[Results of palliative thermochemotherapy for colorectal cancer metastases to the liver].

The purpose of the study is to investigate the effectiveness of thermochemotherapy in patients with colorectal cancer metastases to the liver in palliative mode. Loco-regional hyperthermia in combination with chemotherapy was applied to 33 patients. The comparison group was of 40 patients who underwent only chemotherapy. 5-fluorouracil (5-FU) or capecitabine over standard regimens were used for chemotherapy in both groups. Loco-regional hyperthermia was carried out by capacitive method for 40-90 minutes at a maximum temperature within 41-44 ° C in tumor. No significant differences in dynamics of the overall status, clinical symptoms of the disease and biochemical parameters between the groups were revealed. In the group of patients with thermochemotherapy there were received a complete response in 3 patients (9%), partial response - in 14 patients (44%) while in the group of patients with chemotherapy - in 1 patient (3%) and 11 patients (28%), respectively. The significant difference was found in terms of objective response, i.e. summarized parameters of complete and partial regression (p=0.04). Thermochemotherapy compared with chemotherapy significantly increased survival rates of patients.

[Possibilities of local hyperthermia in treatment for edematous breast cancer patients].

The paper presents an analysis of literature on the results of treatment of edematous breast cancer as well as own data on the use of local hyperthermia for this pathology. Local hy- perthermia in combination with chemotherapy (thermochemo- therapy) was applied in 14 patients with secondary edematous breast cancer. Age of patients ranged from 37 to 72 years (mean 53 years). The study results indicate promising applica- tions of thermochemotherapy in edematous breast cancer: for operable patients as neoadjuvant, for inoperable patients as palliative method of treatment.

[The results of combined treatment of patients with locally advanced laryngeal cancer using preoperative chemoradiotherapy].

The combined treatment with preoperative chemoradiotherapy (CRT) was performed in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) was carried out according to the scheme "1 + 1 Gy" (interval 4-5 hours) 5 times a week till 30-40 Gy. RT was accompanied by simultaneous polychemotherapy: vincristine (1.4 mg/m² per day), cisplatin (20 mg/m²--2-4 days) bleomicetin (10 mg/ m²--5, 6 days), cyclophosphamide (200 mg/m²--7, 8 days). Surgical treatment was carried out in 2.5-3 weeks after CRT. CRT allowed conducting organ-saving surgery on the larynx in 11 (52%) of 21 patients with T3 of primary tumor. All other patients underwent laryngectomy at a different volume. Five-year disease-free survival for the whole group in total (T3-4) was 88%. Relapses of regional metastases (MTS) occurred in 7 of 9 patients including in 4 of 5 patients after lymphadenectomy. The overall survival of patients with T3N02 was 71%, with T4N0-3--20%. Thus we have developed a method of treatment allowing to achieve high local relapse-free survival in patients with locally advanced laryngeal cancer. However organ-saving effectiveness of preoperative CRT and its effect on regional MTS remain low, which requires further research in this direction.

[Forensic medical diagnostics of the impact of the ligatures made from different materials in the cases of strangulation asphyxia].

The identification of the instruments of injury resulting from neck compression not infrequently encounters difficulties. We developed an experimental model allowing to evaluate the impact of ligatures made from different materials on non-biological objects. The use of spectral techniques including X-ray fluorescence spectrometry and emission spectral analysis made it possible to detect and identify the chemical elements transferred from the loop material onto the object's surface. Specifically, the transfer of the elements contained in the rubber of the electric cable braid was demonstrated. The presence of these elements together with microparticles of rubber at the surface of the study objects proved to be a diagnostic sign giving evidence of the impact of the rubber sheath of the electric cable leaving the strangulation mark on the object's surface.. The results of the present experiments confirm the possibility of using spectral methods along with other techniques for the identification of a ligature employed as the instrument of strangulation injury.

[On the method of forensic medical examination of the injuries inflicted and traces left by the objects having the rubber surface].

A method of forensic medical examination of the injuries inflicted and traces left by the objects having the rubber surface is proposed. The method permits to reveal the facts of contact of injurious rubber things with biological and non-biological objects. Its application extends the possibilities for determining the direction of movement and the weight of a vehicle running over the body of the victim.

Resolution of HLA class I sequence-based typing ambiguities by group-specific sequencing primers.

The increasing demand for allele-level human leukocyte antigen (HLA) typing has led the sequence-based typing (SBT) to become the preferred method. In turn, the steady increase in the number of HLA alleles driven by the adoption of SBT as the ultimate typing method leads to the ever increasing number of cis/trans ambiguities. Over the last few years, additional sequencing with the commercially available group-specific sequencing primers (GSSPs) has replaced sequence-specific primer-polymerase chain reaction and group-specific amplification as the means of resolving cis/trans ambiguities in many laboratories. Here we summarize our 3-year experience in designing and utilizing GSSPs for resolution of HLA class I ambiguities. The panel of GSSPs used in our laboratory includes 14 primers for HLA-A, 18 for HLA-B, and 13 primers for HLA-C. The panel resolves 99.9% of all ambiguities.

Powdery mildew resistance of barley accessions from Dagestan.

Powdery mildew caused by the parasitic fungus Blumeria graminis (DC.) Golovin ex Speer f. sp. hordei Marchal is one of the most common diseases of barley. Growing resistant varieties can signif icantly minimize harmful effects of the pathogen. The specif icity in the interaction between the fungus and its host plant requires a continuous search for new donors of the resistance trait. The powdery mildew resistance of 264 barley accessions from Dagestan and genetic control of the trait in resistant forms were studied under f ield and laboratory conditions. Forty-seven barley lines carrying previously identif ied powdery mildew resistance genes were also examined. During three years, the experimental material was evaluated under severe infection pressure at the Dagestan Experiment Station of VIR (North Caucasus, Derbent). Juvenile resistance against the Northwest (St. Petersburg, Pushkin) pathogen population was evaluated in a climatic chamber. The genetic control of B. graminis resistance in the selected accessions was studied with the application of hybridological and molecular analyses. The level of genetic diversity of Dagestan barley for effective resistance to powdery mildew is very low. Only two accessions, VIR-23787 and VIR-28212, are resistant against B. graminis at both seedling and adult plant stages. The high-level resistance of breeding line VIR-28212 originating from barley landrace VIR-17554 (Ep-80 Abyssinien) from Ethiopia is controlled by the recessive gene mlo11. Accession VIR-17554 is heterogeneous for the studied trait, with the powdery mildew resistant genotypes belonging to two varieties, dupliatrum (an awnless phenotype) and nigrinudum (an awned phenotype). In accession VIR-23787, a recessive resistance gene distinct from the mlo11 allele was identif ied. This accession is supposed to be protected by a new, effective pathogen resistance gene.

[Application of spectral methods for the identification of rubber-sole footwear as a trauma implement].

Kicking to death is estimated to account for nearly 0.5% of all forensic medical autopsies and an appreciable share of murders. Meanwhile, the true number of such cases seems to be much in excess of these statistical data due to the difficulty of ascertaining the nature of injuring tools. This paper reports the results of a comprehensive medico-criminalistic investigation of the traces left by kicking with rubber-sole footwear. It is shown that in certain cases the use of spectral techniques (X-ray fluorescence and emission-spectral analysis) in combination with autopsy data, results of comparative forensic biological studies, and inquest information makes it possible to identify a concrete trauma weapon.

[Genetic control of the wheat Triticum monococcum L. resistance to powdery mildew].

Using hybrid analysis and test-clone method, 102 accessions of Triticum monococcum L. from the collection of the Vavilov All-Russia Institute of Plant Industry have been studied. This species of wheat has been found to by considerably polymorphic with respect to the resistance to the fungus Erysiphe graminis DC. f. sp. tritici Marchal. causing powdery mildew. The resistance of most accessions to the fungus population and clones is determined by dominant genes. In rare cases, the resistance was determined by recessive genes or one, two, or three oligogenes. A group of einkorn wheat accessions has been found in which the resistance to powdery mildew was determined by the same dominant factor or different but closely linked ones. Recessive resistance genes of T. monococcum differ from the recessive gene pm5 determining the resistance of T. aestivum plants. The genome of T. monococcum contains various genes of resistance to powdery mildew and is a potential source of effective genes to be used when selecting cultivated species of wheat for immunity.

Constitutive activity of the murine IL-1 beta promoter is regulated by a transcriptional repressor.

Constitutive expression of IL-1 beta is kept under tight control in healthy tissues. So far no repressor elements down-regulating expression of the IL-1 beta gene have been described. In the current study, a deletion analysis approach was utilized to identify a region spanning -306/-292 bp upstream of the transcription start site, which appeared to down-regulate constitutive IL-1 beta promoter activity. Further deletion analysis confirmed that the -306/-292 bp element possessed repressor activity. A putative NF-kappaB binding site and an AATATT palindromic sequence were identified within the 306/-292 bp element. Notably, no binding of NF-kappaB was observed in gel shift assays, suggesting that another nuclear activity binding to the 14 bp sequence suppressed NF-kappaB binding. Further, the results of gel shift assays demonstrated that the AATATT palindromic sequence, which lies immediately downstream of the putative NF-kappaB site, may be responsible, in conjunction with the NF-kappaB site, for constitutive suppression of the IL-1 beta promoter. Thus, our results suggest that a novel repressor element may play a potentially important role in suppressing constitutive activity of the IL-1 beta promoter.

Proximal regulatory elements and nuclear activities required for transcription of the human Na+/H+ exchanger (NHE-1) gene.

We herein demonstrate competence of the 5' upstream region -1374 to +16 of the human growth factor-activatable Na+/H+ exchanger (NHE-1) gene to promote transcription of the chloramphenicol acetyltransferase gene in cells of hepatic origin (HepG2), vascular-smooth-muscle origin (VSM A7r5) and fibroblasts (3T3). We also describe the mapping of the regulatory elements required for such transcription. Sequential 5' end-deletions indicated that the 5' boundary of the positive regulatory elements of NHE-1 transcription is localized downstream of nucleotide -252 in both HepG2 and VSM A7r5 cells but downstream of nucleotide -654 in 3T3 cells. Footprinting analysis of the 0.25-kb promoter fragment using rat liver nuclear extracts identified 4 protected regions as follows: A, -31 to -9; B, -108 to -65; C, -124 to -111; and D, -239 to -215. Internal deletion and nucleotide substitutions within regulatory element D revealed its essential role for transcription of the human NHE-1 gene in HepG2 and VSM A7r5 cells. DNA binding and competition assays using rat liver nuclear extracts indicated that regulatory element D is recognized by 5 nuclear activities. Four of these activities (designated as NHE-1D1-4) are competed out completely by oligonucleotides containing the binding sites of transcription factors CREB, AP3, NFY, and other CCAAT box-binding proteins (C/EBP alpha or related proteins). This competition profile might be explained by the presence of homology between regulatory element D and the consensus sequence of C/EBP as well as the other competitor oligonucleotides. The actual relationship between these nuclear activities and the C/EBP family of proteins (or other transcription factors) remains to be determined.

[Inhibition of formation of complement C5-convertase]. / Ingibirovanie obrazovaniia C5-konvertazy komplementa.

Control of the formation of complement C5-convertase is an important factor in maintaining human homeostasis. Some physiologically active endogenous and exogenous substances were shown to be capable of exerting such control. A method was developed for studying the influence of the effectors on the formation of classical-complement-pathway C5-convertase from C3-convertase stabilized by nickel ions. Immunoglobulins G and M, recombinant alpha and gamma interferons, serotonin, epinephrine, histamine, and ethanol were studied as effectors. The binding constants of the effectors with C3b, the active C3 component, and the values of the maximal effect were determined to evaluate the physiological importance of the effectors. The inhibition of C5-convertase generation was observed in all cases except for IgG and IgM (rheumatoid factor), which showed no effect and activating effect, respectively.

[Radiosensitizing effect of hyperthermia (41.5C, 30 min) in stem cells of mouse spermatogenic epithelium]. / Radiosensibiliziruiushchii éffect gipertermii (41,5, 30 min) dlia stvolovykh kletok spermatogennogo épiteliia myshei.

Mouse testes preheated up to 41.5 degrees C for 30 min exhibit an increased radiosensitivity of testis epithelium stem cells. High death rate is described by a shift (by approximately 4 Gy) in the "dose-response" curve to the Abscissa left. The DMF value for hyperthermia depends on the cell survival rate, at which calculations are made, and varies from 2.1 to 1.4 within the range under study.

[A program of prevention of hereditary lysosomal diseases in the USSR]. / Programma profilaktiki nasledstvennykh lizosomnykh boleznei v SSSR.

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. 53 families at risk (of 277) were prenatally diagnosed. 66 fetuses were diagnosed for mucopolysaccharidoses, type I, II, III, A and B, VI, Tay-Sachs disease, Sandhoff's disease, GM1-gangliosidosis, metachromatic leukodystrophy, mannosidosis, and multiple sulfatidosis. In total 18 affected fetuses were diagnosed and aborted. All the prenatal diagnoses were verified. The prevalence of mucopolysaccharidoses in two Central Asian republics was evaluated as 1:15,000. An Uneven ethnic distribution of different mucopolysaccharides in the USSR has also been shown.

[Problems in the diagnosis of hereditary metabolic defects in pediatric neurology]. / Problemy diagnostiki nasledstvennykh defektov obmena veshchestv v detskoi nevrologii.

The authors have elaborated a program of selective screening of hereditary metabolic defects (HMD) ensuring the identification of over 100 disease entities as well as a program of the biochemical diagnosis and prophylaxis of mucopolysaccharidoses. More than 3000 patients who applied for help to the medical-genetic consultative centre were examined. Data on the incidence and genogeography of HMD were obtained.

[Locus differentiation of hereditary mucopolysaccharidoses]. / Lokusnaia differentsiatsiia nasledstvennykh mukopolisakharidozov.

Locus differentiation of hereditary mucopolysaccharidoses (MPS) was carried out using the methods of enzymodiagnosis and metabolic cooperation. MPS loci were differentiated in 66 patients from 58 families, examined in the Centre of Medical Genetics, as well as in 21 patient from 12 families, found in Uzbek and Turkmen populations. The following MPS types were detected: MPS I H, MPS I H/Sh, MPS II, MPS III A and B, MPSIV A and B, MPS VI. Among the patients examined MPC II was the most widespread type of the disease. Ethnic dissimilarity was noted in the MPS distribution over the USSR regions.

[Fluorometric titration in a method of metabolic cooperation in the differential diagnosis of mucopolysaccharidoses]. / Ispol'zovanie fliuorometricheskogo titrovaniia v metode metabolicheskoi kooperatsii dlia differentsiatsii mukopolisakharidozov

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. As compared with the standard radiometric method of metabolic cooperation the procedure developed exhibited higher sensitivity, which is especially important for differentiation of the mucopolysaccharidoses III (A, B, C, D) and for prenatal diagnosis of these diseases.

[Prenatal diagnosis of hereditary lysosomal diseases]. / Prenatal'naia diagnostika nasledstvennykh lizosomnykh boleznei.

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. In two fetuses was found Hunter disease (twin pregnancy). The results of prenatal diagnosis were corroborated by postnatal studies of the neonates funicular blood and of autopsies of the aborted fetuses tissues. Application of several independent procedures for prenatal diagnosis of hereditary lysosomal diseases enabled to exclude erroneous diagnosis.

[Biochemical diagnosis of mucosulfatidosis]. / Biokhimicheskaia diagnostika mukosul'fatidoza.

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. The following biochemical anomalies were noted: alteration in the GAG spectrum in amniotic fluid, decrease in activity of lysosomal sulfatases in cultivated cells of the amniotic fluid. The pregnancy lead to a premature birth at 31st week of a girl. No alterations were observed in the spectrum of GAG's excreted with urine and in intracellular accumulation of 35S-GAG in the newborn child. Measurement of sulfatases activity in leukocytes enabled to identify conclusively that the child was a heterozygotic bearer mucosulfatidosis.