Characterization of an O-glycosylated plaque-associated protein from Alzheimer disease brain

In this work we characterized a 90-kDa glycoprotein from Alzheimer disease (9OAzgp) brain extracts that is recognized by the GalNAc-specific lectin from Amaranthus leucocarpus (ALL), as determined through Western blot. The 90Azgp was purified by electro-elution, and its amino acid sequence determined from peptides obtained after trypsin digestion through MALDI-TOF (Matrix-assisted laser desorption ionization-time of flight), and compared with the relative values obtained from the NCBInr (Swiss-Prot 10/01/2001) database. The 90Azgp showed 32% and 42% homology with the KIAA0310 protein from human brain and the human gastric mucin, respectively. Presence of O-glycosidically linked glycans in the proteins recognized by ALL was confirmed by inhibition of the lectin-glycoprotein interaction through hapten-inhibition assays and also by elimination of the O-glycosidically linked glycans after treatment with O-glycanase from Diplococcus pneumoniae. Electron transmission microscopy confirmed that the receptor recognized by the lectin is processed in the Golgi apparatus of AD neurons. Although the specific role of this glycoprotein has not been identified, considering that the presence of this lectin receptor co-localized with neuritic plaques and in AD sprouting neurons, it could suggest that the O-glycosyl-protein identified by the A. leucocarpus lectin participates in the pathogenesis of neurodegenerative diseases.     

Prevalence of Chlamydia trachomatis infection in registered female sex workers in northern Mexico

BACKGROUND: Little is known about the epidemiology of Chlamydia trachomatis infection in female sex workers (FSWs) in Mexico. GOAL: The goal of the study was to determine the prevalence of C trachomatis infection in registered FSWs from northern Mexico and to determine the sociodemographic characteristics associated with the infection. STUDY DESIGN: An enzyme immunoassay was used to test 354 FSWs in three northern Mexican cities for cervical C trachomatis infection. All participants were registered in a government health office. Recruitment was consecutive and voluntary. The association between clinical and sociodemographic characteristics of FSWs and infection was evaluated. RESULTS: The overall prevalence of C trachomatis infection among participants in the three cities was 12.4%. Women of low socioeconomic level and those younger than 25 years were the most frequently infected. Among FSWs in Durango, a higher frequency of C trachomatis infection was found for those who did not use condoms. CONCLUSION: C trachomatis is an important pathogen in the sexually transmitted diseases of registered FSWs in northern Mexico.     

Hemispheric differences in global and local processing with orientation classification tasks

Hemispheric differences in global and local processing were examined in one experiment with hierarchical stimuli. The figures consisted of large squares with the right or left side missing made up of small squares with the right or left side missing. The subjects were asked to decide the opening (left/right) of the square either at the global level or at the local level. The findings showed that with the task and stimuli used here global judgements were as fast and accurate as local judgements, the interference was bidirectional and symmetrical and, finally, that the right hemisphere and the left hemisphere had the same ability to manage with global and local information. So, the experiment does not provide evidence for hemispheric specialisation in global and local processing.     

Rescue of a pathogenic Marek's disease virus with overlapping cosmid DNAs: use of a pp38 mutant to validate the technology for the study of gene function

Marek's disease virus (MDV) genetics has lagged behind that of other herpesviruses because of the lack of tools for the introduction of site-specific mutations into the genome of highly cell-associated oncogenic strains. Overlapping cosmid clones have been successfully used for the introduction of mutations in other highly cell-associated herpesviruses. Here we describe the development of overlapping cosmid DNA clones from a very virulent oncogenic strain of MDV. Transfection of these cosmid clones into MDV-susceptible cells resulted in the generation of a recombinant MDV (rMd5) with biological properties similar to the parental strain. To demonstrate the applicability of this technology for elucidation of gene function of MDV, we have generated a mutant virus lacking an MDV unique phosphoprotein, pp38, which has previously been associated with the maintenance of transformation in MDV-induced tumor cell lines. Inoculation of Marek's disease-susceptible birds with the pp38 deletion mutant virus (rMd5 Delta pp38) revealed that pp38 is involved in early cytolytic infection in lymphocytes but not in the induction of tumors. This powerful technology will speed the characterization of MDV gene function, leading to a better understanding of the molecular mechanisms of MDV pathogenesis. In addition, because Marek's disease is a major oncogenic system, the knowledge obtained from these studies may shed light on the oncogenic mechanisms of other herpesviruses.     

Characterization of venom components from the scorpion Androctonus crassicauda of Turkey: peptides and genes.

The soluble venom from the scorpion Androctonus crassicauda was fractionated by high performance liquid chromatography. At least 44 different sub-fractions were resolved and collected for finger print mass analysis using an electrospray mass spectrometer. This analysis revealed the presence of 80 distinct molecular mass components, from which five were further characterized. A peptide, named Acra1 was fully sequenced. It contains 58 amino acid residues cross-bridged by six cysteines forming three disulfide pairs, with a molecular mass of 6497 Da. A second purified peptide named Acra2 was partially sequenced with a molecular mass of 7849 Da. Acra1 is toxic and Acra2 is lethal to mice, at the dose assayed. Additionally, a cDNA library of the venomous gland of one specimen was prepared and several clones were obtained among which is one that codes for Acra1. Three analog gene sequences were found with point mutations either in the section that corresponds to the mature peptide or to the signal peptide. The signal peptide is 22 amino acid residues long. Several other gene sequences obtained suggest the presence in this venom of three distinct groups of peptides, among which are peptides similar to known Na(+)-channel specific toxins of other scorpions. A new type of peptide was identified with odd number of cysteines (seven), allowing the formation of heterodimers with molecular masses in the range of 16,000 atomic mass units (a.m.u.).     

Scientific Evidence of Interventions Using the Mediterranean Diet: A Systematic Review

The Mediterranean Diet has been associated with greater longevity and quality of life in epidemiological studies, the majority being observational. The application of evidence-based medicine to the area of public health nutrition involves the necessity of developing clinical trials and systematic reviews to develop sound recommendations. The purpose of this study was to analyze and review the experimental studies on Mediterranean diet and disease prevention. A systematic review was made and a total of 43 articles corresponding to 35 different experimental studies were selected. Results were analyzed for the effects of the Mediterranean diet on lipoproteins, endothelial resistance, diabetes and antioxidative capacity, cardiovascular diseases, arthritis, cancer, body composition, and psychological function. The Mediterranean diet showed favorable effects on lipoprotein levels, endothelium vasodilatation, insulin resistance, metabolic syndrome, antioxidant capacity, myocardial and cardiovascular mortality, and cancer incidence in obese patients and in those with previous myocardial infarction. Results disclose the mechanisms of the Mediterranean diet in disease prevention, particularly in cardiovascular disease secondary prevention, but also emphasize the need to undertake experimental research and systematic reviews in the areas of primary prevention of cardiovascular disease, hypertension, diabetes, obesity, infectious diseases, age-related cognitive impairment, and cancer, among others. Interventions should use food scores or patterns to ascertain adherence to the Mediterranean diet. Further experimental research is needed to corroborate the benefits of the Mediterranean diet and the underlying mechanisms, and in this sense the methodology of the ongoing PREDIMED study is explained.     

Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms and gastric cancer: a meta-analysis.

BACKGROUND: Polymorphisms of interleukin-1B (IL1B) and its receptor antagonist (IL1RN) genes have been inconsistently associated with gastric cancer risk. We examined these associations by performing meta-analyses. MATERIALS AND METHODS: Twenty-five studies testing the association between IL1B and/or IL1RN gene polymorphisms and gastric cancer were examined: 14 studies of IL1B-511, 14 studies of IL1B-31, 8 studies of IL1B+3954, and 23 studies of IL1RN. Overall and ethnicity-specific summary odds ratios and corresponding 95% confidence intervals for gastric cancer associated with these polymorphisms were estimated using fixed- and random-effects models. Heterogeneity and publication bias were evaluated. RESULTS: IL1B-511T and IL1RN*2 were associated with gastric cancer risk in Caucasians, but not in Asians. For IL1B-511T, the association in Caucasians was stronger when intestinal-subtype and noncardia gastric cancer cases were examined. A nonsignificant trend was observed between IL1B-31C and gastric cancer in Caucasians. No significant association of IL1B+3954T and gastric cancer risk was detected. Studies with better methodologic characteristics reported stronger effects. There was no evidence of publication bias. CONCLUSION: IL1B-511T is associated with gastric cancer susceptibility in Caucasians. The meta-analyses suggest that the conflicting results among studies may be explained by variation in allele frequencies among the ethnic groups and variation in tumor types, as well as by the methodologic quality of the studies.     

A comparative study of HER2/neu amplification and overexpression using fluorescencein situ hybridization (FISH) and immunohistochemistry (IHC) in 101 breast cancer patients

The HER2/neu protooncogene is expressed in the breast, ovarian, gastric and prostatic tumors. Studies done in a number of laboratories have demostrated that 25%–30% of breast cancer contain overexpression of HER2/neu gene. A comparative analysis of the amplification and overexpression of HER2/neu using fluorescencein situ hybridization (FISH) and immunohistochemistry (IHC) was performed to determine the correlation between both techniques. In this study, FISH with HER2/neu probe (Path Vysion) is compared to immunohistochemistry (rabbit anti-human c-erbB-2-DAKO) in a series of 101 prospective human breast cancer specimens. Among 25 patients with score of IHC 3+, 23 (92%) were detected amplified by FISH and in two cases we found overexpression (3+) but without gene amplification. Out of 46 cases with 2+ by IHC, we found 43 not amplified, two moderately amplified (<10 copies) and one highly amplified (>10 copies) (6.5%). No patient with IHC O or 1+, presented amplification of HER2/neu. A good correlation between both techniques was found. FISH technique should have clinical utillity overoat in cases with 2+.     

Failure of cell-mediated effector mechanisms in lung cancer

The status of cell-mediated effector mechanisms was studied in 28 patients with lung cancer (25/28 in stage III). Patients' precultured peripheral blood mononuclear leukocytes, isolated by Ficoll-Hypaque, were tested for lymphocyte proliferation responses to alloantigens in mixed lymphocyte culture (MLC). The influence of autologous patients' sera was studied further on MLC responses from patients and controls. Cell-mediated lympholysis (CML), with the use of allogenic blast cells as targets, and antibody-dependent cell-mediated cytotoxicity (ADCC) against human red blood cells also were tested. Major differences between the cancer patients and controls were not demonstrated by MLC. Inhibition or enhancement of MLC responses by the autologous serum was shown; bimodal influence was significant; 72% of the sera caused inhibition and 28% caused enhancement. CML was depressed in 54% of the patients, and ADCC was depressed in 50%. The decrease in both cytotoxic responses was significant (P less than .005). Thirteen patients died after initiation of the investigative protocol; in 11 of 13, CML or ADCC was diminished. The altered cytotoxic capabilities were more prevalent among the epidermoid type, including the deceased patients. This study provides evidence that a severe impairment of cell-mediated effector mechanisms is frequent in advanced lung cancer and may be associated with poor clinical course and with the histologic type.     

Cyclophosphamide hypersensitivity in a leukemic child

Although hypersensitivity reactions to chemotherapeutic drugs have rarely been reported, they may occur with any of these agents. A Mexican native 44-kg 13-year-old boy suffering from acute lymphoblastic leukemia (ALL) received chemotherapy for 7 years. Three years later, a recurrence of ALL was detected in his right testicle. The patient was scheduled to receive 12 weekly cycles of 50 mg/kg of cyclophosphamide (CPM) as a 1-hour intravenous infusion. The patient did not have any history of drug allergies or any other type of ADR. Immediately after the fourth cycle of CPM, the patient developed itchy, maculopapular rash, sweating, respiratory distress, and anxiety. According to the algorithm developed by Naranjo et al, the ADR was classified as probably secondary to CPM. Skin tests were negative to hypersensitivity to CPM, and a new cycle of CPM was administered. However, the patient developed a similar hypersensitivity reaction to CPM. After an analysis of the clinical course of the ADR and the need to continue the chemotherapeutic treatment with CPM, we decided to desensitize the patient to this drug. Total duration of the procedure was 5 hours and was performed on only 1 occasion. The program of 12 cycles of chemotherapy was successfully completed without any sign or symptom of hypersensitivity to CPM. In conclusion, we have reported a case of hypersensitivity to CPM who was successfully desensitized to CPM.