[Laparoscopic appendectomy for acute appendicitis in pregnancy]. / Laparoskopicheskaya appendektomiya pri ostrom appenditsite u beremennykh.

The review is devoted to the role of laparoscopic appendectomy in surgical management of acute appendicitis in pregnancy. We analyzed reviews, prospective and retrospective studies in the PubMed, Google, the Springer Link online library, the Cochrane Systematic Review databases. The results of laparoscopic and traditional treatment of acute appendicitis in pregnant women were assessed. We analyzed clinical, epidemiological features in these patients, differential diagnosis of acute appendicitis in pregnant women, indications and contraindications for endoscopic treatment, features of laparoscopic procedures. Comparative assessment of laparoscopic and open surgeries for acute appendicitis in pregnant women was carried out. We also estimated the influence of surgical treatment of acute appendicitis on subsequent course of pregnancy.

[Laparoscopic treatment of perforated gastroduodenal ulcers]. / Laparoskopicheskaya tekhnologiya lecheniya probodnykh yazv zheludka i dvenadtsatiperstnoi kishki.

The review is devoted to laparoscopic technology in the treatment of perforated gastroduodenal ulcers. Searching for literature data was performed in the PubMed, Google, Springer Link online library, Cochrane Systematic Review databases. We analyzed reviews, prospective and retrospective studies devoted to various strategies in the treatment of perforated peptic ulcers. Demographic, clinical and epidemiological features of these patients, indications and contraindications for endoscopic suturing of perforations, features of laparoscopic procedures and causes of conversions to open surgery were studied. Finally, we compared the results of laparoscopic and open surgeries.

[Modern minimally invasive technologies for the treatment of cholelithiasis]. / Sovremennye mini-invazivnye tekhnologii lecheniya kholetsistokholedokholitiaza.

Surgical community has not yet reached any consensus on the adequate treatment of gallstone disease with combined stones of the gallbladder and bile ducts. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic papillosphincterotomy (EPST) followed by laparoscopic cholecystectomy (LCE) have been considered the optimal treatment method for the past thirty years. Thanks to improvement of technologies and experience in laparoscopic surgery, many centers in the world offer simultaneous treatment of cholecystocholedocholithiasis, i.e. LCE and laparoscopic choledocholithotomy. Transcystical and transcholedochal extraction of calculi from the common bile duct is the most common. Intraoperative cholangiography and choledochoscopy are used to assess extraction of calculi while T-shaped drainage, biliary stent and primary suture of common bile duct are used to complete choledocholithotomy. Laparoscopic choledocholithotomy is associated with certain difficulties, requires some experience in choledochoscopy and intracorporeal suturing of common bile duct. There are many unresolved issues regarding the choice of laparoscopic choledocholithotomy technique depending on the number and dimensions of stones, diameter of cystic duct and common bile duct. The authors analyze literature data on the role of modern minimally invasive interventions in the treatment of gallstone disease.

[Emergency laparoscopy in the treatment of perforated gastroduodenal ulcers]. / Ekstrennaya laparoskopiya pri lechenii perforativnykh gastroduodenal'nykh yazv.

OBJECTIVE: To compare the results of endoscopic and open treatment of perforated gastroduodenal ulcers. MATERIAL AND METHODS: There were 445 patients with perforated gastroduodenal ulcers between 2013 and 2021. Endoscopic suturing of perforation was performed in 172 patients (38.7%), 273 ones underwent open surgery. RESULTS: Among 172 patients scheduled for endoscopy, 160 (93.6%) ones underwent laparoscopic suturing of perforation. Morbidity rate was 5.0% (n=8), postoperative mortality rate - 1.3% (n=2). Comparison of the outcomes after laparoscopic suturing of ulcers in 160 patients and open surgery in 134 patients showed that laparoscopy was followed by 2.5 times lower incidence of complications and 3 times lower postoperative mortality. CONCLUSION: Diagnostic laparoscopy is advisable in patients with perforated ulcers and no contraindications. In most cases, surgery can be successfully and effectively completed without conversion to laparotomy. Endoscopic closure of ulcerative defect is preferable since this procedure has certain advantages over traditional intervention, contributes to significant reduction in morbidity, mortality and hospital-stay.

Vimentin is a novel AKT1 target mediating motility and invasion.

The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways. In contrast, contradictory data relating to AKT effects on cell motility and invasion, crucial prometastatic processes, have been reported pointing to a potential cell type and isoform type-specific AKT-driven function. By implication, study of AKT signaling should optimally be conducted in an appropriate intracellular environment. Prognosis in soft-tissue sarcoma (STS), the aggressive malignancies of mesenchymal origin, is poor, reflecting our modest ability to control metastasis, an effort hampered by lack of insight into molecular mechanisms driving STS progression and dissemination. We examined the impact of the cancer progression-relevant AKT pathway on the mesenchymal tumor cell internal milieu. We demonstrate that AKT1 activation induces STS cell motility and invasiveness at least partially through a novel interaction with the intermediate filament vimentin (Vim). The binding of AKT (tail region) to Vim (head region) results in Vim Ser39 phosphorylation enhancing the ability of Vim to induce motility and invasion while protecting Vim from caspase-induced proteolysis. Moreover, vimentin phosphorylation was shown to enhance tumor and metastasis growth in vivo. Insights into this mesenchymal-related molecular mechanism may facilitate the development of critically lacking therapeutic options for these devastating malignancies.

UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53.

Epidemiological studies have suggested an association between exposure to solar UV radiation and the incidence of lymphoid malignancies, which has increased substantially worldwide during the last two decades. Findings from animal studies have raised the question of whether UV radiation might influence the development of lymphoid malignancies by means of its immunosuppressive effect. In this study, we examined the effect of UV irradiation on the development of lymphoid malignancies in mice with no or only one functional copy of p53. Mice that lack both copies of p53 spontaneously develop high frequency of lymphoid malignancies in the thymus and spleen. p53 heterozygous mice with only one copy of the wild-type allele also develop lymphoid malignancies, but with a much lower frequency and a long latent period. In our study using mice of the C57BL/6 background, only one of the unirradiated mice lacking one copy of p53 (p53(+/-)) spontaneously developed a lymphoid tumor (6%), whereas 88% of UV-irradiated p53(+/-) mice developed lymphoid tumors in the spleen or liver. None of the control or UV-irradiated p53 wild-type mice developed lymphoid tumors during the 60-week observation period. Both UV-irradiated and unirradiated mice lacking both copies of p53 (p53(-/-)) rapidly developed thymic lymphomas and/or lymphoid tumors in spleen or liver. All of the lymphoid tumors tested were of T cell type. The immune responses of the mice to contact sensitization were identical and were suppressed to the same extent by UV irradiation regardless of the genotype. These results indicate that differences in immune reactivity do not account for the different effects of UV radiation on lymphoid malignancies and, in addition, that p53 is not required for generation of T cell-mediated immunity. Interestingly, whereas p53 mutations or loss of heterozygosity did not account for the accelerated development of lymphoid tumors in UV-irradiated p53(+/-) mice, deletions in the p16(INK4a) gene were quite common. These data provide the experimental evidence that UV irradiation induces lymphoid neoplasms in genetically susceptible mice and support the hypothesis that extensive sunlight exposure contributes to the induction of lymphoma in humans.

From first base: the sequence of the tip of the X chromosome of Drosophila melanogaster, a comparison of two sequencing strategies.

We present the sequence of a contiguous 2.63 Mb of DNA extending from the tip of the X chromosome of Drosophila melanogaster. Within this sequence, we predict 277 protein coding genes, of which 94 had been sequenced already in the course of studying the biology of their gene products, and examples of 12 different transposable elements. We show that an interval between bands 3A2 and 3C2, believed in the 1970s to show a correlation between the number of bands on the polytene chromosomes and the 20 genes identified by conventional genetics, is predicted to contain 45 genes from its DNA sequence. We have determined the insertion sites of P-elements from 111 mutant lines, about half of which are in a position likely to affect the expression of novel predicted genes, thus representing a resource for subsequent functional genomic analysis. We compare the European Drosophila Genome Project sequence with the corresponding part of the independently assembled and annotated Joint Sequence determined through "shotgun" sequencing. Discounting differences in the distribution of known transposable elements between the strains sequenced in the two projects, we detected three major sequence differences, two of which are probably explained by errors in assembly; the origin of the third major difference is unclear. In addition there are eight sequence gaps within the Joint Sequence. At least six of these eight gaps are likely to be sites of transposable elements; the other two are complex. Of the 275 genes in common to both projects, 60% are identical within 1% of their predicted amino-acid sequence and 31% show minor differences such as in choice of translation initiation or termination codons; the remaining 9% show major differences in interpretation.

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

From sequence to chromosome: the tip of the X chromosome of D. melanogaster.

One of the rewards of having a Drosophila melanogaster whole-genome sequence will be the potential to understand the molecular bases for structural features of chromosomes that have been a long-standing puzzle. Analysis of 2.6 megabases of sequence from the tip of the X chromosome of Drosophila identifies 273 genes. Cloned DNAs from the characteristic bulbous structure at the tip of the X chromosome in the region of the broad complex display an unusual pattern of in situ hybridization. Sequence analysis revealed that this region comprises 154 kilobases of DNA flanked by 1.2-kilobases of inverted repeats, each composed of a 350-base pair satellite related element. Thus, some aspects of chromosome structure appear to be revealed directly within the DNA sequence itself.

Identification of regulatory regions driving the expression of the Drosophila spalt complex at different developmental stages.

The zinc finger transcription factors Spalt and Spalt-related have been implicated in multiple developmental processes. In the wing they are regulated by the secreted protein Decapentaplegic and participate in the positioning of the wing veins. The function of Spalt has been also analyzed during tracheal development and embryonic segmentation. Here, we present the isolation and characterization of novel spalt/spalt-related alleles, which analysis indicates that these genes cannot substitute for each other in the developmental processes studied. The mutants present embryonic or pupal lethality, with phenotypes consistent with the loss of spalt function. We also present a detailed functional analysis of the DNA regions implicated in the regulation of these genes. This regulation is complex, integrating the information from both negative and positive regulators, and it is modular, with discrete fragments of DNA directing expression to discrete regions in embryonic and larval tissues.

Detection of mutations and polymorphisms in the p53 tumor suppressor gene by single-strand conformation polymorphism analysis.

Deciphering the genetic mechanisms in cancer development requires analysis of a large number of tumors for consistent genetic alterations. Single-strand conformational polymorphism (SSCP) analysis is a fast and efficient method for detecting mutations, deletions, insertions and loss of alleles. The primary advantage of this method is speed and ability to screen a large number of samples at one time. Here we report the use of the SSCP technique for rapidly screening tumor and normal tissues for mutations and polymorphisms in the p53 tumor suppressor gene. Because the DNA extracted from specific aberrant bands from different samples always give rise to the same nucleotide sequence upon sequencing analysis, the SSCP technique can be used as a diagnostic tool to identify the presence of such genetic alterations without having to spend time on further sequencing analysis.