Susceptibility and resistance to environmental carcinogens in the development of carcinoma of the lung

Eight selected cases are presented to show different effects of the environment on the lung. Some appear to lack resistance to environmental carcinogens. The variations in response and an assessment of the carcinogens involved are discussed. Further study of these poorly understood etiologic factors is needed.     

Induction of capsule growth in Cryptococcus neoformans by mammalian serum and CO(2)

The pathogenic fungus Cryptococcus neoformans has a polysaccharide capsule that is essential for virulence in vivo. Capsule size is known to increase during animal infection, and this phenomenon was recently associated with virulence. Although various conditions have been implicated in promoting capsule growth, including CO(2) concentration, osmolarity, and phenotypic switching, it is difficult to reproduce the capsule enlargement effect in the laboratory. In this study, we report that serum can induce capsule growth, and we describe the conditions that induce this effect, not only by serum but also by CO(2). Capsule enlargement was dependent on the medium used, and this determined whether the strain responded to serum or CO(2) efficiently. Serum was most effective in inducing capsule growth under nutrient-limited conditions. There was considerable variability between strains in their response to either serum or CO(2), with some strains requiring both stimuli. Sera from several animal sources were each highly efficient in inducing capsule growth. The cyclic AMP (cAMP) pathway and Ras1 were both necessary for serum-induced capsule growth. The lack of induction in the ras1 mutant was not complemented by exogenous cAMP, indicating that these pathways act in parallel. However, both cAMP and Ras1 were dispensable for inducing a partial capsule growth by CO(2), suggesting that multiple pathways participate in this process. The ability of serum to induce capsule growth suggests a mechanism for the capsular enlargement observed during animal infection.     

Prevalence and clinical relevance of Blastocystis hominis in diverse patient cohorts

The pathogenicity of Blastocystis hominis is extensively debated in the medical literature. Therefore, we did a prevalence study to investigate the association between the presence of several intestinal parasites and gastrointestinal symptoms in diverse patient cohorts. The study population consisted of 1216 adults, including immunocompromised patients, institutionalized psychiatric or elder subjects, immigrants from developing countries, travellers to developing tropical countries and controls. Several variables for each risk group were considered. Stools specimens, collected in triplicate, were processed by the same technicians. Clinical data about each subject were provided by standardized questionnaires. The presence of gastrointestinal symptoms were related to the presence of any parasite. In addition, on the basis of microbiological results, five subgroups of subjects were evaluated. The results showed a high prevalence of parasites in all the risk groups. Immunocompromised status, recent arrival from developing countries and the presence of behavioural aberrations were significantly related to presence of parasites. B. hominis was the parasite most frequently detected in each studied group. B. hominis showed a significant correlation with gastrointestinal symptoms only when detected in the group including subjects with a severe immunodepression. Immunodepression seems to be a factor of primary importance of the pathogenic role of B. hominis.     

Comparative effects of L-methionine, S-adenosyl-L-methionine and 5'-methylthioadenosine on the growth of preneoplastic lesions and DNA methylation in rat liver during the early stages of hepatocarcinogenesis.

Male Wistar rats, initiated with diethylnitrosamine (DENA), were subjected to a selection treatment, according to the "resistant hepatocyte" model, followed or not followed by phenobarbital (PB). Rats received, for 3 weeks after selection, 4 i.m. doses (96 mmol/kg) of L-methionine, S-adenosyl-L-methionine (SAM), or 5'-methylthioadenosine (MTA), a SAM catabolite formed during polyamine synthesis or by spontaneous splitting of SAM at physiologic temperature and pH. They were then killed. In some rats, SAM and MTA treatments were started 20 weeks after initiation. The animals were killed 3 weeks later and persistent (neoplastic) nodules (PN) were collected. Some rat groups received 1/2 and 1/4 of the above SAM and MTA doses, or 1/8 of the above MTA dose. SAM and MTA, but not methionine, caused a dose-dependent decrease in number and surface area of gamma-glutamyltranspeptidase (GGT)-positive foci, and in labeling index (LI) of focal cells, coupled with remodeling. SAM and MTA liver contents, SAM/S-adenosylhomocysteine (SAH) ratio and overall methylation of liver DNA were low during the development of GGT-positive foci. SAM, but not methionine, caused a dose-dependent recovery of SAM content and DNA methylation, and a partial reconstitution of liver MTA pool. Exogenous MTA only induced the reconstitution of MTA pool, without affecting SAM level and DNA methylation. Recovery of SAM and MTA pool and DNA methylation was found in the rats subjected to SAM plus MTA, indicating the absence of inhibition of DNA methyltransferases in vivo by MTA. MTA also inhibited liver reparative growth in partially hepatectomized rats, without modifying SAM content and DNA methylation of regenerating liver (RL). A high activity of ornithine decarboxylase (ODC) was found in the liver, during the development of preneoplastic foci, and in PN. This activity was inhibited by SAM and MTA treatments. Although MTA was more effective than SAM, the decrease in ODC activity was coupled with a larger fall in DNA synthesis in SAM-treated than in MTA-treated rats. Thus the antipromotion effect of SAM could not merely depend on its (spontaneous) transformation into MTA. Although MTA production may play a role in the SAM antipromotion effect, other mechanisms could be involved. A role of DNA methylation in the inhibition of growth by SAM is suggested. MTA is a potential chemopreventive agent for liver carcinogenesis.     

Changes in the Household Calorie Supply during the 1994 Economic Crisis in Mexico and Its Implications on the Obesity Epidemic

To characterize the effects of the 1994 economic crisis on calorie sources of Mexican households, five nutrition surveys done every leap year (1992–2000) in national representative samples (> 10,000 households) were analyzed. Each household was visited during 7 days to collect data on foods purchased, exchanged or home-grown and their monetary value. We selected 88 food items to calculate kilocalories/ person/day and cost in pesos/megacalorie (CPMC) for rural-urban strata (localities <2500, ≥2500). The food items were classified in 8 groups and the summation of kilocalories and CPMCs of items in each group were our units of analysis. Linear regressions for 1992–2000 were performed, and slopes and intercepts were used to characterize changes. Available calories showed very little change at the height of the economic crisis. Expensive calories (meat in ur-bans, eggs and milk in rurals, and industrialized meat and soft drinks in both) tended to increase, whereas the most inexpensive staples (cereals, legumes, sugars) decreased their share in both strata. An increase in obesigenic calories was seen, notably in soft drinks, despite a cost increase second only to meat. Main conclusions were: (1) the economic crisis did not affect total calories availability in Mexican households; (2) the 1992–2000 trends in calorie sources were contrary to any crisis effect in rurals and urbans (i.e., expensive foods increased and inexpensive staples decreased); (3) there were sizable rural-urban differences in number, source, and cost of calories; and (4) obesigenic calories increased and soft drinks emerged as a food with its own dynamic.     

Isoametropic amblyopia due to high hyperopia in children.

PURPOSE: To identify children with isoametropic amblyopia due to moderate to high hyperopia and evaluate associated findings and visual acuity outcome. METHODS: Charts from two university's pediatric ophthalmology clinics were reviewed retrospectively. Healthy children with > or = +4.5 D spherical equivalent who did not have anisometropia > or = 1.5 D were selected for data collection. The charts of qualifying children with bilateral amblyopia (visual acuity of 20/40 or less) were further analyzed. RESULTS: Identified were 418 children with the above set of criteria for hyperopia; 36 of these children had isoametropic amblyopia (bilateral amblyopia). This gives an estimated prevalence of isoametropic amblyopia of 8.6% in children with at least 4.5 D of hyperopia in one or both eyes. The children with isoametropic amblyopia presented at a later age (5 years, 1 month) than the overall group of hyperopes (3 years, 5 months). Strabismus was less prevalent in this group (64%) than in the entire population of children with high hyperopia (81%). These children's amblyopia responded well to treatment with glasses, and patching in 13 (36%) cases. Surgical intervention for residual strabismus was necessary in very few cases (2 of 36, 5.5%). CONCLUSION: Children with hyperopia > or = 4.5 D have an increased risk of amblyopia and strabismus that further threatens their future visual function. Isoametropic amblyopia is a real risk in these children. Based on these results, hyperopic correction should be prescribed for children with > or = 4.5 D of hyperopia even if no strabismus or fixation preference is detected, to reduce this risk. Screening programs should also be in place to identify these children at an early age.