[A complex method for prophylaxis of laparoscopic cholecystectomy complications].

The clinical examination and treatment results were analyzed in 1282 patients, in whom laparoscopic cholecystectomy, using complex method of the complications prophylaxis, was performed for calculous cholecystitis. The complications have had occurred in 21 (1.64%) patients, the conversion necessity--in 10 (0.78%), 3 (0.23%) patients died.

[Draft macronuclear genome of a ciliate Euplotes crassus].

Basic bioinformatical analysis of the draft Euplotes crassus macronuclear genome and transcriptome suggests that more than a quarter of E. crassus genes contain several exons. A large fraction of all introns is formed by "tiny" introns having length 20-30 bp. Analysis of the transcriptome revealed 63 possible cases of alternative splicing, and also 14 introns with non-standard splicing sites. About 2000 hypothetical genes do not have homologs in other ciliates, and since most of them have the closest homologs in bacterial genomes, they are likely an artifact of the sample preparation. Comparison of the E. crassus genome to the genomes of other ciliates showed an expansion of the same gene families, responsible for the free-living heterotrophic lifestyle.

[The coordinated interaction of multifunctional members of p53 family determines many key processes in multicellular organisms].

First time p53 was found in the complex with viral large T-antigene in the cells transformed by small DNA virus SV40. The cloning of p53 cDNA was done in the beginning of eighties and soon after that the whole p53 gene was cloned. The p53 family is comprised of three genes: TP53,TP63 and TP73, each of which is expressed as a set of structurally and functionally different isoforms. All of them intensively interact with each other forming a united functional network of proteins. In this review we discuss evolution of the p53 family and significance of all its members in embryonic development, reproduction, regeneration, regulation of aging and life span, as well as in the body's defense against cancer. With special attention we review the role of less studied members of the p53 family: p63 and p73, in oncogenesis and tumor progression and show that different isoforms of these proteins might exert a contrary effect on these processes.

[Postoperative complications after surgical interventions for cancer of proximal regions of the rectum].

The results of surgical treatment, performed in 1986-2005 in 1690 patients, suffering proximal rectum cancer, were studied. Resectability had constituted 84.3%. Primarily-restoration operations were performed in 95.9% patients. Of 1425 patients in 85.6%--radical operations were performed, in 14.4%--palliative and in 11.6%--combined. Intraoperative complications had occurred in 7.6% patients and postoperative--in 15.3%. Anastomotic sutures insufficiency was noted in 1.8% patients. Postoperative lethality had constituted 4.2%.

The gastrin gene promoter is regulated by p73 isoforms in tumor cells.

p73, a new p53 family member, is a transcription factor that is increasingly recognized in cancer research as an important player in tumorigenesis as well as in chemotherapeutic drug sensitivity. Despite the substantial structural and functional similarities to p53, accumulating evidence suggests that p53 and p73 may differently regulate their transcriptional targets. In this study, we have investigated the role of p73 in regulation of the gastrin gene promoter. Gastrin is a peptide hormone and an important factor in determining the progression of a number of human malignancies. Our results show that p73 can bind to the gastrin promoter. This leads to transcriptional upregulation of gastrin mRNA. We also found that the levels of gastrin and p73 transcripts correlate in primary gastric tumors. Taken together, our results demonstrate a novel mechanism for regulation of gastrin gene transcription and support a concept that p53 and p73 may have different biological roles in tumors.

Overexpression of the wild type p73 gene in breast cancer tissues and cell lines.

The p73 gene is a structural and, in overexpression systems, functional p53 homologue. Ectopic p73 expression can activate a broad subset of p53-responsive genes, induce apoptosis, and act as a growth suppressor. Yet, viral oncoproteins that antagonize p53 (adenovirus E1B 55K, SV40 large T, and human papillomavirus E6) do not antagonize p73. This could suggest that inactivation of p73, in contrast to p53, is not required for tumorigenesis. Also, p73 is not activated by DNA damage. Because intragenic p73 mutations in tumors have not been reported and imprinting is idiosyncratic, tumor-specific changes in wild-type p73 expression levels become the most reliable guide toward identifying the normal function of p73 and its role in tumorigenesis. We analyzed 77 invasive breast cancers and 7 breast cancer cell lines for p73 mRNA expression levels, allelic origin, intragenic mutations, and COOH-terminal splice variants. A range of normal tissues, including breast, showed very low p73 expression, with little variation from tissue to tissue. In contrast, 38% (29 cases) of breast cancers had elevated p73 mRNA ranging from 5-25-fold above normal, with the remaining tumors (64%) falling within the normal range. Moreover, five of seven cell lines (71%) also exhibited p73 overexpression (13-73-fold). Yet, no correlation with p21 mRNA and protein levels was present, although four of the five lines were mutant for p53. Mutation analysis of the eight highest expressers showed wild type status. Eight of 14 informative samples were biallelic, whereas the remaining 6 samples showed monoallelic expression. Tumors and cell lines with p73 overexpression tended to exhibit a complex profile of up to six different COOH-terminal splice variants, whereas normal and transformed tissues with low p73 mRNA predominantly expressed p73 alpha. We confirm the previously described variants p73 gamma and delta in breast tissue and describe two novel isoforms, p73 epsilon and phi, thereby further enlarging combinatorial possibilities. Together, our in vivo data show that p73 does not have a role as a classic Knudson-type tumor suppressor in breast cancer.

p53, p63 and p73--solos, alliances and feuds among family members.

p53 controls crucial stress responses that play a major role in preventing malignant transformation. Hence, inactivation of p53 is the single most common genetic defect in human cancer. With the recent discovery of two close structural homologs, p63 en p73, we are getting a broader view of a fascinating gene family that links developmental biology with tumor biology. While unique roles are apparent for each of these genes, intimate biochemical cross-talk among family members suggests a functional network that might influence many different aspects of individual gene action. The most interesting part of this family network derives from the fact that the p63 and p73 genes are based on the "two-genes-in-one" idea, encoding both agonist and antagonist in the same open reading frame. In this review, we attempt to present an overview of the current status of this fast moving field.

[Digoxin in treatment of chronic insufficiency and changes of functional state of the pancreas].

The article challenges the issue of combined damage of the cardiovascular and gastroenterological systems. It is recommended differentially manage patients with chorine heart insufficiency and prevalence of systolic or diastolic components of their blood pressure. The authors also consider influence of the treatment on a congestive pancreas. Prevalence of the systolic heart insufficiency (ventricular ejection factor less than 40%) have been observed among patients by the authors; digoxin have been found to be effective in treatment of patients with chronic heart insufficiency and congestive pancreas. Enhancement of left ventricular ejection factor and improvement of ultrasound characteristics of the pancreas have been observed following the treatment.

[Subcardial resection for gastric cancer].

The method of subtotal gastric resection for cancer, stipulating for lower esophageal sphincter and gastric cardia, was elaborated in the clinic. Good immediate results, low rate of postoperative complications, the absence of gastroesophageal anastomosis sutures insufficience together with significant improvement of functional results due to preservation of lower esophageal sphincter function permit to recommend subcardial gastric resection as a method of choice in a distal gastric third cancer as well as in the early gastric corpus cancer.

[Prophylaxis of postgastrectomy complications in patients with gastric cancer].

There are presented the results of surgical treatment of 447 patients. suffering gastric cancer, in whom gastrectomy was performed. Esophago-initestinal anastomosis was performed according to method of G. V. Bondahr. Interintestinal anastomosis (IIA) was formed using traditional Braun method and also was applied the longitudinal-transversal method, elaborated in the clinic. Usage of the method proposed did not worsen the immediate and late results, but have promoted significant improvement of the gastrectomy functional results. The method application secures the trustworthy lowering of the postgastrectomy complications rate while performing gastrectomy (dumping syndrome, reflux-esophagitis, the adduced loop syndrome) comparing with such, using Braun IIA--accordingly 30.5 and 52.8% (P = 0.016); fair, good and excellent the patients quality of life--accordingly in 67.8 and 47.2% (P = 0.024). The elaborated procedure of the IIA formation constitutes the method of choice while performing gastrectomy.

Nuclear and mitochondrial apoptotic pathways of p53.

In contrast to p53-mediated cell cycle arrest, the mechanisms of p53-mediated apoptosis in response to cellular stresses such as DNA damage, hypoxia and oncogenic signals still remain poorly understood. Elucidating these pathways is all the more pressing since there is good evidence that the activation of apoptosis rather than cell cycle arrest is crucial in p53 tumor suppression. Moreover, the therapeutic interest in p53 as the molecular target of anticancer intervention rests mainly on its powerful apoptotic capability. This puzzling elusiveness suggests that p53 not only engages a plethora of downstream pathways but itself might possess a biochemical flexibility that goes beyond its role as a mere transcription factor. Recent evidence of a direct pro-apoptotic role of p53 protein at mitochondria suggests a synergistic effect with its transcriptional activation function and brings an unexpected new level of complexity into p53 apoptotic pathways.

Hypoxia death stimulus induces translocation of p53 protein to mitochondria. Detection by immunofluorescence on whole cells.

Evidence suggests that p53 induces cell death by a dual mode of action involving activation of target genes and transcriptionally independent direct signaling. Mitochondria are major signal transducers in apoptosis. We recently discovered that a fraction of induced p53 protein rapidly translocates to mitochondria during p53-dependent apoptosis, but not during p53-independent apoptosis or p53-mediated cell cycle arrest. Importantly, specific targeting of p53 to mitochondria was sufficient to induce apoptosis in p53-deficient tumor cells. This led us to propose a model where p53 exerts a direct apoptogenic role at the mitochondria, thereby enhancing the transcription-dependent apoptosis of p53. Here we show for the first time that mitochondrial localization of endogenous p53 can be visualized by immunofluorescence of whole cells when stressed by hypoxic conditions. Suborganellar localization by limited trypsin digestion of isolated mitochondria from stressed cells suggests that a significant amount of mitochondrial p53 is located at the surface of the organelle. This mitochondrial association can be reproduced in vitro with purified p53. Together, our data provide further evidence for an apoptogenic signaling role of p53 protein in vivo at the level of the mitochondria.

Lack of defective expression of the ATM gene in sporadic breast cancer tissues and cell lines.

Homozygous mutations of the gene mutated in ataxia telangiectasia (ATM) causes the AT syndrome, a pleiotropic phenotype that includes an increased risk of cancer. Most of the known mutations at the ATM gene lead to truncations which are usually associated with instability of mRNA and protein. A decrease or loss of ATM protein expression is associated with specific lymphoid malignancies in AT and non-AT patients. ATM is located within a region in chromosome 11q22-23 that is frequently undergoing loss of heterozygosity in sporadic breast cancer. Epidemiological studies estimated a 4-fold increase in breast cancer risk in heterozygous women. However, direct mutational analysis failed to clearly support a role for mutant ATM alleles in breast carcinogenesis. If ATM does have a suppressor role in this tissue, one would expect deficient ATM expression. We therefore tested the hypothesis that the expression of the ATM gene is reduced in sporadic breast cancer. We determined ATM transcript levels using competitive RT-PCR on 89 randomly selected sporadic breast cancer samples and 29 normal breast tissues. Of these, 11 were matched normal/cancer pairs. We also evaluated 7 breast cancer cell lines. Deficiency in ATM expression was not observed. Of the 11 matched pairs, 7 tumors expressed mildly higher levels, 3 tumors expressed the same amount and only 1 tumor expressed <50% of the normal match. In addition, 3 cancers with tumor-associated LOH of the ATM gene expressed higher mRNA levels in the tumors than in their normal tissue matches, suggesting that no correlation exists between tumors with LOH and decreased ATM expression. In summary, our results do not support a suppressor role for ATM in the development of sporadic breast cancer.

[Interhemisphere asymmetry of neuromediators in the brain of albino rats]. / Mezhpolusharnaia aimmetriia neiromediatorov v mozgu belykh krys.

The presence of interhemispherical asymmetry in the content of acetylcholine, norepinephrine, epinephrine, and dopamine is shown in experiments on albino rats. In this case no differences are observed in the acetylcholinesterase, monoamineoxidase and dopadecarboxylase activities in the left and right hemispheres. An assumption is advanced that neuromediatory interhemispherical asymmetry of the brain is connected with interhemispherical peculiarities of their storage, excretion and inverse capture. The data obtained should be taken into account in the study of pathogenesis of nervous-physical diseases and in the study of the mechanism of neurotropic drugs action.

[The dynamic status of the gallbladder and pancreas at different phases of interdigestive duodenal motility]. / Dynamichnyi stan zhovchnoho mikhura ta pidshlunkovoï zalozy v rizni fazy mizhtravnoï motoryky dvanadtsiatypaloï kyshky.

It is shown in the article that the ultrasonic monitoring of the pancreas with dyskinesia of the gallbladder during different phases of interdigestive motility can be helpful in the diagnosis of early stages of pancreatitis, especially in the absence of clinical symptoms.

[The current methods for treating chronic calculous cholecystitis and reactive hepatitis]. / Suchasni metody likuvannia khronichnoho kal'kul'oznoho kholetsystytu ta reaktyvnoho hepatytu.

In conducting pathogenetic treatment of chronic calculous cholecystitis it is necessary that special characteristics of development of the clinical course in the above condition be studied together with phase contractile function of the gallbladder, liver, as per duodenum motility phases. The above methodological approach to the treatment of chronic calculous cholecystitis, reactive hepatitis will, we believe, come to be widely used by medical practitioners.

[Effect of perindopril on hemostasis and functional status of pancreas in patients with ischemic heart disease]. / Vplyv peryndoprylu na hemostaz ta funktsional'nyi stan pidshlunkovoï zalozy u khvorykh na ishemichnu khvorobu sertsia.

Systemic circulation compromise in patients with cardiac insufficiency results in disturbances of functional state of pancreas. The Willebrand's Factor takes a definite role in this pathological process. The usage of Peridopril 4 mg daily during the treatment decreases significantly Willebrand's Factor activity and normalizes function of the pancreas.

[The diagnosis of chronic cholecystitis and pancreatitis]. / Diagnostika khronicheskogo kholetsistita i pankreatita.

Results are submitted of ultrasonic monitoring of gallbladder, pancreas and duodenum during the I, II, III phases of digestion in 186 patients who ranged from 30 to 60 years old. The form was studied of the gallbladder as was its size and location together with the volume, thickness of walls, presence of deformities; echogenicity of pancreas, outline, state of the main duct. Interdigestive duodenal motility and intracavitary pressure were recorded. Relationship has been established of the gallbladder and pancreas contraction phases to the condition of the intracavitary pressure in the duodenum.

[Instrumental methods for studying the pancreaticobiliary system]. / Instrumental'ni metody doslidzhennia pankreatobiliarnoï systemy.

Ultrasonic monitoring was conducted in patients with chronic cholecystitis, pancreatitis (n = 186) to study contractile and functional activities of the gallbladder, pancreas, duodenum. The motor and evacuatory function of the gallbladder and pancreas was found out to be dependable upon the phase dyskinesias of duodenum. An increased pressure in duodenal cavity tends to impair the processes of intracavitary digestion and motor and evacuatory function of the gallbladder, pancreas, and to affect the phase outflow of bile and pancreatic juice.

[Effect of titanium on the osteogenic and proliferative potentials of bone marrow cells in vitro]. / Vliianie titana na osteogennyi i proliferativnyi potentsial kletok kostnogo mozga in vitro.

The impact of titanium (BT-1.0) on proliferative and osteogenic potential of in vitro bone marrow was studied in rabbits. Titanium showed no influence on proliferation and differentiation of osteogenic determined cells precursors in the bone marrow. These cells' growth showed a titanium-tropicity. The authors came to a conclusion that the use of titanium in combination with automyeloplasty can be successfully used to accelerate the bone integration in implanted dental patients.