Molecular Factors of Cytokine-Dependent Activation of T Cells in Pulmonary Tuberculosis.

The parameters characterizing antituberculous immune response at the stage of cytokinedependent activation of T cells were analyzed in 90 patients with pulmonary tuberculosis before etiotropic therapy. Immunophenotyping of T cells for IL-12Rß2, WSX-1, and gp130 surface markers and T-bet intracellular transcription factor was carried out after specific IL-12/IL-27 induction of cells in vitro. An increase in the counts of CD3(+)T-bet(+), CD3(+)IL-12Rß2 (+), and CD3(+)WSX-1(+)gp130(+) cells and the level of T cells with high expression of WSX-1 inhibitory molecule (CD3(+)WSX-1(hi+)gp130(-) and CD3(+)WSX-1(hi+)gp130(+)) was detected. The type of disorders in the inductive stage of antituberculous immune response did not depend on the clinical form of disease.

[Dysembryogenesis in hereditary nephritis]. / O priznakakh disémbriogeneza pri nasledstvennom nefrite

In 75 children with hereditary nephritis, in 27 ones with hematuric form of acquired nephritis and in 55 parents dysplastic symptoms were investigated. A high differential and diagnostic value of disembriogenetic stigmata for hereditary nephritis is demonstrated. It is considered that connective tissue stigmata are one of the symptoms of hereditary nephritis. Some genetic and ontogenetic aspects of displastic symptoms formation in this case are discussed.

[Current ideas of hereditary nephropathies]. / Sovremennye predstavleniia o nasledstvennykh nefropatiiakh.

The paper describes a number of hereditary nephropathies, including hereditary nephritis (Alport's syndrome), the most common genetically determined renal disease, in the context of recent genetic studies. The specific features of tuberous sclerosis, a systemic disease inherited in a monogenic manner are outlined. Dysmetabolic nephropathy with oxalate-calcium crystalluria is presented as an example of multifactorial pathology.

[Viral antigens in kidney biopsies of children with glomerulonephritis]. / Virusnye antigeny v bioptatakh pochechnoi tkani u detei s glomerulonefritom.

A relationship between clinical forms of glomerulonephritis and incidence of viral antigens in renal tissue was revealed: Hepatitis B virus antigens (HBsAg) are more frequently detected in the glomeruli in the patients with nephrotic glomerulonephritis, Herpes simplex antigens are detected in the glomeruli in mixed glomerulonephritis, and cytomegaloviral and Herpes simplex antigens are detected in the epithelium of the proximal canaliculi in patients with hematuric glomerulonephritis. No correlations between the persistence of Herpes simplex type 1, cytomegalovirus, and HBsAg in the renal tissue were detected. HBsAg is detected in the renal tissue mainly in the children without free HBsAg in the blood serum. This may be indicative of an important role of specific immune complexes in the pathogenesis of glomerulonephritis associated with hepatitis B viral infection. The results point to an appreciable contribution of a persistent viral infection to the progress of glomerulonephritis.

[HB viral infection in kidney diseases in children]. / HB-virusnaia infektsiia pri zabolevaniiakh pochek u detei.

A total of 142 children aged 2-15 years with different nephropathies, among them 94 children with glomerulonephritis (GN), 26 children with pyelonephritis and 22 children with oxalate nephropathy, were examined. The diagnosis was histologically confirmed in 36 children. Mesangial proliferative GN was detected in 22 patients and membrane proliferative GN, in 14 children. The presence of the markers of HBV infection (HBsAg, anti-HBs and anti-HBc total immunoglobulins, anti-HBc IgM) was detected in the sera of all patients by the enzyme immunoassay. As the result of this examination, essential changes in the distribution of different markers of HBV infection in children with nephropathies were detected. The combination of HBsAg with anti-HBc IgM proved to be the most characteristic feature of patients with the nephrotic syndrome; this was indicative of active HBV infection, and in patients with the mixed form of GN this combination occurred twice as frequently. The established correlation between the activity of HBV infection and the severity of the course of GN made it possible to suggest the participation of HBV in the pathogenesis of GN. This suggestion was indirectly confirmed by a higher detection rate of HBsAg and anti-HBc IgM in patients with the membrane proliferative form of GN.

[The incidence of detecting HB viral infection in the families of patients with kidney diseases]. / Chastota vyiavleniia HB-virusnoi infektsii v sem'iakh bol'nykh s zabolevaniiami pochek.

A total of 33 families were surveyed with a view to determine the presence of viral hepatitis B markers in persons with diagnosed renal diseases. In all patients markers of hepatitis B virus infection (HBsAg, anti-HBs antibodies, anti-HBc total and IgM antibodies) were determined in the enzyme immunoassay. Those families in which examinees with renal pathology were found to have markers of hepatitis B virus infection exhibited a high level of contamination with hepatitis B virus. A high proportion of examinees with viral hepatitis B was established in the families where mothers were found to have markers of hepatitis B virus infection. These facts indicate that everyday contacts play an important role in the transmission of the virus. The study points out that in the family foci of hepatitis B virus infection non-manifest or slightly manifest forms of this infection are mainly registered.

[Course and outcome of nephropathies of structural renal dysembryogenesis]. / Techenie i iskhod nefropatii pri strukturnom pochechnom dizémbriogeneze.

The authors elucidate the role played by structural renal dysembryogenesis in the development, progress and outcome of nephropathies. Based on an analysis of mainly morphobiopsies of the kidneys in 298 patients aged 2.5 to 15 years a high incidence of renal dysembryogenesis is shown as an independent disease entity and as combined with acquired nephropathies. This provides basis for regarding structural deficiency of the kidneys as predisposing factor to the development of immune or microbial inflammation. The long-term (up to 18 years) observation over children with the most frequently occurring variant of renal dysembryogenesis, hypoplastic dysplasia, made it possible to define the main clinico-laboratory characteristics and outcome of the pathology determined by a high rate of the formation of chronic renal failure.

[Health status of children born to women with renal pathology]. / Sostoianie zdorov'ia detei, rozhdennykh zhenshchinami s patologiei pochek.

The children born to mothers suffering from glomerulonephritis, pyelonephritis and hereditary nephritis were followed up for 4-5 and more years. This allowed a conclusion about a considerable rate of the birth of children with pathology of the urinary system organs (USO) and with diseases of other organs which were diagnosed for the first time at the age of 3-10 years as a result of goal-oriented investigations. The groups of the children born to women with renal diseases were marked by a high perinatal lethality studied by means of retrospective questionnaire. As for the structure of the USO diseases, the children manifested the predominance of the disease patterns associated with dysembryogenesis at the organ (anatomic abnormalities), tissue (dysplasia of the renal tissue) and at the cellular levels (metabolic nephropathies). In children born to women with hereditary nephritis, USO pathology was of the same kind and occurred only in the form of hereditary nephritis, which corresponds to the concepts of monogenously inherited pathology. The demonstration during pregnancy of a considerable rate of the environmental effects capable of exerting a damaging action on the embryonal development of children born to women with glomerulo- and pyelonephritis suggests a concomitant genesis of USO diseases in children born to mothers suffering from renal diseases. The authors discuss measures aimed at the prevention or reduction of the incidence of USO pathology in children as well as at the recognition of pathologies in children born to women with renal diseases at the predisease stage.

[The first experience in Russia of using DNA diagnosis in Alport's syndrome in a family with a unique morphological picture of the kidney lesion]. / Pervyi v Rossii opyt ispol'zovaniia DNK-diagnostiki pri sindrome Al'porta v sem'e so svoeobraznoi morfologicheskoi kartinoi pochechnogo porazheniia.

Clinicomorphological findings are reported for two children from families with hereditary predisposition to hematuria characterized by early occurrence of chronic renal insufficiency, neurosensory hypoacusis, congenital ocular abnormalities inherited by sex-linked dominant type. Light microscopy of nephrobiopsies revealed diffuse mesangial proliferation in both children. Final diagnosis of Alport's syndrome was feasible only on molecular-genetic level after polymerase chain reactions had identified mutation in collagen type 4 alpha-5-chain gene on a long arm of X-chromosome in genotypes of both patients and their mothers. Genetical, clinical, morphological, evolutional and diagnostic aspects of Alport's syndrome are reviewed.

[The first experience of using membranotropic agents in the treatment of the nephrotic syndrome]. / Pervyi opyt ispol'zovaniia membranotropnykh sredstv v lechenii nefroticheskogo sindroma.

To treat children suffering from the nephrotic syndrome, use was made of the membrano-stabilizing agents: zaditen that also has an antiallergic action; dimephosphon, a membrano-stabilizer and immunomodulator. The basis for differentiated use of the drugs was formed by the examination data which enabled one to identify the signs of atopy in children with the hormone-dependent nephrotic syndrome, marked signs of the instability of cellular membranes and different immunologic deviations in children with the hormone-resistant variety of the nephrotic syndrome. During zaditen treatment, the majority of the children with the hormone-resistant nephrotic syndrome manifested an appreciable decrease of the process activity; in some cases, including those with hormone dependence, the treatment with prednisolone could be reduced. In part of the children with the hormone-resistant nephrotic syndrome, the treatment with dimephosphone resulted in a decrease of proteinuria, reduced the instability of cellular membranes, and improved the immunologic parameters.

[Hormonal interactions and glucocorticoid receptors in patients with the nephrotic syndrome]. / Gormonal'nye vzaimodeistviia i gliukokortikoidnye retseptory u bol'nykh s nefroticheskim sindromom.

As many as 27 children aged 6 to 15 years with morphologically verified nephropathies were examined. Four variants of changes in the thyroid status, characteristic of children with different variants of nephrotic syndrome were distinguished: 1) biochemical signs of primary hypothyroidism, 2) biochemical signs of secondary hypothyroidism, 3) low content of T3, 4) dysfunction of the hypophyseal and thyroid system. It is shown that the low level of steroid receptors, thyroid hormones that the low level of steroid receptors, thyroid hormones (T3 and T4) and cortisol is typical of children with the signs of renal dysplasia. It is assumed that superaddition under such conditions of immune glomerulopathy (glomerulonephritis and nephrotic syndrome) gives rise to the resistance to the treatment with glucocorticoids.

[The modern concepts of hereditary nephritis]. / Sovremennye predstavleniia o nasledstvennom nefrite.

The authors describe the results of modern studies into the problems of genetics, clinical picture, prognosis and prospects of the treatment of inherited nephritis. It is assumed that at the basis of inherited nephritis there lies generalized impairment of the basal membranes, which is determined by mutation of X chromosome that codes the structure of the chains of the fourth fraction of collagen. The phenotypic heterogeneity of the disease is accounted for by mutation of different alleles in a solitary locus. The clinical characteristics of inherited nephritis without hypoacusis and Alport's syndrome in inbred and outbred families is provided as are specific features of the disease evolution. The results and efficacy of kidney transplantation in patients with inherited nephritis in the phase of chronic renal failure are discussed.

[Current concepts of oxalate nephropathies (clinical and population studies)]. / Sovremennye predstavleniia ob oksalatnykh nefropatiiakh (klinicheskie i populiatsionnye issledovaniia).

The paper presents the results of clinical and laboratory examination made in 3 groups of children: populational, hospital and control (a total of 176 patients). The children were diagnosed to have variants of dysmetabolic nephropathy (DN) which had become a problem not only for urolithiasis-endemic regions, but also for the Middle Russia. The study involving characterization of cytomembranes, renal tissue biopsy allowed conclusion on nonspecific DN symptoms. Obligatory symptoms were those of OCC, microhematuria and/or mild proteinuria, changes in cytomembranes, weak tubular function, tubulo-interstitial changes. DN genesis is thought multifactorial, involving genetic predisposition, biochemical defects, ecological hazards.

[Ecopathology of the kidneys and individual sensitivity to heavy metal salts]. / Ekopatologiia pochek i individual'naia chuvstvitel'nost' k soliam tiazhelykh metallov.

Investigations performed in the region contaminated with heavy metal salts revealed high prevalence of renal diseases in children. The test for blood polymorphic proteins indicated signs of genetic predisposition to renal damage. Greater occurrence in the population with econephropathy of a rare allele of transferrin C3 may be the cause of enhanced oxidative-radical processes in renal cells. Individual sensitivity of children to heavy metal salts assessed by leukocytolysis and high incidence of somatic mutations to determine T-lymphocyte microclones deficient by HGPRT may help in specification of the affections detected in the regions contaminated with heavy metal salts.

[Nephropathies in a region contaminated by heavy metal salts and the possibilities for therapeutic and prophylactic measures]. / Nefropatii v regione, zagriaznennom soliami tiazhelykh metallov, i vozmozhnosti lechebno-profilakticheskikh meropriiatii.

The study of the population in the region contaminated with heavy metal salts has revealed high incidence of nephropathies even in preschool children manifesting initially in the majority of cases with hematuria. All the patients had the signs of urinary dysembryogenesis and marked membranopathological process. Long-term exposure to even small doses of heavy metals is supposed to cause nephropathy. Urinary disease arose more frequently in those genetically predisposed to renal and urinary tract affections. Because urolithiasis is a frequent result of dismetabolic nephropathy in endemic regions, it is advisable to perform active monitoring of children with environmental nephropathy using membrane-stabilizing measures. Optimal for these purpose could be xidifon. Further studies are needed to elucidate the problem of rapid elimination of heavy metals with chelating agents.

[Plasmapheresis in the combined therapy of progressive forms of glomerulonephritis]. / Plazmaferez v kompleksnoi terapii progressiruiushchikh form glomerulonefrita.

29 patients aged 6-16 with glomerulonephritis lasting 4-5 years received multimodality treatment with plasmapheresis as a component. The majority of the patients suffered from primary glomerulonephritis in mesangio- or membrano-proliferative morphological variants. Previous long-term conventional therapy (prednisolone, cytostatics, anticoagulants and antiaggregation drugs) failed. The test course comprised 1-3 plasmapheresis sessions (centrifuge method on [symbol: see text] apparatus), cyclophosphamide or maintenance methyl-prednisolone pulse therapy, heparin and curantil. One-third of the patients achieved remission lasting from 5 months to 3 years, in the other one-third the improvement was as short as 2-4 weeks, and the last one-third appeared non-responders. Improvement of clinical indices occurred in parallel with trends to reduction in the levels of CIC, IgG, B-lymphocytes, T-helpers, inhibition of lymphocyte succinate dehydrogenase activity, better phagocytosis. No complications which may prohibit plasmapheresis use in glomerulonephritis were observed. Adjuvant plasmapheresis use in glomerulonephritis treatment needs further studies.