Carcinogenic mechanisms: A critical review and a suggestion that oncogenesis may be adaptive ontogenesis

The precise mechanism(s) whereby normal cells become malignant are not known with any degree of certainty. However, many mechanisms have been proposed on the basis of available experimental evidence as interpreted by the proposer. These fall into two main groups and are based upon changes in genetic structure (somatic mutation hypotheses) or in genetic expression (epigenetic hypotheses). Yet a third group embodies elements of the first two. The more important of all these proposals are critically reviewed and yet another hypothesis is ventured.In this hypothesis, the induction of neoplasia is envisaged as embodying (a) initiation of preferentially partly-differentiated and resting stem cells and (b) promotion of the initiated cells, through mitosis and further differentiation and by adaptations of normal ontogenic mechanisms, into a variety of novel phenotypes which are malignant or potentially so. Cancer-specifying genes, altered chromosomes, de-differentiations and interrupted re-differentiations are not considered to be causally involved, although the last three of these can be present as epiphenomena. Evidence cited in support of this proposal appears to show a general absence from cancer cells of any single property, including an abnormality in genetic constitution or in cellular expression, which is specific to malignancy. Malignancy is thus envisaged as abnormal expressions of the genetic potential of the zygote. Some practical and theoretical implications of this concept are discussed.     

Occurrence of melanin granules and melanosynthesis in the kidney of Sparus auratus

An optical, ultrastructural, and biochemical study of the melanin accumulation nodules found in the kidney of the teleost fish Sparus auratus is presented. These nodules are randomly distributed in the interstitium of the renal tissue. They are formed by large aggregates of cells replete with melanin granules. The melanin granules occur singly or also in aggregates inside the cells. Most of the granules are electron-dense, but sometimes small electron-lucent spaces within them can be seen. Some secondary lysosomes and dendritic processes can also be observed. Biochemical studies have proved for the first time the existence of measurable tyrosinase activity in those nodules. That activity was assayed using three methods: tyrosine hydroxylation, dopa oxidation, and melanin formation. Furthermore, inhibitors of well-characterized plant and animal skin tyrosinases were effective agents for inhibiting those activities in fish kidney preparations. This finding supports the notion of the existence of true tyrosinase in the melanin accumulation nodules of this tissue. Taking into account the results obtained, the origin and functions of the melanin-containing cells found in the teleost fish kidney are discussed.     

Transport of L-tyrosine by B16/F10 malignant melanocytes: characterization of the process

The main characteristics of L-tyrosine (L-Tyr) uptake by B16/F10 malignant melanocytes are reported. This amino acid can be taken up by two systems, both of them being saturable. The first one would be system L. This system can be studied in cells preloaded with amino acids that are a good substrate for system L, such as L-methionine or L-tryptophan. The kinetic parameters for L-Tyr uptake by this transport system are Vm = 6.5 pmol L-Tyr/10(3) cells.min and Km around 130 microM. The second system, probably the system ASC, shows lower capacity but higher affinity than the former. This system can be detected only in cells previously depleted of amino acids, showing approximate kinetic values of Vm 0.05 pmol L-Tyr/10(3) cells.min and Km around 5 microM. It is shown that the increase in cell density yields a decrease in the rate of L-Tyr uptake by system L, but this increase does not affect the high affinity system, alpha-MSH does not affect significantly the L-Tyr uptake by both systems. 2-Amino bicyclo-(2,2,1)-heptane-2-carboxylic acid produces a remarkable inhibition of the rate of L-Tyr uptake, but alpha-methylaminoisobutyric acid does not affect the rate of transport of this amino acid. The absence of sodium produces a slight but reliable decrease in the rate of L-Tyr uptake, supporting the involvement of two different transport systems. The ionophores monensin and nigericin enhance the transport by system L, but this effect is suppressed by the presence of ouabain. This finding indicates that the (Na+ -K+)-ATPase is essential for the stimulating action of ionophores.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evolución del microprolactinoma a largo plazo con tratamiento médico

IntroductionProlactinoma is the most frequent functioning pituitary adenoma. Most commonly occurs as microprolactinoma (less than 1 cm in size), which may be cured with medical therapy, but few long-term studies are available about optimal duration of treatment with dopamine agonists to ensure cure after drug discontinuation and its withdrawal without recurrence are do not report consistent results.ObjectiveTo establish criteria for cure of microprolactinoma with medical treatment and to analyze the potential predictors involved.PatientsA retrospective study was conducted on 47 adult women with microprolactinoma followed up between 1975 and 2010; none of them had undergone prior surgery or radiotherapy, and all of them received treatment with a dopamine agonist for at least 4 years. They were divided into two groups for analysis: cured patients with at least 4 years with normal prolactin levels after drug discontinuation, and not cured patients.ResultsCure was achieved in 57.4% of patients. Only age at diagnosis was a significant predictor: there were more young patients in the cured group and youngest patients needed less time to cure. Development of empty sella turcica or normal MRI were similar regarding time to cure.ConclusionsMicroprolactinoma may be cured with dopamine agonists, and life-long treatment is not required, although more than 10 years may be required to achieve cure, 11,6 ± 5,3 years in our experience.     

SNPs selected by information content outperform randomly selected microsatellite loci for delineating genetic identification and introgression in the endangered dark European honeybee (Apis mellifera mellifera)

The honeybee (Apis mellifera) has been threatened by multiple factors including pests and pathogens, pesticides and loss of locally adapted gene complexes due to replacement and introgression. In western Europe, the genetic integrity of the native A. m. mellifera (M‐lineage) is endangered due to trading and intensive queen breeding with commercial subspecies of eastern European ancestry (C‐lineage). Effective conservation actions require reliable molecular tools to identify pure‐bred A. m. mellifera colonies. Microsatellites have been preferred for identification of A. m. mellifera stocks across conservation centres. However, owing to high throughput, easy transferability between laboratories and low genotyping error, SNPs promise to become popular. Here, we compared the resolving power of a widely utilized microsatellite set to detect structure and introgression with that of different sets that combine a variable number of SNPs selected for their information content and genomic proximity to the microsatellite loci. Contrary to every SNP data set, microsatellites did not discriminate between the two lineages in the PCA space. Mean introgression proportions were identical across the two marker types, although at the individual level, microsatellites' performance was relatively poor at the upper range of Q‐values, a result reflected by their lower precision. Our results suggest that SNPs are more accurate and powerful than microsatellites for identification of A. m. mellifera colonies, especially when they are selected by information content.     

Somatomedin levels in the diagnosis and therapy of growth hormone deficiency

Serum somatomedin-C (SM-C) and somatomedin (SM) concentrations were measured by, respectively, radioimmuno (SM-C RIA) and radioreceptor assays (SM RRA) in 3 groups of children with short stature. The patient population was different from previously reported series in that it was urban Brazilian, low income, and significantly older. Group A consisted of 6 male and 3 female children, aged 7.7-16.0 years, whose average peak plasma immunoreactive growth hormone (GH) was above 10 ng/ml. Group B contained 8 male and 5 female untreated GH-deficient patients, ranging in age from 9.5 to 21.0 years. In Group C there were 4 male and 1 female GH-deficient subjects treated with I.M. injections of GH (0.1 U/kg) from 1 month to 7 years. The mean +/- SE basal RIA SM-C (ng/ml) concentrations were significantly lower in groups B (34.2 +/- 8.8) and C (43.8 +/- 13.7) than A (214.3 +/- 42.7): A X B, P less than 0.001 and A X C, P less than 0.02. Likewise the mean +/- SE basal RRA SM (ng/ml) concentrations were significantly lower in groups B (78.9 +/- 17.6) and C (90.8 +/- 19.3) than group A (316.3 +/- 43.0): A X B, P less than 0.001 and A X C, P less than 0.002. A significant linear correlation was observed between RIA and RRA in group B (r = 0.84; P less than 0.001) and C (r = 0.96; P less than 0.01), but not for A (r = 0.61; P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Flow cytometric determination of lipid content in a marine dinoflagellate, Crypthecodinium cohnii

Since flow cytometry allows rapid,simultaneous and quantitative measurementsrelated to cell morphology andphysiologicy, the lipid-specificfluorescent dye, Nile Red, was employed forthe in vivo lipid quantification of Crypthecodinium cohnii, a heterotrophicmarine dinoflagellate rich inpolyunsaturated long chain fatty acids. Thefluorescence signal was linearly correlatedwith the neutral and polar lipid content asdetermined by gravimetric techniques. Asignificant correlation of NR signal wasalso observed between the polar to neutrallipid ratio and docohexaenoic acid percell. The results demonstrate a method forrapid lipid quantification that can be usedin the selection, isolation and culturecontrol of C. cohnii clones with highlipid and DHA content.     

Correlation between Central Memory T Cell Expression and Proinflammatory Cytokine Production with Clinical Presentation of Multibacillary Leprosy Relapse

BackgroundDespite the efficacy of multidrug therapy, surviving Mycobacterium leprae causes relapse in some leprosy patients, and these patients present signs and symptoms of disease after healing. This study focused on the cellular immune response in relapsed multibacillary patients but also included non-relapsed multibacillary cured individuals, newly diagnosed and untreated multibacillary patients, paucibacillary patients just before the beginning of treatment, and voluntary healthy individuals for comparative analysis.Conclusions/SignificanceInhibition of CD86 expression may function to reduce effector T cell responses against the M. leprae antigen. Furthermore, the predominance of central memory T cells in association with the high TNF/IL-10 ratio and no observed IFN-γ production may be related to the pathogenesis of relapse in multibacillary leprosy. Therefore, our findings may be a direct result of the clinical presentation, including a number of skin lesions and bacterial load, of relapsed patients. To our knowledge, this is the first study correlating immune response parameters with the clinical presentation of relapsed multibacillary patients.