Preparation,characterisation and properties of poly(ether-amide)s bearing hydroxyl side groups and of their derivatives with the synthetic auxin 1-naphthylacetic acid

New water-soluble poly(ether-amide)s (PEA)s were synthesised by polycondensation of diethyl L-tartrate and commercial polyethers having isopropylamino end-groups (Jeffamine ED-600 or Jeffamine ED-900). PEAs were derivatised with the synthetic auxin 1-naphthylacetic acid (NAA). It was shown that PEA and their esters with NAA (PEA-NAA) form interpolymer complexes with polyacids and that the complex formation is favoured by the hydrophobic NAA-residues in PEA-NAA. The hydrolysis of PEA-NAA was found to proceed mainly by cleavage of the ester bonds linking the pendant NAA-residues. The pòly-(ether-amide) main chain was found to be more stable than the similar poly(ether-ester) chain of poly[oxytartaroyloxypoly(oxyethylene)].     

Establishment of tumor cell culture (ILA) derived from hamster pancreatic islets treated with BOP

ILA cells were established from tumors induced by the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) in hamster islets. The proliferation, morphology, karyotype, immunoreactivity with certain antibodies and growth factor secretion of these tumor cells were compared with the same parameters in tumor cells induced by BOP in hamster ductal cells (TAKA-1-BOP) established in a previous study. Minor differences were found in the morphology and ultrastructure of the 2 cell lines. Contrary to TAKA-1-BOP cells, ILA cells did not express cytokeratins 8.13, 13 or 18 but did express DU-PAN-2 and TAG-72, 2 known human pancreatic cancer–associated antigens. No endocrine cell markers were expressed. A significant difference also was found in the chromosomal pattern in that there were more abnormalities and marker chromosomes in ILA cells than in TAKA-1-BOP cells and the Y or X chromosomes were missing in ILA cells. ILA cells produced TGF-α, IGF-1, bombesin and gastrin and expressed specific binding sites for hEGF. TGF-α secretion from ILA cells was much greater than that from TAKA-1-BOP cells. Our results indicate that pancreatic cancer cells grown in vitro are not a single clone. We conclude that there are some genetic and biological differences between tumors arising from pancreatic duct and islets and that pancreatic ductal adenocarcinomas originating from islets have a profound malignant potential. Int. J. Cancer 78:636–641, 1998. © 1998 Wiley-Liss, Inc.     

Prolonged catheter-induced coronary artery spasm mimicking fixed stenosis

Two cases of prolonged catheter-induced right coronary artery spasm, mimicking fixed stenoses, are presented. In one case, the spasm appeared at the same place in sequential catheterizations. This angiographic finding may be easily misinterpreted as a fixed lesion, leading to unnecessary attempts at angioplasty. Cathet. Cardiovasc. Diagn. 41:170–173, 1997. © 1997 Wiley-Liss, Inc.     

Sodium-23 solid-state nuclear magnetic resonance of commercial sodium naproxen and its solvates

We report on the investigation of sodium coordination environments with solid-state 23Na nuclear magnetic resonance (NMR) spectroscopy of various hydrates and solvates of sodium naproxen (SN), a commercially available anti-inflammatory drug sold over the counter as Aleve?, among other names. The 23Na quadrupolar coupling constant is found to change significantly depending on the hydration state, and subtle changes in oxygen coordination environment about the sodium cations were apparent in the NMR spectra. High-resolution double-rotation NMR experiments are also performed on powdered samples to obtain solution-like 23Na NMR spectra. Our attempts at crystallizing various solvates of SN have led to the characterization of the first crystal structure for the heminonahydrated form. The composition of commercial SN is also investigated and it is shown that Aleve? is composed of approximately 80% monohydrate solvate. Density-functional theory calculations, using the gauge-including projector-augmented-wave formalism, allow for the assignment of 23Na NMR peaks to specific sodium sites in the reported X-ray crystal structure.     

Circulating serologic and molecular biomarkers in malignant melanoma

The worldwide incidence of malignant melanoma has been increasing during the past decade and is a public health concern because this disease accounts for up to 90% of deaths from cutaneous malignancies. It remains a devastating disease with few therapeutic options once in an advanced stage. Current methods of detection, prognostication, and monitoring of melanoma focus on clinical, morphologic, and histopathologic characteristics of measurable tumor. Although this information provides some insight into disease behavior and outcome, melanoma is still an unpredictable disease. Significant effort has been put into finding an informative serologic biomarker. However, the marker remains elusive, and investigations continue. Using the PubMed database, we reviewed the published literature on serologic melanoma biomarkers and present a synopsis of the extensive investigations that have been performed thus far, provide some insight into why most have failed to become incorporated into routine clinical use, and present an overview of innovative methods currently being explored.     

IL-6 Levels,Nutritional Status,and Mortality in Prevalent Hemodialysis Patients

Summary

Background and objectives

The influence of serum IL-6 levels on nutritional status in chronic hemodialysis (HD) patients remains to be elucidated. The present report describes a prospective longitudinal study of IL-6 levels and nutritional parameters to determine whether high IL-6 levels are independently associated with nutritional status over time in a cohort of prevalent hemodialysis patients.

Design, setting, participants, & measurements

85 clinically stable hemodialysis patients (37.6% women), with a mean age of 66.5 ± 10.6 years, were studied after exclusion of patients with BMI < 20 kg/m² and/or serum albumin <35 g/L. IL-6, dietary energy and protein intake, and biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18, and 24 months following enrollment. Observation of this cohort was continued over 2 additional years.

Results

IL-6 levels increased with time in both unadjusted (linear estimate: 2.57 ± 0.44 pg/ml per 2 yrs; P = 0.001) and adjusted models (linear estimate: 2.35 ± 0.57 pg/ml per 2 yrs; P = 0.049). Significant reductions of daily energy intake, laboratory markers (albumin, transferrin, cholesterol, creatinine), and body composition (fat mass) with higher IL-6 levels were observed over the duration of the longitudinal observation period. However, none of the studied parameters were associated with changes in IL-6 levels over time (IL-6-by-time interactions were NS). Furthermore, cumulative incidences of survival were correlated with the baseline serum IL-6 levels (P = 0.004 by log-rank test). Finally, for each pg/ml increase in IL-6 level, the hazard ratio for death from all causes was 1.06 (95% CI 1.01 to 1.10) after adjustment for demographic and clinical parameters.

Conclusions

Our results suggest that higher serum IL-6 levels are associated with all-cause mortality without additional changes in clinical and laboratory markers of nutritional status in clinically stable HD patients.     

Oligomeric-induced activity by thienyl pyrimidine compounds traps prion infectivity

Accumulation of PrP(Sc), an abnormal form of cellular prion protein (PrP), in the brain of animals and humans leads to fatal neurodegenerative disorders known as prion diseases. Limited protease digestion of PrP(Sc) produces a truncated form called PrP(27-30) that retains prion infectivity and is the main marker of disease targeted in most diagnostic tests. In the search for new anti-prion molecules, drug-screening assays on prion-infected murine cells have been oriented toward decreasing levels of PrP(27-30). In contrast, we screened for drugs promoting multimers of PrP(27-30), illustrating a possible stabilization of mouse PrP(Sc) species, because recent studies aiming to characterize the conformational stability of various prion strains showed that stable recombinant amyloids produced more stable prion strain, leading to longest incubation time. We identified a family of thienyl pyrimidine derivatives that induce SDS-resistant dimers and trimers of PrP(27-30). Bioassays performed on mice brain homogenates treated with these compounds showed that these thienyl pyrimidine derivatives diminished prion infectivity in vivo. Oligomeric-induced activity by thienyl pyrimidine compounds is a promising approach not only to understanding the pathogenesis of prions but also for prion diagnostics. This approach could be extended to other neurodegenerative "prionopathies," such as Alzheimer's, Huntington, or Parkinson's diseases.