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PubMedDate not supplied

Flexible modelling in survival analysis. Structuring biological complexity from the information provided by tumor markers.

The aim of the present article is to introduce and discuss the problem of optimal modelling of the prognostic information provided by putative prognostic variables, possibly measured on a quantitative scale. A number of methodological aspects will be treated, with particular reference to the role of spline functions and artificial neural networks, which will be discussed in the context of the analysis of survival data. The problem of the evaluation and the choice of the optimal statistical models will be examined, with particular attention to the critical aspects related to the definition of prognostic indexes on the basis of the results of the selected models. Clinical examples in breast cancer on the evaluation of the prognostic impact of several tumor markers are provided. This paper is addressed to all researchers who are interested in the evaluation of the prognostic role of tumor markers, therefore we will stress the necessity of integrating the methodologies of biological, clinical and statistical research in the assessment of prognosis.

Biomarkers, Tumor↗
PubMed2002

Mother nature's combinatorial libraries; their influence on the synthesis of drugs.

Natural products or secondary metabolites, whether from the microbial, plant or marine worlds, represent the results of evolutionary pressures to preserve and enhance the life of their producing organism. They have evolved into structurally and usually stereochemically complex compounds with specific bioactivities. They thus represent a diverse 'combinatorial library' that may have potential pharmaceutical use. In principle, the combination of this diverse library with the methods of combinatorial chemistry could lead to an unlimited supply of diverse and complex structures, and is recommended as a fruitful approach for future drug development. Examples of the application of combinatorial methods to nature's combinatorial library will be presented and discussed, with an emphasis on the antitumor, anti-infective and pain control disease areas.

Analgesics↗
PubMed1992

On the fine structure and complex carbohydrate cytochemistry of the rabbit parotid gland.

The parotid gland of the rabbit, a lagomorph species, was studied by ultrastructural techniques and carbohydrate ultracytochemical stainings. The rabbit parotid gland is a peculiar mixed gland consisting of serous and mucous secretory cells due to their histochemical properties supported by biochemical findings. Acinar cells exhibit heterogeneous features of secretory granules with different electrondensity and occasional presence of subunits. Intercalated duct cells show nuclei with deep indentation and apical granules partly similar to acinar secretory products. Striated ducts are characterized by three different cell populations, namely "light cells" with small secretory granules, "dark cells" rich of scattered mitochondria and typical striated cells. The presence of differentiated cell types within striated duct segments lends credence to the idea that, in addition to the role in electrolyte transport, some ductal cells may be involved in secretion and/or absorption of glycosylated products.

Animals↗
PubMed2006

Stochasticity, complex spatial structure, and the feasibility of the shifting balance theory.

Sewall Wright's shifting balance theory of evolution posits a mechanism by which a structured population may escape local fitness optima and find a global optimum. We examine a one-locus, two-allele model of underdominance in populations with differing spatial arrangements of demes, both analytically and with Monte Carlo simulations. We find that inclusion of variance in interpatch connectivities can significantly reduce the number of generations required for fixation of the more favorable allele relative to island and stepping-stone models. Although time to fixation increases with migration rate in all cases, the presence of one or two relatively isolated demes may reduce the number of generations by 80% or more. These results suggest that the shifting balance process may operate under less restrictive conditions than those found with a simple spatial arrangement of demes.

Biological Evolution↗
PubMed1990

[Functional morphology of the kidney. A review of the histophysiology of the kidney glomerulus, the nephrons and the collecting tubule system].

The kidney is a composite organ, the specific activities of which are attributable to the peculiar construction of the individual components of the glomerula, nephrons and collecting tubules. This comprehensive review will address the essential physiological mechanisms of urine formation, such as filtration, secretion, reabsorption and concentration, and correlate these functions to morphological structures where possible. The complex structure of the renal glomerulus as the basis for the formation of primary urine (blood-urine barrier) will be documented on the basis of electron micrographs. In addition to this, the ultrastructure of the epithelium in the various tubular segments and collecting tubules will be discussed from a histophysiological stand-point, including its significance in the excretion of waste substances and maintenance of a constant fluid environment in the body (Homeostasis).

Animals↗
PubMed1977

Hypotensive activity of sodium nitroprusside and structurally related complexes of sodium pentacyanoamine ferrate with amylnitrite, butylnitrite and n-octylamine.

Complexes of sodium pentacyanoamine ferrate (TPF) with amylnitrite and with butylnitrite showed hypotensive activity equal to that of sodium nitroprusside, as tested intravenously, in unanesthetized , instrumented Rhesus, monkeys. The complex with n-octylamine, on the other hand, had significantly lower activity. These complexes produced only marginal hypotensive effects when administered orally in a dose of 10 mg/kg to spontaneously hypertensive rats.

Administration, Oral↗