[Recurrent petrosal tumor: meningioma or solitary fibrous tumor?] / Retsidivnaya petrozal'naya opukhol': meningioma ili solitarnaya fibroznaya opukhol'?

Intracranial meningeal solitary fibrous tumors (SFT) originating from mesenchymal tissue are much less common than those with lesions of the visceral pleura or liver and were isolated as a nosological form only in 1996. These tumors are identical in clinical manifestations, MRI and light microscopy data to meningiomas. The pathognomonic difference of SFT, according to the 5th edition of the WHO classification, is the detection of overexpression of the protein encoded by the STAT6 gene. Estimation of other immunohistochemical markers is variable. At the same time, SFT has a tendency to more frequent recurrence and delayed malignancy. Transitional forms are possible. To form a clearer nosological outline of the SFT, it is necessary to accumulate clinical observations. A case of a giant meningioma of the posterior cranial fossa, which recurred 18 years after total removal at a 5-year annual control, is presented. Light microscopy of both primary and recurrent tumors revealed fibrous meningioma (WHO GI). Immunohistochemically revealed diffuse overexpression of CD34 and CD99. Determining the expression of the STAT6 protein was not technically possible. This case is regarded as a meningioma of the posterior surface of the pyramid of the temporal bone, growing into the cavity of the IV ventricle, with late recurrence without malignancy, with specific immunohistochemical profile.

[The study of mRNA expression profiles of main cell function regulator genes in unchanged colonic mucosa from healthy donors]. / Issledovanie profilei ékspressii mRNK genov, uchastvuiushchikh v reguliatsii osnovnykh kletochnykh funktsii v neizmenennom épitelii tolstoi kishki u zdorovykh donorov.

A comparative analysis of molecular genetic phenotypes of mucous membrane cells in five anatomical regions of the colon in a group of healthy donors was conducted by comparing mRNA expression profiles of 62 genes involved in the regulation of vital cellular function. We used 181 biopsy samples of morphologically unchanged colonic mucosa, obtained from the colon (ascending, transverse-colon, descending, sigmoid) and rectum sections during prophylactic colonoscopy of 58 donors with no colon pathology. The mRNA levels for 62 genes involved in the regulation of apoptosis, proliferation, transcription, differentiation, cell-cell adhesion, and immune response were assessed by RT-PCR. Statistically significant differences were found for the molecular phenotypes of five sections of the colon. The results of the study can serve as a basis for creating a reference database (values of expression profiles), developing methods of differential diagnostics and screening of various pathologies of the colon.

Human immunoglobulin light chains lambda form amyloid fibrils and granular aggregates in solution.

Myeloma nephropathy is a disorder characterized by deposition of monoclonal immunoglobulin light chains in the kidneys. The chains deposited form either amyloid fibrils or granular (amorphous) aggregates. Distinct molecular mechanisms leading to the formation of different aggregate types in kidney of patients with multiple myeloma are poorly understood. Here we describe the self-association kinetics of human monoclonal immunoglobulin light chains lambda (GRY) isolated from urine of a patient with multiple myeloma. Under physiological conditions, the isolated light chain exists predominantly in a form of covalent dimer with apparent molecular mass of 50.1 kD. Spectral probe binding, analytical gel filtration, Western blot analysis, and electron microscopy indicate that GRY dimer aggregation occurs via two different pathways producing either amyloid fibrils or amorphous aggregates depending on microenvironment. Incubation of GRY (25 microM) for 4-14 days at 37 degrees C in phosphate buffered saline (PBS), pH 7.0, or in PBS containing urea (0.8 M), pH 6.5, leads to amyloid fibril formation. Under electron microscopy, the fibrils show unbranched thread-like structures, approximately 60-80 x 1000 A in size, which can bind thioflavin T and Congo Red. GRY maintained in acetate buffer, pH 3.5, forms granular aggregates. The structure of GRY oligomers formed during the early stage of amyloid fibril formation (1-4 days) has been examined by means of protein cross-linking with homobifunctional reagents. These oligomers are predominantly trimers and tetramers.

Thermodynamic, conformational and functional properties of the human C1q globular heads in the intact C1q molecule in solution.

Thermodynamic. conformational and functional properties of the human C1q globular heads (hgC1q) were studied with the experimental approaches, which allow investigating these properties in the intact hC1q molecule in solution. Surprisingly, the scanning calorimetry data reveal a low level of cooperativity of interactions between the hgC1q A, B and C domains even at a neutral pH area. Ionization of His residues due to acidification of the medium at the pH range from 6 to 5 or the chemical modification of His residues completely abolishes the cooperative interactions between the domains without significant effect on their conformation. The thermodynamic data provide evidence that the hgC1q module is composed of three structurally independent A, B and C globular domains characterized by the practically identical thermal stability and very similar enthalpy of melting. The spectroscopic studies and modification with 2-oxy-5-nitrobenzylbromide (ONBB) indicate that Trp residues in the hgC1q A and C domains are accessible to the solvent that has been confirmed by the hgC1q crystal structure solved and refined to 1.9 A. The modification of Trp residues significantly affects the complement-dependent cytotoxicity without noticeable effect on the hC1q conformation. These data provide evidence that Trp residues are the components of immunoglobulin-binding sites both in the hgC1q A and C domains.