[Inhibition of Invasive Properties of Murine Melanoma by Bovine Pancreatic DNase I In Vitro and In Vivo].

After a long pause, the accumulation of data on the involvement of tumor-specific DNA and extracellular DNA in metastasis has again placed enzymes with deoxyribonuclease activity in the focus of the search for antitumor and antimetastatic drugs. In this work, the ability of bovine pancreatic DNase I to reduce the invasive potential of B16 melanoma has been investigated in vitro and in vivo. It was found that DNase I had a cytotoxic effect on B16 melanoma cells (IC50 ≈ 10^(4) U/mL). At the same time, significantly lower doses of DNase I (10^(2)-10^(3) U/mL) inhibited the migratory activity of melanoma cells in vitro, causing a decrease in the distance of cell front migration and in the area of scratch healing 48 h after the enzyme addition, as well as reducing the rate of cell migration. In mice with B16 metastatic melanoma, intramuscular administration of DNase I in the dose range of 0.12-1.20 mg/kg resulted in a two- to threefold decrease in the number of surface lung metastases and caused nonspecific antigenic immune stimulation.

Morphological changes in human skin melanoma treated by high-energy pulsed neodymium laser radiation.

PURPOSE: The neodymium (Nd) laser irradiation has been successfully applied to the treatment of slightly elevated skin melanoma. At the same time the histologic aspects of such a treatment have not been precisely investigated. The aim of this study was to retrace the histological features in human primary cutaneous melanomas after 1060 nm high energy mono pulsed Nd laser treatment in the dynamic healing of the affected tissues. METHODS: Histologic analysis of cutaneous melanomas irradiated by Nd laser was carried out. Tissue specimens were taken before and immediately after exposure to laser and 1 hour, and 1, 2 and 3 days after wards. Also the wounds that appeared after the scab fell off and the scars formed following laser irradiation were also the subject of histologic analysis at 2, 4 and 6 months post-treatment. RESULTS: The Nd laser irradiation caused coagulation necrosis of melanoma, epidermis and dermis with skin appendices and superficial layers of subcutaneous fatty tissue. Foci of laser destruction were characterized by strict locality and efficient separation from the adjacent tissues, by the presence of stasis, thrombosis and coagulation of blood and lymphatic vessels. There was an increase of lymphocytes, macrophages and histiocytes in the area damaged by laser as well as in wounds and scars. CONCLUSION: The pulsed Nd laser induces acute photothermal damages of melanoma tissue, which differs from the usual thermal lesions and the most critical difference of the effect of this modality is gain of immunocompetent cells in the affected tissue after laser beam application.

Inhibitors of Epstein-Barr virus reproduction--ribonucleosides of 3-substituted 1,2,4-triazino[5,6-b] [1,4] benzothiasines.

Studying of antiviral effect of condensed triazine derivatives--3-oxo- triazinobenzothiazine (the preparation No 1), its ribonucleoside (the preparation No 3) and ribonucleoside of its 3-thio-analogue (the preparation No 2) on reproduction of Epstein-Barr virus (EBV) in lymphoblastoid Raji cells is reported in present work. The cytotoxic action of these preparations on test cells was determined and CC50 index was 125 microg/ml for the preparation No 1, for preparation No 2 - 625 microg/ml, and for preparation No 3 - 750 microg/ml. Antiviral activity of the preparations was tested by inhibition level of accumulation of viral DNA in the cell culture, and effective concentration (EC50 index) was determined for each preparation. EC50 constituted 1 microg/ml for each triazinobenzothiazines. Selectivity index (SI) was 125 for preparation No 1, for preparation No 2 - 625, and for preparation No 3 - 750. The obtained results of studying of triazinobenzothiazines as inhibitors of EBV-infection support their high antiEBV activity and can be interesting for further investigations.

Organochlorine pesticide and trace metal monitoring of Russian rivers flowing to the Arctic Ocean: 1990-1996.

Information is presented on the concentrations of organochlorine pesticides (HCHs and DDT residues) and trace metals (Fe, Cu, Zn and Ni) in waters of 15 large Russian rivers flowing to the Arctic Ocean during 1990-1996. Estimates of the corresponding annual fluxes are made. Other contaminants (Hg, Pb, Cr, Mn, beta-HCH and dihydroheptachlor) were examined briefly. Concentration data are presented as averaged annual means for each of the seven years with the ranges, standard deviations and numbers of samples. Also given are data on locations, the methods of analysis and limited quality assurance data. Data on discharges to the Northern Seas for the more frequently monitored contaminants are given for rivers accounting for >70% of the total northerly flows. Scaled-up fluxes to account for unmonitored rivers as well are given for each sea; totals over the period were: Fe, 1452; Cu, 15; Zn, 59 (x 10(3) t yr(-1)); alpha-HCH, 25; gamma-HCH, 44 (t yr(-1)). Ni was monitored at too few rivers to estimate its total Russian flux. The fluxes for the HCHs considerably exceed previous estimates and indicate that the Arctic Ocean is not in balance as much as was previously believed.

Contaminants in the Canadian Arctic: 5 years of progress in understanding sources, occurrence and pathways.

Recent studies of contaminants under the Canadian Northern Contaminants Program (NCP) have substantially enhanced our understanding of the pathways by which contaminants enter Canada's Arctic and move through terrestrial and marine ecosystems there. Building on a previous review (Barrie et al., Arctic contaminants: sources, occurrence and pathways. Sci Total Environ 1992:1-74), we highlight new knowledge developed under the NCP on the sources, occurrence and pathways of contaminants (organochlorines, Hg, Pb and Cd, PAHs, artificial radionuclides). Starting from the global scale, we examine emission histories and sources for selected contaminants focussing especially on the organochlorines. Physical and chemical properties, transport processes in the environment (e.g. winds, currents, partitioning), and models are then used to identify, understand and illustrate the connection between the contaminant sources in industrial and agricultural regions to the south and the eventual arrival of contaminants in remote regions of the Arctic. Within the Arctic, we examine how contaminants impinge on marine and terrestrial pathways and how they are subsequently either removed to sinks or remain where they can enter the biosphere. As a way to focus this synthesis on key concerns of northern residents, a number of special topics are examined including: a mass balance for HCH and toxaphene (CHBs) in the Arctic Ocean; a comparison of PCB sources within Canada's Arctic (Dew Line Sites) with PCBs imported through long-range transport; an evaluation of concerns posed by three priority metals--Hg, Pb and Cd; an evaluation of the risks from artificial radionuclides in the ocean; a review of what is known about new-generation pesticides that are replacing the organochlorines; and a comparison of natural vs. anthropogenic sources of PAH in the Arctic. The research and syntheses provide compelling evidence for close connectivity between the global emission of contaminants from industrial and agricultural activities and the Arctic. For semi-volatile compounds that partition strongly into cold water (e.g. HCH) we have seen an inevitable loading of Arctic aquatic reservoirs. Drastic HCH emission reductions have been rapidly followed by reduced atmospheric burdens with the result that the major reservoir and transport agent has become the ocean. In the Arctic, it will take decades for the upper ocean to clear itself of HCH. For compounds that partition strongly onto particles, and for which the soil reservoir is most important (e.g. PCBs), we have seen a delay in their arrival in the Arctic and some fractionation toward more volatile compounds (e.g. lower-chlorinated PCBs). Despite banning the production of PCB in the 1970s, and despite decreases of PCBs in environmental compartments in temperate regions, the Arctic presently shows little evidence of reduced PCB loadings. We anticipate a delay in PCB reductions in the Arctic and environmental lifetimes measured in decades. Although artificial radionuclides have caused great concern due to their direct disposal on Russian Shelves, they are found to pose little threat to Canadian waters and, indeed, much of the radionuclide inventory can be explained as remnant global fallout, which was sharply curtailed in the 1960s, and waste emissions released under license by the European reprocessing plants. Although Cd poses a human dietary concern both for terrestrial and marine mammals, we find little evidence that Cd in marine systems has been impacted by human activities. There is evidence of contaminant Pb in the Arctic, but loadings appear presently to be decreasing due to source controls (e.g. removal of Pb from gasoline) in Europe and North America. Of the metals, Hg provokes the greatest concern; loadings appear to be increasing in the Arctic due to global human activities, but such loadings are not evenly distributed nor are the pathways by which they enter and move within the Arctic well understood.

Prevalence of rheumatoid arthritis in circumpolar native populations.

OBJECTIVE: To compare the prevalence of rheumatoid arthritis (RA) in related, but geographically separate, indigenous circumpolar populations. METHODS: Cases were identified by community survey in Russia and by examination of cases located through arthritis registries, a computerized patient information database, and query of local health care providers in Alaska. All possible cases were verified by examination and application of the American College of Rheumatology 1987 criteria. RESULTS: The prevalence rates of RA (age standardized to US population of 1980) varied from 0.62% in the Alaskan Yupik to 1.78% in the Alaskan Inupiat. The Russian Chukchi rate was 0.73% and that of the Siberian Eskimo was 1.42%. CONCLUSION: The Alaskan Yupik Eskimo and Chukchi natives had prevalence rates of RA within the usual range of North American Caucasian groups, in contrast to the Russian Siberian Eskimo and the Alaskan Inupiat Eskimo of the Barrow region, whose high rates approached those of unrelated North American native groups living in very different environments. The Alaskan Inupiat rate was significantly higher than that of the Alaskan Yupik (OR = 2.51, 95% CI 1.25-5.07; p = 0.013), but statistical inferences are limited in the Russian study populations by the small case numbers. The high prevalence rates probably have a genetic basis, although an environmental influence cannot be excluded.

Spondylarthropathic diseases in indigenous circumpolar populations of Russia and Alaska.

AIMS: To compare the nature and frequency of spondylarthropathy in geographically separated but genetically related populations with a high prevalence of HLA-B27. METHODS: Using a common questionnaire and disease criteria, cases were ascertained through cross-sectional community surveys in Russia and by examination and study of possible cases identified through rheumatic disease registries and the Native Health Service's computerized patient care data system in Alaska. RESULTS: Similar overall prevalences of spondyloarthropathy (2.0-3.4%) and a similar spectrum of disease were found, including reactive arthritis, ankylosing spondylitis and undifferentiated spondylarthropathy. Psoriatic arthritis was very rare. CONCLUSION: No predisposition to one particular form of spondyloarthropathy was observed; genetic and microbial settings for a spectrum of disease were present. Among adults positive for the presence of HLA-B27 the prevalence of all types of spondylarthropathies was estimated to be 4.5%, all populations combined, and the prevalence of AS was estimated to be 1.6%.

Spondyloarthropathies in circumpolar populations: II. Characterization of the populations.

For epidemiologic studies of spondyloarthropathy in circumpolar peoples of Chukotka, Russia and Alaska, we gathered demographic, physical and laboratory data to provide a background for evaluating and comparing factors that may influence susceptibility and clinical expression of disease. The study groups included the Chukchi and Siberian Eskimo of Russia and the Inupiat and Yupik Eskimo of Alaska. The 4 groups were remarkably similar in population structure, educational attainment, mean hemoglobin concentrations and frequency of the Class I histocompatibility antigen HLAB27. The Alaskan and Chukotkan groups were similar in mean height, but the Alaskans had higher body weights and significantly greater body mass indexes, probably a reflection of a shift away from traditional lifestyle and diet. Differences in the frequencies of ABO and MN blood group antigens were also apparent, with higher frequencies of blood group M in the Alaskan populations, particularly the Inupiat.

Spondyloarthropathies in circumpolar populations: I. Design and methods of United States and Russian studies.

Parallel epidemiologic studies of spondyloarthropathy in aboriginal circumpolar populations were carried out by U.S. and Russian investigators. These complementary studies used the same data collection instrument and disease criteria to facilitate comparisons. During three expeditions to Siberia, Russian investigators collected cross-sectional data from four settlements of Eskimos and Chukchi Indians on the Chukotka peninsula for a study of disease prevalence. U.S. researchers collected cross-sectional data from Eskimos in four Alaskan regions for studies of prevalence and longitudinal data for studies of clinical manifestations, natural history, disease impact, and health care utilization. The aims of these studies were to describe the spectrum of spondyloarthropathy in these populations, and to lay the groundwork for investigations of the role of specific genetic and environmental factors in the pathogenesis and expression of disease. These studies were carried out with a minimum disruption to the native people.

HLA class II and HLA-B27 oligotyping in two Siberian native population groups.

It was the purpose of this study to better define the frequency of HLA-B27 subtypes and HLA class II alleles among indigenous populations from the eastern tip of the Chukotka Peninsula of Siberia, Russia, which have higher frequencies of HLA-B27 (40%) and spondyloarthropathies (2%) than Caucasian populations and test the hypothesis that these populations are more closely related to Orientals. Siberian Eskimos and Chukchi residing in four coastal villages on the Chukotka Peninsula inhabited by Siberian Eskimos and Chukchi people were examined using oligotyping of the polymerase-chain reaction-amplified second and third exons of the HLA-B27 gene. HLA-class II alleles (DRB1, DQA1 and DQB1) were similarly determined. Of 88 HLA-B27 positive individuals from these villages, all had HLA-B*2705, including the four patients with Reiter's syndrome and the five ankylosing spondylitis, except one Eskimo control who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. HLA-class II typing in 70 Siberian Eskimos and 71 Siberian coastal Chukchi revealed HLA-DRB1*0401, DRB1*0802, *0901 and *1402 to account for nearly all the DRB1 alleles found in this population, similar to what has been described in Eskimos in Alaska, but different from Chinese or native Americans in the U.S. The overwhelming majority of the individuals examined had HLA-DQB1*0301, similar to what has been observed in Native Americans. The Siberian Eskimos differed from the coastal Chukchi only in the occurrence of HLA-DRB1*0701, DQA1*0201, DQB1*0201 alleles, which occurred only in the former group. These data suggest that the Chukotka population is genetically more closely related to Caucasians and native Americans and less to other Oriental populations.

HLA-B27 subtypes among the Chukotka Native groups.

The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondyloarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter's syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientalis.

Prevalence of spondyloarthropathies and HLA-B27 in the native population of Chukotka, Russia.

OBJECTIVE: We sought to determine the prevalence and nature of spondyloarthropathies (SPA) and the prevalence of HLA-B27 in the native selected circumpolar population of Chukotka, Russia. METHODS: We conducted a cross sectional study that included medical examinations and interviews of 355 of 498 (71.3%) native residents of 2 Eastern Chukotka settlements, Enmelen and Nunligran. RESULTS: Among them were 268 Chukchas, 7 Eskimos, and 80 subjects of mixed race. There were 9 subjects (2.5%) with SPA, 3 of 7 Chukchas had ankylosing spondylitis (AS) (1.1%), 2 reactive arthritis (ReA), 2 with undifferentiated SPA. Among the mixed race persons one Chukcha-Eskimo had AS, one Eskimo-Russian had psoriatic arthritis (PsA). We found a high percentage of HLA-B27 antigen in the population, 34% in Chukcha natives and 25% in mixed race. CONCLUSION: Our data complement other studies of circumpolar populations and reinforce the reported high prevalences of SPA and HLA-B27 among those populations.