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Biomedical subjects

J Jimenez

Publications and source records attributed to J Jimenez.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of Toxoplasma gondii in cats from Colombia, South America and genetic characterization of T. gondii isolates.

Cats are important in the epidemiology of Toxoplasma gondii infection because they are the only hosts that can excrete the environmentally-resistant oocysts. In the present study, prevalence of T. gondii was determined in serum, feces, and tissues of 170 unwanted cats from Colombia, South America. Antibodies to T. gondii were assayed by the modified agglutination test and found in 77 of 170 (45.2%) cats with titers of <1:5 in 93, 1:5 in eight, 1:10 in 17, 1:20 in 10, 1:40 in seven, 1:80 in four, 1:160 in eight, 1:320 in six, and 1:640 or higher in 17 cats. T. gondii oocysts were not found in feces of any cat as ascertained by bioassay in mice. Tissues (brain, heart, tongue) of 116 cats were bioassayed in mice or cats. T. gondii was isolated from tissues of 15 of the 42 cats with titers of 1:40 or higher and not from any of the 90 cats titers of 1:20 or lower. Of the 29 cats whose tissues were bioassayed individually, T. gondii was isolated from the tongues of nine, hearts of eight, and brains of five. Mice inoculated with tissues of 12 of 15 infected cats died of toxoplasmosis; with nine T. gondii isolates all infected mice died. Overall, 65 of 92 (70%) of T. gondii-infected mice died of toxoplasmosis. Genotyping of these 15 isolates using polymorphisms at the SAG1, SAG2, SAG3, BTUB, and GRA6 loci revealed that three isolates (TgCtCo1, 2, and 7) had Type I alleles and one isolate (TgCtCo8) had Type II allele at all five loci. Eleven isolates contained the combination of Type I and III alleles and were divided into three genotypes, with TgCtCo3,5,6,9,12,13 and 15 had alleles I, I, III, I and III, TgCtCo4,10,11 had alleles I, III, III, I and I, and TgCtCo14 had alleles I, III, III, III, and III, at loci SAG1, SAG2, SAG3, BTUB and GRA6, respectively. All infected mice from each group had identical genotype except one mouse infected with TgCtCo5 had a Type III allele at locus BTUB and a unique allele (u-1) at locus SAG1 indicating mixed infection for TgCtCo5, whereas the rest seven mice had a Type I alleles at both loci.

Agglutination Tests↗
PubMed2005

Antibiotic prescription for community-acquired pneumonia in the intensive care unit: impact of adherence to Infectious Diseases Society of America guidelines on survival.

BACKGROUND: The purpose of our study was to analyze prognostic factors associated with mortality for patients with severe community-acquired pneumonia (CAP). METHODS: We conducted a prospective multicenter study including all patients with CAP admitted to the intensive care unit during a 15-month period in 33 Spanish hospitals. Admission data and data on the evolution of the disease were recorded. Multivariate analysis was performed using the SPSS statistical package (SPSS). RESULTS: A total of 529 patients with severe CAP were enrolled; the mean age (+/-SD) was 59.9+/-16.1 years, and the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/-SD) was 18.9+/-7.4. Overall mortality among patients in the intensive case unit was 27.9% (148 patients). The rate of adherence to Infectious Diseases Society of America (IDSA) guidelines was 57.8%. Significantly higher mortality was documented among patients with nonadherence to treatment (33.2% vs. 24.2%). Multivariate analysis identified age (odds ratio [OR], 1.7), APACHE II score (OR, 4.1), nonadherence to IDSA guidelines (OR, 1.6), and immunocompromise (OR, 1.9) as the variables present at admission to the intensive care unit that were independently associated with death in the intensive care unit. In 15 (75%) of 20 cases of Pseudomonas aeruginosa infection, the antimicrobial treatment at admission was inadequate (including 8 of 15 cases involving patients with adherence to IDSA guidelines). Chronic obstructive pulmonary disease (OR, 17.9), malignancy (OR, 11.0), previous antibiotic exposure (OR, 6.2), and radiographic findings demonstrating rapid spread of disease (OR, 3.9) were associated with P. aeruginosa pneumonia. CONCLUSIONS: Better adherence to IDSA guidelines would help to improve survival among patients with severe CAP. Pseudomonas coverage should be considered for patients with chronic obstructive pulmonary disease, malignancy, or recent antibiotic exposure.

Anti-Bacterial Agents↗
PubMed2003

Myocardial infarction risk in relation to zinc concentration in toenails.

Zn is an essential mineral. The role of Zn in atherosclerosis is not clear. Epidemiological studies, which have reported contradictory results, are limited by the use of serum Zn levels as a marker of intake. We assessed the association of toenail Zn, which integrates dietary Zn intake over 3 to 12 months, with the risk of a first myocardial infarction. Toenail Zn concentrations were determined by neutron activation analysis in the European multi-centre case-control study on antioxidants, myocardial infarction and breast cancer. This multi-centre case-control study included 684 cases and 724 controls from eight European countries and Israel. Toenail Zn levels of controls (adjusted for age and study centre) were positively associated with age, alpha-tocopherol and Se, but not with additional dietary variables or with classical risk factors for CHD. Average toenail Zn was 106.0 mg/kg in cases (95 % CI 103.1, 108.9) and 107.5 mg/kg in controls (95 % CI 104.5, 110.7). After controlling for cardiovascular risk factors and for centre, the adjusted odds ratios of myocardial infarction for quintiles 2-5 of toenail Zn with respect to the first quintile were 0.97 (95 % CI 0.59, 1.58), 1.15 (95 % CI 0.72, 1.85), 0.91 (95 % CI 0.56, 1.50), and 0.85 (95 % CI 0.52, 1.39). The P for trend was 0.45. In conclusion toenail Zn levels (reflecting long-term dietary intake) were not significantly associated with acute myocardial infarction.

Adipose Tissue↗
PubMed2002

Poly(A) site choice during mRNA 3'-end formation in the Schizosaccharomyces pombe wos2 gene.

In the fission yeast Schizosaccharomyces pombe, the wos2 gene encodes p23, a highly conserved protein which functions as a co-chaperone for the heat shock protein Hsp90. This p23 protein binds to Hsp90, but its activities and regulatory mechanisms are still unclear. Northern analysis has shown that the wos2 gene produces three transcripts of about 1.1, 0.9 and 0.8 kb, which are expressed differentially depending on the growth temperature. The largest and the smallest transcripts were most abundant at 25 degrees C, whereas the 0.9-kb transcript predominated at 37 degrees C. A time-course analysis indicated that this 0.9-kb species rapidly increased in abundance after a shift from 25 degrees C to 37 degrees C, reaching a maximum after 15 min. A shift back to 25 degrees C resulted in a decline in the amount of this transcript, albeit at a slower rate. Expression analysis of wos2:ura4 and nmt1:wos2 constructs showed that the 3' untranslated region of wos2 alone directs the formation of these multiple, discrete wos2 mRNAs. Sequence analysis of cDNAs derived from these mRNAs showed that the use of different polyadenylation sites results in the production of the three differently sized wos2 transcripts. In the case of the 0.9- and 0.8-kb mRNA species, these sites lie in a predicted hairpin loop in the mRNA, suggesting that polyadenylation signals in wos2 transcripts may be mediated by RNA secondary structure. The possibility that differential thermal stability of these hairpin structures could influence polyadenylation site choice during formation of the 3'-ends of the mRNAs is discussed.

3' Untranslated Regions↗
PubMed2002

Macrophage inducible nitric oxide synthase gene expression is blocked by a benzothiophene derivative with anti-HIV properties.

Nitric oxide (NO) has been shown to mediate multiple physiological and toxicological functions. The inducible nitric oxide synthase (iNOS) is responsible for the high output generation of NO by macrophages following their stimulation by cytokines or bacterial antigens. The inhibition of TNF alpha-stimulated HIV expression and the anti-inflammatory property of PD144795, a new benzothiophene derivative, have been recently described. We have now analyzed whether some of these properties could be mediated by an effect of PD144795 on NO-dependent inflammatory events. We show that PD144795 suppresses the lipopolysaccharide-elicited production of nitrite (NO(-)(2)) by primary peritoneal mouse macrophages and by a macrophage-derived cell line, RAW 264.7. This effect was dependent on the dose and timing of addition of PD144795 to the cells. Suppression of NO(-)(2) production was associated with a decrease in the amount of iNOS protein, iNOS enzyme activity and mRNA expression. The effect of PD144795 was partially abolished by coincubation of the cells with LPS and IFN gamma. However, the inhibitory effect of PD144795 was not abrogated by the simultaneous addition of LPS and TNF alpha, which indirectly suggests that the effect of PD144795 was not due to the inhibition of TNF alpha synthesis. Additionally, PD144795 did not block NF-kappa B nuclear translocation induced by LPS. Inhibition of iNOS gene expression represents a novel mechanism of PD144795 action that underlines the anti-inflammatory effects of this immunosuppressive drug.

Animals↗
PubMed2001

Vaccines--a wonderful tool for equity in health.

Equity is a word representing one of the most important concerns for planners, politicians and the academia. It comes as an answer to the permanent rediscovery of inequity in the benefits of progress among the peoples of the world. Inequity in the distribution of risks for health and disease is a finding that comes on and on again in real life and in the literature. Inequity in disease burden is clearly related to poverty and the eradication of poverty is the mission for every government and international assistance organisations. Development is also not only a precondition for justice but for peace and stability. Health is seen more and more as preceding development and not only as a consequence of wealth. Therefore many things can and must be done in health to achieve development and of course, equity. This concept has been crucial in the new orientation of WHO and our agency is working hard on its promotion at every level. Vaccines are with us as a simple and effective tool for two centuries. The research and development of new vaccines and all in the underlining knowledge has been much faster than its utilization and there is a huge gap to fill in accessibility and actual coverage. World Health Organization (WHO) has been involved all its life in the promotion of disease control and eradication through the use of immunisation techniques. Presently we are part of GAVI and our Vaccines and Biologicals Department has undergone an important modernisation in order to achieve better performance in pursuing three main objectives: Innovation, Immunisation Systems improvement and Accelerated Disease Control. Therefore in order to walk at a faster pace in the better utilisation of vaccines as a tool for equity, we must join forces and participate actively in all the initiatives that are underway.

Humans↗
PubMed2001

Cellular rejection and rate of progression of transplant vasculopathy: a 3-year serial intravascular ultrasound study.

Intravascular ultrasound (IVUS) is established as the optimal method for early detection of transplant vasculopathy. The association between cellular rejection and development of transplant vasculopathy remains controversial. This study attempts to determine the rate of progression of transplant vasculopathy lesions and its relationship with cellular rejection in a long-term (> 1 year) IVUS serial follow-up.A study cohort of 47 patients undergoing heart transplantation from 1993 to 1995 was evaluated. Intravascular ultrasound was performed at baseline (within 8 weeks) and annually for a period of 3 years to determine maximum intimal thickness and maximum plaque area in each coronary segment. Significant allograft vasculopathy was defined as a site with intimal thickness > 0.5 mm not present at baseline. Biopsy results were scored by assigning a numerical weight to each ISHLT grade during the first year. Donor lesions ranged from 0.86 to 1.1 mm, showing no evidence of progression at serial follow-up. De novo lesions were identified in 30 patients. These lesions appeared yearly but progressed slowly. The average biopsy score in the entire cohort was 1.1 +/- 0.8. Average biopsy score was > 1.0 in 35 patients with significant linear correlation between the rate of intimal progression and biopsy score (r = 0.42, p = 0.01). Multivariate analysis demonstrated that only the biopsy score correlated with the rate of progression. Lesions of donor atherosclerosis do not change significantly after transplantation. However, de novo lesions continue to develop every year. In patients with evidence of rejection, the rate of progression of transplant vasculopathy correlates with the severity of rejection.

Adult↗
PubMed2000

Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses.

Chronic myelogenous leukemia (CML) presents a unique opportunity to develop therapeutic strategies using vaccination against a truly tumor-specific antigen that is also the oncogenic protein required for neoplasia. CML is characterized by the t(9;22) that results in the bcr-abl fusion oncogene and in the expression of a chimeric protein product p210. Previously we have shown that peptides derived from amino acid sequences crossing the b3a2 fusion breakpoint in p210 elicit class I restricted cytotoxic T lymphocytes and class II responses, respectively, in vitro. Such sequences may thus comprise absolutely tumor-specific antigens in a peptide-based vaccine. We evaluated the safety and immunogenicity of a multidose, bcr-abl breakpoint peptide vaccine in 12 adults with chronic-phase CML. Cohorts of 3 patients each received either 50 microg, 150 microg, 500 microg, or 1500 microg total peptide mixed with 100 microg QS-21 as an immunological adjuvant. Delayed-type hypersensitivity (DTH), humoral responses, and unprimed ex vivo autologous proliferation ((3)H-thymidine incorporation) and cytotoxicity (chromium-51 release) responses were measured. All 68 vaccinations were well tolerated without significant adverse effects. In 3 of the 6 patients treated at the 2 highest dose levels of vaccine, peptide-specific, T-cell proliferative responses (n = 3) and/or DTH responses (n = 2) were generated that lasted up to 5 months after vaccination. Cytotoxic T lymphocytes have not been identified. In conclusion, a tumor-specific, bcr-abl derived peptide vaccine can be safely administered to patients with chronic-phase CML and can elicit a bcr-abl peptide-specific immune response despite the presence of active disease in these patients and approximately 10(12) leukemia cells. (Blood. 2000;95:1781-1787)

Adjuvants, Immunologic↗
PubMed2000

Differentiating Taenia solium and Taenia saginata infections by simple hematoxylin-eosin staining and PCR-restriction enzyme analysis.

Species-specific identification of human tapeworm infections is important for public health purposes, because prompt identification of Taenia solium carriers may prevent further human cysticercosis infections (a major cause of acquired epilepsy). Two practical methods for the differentiation of cestode proglottids, (i) routine embedding, sectioning, and hematoxylin-eosin (HE) staining and (ii) PCR with restriction enzyme analysis (PCR-REA), were tested on samples from 40 individuals infected with T. solium (n = 34) or Taenia saginata (n = 6). Microscopic examination of HE staining of sections from 24 cases, in which conserved proglottids were recovered, clearly revealed differences in the number of uterine branches. Distinct restriction patterns for T. solium and T. saginata were observed when the PCR products containing the ribosomal 5.8S gene plus internal transcribed spacer regions were digested with either AluI, DdeI, or MboI. Both HE histology and PCR-REA are useful techniques for differentiating T. solium from T. saginata. Importantly, both techniques can be used in zones of endemicity. HE histology is inexpensive and is currently available in most regions of endemicity, and PCR-REA can be performed in most hospital centers already performing PCR without additional equipment or the use of radioactive material.

Animals↗
PubMed1999

Osmotic response element is required for the induction of aldose reductase by tumor necrosis factor-alpha.

Induction of aldose reductase (AR) was observed in human cells treated with tumor necrosis factor-alpha (TNF-alpha). AR protein expression increased severalfold in human liver cells after 1 day of exposure to 100 units/ml TNF-alpha. An increase in AR transcripts was also observed in human liver cells after 3 h of TNF-alpha treatment, reaching a maximum level of 11-fold at 48 h. Among the three inflammatory cytokines: TNF-alpha, interleukin-1, and interferon-gamma, TNF-alpha (100 units/ml) gave the most induction of AR. Differences in the pattern of AR induction were observed in human liver, lens, and retinal pigment epithelial cells with increasing concentrations of TNF-alpha. A similar pattern of AR promoter response was observed between TNF-alpha and osmotically stressed human liver cells. The deletion of the osmotic response element (ORE) abolished the induction by TNF-alpha and osmotic stress. A point mutation that converts ORE to a nuclear factor-kappaB (NF-kappaB) sequence abolished the osmotic response but maintained the TNF-alpha response. Electrophoretic gel mobility shift assays showed two NF-kappaB proteins, p50 and p52, capable of binding ORE sequence, and gel shift Western assay detected NF-kappaB proteins p50 and p65 in the ORE complex. Inhibitors of NF-kappaB signaling, lactacystin, and MG132 abolished the AR promoter response to TNF-alpha.

Aldehyde Reductase↗
PubMed1999

Genetic interactions between Hsp90 and the Cdc2 mitotic machinery in the fission yeast Schizosaccharomyces pombe.

In Schizosaccharomyces pombe, wee1 encodes a tyrosine kinase that inhibits entry into mitosis by phophorylating Cdc2, the universal cyclin-dependent kinase (Cdk) that regulates the G2/M transition in all eukaryotic cells. A search for suppressors of the G2 arrest caused by overexpression of weel led to the isolation of a new allele of swo1 (named swo1-w1), the gene coding for chaperone Hsp90, which is required to stabilise Weel. The swo1-w1 allele carries a glycine to aspartic acid substitution at amino acid 155 that results in a partial loss of Hsp90 function. Cells bearing the swo1-w1 mutation in combination with the point mutation cdc2-33 or cdc2-M26 showed severe mitotic defects. Genetic interactions were not observed in combination with point mutations in other cdc genes, suggesting that Cdc2 specifically interacts with Hsp90. This synthetic lethal swo1-w1 cdc2-33 (or cdc2-M26) strain had normal levels of Cdc2 protein and histone H1 phosphorylation activity, indicating that Hsp90 is required to enable Cdc2 to interact with its mitotic substrates or regulators, rather than for its proper folding or stabilisation. In a wild-type background, swo1-w1 mutant cells were sensitive to temperature as well as to other stress agents, such as KCI, ethanol and formamide. Under these stressful growth conditions, the swo1-w1 cells displayed anaphase B arrest and aberrant septation patterns, indicating that a subset of proteins involved in mitosis and cytokinesis is highly dependent on chaperone Hsp90 for function.

Alleles↗
PubMed1999

Early gene expression during androgen-induced inhibition of proliferation of prostate cancer cells: a new suppressor candidate on chromosome 13, in the BRCA2-Rb1 locus.

In the prostate gland cell numbers are regulated by androgens through three separate pathways: (a) inhibition of cell death (apoptosis), (b) induction of cell proliferation (step 1), and (c) inhibition of cell proliferation (step 2, proliferative shutoff). The precise regulation of these control pathways is still elusive. The human prostate carcinoma LNCaP cell line variants express a subset of proliferative pathways comparable to those present in normal prostate cells (LNCaP-FGC expresses both steps, LNCaP-LNO expresses step 2, LNCaP-TAC expresses step 1, LNCaP-TJA expresses neither). The purpose of the present work is to identify the genes involved in the androgen-induced proliferative arrest of these cells. Using a Wang-Brown subtracted library, a set of shutoff specific genes has been isolated. One of these new genes, AS3, shows high expression in the early regulatory phase of androgen-induced proliferative shutoff in the cell variants and in the prostates of castrated rats. The putative 1391-residue polypeptide has the molecular size of about 186 kDa. It has coiled-coil structures that usually participate in protein-protein interactions, a perfect leucine-zipper that suggests DNA binding, nuclear localization motifs, proline- and serinerich domains, unique C-terminal acidic-basic repeats, and ATP- and DNA-binding motifs. The transcript has 34 exons in a 200,000 bp region on chromosome 13q12-q13, downstream of the breast cancer susceptibility gene BRCA2, and centromeric to the retinoblastoma (Rb1) locus. This area is subject to frequent allelic losses in cancers, and is believed to carry a number of cryptic suppressor genes. The AS3 gene seems to be a novel candidate in the regulation of androgen-induced proliferative arrest of human prostate cells.

Amino Acid Sequence↗
PubMed1999

Hydrodynamic modelling of stress.

This work is a qualitative study of an organism's physiological adaptative response to stress. The experimental data were selected from a previous study leading to the conclusion that stress may be considered as a topological retraction within a vital space that must be more precisely defined. The experimental methodology uses rat poisoning by neurotoxins. The control parameter is the intensity of the toxic doses. Measured parameters are the animals' survival rate and the kinetics of cerebral acetylcholinesterase activity. The results, when expressed as a function of the inverted doses, show a characteristic evolution. The pattern of the curve closely resembles a vortex profile. This analogy is studied more extensively in both the physical and biological domains. These findings help to clarify the concept of biological stress which presents the same vectorial properties as hydrodynamic vorticity. In particular, the dissipation of stress and the dissipation of vorticity seem to obey the same laws. This observation is valid for both diffusion and convection processes. The decompensation phase of stress could be compared with the instability and turbulence in flows. Our approach in this paper is mainly to establish a general and phenomenological description of the stress response fitting experimental observations.

Acetylcholinesterase↗