Frequency of lethal chromosomal and genome mutations in man

According to the cytogenetic studies chromosome anomalies frequency in 209 children who died in the perinatal period was 7.2 per cent. These cases were found to consist of 8 autosome trisomies, 5 anomalies in sex chromosome system, 1 case of triploidy and 1 case of structural reorganization. Accounting for the elimination of chromosome anomalies during the early periods of fetus development, the frequency of chromosome lethals was shown to be 6.44 X 10(-2) in registered pregnancies and 54.89 X 10-2 in conceptions.     

Del(1)(q22-q25) syndrome. Cytogenetics and phenotype

A male infant is described with dysmorphology of the head and face, neck, extremities and genitalia, as well as growth and mental retardation and with the de novo interstitial deletion of the proximal segment of the long arm of chromosome 1-del (1) (q22-q25). Comparison of the phenotypic characteristics of this patient with those of previously described patients with similar deletion confirms the existence of the proximal 1q deletion syndrome.     

Miniature endplate currents of muscle fibers from rat diaphragm during galantamine-induced acetylcholinesterase inhibition

Miniature endplate currents (MEPC) were recorded in muscle fibers of rat diaphragm using voltage clamp technique during acetylcholinesterase (AChE) inhibition induced by various concentrations of galantamine. Their amplitude and time course began to increase at a galantamine concentration of 3.16·10^–8 g/ml. Increased concentrations of galantamine produced a greater effect. Maximum amplitude and time course were reached at a concentration of 10^–6 g/ml. The input resistance of muscle fibers increased under the effects of galantamine. In all cases MEPC fell exponentially. At a concentration of 10^–5 g/ml galantamine produced a curarelike effect; amplitude and time course of decay increased to a lesser extent than at a concentration of 10^–6 and the decay in MEPC became biphasic. Following washout of galantamine (10^–5 g/ml) the time course of MEPC first rose, then fell, returning to the initial level in 3 h, and decay again became exponential. Changes in MEPC parameters under the effects of different concentrations of galantamine and washout were closely correlated. A positive correlation was found between the time course of decay and MEPC amplitude both in the presence and absence of AChE inhibition. It is postulated that the functional importance of synaptic AChE in repressing the postsynaptic action of acetylcholine is limited and that parameters of postsynaptic response may therefore be used to evaluate its action.A. A. Ukhtomskii Institute of Physiology, A. A. Zhdanov State University, Leningrad. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 607–614, September–October, 1985.     

Phenotype and "critical segments" of chromosomes during partial aneuploidy for chromosome 4 in man

Computerized analysis of sparse matrix, based on the list of involved organs, body parts, extremities, function etc. (total item number about 600) was performed for different cytogenetically identified anomalies of human chromosome 4 (35 cases of 4p-, 32 cases of 4p+, 39 cases of 4q-, 39 cases of 4q+; both published and original data were used). For each of the four types of partial aneusomy, 4 specific enough groups of traits were revealed which had been found in 50% of respective patients, at least. Such "nuclei" of traits were highly similar to those given in comprehensive modern manuals. However, 4p- and 4q- could only be classified as strictly enough delineated chromosomal syndromes. The 4(p14-pter) region was found to be the most likely crucial segment for the Wolf-Hirschhorn syndrome.     

Base-Calling Algorithm with Vocabulary (BCV) Method for Analyzing Population Sequencing Chromatograms

Sanger sequencing is a common method of reading DNA sequences. It is less expensive than high-throughput methods, and it is appropriate for numerous applications including molecular diagnostics. However, sequencing mixtures of similar DNA of pathogens with this method is challenging. This is important because most clinical samples contain such mixtures, rather than pure single strains. The traditional solution is to sequence selected clones of PCR products, a complicated, time-consuming, and expensive procedure. Here, we propose the base-calling with vocabulary (BCV) method that computationally deciphers Sanger chromatograms obtained from mixed DNA samples. The inputs to the BCV algorithm are a chromatogram and a dictionary of sequences that are similar to those we expect to obtain. We apply the base-calling function on a test dataset of chromatograms without ambiguous positions, as well as one with 3–14% sequence degeneracy. Furthermore, we use BCV to assemble a consensus sequence for an HIV genome fragment in a sample containing a mixture of viral DNA variants and to determine the positions of the indels. Finally, we detect drug-resistant Mycobacterium tuberculosis strains carrying frameshift mutations mixed with wild-type bacteria in the pncA gene, and roughly characterize bacterial communities in clinical samples by direct 16S rRNA sequencing.     

Synthesis and antioxidant activity of azole derivatives of hemin

New derivatives of proto- and deuterohemin IX containing tri- and tetrazole rings were synthesized and characterized. A pronounced antioxidant activity was found for these compounds in the Fe(II)/ascorbate-dependent system of lipid peroxidation in murine liver homogenates.     

A system for assessment of chemical substances on mutagenicity in man: general priniciples, practical recommendations and further elaboration]

As a basis of the suggested test-system, the following conditions are observed: 1) the economy of fulfilment in a short time; 2) the analysis of gene and chromosome mutations in germ and somatic cells; 3) the evaluation of mutagenic effects of not only substance, but also of the products of its metabolism; 4) including in the system only the tests which give the minimal variability between separate experiments; 5) the evaluation of dose-effect relationship. The practical scheme of testing is divided into two parts: a screening and a complete one. The screening programme consists of two tests: a) a test on microorganisms with a metabolic activation in vitro; b) a cytogenetic analysis of bone marrow of mammals. The complete programme of testing includes 4 tests: a) a test on microorganisms with a metabolic activation in vitro and in vivo; b) a test of dominant lethal mutations on mammals; c) a cytogenetic analysis of bone marrow of mammals; d) a cytogenetic analysis in the culture of human lymphocytes. There are good reasons for the principles of selection of substance for testing according to the screening and complete programme: population occurence, economic (or medical) significance, information about relative chemicals showing mutagenic, carcinogenic and teratogenic effect. In the group of chemicals which are to be tested according to the screening programme, such ones can be included: industrial chemicals, phosphoorganic insecticides, drugs which are taken by a limited group of patients. The group of chemicals which are to be tested according to the complete programme consists of the following ones: pesticides, food additices, widespread drugs, the chemicals of the group 1, if during one of the tests of the screening programme a genetic effect is detected. At the genetic risk estimation it is advisable to keep to the following rule: a positive effect, identified in any object of the system must in the direct meaning extrapolate on men. The quantitative evaluation of the mutagenic danger of a chemical can be determined by the increase of the spontaneous level of mutations in the test-object on the basis of an average dose and exposition of the given chemical in the human population. Those chemicals are subject to the quantitative evaluation, which have shown a mutagenic activity during any of the test-objects; they are also widespread and because of their social or economic value can not be replaced or excluded from taking. From the point of view of genetics any substance with a mutagenic activity is dangerous and must be prohibited from using or replaced by any other non-mutagenic chemical, or limited by the contact of persons of non-reproductive age. As a temporary measure from a hygienic point of view, it is recommended to evaluate this chemical as especially mutagenic and prohibit or limit its using, when its average population dose produces 1/10 or more increase of the spontaneous level of mutations.     

Ignition of a combustible gas mixture by a high-current electric discharge in a closed volume

Results are presented from experimental studies and numerical calculations of the ignition of a stoichiometric CH₄: O₂ gas mixture by a high-current gliding discharge. It is shown that this type of discharge generates an axially propagating thermal wave (precursor) that penetrates into the gas medium and leads to fast gas heating. This process is followed by an almost simultaneous ignition of the gas mixture over the entire reactor volume.     

Frequency of chromosome anomalies in children dying in the perinatal period]

348 different tissues were sampled for cultivation from 300 infants perinatally, died: a) from 118 fetuses, died at the antenatal period, 143 samples of four types of tissues were taken (kidney type -27, skin type-10, gonad type-74, blood type -32); b) 72 samples of blood and 13 samples of gonad were taken from 75 fetuses died at the intranatal period; c) 120 samples (blood type -86, gonad type -86) were taken from 97 newborn infants, died at the early neonatal period. Positive results of the growth of cultures were found in 46% (15.4% -from antenatally dead fetuses, 71.8% -intranatal deaths of infants, 64.2% -early mortality of the newborn). Among the 22 antenatally dead infants 3 appeared to have chromosome anomalies (13.6%); 1) 47, XY, +22; 2) 69, XXX; 3) 46, XX/46, XY. Among 61 intranatally dead infants 3 were found to have karyotype anomalies (4.9%): 1) 47, XX, +18; 2) 47, XY, +21;3) 46, XX/46, XY. 5 (6.5%) of the 77 newborn, dead in the first days after parturition, had the anomalies of the following types: 1) 45, XO; 2) 47, XYY; 3) 47, XY; +13; 4) 47, XY, +21; 5) 46, XX, 13q-. The total frequency of chromosome anomalies among 160 perinatally dead infants was 6.9%.