[Use of the method of DNA analysis in the diagnosis of hereditary diseases].
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Biomedical subjects
Publications and source records attributed to J Bal.
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Having been confronted with a post-operative toxic shock syndrome, we made a study of European literature and were struck by the more favorable course the disease promptly took when penicillinase-resistant antibiotics were used. We suggest that a new case, based on bacteriological analysis and phagotyping of the offending organism and wound appearance, was prevented by us when immediate antibiotic treatment was given.
The construction and some properties of new hybrid plasmids which are able to replicate in both Escherichia coli and Bacillus subtilis are presented. A 5.5 Md hybrid plasmid pJP9 was constructed from pBR322 (Tc, Ap) and pUB110 (Nm) plasmids. pIM1 (7.0 Md) and pIM3 (7.7 Md) plasmids are its different erythromycin resistant derivatives. Tetracycline, ampicillin, neomycin and possibly erythromycin resistance genes are expressed in E. coli while neomycin and erythromycin resistance genes are expressed in B. subtilis. Insertional inactivation of only one gene is possible using the pJP9 plasmid as a vector in B. subtilis. However, insertional inactivation of at least two different genes can be achieved and monitored in E. coli and B. subtilis transformants in cloning experiments with PIM1 and pIM3 plasmids. Insertional inactivation of antibiotic resistance genes present in pJP9 plasmid was achieved by cloning of Streptococcus sanguis DNA fragments generated by appropriate restriction endonucleases. The pJP9 plasmid and its derivatives were found to be stable in both hosts cells.
The influence of microwaves on genetic processes in Aspergillus nidulans and Physarum polycephalum was investigated. Suspensions of organisms were exposed in the far zone to 2450-MHz waves at 10 mW/cm2 for one hour in both CW and pulsed (1 microsecond, 600 pps) fields. Spores of A. nidulans were irradiated before and during germination. No changes in survival rate or in frequency of morphological mutation were found. Polycephalum under the influence of CW microwaves incorporated 3H-Thymine into DNA at a rate five times that of controls and twice that of thermal controls. The accelerated synthesis may reflect more efficient volume heating by microwaves, or in the presence of microthermal gradients in suspensions, or field-specific influences in concern with focal or volume heating.
The blood circulation and the oxygen consumption of the tissues during general hypotensive anesthesia for stapes surgery is quantitatively studied on 40 patients. The rate of oxygen consumption of the whole body and of the tissue of an upper extremity is determined together with the rate of blood flow in that extremity. A series of other parameters such as the PaCO2 and the acid-base balance of arterial and venous blood, the blood pressure, the pulse frequency and the temperature are also measured. Most measurements are performed before premedication, after premedication and after surgery. The state of the patient in the immediate postoperative period is completely comparable with the peroperative anesthetic state. Some of the parameters mentioned above are measured also on a series of 8 normal persons at awake and at asleep state. The numerical results show clearly that the used type of general anesthesia "Protected Sleep" obeys the demands necessary for performing microsurgery of the ear in a successful way. (Acta anaesth. belg., 1980, 31, 15-27).
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Using N-methyl-N'-nitro-N-nitrosoguanidine, ultraviolet irradiation, ethyl methanesulphonate or 4-nitroquinoline-1-oxide mutagenesis and an enrichment method for the isolation of auxotrophs, 25 mutants with defects in the adA locus were obtained after screening 41,376 colonies. One of these, adA24, did not complement with any of the other adA mutants, had a very high reversion rate and had some other properties which usually characterize strains carrying nonsense mutations. All revertants of adA24 carried dominant suppressor mutations. A group of adA24 suppressors was tested for allele and locus specificity. They were found to suppress only some adA alleles, and at the same time, some mutations in the methG, methH, argB and proA loci. It is proposed that the allele specific and locus non-specific adenine suppressors are suppressors of nonsense mutations.
Simultaneous reversion of mutations in two different Aspergillus nidulans loci adA and metG was found to be due monogenic suppressor mutations. Preliminary evidence for the existance of supersuppressors in A. nidulans is presented.
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The existence of two postulated pathways of anabolic cysteine biosynthesis in Aspergillus midulans was investigated. No activities of the postulated pathway involving S-sulfocysteine as intermediate have been detected. Investigations on cyteine and methionine requiring mutants revealed independent regulation of O-acetylserine sulfhydrylase by endogeneous cysteine and methionine pools. The reaction catalysed by O-acetylserine sulfhydrylase is postulated as the only anabolic pathway of cysteine biosynthesis in A. nidulans.
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Mutations in the genes encoding different parts of phenylalanine hydroxylation system cause persistent hyperphenylalaninaemia. The most frequent form of hyperphenylalaninaemia is caused by mutations in the PAH gene. The most common variant result from defect of tetrahydrobiopterin synthase. Mutations in the PAH and PTS genes in the Polish population are presented. Genotype--phenotype correlations are discussed.
Polish CF patients were screened extensively for mutations in the CFTR gene. Screening data demonstrated a high heterogeneity of CFTR mutations in the Polish population. Total 30 different mutations were characterised in 24 exons or introns of the gene. Among them, six mutations have been reported for the first time and submitted to the CF Genetic Analysis Consortium. In addition, 15 different polymorphisms were found, including three new ones. The screening resulted in 9% increase of the detection rate of CFTR alleles in the tested population. Frequencies of two of the identified mutations (CFTRdele2,3 and 2184insA) are relatively high (2.6% and 1%, respectively) and justify their inclusion into routinely screened mutations in genetic testing of Polish CF population.
Deafness is one of the most frequent congenital hearing impairments. Knowledge of its causes will result in elimination of risk factors and applying prophylactic activities. It is recognized that about 40% of hearing impairments have genetic origin and 80% of these are autosomal recessive. Introducing molecular diagnosis to medical practice makes precise identification of hearing impairment and genetic counseling possible. The authors present results of DNA examination in patients with hereditary deafness, performed at the National Research Institute of Mother and Child in Warsaw. Genetic cause of deafness was confirmed in 60% cases.