A possible mechanism for exonuclease 1-independent eukaryotic mismatch repair

Mismatch repair contributes to genetic stability, and inactivation of the mammalian pathway leads to tumor development. Mismatch correction occurs by an excision-repair mechanism and has been shown to depend on the 5′ to 3′ hydrolytic activity exonuclease 1 (Exo1) in eukaryotic cells. However, genetic and biochemical studies have indicated that one or more Exo1-independent modes of mismatch repair also exist. We have analyzed repair of nicked circular heteroduplex DNA in extracts of Exo1-deficient mouse embryo fibroblast cells. Exo1-independent repair under these conditions is MutLα-dependent and requires functional integrity of the MutLα endonuclease metal-binding motif. In contrast to the Exo1-dependent reaction, we have been unable to detect a gapped excision intermediate in Exo1-deficient extracts when repair DNA synthesis is blocked. A possible explanation for this finding has been provided by analysis of a purified system comprised of MutSα, MutLα, replication factor C, proliferating cell nuclear antigen, replication protein A, and DNA polymerase δ that supports Exo1-independent repair in vitro. Repair in this system depends on MutLα incision of the nicked heteroduplex strand and dNTP-dependent synthesis-driven displacement of a DNA segment spanning the mismatch. Such a mechanism may account, at least in part, for the Exo1-independent repair that occurs in eukaryotic cells, and hence the modest cancer predisposition of Exo1-deficient mammalian cells.     

Heparin and aspirin attenuate placental apoptosis in vitro: implications for early pregnancy failure

OBJECTIVE: Live birth rates are increased by treatment with heparin and aspirin in cases of poor pregnancy outcome such as antiphospholipid syndrome. Both drugs may attenuate miscarriage by inhibiting aberrant coagulation or by modulating trophoblast apoptosis. Here we assessed their roles in trophoblast apoptosis in vitro. STUDY DESIGN: BeWo cells and placental villi were cultured in sera from women with successful or failing in vitro fertilization, with and without heparin or aspirin. Apoptosis was assessed by using DNA laddering, cytokeratin 18 neoepitope formation, Bcl-2, and caspase 7 expression. RESULTS: In BeWo cells, sera from in vitro fertilization failure increased trophoblast apoptosis, whereas heparin and aspirin reversed these effects. In villous trophoblast, heparin increased Bcl-2 and cytokeratin 18 protein expression. Heparin and aspirin inhibited DNA laddering. CONCLUSION: Heparin and aspirin modulate trophoblast apoptosis suggesting a direct impact on trophoblast biology, thus providing an additional mechanism to explain the clinical benefits of heparin and aspirin on recurrent pregnancy loss.     

Quamatel application in three-drug eradication therapy of duodenal ulcer and gastroduodenal ulcerations associated with helicobacter pylori infection

Combination of famotidine, amoxicilline and metronidasole was applied in the treatment of 71 patients with erosive-ulcerative affection of the upper gastrointestinal tract. The combination more rapidly relieved pain (within 5-6 days), dyspepsia (for 7-8 days), enabled healing of the ulcer defect for 2-3 weeks, raised gastric pH to 5.7-5.8 and eradicated Helicobacter pylori in 87.3% of the cases.     

The prevention and treatment of postoperative intestinal paralysis in peptic ulcer surgery]

Under analysis were results of using intraintestinal electrostimulation with autonomous electrostimulators of gastrointestinal tract and graded enteral probe nutrition under control of intraintestinal pressure in 68 patients after operation on the stomach and duodenum. The method gives more rapid recovery of the intestine mobility, is economically profitable, makes the risk of insufficiency of the duodenal stump after gastric resection considerably less. The method is recommended for clinical practice.     

K20 and ICO-10 monoclonal antibodies (gp120/200; Thy-1): immunophenotyping of human solid tumours

Solid tumour cells were shown to express VLA-beta and Thy-1 antigens. For identification of these molecules two monoclonal antibodies, K-20 and ICO-10, characterised in detail previously, were used. Four groups of solid tumours have been identified according to their immunophenotype: VLA-beta+ and Thy-1-; VLA-beta+ and Thy-1+; VLA-beta- and Thy-1+; VLA-beta- and Thy-1-. To a certain extent these groups have been shown to reflect tumour histogenesis: tumours of epithelial origin never expressed an ICO-10+, K20-phenotype while soft tissue sarcomas and neuroblastoma cells never expressed the beta-chain of VLA molecular complexes.     

Principles of concervative therapy of urolithiasis and prevention of stone formation recurrence

The modern view of treatment for various forms of nephrolithiasis reflects the main features of nephrolithiasis pathogenesis, but changes in metabolic condition, the presence of dysmetabolism, and the course of pathologic process are not taken into account. Considering that the disease is easier to prevent than to treat, it would be more appropriate to base preventive measures not only on the data from general clinical and biochemical examination, but also on the results of aggregatometry and complex chromato-mass-spectrometric examination allowing prediction of the development of the pathologic process.     

Videoendoscopic ligation of the internal seminal veins in bilateral varicocele

Varicocele diagnosis should be based not only on physical methods but on ultrasound dopplerography as well (flebography or scrotal thermography) to detect a subclinical form and bilateral process. Bilateral varicocele (BV) occurs more often than is diagnosed. It results in more changes in spermogram and is a prognostic infertility factor. Bilateral pain, impairment of spermatogenesis and infertility are indications for bilateral ligation of the seminal veins in BV patients. Bilateral ligation is much more effective than unilateral. Laparoscopic and microsurgical methods are most effective and low invasive in correction of BV and present a method of choice in the treatment of such patients.