HNPCC mutations in hMSH2 result in reduced hMSH2-hMSH6 molecular switch functions.

Mutations in the human mismatch repair (MMR) gene hMSH2 have been linked to approximately 40% of hereditary nonpolyposis colorectal cancers (HNPCC). While the consequences of deletion or truncating mutations of hMSH2 would appear clear, the detailed functional defects associated with missense alterations are unknown. We have examined the effect of seven single amino acid substitutions associated with HNPCC that cover the structural subdomains of the hMSH2 protein.

Angiogenesis and Bcl-2 protein expression in patients with endometrial carcinoma.

Considering the particular importance of angiogenesis and tumor suppressor genes expression in solid tumors, angiogenesis and Bcl-2 protein expression were evaluated in order to specify their role in the biology of endometrial carcinoma. Clinical material comprised 66 patients (postmenopausal, aged 52 to 76 years) with endometrial adenocarcinoma. For evaluation of angiogenesis immunohistochemical method was applied using DAKO EPOS Anti-Human Von Willebrand Factor/HRP antibodies.

Biological investigation of the platinum(II)-[*I]iodohistamine complexes of potential synergistic anti-cancer activity.

Cisplatin chemotherapy in combination with external irradiation or with low-dose continuous internal radiotherapy produces significant supra-additive treatment effects towards several tumor cells. The purpose of our research is to develop a new class of platinum-based anticancer drugs containing moieties of synergistic potency such as platinum core and a radiotherapeutic isotope which, delivered directly to the tumorous cells by a specifically designed vectors, should produce a local enhancement of therapeutic dose. Thus, we have synthesized a new platinum-iodohistamine complex and its radioactive analogues labeled with I-125 and I-131.

HSP70 overexpression increases resistance of V79 cells to cytotoxicity of airborne pollutants, but does not protect the mitotic spindle against damage caused by airborne toxins.

Exposure of Chinese hamster V79 cells to extracts of airborne pollutants induced formation of multipolar or incomplete mitotic spindles. To find out whether overexpression of the HSP70 chaperone protein could protect spindles against airborne toxins we constructed V79 cells stably transfected with an expression vector containing rat heat-inducible hsp70.1 gene under the control of a constitutive CMV promoter.

Activation of human MutS homologs by 8-oxo-guanine DNA damage.

The DNA lesion 8-oxo-guanine (8-oxo-G) is a highly mutagenic product of the interaction between reactive oxygen species and DNA. To maintain genomic integrity, cells have evolved mechanisms capable of removing this frequently arising oxidative lesion. Mismatch repair (MMR) appears to be one pathway associated with the repair of 8-oxo-G lesions (DeWeese, T.

Immunoperoxidase detection of polycyclic aromatic hydrocarbon-DNA adducts in breast tissue sections.

Although the etiology of the majority of human breast cancers is unknown, environmental carcinogens are suspected to play a role. In this study, we investigated polycyclic aromatic hydrocarbon-DNA adducts in 78 breast cancer patients and benign breast disease patients with lifetime environmental exposure to polycyclic aromatic hydrocarbon (PAH) compounds. Adducts were detected in paraffin sections by immunoperoxidase method using polyclonal antiserum and were quantitated by the image-analyzing system.

Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1.

We have identified the physical interaction between the Breast Cancer susceptibility gene product BRCA1 and the Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and DNA mismatch repair (MMR) gene product hMSH2, both in vitro and in vivo. The BRCA1-hMSH2 association involved several well-defined regions of both proteins which include the adenosine nucleotide binding domain of hMSH2. Moreover, the interaction of BRCA1 with purified hMSH2-hMSH6 appears to be modulated by adenosine nucleotide much like G protein downstream interaction/signaling is modulated by guanosine nucleotide.

NMR studies on three optical active drug molecules.

NMR spectroscopy is one of very few methods that enable deep insight into molecular structure and distinguishing of enantiomers. It usually requires the use of optically active agents that differentiate S and R forms through an interaction with studied molecule differentiate S and R forms. The aim of the present studies was to perform a preliminary NMR study on three chiral drugs: Fluoxetine hydrochloride, Ibuprofen, and Zolmitriptan by use of three optical solvating agents: R(-) 2,2,2-trifluoro-1-(9-anthryl)ethanol (I), (R)(+) 1,1'-bi-2-naphthol (II), and (S) tert-butyl-phenylphosphinothioic acid (III).

Lidocaine as a protective agent during pancreas cold ischemia.

Pancreatic islet transplantation in humans is a promising alternative for substitutive insulin therapy of IDDM (Insulin Dependent Diabetes Mellitus). Storage of harvested organs is a one of the most important factors, which influence efficacy of islet isolation process. In this sense, appropriate pancreas storage is the main point the successful pancreatic islet isolation.

A nicked duplex decamer DNA with a PEG(6) tether.

A dumbbell double-stranded DNA decamer tethered with a hexaethylene glycol linker moiety (DDSDPEG), with a nick in the centre of one strand, has been synthesised. The standard NMR methods, E.COSY, TOCSY, NOESY and HMQC, were used to measure (1)H, (31)P and T:(1) spectral parameters.

Anticancer activity of genistein-piperazine complex. In vitro study with HL-60 cells.

Genistein, a principal soy isoflavone, has recently aroused interest in medical research owning to its numerous biochemical properties such as: inhibition of the activity of tyrosine-specific protein kinases and topoisomerase II, estrogenic and antioxidant activity as well as antiproliferative and antiangiogenic effects. Therefore, genistein is extensively investigated as a novel anticancer drug. To improve physicochemical properties of genistein (e.

Biological properties of genistein. A review of in vitro and in vivo data.

Genistein--a soy derived isoflavone has recently attracted much attention of the medical scientific community. This compound was found to be a potent agent in both prophylaxis and treatment of cancer as well as other chronic diseases. The great interest that has focused on genistein led to the identification of numerous intracellular targets of its action in the live cell.

The effect of O6-methylguanine DNA adducts on the adenosine nucleotide switch functions of hMSH2-hMSH6 and hMSH2-hMSH3.

The human homologs of prokaryotic mismatch repair have been shown to mediate the toxicity of certain DNA damaging agents; cells deficient in the mismatch repair pathway exhibit resistance to the killing effects of several of these agents. Although previous studies have suggested that the human MutS homologs, hMSH2-hMSH6, bind to DNA containing a variety of DNA adducts, as well as mispaired nucleotides, a number of studies have suggested that DNA binding does not correlate with repair activity. In contrast, the ability to process adenosine nucleotides by MutS homologs appears to be fundamentally linked to repair activity.

Evaluation of radioiodinated histamine as isotope carrier in vivo.

The iodo derivative of histamine labelled with 125I has been used for many years to prepare tracers used in RIA systems. The aim of this study was to evaluate radioiodinated histamine as a potential isotope carrier for in vivo applications. The biological behaviour of radioiodinated histamine has been investigated in rodents.

Monitoring of rat islet allografts with dithizone after induction of donor specific transplant tolerance by intrathymic administration of soluble alloantigens.

Transplantation of whole pancreas or pancreatic islets remains a promising approach to treatment of diabetes mellitus. Since there is no efficient method presently known for in vivo detection of pancreatic islet rejection, we have utilized dithizone [DTZ] to monitor the survival of transplanted islet allografts following the induction of tolerance by a new strategy of deliberate introduction of donor antigens into the adult thymus. In this study, we examined the morphology of islet allografts in vivo and in vitro following pretreatment with intrathymic (IT) inoculation of 2 mg soluble Ag obtained from 3M KCl extracts of resting T-cells with or without ALS immunosuppression in the WF-to-Lewis combination.

[Immunoregulatory mechanisms of action of intravenous gammaglobulin in Kawasaki syndrome].

Kawasaki Syndrome (KS) is an acute vasculitis in young children associated with the development of coronary artery abnormalities. KS has been reported to occur in over 40 countries including Poland. The etiology of this disease remains controversial.

Angiogenesis in endometrial cancer.

We evaluated the level of angiogenesis in endometrial adenocarcinoma and investigated the relationship between tumor vascularity and clinicopathological parameters. The level of angiogenesis in noninvaded uterine smooth muscle was also studied. Angiogenesis was studied in uteri of 29 post-menopausal women operated on for endometrial cancer.

Synergistic activation of protein kinase Calpha, -betaI, and -gamma isoforms induced by diacylglycerol and phorbol ester: roles of membrane association and activating conformational changes.

Protein kinase Calpha (PKCalpha) has been shown to contain two discrete activator sites with differing binding affinities for phorbol esters and diacylglycerols. The interaction of diacylglycerol with a low-affinity phorbol ester binding site leads to enhanced high-affinity phorbol ester binding and to a potentiated level of activity [Slater, S. J.

Mitochondrial activity after cold preservation of pancreatic islet cells treated with pefloxacin (PFX).

Mitochondrial energetic and oxidative dysfunctions caused by free radical production trigger release of proinflammatory cytokines involved in organ rejection. The aim of this study was to investigate the role of a fluoroquinolone drug, pefloxacin (PFX) and those of various cold preservation solutions on pancreatic beta cell viability. Our data clearly demonstrate that islet cell viability, as determined by glucose-stimulated insulin secretion, is directly correlated with reduced expression of microsomal cytochrome P-450IIIA.

Rocuronium versus succinylcholine: are they equally effective during rapid-sequence induction of anesthesia?

Unlabelled: The purpose of our study was to assess the onset and quality of muscle paralysis and intubation conditions with succinylcholine (Sch) or rocuronium (Roc) during rapid-sequence induction. Patients were randomly assigned to receive thiopental (5 mg/kg) and Sch (1.5 mg/kg) or thiopental (5 mg/kg) and Roc (1.