<Emphasis Type="Italic">In vivo</Emphasis> study of dihydroquercetin genotoxicity

Genotoxic properties of dihydroquercetin were in vivo studied by the method of chromosome aberrations counting and DNA-comet assay. Dihydroquercetin administered repeatedly (5 times, 0.15 and 1.5 mg/kg) or once in doses of 15, 150, and 2000 mg/kg induced no DNA damages in mouse bone marrow, blood, liver, and rectal cells. Single administration of this preparation in doses of 1.5 and 150 mg/kg and 5-fold administration in a dose of 1.5 mg/kg had no effect on the level of chromosome aberrations in mouse bone marrow cells. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 309–312, March, 2008     

Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR

Ophthalmological and molecular genetic studies were performed in a consanguineous family with individuals showing either retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive) inheritance of allelic defects, linkage analysis positioned the causal gene at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR gene involved in Stargardt's disease (STGD) and age- related macular degeneration (AMD). We completed the exon-intron structure of the ABCR gene and detected a severe homozygous 5[prime] splice site mutation, IVS30+1G->T, in the four RP patients. The five CRD patients in this family are compound heterozygotes for the IVS30+1G- >T mutation and a 5[prime] splice site mutation in intron 40 (IVS40+5G- >A). Both splice site mutations were found heterozygously in two unrelated STGD patients, but not in 100 control individuals. In these patients the second mutation was either a missense mutation or unknown. Since thus far no STGD patients have been reported to carry two ABCR null alleles and taking into account that the RP phenotype is more severe than the STGD phenotype, we hypothesize that the intron 30 splice site mutation represents a true null allele. Since the intron 30 mutation is found heterozygously in the CRD patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime] splice site partially functional. These results show that mutations in the ABCR gene not only result in STGD and AMD, but can also cause autosomal recessive RP and CRD. Since the heterozygote frequency for ABCR mutations is estimated at 0.02, mutations in ABCR might be an important cause of autosomal recessive and sporadic forms of RP and CRD.      

Organization, expression and polymorphism of the human persyn gene

Persyn is a recently identified member of the synuclein family with a distinct pattern of expression during pre- and postnatal development of the mouse peripheral and central nervous systems. As with other synucleins, persyn is believed to be involved in the pathogenesis of human neurodegenerative diseases. However, in contrast to other synucleins, high levels of persyn mRNA expression were also found in advanced breast carcinomas, suggesting an involvement of the encoded protein in breast tumour progression. Here we have used an antibody specific to human persyn to demonstrate that the level of this protein is increased in ageing cerebral cortex and in breast tumours. We cloned, characterized and sequenced the human persyn genomic locus and localized it to the long arm of chromosome 10 in the q23.2-q23.3 region. Sequence information was used to search for specific mutations in the protein coding regions of persyn mRNA and the persyn gene in breast tumours and tumour cell lines. No tumour-specific mutations were found, but two linked polymorphisms in the coding region were detected, both in mRNA and exons III and IV of the gene. These results suggest that development of breast tumours correlates with overexpression of the wild-type persyn protein. Detailed characterization of the human persyn locus is important for further studies of the involvement of persyn in neurodegeneration and malignancy.      

A clinico-serological study of Lyme disease in the northwestern USSR

To reveal clinical signs and symptoms of Lyme's disease in the population of the endemic area, clinical and serological examinations of 416 persons have been performed. Preliminary screening, using indirect immunofluorescence, has revealed in 230 persons (group I) antibodies to the agent of the disease at a titre of greater than or equal to 1:20. Group II consisted of 186 patients who had not been serologically examined. Lyme's disease diagnosed in most cases by erythema annulare was found in 8 patients from group I and 12 patients from group II, all in all in 20 patients (4.8%) of all the patients examined. No typical late signs and symptoms of Lyme's disease have been observed. High antibody titres (greater than or equal to 1:80) were found in 24% of patients in group I and in 4.1% of patients in group II. Different clinical and immunological courses of borreliosis in the endemic area are discussed.     

Present-day classification and nomenclature of rheumatic fever

The paper presents a new classification of rheumatic fever, which has been adopted by the Plenary Session of the Association of Rheumatologists of Russia in May 2003. This classification envisages the abandonment of the term "rheumatism" in its former interpretation. The term "acute rheumatic fever" (ARF) appears to be more justified since it makes a physician elucidate its association with Group A streptococcal infection of the throat and prescribe antibiotics for eradication of this infection in its acute period (primary prophylaxis) and for prevention of repeated attacks (secondary prophylaxis). The current interpretation of the clinical syndromes/symptoms and laboratory parameters that enter into diagnostic criteria for ARF is presented. There are 2 types of outcome of the disease. In case of recovery, we are dealing with the complete regression of the clinical symptomatology of ARF, normalized laboratory parameters and no residual changes. Chronic rheumatic diseases of the heart are considered to mean a disease characterized by a cardiac valvular lesion as postinflammatory marginal fibrosis of valvular leaflets or cardiac abnormality (failure and/or stenosis) developed after prior ARF. Emphasis is laid on the significance of evidence of Group A streptococcal infection that precedes the development of the disease. Examples of clinical diagnosis in accordance with the terminology of the International Classification of Diseases, the 10th edition, are given in the paper.     

Clinical value of soluble adhesion molecules in systemic scleroderma

The aim of the trial was to study clinical significance of estimation of cell adhesion soluble molecules (CASM) in scleroderma systematica (SS). Quantitation of CASM VCAM-1, ICAM-1 and R-selectin was made with enzyme-immunoassay (R&D System kits, USA) in 38 patients with SS (11 with limited SS and 27 with diffuse SS). The levels of VCAM-1, ICAM-1 and R-selectin was elevated in 30 (79%), 17 (45%) and 20 (53%) patients, respectively. Mean values of VCAM-1 and ICAM-1 in patients were significantly higher than in healthy donors. R-selectin was also higher but insignificantly. A mean CASM level and a relative number of patients with elevated count of CASM in patients with diffuse and limited forms of SS did not differ. In 15 patients with active (progressive) course of the disease the level of VCAM-1 was significantly higher than in patients with chronic (non-progressive) course of SS while concentrations of ICAM-1 and R-selectine were almost the same. Thus, SS patients have elevated levels of CASM. CASM VCAM-1 concentration is the most sensitive marker of SS activity compared to other CASM.     

Soluble receptors of TNF-alpha with molecular mass 55 kDa in rheumatoid arthritis: clinical role

To evaluate clinical implications of the serum level of soluable receptors of tumor necrosis factor alpha (TNFa) with molecular mass 55 kDa (rTNF-55R) in rheumatoid arthritis, serum levels of rTNF-55R and rTNF-75R were measured with the use of radioimmunoassay in 76 RA patients, 38 donors and in 25 RA patients, 10 donors, respectively. RESULTS: Elevated serum level of rTNF-55R was recorded in 55.3% RA patients. This level correlated with basic clinical and laboratory parameters of RA, the disease activity, values of DAS indices. It is concluded that a serum level of rTNF-55R adequately reflects clinico-laboratory activity of RA and its measurement can be used for assessment of RA activity and treatment efficiency.     

Synovial membrane in the early stage of rheumatoid arthritis: clinico-morphological comparisons

AIM: To evaluate implications of pathomorphological alterations of synovial membrane at an early stage of rheumatoid synovitis (RS) for further course of rheumatoid arthritis (RA) and prognosis of the disease. MATERIAL AND METHODS: 92 new cases of RA (22 males, 70 females, mean age 31.1 +/- 10.5 years, mean duration of RA 5.99 +/- 3.27) subjected to puncture biopsy of the synovial membrane of the knee joint in 1967-1983. At admission to hospital 54.3, 45.7 and 29.3% patients had polyarthritis, mono- and oligoarthritis, rheumatoid factor, respectively. The RA diagnosis was confirmed in 68 (73.9%) patients, 26 (28.3%) of them were observed for 1-2 years, 42 (45.6%)--for 11.8 +/- 8.8 years, on the average. In 9 (9.8%) patients the diagnosis was changed for Bechterew's disease (n = 6), polymyositis (n = 1), rheumatism (n = 1), reactive arthritis (n = 1), 15 (16.3%) patients with seronegative oligoarthritis of large joints were lost for follow-up. Now (the beginning of 2002) synovial biopsies were investigated in "blind" mode by one morphologist (using the semiquantitative method) and compared to clinical and x-ray evidence. RESULTS: The most frequent changes were the following: proliferation of lining synovial cells (82.6%), lymphoid infiltration (64.1%), angiomatosis (60.9%), fibrinoid changes (60.9%). Accumulation of large amounts of macrophages and lymphocytes in the infiltrate was detected in RA significantly more often than in non-RA patients. Among 68 patients with definite RA morphological picture in biopsies obtained from the knee joints with manifest synovitis (69.1%) and from clinically intact joints (30.9%) was practically the same. The most important morphological sign was angiomatosis associated with early polyarticular involvement, early development of joint erosions and early disability (patients with marked angiomatosis were disabled after 4 years of illness, on the average, without angiomatosis--after 11 years). Statistically significant associations of parameters of RA development with other histological signs of synovitis were not detected. CONCLUSION: Angiomatosis in the synovial membrane occurs at early (including preclinical) stages of RA and, as a manifestation of angiogenesis, is an unfavorable prognostic factor of early polyarticular involvement, early development of joint erosions and early disability. Synovial biopsy at an early stage of arthritis is of differential-diagnostic value and helps to define a long-term outcome. Therefore, synovial biopsy of the knee joint must be in the list of standard examinations of patients with early RA.