Obesity as disease and as social problem

This text is part of a broader line of study that aims to analyze how and why certain eating habits and bodily practices have become social problems, as is the case with fatness. We will show that the ideas that support the definition of obesity as a chronic and avoidable disease are leading experts and health authorities, and other social workers, to know and to think about its evolution in terms of "global" illness (epidemic) and to consider cultural factors as their main cause (obesogenic environment). Paradoxically, the international and national preventive measures taken are focused on changing individual behavior and, in particular, eating habits. The concepts about the regulation of excess weight and food provide interesting information about a particular understanding of lifestyles and culture and they take into account the current promotion of health patterns.     

Lyn deficiency affects B-cell maturation as well as survival

Lyn, an Src-family protein tyrosine kinase expressed in B lymphocytes, contributes to initiation of BCR signaling and is also responsible for feedback inhibition of BCR signaling. Lyn-deficient mice have a decreased number of follicular B cells and also spontaneously develop a lupus-like autoimmunity. We used flow cytometric analysis, BrdU labeling and our mathematical models of B-cell population dynamics, to analyze how Lyn deficiency impacts B-cell maturation and survival. We found that Lyn-deficient transitional 1 (T1) cells develop normally, but T2 cells develop primarily from the T1 subset in the spleen and fail to also develop directly from BM immature B cells. Lyn-deficient T2 cells either mature to the follicular B-cell type at a close to normal rate, or die in this compartment rather than access the T3 anergic subset. The ≈ 40% of WT follicular cells that were short-lived exited primarily by joining the T3 anergic subset, whereas the ≈ 15% Lyn(-/-) follicular cells that were not long lived had a high death rate and died in this compartment rather than entering the T3 subset. We hypothesize that exaggerated BCR signaling resulting from weak interactions with self-antigens is largely responsible for these alterations in Lyn-deficient B cells.     

Pharmacogenetic testing: not as simple as it seems

Pharmacogenetics has the potential to help guide treatment decisions by tailoring appropriate drugs and dosages to patients most likely to benefit. This straightforward clinical goal has led some to suggest that pharmacogenetic testing is free of ethical concerns. However, a number of potential risks and clinical uncertainties arise in considering the use of these new tools in clinical care. We propose a classification of pharmacogenetic tests to identify and prioritize the policy issues that will need to be addressed to ensure appropriate delivery of pharmacogenetic testing. We use the classification framework to consider the benefits and risks associated with ancillary information, timing of testing, and storage and retrieval of pharmacogenetic test results among health professionals. These issues have implications for informed consent and genetic counseling requirements, and for the role of health professionals.     

Human vascular tissues produce thromboxane as well as prostacyclin

Four different types of human blood vessels were examined for spontaneous and arachidonate-stimulated release of prostacyclin (PGI2) and thromboxane A2 (TXA2). Spontaneous PGI2 release was umbilical veins greater than umbilical arteries greater than saphenous veins greater than internal mammary arteries. With stimulation, PGI2 release by all four different vessels increased significantly (P less than 0.001) and was similar. Spontaneous release of TXA2 was also identified from all vessels examined and was similar. With stimulation, TXA2 release from all vessels increased significantly (P less than 0.001). Internal mammary artery released more TXA2 than other vessels on stimulation. The identity of TXA2 was confirmed by similar displacement of TXB2 antibody by TXB2 standards and by multiple dilutions of supernates. Treatment of vessels with aspirin inhibited PGI2 as well as TXA2 release, whereas treatment with OKY 1581 (TXA2 synthetase inhibitor) inhibited TXA2 release only. Two-dimensional thin-layer chromatography showed [14C]arachidonate conversion to PGI2 and TXA2 similar to that measured by radioimmunoassay. These data suggest that TXA2 is synthesized by human vessels. In older vessels when PGI2 generation is decreased, TXA2 production may by of pathophysiological significance.     

Guitarfish possess ipsilateral as well as contralateral retinofugal projections

Autoradiographic analysis of the primary retinal projections in the thornback guitarfish reveals both contralateral and ipsilateral projections to diencephalic, pretectal, and tegmental nuclei and the optic tectum. A total of 12 retino-recipient cell groups receive ipsilateral as well as contralateral inputs.     

Integral as well as proportional adrenal responses to ACTH

To characterize adrenal responses to ACTH, conscious dogs were infused for 40 min with normal saline or 20-1,500 ng/min alpha-ACTH. Plasma ACTH and corticosteroid levels were measured during the infusion and for 80 min after the end of the infusion. Half-maximal plateau corticosteroid responses were achieved with ACTH levels of 105 pg/ml (23 pM); a maximal plateau corticosteroid response (10.2 micrograms/100 ml) resulted from ACTH levels greater than 335 pg/ml (74 pM). When levels of ACTH between 335 and 3,000 pg/ml were achieved during the 40-min infusion, the duration of maximal corticosteroid levels was prolonged beyond the duration of the ACTH infusion. Plasma ACTH concentration decreased after the end of the infusion with a half-disappearance time of 3.6 +/- 0.2 min, but plasma corticosteroid concentrations and cortisol and corticosteroid secretory rates remained at or above the plateau secretory rates during the infusion and for about 80 min after the end of an infusion of 1,000 ng ACTH/min. When the total corticosteroid responses to the ACTH infusions were estimated, the relationship between the total corticosteroid response and the logarithm of the ACTH concentration was linear for 80-3,000 pg ACTH/ml.     

Peer review as professional responsibility: a quality control system only as good as the participants

The peer-review process remains a central part of the value and validity of scientific and technical publishing and proposal assessment. The peer review mechanism has many delicate components that should function most professionally and effectively for best results. An important central tenet is that all who seek to publish should freely avail themselves to review a commensurate load, considering many elements of professional conduct, ethics and responsibility in this process. The review itself should provide timely, unbiased, quality feedback to improve contributions to the system reviewers are serving. An additional component involves follow-on policing of published literature to assert its validity through consensus and validation. This short essay examines our collective duties as contributors, reviewers, and readers to the integrity and safekeeping of this essential quality control process.     

'Microfluidic' Device Simulates Cancer Treatment as Effectively as Research Animals

正A new technology that simulates tumors has been shown to perform as well as research animals in testing chemotherapy drugs,representing a potential tool for screening drugs before treating a patient.A long-term goal is to incorporate biopsied cancer cells from patients and test the effectiveness of different drugs on the patient-derived cells.     

Why technology matters as much as science in improving healthcare

ABSTRACT: BACKGROUND: More than half a million new items of biomedical research are generated every year and added to Medline. How successful are we at applying this steady accumulation of scientific knowledge and so improving the practice of medicine in the USA? DISCUSSION: The conventional wisdom is that the US healthcare system is plagued by serious cost, access, safety and quality weaknesses. A comprehensive solution must involve the better translation of an abundance of clinical research into improved clinical practice.Yet the application of knowledge (i.e. technology) remains far less well funded and less visible than the generation, synthesis and accumulation of knowledge (i.e. science), and the two are only weakly integrated. Worse, technology is often seen merely as an adjunct to practice, e.g. electronic health records.Several key changes are in order. A helpful first step lies in better understanding the distinction between science and technology, and their complementary strengths and limitations. The absolute level of funding for technology development must be increased as well as being more integrated with traditional science-based clinical research. In such a mission-oriented federal funding strategy, the ties between basic science research and applied research would be better emphasized and strengthened.     

Asthma as a child. Symptom-free as an adult?

Of 123 individuals hospitalized as children (aged 5-15 years) because of asthma over a 10-year period (1953-1962), four are dead of whom three died of asthma at follow-up 23-31 years later. Using a survey questionnaire, 64 (53%) of the 117 responders (response rate 98%) claimed to be completely symptom-free. The rest were still suffering from their disease. Of the 31 symptom-free individuals still living in the community, two had decreased lung volumes and seven had positive methacholine provocation tests at re-examination, thus indicating hyperreactivity. Twenty-five individuals showed both positive skin prick tests and Phadiatop allergy tests. Nineteen individuals were suffering from allergic rhinoconjunctivitis. So, of symptom-free adults hospitalized for asthma in childhood, nearly a quarter (23%) had hyperreactive airways. The occurrence of positive skin prick test/Phadiotop and rhinoconjunctivitis was, however, even higher (80% and 61% respectively), thereby indicating that the disappearance of allergy may not be a prerequisite for restoration to health in asthma.     

Azo-dyes as labels and as photoisomerizable units in chiral polyisocyanates

Polyisocyanates (nylon 1) with azochromophores in the side chains were prepared for the first time. For this purpose we have synthesized two new azo dyes containing isocyanato groups. The monomers were copolymerized with alkyl isocyanates to prepare chiral dye-containing polyisocyanates. Optical rotatory dispersion and circular dichroism measurements support the helical polymer structure with predominantly one twist sense (due to the chiral side chains, P and M helices are diastereomeric). The completely reversible photochemical isomerization (trans to cis) of the azochromophores reaches high conversions (about 80%), but does not change the conformation of the main chain.     

Enkephalins as immunomodulators

The protective effects of methionine enkephalin as well as leucine enkephalin were studied in BDF1 mice inoculated with 1 X 10(4) and 1 X 10(2) cells of L1210 murine leukemia. Significant increases in number of survivors were observed in mice treated with enkephalins. Methionine enkephalin in the presence of PHA was found to stimulate lymphocyte blastogenesis at concentrations of 1 mg/ml to 10(-8) mg/ml. In the case of leucine enkephalin, concentrations of 1 mg/ml to 10(-10) mg/ml stimulated blastogenesis. Stimulation of blastogenesis was seen at PHA dilutions of 1:100, 1:250, 1:750, with both methionine enkephalin and leucine enkephalin. The results are discussed in terms of immunomodulation. It is proposed that endogenous enkephalins play a neuroendocrine role between the central nervous system and the immune system and are direct immunostimulants.