Sergio Alberto Ramirez-Garcia

Bio: Sergio Alberto Ramirez-Garcia is an academic researcher. The author has contributed to research in topics: Medicine & Humanities. The author has an hindex of 6, co-authored 35 publications receiving 99 citations.

Cantu syndrome and lymphoedema.

Abstract: Three female patients with Cantu syndrome were studied, two of whom were adults presenting with the complication of lymphoedema, as described earlier in a male patient with this syndrome. The aim of this study is to report the clinical characteristics of these three new cases and to emphasize that lymphoedema, as observed in two of the patients described here, has been observed in 11.5% of patients with Cantu syndrome and that heterochromia iridis, observed in one patient, is probably a new feature of this condition.

Cytochrome P450 from Plants: Platforms for Valuable Phytopharmaceuticals

Abstract: Cytochrome P450 enzymes are important for biotechnology due to their capacity to modify diverse secondary metabolites that may produce chemicals with pharmacological properties. Most terpenes, flavonoids and alkaloids require P450 catalytic functions to reach their biological activity. In the last ten years, several efforts have focused on the expression and production of these three main types of secondary metabolites in engineered microorganisms and plants using P450 of ethnobotanical origin. Despite this, several P450 coding sequences from plant sources are discovered yearly but only a few have been screened by functional genomics. Amongst them, only a few have shown potentials for use in sustainable production of novel drugs and highly valuable products. Cytochrome P450 involvement in the biosynthesis of these products is discussed in this work. Keywords : Biotechnological platforms, Cytochrome P450, Phytopharmaceuticals, Yield improvement, Terpenes, Flavonoids, Alkaloids, Microbial expression

[(CAG)n polymorphism of the ATXN2 gene, a new marker of susceptibility for type 2 diabetes mellitus].

Abstract: RESUMEN Objetivo Estimar si hay asociacion del repetido (CAG)n del gen ATXN2 en poblacion mexicana con diabetes mellitus (DM) tipo 2. Metodos Estudio epidemiologico de casos y controles. Se incluyeron personas sanas y personas diabeticas. La deteccion de la expansion (CAG)n se realizo por reaccion en cadena de la polimerasa (PCR)-punto final. Los productos de PCR se analizaron mediante electroforesis (PAGE al 8%) y tincion con nitrato de plata. Resultados La distribucion de alelos del trinucleotido (CAG)n en la poblacion analizada resulto similar a la reportada en el centro del pais. El alelo mas frecuente es el de 22 repetidos; sin embargo, hay asociacion con los portadores de los repetidos largos dentro del rango normal con diabetes. Conclusiones Los resultados sugieren que el repetido (CAG)n del gen de ATXN2 podria ser un factor causal de DM tipo 2.

A clinical report of the massive CAG repeat expansion in spinocerebellar ataxia type 2: Severe onset in a Mexican child and review previous cases.

Abstract: The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow ocular saccades, nystagmus, ophthalmoplegia, dysarthria, dysphagia, cognitive deterioration, mild dementia, peripheral neuropathy. Infantile onset is a rare presentation that only has been reported in four instances in the literature. In the present work a boy aged 5 years 7 months was studied due to horizontal gaze-evoked nystagmus, without saccades, ataxic gait, dysarthria, dysphagia, dysmetria, generalized spasticity mainly pelvic, bilateral Babinsky. The mother aged 27 years-old presented progressive cerebellar ataxia, dysarthria, dysmetria, dysdiadochokinesis, limb ataxia and olivopontocerebellar atrophy. The molecular analysis was made by identifying the expansion repeats in tandem by long PCR to analyze the repeats in the ATXN2 gene. We found an extreme CAG expansion repeats of ~884 repeats in the child. We describe a Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon.

Implicaciones en la atención primaria en salud de la genética y genómica en la diabetes mellitus tipo 2

Abstract: aType 2 diabetes mellitus is a complex disease and a global health problem. Therefore, the fi rst level of health care should handle the approaches of medical genetics and genomics to reduce its incidence. The aim is to present perspectives analyzed by our group in two areas of genetics and its clinical application. Emphasis is placed on the coexistence of several genetic forms clinically detectable in patients with diabetes, missing heritability associated with low penetrance, and epigenomics mechanism. It is discussed the effect of genetic variation associated with resistance to insulin, beta-cell dysfunction, shaft incretin, and other points of interest, such as thrifty genotype hypothesis, conformational disease, genetically unknown foods, phenocopies as clinically silent hypercortisolism, molecular phytopharmacology in the clinical management. Finally, the result was displayed in the Mexican population from genetic studies and new fi ndings of clinical importance, such as involvement of melatonin and effect of variations in the number of copies in a genomic region.

The Lymphatic System in Disease Processes and Cancer Progression

Abstract: Advances in our understanding of the structure and function of the lymphatic system have made it possible to identify its role in a variety of disease processes. Because it is involved not only in fluid homeostasis but also in immune cell trafficking, the lymphatic system can mediate and ultimately alter immune responses. Our rapidly increasing knowledge of the molecular control of the lymphatic system will inevitably lead to new and effective therapies for patients with lymphatic dysfunction. In this review, we discuss the molecular and physiological control of lymphatic vessel function and explore how the lymphatic system contributes to many disease processes, including cancer and lymphedema.

KATP Channels and Cardiovascular Disease Suddenly a Syndrome

Abstract: ATP-sensitive potassium (KATP) channels were first discovered in the heart 30 years ago. Reconstitution of KATP channel activity by coexpression of members of the pore-forming inward rectifier gene family (Kir6.1, KCNJ8, and Kir6.2 KCNJ11) with sulfonylurea receptors (SUR1, ABCC8, and SUR2, ABCC9) of the ABCC protein subfamily has led to the elucidation of many details of channel gating and pore properties. In addition, the essential roles of Kir6.x and SURx subunits in generating cardiac and vascular KATP(2) and the detrimental consequences of genetic deletions or mutations in mice have been recognized. However, despite this extensive body of knowledge, there has been a paucity of defined roles of KATP subunits in human cardiovascular diseases, although there are reports of association of a single Kir6.1 variant with the J-wave syndrome in the ECG, and 2 isolated studies have reported association of loss of function mutations in SUR2 with atrial fibrillation and heart failure. Two new studies convincingly demonstrate that mutations in the SUR2 gene are associated with Cantu syndrome, a complex multi-organ disorder characterized by hypertrichosis, craniofacial dysmorphology, osteochondrodysplasia, patent ductus arteriosus, cardiomegaly, pericardial effusion, and lymphoedema. This realization of previously unconsidered consequences provides significant insight into the roles of the KATP channel in the cardiovascular system and suggests novel therapeutic possibilities.

Cantú Syndrome Is Caused by Mutations in ABCC9

Abstract: Cantu syndrome is a rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. Using an exome-sequencing approach applied to one proband-parent trio and three unrelated single cases, we identified heterozygous mutations in ABCC9 in all probands. With the inclusion of the remaining cohort of ten individuals with Cantu syndrome, a total of eleven mutations in ABCC9 were found. The de novo occurrence in all six simplex cases in our cohort substantiates the presence of a dominant disease mechanism. All mutations were missense, and several mutations affect Arg1154. This mutation hot spot lies within the second type 1 transmembrane region of this ATP-binding cassette transporter protein, which may suggest an activating mutation. ABCC9 encodes the sulfonylurea receptor (SUR) that forms ATP-sensitive potassium channels (KATP channels) originally shown in cardiac, skeletal, and smooth muscle. Previously, loss-of-function mutations in this gene have been associated with idiopathic dilated cardiomyopathy type 10 (CMD10). These findings identify the genetic basis of Cantu syndrome and suggest that this is a new member of the potassium channelopathies.

Hypotension due to Kir6.1 gain-of-function in vascular smooth muscle.

Abstract: Background KATP channels, assembled from pore-forming (Kir6.1 or Kir6.2) and regulatory (SUR1 or SUR2) subunits, link metabolism to excitability. Loss of Kir6.2 results in hypoglycemia and hyperinsulinemia, whereas loss of Kir6.1 causes Prinzmetal angina–like symptoms in mice. Conversely, overactivity of Kir6.2 induces neonatal diabetes in mice and humans, but consequences of Kir6.1 overactivity are unknown. Methods and Results We generated transgenic mice expressing wild-type (WT), ATP-insensitive Kir6.1 \[Gly343Asp\] (GD), and ATP-insensitive Kir6.1 \[Gly343Asp,Gln53Arg\] (GD-QR) subunits, under Cre-recombinase control. Expression was induced in smooth muscle cells by crossing with smooth muscle myosin heavy chain promoter–driven tamoxifen-inducible Cre-recombinase (SMMHC-Cre-ER) mice. Three weeks after tamoxifen induction, we assessed blood pressure in anesthetized and conscious animals, as well as contractility of mesenteric artery smooth muscle and KATP currents in isolated mesenteric artery myocytes. Both systolic and diastolic blood pressures were significantly reduced in GD and GD-QR mice but normal in mice expressing the WT transgene and elevated in Kir6.1 knockout mice as well as in mice expressing dominant-negative Kir6.1 [AAA] in smooth muscle. Contractile response of isolated GD-QR mesenteric arteries was blunted relative to WT controls, but nitroprusside relaxation was unaffected. Basal KATP conductance and pinacidil-activated conductance were elevated in GD but not in WT myocytes. Conclusions KATP overactivity in vascular muscle can lead directly to reduced vascular contractility and lower blood pressure. We predict that gain of vascular KATP function in humans would lead to a chronic vasodilatory phenotype, as indeed has recently been demonstrated in Cantu syndrome.

Genetic and Epigenetic Studies in Diabetic Kidney Disease

Abstract: Chronic kidney disease is a worldwide health crisis, while diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease (ESRD). DKD is a microvascular complication and occurs in 30-40% of diabetes patients. Epidemiological investigations and clinical observations on the familial clustering and heritability in DKD have highlighted an underlying genetic susceptibility. Furthermore, DKD is a progressive and long-term diabetic complication, in which epigenetic effects and environmental factors interact with an individual's genetic background. In recent years, researchers have undertaken genetic and epigenetic studies of DKD in order to better understand its molecular mechanisms. In this review, clinical material, research approaches and experimental designs that have been used for genetic and epigenetic studies of DKD are described. Current information from genetic and epigenetic studies of DKD and ESRD in patients with diabetes, including the approaches of genome-wide association study (GWAS) or epigenome-wide association study (EWAS) and candidate gene association analyses, are summarized. Further investigation of molecular defects in DKD with new approaches such as next generation sequencing analysis and phenome-wide association study (PheWAS) is also discussed.