Publications by authors named "José Elías García"

5 Publications

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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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http://dx.doi.org/10.1210/clinem/dgaa065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108682PMC
May 2020

[Initial evaluation of febrile neutropenic patients: risk quantification].

Enferm Infecc Microbiol Clin 2005 Dec;23 Suppl 5:19-23

Servicio de Hematología, Hospital Clínico Universitario, Salamanca, España.

Infection in immunocompromised hosts represents a serious clinical situation due the high morbidity and mortality it produces and is one of the most frequent complications in patients with cancer. In patients treated with chemotherapy the risk of infection mainly depends on the duration and intensity of neutropenia. It is essential to evaluate which pathogens are involved so that the most appropriate treatment can be selected a priori, as well as to determine the patient's general clinical status so that more or less aggressive treatment can be provided from the beginning, bearing in mind that "low risk" patients can be managed in the home. These questions can be determined by evaluating the patient's clinical history, physical examination, laboratory investigations, and radiological tests. Prompt initiation of broad-spectrum antibiotic therapy adapted to the the patient's risk is crucial.
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http://dx.doi.org/10.1157/13091242DOI Listing
December 2005

Aging of oocyte, ovary, and human reproduction.

Ann N Y Acad Sci 2004 Dec;1034:117-31

NIA/NIH IRP, Laboratory of Genetics, Suite 3000, Triad Technology Center, 333 Cassell Drive, Baltimore MD 21224, USA.

We review age-related changes in the ovary and their effect on female fertility, with particular emphasis on follicle formation, follicle dynamics, and oocyte quality. The evidence indicates that the developmental processes leading to follicle formation set the rules determining follicle quiescence and growth. This regulatory system is maintained until menopause and is directly affected in at least some models of premature ovarian failure (POF), most strikingly in the Foxl2 mouse knockout, a model of human POF with monogenic etiology (blepharophimosis/ptosis/epicanthus inversus syndrome). Several lines of evidence indicate that if the ovarian germ cell lineage maintains regenerative potential, as recently suggested in the mouse, a role in follicle dynamics for germ stem cells, if any, is likely indirect or secondary. In addition, age-related variations in oocyte quality in animal models suggest that reproductive competence is acquired progressively and might depend on parallel growth and differentiation of follicle cells and stroma. Genomewide analyses of the mouse oocyte transcriptome have begun to be used to systematically investigate the mechanisms of reproductive competence that are altered with aging. Investigative and therapeutic strategies can benefit from considering the role of continuous interactions between follicle cells and oocytes from the beginning of histogenesis to full maturation.
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http://dx.doi.org/10.1196/annals.1335.015DOI Listing
December 2004

Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development.

Hum Mol Genet 2004 Jun 31;13(11):1171-81. Epub 2004 Mar 31.

Laboratory of Genetics, National Institute on Aging, Baltimore, MD 21224, USA.

FOXL2 mutations cause gonadal dysgenesis or premature ovarian failure (POF) in women, as well as eyelid/forehead dysmorphology in both sexes (the 'blepharophimosis-ptosis-epicanthus inversus syndrome', BPES). Here we report that mice lacking Foxl2 recapitulate relevant features of human BPES: males and females are small and show distinctive craniofacial morphology with upper eyelids absent. Furthermore, in mice as in humans, sterility is confined to females. Features of Foxl2 null animals point toward a new mechanism of POF, with all major somatic cell lineages failing to develop around growing oocytes from the time of primordial follicle formation. Foxl2 disruption thus provides a model for histogenesis and reproductive competence of the ovary.
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http://dx.doi.org/10.1093/hmg/ddh124DOI Listing
June 2004