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Biomedical subjects

Tamara S Hannon

Publications and source records attributed to Tamara S Hannon.

10 recordsLinked to original sources
PubMed2006

Longitudinal study of physiologic insulin resistance and metabolic changes of puberty.

Cross-sectional studies have shown that 1) adolescents are insulin resistant compared with prepubertal children and adults, 2) pubertal insulin resistance is likely mediated by growth hormone (GH), and 3) pubertal insulin resistance is associated with increased fat oxidation and decreased glucose oxidation. The aim of this study was to assess the validity of these cross-sectional observations by performing a longitudinal study in normal children during the prepubertal and pubertal periods. Nine healthy, normal weight, prepubertal children underwent hyperinsulinemic-euglycemic and hyperglycemic clamp studies for evaluation of insulin sensitivity and insulin secretion. Children had repeat evaluations during puberty. Consistent with cross-sectional observations, this longitudinal study demonstrated that during puberty: 1) insulin sensitivity decreased by approximately 50%, 2) the decrease in insulin sensitivity was compensated by a doubling in insulin secretion, and 3) the decrease in insulin sensitivity was independent of changes in percentage of body fat. Puberty was associated with increased total body lipolysis and decreased glucose oxidation. A novel observation is the demonstration of approximately 50% decrease in adiponectin levels at the pubertal time point. These metabolic changes are proposed to be partially mediated by increased GH secretion and are consistent with the Randle cycle of competition between glucose and fat oxidation.

Adiponectin↗
PubMed2006

Use of markers of dyslipidemia to identify overweight youth with insulin resistance.

CONTEXT: Markers to identify overweight youth with insulin resistance are of clinical importance. OBJECTIVE: To determine if markers of dyslipidemia could identify overweight adolescents with insulin resistance. SETTING, PARTICIPANTS, AND STUDY DESIGN: We retrospectively examined the association between markers of dyslipidemia and insulin resistance in 35 overweight [body mass index (BMI) of > or =95th percentile], white adolescents [mean age 13.5 +/- (SD) 1.6 yr] who had participated in hyperinsulinemic-euglycemic clamp studies to evaluate insulin action. Total body fat was measured by dual-energy X-ray absorptiometry and abdominal fat with computed tomography. Using receiver-operating curves, cut-points for triglyceride (TG)/high-density lipoprotein (HDL) and TG level to identify overweight individuals in the lowest tertile for insulin sensitivity were determined. MAIN OUTCOME MEASURE: Difference in the values for insulin sensitivity among the groups. RESULTS: Of the markers examined (TG, TG/HDL, adiponectin, measures of adiposity and fasting insulin), fasting insulin was the strongest correlate of insulin sensitivity (r = 0.87, p < 0.001). Youth with TG/HDL level > or =3 had lower insulin sensitivity (50% lower median values, p < 0.01) and higher visceral fat (p < 0.05) despite BMI comparable to that of youth with TG/HDL level <3. Youth with TG/HDL > or =3 had a sensitivity of 61% and specificity of 82% for identifying participants with the greatest degree of insulin resistance. CONCLUSIONS: TG and TG/HDL are easily obtained markers associated with insulin resistance. Further research is needed to determine if a constellation of clinical findings, such as components of the metabolic syndrome along with other metabolic markers including adiponectin, better predicts insulin resistance in overweight youth.

Abdominal Fat↗
PubMed2005

Childhood obesity and type 2 diabetes mellitus.

Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.

Administration, Oral↗
PubMed2005

Childhood obesity: a simple equation with complex variables.

The prevalence of childhood obesity is rising rapidly, as are the associated medical complications, including type 2 diabetes, hypertension, and coronary heart disease. This has significant medical and socioeconomic implications. The definition of obesity in adults is based on body mass index (BMI), which has been correlated with morbidity and mortality. Similarly, the definition of childhood obesity is currently based on BMI; however, there are currently no data to relate morbidity and mortality to BMI values in children. The known and potential causes of childhood obesity are many, but they can be categorized as genetic, endocrine, prenatal/early life, physical activity, diet, and socioeconomic. These factors influence the basic equation: energy input = energy output. Imbalances in this equation can result in obesity. Here we present a review of recent literature and highlight the etiologies, certain complications, and potential prevention and treatment strategies of childhood obesity.

Adolescent↗
PubMed2004

Mechanisms regulating the constitutive activation of the extracellular signal-regulated kinase (ERK) signaling pathway in ovarian cancer and the effect of ribonucleic acid interference for ERK1/2 on cancer cell proliferation.

The ERK1/2 MAPK pathway is a critical signaling system that mediates ligand-stimulated signals for the induction of cell proliferation, differentiation, and cell survival. Studies have shown that this pathway is constitutively active in several human malignancies and may be involved in the pathogenesis of these tumors. In the present study we examined the ERK1/2 pathway in cell lines derived from epithelial and granulosa cell tumors, two distinct forms of ovarian cancer. We show that ERK1 and ERK2 are constitutively active and that this activation results from both MAPK kinase-dependent and independent mechanisms and is correlated with elevated BRAF expression. MAPK phosphatase 1 (MKP-1) expression, which is involved in ERK1/2 deactivation, is down-regulated in the cancer cells, thus further contributing to ERK hyperactivity in these cells. Treatment of these cancer cell lines with the proteasome inhibitor ZLLF-CHO increased MKP-1 but not MKP-2 expression and decreased ERK1/2 phosphorylation. More importantly, silencing of ERK1/2 protein expression using RNA interference led to the complete suppression of tumor cell proliferation. These results provide evidence that the ERK pathway plays a major role in ovarian cancer pathogenesis and that down-regulation of this master signaling pathway is highly effective for the inhibition of ovarian tumor growth.

Cell Division↗
PubMed2003

Is McCune-Albright syndrome overlooked in subjects with fibrous dysplasia of bone?

OBJECTIVE: McCune-Albright syndrome (MAS) is characterized by a clinical triad of endocrinopathies, café au lait pigmentation, and polyostotic fibrous dysplasia of bone. We hypothesized that children diagnosed with fibrous dysplasia are not routinely being evaluated for coexisting endocrine dysfunction or MAS. Our objective was to prospectively screen subjects with fibrous dysplasia for endocrine disease and G(s)alpha gene (GNAS1 )-activating mutations. STUDY DESIGN: Nine subjects who presented with fibrous dysplasia and were followed in orthopedic clinics were evaluated for other manifestations of MAS. Genomic DNA was isolated from blood, and mutation analysis of GNAS1 was performed. RESULTS: On physical examination, 5 of 9 subjects were found to have café au lait pigmentation. Three of 9 subjects had TSH levels below the normal range. One of these subjects was found to have hyperthyroidism and was treated by total thyroidectomy. GNAS1 mutations were identified in 5 of 9 subjects with either monostotic or polyostotic fibrous dysplasia of bone. CONCLUSIONS: We conclude that a substantial proportion of children being followed for fibrous dysplasia of bone have unrecognized clinical and laboratory features of MAS. These children are at risk for endocrinopathy and should be screened accordingly.

Adolescent↗
PubMed2003

Differential expression of GRK isoforms in nonmalignant and malignant human granulosa cells.

Granulosa cell tumors are serious ovarian neoplasms that can occur in women of all ages. While there have been numerous attempts to understand the cause of these malignancies, the pathogenesis of granulosa cell tumors (GCTs) still remains largely unknown. G-protein coupled receptor kinases (GRKs) are important regulators of signal transduction through the process of receptor desensitization and internalization. Receptors that are regulated by GRKs are members of the large family of seven-transmembrane receptors and include the follicle stimulating hormone receptor (FSHR). In granulosa cells, the FSH signaling system is responsible for cell proliferation, differentiation, and steroidogenesis. In the studies presented, we examined GRK mRNA and protein expression in nonmalignant human granulosa cells, in KGN cells, a human GCT cell line, and in a panel of human GCT samples. The KGN tumor cells express significantly less GRK4 alpha/beta protein and higher levels of GRK2 and GRK4 gamma/delta protein as compared to nonmalignant human granulosa cells. In human GCT samples, GRK4 alpha/beta protein was detected in 3 of the 13 tumor samples, whereas gamma/delta proteins expression was detected in all samples. These findings suggest that GRK protein expression is altered in GCTs and may be involved in the pathogenesis of these tumors.

Blotting, Western↗
PubMed2002

Premature thelarche and granulosa cell tumors: a search for FSH receptor and G5alpha activating mutations.

Activating mutations of the Gsalpha gene are responsible for McCune-Albright syndrome and have also been identified in sporadic tumors of the pituitary and thyroid. When associated with malignancy, activating Gsalpha mutations are known as gsp-oncogenes. We hypothesized that similar activating mutations might also account for some cases of premature thelarche and/ or granulosa cell tumors. Polymerase chain reaction and DNA sequencing was used to screen for activating mutations of Gsalpha genes in children with premature thelarche and in pathologic specimens from juvenile and adult granulosa cell tumors. Because these disorders involve over-activity of the FSH-signaling pathway, we also screened for activating mutations of the FSH receptor. No mutations were detected in either the Gsalpha or the FSHR fragment studied. Previously reported polymorphisms (Ser680Asn and Ala307Thr) of the FSHR were detected in 25/27 tumor samples and 9/9 premature thelarche samples. We conclude that activating mutations in previously identified mutation 'hot-spots' in the Gsalpha and FSH receptor genes are probably not a major cause of premature thelarche or granulosa cell tumors. In contrast, polymorphisms of the FSH receptor are common.

Age Determination by Skeleton↗