Antitumor vaccines: is it possible to prevent a tumor?

The main medical use of vaccines is to induce a state of immunity in healthy individuals to protect them from deadly or dangerous diseases. In the field of cancer immunology, however, vaccines are being used in patients as therapy, often with a very poor success rate against advanced disease. This paper reviews recent preclinical evidence in favor of the prophylactic use of immunological approaches to cancer. Successful attempts at immunological cancer prevention in HER-2/neu transgenic mice are described as an example. The specific properties of the HER-2/neu gene product as a tumor antigen, and the nature of the immune responses induced by effective preventive treatments are reviewed. Although the very high rate of mammary carcinoma prevention in mice has generated enthusiasm, it should not be forgotten that such treatments, when administered to healthy humans at risk of cancer, may carry the risk of inducing autoimmunity. These issues can be addressed in preclinical studies in appropriate animal models.     

Mexical plant phenology: is it similar to Mediterranean communities?

The sclerophyllous, evergreen vegetation found in Mexico under tropical climate is named 'Mexical' (MEX) and presents many traits that have been thought to converge under a Mediterranean climate. Flowering phenology is strongly similar across Mediterranean-type ecosystems (MTEs) and this paper investigates MEX plant phenology in this context. The common history of the vegetation and the differences in the climatic conditions experienced by MEX and MTE taxa provide an ideal scenario to infer the relative importance of natural selection and historical constraints in the phenological response of plants to climatic conditions. This study has involved collecting field and bibliographic data on flowering phenology of MEX communities to detect (1) similarities at the community level between MTEs and MEX, (2) similarities between Tertiary and Quaternary taxa in MTEs and MEX, and (3) similarities between congeneric taxa from MEX and MTEs (taxa sharing a common ancestor but having evolved under different climates). Flowering in MEX does not occur mainly in spring, as in MTEs, but in summer, suggesting a response that maximizes water use in the rainy season. Flowering phenology of MEX species differed from their MTE congeneric species, suggesting that even though a common ancestor is shared, environmental pressures have led to different phenological responses in MEX and MTE plants. The flowering season for species that originated in the Tertiary and Quaternary did not differ in MEX, as expected, because of climatic uniformity along the whole time line. In MTEs, flowering differences between Tertiary and Quaternary species were not congruent, suggesting that the balance between the historical constraints and the selective force of the Mediterranean climate is different among the three MTEs, and a particular explanation is needed for each. © 2002 The Linnean Society of London, Botanical Journal of the Linnean Society , 2002, 138 , 297–303.     

Biogas from Macroalgae: is it time to revisit the idea?

The economic and environmental viability of dedicated terrestrial energy crops is in doubt. The production of large scale biomass (macroalgae) for biofuels in the marine environment was first tested in the late 1960’s. The culture attempts failed due to the engineering challenges of farming offshore. However the energy conversion via anaerobic digestion was successful as the biochemical composition of macroalgae makes it an ideal feedstock. The technology for the mass production of macroalgae has developed principally in China and Asia over the last 50 years to such a degree that it is now the single largest product of aquaculture. There has also been significant technology transfer and macroalgal cultivation is now well tried and tested in Europe and America. The inherent advantage of production of biofuel feedstock in the marine environment is that it does not compete with food production for land or fresh water. Here we revisit the idea of the large scale cultivation of macroalgae at sea for subsequent anaerobic digestion to produce biogas as a source of renewable energy, using a European case study as an example.     

Visiting sick people: is it really detrimental to our health?

Intuitively, keeping ones distance from a source of infection would appear to be the best way to limit the occurrence of disease. However, this overlooks the importance of repeated infections in maintaining efficient immune defenses. When acquired immunity has partly waned, re-exposure to the pathogenic agent may lead to mild disease that boosts the immune system. This prevents the total loss of immunity that would lead to classical disease in cases of re-infection. Here, using a mathematical model, we show that avoiding the pathogenic agent is detrimental in some situations, e.g. for pathogens that are highly transmissible, are not excessively lethal and that induce rapidly waning immunity. Reducing exposure to pathogenic agents is among the objectives of most, if not all, public health measures. A better understanding of the factors influencing the severity of a disease is required before applying measures that reduce the circulation of pathogenic agents.     

Lipid screening: is it enough to measure total cholesterol concentration?

OBJECTIVES--To determine whether measurement of total cholesterol concentration is sufficient to identify most patients at lipoprotein mediated risk of coronary heart disease without measurement of triglyceride and high density lipoprotein (HDL) cholesterol concentrations. DESIGN--Cross sectional screening programme. SETTING--Six general practices in Oxfordshire. PATIENTS--1901 Men and 2068 women aged 25-59. MAIN OUTCOME MEASURE--Cardiovascular risk as assessed by fasting venous plasma concentrations of total cholesterol, triglyceride, and HDL cholesterol. RESULTS--2931 Patients (74% of those screened) had a total cholesterol concentration of less than 6.5 mmol/l. If the triglyceride concentration had not been measured in these patients isolated hypertriglyceridaemia (greater than or equal to 2.3 mmol/l) would have remained undetected in 185. Among these 185 patients, however, 123 were overweight or obese and only 18 (0.6% of those screened) had an increased risk associated with both a raised triglyceride concentration (greater than or equal to 2.3 mmol/l) and a low HDL cholesterol concentration (less than 0.9 mmol/l). Conversely, in the 790 patients with predominant hypercholesterolaemia (cholesterol concentration greater than or equal to 6.5 mmol/l and triglyceride concentration less than 2.3 mmol/l) measurement of HDL cholesterol concentration showed that 348 (9% of those screened) had only a moderately increased risk with a ratio of total to HDL cholesterol of less than 4.5 and 104 had a low risk with a ratio of less than 3.5. CONCLUSIONS--Fasting triglyceride and HDL cholesterol concentrations identify few patients at increased risk of coronary heart disease if the total cholesterol concentration is less than 6.5 mmol/l. HDL cholesterol and triglyceride concentrations should, however, be measured in patients with a total cholesterol concentration exceeding this value. Total cholesterol concentration alone may overestimate risk in a considerable number of these patients, and measurement of HDL cholesterol concentration allows a more precise estimate of risk. Measurement of the triglyceride concentration is required to characterise the lipoprotein abnormality. A patient should not be started on a drug that lowers lipid concentrations without having had a full lipoprotein assessment including measurement of HDL cholesterol concentration.     

Estrogen-inducible uterine flavonoid binding sites: is it time to reconsider?

Epidemiological data support the beneficial effect of plant flavonoids on human health including anti-inflammatory and cancer preventing actions. The phytoestrogen flavonoids might interfere with estrogen action. The possible relations between the steroid- and the flavonoid-signalling in animal and plant cells have been addressed in numerous studies in the past decade. In search for possible sites of conjunction between these phenomena the post-receptor targets must not be disregarded.

The estrogen-inducible type II estrogen binding sites of rat uteri have first been reported 25 years ago by Clark and coworkers [Biochem. Biophys. Res. Commun. 81 (1978) 1]. These sites are known to bind catecholic flavonoids with considerable affinity. Behaviour of the tyrosinase-like enzymatic activity associated with these sites appeared reminiscent to the recently described dopachrome oxidase or tautomerase activity exhibited by the cytokine macrophage migration inhibitory factor (MIF) inasmuch as it also accepts a broad range of catecholic melanogenic precursors. Therefore we assessed, whether the known type II ligand flavonoids interfere with the MIF tautomerase. We report here, that luteolin and quercetin have a biphasic effect on the enol–keto conversion of phenylpyruvate mediated by MIF tautomerase. We also demonstrate the presence of MIF immunoreactivity by Western blotting in rat uterine nuclear extracts prepared according to the method that yields high type II binding activity. These data support the possible participation of MIF in type II estrogen binding phenomena.