[Nosocomial infectious complications after transplantation of allogenic kidneys from the related donor].

The comprehensive evaluation of infectious complications after kidney transplantation from the living related donor was performed. Microbes predominantly encountered in urinary tract infection (P. aeruginosa, K. pneumoniae, E. coli, E. cloacae, S. epidermidis, E. faecalis) were studied. Prevention patterns and dosing regimens for the antibacterial therapy were developed considering data from the retrospective analysis of the isolated flora and its resistance. This resulted in the reduced rate of infectious complications.

[Chronic hepatitis B, hemosiderosis, and hepatic fibrosis in a renal graft recipient].

Chronic hepatitis B is a frequent concomitant disease in recipients of a renal graft that worsens results of kidney transplantation due to renal and extrarenal complications. Much rarer hemochromatosis either has genetic roots (hereditary hemochromatosis) or results from multiple blood transfusions and hemolysis during treatment by hemodialysis (secondary hemochromatosis). Combination of chronic hepatitis B and hemochromatosis increases the risk of chronic liver disease leading to cirrhosis and hepatocellular carcinoma. Success of antiviral therapy combined with massive phlebotomy is illustrated by a case of kidney transplantation to a patient with chronic hepatitis B of large duration and iron overload syndrome.

Treatment of chronic hepatitis B with lamivudine in renal transplant recipients.

Treatment of chronic hepatitis B in renal transplant recipients remains one of the major problems in clinical nephrology. Lamivudine is considered to be a drug of choice for these patients, however, its efficacy in patients with hepatitis B after renal transplantation (RT) has not been completely proven. Twenty-two RT recipients treated with lamivudine were evaluated. The duration of treatment was 15.6+/-1.9 months. Fourteen patients (64%) had normalization of aminotransferase (ALT); in 9 of them (41% of the whole group), serum HBV DNA was eliminated. Serum HBeAg was undetectable in 4 out of 15 (27%) previously positive patients. It has been statistically proven that the efficacy of lamivudine therapy correlates with degree of fibrosis and higher histological activity index values. We could not establish any correlation between the outcome of antiviral therapy and patients' age, sex, conditions of contagion (while on dialysis or after RT), time lapsed after the infection had been detected, duration of post-transplant period, type of immunosuppression, HBeAg positivity or negativity, ALT levels, concomitant HCV infection. The efficacy of antiviral HBV therapy is limited by the duration of lamivudine treatment: in 4 out of 5 patients with virologic response, the viremia condition relapsed several weeks after the medication had been stopped. Two patients continued to sustain their biochemical response and 1 patient had ALT levels elevated to above normal, but the value was almost twice as low as initially reported. Liver biopsy was repeated in 4 RT recipients after the end of antiviral therapy; in 3 of them positive morphologic changes were observed.

[Chronic hepatitis B and C in renal graft recipients].

Clinical and morphological features of chronic hepatitis B (CHB), C (CHC), and B+C (CHB+C) were studied in 283 renal graft recipients. High total bilirubin serum levels were detected significantly more often in CHB and CHB+C patients vs. CHC patients. High ALT activity was noted in 65% of CHB patients and only in 45% of CHC patients (p = 0.003). Stable low activity of hepatitis prevailed in renal recipients; it was noted in 56.7% of CHB patients, 66.2% of CHC patients, and 62% of CHB+C patients. The character of pathomorphological liver changes in chronic viral hepatitis was studied in 53 renal graft recipients using puncture biopsy. Histopathological activity index (HAI, Knodell R.G. et al., 1981) witnessed a more severe liver lesion in CHB vs. CHC and CHB+C. Thus, inflammatory activity in CHB was found to be minimal or low in 13 patients, and moderate or high in 11 patients, whilst a minimal or low activity in CHC or CHB+C was found in 16 and 10 patients, respectively, and a moderate activity was detected only in two and one, respectively (p = 0.016 and 0.024 compared with CHB). Advanced hepatic fibrosis or cirrhosis was significantly more frequent (p = 0.006) in CHB patients (eight out of 24) than in CHC ones (none out of 18). The rate of advanced sclerotic changes in CHB+C was lower (one out of 10 patients) than that in CHB, and similar to CHC. Thus, clinico-morphological manifestations were more prominent in renal graft recipients with CHB vs. CHC.

[Pseudogenes: structure conservation, expression, and functions]. / Psevdogeny: konservatsiia struktury, ékspressiia i funktsiia.

Pseudogenes have been defined as nonfunctional sequences of genomic DNA (junk DNA) originally derived from functional genes. It is therefore assumed that pseudogenes are not subject to natural selection and consequently pseudogene mutations are selectively neutral and have equal probability to become fixed in the population. We describe some unexpected features of pseudogenes in diverse organisms that are inconsistent with this widely accepted point of view. Pseudogenes are often evolutionary conserved and transcriptionally active. Moreover, pseudogenes that have been suitably investigated often exhibit functional roles, such as gene regulation, generation of genetic diversity, and other features that are expected in genes or DNA sequences that have functional roles. A review of the evidence leads to the conclusion that pseudogenes are important components of genomes, representing a repertoire of sequences available for functional evolution and subject to non-neutral evolutionary changes. Pseudogenes might be considered as potogenes, i.e. DNA sequences with a potentiality for becoming new genes or acquire new functions. Furthermore we conjecture that some pseudogenes along with their parental sequences may constitute sets of indivisible functionally interacting entities (intergenic complexes or "intergenes"), in which all the component elements are required in order to fulfill a collective functional role.

[Evaluation of genetic variability of the Kamchatka crab Paralithodes camtschaticus (Tilesius) using allozyme markers]. / Otsenka geneticheskoi izmenchivosti kamchatskogo kraba Paralithodes camtschaticus (Tilesius) s ispol'zovaniem allozimnykh markerov.

Interspecific genetic variation in populations of red king crab Paralithodes camtschaticus Tilesius (Litholidae, Decapoda: Crustacea) was examined using allozyme markers. The activity of 57 enzymes and the general protein presumably encoded by 92 loci was detected. The level of allozyme variability was low: the expected heterozygosity and the proportion of polymorphic loci were respectively 0.027 +/- 0.008 and 6.5%. This level of heterozygosity is three times lower than the average value for 122 crustacean species (0.082 +/- 0.007). Although genetic variants were found at 22 loci, their frequencies were generally low: only in loci 6-Pgd, Alp-1, and Pep-1 did the frequencies of the most common alleles not exceed 0.9. All polymorphic loci except one had two alleles; the exception was 6-Pgd, which had three alleles. The possible reasons for the low level of allozyme variability in red king crab are discussed.

Molecular evolution of two linked genes, Est-6 and Sod, in Drosophila melanogaster.

We have obtained 15 sequences of Est-6 from a natural population of Drosophila melanogaster to test whether linkage disequilibrium exists between Est-6 and the closely linked Sod, and whether natural selection may be involved. An early experiment with allozymes had shown linkage disequilibrium between these two loci, while none was detected between other gene pairs. The Sod sequences for the same 15 haplotypes were obtained previously. The two genes exhibit similar levels of nucleotide polymorphism, but the patterns are different. In Est-6, there are nine amino acid replacement polymorphisms, one of which accounts for the S-F allozyme polymorphism. In Sod, there is only one replacement polymorphism, which corresponds to the S-F allozyme polymorphism. The transversion/transition ratio is more than five times larger in Sod than in Est-6. At the nucleotide level, the S and F alleles of Est-6 make up two allele families that are quite different from each other, while there is relatively little variation within each of them. There are also two families of alleles in Sod, one consisting of a subset of F alleles, and the other consisting of another subset of F alleles, designed F(A), plus all the S alleles. The Sod F(A) and S alleles are completely or nearly identical in nucleotide sequence, except for the replacement mutation that accounts for the allozyme difference. The two allele families have independent evolutionary histories in the two genes. There are traces of statistically significant linkage disequilibrium between the two genes that, we suggest, may have arisen as a consequence of selection favoring one particular sequence at each locus.

Is esterase-P encoded by a cryptic pseudogene in Drosophila melanogaster?

We have amplified and sequenced the gene encoding Esterase-P (Est-P) in 10 strains of Drosophila melanogaster. Three premature termination codons occur in the coding region of the gene in two strains. This observation, together with other indirect evidence, leads us to propose that Est-P may be a pseudogene in D. melanogaster. Est-P would be a "cryptic" pseudogene, in the sense that it retains intact the coding sequence (without stop codons and other alterations usually observed in pseudogenes) in most D. melanogaster strains. We conjecture that the beta-esterase cluster may consist in other Drosophila species of functional and nonfunctional genes. We also conjecture that the rarity of detected pseudogenes in Drosophila may be due to the difficulty of discovering them, because most of them are cryptic.

[A simple method for detecting the order of relation location of fragments in constructing a paired restriction map]. / Prostoi metod nakhzhdeniia poriadka vzaimnogo raspolozheniia fragmentov pri postroenii parnykh restriktsionnykh kart.

A simple method for the ordering of fragments and the determination of relative positions of restriction sites when constructing pair restriction maps of linear and circular DNAs is described. The major advantages of the suggested approach as compared to the routine strategy of exhaustive search are as follows: (1) One does not need to begin the construction of the map by searching for the restrictases that produce the least number of fragments; (2) the method allows one to construct quite complicated maps, the main limiting parameter being the number of fragments during double digestion (no more than 10-12); and (3) construction of the map using this approach is less labor- and time-consuming than the routine strategy.

[Prognostic signs of accelerated progression of nephrotic types of chronic glomerulonephritis]. / Predvestniki uskorennogo progressirovaniia nefroticheskikh tipov khronicheskogo glomerulonefrita.

A prognostic value of some clinical and morphological signs was followed up in 43 patients with chronic glomerulonephritis concurrent with the nephrotic syndrome versus 85 with other clinical types of the disease. There was a statistically significant incidence of disease progression in combination with arterial hypertension, resistance of the nephrotic syndrome over 12 months and detection of sclerosing renal glomeruli and interstitium within 2 years after onset of the disease. The protracted course of the nephrotic syndrome is a precursor of occurrence of chronic renal failure. With less prolonged phases of the syndrome there is evidence for a long-term period of functional compensation. Occurrence of arterial hypertension early in the disease, as early renal parenchymal sclerosis, fails to predict the rates of chronic renal failure development. In the absence of these factors, the possibility of prompt disease progression may be rejected in all likelihood.

[Factors affecting survival of patients and graft after transplantation of a cadaver kidney]. / Faktory, vliiaiushchie na vyzhivaemost' bol'nykh i transplantata posle peresadki trupnoi pochki.

The following factors were found to contribute to survival rate of 5 years and longer in the patients with transplanted cadaver kidneys: patients' age of 20 to 40, a non-autoimmune nature of the underlying disease (chronic pyelonephritis and renal polycystosis), hemodialysis treatment for not longer than 6 months, and 4-5 preoperative blood transfusions. A good initial status of the recipients, no presensitization, and HLA histocompatibility of the donor and recipient for 3-4 A and B loci are the necessary conditions for prolonged survival of kidney transplants and patients. Programmed hemodialysis is preferable for the patients with a high sensitization, for no long survivals were recorded among them, high mortality rate being registered within the first two years after kidney allotransplantation.

[Clinical and morphologic predictors of the progress of chronic glomerulonephritis]. / Klinicheskie i morfologicheskie prediktory progressirovaniia khronicheskogo glomerulonefrita.

Observation over 183 patients with a morphologically verified diagnosis of chronic glomerulonephritis (CGN) made it possible to establish on a mathematic basis a highly significant relationship between the disease progress and the clinical and morphological disease patterns. In the active nephritic patterns and in the nephrotic-hypertonic pattern, chronic renal failure (CRF) occurred in the majority of the patients within the first 5 years. Meanwhile in the inactive nephritic pattern and in the nephrotic pattern, a corticoid-sensitive one, characterized by the phasic course, CRF could not almost be seen over up to 20 years after the disease onset. As far as the morphological patterns are concerned, focal-segmental glomerular hyalinosis/sclerosis turned out most unfavourable. In patients with this pattern, CRF was diagnosed during 5 years in almost half of the patients. The mesangio proliferative and membranous patterns appeared most favourable. The incidence of CRF during 5 years after the disease onset, common to the definite clinical patterns, did not depend on the concomitant morphological pattern. Provided there were sclerotic lesions throughout 2 years after the disease onset, CRF occurred in 65% of the cases for 10 years, whereas with their lack in 9% of the cases. The most important predictors of CRF were as follows: the clinical pattern of CGN and the presence of sclerotic lesions in the renal biopsy specimen. Of definite significance might be the morphological pattern of CGN.

Organization of treatment of patients with cardiac insufficiency of different origin.

Assisted circulation is now used in the treatment of severe forms of heart failure which complicate the course of many diseases. Application of one method of assisted circulation--intra-aortic counterpulsation by a balloon pump in cardiogenic shock--was successful: prolonged survival (over 1 year) was obtained in 18% of the patients. A further decrease in the mortality rate is dependent on the rational organization of treatment for these patients. This poses two major problems: the organization of treatment of patients in cardiogenic shock and postoperative heart failure in large cardiologic and heart surgery centers, and treatment of heart failure in patients in whom it has occurred secondarily. We developed a method of organizing the treatment of these patients beginning in the prehospital stage and continuing in a specialized hospital. In addition to methods of assisted circulation, various intensive care methods and hemosorption (in poisoning by liver toxins), hemodialysis (in anuria), etc., are used. Although this type of organization complicates therapy, the results are significantly improved.