The etiological heterogeneity of idiopathic diabetes has been recognized for 25 years, and subdivision into type 1 and type 2 diabetes is fundamental to the way we think about the disease. Review of the literature suggests that the concept of type 1 diabetes as an immunemediated disease emerged rapidly over the period from 1974 to 1976 and showed many of the features of a classic paradigm shift. A few key observations triggered recognition and acceptance of the new paradigm, but the necessary context was provided by scientific developments in areas mainly unrelated to diabetes. The disease paradigm established by 1976 is still widely accepted, and its essential features have been modified only in detail by the revolution in molecular biology that has occurred over the intervening period. Notwithstanding, some of the underlying assumptions remain imprecise, unchallenged, or unconfirmed. Appreciation of the historical origin and subsequent evolution of these fundamental concepts could stimulate critical analysis and help prepare the way for a new paradigm. (+info)
Adrenomedullin from a pheochromocytoma to the eye: implications of the adrenomedullin research for endocrinology in the 21st century.
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In the last several decades, the concept of "endocrinology" has been greatly changed. One major change was due to the discovery of peptide hormones secreted by the organs that were not "classical" endocrine organs. For example, corticotropin-releasing hormone and many neuropeptides are secreted by the neurons, atrial natriuretic peptide by the heart, endothelin-1 by the vascular endothelial cells, and leptin by the adipose tissues. Now, the brain, heart, vascular tissue and adipose tissue can be considered to be endocrine organs. Cardiovascular diseases and obesity are therefore important targets of the endocrine research. Adrenomedullin is a potent vasodilator peptide consisting of 52 amino acids. It was originally discovered from a human pheochromocytoma, and belongs to the calcitonin gene-related peptide (CGRP) family. Adrenomedullin is produced and secreted by various types of cells, for example, vascular endothelial and smooth muscle cells, cardiomyocytes, fibroblasts, macrophages, neurons, glial cells, and retinal pigment epithelial cells. Such ubiquitous expression has not been observed in other neuropeptides, including neuropeptide Y and CGRP. Expression of adrenomedullin is induced by hypoxia and proinflammatory cytokines. In addition to vasodilator actions, this peptide has central inhibitory actions on water drinking and salt appetite, effects on the secretion of some hormones and cytokines, inotropic actions and effects on cell growth and apoptosis. Adrenomedullin is produced by various non-endocrine tumors, as well as endocrine tumors, and acts as a growth stimulatory factor for the tumor cells. Adrenomedullin seems to be involved in the pathophysiology of many diseases, including ischemic heart diseases, inflammatory diseases, tumors, and even eye diseases. The adrenomedullin research implies that "the neuroendocrine system" exists in much broader types of cells than previously thought, and that the endocrine research is able to contribute to the understanding of the pathophysiology of many diseases. (+info)
Evolutionary biology of plant defenses against herbivory and their predictive implications for endocrine disruptor susceptibility in vertebrates.
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Hormone disruption is a major, underappreciated component of the plant chemical arsenal, and the historical coevolution between hormone-disrupting plants and herbivores will have both increased the susceptibility of carnivores and diversified the sensitivities of herbivores to man-made endocrine disruptors. Here I review diverse evidence of the influence of plant secondary compounds on vertebrate reproduction, including human reproduction. Three of the testable hypotheses about the evolutionary responses of vertebrate herbivores to hormone-disrupting challenges from their diet are developed. Specifically, the hypotheses are that a) vertebrate herbivores will express steroid hormone receptors in the buccal cavity and/or the vomeronasal organ; b) absolute sex steroid concentrations will be lower in carnivores than in herbivores; and c) herbivore steroid receptors should be more diverse in their binding affinities than carnivore lineages. The argument developed in this review, if empirically validated by support for the specific hypotheses, suggests that a) carnivores will be more susceptible than herbivores to endocrine-disrupting compounds of anthropogenic origin entering their bodies, and b) diverse herbivore lineages will be variably susceptible to any given natural or synthetic contaminant. As screening methods for hormone-disrupting potential are compared and adopted, comparative endocrine physiology research is urgently needed to develop models that predict the broad applicability of those screening results in diverse vertebrate species. (+info)
Disposition of sperm donors with resultant abnormal pregnancies.
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We wished to determine how clinicians manage sperm donors whose offspring have chromosomal or structural abnormalities. A directed, multiple-choice survey was given to reproductive endocrinologists and obstetrical geneticists to assess management of sperm donors whose offspring have chromosomal or structural abnormalities. The questionnaire was completed by 66 reproductive endocrinologists and obstetrical geneticists. Abnormalities and the most common inheritance modes included: Trisomy 21 (aneuploidy, maternal origin), Turner syndrome (aneuploidy, paternal origin), cleft lip/palate (multifactorial), VATER sequence (vertebral defects, imperforate anus, tracheo-esophageal fistula, radial and renal dysplasia, sporadic inheritance), and Hurler syndrome (autosomal recessive). Response choices were: (i) remove donor from programme, (ii) inform potential recipients of prior pregnancy outcomes and continue to use donor, or (iii) further study donor to assess karyotype/mutations. Inheritance mode appeared to influence decisions to remove donors from sperm banks; however, no clear consensus was noted. Guidelines exist for screening potential gamete donors, but not for managing donors whose offspring has a chromosomal or structural abnormality. Guidelines must be developed to manage sperm donors with untoward pregnancy outcomes. (+info)
Conditional transgenic technologies.
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Transgenic technology has been revolutionised by the development of techniques that allow temporo-spatial control of gene deletion or expression in transgenic animals. The ability to switch gene expression 'on' or 'off' in restricted tissues at specific times allows unprecedented flexibility for exploring gene function in both health and disease. As use of these techniques grows in all areas of biomedical research, an understanding of this topic is essential. In this review we examine the theory, application and limitations of these strategies, with particular reference to endocrine research. (+info)
Immunological testing and treatment in reproduction: frequency assessment of practice patterns at assisted reproduction clinics in the USA and Australia.
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BACKGROUND: The roles that alloimmunity and autoimmunity may play in reproductive failure, including recurrent pregnancy loss and failed IVF, have not been clearly established. To help define practice patterns, we investigated what tests clinicians in the USA and Australia were offering, to which patients (diagnostic groups) the tests were recommended, and in what situations immunological/anticoagulation treatment was advised. METHODS: A five section survey was completed by senior physicians attending the annual national fertility society meetings in the USA and Australia. Results were tabulated and analysed. RESULTS: Antiphospholipid antibody testing was offered to patients with recurrent pregnancy loss by almost all physicians surveyed. Patients with previous failure of IVF were tested much less often. Other immune tests (embryotoxic assay, natural killer cells and leukocyte antibodies) were ordered by none of the Australian participants and approximately 25% of the American participants. The use of immunotherapy and anticoagulation therapy for patients who tested positive for various immunological tests was also evaluated for frequency of use and reported secondary complications. CONCLUSIONS: Large, well-structured studies examining the benefits of immunological evaluation and treatment are necessary before definite recommendations can be made. (+info)
A psycho-endocrinological overview of transsexualism.
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The technical possibility of surgical sex change has opened up a debate concerning the legitimacy and utility of carrying out such an intervention at the request of the transsexual. Diagnostic, psychological, medical and ethical arguments have been brought forth, both for and against. Nonetheless, anatomical transformation by surgical means has currently become a practice as the frequency of serious gender identity disorders is constantly progressing. After a brief introduction, the present paper will consider typological, aetiological and epidemiological aspects of transsexualism. Treatment of the sex change applicant is then defined and discussed in terms of psychological, psychiatric, endocrinological and surgical aspects. Finally, the question of post-operation follow-up will be examined. (+info)
Problem-based learning within endocrine physiology lectures.
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Methods were needed to improve the interest of medical students in the 10-lecture Endocrine Physiology block at the end of the second semester of study. Other incentives for improvement included the possibility of attracting students into endocrine research electives and the pressure to improve teaching approaches that results from the high tuition they pay. The principal approach adopted was that of whole class problem-based learning sessions (PBLS) in which the lecture period begins with a brief overview of one to three simplified cases, followed by the usual didactic lecture. At the end of the lecture, each PBL case is read in detail, with several questions posed to the students. Their answers are then used to reinforce concepts from the lecture material. This method can also provide some continuity between lectures, either by using a case in several lectures to illustrate different points, or by posing a question at the beginning of class that illustrates a point from the prior lecture. The outcome of this approach has been very successful: student evaluations of the lecture block and their attendance have significantly improved. (+info)