[Herpes simplex virus infection of human spermatozoa correlates with decreased frequency of blastocyst formation and frequency of embryo implantation during in vitro fertilization].

We have conducted a comparative analysis of developing human embryos in the course of in vitro fertilization (IVF) as a method of sterility treatment of two groups of patients: herpes simplex virus (HSV) was detected in the fraction of motile sperm of male partners in group I (n = 28) and no HSV was found in sperm in group II (n = 103). W assessed number of fertilized ova, embryos during cleavage, and blastocysts as well as such parameters as frequency of implantation and frequency of pregnancy in IVF cycles. It was established that the presence of HSV in spermatozoa did not affect the efficiency of fertilization or cleavage of zygotes.

[Identification of mutations in the arylsulfatase B gene in Russian mucopolysaccharidosis type VI patients].

Molecular genetic analysis of the gene for arylsulfatase B (ASB) was conducted in ten Russian patients with type VI mucopolysaccharidosis (MPS VI) of different severity. Eight exons from the translated region of the ASB gene of each patient were amplified and sequenced using the nonradioactive method. Fourteen mutant alleles were identified in the sample studied by means of DNA analysis; 13 of them had not been described before.

[Information and retrieval diagnostic system for inherited metabolic diseases].

The paper analyzes a procedure for construction and practical use of an information and retrieval diagnostic system (IRDS) for inherited metabolic diseases (IMD) in the context of an automatic working place for consulting genetics. An IRDS structure for IMD is proposed, which involves the following functional elements: 1) a genetic register; 2) an inherited metabolic disease database (IMDD); 3) a special module for searching for the probable range of diagnoses; 4) an archive; 5) a special model for statistical analysis of the clinical polymorphism of IMD. The full insight into each nosological entity (n = 316) as part of IMD IRDS is gained by using a set of catalogues, such as a catalogue IMD classes (n = 22), that of IMD clinical symptoms and signs (n = 1215); that of IMD biochemical markers (n = 934); a list of all symptoms and signs for each nosological entity; that of major diagnostic signs for each nosological entity.

[Program for diagnosis and prevention of inherited metabolic diseases of cellular organelles].

A programme for diagnosis and prevention of lysosomal, peroxisomal, and mitochondrial [respiratory chain diseases (RCD)] diseases was developed on clinical, biochemical, and molecular approaches. The authors made postnatal diagnosis was made in 674 patients from 516 families and prenatal diagnosis in 124 fetuses in 94 families at risk. DNA analysis of mutant alleles in the mucopolysaccharidoses (MPS) I, II, and VI revealed 14, 13, and 4 new mutant alleles in IDS, ASB, IDUA genes, respectively.

[Monogenic hereditary diseases in Gorno-Mariĭskiĭ district of Mariĭ El republic].

The population of Gornomariiskii raion, Marii El Republic, primarily made up of mountain Marii, was subjected to medical genetic examination. The size of the entire population is 54853. Estimates of hereditary pathology in urban and rural populations of the raion were obtained.

[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].

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.

[Expression of lysosomal enzymes in pregnancy].

Activities of 6 lysosomal enzymes in leukocytes and 3 enzymes in blood serum were studied in pregnant women. Only activity of beta-D-glucosidase was not altered within all the pregnancy of I-III trimesters, while activity of all the other enzymes studied was distinctly increased to the third trimester. Use of the data obtained in prenatal diagnosis of lysosomal storage diseases is discussed.

[Use of an information-search diagnostic system for recognizing acute hereditary metabolic diseases with early lethal outcomes].

An information retrieval diagnostic system for hereditary metabolic diseases that are characterized by acute progression and early fatal outcome was developed. The system includes four databases: a list of nosological forms (n = 152), a list of clinical symptoms and characteristics (n = 1094), clinical portraits of every disease, and a list of biochemical characteristics (n = 1072). The system describes each disease as follows: clinical phenotype, etiology, genetics, pathogenesis, biochemical phenotype, paraclinical investigations, differential diagnosis, treatment, and prevention.

[Biochemical genetics of peroxisomal disorders].

This review is the first one dealing specifically with a class of peroxisomal disorders that remain virtually unfamiliar to Russian medical genetic consultants and pediatricians. Data are presented that concern classification, genetics, characterization of clinical and biochemical phenotype, prevention, and therapy of 18 nosological units included in the class of peroxisomal disorders. Problems of general biological significance are reviewed, which can be solved using peroxisomal disorders as a valuable experimental model.

[Analysis of hydroxypyridine cross-links of collagen from human rib cartilage].

Ion-paired reversed-phase high performance liquid chromatography (HPLC) has been used for the analysis of the content of mature collagen crosslinks--hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) in biopsy specimens of human rib cartilage from healthy donors (n = 14) and patients with inherited diseases of the connective tissue complicated with funnel chest (n = 17). Analysis of normal tissues reveal the presence of LP (alongside with HP) in embryonal rib cartilage. LP has been found in the rib cartilage of 4 out of 6 patients with funnel chest (FC) associated with Ehlers-Danlos syndrome (EDS); with no signs of this pathology detected in individuals with isolated FC.

[The determination of fragments of the N-terminal propeptide of collagen type III in human blood serum by sandwich immunoenzyme solid-phase analysis].

Solid-phase sandwich enzyme immunoassay has been developed to determine Col1+Col2 fragments of a N-terminal propeptide of Type III collagen in human serum, using polyclonal antibodies. The procedure allows one to obtain a sensitivity of 0.5 ng of native antigen and a linearity in the range of 0.

[A program of prevention of hereditary lysosomal diseases in the USSR].

The organization of genetic counselling for the families of patients with lysosomal storage diseases (LSD) was based on the interaction of the genetic counselling units of this country with a laboratory of inherited metabolic diseases of the National Research Center of Medical Genetics, USSR AMS. All the patients from 705 families at risk were examined using biochemical techniques and methods of somatic cell genetics. In total the loci differentiation was performed for 309 patients with mucopolysaccharidoses, glycoproteinoses, mucolipidoses, sphingolipidoses and other LSD.

[Fractures as a possible complication of osteoporosis in women in the climacteric].

The author has analyzed the incidence of bone fractures in women of various age groups, residents of the Cheryomushki District of Moscow in 1988-1989, using the records of the traumatologic service of the district and the census data. The incidence of bone fractures was the highest in women aged over 45 (up to 2.5%), and was the higher the older the woman grew, 2/3 of all the fractures occurred in women aged 45-64.

[Isolation and characteristics of hexosaminidase A and activator protein from human kidney].

Hexosaminidase A (HA) was isolated from human kidney and purified to an electrophoretically homogeneous state. The purification procedure included ion-exchange chromatography on DEAE-cellulose, gel filtration on Toyopearl HW-55 and chromatofocusing on PBE 94 (enzyme yield 26.6%, 1133.

[Biochemical diagnosis of mucosulfatidosis].

Biochemical anomalies in proband involved alterations in the spectrum of glycosaminoglycans (GAG) excreted with urine as well as a decrease in activity of lysosomal sulfatases (arylsulfatases A and B, heparan-N-sulfatase) in homogenates of leukocytes and cultivated fibroblasts. In healthy parents of the proband activity of the sulfatases was lower than in control donors but higher as compared with the proband. Antenatal diagnostics of mucosulfatidosis was carried out in fetus during the repeated pregnancy.

[Study of the genetic heterogeneity of gangliosidoses in humans].

A study of genetic heterogeneity of GM1 and GM2 gangliosidoses was performed using a wide set of cultured fibroblast lines of patients with leukodystrophies. In addition to commonly used methods for enzyme diagnosis and for isozyme fractionating, following assays were developed for locus and allele differentiation: loading tests with 3H-GM1 and 3H-GM2, analytical chromatofocusing and activity determination of activator protein for GM2.

[The use of loading tests with labeled GM1-ganglioside for differential diagnosis of GM1-gangliosidosis].

Kinetics of GM1-ganglioside accumulation was studied in fibroblast cultures from patients with various forms of GM1-gangliosidosis using the labelled native substrate GM1-ganglioside isolated from human brain. A shape of accumulation curves in the plot was shown to depend on GM1-ganglioside concentration in a medium in juvenile form of the disease. Use of a number of the fibroblast strains and optimal concentration of GM1-ganglioside 20 micrograms/ml enabled to carry out allele differentiation of the juvenile form of GM1-gangliosidosis from infantile and normal forms, thus suggesting that the loading tests could be applied to pre- and postnatal diagnosis of GM1-gangliosidosis.

[Molecular heterogeneity of proteoglycan aggregates of human hyalin cartilage in normal conditions and in systemic bone dysplasia].

Components of proteoglycan aggregates of human hyalin cartilage were studied under conditions of normal state and in some forms of osteochondrodysplasia. Extraction of uronic acids and protein from the tissue, amount of fractions and electrophoretic mobility of proteoglycan monomers, rations protein/glycosaminoglycans, keratan sulfate/chondroitin sulfate, a level and type of sulfatation as well as molecular mass of chondroitin sulfate, amino acid composition of rod protein, heterogeneity of binding proteins (concerning their isoelectric points and molecular masses) and immunoreactivity of protein moiety in proteoglycan aggregates were studied in rib cartilage, knee joint and ala ossis ilii. Structural parameters of proteoglycan aggregates proved to be dissimilar and depended on cartilage localization and age of the donors.

[Prenatal diagnosis of hereditary lysosomal diseases].

Prenatal diagnosis was carried out in 10 families suffering from lysosomal diseases: Tay-Sachs disease--5 families, Sandhoff disease--1 family, GM1-gangliosidosis--1 family and Hunter disease--3 families. Diagnosis of Tay-Sachs disease was excluded in fetuses of two families, Sandhoff disease--in one family, GM1-gangliosidosis--in one family, Hunter disease--in two families. Tay-Sachs disease was found in two fetuses and in one neonate.

[Fluorometric titration in a method of metabolic cooperation in the differential diagnosis of mucopolysaccharidoses].

Content of intracellular glycosaminoglycans (GAG) was studied in a procedure of metabolic cooperation by means of the polysaccharides fluorimetric titration in order to differentiate between various types of mucopolysaccharidoses and to establish prenatal diagnosis of these diseases. The procedure involved electrostatic interaction of fluorochrome 4,6-diamidino-2-phenylindol. HCl with GAG's.

[Identification of GM2-gangliosidosis using an in vitro loading test].

A test system was developed for identification of conventional and atypical forms of GM2-gangliosidoses. The test system was based on a loading test using a culture of the patients skin fibroblasts. Gangliosides, isolated from small samples (several mg) of various tissues, were identified by means of thin-layer chromatography on silica gel plates.