[Efferent therapy in the treatment of solid tumors].

Endogenous intoxication and immune insufficiency accompany neoplastic process. Complex therapy for cancer worsens these pathologic conditions by its adverse effects (AE) and thus complicates treatment. Efferent therapy can provide continuity of antineoplastic therapy with normalization of hemostasis and decreasing the rate of AE and their intensity. Efferent therapy meaningfully increases patient's quality of life and decreases the needed drug support when used as a part of complex therapy. Proper use of efferent therapy can markedly increase efficacy of surgical treatment, radiation therapy and drug therapy.

[Systemic therapy of soft tissue sarcomas].

Soft tissue sarcomas (STS) comprise a heterogeneous group of rare malignancies from mesenchymal tissues. The biology of STS causes high aggressiveness, poor prognosis due to early development of distant metastases and limited chemotherapeutic options due to tumor resistance. The paper considers the current principles of chemotherapy for early and metastatic disease. Results of own experience of advanced STS patients' treatment are presented and discussed.

Maternal and child health statistics: Russian Federation and United States, selected years 1985-95.

This report provides comparative maternal and child health data for recent years for the Russian Federation and the United States. Statistical data for Russia are from the Ministry of Health of Russia and from Goskomstat, the central statistical organization of Russia. Information for the United States comes from various data systems of the National Center for Health Statistics as well as other parts of the Department of Health and Human Services. A background section provides a description of each country's health care system and national guidelines for maternal and child health care. This information is intended to assist the reader in interpreting the subsequent sections on various aspects of maternal and child health. The report uses tables, figures, and commentary to present information on many different health measures for mothers, infants, children, and adolescents in the two countries. Topics covered include population size, prenatal and obstetrical care, abortions, natality, breastfeeding, mortality, immunization, communicable diseases, and other morbidity measures. The commentary includes a discussion of data quality issues that affect the accuracy and comparability of the information presented. Data are provided for selected years from 1985 to 1995. When available, additional detail is provided for key subgroups of each population: for the Russian Federation, urban and rural populations; for the United States, black and white racial groups. A glossary of terms at the end of the report provides additional information on definitions and data sources and limitations.

Cold related mortalities and protection against cold in Yakutsk, eastern Siberia: observation and interview study.

OBJECTIVE: To assess how effectively measures adopted in extreme cold in Yakutsk control winter mortality. DESIGN: Interviews to assess outdoor clothing and measure indoor temperatures; regressions of these and of delayed cause-specific mortalities on temperature. Setting Yakutsk, east Siberia, Russia. SUBJECTS: All people aged 50-59 and 65-74 years living within 400 km of Yakutsk during 1989-95 and sample of 1002 men and women who agreed to be interviewed. MAIN OUTCOME MEASURES: Daily mortality from all causes and from ischaemic heart, cerebrovascular, and respiratory disease. RESULTS: Mean temperature for October-March 1989-95 was -26.6 degreesC. At 10.2 degrees C people wore 3.30 (95% confidence interval 3.08 to 3.53) layers of clothing outdoors, increasing to 4.39 (4.13 to 4.66; P<0. 0001) layers at -20 degrees C. Thick coats, often of fur, replaced anoraks as temperature fell to -48.2 degrees C. 82% of people went out each day when temperatures were 10.2 degrees C to -20 degrees C, but below -20 degrees C the proportion fell steadily to 44% (35% to 53%) at -48.2 degrees C (P<0.001), and overall shivering outdoors did not increase. Living room temperature was 17.9 (17.2 to 18.5) degrees C at 10.2 degrees C outdoors, 19.6 (18.8 to 20.4) degrees C at -20 degrees C, and 19.1 (18.6 to 19.6) degrees C at -48.2 degrees C. Mortality from all causes and from ischaemic heart and respiratory disease was unaffected by the fall in temperature. Mortality from respiratory disease (daily deaths per million) rose from 4.7 (4.3 to 5.1) to 5.1 (4.4 to 5.7) (P=0.03), but this was offset by a fall in deaths from injury. CONCLUSIONS: People in Yakutsk wore very warm clothing, and in extremely cold weather stayed indoors in warm housing, preventing the increases in mortality seen in winter in milder regions of the world. Only respiratory mortality rose, perhaps because of breathing cold air.

Causes of declining life expectancy in Russia.

CONTEXT: Russian life expectancy has fallen sharply in the 1990s, but the impact of the major causes of death on that decline has not been measured. OBJECTIVE: To assess the contribution of selected causes of death to the dramatic decline in life expectancy in Russia in the years following the breakup of the Soviet Union. DESIGN: Mortality and natality data from the vital statistics systems of Russia and the United States. SETTING: Russia, 1990-1994. POPULATION: Entire population of Russia. MAIN OUTCOME VARIABLES: Mortality rates, life expectancy, and contribution to change in life expectancy. METHODS: Application of standard life-table methods to calculate life expectancy by year, and a partitioning method to assess the contribution of specific causes of death and age groups to the overall decline in life expectancy. United States data presented for comparative purposes. RESULTS: Age-adjusted mortality in Russia rose by almost 33% between 1990 and 1994. During that period, life expectancy for Russian men and women declined dramatically from 63.8 and 74.4 years to 57.7 and 71.2 years, respectively, while in the United States, life expectancy increased for both men and women from 71.8 and 78.8 years to 72.4 and 79.0 years, respectively. More than 75% of the decline in life expectancy was due to increased mortality rates for ages 25 to 64 years. Overall, cardiovascular diseases (heart disease and stroke) and injuries accounted for 65% of the decline in life expectancy while infectious diseases, including pneumonia and influenza, accounted for 5.8%, chronic liver diseases and cirrhosis for 2.4%, other alcohol-related causes for 9.6%, and cancer for 0.7%. Increases in cardiovascular mortality accounted for 41.6% of the decline in life expectancy for women and 33.4% for men, while increases in mortality from injuries (eg, falls, occupational injuries, motor vehicle crashes, suicides, and homicides) accounted for 32.8% of the decline in life expectancy for men and 21.8% for women. CONCLUSION: The striking rise in Russian mortality is beyond the peacetime experience of industrialized countries, with a 5-year decline in life expectancy in 4 years' time. Many factors appear to be operating simultaneously, including economic and social instability, high rates of tobacco and alcohol consumption, poor nutrition, depression, and deterioration of the health care system. Problems in data quality and reporting appear unable to account for these findings. These results clearly demonstrate that major declines in health and life expectancy can take place rapidly.

The metabolic pathway collection: an update.

The Metabolic Pathway Collection from EMP is an extraction of data from the larger Enzymes and Metabolic Pathways database (EMP). This extraction has been made publicly available in the hope that others will find it useful for a variety of purposes. The original release in October 1995 contained 1814 distinct pathways. The current collection contains 2180. Metabolic reconstructions for the first completely sequenced organisms-Haemophilus influenzae,Mycoplasma genitalium,Saccharomyces cerevisiaeandMethanococcus janaschii-are all included in the current release. All of the pathways in the collections are available as ASCII files in the form generated by the main curator, Evgeni Selkov. In addition, we are offering a more structured encoding of a subset of the collection; our initial release of this subcollection includes all of the pathways inMycoplasma genitalium, and we ultimately intend to offer the entire collection in this form as well.

Fluorescence study of the conformational properties of myoglobin structure. 1. pH-dependent changes of tryptophanyl fluorescence in intact and chemically modified sperm whale apomyoglobins.

The pH-dependent fluorescence of intact sperm whale apomyoglobin (apo-Mb) containing two tryptophans at positions 7 and 14, and of apo-Mb derivatives modified on Trp7 by 2-hydroxy-5-nitrobenzyl bromide (Koshland reagent) and o-nitrophenylsulphenyl chloride, has been studied. The fluorescence of apomyoglobins modified at His residues by iodoacetamide and bromoacetate, and at the N-terminal alpha-NH2 group by methylisothiocyanate, has also been investigated. The individual fluorescent properties of both tryptophans and their contributions to the total spectrum of apo-Mb have been resolved within the pH range 2-12.5. The quantum yield of the 'buried' Trp14 (lambda max at 326 nm) is shown to be twofold higher at pH greater than 8.5 than that of the 'exposed' Trp7 (lambda max at 333 nm). At pH 8.5-5.5 the fluorescence of Trp14 diminished approximately twofold due to quenching by the ionized His residue, most probably His119. The quenching is evidently dynamic because the fluorescence lifetime is shown to be linearly proportional to quantum yield in this pH range. The fluorescence of Trp7 practically does not change between pH 5.5 and 10.0 but increases 2.5-3-fold in the pH range 5.5-4.3 while the contribution of Trp14 remains constant. The conformational changes at the N-terminal and in the region adjacent to it, as well as in the whole apo-Mb molecule in acidic, alkaline and neutral pH ranges, are considered. A relationship is revealed between conformational states of the heme crevice and the N-terminal part of apo-Mb.

Fluorescence study of the conformational properties of myoglobin structure. 2. pH- and ligand-induced conformational changes in ferric- and ferrousmyoglobins.

Tryptophanyl fluorescence of high-spin and low-spin complexes of sperm whale ferric- and ferrousmyoglobins, met-, azide- and cyanomyoglobins and deoxy-, oxy- and carboxymyoglobins has been studied in the pH range 2.5-13. The pH-dependent fluorescence of sperm whale metmyoglobin acylated at the N-terminal alpha-amino group by methylisothiocyanate and of bovine metmyoglobin, which contains invariant Trp7 and Trp14 but lacks Tyr151, have also been examined. Drastic changes in the fluorescence were registered in the acidic and alkaline pH ranges which are due to denaturation of Mb. Fluorescent and CD data indicate that at pH less than 4.5 and pH greater than 11.5 the unique spatial structure of the protein is destroyed whereas the secondary structure and integrity are essentially preserved. In all sperm whale and bovine myoglobins studied a local conformational change in the surroundings of Trp is observed which precedes alkaline denaturation. It seems to be due to deprotonation of lysine residues and breakage of the salt bridges essential for the maintenance of the native conformation of the N-terminal and the adjacent region. The parameters of this conformational transition are found to correlate with the spin state of the heme complex. However, analysis of the fluorescence behaviour of different ligand derivatives of myoglobin in the whole pH range studied enables one to conclude that the exact protein conformation depends not only on the spin state of the Fe atom but, to a greater extent, probably on the chemical nature of the ligand and its interaction with the protein groups in the heme cavity. Local conformational changes induced by the replacement of the sixth ligand or by varying pH seem to involve the same region of contacts between the A helix and GH fragment (or between the AE and GH helical complexes) though the extent of the changes may be different.

Formation of mixed hemagglutinin trimers in the course of double infection with influenza viruses belonging to different subtypes.

Chick embryo primary cultured cells were infected with influenza viruses belonging to H1, H2, H3, H5 or H7 subtypes of hemagglutinin. The cells were subjected to a single or a double infection, labelled with 14C-amino acids from 2 to 6 hours postinfection, lysed with a mixture of ionic and non-ionic detergents, and the lysates were clarified by low-speed centrifugation. The clarified lysates contained 14C-labelled hemagglutinin mostly in the form of 9S trimers, as shown by velocity sedimentation in sucrose gradients with polyacrylamide gel electrophoresis (PAGE) analysis of the gradient fractions. The lysates were immunoprecipitated with antihemagglutinin antibodies specific for one of the co-infecting viruses. The immunoprecipitates were analysed by PAGE. Cells infected separately with each virus and mixed before lysis were used as a control sample in every experiment. In the lysates of cells doubly infected with H2 and H5 influenza viruses the analysis revealed the presence of structures containing HA monomers of both viruses, whereas no such structures were revealed in the lysate of a mixture of separately infected cells. Mixed structures (most likely HA trimers containing monomers of the two co-infecting viruses) were also found in the lysates of cells doubly infected with strains belonging to H1 and H2 subtypes. No such structures were revealed when the cells were co-infected with viruses belonging to H1 and H3 subtypes or H3 and H7 subtypes. The results suggest an extensive formation of mixed HA trimers in the course of double infection with viruses belonging to closely related subtypes, whereas the formation of mixed trimers by more distantly related HA monomers does not occur or is very scarce. The identity of the mixed structures as HA trimers was confirmed by immunoprecipitation experiments with 9S structures.