Hugo Laviada-Molina

Fatal Human Infection with Rickettsia rickettsii, Yucatán, Mexico

The first fatal Rickettsia rickettsii infection was diagnosed in the southwest of Mexico. The patient had fever, erythematous rash, abdominal pain, and severe central nervous system involvement with convulsive crisis. The diagnosis of R. rickettsii infection was established by immunohistochemistry and specific polymerase chain reaction.

Clinical-epidemiological study of leptospirosis in humans and reservoirs in Yucatán, México

A leptospirosis clinical-epidemiological study was made in humans and reservoirs in the state of Yucatán, México. Interviews and serological analyses were made on 400 persons from an open population, 439 probable cases of leptospirosis and 1060 animal reservoirs (cows, pigs, dogs, rats and opossums). IgM Leptospira Dipstick and Microscopic Agglutination Test (MAT) was used to detect human antibodies to leptospiras and serovar respectively. Leptospirosis incidence in humans was 2.2/100,000 inhab. in 1998, 0.7/100,000 in 1999 and 0.9/100,000 in 2000. Overall seroprevalence was 14.2%, relatively unchanged from seroprevalences observed 20 years ago. Highest seropositivity was found in people over 56 years of age, predominating males over females. Predominant serovars in the open population were tarassovi, hardjo, pomona and panama. Leptospirosis cases were most frequent in rural areas, and the anicteric course predominated over the icteric. The panama, icterohaemorrhagiae and pomona serovars predominated in both anicteric and icteric courses. Dogs, pigs and rodents had the highest seropositivity among the reservoirs. Contact with rodents and natural water sources were significant factors (p < or = 0.05). Human cases (74%) occurred during the rainy season. It is concluded that leptospirosis is still a serious illness with important clinical and epidemiological implications in the state of Yucatán, Mexico.

Heritability and genetic correlations of metabolic disease-related phenotypes in Mexico: Preliminary report from the GEMM family study

ABSTRACT Cardiovascular disease (CVD) is a major cause of mortality in the Republic of Mexico, and metabolic syndrome, a complex of CVD risk factors, is increasingly prevalent. To date, however, there have been few studies of the genetic epidemiology of metabolic syndrome in Mexico. As a first step in implementing the GEMM Family Study, a large, multicenter collaborative study, we recruited 375 individuals in 21 extended families, without ascertainment on disease, at 9 medical institutions across Mexico. Participants were measured for anthropometric (stature, weight, waist circumference) and hemodynamic (blood pressure, heart rate) phenotypes; glucose, cholesterol, and triglyceride levels were measured in fasting blood. Variance components–based quantitative genetic analyses were performed using SOLAR. All phenotypes except diastolic blood pressure were significantly heritable. Consistent with the definition of metabolic syndrome, many phenotypes exhibited significant environmental correlation, and significant genetic correlations were found between measures of adiposity and fasting glucose and fasting triglyceride levels. These preliminary data represent the first heritability estimates for many of these phenotypes in the Republic of Mexico and indicate that this study design offers excellent power for future gene discovery relative to metabolic disease.

Hemorrhagic pulmonary leptospirosis: three cases from the Yucatan peninsula, Mexico

Three leptospirosis cases with lung involvement are reported from the Yucatan Peninsula, Mexico. All three patients were admitted to the intensive care unit due to acute respiratory failure. Treatment with antibiotics resulted in favorable evolution despite the negative prognosis. Leptospirosis should be included in the differential diagnosis of patients with fever and lung involvement.

Replication of obesity and diabetes-related SNP associations in individuals from Yucatán, México

The prevalence of type 2 diabetes (T2D) is rising rapidly and in Mexicans is ~19%. T2D is affected by both environmental and genetic factors. Although specific genes have been implicated in T2D risk few of these findings are confirmed in studies of Mexican subjects. Our aim was to replicate associations of 39 single nucleotide polymorphisms (SNPs) from 10 genes with T2D-related phenotypes in a community-based Mexican cohort. Unrelated individuals (n = 259) living in southeastern Mexico were enrolled in the study based at the University of Yucatan School of Medicine in Merida. Phenotypes measured included anthropometric measurements, circulating levels of adipose tissue endocrine factors (leptin, adiponectin, pro-inflammatory cytokines), and insulin, glucose, and blood pressure. Association analyses were conducted by measured genotype analysis implemented in SOLAR, adapted for unrelated individuals. SNP Minor allele frequencies ranged from 2.2 to 48.6%. Nominal associations were found for CNR1, SLC30A8, GCK, and PCSK1 SNPs with systolic blood pressure, insulin and glucose, and for CNR1, SLC30A8, KCNJ11, and PCSK1 SNPs with adiponectin and leptin (p < 0.05). P-values greater than 0.0014 were considered significant. Association of SNPs rs10485170 of CNR1 and rs5215 of KCNJ11 with adiponectin and leptin, respectively, reached near significance (p = 0.002). Significant association (p = 0.001) was observed between plasma leptin and rs5219 of KCNJ11.

Integrating genomic analysis with the genetic basis of gene expression: preliminary evidence of the identification of causal genes for cardiovascular and metabolic traits related to nutrition in Mexicans

Whole-transcriptome expression profiling provides novel phenotypes for analysis of complex traits. Gene expression measurements reflect quantitative variation in transcript-specific messenger RNA levels and represent phenotypes lying close to the action of genes. Understanding the genetic basis of gene expression will provide insight into the processes that connect genotype to clinically significant traits representing a central tenet of system biology. Synchronous in vivo expression profiles of lymphocytes, muscle, and subcutaneous fat were obtained from healthy Mexican men. Most genes were expressed at detectable levels in multiple tissues, and RNA levels were correlated between tissue types. A subset of transcripts with high reliability of expression across tissues (estimated by intraclass correlation coefficients) was enriched for cis-regulated genes, suggesting that proximal sequence variants may influence expression similarly in different cellular environments. This integrative global gene expression profiling approach is proving extremely useful for identifying genes and pathways that contribute to complex clinical traits. Clearly, the coincidence of clinical trait quantitative trait loci and expression quantitative trait loci can help in the prioritization of positional candidate genes. Such data will be crucial for the formal integration of positional and transcriptomic information characterized as genetical genomics.

Nutritional genomics: an approach to the genome-environment interaction

Nutritional genomics forms part of the genomic sciences and addresses the interaction between genes and the human diet, its influence on metabolism and subsequent susceptibility to develop common diseases. It encompasses both nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome; and nutrigenetics, that explores the effects of genetic variations on the diet/disease interaction. A number of mechanisms drive the gene/diet interaction: elements in the diet can act as links for transcription factor receptors and after intermediary concentrations, thereby modifying chromatin and impacting genetic regulation; affect signal pathways, regulating phosphorylation of tyrosine in receptors; decrease signaling through the inositol pathway; and act through epigenetic mechanisms, silencing DNA fragments by methylation of cytosine. The signals generated by polyunsaturated fatty acids are so powerful that they can even bypass insulin mediated lipogenesis, stimulated by carbohydrates. Some fatty acids modify the expression of genes that participate in fatty acid transport by lipoproteins. Nutritional genomics has myriad possible therapeutic and preventive applications: in patients with enzymatic deficiencies; in those with a genetic predisposition to complex diseases such as dyslipidemia, diabetes and cancer; in those that already suffer these diseases; in those with altered mood or memory; during the aging process; in pregnant women; and as a preventive measure in the healthy population.

Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design

Ultrasound‐targeted microbubble destruction (UTMD) is a novel means of tissue‐specific gene delivery. This approach systemically infuses transgenes precoupled to gas‐filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP‐1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)‐treated mice and baboons. We hypothesized that gene therapy with BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with UCP‐1 overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD‐based gene delivery in enhancing SKM overexpression of the UCP‐1 gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of PRDM16, PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in vivo. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD gene therapy, engineered a BAT phenotype with UCP‐1 over‐expression.

Friendship Concept and Community Network Structure among Elementary School and University Students

We use complex network theory to study the differences between the friendship concepts in elementary school and university students. Four friendship networks were identified from surveys. Three of these networks are from elementary schools; two are located in the rural area of Yucatán and the other is in the urban area of Mérida, Yucatán. We analyzed the structure and the communities of these friendship networks and found significant differences among those at the elementary schools compared with those at the university. In elementary schools, the students make friends mainly in the same classroom, but there are also links among different classrooms because of the presence of siblings and relatives in the schools. These kinds of links (sibling-friend or relative-friend) are called, in this work, “mixed links”. The classification of the communities is based on their similarity with the classroom composition. If the community is composed principally of students in different classrooms, the community is classified as heterogeneous. These kinds of communities appear in the elementary school friendship networks mainly because of the presence of relatives and siblings. Once the links between siblings and relatives are removed, the communities resembled the classroom composition. On the other hand, the university students are more selective in choosing friends and therefore, even when they have friends in the same classroom, those communities are quite different to the classroom composition. Also, in the university network, we found heterogeneous communities even when the presence of sibling and relatives is negligible. These differences made up a topological structure quite different at different academic levels. We also found differences in the network characteristics. Once these differences are understood, the topological structure of the friendship network and the communities shaped in an elementary school could be predicted if we know the total number of students and the ties between siblings and relatives. However, at the university, we cannot do the same. This discovery implies that friendship is a dynamic concept that produces several changes in the friendship network structure and the way that people make groups of friends; it provides the opportunity to give analytic support to observational studies. Communities were also studied by gender and we found that when the links among relatives and siblings were removed, the number of communities formed by one gender alone increased. At the university, many communities formed by students of the same gender were also found.

Frecuencia de seropositividad para Chlamydia pneumoniae en adultos de Yucatán, México.

Vol. 13/No. 1/Enero-Marzo, 2002 Solicitud de sobretiros: M. en C. Jorge Zavala-Velázquez, Departamento de Patología Tropical, Facultad de Medicina, Universid ad Autónoma de Yucatán. Avenida Itzáes No. 498 x 59 y 59-A, C.P. 97000, Mérida, Yucatán, México. Tel. (999) 928-53-29 y Fax: 924-05-54. E-mail: hugola@mid.cablered.com.mx Recibido el 6/Diciembre/2000. Aceptado para publicación el 21/Junio/2001.