years-old woman examined for pancytopenia recently diagnosed during hospitalization for bilateral interstitial pneumonia without any confirmed etiological agents. Concomitantly, some systemic symptoms like lack of appetite and weight loss were present. Primary hematological disease was ruled out. Positivity of serological screening for HIV-1,2 was rather surprising. Absolute count of CD4+ lymphocytes was 8/#956;l. Thus, HIV infection was already in stage of AIDS and retrospectively, the interstitial pneumonia has to be judged as AIDS-indicative illness.

Indeterminate cell histiocytosis is a rare disease belonging to the group of malignant histiocytic diseases. The disease predominantly affects the skin. The disease appeared in the described patient at the age of 80 years. Morphs began to develop on the skin and rapidly spread over the whole body including the face. Only the hands and feet were left uncovered. The patients skin samples were taken from 2 sites for histological examination. The resulting conclusion was indeterminate cell histiocytosis. The treatment we chose was analogous to the procedures for Langerhans cell histiocytosis. We chose PUVA phototherapy as the first-line treatment. This treatment is frequently efficient for skin forms of Langerhans cell histiocytosis. In the described case, however, PUVA phototherapy did not influence the disease activity at all. As the second-line treatment, we used low-energy electron beam irradiation in the total dose of 36.2 Gy. This treatment had a positive impact, morphs began to diminish and slowly disappear from the skin. But they have not disappeared completely, therefore we assessed the treatment effect of the radiotherapy itself as partial remission of the disease. Within the third-line treatment, we used 2-chlorodeoxyadenosine in a dose of 5 mg/m2/per day, administered via subcutaneous injection over 5 consecutive days in monthly intervals. There were three cycles of this treatment administered overall. The treatment with 2-chlorodeoxyadenosine was tolerated without any adverse effects. The patient aged 82 years was only administered 3 cycles of 2-chlorodeoxyadenosine. When after the 3rd cycle the skin was free from any pathological morphs and only some pigmentation spots remained, we finished the treatment. The skin expressions of indeterminate cell histiocytosis completely disappeared after electron beam irradiation and the following administration of 3 cycles of 2-chlorodeoxyadenosine. The remission was short, however, after 6 months the disease recurred and the treatment is planned to resume. We assume the disease regresses following administration of 2-chlorodeoxyadenosine, but more than 3 treatment cycles will probably be needed to reach a longer-term response.Key words: electron beam irradiation - indeterminate cell histiocytosis - 2-chlorodeoxyadenosine.

We present a case of 64 - year - old man with mantle cell lymphoma (MCL) diagnosed in radical prostatectomy for adenocarcinoma. Lymphoma of the prostate, either primary or secondary, is a rare entity. The prognosis of lymphoma involving the prostate is usually poor. The most common form of leukemia/lymphoma involving the prostate is that of chronic lymphocytic leukemia/lymphoma (CLL/SLL). Mantle cell lymphoma of the prostate is an exceedingly rare entity. The association between MCL and urologic cancer was previously described, however the etiologic connection between these two conditions remains unknown. The pathologists should pay attention to all lymphoid infiltrates in the prostate, especially in cases when these are dense.

Lung adenocarcinoma (LAC) is the most common form of lung cancer that increases in non-smokers at younger age. Altered protein glycosylation is one of the hallmarks of malignancy, its role in cancer progression is still poorly understood. In this study, we report mass spectrometric (MS) analysis of N-glycans released from fresh or defrosted tissue specimens from 24 patients with LAC. Comparison of cancerous versus adjacent healthy tissues revealed substantial differences in N-glycan profiles associated with disease. The significant increase in paucimannose and high-mannose glycans with 6-9 mannose residues and decline in the sialylated complex biantenary core fucosylated glycan with composition NeuAcGal(2)GlcNAc(2)Man(3)GlcNAc(2)Fuc were general features of tumors. In addition, 42 new N-glycan compositions were detected in cancerous tissues. The prominent changes in advanced disease stages were mostly observed in core fucosylated N-glycans with additional fucose (Fuc) residue/s and enhanced branching with non-galactosylated N-acetyl-glucosamine (GlcNAc) units. Both of these monosaccharide types were linked preferably on the 6-antenna. Importantly, as compared with noncancerous tissues, a number of these significant changes were clearly detectable early on in stage I. Application of N-glycan data obtained from tissues was next assessed and validated for evaluation of small sized biopsies obtained via bronchoscopy. In summary, observed alterations and data of newly detected N-glycans expand knowledge about the glycosylation in LAC and may contribute to research in more tailored therapies. Moreover, the results demonstrate effectiveness of the presented approach for utility in rapid discrimination of cancerous from healthy lung tissues.

γ-Tubulins are highly conserved members of the tubulin superfamily essential for microtubule nucleation. Humans possess 2 γ-tubulin genes. It is thought that γ-tubulin-1 represents a ubiquitous isotype, whereas γ-tubulin-2 is found predominantly in the brain, where it may be endowed with divergent functions beyond microtubule nucleation. The molecular basis of the purported functional differences between γ-tubulins is unknown. We report discrimination of human γ-tubulins according to their electrophoretic and immunochemical properties. In vitro mutagenesis revealed that the differences in electrophoretic mobility originate in the C-terminal regions of the γ-tubulins. Using epitope mapping, we discovered mouse monoclonal antibodies that can discriminate between human γ-tubulin isotypes. Real time quantitative RT-PCR and 2-dimensional-PAGE showed that γ-tubulin-1 is the dominant isotype in fetal neurons. Although γ-tubulin-2 accumulates in the adult brain, γ-tubulin-1 remains the major isotype in various brain regions. Localization of γ-tubulin-1 in mature neurons was confirmed by immunohistochemistry and immunofluorescence microscopy on clinical samples and tissue microarrays. Differentiation of SH-SY5Y human neuroblastoma cells by all-trans retinoic acid, or oxidative stress induced by mitochondrial inhibitors, resulted in upregulation of γ-tubulin-2, whereas the expression of γ-tubulin-1 was unchanged. Fractionation experiments and immunoelectron microscopy revealed an association of γ-tubulins with mitochondrial membranes. These data indicate that in the face of predominant γ-tubulin-1 expression, the accumulation of γ-tubulin-2 in mature neurons and neuroblastoma cells during oxidative stress may denote a prosurvival role of γ-tubulin-2 in neurons.-Draberova, E., Sulimenko, V., Vinopal, S., Sulimenko, T., Sladkova, V., D'Agostino, L., Sobol, M., Hozak, P., Křen, L., Katsetos, C. D., Draber, P. Differential expression of human γ-tubulin isotypes during neuronal development and oxidative stress points to γ-tubulin-2 prosurvival function.

We report a rare case of anaplastic large cell ALK+ lymphoma (ALCL) with initial asymptomatic cardiac involvement. A 59-year-old male with infiltration of the right ventricular wall underwent standard combined chemotherapy (CHOP) and achieved remission without significant cardiac impairment. Additionally, we report the actual incidence of cardiac lymphoma in newly diagnosed non-Hodgkin Lymphomas (NHLs). In total, 16 patients with cardiac lymphoma were found (0.1% NHLs) in the Czech Lymphoma Study Group database. DLBCL was the most frequent histology subtype (50%), and ALCL was identified in 12.5% of cases. At initial diagnosis, the median age was 55.5 (range 21-74) years and 59% were men. None of the 16 patients with cardiac involvement had isolated heart lymphoma. The response to first-line therapy was 79% in 14/16 evaluable patients. The median progression-free survival and overall survival were nearly the same – approximately 3.5 years (range; 0.05-16.7ys), while the median follow up was 4 years.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a very rare disease belonging to a group of histiocytoses (more precisely non-Langerhans cell histiocytoses). Rosai-Dorfman disease is characterised by the presence of atypical histiocytic cells in the sinuses of lymph nodes or in the extranodal lymphoid tissue, absorbing lymphocytes and plasma cells. The structure and function of the absorbed cells is not impaired and they can leave histiocytes as viable cells. This effect is called emperipolesis, whereas ingestion of cells with their destruction is called phagocytosis. In our text we describe a patient with this disease located, characteristically, in supraclavicular lymph nodes, but also in mediastinal lymph nodes. Along with lymphadenopathy skin alterations appeared which were both clinically and histologically described as eczema dermatitis. At the same time as lymphadenopathy also strong headaches started which the patient had never suffered before. Within the first-line treatment prednisone was administered, but no effect was achieved. 2-chlorodeoxyadenosine in 5 mg/m2 s. c. dose was used in the second-line treatment, for 5 successive days in monthly intervals. There were four cycles of this treatment administered overall. Therapy was tolerated without any manifestations of toxicity. Already after the 1st cycle skin alterations as well as headaches entirely disappeared. To assess the effect of treatment the PET/CT examination with 18F-fluorodeoxyglucose (FDG-PET/CT) was made. After 4 cycles of treatment the mediastinal lymph nodes diminished to a physiological size and the accumulation of fluorodeoxyglucose in them was assessed as physiological. Lymphadenopathy in the neck area also significantly diminished by 50-75 % and the accumulation of fluorodeoxyglucose was reduced as well, though it did not reach the norm. Therefore we evaluate the effect of treatment as a partial remission with complete disappearance of skin alterations and headaches. The cause of the eczema and headaches has not been clarified, however considering the same time of their arising and then disappearance after the application of 2-chlorodeoxyadenosine the causal connection with Rosai-Dorfman disease is likely.Castlemans disease - lenalidomide - Rosai-Dorfman disease - rituximab - sinus lymphadenopathy with massive lymphadenopathy - thalidomide - 2-chlorodeoxyadenosine.

Summary Schwannomas represent about 8 % of all intracranial tumours, however, ventricular location of schwannomas is extremely rare. If they occur, they are located mostly in the lateral ventricle. To our knowledge there was only one case of third ventricular schwannoma described in the literature. Our case is the second one.

The aim of the study was to verify whether there is a difference in the lengthwise growth of the femurs and in their angular deformity when comparing preventive vs. therapeutic transplantation of allogeneic mesenchymal stem cells (MSCs) to an iatrogenic defect in the distal physis of femur. Modified composite chitosan/collagen type I scaffold with MSCs was transplanted to an iatrogenically created defect of the growth cartilage in the lateral condyle of the left femur in 20 miniature male pigs. In Group A of animals (n = 10) allogeneic MSCs were transplanted immediately after creating the defect in the distal physis of femur (preventive transplantation). In Group B of animals (n = 10) the same defect of the growth cartilage was treated by transplantation of allogeneic MSCs four weeks after its creation (therapeutic transplantation), after the excision of the bone bridge that had formed in it. On average, left femurs with a damaged distal physis and preventively transplanted allogeneic MSCs (Group A) grew during 4 months from transplantation by 0.56 ± 0.44 cm more than right femurs without the transplantation of MSCs, whereas left femurs with physeal defects treated with a therapeutic transplantation of allogeneic MSCs (Group B) by 0.14 ± 0.72 cm only, compared to right femurs without transplanted MSCs. Four months after preventive transplantation of MSCs (Group A), valgus deformity of the distal part of left femur with the defect was 0.78 ± 0.82°; in the control group (right femur in the same animal without MSCs transplantation) it was 3.7 ± 0.82°. After therapeutic transplantation of MSCs (Group B) 0.6 ± 3.4°, in the control group (right femur in the same animal without MSCs transplantation) it was 2.1 ± 2.9°. In all the animals of Groups A and B, the presence of newly formed hyaline cartilage was confirmed histologically and immunohistochemically. In the distal physis of right femurs with an iatrogenic defect of the growth cartilage without the transplantation of MSCs (control) bone bridge was formed. Preventive transplantation of allogeneic MSCs into the defect of the distal growth zone of femur appears more suitable compared to the therapeutic transplantation, with regard to the more pronounced lengthwise bone growth. Differences found in the extent of valgus deformity were non-significant comparing preventive and therapeutic transplantations of MSCs. MSCs, growth plate, deformity, bone bridge Injury of the growth cartilage of the long bones of the extremities usually leads to the formation of a bone bridge between epiphysis and metaphysis of the long bone (Key and Ford 1958; Bright 1974). At the same time, in approximately 25 - 30% of cases the lengthwise bone growth is reduced and its angular deformity occurs (Ahn et al. 2004). Besides, in 10% of these cases, the function of the relevant joint is impaired (Mann and

Objectives: Intracoronary cell transplantation during catheter balloon inflations may be associated with adverse events. We studied the effectiveness of an alternative transplantation technique – intracoronary cell infusion. Methods: Fourteen pigs, which had survived acute myocardial infarction, were randomized into 2 treatment groups and 2 controls. Three days after infarction, 12 pigs underwent allogeneic intracoronary mononuclear bone marrow cell transplantation using either the standard technique (short-term cell injections during repeat balloon inflations, technique A, n = 6) or continuous intracoronary cell infusion without balloon inflations (technique B, n = 6). Implanted cells were stained with fluorescent dye. After transplantation, the pigs were euthanized and myocardial samples were analyzed by fluorescent microscopy. Results: The mean numbers of fluorescently labeled bone marrow cells in the infarction border zone, in the infarction mid-area and in the center of myocardial infarction were 84, 72 and 55 using technique A, and 29, 57 and 46 using technique B, respectively. The mean cell retention in the infarction border zone of 84 cells for technique A and 29 cells for technique B differed significantly (p = 0.034, two-tailed t test). Conclusion: The continuous intracoronary cell infusion technique is a less efficient cell delivery technique as compared with the standard technique using repeat intracoronary balloon inflations.

Physeal cartilage is known to have poor self-repair capacity after injury. Evaluation of the ability of cultured mesenchymal stem cells to repair damaged physis is the topic of current research. In 10 immature New Zealand white rabbits autogenous mesenchymal stem cells were transplanted into a iatrogenic physeal defect in a lateral portion of the distal growth plate of the right femur. The same defect without stem cells transplantation in the left femoral distal physis served as a control. In our study, we used our own technique of implantation of MSCs with a newly modified gel scaffold (New Composite Hyaluronate/Collagen Type I/Fibrin Scaffold). The rabbits were euthanized 4 months after transplantation. Bone length discrepancy and valgus deformity were measured from femoral radiographs. Healing of the defect was investigated histologically. The ability of mesenchymal stem cells to survive and promote cartilage healing in the physeal defect was assessed by immunofluorescence. Average difference in femur length measured from surgery to euthanasia (4 months) was 0.61 ± 0.19 cm after preventive transplantation of MSCs in the right femur, but only 0.11 ± 0.07 cm in the left femur. Average angular (valgus) deformity of the right femur with MSCs preventively transplanted to iatrogenically damaged distal femoral physis was 1.2 ± 0.72 °. Valgus deformity in the left femur was 5.4 ± 2.5 °. Prophylactic transplantation of autogenous mesenchymal stem cells to iatrogenically damaged distal growth plate of the rabbit femur prevented a bone bridge formation and resulted in healing of the physeal defect with hyaline cartilage. Immunofluorescence examination showed that the chondrocytes newly formed in growth zone are the result of implanted MSCs differentiation. Femur growth in traumatized physis was maintained even after transplantation of autogenous MSCs. As compared with the opposite femur (with physeal defect but without transplanted MSCs), the bone showed no significant shortening or valgus deformity (p = 0.018).

Gal P., A. Neaas, L. Planka, H. Kecova, L. Kfien, P. Krupa, J. Hluailova, D. Usvald: Chondrocytic Potential of Allogenic Mesenchymal Stem Cells Transplanted without Immunosuppression to Regenerate Physeal Defect in Rabbits. Acta Vet. Brno 2007, 76: 265-275. Mesenchymal stem cells (MSCs) from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal a defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. A iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, weighing 2.25 ± 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (three weeks and four months after implantation) and also histologically, by Pearl’s reaction and with immunofluorescence (four months after implantation). The results were compared with the data for the control defects (without stem cell implantation) in left distal femoral physes. On average, right femurs with a damaged distal physis and transplanted MSCs grew more in length (0.55 ± 0.21 cm) compared with left femurs with a physeal defect without stem cell transplantation (0.46 ± 0.23 cm). Valgus deformity of right femurs with a physeal defect and transplanted MSCs was mild (0.2 ± 0.1 °). On the contrary, left femurs with a physeal defect without transplanted MSCs showed a significant valgus deformity (2.7 ± 1.6 °). For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no lymphocytic infiltration occurred. At four months after transplantation, hyaline cartilage had formed throughout the defects treated with allogenic MSCs. Labelled mesenchymal stem cells/differentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescence. The results of this study demonstrated that allogenic mesenchymal stem cells in a new composite hyaluronate/collagen type I/fibrin scaffold repaired iatrogenic defects in the distal femoral physes in rabbits without the use of immunosuppressive therapy. The use of allogenic mesenchymal stem cells for the repair of physeal defects may be an alternative to autologous MSCs transplantation. An allogenic approach would enable mesenchymal stem cells to be isolated from any donor, providing a readily available source of cells for cartilage tissue repair.

We describe a case of multicentric Castleman disease with generalized lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15 kg, fever of non-infectious origin, night sweats, symptoms of anemia. Histological examination of the nodes with the highest accumulation of fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8 (HHV-8) were negative. Three recurrences of herpes zoster indicating an alteration of immunity preceded the dia-gnosis of disease. Treatment was initiated with combination of thalidomide, dexamethasone, and cyclophosphamide. The response after 2 months therapy was not clear and patient doesn't tolerated the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera - rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced during the 2 cycles of treatment, however, serious infectious complications accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2 was administered in 28-day intervals. This treatment has shown efficacy and tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose. Monotherapy with Mabthera has proved to be effective and well tolerated drug in this case. Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In the case of ineffectiveness of one treatment option must be tested other alternative. In this case the therapy based on thalidomide wasn't successful, whereas the treatment with Mabthera has achieved disappearance of disease symptoms.

Controversies still exist regarding definition of the thrombotic risks in Ph-(BCR/ABL1-) myeloproliferative disorders with thrombocythemia (MPD-T). Platelet counts at diagnosis are currently not taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD-T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 9 10(9)/L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2(V617F) mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V `Leiden' and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (+/- aspirin), we documented a decrease in both venous (6.7-fold) and arterial events (1.8-fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value.

Oncocytic cardiomyopathy is a rare arrhythmogenic disorder usually associated with female sex, difficult-to-control arrhythmias, or sudden death of infants and children. Morphologically, it is characterized by the presence of oncocytic cells, which are diffusely distributed or form the nodular structures within the myocardium, occasionally involving the valves, with a large number of mitochondria in cytoplasms. We present two cases of oncocytic cardiomyopathy. The first case had a fatal clinical outcome, and the other case was surgically treated. The nuclear expression of skeletal muscle transcription factor MyoD1 was demonstrated in the first case, supporting the theory that oncocytic cardiomyopathy is a conduction system developmental disorder. To confirm this hypothesis, it is necessary to further investigate myogenic transcription factor program in human cardiac conduction system cells.

In 2006, a 26-year-old woman presented with tender cervical and retroauricular lymphadenopathy accompanied by fever, lower limb paraparesis, skin rash and generalized myalgia. Her past medical history was unremarkable. Full blood count and renal and hepatic profi les were within normal ranges, with the exception of mild lactate dehydrogenase elevation (237 U/L). Microbiological and radiological screening revealed no infectious etiology, and immunological fi ndings were negative or normal. In contrast to increased C-reactive protein levels (140 mg/L), the serum procalcitonin level was low. Brain magnetic resonance and lumbar puncture showed no pathology.

The expression, cellular distribution, and subcellular sorting of the microtubule (MT)-nucleating γ-tubulin small complex (γTuSC) proteins, GCP2 and GCP3, were studied in human glioblastoma cell lines and in clinical tissue samples representing all histologic grades of adult diffuse astrocytic gliomas (n = 54). Quantitative real-time polymerase chain reaction revealed a significant increase in the expression of GCP2 and GCP3 transcripts in glioblastoma cells versus normal human astrocytes; these were associated with higher amounts of both γTuSC proteins. GCP2 and GCP3 were concentrated in the centrosomes in interphase glioblastoma cells, but punctate and diffuse localizations were also detected in the cytosol and nuclei/nucleoli. Nucleolar localization was fixation dependent. GCP2 and GCP3 formed complexes with γ-tubulin in the nucleoli as confirmed by reciprocal immunoprecipitation experiments and immunoelectron microscopy. GCP2 and GCP3 depletion caused accumulation of cells in G2/M and mitotic delay but did not affect nucleolar integrity. Overexpression of GCP2 antagonized the inhibitory effect of the CDK5 regulatory subunit-associated tumor suppressor protein 3 (C53) on DNA damage G2/M checkpoint activity. Tumor cell GCP2 and GCP3 immunoreactivity was significantly increased over that in normal brains in glioblastoma samples; it was also associated with microvascular proliferation. These findings suggest that γTuSC protein dysregulation in glioblastomas may be linked to altered transcriptional checkpoint activity or interaction with signaling pathways associated with a malignant phenotype.

Temporal arteries are typically below detectable levels of PET scanners, which repeatedly showed to be limiting in finding increased F-FDG accumulation even in histologically proven cases of giant cell arteritis. In 2010, Gaemperli and coworkers showed metabolic active inflammation in temporal arteries in an experimental study using PET with [C]-PK11195 combined with CT angiography. Herein, we present the case where an increased accumulation of routinely used tracer F-FDG can be identified directly in temporal and occipital arteries and even in smaller branches using a common hybrid PET/CT scanner if a brain acquisition protocol is applied.

The rationale of the Czech Hematological Society guidelines for diagnosis and treatment of Philadelphia chromosome-negative myeloproliferative disorders with thrombocythemia (MPD-T) is reviewed. For diagnosis of MPD-T, the classification according to the World Health Organization or to the Rotterdam criteria is preferred because they distinguish true essential thrombocythemia from prefibrotic or early fibrotic idiopathic myelofibrosis and prepolycythemic polycythemia vera. The histopathology-based nosological distinction provided by these classifications yields valuable information on prognosis (including the risks of transition into secondary acute myeloid leukemia and myelofibrosis). Another serious complication in MPD-T is thrombosis (arterial or venous), the main risk factors of which are age, previous thrombosis, platelet counts 350 to 2,200 x 10 (9)/L (peak at approximately 900 x 10 (9)/L) and the presence of additional thrombophilic risk factors (hereditary thrombophilia, any hypercoagulable state, cardiovascular disease). The hemorrhagic risk starts increasing progressively at platelet counts > 1,000 x 10 (9)/L. Treatment should be stratified with respect to the thrombotic and hemorrhagic risks. In high-risk patients, thromboreductive therapy is warranted. All of the cytostatic drugs, including hydroxyurea, may be leukemogenic and should be given only to patients > 60 years old, whereas anagrelide or interferon alpha are preferred in younger individuals. In low-risk patients, antiaggregation therapy is sufficient, unless the platelet count exceeds 1,000 x 10 (9)/L, which is another indication for thromboreduction. Thrombopheresis is indicated in thrombocythemia > 2,000 x 10 (9)/L.

The WHO 2008 classification of Ph-myeloproliferative disorders: statement of the Czech MPD Working Group

This study appears from an experiment previously carried out in New Zealand white rabbits. Allogenic mesenchymal stem cells (MSCs) were transplanted into an iatrogenically-created defect in the lateral section of the distal physis of the left femur in 10 miniature pigs. The right femur with the same defect served as a control. To transfer MSCs, a freshly prepared porous scaffold was used, based on collagen and chitosan, constituting a compact tube into which MSCs were implanted. The pigs were euthanized four months after the transplantation. On average, the left femur with transplanted MSCs grew more in length (0.56+/-0.14 cm) compared with right femurs with physeal defect without transplanted MSCs (0.14+/-0.3 cm). The average angular (valgus) deformity of the left femur had an angle point of 0.78 degrees , following measurement and X-ray examination, whereas in the right femur without transplantation it was 3.7 degrees. The initial results indicate that preventive transplantation of MSCs into a physeal defect may prevent valgus deformity formation and probably also reduce disorders of the longitudinal bone growth. This part of our experiment is significant in the effort to advance MSCs application in human medicine by using pig as a model, which is the next step after experimenting on rabbits.

The aim of this study was to evaluate macroscopically, histologically and immunohistochemically the quality of newly formed tissue in iatrogenic defects of articular cartilage of the femur condyle in miniature pigs treated with the clinically used method of microfractures in comparison with the transplantation of a combination of a composite scaffold with allogeneic mesenchymal stem cells (MSCs) or the composite scaffold alone. The newly formed cartilaginous tissue filling the defects of articular cartilage after transplantation of the scaffold with MSCs (Group A) had in 60 % of cases a macroscopically smooth surface. In all lesions after the transplantation of the scaffold alone (Group B) or after the method of microfractures (Group C), erosions/fissures or osteophytes were found on the surface. The results of histological and immunohistochemical examination using the modified scoring system according to O’Driscoll were as follows: 14.7±3.82 points after transplantations of the scaffold with MSCs (Group A); 5.3±2.88 points after transplantations of the scaffold alone (Group B); and 5.2±0.64 points after treatment with microfractures (Group C). The O’Driscoll score in animals of Group A was significantly higher than in animals of Group B or Group C (p