Publications by authors named "Orlando Perez"

4 Publications

  • Page 1 of 1

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

J Clin Endocrinol Metab 2020 05;105(5)

Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, North Carolina.

Context: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed.

Objective: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures.

Methods: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients.

Results: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient.

Conclusions: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.
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May 2020

Body shape: Implications in the study of obesity and related traits.

Am J Hum Biol 2020 03 10;32(2):e23323. Epub 2019 Sep 10.

Instituto Patagónico de Ciencias Sociales y Humanas (IPCSH), Centro Nacional Patagónico (CENPAT - CONICET), Puerto Madryn, Argentina.

Objectives: The diagnosis and treatment of obesity are usually based on traditional anthropometric variables including weight, height, and several body perimeters. Here we present a three-dimensional (3D) image-based computational approach aimed to capture the distribution of abdominal adipose tissue as an aspect of shape rather than a relationship among classical anthropometric measures.

Methods: A morphometric approach based on landmarks and semilandmarks placed upon the 3D torso surface was performed in order to quantify abdominal adiposity shape variation and its relation to classical indices. Specifically, we analyzed sets of body cross-sectional circumferences, collectively defining each, along with anthropometric data taken on 112 volunteers. Principal Component Analysis (PCA) was performed on 250 circumferences located along the abdominal region of each volunteer. An analysis of covariance model was used to compare shape variables (PCs) against anthropometric data (weight, height, and waist and hip circumferences).

Results: The observed shape patterns were mainly related to nutritional status, followed by sexual dimorphism. PC1 (12.5%) and PC2 (7.5%) represented 20% of the total variation. In PCAs calculated independently by sex, linear regression analyses provide statistically significant associations between PC1 and the three classical indexes: body mass index, waist-to-height ratio, and waist-hip ratio.

Conclusion: Shape indicators predict well the behavior of classical markers, but also evaluate 3D and geometric features with more accuracy as related to the body shape under study. This approach also facilitates diagnosis and follow-up of therapies by using accessible 3D technology.
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March 2020

Genetic Variations in the TP53 Pathway in Native Americans Strongly Suggest Adaptation to the High Altitudes of the Andes.

PLoS One 2015 18;10(9):e0137823. Epub 2015 Sep 18.

Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil.

The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; and LIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara, Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Ñandeva, and Guarani Kaiowá populations, characterized as Native American or as having a high level (> 90%) of Native American ancestry. In addition, published data pertaining to 100 persons from five other Native American populations (Surui, Karitiana, Maya, Pima, and Piapoco) were analyzed. The populations were classified as living in high altitude (≥ 2,500 m) or in lowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2-T showed significant evidence that they were selected for in relation to harsh environmental variables related to high altitudes. Our results show for the first time that alleles of classical TP53 network genes have been evolutionary co-opted for the successful human colonization of the Andes.
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May 2016

Comparing analgesia and mu-opioid receptor internalization produced by intrathecal enkephalin: requirement for peptidase inhibition.

Neuropharmacology 2007 Oct 2;53(5):664-76. Epub 2007 Aug 2.

Center for Neurovisceral Sciences and Women's Health and CURE: Digestive Diseases Research Center, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA.

Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude mu-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is also precluded by peptidases, and whether it is mediated by MORs or delta-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu-enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol, whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at 1 nmol. Leu-enkephalin was 10 times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-enkephalin. Unlike Leu-enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia.
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October 2007