Medico-genetic study of the population of Uzbekistan. VII. Variability of hereditary pathology in 4 regions of Khorezm province

Medical-genetic study was carried out in the population of Khorezm province (population size above 200 000 persons). Hereditary pathology was ascertained among families having two or more members affected with chronic non-infectious diseases. 155 families with 348 members affected with hereditary diseases were registered. The most frequent were autosomal recessive diseases (55 nosological forms in 104 families with 271 affected), then followed the autosomal dominant conditions (10 nosological forms in 21 families with 53 affected). The less frequent was X-linked recessive pathology (6 forms in 12 families with 20 affected). The main part of cases of autosomal recessive pathology were found in separate families and were not observed during previous medical-genetic studies in Uzbekistan. Three autosomal recessive conditions are probably new forms of hereditary pathology. The important role of assortative matings in manifestation of rare autosomal recessive genes in Uzbek population is discussed.     

Prevalence of hereditary pathology in Altai Republic

Medical genetic study of the population of Altai Republic (Russia) has been performed. The population sample comprises 203 148 subjects, including 59 196 Altaians, 134 972 Russians, and 8980 Kazakhs. For each nosological group, the loads of Mendelian pathology with different modes of inheritance and their prevalence rates in urban and rural populations have been determined. Thirty-six autosomal dominant (AD) diseases have been found in a total of 121 subjects, with hereditary syndromes being the most prevalent. Autosomal recessive (AR) pathology is represented by 24 diseases found in 158 subjects, with metabolic disorders being the most prevalent; and X-linked pathology, by four diseases in nine subjects. The prevalence rate has been calculated for each nosological form in the district where it has been found. The loads of AD, AR, and X-linked pathologies in the urban population were, respectively, 2.98 and 9.62 per 1000 people and 0.56 per 1000 men in Altaians; 0.86 and 0.94 per 1000 people and 0.23 per 1000 men in Russians; 0.34 and 1.16 per 1000 people in Kazakhs. In the rural population, the genetic load has been calculated for each district. The spectrum of hereditary pathology in the populations studied is described.     

Relative role of selective migration and pathology in the formation of genetic structure

It is shown that elective migration, with respect to polymorphic loci genotypes, and their association with pathology affect unequally formation of genetic structure features of the population analysed. The correlative role of two processes mentioned is more or less specific, with respect to every concrete locus: the elective migration and the pathology have unidirectional impact in all groups, which leads to maximum dynamics of genotypes in groups with different duration of dwelling under extreme conditions (AcP, Pp loci). These processes act as antagonists, preserving constant genotype frequency (AK locus). Genotype frequency dynamics is mainly determined by the elective migration (Rh locus) or the pathology (PGD locus). The correlative role of the elective migration and the pathology is often unequal in groups with different duration of dwelling under the North-East conditions, as applied to concrete locus (GLO-1, PGM1), though the elective migration participates in groups with comparatively small dwelling-term in the North and the pathology has more influence as this term increases. The problem of genetic aspects of human adaptation is under discussion.     

Medico-genetic study of the residents of the Kostroma province. XI. Diversity of hereditary pathology in Kostroma

The diversity of hereditary pathology in Kostroma was studied. An attempt was made to classify all isolated cases by genetic and clinical analysis. 57 nosological forms of autosomal dominants, 41 autosomal recessive and 14 X-linked recessive disorders were found. The analysis of marriage distances in the whole population and in the families of the probands was carried out. The spectra of hereditary pathology in Kostroma and Kostroma Province were compared. The sources of the load of hereditary pathology in Kostroma are discussed.     

Mitochondrial damage and dysfunction in traumatic brain injury

The enduring cognitive deficits and histopathology associated with traumatic brain injury (TBI) may arise from damage to mitochondrial populations, which initiates the metabolic dysfunction observed in clinical and experimental TBI. The anecdotal evidence for in vivo structural damage to mitochondria corroborates metabolic and physiologic dysfunction, which depletes substrates and promotes free radical generation. Excessive calcium pathology differentially disrupts the heterogeneous mitochondrial population, such that calcium sensitivity increases after TBI. The ongoing pathology may escalate to include protein and DNA oxidation that impacts mitochondrial function and promotes cell death. Thus, in vivo TBI damages, if not eliminates, mitochondrial populations depending on injury severity, with the remaining population left to provide metabolic support for survival or repair in the wake of cellular pathology. With a considerable understanding of post-injury mitochondrial populations, therapeutic interventions targeted to the mitochondria may delay or prevent secondary cascades that lead to long-term cell death and neurobehavioral disability.     

Prevalence of hereditary pathologies in residents of the Kirov Province]

Medical-genetic study was carried out in the population of Kirov Province (population size about 120.000). 203 families with 334 affected with hereditary disorders were registered. The correctness of pathology classification for the inheritance type was confirmed by segregational analysis. The load of hereditary diseases in the population was: 1.25 +/- 0.06 for autosomal dominant, 1.37 +/- 0.07 for autosomal recessive and 0.22 +/- 0.06 for X-linked recessive disorders. It is suggested that variability in the values of the load of autosomal recessive disorders is determined to the large extent by genetic structure of the population.     

Laboratory medicine needs higher profile with medical students,MDs, pathologists say.

Laboratory medicine is a troubled specialty these days, buffeted by the conflicting pressures of reduced funding for more work and a declining physician population. A consortium of laboratory physicians has produced a report on the future of pathology and laboratory medicine, which explores the problems facing the specialties and some potential solutions. Raising the profile of laboratory medicine among medical students and eventual unification of pathology and the various arms of laboratory medicine are among the suggested solutions.     

An aeromonad epidemic in the brown trout (Salmo trutta L.)

The pathology and bacteriology of an aeromonad epidemic in the spawning population of brown trout ( Salmo trutta L.) of the freshwater Loch Leven, Kinross, Scotland, is described, together with estimates of its quantitative effect on the stock of trout.     

The role of the Notch pathway in healthy and osteoarthritic articular cartilage: from experimental models to <Emphasis Type="Italic">ex vivo</Emphasis> studies

Osteoarthritis is the most prevalent form of arthritis in the world. With the progressive ageing of the population, it is becoming a major public health problem. The involvement of certain signaling pathways, such as the Notch pathway, during cartilage pathology has been reported. In this review, we report on studies that investigated the expression pattern of the Notch family members in articular cartilage and the eventual involvement of this pathway in the modulation of the physiology and pathology of chondrocytes. Temporal and/or spatial modulation of this signaling pathway may help these cells to synthesize a new functional extracellular matrix and restore the functional properties of the articular cartilage.     

Medico-genetic studies of the Kostroma oblast population. X. Load of hereditary diseases in the population of Kostroma

Medical-genetic study of the population of Kostroma (the total size of the population analysed approx. 250,000) was carried on. The load of hereditary diseases in the population (per 1000) was 0.75 for autosomal dominant, 0.49 for autosomal recessive and 0.17 for X-linked recessive disorders. Significant differences in the prevalence of autosomal recessive hereditary disorders between rural populations and the population of Kostroma were observed. The dependence of the load of autosomal recessive pathology on random inbreeding was shown for the whole Kostroma province.     

Pathogen persistence in infectious pathology

Problems of microorganism's persistence in infectious pathology are discussed in this work. Persistence of bacteria as the form of procaryotic and eucaryotic cells symbiosis unlimitedly long coexistence is considered. Questions of the microbial evolution formed in constant collision of the infective agent with macroorganism defense mechanisms are discussed. The spectrum of known mechanisms bacterial survival in conditions of an infected organism is considered. For discussion the problem of microbial persistence it is offered to include as model alongside with an independent cell, a microbial population as complex self-organizing system--the original "superorganism" having universal chemical regulation, the determining density of a population and equation of some physiological functions. It is offered to consider the host colonization resistance as a phenomenon of general biology directed on maintenance of a microecological homeostasis as a result of symbiotic interactions of an organism and it autochthonous microflora with the "key" kinds of biotope protection. The use of persistence characteristics of microorganisms is proved as a target in conditions of intermicrobial interaction of its allochthonous and autochthonous microflorae. Practical value of such approach in infectious pathology is shown.     

Genetic epidemiological study of Bashkortostan Republic: The effect of genetic structure of population on the load of monogenic hereditary diseases

Here we present the data obtained during medical genetic examination of the population of five districts of Bashkortostan Republic (Burzyanskii, Baimakskii, Abzelilovskii, Salavatskii, and Arkhangelskii) populated with 168050 persons including 135748 Bashkirs. The study involved all the population of the districts including each ethnic group and was conducted according to standard protocol developed in the Laboratory of Genetic Epidemiology, Medical Genetic Research Center, Russian Academy of Medical Sciences. Based on segregation analysis, the values of prevalence rates of the major types of Mendelian pathology (AD, AR, and X-linked diseases) was calculated in five regions of the Republic as well as for Bashkirs alone. Significant differences in the prevalence rates of AD and AR pathologies between individual districts, in particular upon division in rural and urban population, was observed. The prevalence rates comparison of monogenic hereditary pathology among Bashkirs compared to other previously examined populations have shown that the patterns of the hereditary disease load in the inspected districts of Bashkortostan were similar to that observed in the population of some districts in Udmurtia, Marii El and Chuvashiya. Russian European populations have shown significantly lower load of hereditary diseases. Correlation analysis of local inbreeding, endogamy and prevalence rates of AD and AR pathologies has shown that development of hereditary diseases load is significantly affected by gene drift.     

Genetic and clinical study of a family with abnormal hemoglobin Hb D Punjab 121 beta Glu----Gln

A second case of discovery of HbD Punjab in Russian population is reported. Abnormal hemoglobin was found in women with recurrent fetal wastage. The possibility of casual relationship between the presence of HbD Punjab and this type of pathology was rejected on the basis of detailed clinical and genetical investigation.     

Prevalence of Hereditary Pathology in Altai Republic

Medical genetic study of the population of Altai Republic (Russia) has been performed. The population sample comprises 203148 subjects, including 59196 Altaians, 134972 Russians, and 8980 Kazakhs. For each nosological group, the loads of Mendelian pathology with different modes of inheritance and their prevalence rates in urban and rural populations have been determined. Thirty-six autosomal dominant (AD) diseases have been found in a total of 121 subjects, with hereditary syndromes being the most prevalent. Autosomal recessive (AR) pathology is represented by 24 diseases found in 158 subjects, with metabolic disorders being the most prevalent; and X-linked pathology, by four diseases in nine subjects. The prevalence rate has been calculated for each nosological form in the district where it has been found. The loads of AD, AR, and X-linked pathologies in the urban population were, respectively, 2.98 and 9.62 per 1000 people and 0.56 per 1000 men in Altaians; 0.86 and 0.94 per 1000 people and 0.23 per 1000 men in Russians; 0.34 and 1.16 per 1000 people in Kazakhs. In the rural population, the genetic load has been calculated for each district. The spectrum of hereditary pathology in the populations studied is described.     

Potential mechanisms and implications for the formation of tau oligomeric strains

The culmination of many years of increasing research into the toxicity of tau aggregation in neurodegenerative disease has led to the consensus that soluble, oligomeric forms of tau are likely the most toxic entities in disease. While tauopathies overlap in the presence of tau pathology, each disease has a unique combination of symptoms and pathological features; however, most study into tau has grouped tau oligomers and studied them as a homogenous population. Established evidence from the prion field combined with the most recent tau and amyloidogenic protein research suggests that tau is a prion-like protein, capable of seeding the spread of pathology throughout the brain. Thus, it is likely that tau may also form prion-like strains or diverse conformational structures that may differ by disease and underlie some of the differences in symptoms and pathology in neurodegenerative tauopathies. The development of techniques and new technology for the detection of tau oligomeric strains may, therefore, lead to more efficacious diagnostic and treatment strategies for neurodegenerative disease.     

Tumors of the testis and midgut in aging flies

In order to better understand the pathology of aging in the fly we used standard techniques of surgical pathology to conduct a histologic screen of approximately 1400 adult male flies ranging in age from one to five weeks. We found that flies developed tumors of the testis and gut and that the incidence of these tumors increased with age. Aging is the greatest single risk factor for the development of tumors in the general human population. Here, we show for the first time that aging is also a risk factor for tumor development in flies. These findings in one of the world's best-studied and genetically tractable model organisms open up opportunities for deeper experimental exploration of the relationship between aging and neoplasia.     

Cellular immune responses are essential for the development of Helicobacter felis-associated gastric pathology.

The bacteria Helicobacter pylori is a major human pathogen that infects over half of the world's population. Infection initiates a series of changes in the gastric mucosa, beginning with atrophic gastritis and leading in some patients to peptic ulcer disease, mucosa-associated lymphomas, and gastric adenocarcinoma. Although this cascade of events clearly occurs, little is known about the role of the host immune response in disease progression. We have utilized the C57BL/6 Helicobacter felis mouse model to critically analyze the role of the adaptive immune response in the development of Helicobacter-associated gastric pathology. Infection of B and T cell-deficient RAG-1-/- mice or T cell-deficient TCRbetadelta-/- mice with H. felis resulted in high levels of colonization, but no detectable gastric pathology. Conversely, infection of B cell-deficient microMT mice resulted in severe gastric alterations identical with those seen in immunocompetent C57BL/6-infected mice, including gastric mucosal hyperplasia and intestinal metaplasia. These results demonstrate that the host T cell response is a critical mediator of Helicobacter-associated gastric pathology, and that B cells and their secreted Abs are not the effectors of the immune-mediated gastric pathology seen after H. felis infection. These results indicate that in addition to specific Helicobacter virulence factors, the host immune response is an important determinant of Helicobacter-associated disease.     

Ensuring the sanitary and epidemiological safety of the child population in Russia

The summarizing data on new negative tendencies in the state of health of children and adolescents in Russia are presented. The two-fold increased proportion of children with chronic pathology and disability is noted. Special attention is drawn to a high level of child morbidity in diseases of respiratory organs, especially bronchial asthma. Measures ensuring the sanitary and hygienic safety of the child population in Russia, including improvements in the organization of nourishment, vaccinal prophylaxis, working out hygienic criteria and health-saving technologies, have been analyzed. Priorities in the work aimed at the liquidation of negative tendencies in the health of the child population in Russia have been determined.     

Medico-genetic characteristics of the Udegey in the Maritime Territory

The results of medico-genetical investigation of Udegey population of Primorski territory were described. These studies were carried out by Moscow Institute of Medical Genetics. Marriage structure of population investigated was studied which demonstrated a low level of inbreeding and high frequency of intranational marriages. The structure of population morbidity was characterized by the absence of accumulation of specific hereditary pathology. Data obtained are of great interest for comparative analysis of populations of a different marriage structure.