Differential gene-expression analysis defines a molecular pattern related to olive pollen allergy.

Analysis of gene-expression profiles by microarrays is useful for characterization of candidate genes, key regulatory networks, and to define phenotypes or molecular signatures which improve the diagnosis and/or classification of the allergic processes. We have used this approach in the study of olive pollen response in order to find differential molecular markers among responders and non-responders to this allergenic source. Five clinical groups, non-allergic, asymptomatic, allergic but not to olive pollen, untreated-olive-pollen allergic patients and olive-pollen allergic patients (under specific-immunotherapy), were assessed during and outside pollen seasons. Whole-genome gene expression analysis was performed in RNAs extracted from PBMCs. After assessment of data quality and principal components analysis (PCA), differential gene-expression, by multiple testing and, functional analyses by KEGG, for pathways and Gene-Ontology for biological processes were performed. Relevance was defined by fold change and corrected P values (less than 0.05). The most differential genes were validated by qRT-PCR in a larger set of individuals. Interestingly, gene-expression profiling obtained by PCA clearly showed five clusters of samples that correlated with the five clinical groups. Furthermore, differential gene expression and functional analyses revealed differential genes and pathways in the five clinical groups. The 93 most significant genes found were validated, and one set of 35 genes was able to discriminate profiles of olive pollen response. Our results, in addition to providing new information on allergic response, define a possible molecular signature for olive pollen allergy which could be useful for the diagnosis and treatment of this and other sensitizations.

The detection, treatment and control of high blood pressure in older British adults: cross-sectional findings from the British Women's Heart and Health Study and the British Regional Heart Study.

Among older people, the detection and control of hypertension is particularly important to reduce cardiovascular disease risk. This cross-sectional survey aimed to describe the detection, treatment and control of hypertension in older British adults. A total of 3059 women and 3007 men aged 60-79 years were randomly selected from general practice age/sex registers in 24 British towns and examined from 1998 to 2001. Of these, 52.6% women and 47.9% men had at least one indicator of hypertension (high blood pressure on examination, or taking antihypertensive medication or recalled a doctor diagnosis of high blood pressure). Among women, 50% of those with any indication of hypertension were on treatment and 29% were well controlled, and among men 45% were on treatment and 16% were well controlled. With the exception of alcohol use in men (adjusted odds ratio 0.67 (0.46, 0.98)), socioeconomic factors, area of residence and behavioural risk factors were not associated with good control among those with hypertension in either sex. Of those on treatment, 20.7% of women and 28% of men were on two classes of antihypertensive medication and 3.5 and 4.9%, respectively, were on three or more classes of antihypertensive medication. Among those with a doctor diagnosis of hypertension and taking antihypertensive medication, the proportion with well controlled blood pressure did not differ between those on more than one antihypertensive and those on just one in either sex. We conclude that targets of good control are rarely met in older individuals, who would benefit from the associated reduction in cardiovascular disease risk.

A novel locus for a hereditary recurrent neuropathy on chromosome 21q21.

Hereditary recurrent neuropathies are uncommon. Disorders with a known molecular basis falling within this group include hereditary neuropathy with liability to pressure palsies (HNPP) due to the deletion of the PMP22 gene or to mutations in this same gene, and hereditary neuralgic amyotrophy (HNA) caused by mutations in the SEPT9 gene. We report a three-generation family presenting a hereditary recurrent neuropathy without pathological changes in either PMP22 or SEPT9 genes. We performed a genome-wide mapping, which yielded a locus of 12.4 Mb on chromosome 21q21. The constructed haplotype fully segregated with the disease and we found significant evidence of linkage. After mutational screening of genes located within this locus, encoding for proteins and microRNAs, as well as analysis of large deletions/insertions, we identified 71 benign polymorphisms. Our findings suggest a novel genetic locus for a recurrent hereditary neuropathy of which the molecular defect remains elusive. Our results further underscore the clinical and genetic heterogeneity of this group of neuropathies.

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information.

Undifferentiated and poorly differentiated thyroid tumors are responsible for more than half of thyroid cancer patient deaths in spite of their low incidence. Conventional treatments do not obtain substantial benefits, and the lack of alternative approaches limits patient survival. Additionally, the absence of prognostic markers for well-differentiated tumors complicates patient-specific treatments and favors the progression of recurrent forms. In order to recognize the molecular basis involved in tumor dedifferentiation and identify potential markers for thyroid cancer prognosis prediction, we analysed the expression profile of 44 thyroid primary tumors with different degrees of dedifferentiation and aggressiveness using cDNA microarrays. Transcriptome comparison of dedifferentiated and well-differentiated thyroid tumors identified 1031 genes with >2-fold difference in absolute values and false discovery rate of <0.15. According to known molecular interaction and reaction networks, the products of these genes were mainly clustered in the MAPkinase signaling pathway, the TGF-beta signaling pathway, focal adhesion and cell motility, activation of actin polymerization and cell cycle. An exhaustive search in several databases allowed us to identify various members of the matrix metalloproteinase, melanoma antigen A and collagen gene families within the upregulated gene set. We also identified a prognosis classifier comprising just 30 transcripts with an overall accuracy of 95%. These findings may clarify the molecular mechanisms involved in thyroid tumor dedifferentiation and provide a potential prognosis predictor as well as targets for new therapies.

Coronary heart disease prevention in clinical practice: are patients with diabetes special? Evidence from two studies of older men and women.

OBJECTIVE: To assess whether the extent of primary and secondary coronary heart disease (CHD) prevention in older British men and women differs between patients with and without diabetes. DESIGN: Two prospective cardiovascular cohort studies. SETTING: 24 British towns. PATIENTS: 4252 men and 4286 women aged 60-79 years examined between 1998 and 2001. MAIN OUTCOME MEASURES: Use of aspirin, statin, and blood pressure lowering treatment and risk factor control, examined by diabetic status and history of established CHD. RESULTS: About 20% of the men and 12% of the women had established CHD at age 60-79 years and 7% of the men and 5% of the women had diabetes. In primary CHD prevention, patients with diabetes were more likely to receive CHD risk reducing medications than those without diabetes, but the proportions receiving preventive treatments in both groups were low. In secondary prevention, diabetic and non-diabetic patients received similar levels of treatment, with the exception of angiotensin converting enzyme inhibitors and (for women only) blood pressure lowering treatment, which were more widely used among diabetic patients. There were no clear differences in blood pressure control or cigarette smoking by diabetic status in primary or secondary prevention. Mean total cholesterol concentrations were lower in diabetic patients independently of treatment with statins. CONCLUSIONS: Despite their exceptionally high CHD risk, many opportunities to reduce CHD risk among patients with diabetes have not been taken.

Compromiso cardiovascular en el lupuseritematoso sistémico / Cardiovascular involvement in patient with systemic lupus erythematosus

Lupus erythematosus is a multisystemic disease that compromises principally women in fertile age. The principal affected organs are kidney, SNC, bone marrow and serous membranes. Cardiovascular affection includes pericardium, conduction system, myocardium, valves and coronary arteries. The most frequent valve disease is Libman-Sacks endocarditis, although valvulitis or valve dysfunction can exist as well. The mitral valve is the most affected, followed by the aortic valve. The most frequent valve abnormality is slight to moderate aortic insufficiency, while serious insufficiency or valve disruption is very rare. A physical examination has limited efficacy in the diagnosis of valve disease. A high degree of suspicion associated with echocardiography helps to establish the diagnosis. If surgery is not needed, antiplatelet therapy is recommended for asymptomatic patients, and oral anticoagulation treatment is advised for those with valve disease and evidence of thromboembolic phenomena. Recurrence of the disease has been observed in biological grafts, which makes the use of mechanical prostheses advisable when valve replacement indication exists. The following case shows the clinical evolution of a female patient with a rare but very serious lupus erythematosus complication.