Catalytic oxidative coupling promoted by bismuth TEMPOxide complexes.

Bismuth(iii) TEMPOxide compounds have been synthesized from the coupling of Bi(ii) species with the TEMPO˙ radical. The steric profile of the supporting bis(amido)disiloxane ligand promotes different fluxional behaviour in solution, and DFT calculations suggest variation in the Bi-O bond character. These compounds are active catalysts for oxidative coupling of TEMPO and silane substrates, believed to proceed via metathesis of Bi-O and Si-H bonds followed by decomposition of bismuth-hydride intermediate species.

Carbodiimides as catalysts for the reduction of a cadmium hydride complex.

A rare terminal cadmium hydride complex [(BDI)CdH] (BDI = [{N(2,6-iPr2C6H3)C(Me)}2CH]) has been synthesised from [(BDI)CdCl] and LiEt3BH. The hydride can be reduced to the cadmium(i) dimer, [(BDI)CdCd(BDI)] upon treatment with a catalytic amount of diisopropyl- or dicyclohexylcarbodiimide.

Neutral and cationic bismuth compounds supported by bis(amidodimethyl)disiloxane ligands.

Bis(amidodimethyl)disiloxane ligands derived from O{SiMe2N(H)R}2 (abbreviated as (NONR)H2) are a stable support for neutral and cationic bismuth compounds. Attempts to extend the series Bi(NONR)Cl (R = Ar = 2,6-iPr2C6H3; R = tBu) to include compounds where R = Ar' = 2,6-Me2C6H3 were complicated by concomitant formation of the bimetallic compound {Bi(NONAr')}2(µ-NONAr'). Compounds containing [Bi(NONR)]+ cations were obtained from reactions with group 13 chlorides MCl3 (M = Al, Ga). X-ray crystallographic analysis showed intermolecular interactions with the [MnCl(3n+1)] anion.

Hydrophosphination-type reactivity promoted by bismuth phosphanides: scope and limitations.

Phenyl isocyanate inserts into the Bi-P bond of the terminal phosphanide Bi(NONAr)(PCy2) (NONAr = [O(SiMe2NAr)2]2- Ar = 2,6-iPr2C6H3) to afford the κ2N,O-phosphanylcarboxamidate complex. Liberation of the hydrophosphination product from the metal is achieved by reaction with HPPh2. The diphenylphosphanide product, Bi(NONAr)(PPh2), is however unstable and decomposes to generate reduced species, preventing catalytic turnover.

Dissecting the non-canonical functions of telomerase.

It is now well established that the canonical function of telomerase protects the telomere repeats from erosion and the consequent induction of replicative senescence or apoptosis. In the absence of key cell cycle checkpoint proteins, the canonical function of telomerase also prevents chromosome fusions and immortalizes human cells. The canonical function of telomerase requires both the telomerase reverse transcriptase enzyme (TERT) which adds telomere (TTAGGG) repeats to the chromosome ends and the telomerase RNA component (TERC), which provides the template for TERT. However, there is growing evidence that telomerase has other (non-canonical) functions. These functions can be divided further into those that require telomerase activity but not telomere lengthening (non-canonical I or NC I) and those that require neither telomerase activity nor telomere lengthening (non-canonical II or NC II). NC I functions are associated with the induction of neoplasia in both epidermis and mammary gland, the correct response to DNA damage, and insensitivity to transforming growth factor beta. In contrast, NC II functions are not sufficient for the induction of neoplasia and are associated with the activation of the WNT and MYC signaling pathways in keratinocytes and a more general resistance to the induction of apoptosis by a variety of stimuli. The overexpression of either TERT or TERC appears to be capable of providing NC I functions but NC II functions require neither TERC nor the integrity of the TERT catalytic site. The molecular mechanisms underpinning both NC I and NC II are largely obscure but transcriptional profile changes have been reported by some groups. In this article, we will discuss the proposed mechanisms of NC I and NC II and their relevance to normal and neoplastic cell functions.

Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83.

Early reports indicated that ECV304 was a spontaneously-transformed line derived from a Japanese human umbilical vein endothelial cells (HUVEC) culture. Many morphological, immunochemical, and genetic studies provided further evidence that ECV304 was a valuable biomedical research tool and could be used to study processes that include angiogenesis in vitro and signal transduction by a variety of G protein-coupled receptors. However, several distinct differences between ECV304 and HUVEC are now apparent and recent reports have indicated genetic similarity between ECV304 and T24/83, a human bladder cancer cell line. To further assess the utility of ECV304 as a human endothelial cell model, we compared the functional responses of ECV304 and T24/83 to a range of G protein-coupled receptor agonists. We also used DNA fingerprinting to karyotype both ECV304 and T24/83. Both ATP and uridine triphosphate (UTP) stimulated inositol phosphate metabolism in ECV304 without alteration of cAMP levels. Comparative data using selective P2Y receptor agonists indicated that this response, leading to calcium mobilization from intracellular stores, was predominantly mediated by the activation of P2Y2 receptors. Similar responses were recorded from both ECV304 and T24/83 cells. ECV304 expressed a relatively high basal activity of NOS that was reduced by L-NAME and stimulated by P2Y2 receptor agonists. In contrast, P2Y2 receptor activation did not induce prostaglandin synthesis in ECV304. Both ECV304 and T24/83 express receptors for adenosine, adrenaline, and calcitonin, which stimulate adenylate cyclase. Proliferation of ECV304 and T24/83 cells, measured by the incorporation of [3H]thymidine into DNA, was largely serum-independent. This was in contrast to parallel experiments with porcine and bovine aortic endothelial cells that indicated a marked serum-dependent increase in DNA synthesis. Genetic analysis confirmed that ECV304 and T24/83 are identical. ECV304 displays some endothelial characteristics and is useful for the study of receptor pharmacology. However, ECV304 is not of HUVEC origin and is therefore an inappropriate cell line to study endothelial cell biology.

Laparoscopic-assisted colectomy. Initial experience.

OBJECTIVE: The authors studied the results of laparoscopic colectomies performed by a surgical team on 80 consecutive patients and compared these results with standard open colectomies. METHODS: Eight consecutive laparoscopic-assisted colectomies were performed by Norfolk Surgical Group in a 14-month period and compared to 53 patients who had a conventional open colectomies. Analysis included indications for surgery, types of procedure, complications, incidence and causes for conversion, length of procedure, duration of postoperative ileus, hospital stay, operating room and total hospital charges, and examination of the pathologic specimens. RESULTS: Many different types of colectomies were performed successfully and safely for a variety of surgical indications. The conversion rate was 22.5%, which decreased to 15% in the second half of the series. Complications in patients who underwent laparoscopic operations were not severe in number of type. The length of the operative procedure, operating room charge, and the total hospital charge were greater for patients undergoing laparoscopic-assisted colectomies. Patients who underwent laparoscopic operations had a shorter period of postoperative ileus and less pain, resumed a regular diet sooner, and were discharged from the hospital sooner than patients who underwent open colectomies. There was no significant difference in the pathology specimens obtained by laparoscopic-assisted colectomies compared with conventional open colectomies for length of specimen, surgical margins, and number of lymph nodes retrieved. CONCLUSIONS: This study indicated that laparoscopic techniques can be applied safely and effectively to a broad range of colonic operations. Laparoscopic-assisted colectomies take longer to perform and are more costly, but are associated with less paralytic ileus, less pain, and reduced hospital stay. Laparoscopic colectomies for the treatment of malignancy are achievable technically, but will require careful long-term study.

Obstructing malignant lesions of the colon.

Evidence has been presented to suggest that the patient with an obstructed carcinoma of the colon may have a more malignant form of the disease independent of lymph node status or tumor encirclement of the bowel. Rate of tumor growth is never consistent in patients with this disease. Patients who develop colon obstruction early in the course of the disease seem to have more aggressive tumors with rapid growth and a much poorer long-term prognosis. Perforations frequently accompany obstructions of the colon. Patients in this group have a dismal prognosis. Individuals with obstructed carcinoma of the colon have a higher operative mortality and morbidity and a shorter long-term survival. The higher operative mortality and morbidity may depend entirely on the choice of operative procedures. Tumor location affects prognosis. Obstructing tumors in the left colon have a more favorable prognosis than those in the right colon. Obstructing right colon tumors have a much poorer survival (three times worse) than nonobstructing carcinomas of the right colon. Obstructing tumors in the rectum have a very poor prognosis. Evidence exists that resection of the tumor without preliminary proximal decompression may reduce hospital mortality and morbidity and increase long-term survival. In selected cases, primary resection can be done as safely as staged operative procedures. Primary anastomosis with resection of the left colon carries a higher operative mortality because of anastomotic leaks. Resection without anastomosis is much safer. Primary resection with anastomosis is the procedure of choice in obstructing lesions of the right colon. This has a lower operative mortality and morbidity than a staged procedure. This primary resection with anastomosis is certainly as safe as an ileotransverse colostomy. It is important not to abandon the time-honored surgical principle of never suturing obstructed bowel. Primary resection without anastomosis confirms this surgical principle. Meticulous preoperative and postoperative care employing physiological monitoring, multiple antibiotics, total parenteral hyperalimentation, and respiratory and circulatory support will further reduce the hospital mortality and morbidity. Patients who initially appear to be obstructed on barium enema, but who in truth are only partially obstructed, can be properly managed so that an elective primary resection with anastomosis can be done with the same operative mortality and morbidity as in other elective colon cancer patients.