Self-propagating high-temperature synthesis of (Ho1-xLax)2O3 nanopowders for magneto-optical ceramics.

Weakly agglomerated nanoparticles of (Ho1-xLax)2O3 solid solutions were synthesized with the help of a self-propagating high-temperature synthesis (SHS). The nanopowders were studied by a simultaneous thermal analysis (TG-DSC), X-ray diffraction (XRD), BET and FT-IR spectroscopy methods. Changes of the particles morphology after annealing at different temperatures and ball milling were investigated by a scanning electron microscopy (SEM) and a dynamic light scattering (DLS) method. It was found that annealing at a temperature of 900 °C in air and ball milling of the SHS nanopowders allow obtaining rounded shape particles with a mean diameter of about 20 nm and C-type cubic crystal structure. Up to 10 mol.% of the lanthana was shown to dissolve in the holmium oxide nanoparticles.

Magneto-optical Faraday effect in dysprosium oxide (Dy2O3) based ceramics obtained by vacuum sintering.

The method of self-propagating high-temperature synthesis of submicron powders with subsequent vacuum sintering was used to produce a series of optical ceramics based on dysprosium oxide (DyxY0.95-xLa0.05)2O3, where x=0.7, 0.85, and 0.9. The influence of ceramics composition on optical transmission of the obtained samples was investigated. The studied materials had several transparency windows in the visible 500-730 nm, near-IR 1900-2300 nm, and mid-IR 3500-7500 nm ranges. The dependence of the Verdet constant on wavelength in the 400-1940 nm range was measured for each ceramics composition, and analytical approximations were obtained. When Y and La dopants were used, the Verdet constant depended linearly on the concentration of Dy3+ ions, and its value in the visible wavelength range was about twice that of the analogous value for a terbium gallium garnet crystal. The high transmission and relatively high Verdet constant make the produced materials highly promising for fabricating Faraday devices for Tm3+ and Ho3+ lasers and for lasers emitting in the visible spectrum.

A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells.

Telomere biology is frequently associated with disease evolution in human cancer and dysfunctional telomeres have been demonstrated to contribute to genetic instability. In BCR-ABL(+) chronic myeloid leukemia (CML), accelerated telomere shortening has been shown to correlate with leukemia progression, risk score and response to treatment. Here, we demonstrate that proliferation of murine CML-like bone marrow cells strongly depends on telomere maintenance. CML-like cells of telomerase knockout mice with critically short telomeres (CML-iG4) are growth retarded and proliferation is terminally stalled by a robust senescent cell cycle arrest. In sharp contrast, CML-like cells with pre-shortened, but not critically short telomere lengths (CML-G2) grew most rapidly and were found to express a specific 'telomere-associated secretory phenotype', comprising secretion of chemokines, interleukins and other growth factors, thereby potentiating oncogene-driven growth. Moreover, conditioned supernatant of CML-G2 cells markedly enhanced proliferation of CML-WT and pre-senescent CML-iG4 cells. Strikingly, a similar inflammatory mRNA expression pattern was found with disease progression from chronic phase to accelerated phase in CML patients. These findings demonstrate that telomere-induced senescence needs to be bypassed by leukemic cells in order to progress to blast crisis and provide a novel mechanism by which telomere shortening may contribute to disease evolution in CML.

Skeletal spread of an anaplastic astrocytoma (WHO grade III) and preservation of histopathological properties within metastases.

BACKGROUND: The incidence of extraneural metastases of glioma is low. Metastases occur at different sites and, infrequently, as diffuse bone marrow infiltration. Direct contact of a glioma with extrameningeal tissues might be a reason for extraneural metastases. However, the role of haematogenous spread remains unclear. METHODS: We report on a young patient who suffered from a left frontal anaplastic WHO grade III astrocytoma, which was treated with gross total resection and irradiation (60 Gy). No local relapse occurred during the following course, but a diffuse infiltration of the bone marrow was diagnosed 12 months after the initial diagnosis. The patient died 6 months later, as a result of hypercalcaemia and pancytopenia. The histopathological properties of the tumour and its bone metastases were analysed, as well as the mutations of the isocitrate dehydrogenase 1 gene (IDH1). To study the route of tumour dissemination, the peripheral blood of the patient was analysed for circulating tumour cells (CTCs). RESULTS: This study describes a rare case of an extraneurally metastasised WHO grade III anaplastic astrocytoma. The occurrence of bone marrow infiltration coinciding with the finding of a stable intracranial tumour is a notably unusual situation. The properties of the primary tumour were maintained within the metastases in our patient. No CTCs were found in the peripheral blood at one random time point after the diagnosis of bone metastases. CONCLUSIONS: Despite young patient age, a stable intracranial course with a single location and mutations in the IDH1 gene, the patient's overall survival was short at 18 months after diagnosis. This finding illustrates the therapeutic dilemma in patients with bone marrow involvement complicating the use of alkylating agents, such as temozolomide. Repeated and systematic blood sampling in a large cohort of patients is needed for the detection of CTCs in glioma patients with systemic tumour spread. Future studies investigating how intrinsic factors in glioma cell biology cause rare metastases in these tumours are needed.

Anti-tumour activity of two novel compounds in cisplatin-resistant testicular germ cell cancer.

BACKGROUND: Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo. METHODS AND RESULTS: Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes. CONCLUSION: The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin.

Telomere length analysis in monocytes and lymphocytes from patients with systemic lupus erythematosus using multi-color flow-FISH.

In order to analyse telomere length in subsets of human peripheral blood lymphocytes and monocytes, we modified a recently developed multicolor flow- fluorescent in situ hybridization (FISH) methodology that combines flow-FISH and antibody staining for cell surface antigens. We analysed telomere length of peripheral blood mononuclear cells in a group of 22 patients with systemic lupus erythematosus (SLE) and 20 age-matched healthy donors. We found that neither CD4+, CD8+, CD19+ cells nor CD14+ monocytes have significantly shorter telomeres compared with their healthy counterparts. On the basis of these findings, we then used monocyte telomere length as internal reference in order to control for intra-individual variability in telomere length. By using this approach, we could demonstrate significant telomere shortening in all three lymphocyte subsets (in all cases P < 0.05) compared with monocytes. However, these differences did not vary significantly between SLE patients and controls. In summary, telomere lengths in subpopulations of hematopoietic cells can be monitored in patients with SLE using multicolor flow-FISH. While confirming data by other groups on telomere length in lymphocyte subpopulations, our data argue against an increased proliferation rate of peripheral blood monocytes reflected by accelerated telomere shortening in patients with SLE.

Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover.

Telomeres both reflect and limit the replicative lifespan of normal somatic cells. Immature sub-populations of human CD34+38- hematopoietic stem cell (HSC) can be identified in vitro based on their growth kinetics and telomere length. Fluorescence in situ hybridization and flow cytometry (flow-FISH) has been used to characterize telomere length dynamics as a surrogate marker for HSC turnover in vivo. Investigations in normal steady-state hematopoiesis provided the basis for follow-up studies in model scenarios characterized by increased HSC turnover. Disorders with underlying malignant transformation of HSC (e.g., chronic myeloid leukemia (CML)) can be discriminated from disease states with increased HSC turnover rates secondary to depletion of the stem cell compartment, for example, as in defined bone marrow failure syndromes. In some of these model scenarios, the degree of telomere shortening can be correlated with disease duration, disease stage and severity as well as with response to disease-modifying treatment strategies. Whether increased telomere shortening represents a causal link between HSC turnover, replicative senescence and/or the induction of genetic instability in acquired HSC disorders remains to be shown. However, data from congenital disorders, like dyskeratosis congenita (DKC), suggest that disturbed telomere maintenance may play a role for replicative exhaustion of the HSC pool in vivo.

Tumour-related enzyme alterations in the clear cell type of human renal cell carcinoma identified by two-dimensional gel electrophoresis.

To identify tumour-related enzyme alterations we have used 2D-gels to analyse the proteome from dissected malignant and benign kidney areas from patients with clear-cell-type renal carcinoma. The expression of 12 proteins was diminished in tumour. Four proteins were characterized by mass spectrometry and were identified as enoyl-CoA hydratase, alpha-glycerol-3-phosphate dehydrogenase, aldehyde dehydrogenase 1 and aminoacylase-I.

Differential expression of the subunits of the glucose-6-phosphatase system in the clear cell type of human renal cell carcinoma - no evidence for an overexpression of protein kinase B.

The expression of two components of the glucose-6-phosphatase system, the catalytic subunit (G6PaseC) and the glucose-6-phosphate transporter, was analyzed in the clear cell type of human renal cell carcinoma. The expression of G6PaseC was decreased in tumours compared with non-tumourous tissue of the same patient. The expression of G6PaseT varied with no general trend between tumours and control tissue. The expression of protein kinase B (PKB) was unchanged in the tumours, suggesting that the down-regulation of G6PaseC in clear cells and the maintenance of the transformed phenotype are not predominantly caused by an overexpression of PKB.

[Higher medical schools and medical institutions: feedback problems]. / Vuz i meditsinskie uchrezhdeniia: voprosy obratnoi sviazi.

Sociological study of graduates from Nizhny Novgorod State Medical Academy was carried out in 1997. The opinions of 199 physicians on the quality of training at the Academy, on employment and continuous education, etc., are analyzed. Proposals on improving the quality of staff training from a practitioners' viewpoint are collected and classified.

Immunoreactive parathyroid hormone, calcium, and magnesium in human cerebrospinal fluid.

Parathyroid hormone (PTH) was measured radioimmunologically in simultaneous plasma and cerebrospinal fluid (CSF) samples obtained from 72 patients aged 20 to 80 years without endocrine or psychiatric diseases and from 2 patients aged 40 and 70 years with secondary hyperparathyroidism due to renal insufficiency. They underwent routine diagnostic lumbar puncture because of suspected prolapse of a disc. Total calcium (Ca) and magnesium (Mg) were also determined in these samples by complexometry . The following findings were obtained (ng/ml, median, range in brackets): Plasma PTH 1.7 (0.7-6.6); CSF PTH 0.8 (0.5-2.3), respectively. No correlation was found between PTH concentrations in plasma and CSF in all 74 samples. The Ca concentrations in plasma, with a median of 2.3 mmol/l (2.1-2.6) were significantly higher than the Ca concentrations in CSF (median 1.1 mmol/l, range 0.4-1.3). The correlation between PTH and calcium levels in CSF was only weak (r = 0.284 P less than 0.05). The Mg levels in CSF (median 1.1 mmol/l, range 0.7-1.6) were higher than Mg concentrations in plasma (median 0.9 mmol/l, range 0.6-1.1). No correlation was found between PTH and Mg in CSF. Our study demonstrated that in man PTH is a normal constituent of CSF.