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1.
BMJ Case Rep ; 17(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38442972

RESUMO

A newborn baby born at 34 weeks and 5 days gestation was admitted for prematurity, dysmorphic features and congenital heart defects. Antenatal scan at 21 weeks showed a large-for-gestational-age foetus with a large abdominal circumference and liver, ventricular septal defect, right prominent renal pelvis and echogenic bowel. Antenatal genetic tests for overgrowth syndromes were negative. The mother had early onset pre-eclampsia. After birth, an overgrowth syndrome was still suspected despite the baby having normal birth parameters. Raw data of the trio whole exome sequencing from the amniocentesis sample were manually inspected. Hemizygous exon 7 deletion in the GPC3 gene was found, and a postnatal diagnosis of Simpson-Golabi-Behmel syndrome, a rare overgrowth syndrome, was made. This case report discusses the significance of antenatal findings, an atypical presentation of a rare syndrome and the obstacles of diagnostic genetic testing.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X , Gigantismo , Cardiopatias Congênitas , Deficiência Intelectual , Feminino , Humanos , Recém-Nascido , Gravidez , Arritmias Cardíacas , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Gigantismo/diagnóstico , Gigantismo/genética , Glipicanas/genética , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética
2.
Front Endocrinol (Lausanne) ; 15: 1345363, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481440

RESUMO

X-linked acrogigantism (X-LAG) is a rare form of pituitary gigantism that is associated with growth hormone (GH) and prolactin-secreting pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) that develop in infancy. It is caused by a duplication on chromosome Xq26.3 that leads to the misexpression of the gene GPR101, a constitutively active stimulator of pituitary GH and prolactin secretion. GPR101 normally exists within its own topologically associating domain (TAD) and is insulated from surrounding regulatory elements. X-LAG is a TADopathy in which the duplication disrupts a conserved TAD border, leading to a neo-TAD in which ectopic enhancers drive GPR101 over-expression, thus causing gigantism. Here we trace the full diagnostic and therapeutic pathway of a female patient with X-LAG from 4C-seq studies demonstrating the neo-TAD through medical and surgical interventions and detailed tumor histopathology. The complex nature of treating young children with X-LAG is illustrated, including the achievement of hormonal control using a combination of neurosurgery and adult doses of first-generation somatostatin analogs.


Assuntos
Acromegalia , Doenças Genéticas Ligadas ao Cromossomo X , Gigantismo , Hormônio do Crescimento Humano , Neoplasias Hipofisárias , Adulto , Humanos , Criança , Feminino , Pré-Escolar , Gigantismo/genética , Gigantismo/terapia , Gigantismo/metabolismo , Acromegalia/patologia , Hormônio do Crescimento/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia
3.
Int J Mol Sci ; 25(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38396763

RESUMO

Epidemiological evidence emphasizes that excess fat mass is associated with an increased risk of severe COVID-19 disease. Nevertheless, the intricate interplay between SARS-CoV-2 and adipocytes remains poorly understood. It is crucial to decipher the progression of COVID-19 both in the acute phase and on long-term outcomes. In this study, an in vitro model using the human SGBS cell line (Simpson-Golabi-Behmel syndrome) was developed to investigate the infectivity of SARS-CoV-2 in adipocytes, and the effects of virus exposure on adipocyte function. Our results show that SGBS adipocytes expressing ACE2 are susceptible to SARS-CoV-2 infection, as evidenced by the release of the viral genome into the medium, detection of the nucleocapsid in cell lysates, and positive immunostaining for the spike protein. Infected adipocytes show remarkable changes compared to uninfected controls: increased surface area of lipid droplets, upregulated expression of genes of inflammation (Haptoglobin, MCP-1, IL-6, PAI-1), increased oxidative stress (MnSOD), and a concomitant reduction of transcripts related to adipocyte function (leptin, fatty acid synthase, perilipin). Moreover, exogenous expression of spike protein in SGBS adipocytes also led to an increase in lipid droplet size. In conclusion using the human SGBS cell line, we detected SARS-CoV-2 infectivity in adipocytes, revealing substantial morphological and functional changes in infected cells.


Assuntos
Arritmias Cardíacas , COVID-19 , Doenças Genéticas Ligadas ao Cromossomo X , Gigantismo , Cardiopatias Congênitas , Deficiência Intelectual , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Cultivadas , COVID-19/metabolismo , SARS-CoV-2 , Adipócitos/metabolismo , Fenótipo , Expressão Gênica
4.
Eur J Endocrinol ; 190(3): 193-200, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38391173

RESUMO

OBJECTIVES: Increased height in patients with acromegaly could be a manifestation of growth hormone (GH) excess before epiphysis closure. The aim of this study was to evaluate the relationship between the height of adult patients with GH excess related to mid-parental height (MPH) and population mean and to find whether taller patients with acromegaly come from tall families. METHODS: This is a single-centre, observational study involving 135 consecutive patients with acromegaly diagnosed as adults and no family history of GH excess. We established three categories for height for patients with acromegaly: normal stature, tall stature (TS, height above the 97th percentile (1.88 standard deviations (SD)) to <3 SD for gender- and country-specific data or as a height which was greater than 1.5 SD but less than 2 SD above the MPH) and gigantism (height which was greater than 3 SD) above the gender- and country-specific mean or greater than 2 SD above MPH). RESULTS: Thirteen percent (17/135) of patients (53% females) met the criteria for gigantism, 10% (14/135) fulfilled the criteria for TS (57% females). Parents and adult siblings were not taller than the population mean. CONCLUSION: In a group of 135 consecutive adult patients with acromegaly, 23% had increased height based on country-specific and MPH data: 13% presented with gigantism while 10% had TS. The frequency of gigantism and TS in patients diagnosed with GH excess as adults is not higher in males than in females. Patients with acromegaly come from normal-stature families.


Assuntos
Acromegalia , Gigantismo , Adulto , Feminino , Masculino , Humanos , Acromegalia/complicações , Acromegalia/epidemiologia , Gigantismo/etiologia , Osteogênese , Pais
6.
Sci Rep ; 13(1): 22124, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212342

RESUMO

Tyrannosaurid dinosaurs dominated as predators in the Late Cretaceous of Laurasia, culminating in the evolution of the giant Tyrannosaurus rex, both the last and largest tyrannosaurid. Where and when Tyrannosaurini (T. rex and kin) originated remains unclear. Competing hypotheses place tyrannosaurin origins in Asia, or western North America (Laramidia). We report a new tyrannosaurin, Tyrannosaurus mcraeensis, from the Campanian-Maastrichtian Hall Lake Formation of New Mexico, based on a fossil previously referred to T. rex. T. mcraeensis predates T. rex by ~ 6-7 million years, yet rivaled it in size. Phylogenetic analysis recovers T. mcraeensis as sister to T. rex and suggests Tyrannosaurini originated in southern Laramidia. Evolution of giant tyrannosaurs in southern North America, alongside giant ceratopsians, hadrosaurs, and titanosaurs suggests large-bodied dinosaurs evolved at low latitudes in North America.


Assuntos
Dinossauros , Gigantismo , Animais , Filogenia , Fósseis , América do Norte , New Mexico , Dinossauros/anatomia & histologia , Evolução Biológica
7.
Clin Neuropathol ; 43(1): 10-22, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38085092

RESUMO

Two of the rarest radiation-induced adverse effects are focal neuronal gigantism (FNG) and SMART syndrome (stroke-like migraine attacks after radiation therapy). Both conditions develop years, and sometimes decades, after receipt of therapeutic radiation to the brain. To date, there are only 3 previously reported cases of FNG, all of which describe cortical thickening, enlarged "hypertrophic" neurons, and neuronal cytological changes. No detailed studies exist of histological features of SMART or the comparison between FNG and SMART. In this study, we contrast histological and neuroimaging features of 3 FNG vs. 4 SMART cases, the latter diagnosed by a neuroradiologist, neurooncologist, and/or neurosurgeon. We confirm the cortical thickening, dyslamination, neuronal cytomegaly, and gliosis in FNG vs. cortical architectural preservation and normal neuronal cytology in SMART, although both showed gliosis, scattered neurons with cytoplasmic accumulation of tau and neurofibrillary protein and variable co-existence of other radiation-induced lesions. Both conditions lacked significant inflammation or consistent small vessel hyalinization throughout the entire resection specimen. The absence of pathognomonic histologic alterations in SMART cases suggests underlying vascular dysregulation. Despite differing histology, some overlap may exist in neuroimaging features. Molecular assessment conducted in 2 cases of FNG was negative for significant alterations including in the MAPK pathway.


Assuntos
Gigantismo , Humanos , Gigantismo/patologia , Gliose/patologia , Encéfalo/patologia , Neuroimagem , Neurônios
8.
J Mol Graph Model ; 127: 108676, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38006624

RESUMO

GPR101 is a G protein-coupled receptor (GPCR) implicated in a rare form of genetic gigantism known as X-linked acrogigantism, or X-LAG. In particular, X-LAG patients harbor microduplications in the long arm of the X-chromosome that invariably include the GPR101 gene. Duplications of the GPR101 gene lead to the formation of a new chromatin domain that causes over-expression of the receptor in the pituitary tumors of the patients. Notably, GPR101 is a constitutively active receptor, which stimulates cells to produce the second messenger cyclic AMP (cAMP) in the absence of ligands. Moreover, GPR101 was recently reported to constitutively activate not only the cAMP pathway via Gs, but also other G protein subunits (Gq/11 and G12/13). Hence, chemicals that block the constitutive activity of GPR101, known as inverse agonists, have the potential to be useful for the development of pharmacological tools for the treatment of X-LAG. In this study, we provide structural insights into the putative structure of GPR101 based on in-house built homology models, as well as third party models based on the machine learning methods AlphaFold and AlphaFold-Multistate. Moreover, we report a molecular dynamics study, meant to further probe the constitutive activity of GPR101. Finally, we provide a structural comparison with the closest GPCRs, which suggests that GPR101 does not share their natural ligands. While this manuscript was under review, cryo-electron microscopy structures of GPR101 were reported. These structures are expected to enable computer-aided ligand discovery efforts targeting GPR101.


Assuntos
Acromegalia , Gigantismo , Humanos , Gigantismo/genética , Gigantismo/patologia , Microscopia Crioeletrônica , Agonismo Inverso de Drogas , Acromegalia/genética , Acromegalia/patologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/química
9.
Biol Lett ; 19(11): 20230331, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37935371

RESUMO

The order Lamniformes contains charismatic species such as the white shark Carcharodon carcharias and extinct megatooth shark Otodus megalodon, and is of particular interest given their influence on marine ecosystems, and because some members exhibit regional endothermy. However, there remains significant debate surrounding the prevalence and evolutionary origin of regional endothermy in the order, and therefore the development of phenomena such as gigantism and filter-feeding in sharks generally. Here we show a basal lamniform shark, the smalltooth sand tiger shark Odontaspis ferox, has centralized skeletal red muscle and a thick compact-walled ventricle; anatomical features generally consistent with regionally endothermy. This result, together with the recent discovery of probable red muscle endothermy in filter feeding basking sharks Cetorhinus maximus, suggests that this thermophysiology is more prevalent in the Lamniformes than previously thought, which in turn has implications for understanding the evolution of regional endothermy, gigantism, and extinction risk of warm-bodied shark species both past and present.


Assuntos
Gigantismo , Tubarões , Animais , Tubarões/fisiologia , Ecossistema , Prevalência , Músculo Esquelético
10.
Ann Bot ; 132(7): 1233-1248, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-37818893

RESUMO

BACKGROUND AND AIMS: Gigantism is a key component of the domestication syndrome, a suite of traits that differentiates crops from their wild relatives. Allometric gigantism is strongly marked in horticultural crops, causing disproportionate increases in the size of edible parts such as stems, leaves or fruits. Tomato (Solanum lycopersicum) has attracted attention as a model for fruit gigantism, and many genes have been described controlling this trait. However, the genetic basis of a corresponding increase in size of vegetative organs contributing to isometric gigantism has remained relatively unexplored. METHODS: Here, we identified a 0.4-Mb region on chromosome 7 in introgression lines (ILs) from the wild species Solanum pennellii in two different tomato genetic backgrounds (cv. 'M82' and cv. 'Micro-Tom') that controls vegetative and reproductive organ size in tomato. The locus, named ORGAN SIZE (ORG), was fine-mapped using genotype-by-sequencing. A survey of the literature revealed that ORG overlaps with previously mapped quantitative trait loci controlling tomato fruit weight during domestication. KEY RESULTS: Alleles from the wild species led to lower cell number in different organs, which was partially compensated by greater cell expansion in leaves, but not in fruits. The result was a proportional reduction in leaf, flower and fruit size in the ILs harbouring the alleles from the wild species. CONCLUSIONS: Our findings suggest that selection for large fruit during domestication also tends to select for increases in leaf size by influencing cell division. Since leaf size is relevant for both source-sink balance and crop adaptation to different environments, the discovery of ORG could allow fine-tuning of these parameters.


Assuntos
Gigantismo , Solanum lycopersicum , Solanum , Solanum lycopersicum/genética , Tamanho do Órgão/genética , Gigantismo/genética , Locos de Características Quantitativas/genética , Solanum/genética , Frutas/genética
11.
Proc Natl Acad Sci U S A ; 120(27): e2218153120, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37364100

RESUMO

The evolution of the extinct megatooth shark, Otodus megalodon, and its close phylogenetic relatives remains enigmatic. A central question persists regarding the thermophysiological origins of these large predatory sharks through geologic time, including whether O. megalodon was ectothermic or endothermic (including regional endothermy), and whether its thermophysiology could help to explain the iconic shark's gigantism and eventual demise during the Pliocene. To address these uncertainties, we present unique geochemical evidence for thermoregulation in O. megalodon from both clumped isotope paleothermometry and phosphate oxygen isotopes. Our results show that O. megalodon had an overall warmer body temperature compared with its ambient environment and other coexisting shark species, providing quantitative and experimental support for recent biophysical modeling studies that suggest endothermy was one of the key drivers for gigantism in O. megalodon and other lamniform sharks. The gigantic body size with high metabolic costs of having high body temperatures may have contributed to the vulnerability of Otodus species to extinction when compared to other sympatric sharks that survived the Pliocene epoch.


Assuntos
Gigantismo , Tubarões , Animais , Tubarões/fisiologia , Filogenia , Regulação da Temperatura Corporal/fisiologia , Tamanho Corporal
12.
Pituitary ; 26(4): 333-339, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37270760

RESUMO

PURPOSE: We present a historical overview on neuropathic ulcers in patients with acromegalic gigantism. MATERIALS AND METHODS: The case histories of 6 famous patients with acromegalic gigantism and living in the twentieth century were analyzed. The combined final height and maximum weight of these giants were: 272 cm. & 215.9 kg., 218.4 cm. & 125 kg., 242 cm. & 165 kg., 220.5 cm. & 135 kg., 235 cm. & 136 kg. and 224.8 cm. & 174 kg. CONCLUSIONS: Neuropathic foot ulcers leading to hospital admissions and surgical and medical interventions were reported in 6 patients with acromegalic gigantism. These ulcers significantly impaired the daily activities of these individuals. Neuropathies of the sural nerve in patients with acromegalic gigantism can lead to hypoesthesia and hypoalgesia of the lower legs and feet. Potential contributing factors for the development of neuropathic ulcers of the feet in patients with acromegalic gigantism and neuropathy might be leg and foot deformities, muscle weakness and poor quality footwear. Diabetes mellitus, or impaired glucose intolerance does not necessarily seem to play a role.


Assuntos
Acromegalia , Pé Diabético , Gigantismo , Humanos , Úlcera ,
13.
Hum Mol Genet ; 32(14): 2318-2325, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37070740

RESUMO

Pituitary gigantism is a rare endocrinopathy characterized by tall stature due to growth hormone (GH) hypersecretion. This condition is generally linked to a genetic predisposition to tumors that produce GH or GH-releasing hormone (GHRH). Here, we report a Japanese woman who exhibited prominent body growth from infancy to reach an adult height of 197.4 cm (+7.4 standard deviation). Her blood GH levels were markedly elevated. She carried no pathogenic variants in known growth-controlling genes but had a hitherto unreported 752 kb heterozygous deletion at 20q11.23. The microdeletion was located 8.9 kb upstream of GHRH and encompassed exons 2-9 of a ubiquitously expressed gene TTI1 together with 12 other genes, pseudogenes and non-coding RNAs. Transcript analyses of the patient's leukocytes showed that the microdeletion produced chimeric mRNAs consisting of exon 1 of TTI1 and all coding exons of GHRH. In silico analysis detected promoter-associated genomic features around TTI1 exon 1. Genome-edited mice carrying the same microdeletion recapitulated accelerated body growth from a few weeks after birth. The mutant mice developed pituitary hyperplasia and exhibited ectopic Ghrh expression in all tissues examined. Thus, the extreme phenotype of pituitary gigantism in the patient likely reflects GHRH overexpression driven by an acquired promoter. The results of this study indicate that germline submicroscopic deletions have the potential to cause conspicuous developmental abnormalities due to gene overexpression. Furthermore, this study provides evidence that constitutive expression of a hormone-encoding gene can result in congenital disease.


Assuntos
Gigantismo , Feminino , Humanos , Camundongos , Animais , Gigantismo/genética , Hormônio do Crescimento/genética , Éxons/genética , Regiões Promotoras Genéticas , Genoma
14.
Evolution ; 77(6): 1303-1314, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36881990

RESUMO

Insular gigantism is an evolutionary phenomenon whereby small animals become bigger on islands compared to their mainland relatives. The abundance of insular giant taxa in the fossil record suggests the presence of a universal "giant niche" present on islands, with resource limitation as a potential driver for this process. However, insular habitats are ecologically diverse, suggesting that island taxa adopt different survival strategies, including adaptations for foraging behaviors. Here, we used finite element analysis to evaluate insular feeding niche adaptations in some of the most extreme examples of insular gigantism: Mediterranean giant dormice. We calculated stress, strain, and mechanical advantage during incisor and molar biting for 3 extinct insular giant species (Leithia melitensis, Hypnomys morpheus, and H. onicensis), an extant giant (Eliomys quercinus ophiusae), and their extant non-giant mainland relative, the generalist-feeder Eliomys quercinus. Our results show that dietary adaptations vary between giant taxa on different islands, and can occur relatively rapidly. Furthermore, the functional mandibular morphology in some insular taxa indicate adaptations moving away from a generalist feeding strategy toward greater trophic specialization. We show that the "insular giant niche" varies between islands and across time periods, arguing against a universal ecological driver for insular gigantism in small mammals.


Assuntos
Gigantismo , Animais , Tamanho Corporal , Fenômenos Biomecânicos , Evolução Biológica , Ecossistema , Mamíferos
15.
J Pediatr Endocrinol Metab ; 36(2): 199-202, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36597712

RESUMO

OBJECTIVES: Pituitary gigantism is a rare condition and it often has an identifiable genetic cause. In this article we report a case of a young girl with pituitary gigantism and two genetic changes. CASE PRESENTATION: A 15-year-old girl with primary amenorrhea was diagnosed with a growth hormone (GH) and prolactin (PRL)-producing tumor, needing surgery and medical treatment with octreotide in order to achieve disease control. The co-occurrence of an AIP mutation and a MEN1 variant of uncertain significance was demonstrated in this patient. The germline mutation involving AIP was inherited from her father who at the age of 55 was unaffected and the MEN1 variant was a de novo duplication of the region 11q13.1. The latter variant, not previously reported, is unlikely to be pathogenic. Nonetheless, screening for other components of multiple endocrine neoplasia type 1 (MEN1) was performed and proved negative. CONCLUSIONS: The rare co-occurrence of an AIP mutation and a MEN 1 variant of uncertain significance was demonstrated in this patient.


Assuntos
Gigantismo , Hormônio do Crescimento Humano , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias Hipofisárias , Adolescente , Feminino , Humanos , Mutação em Linhagem Germinativa , Gigantismo/etiologia , Hormônio do Crescimento/genética , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/genética , Mutação , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/complicações , Prolactina
16.
Hormones (Athens) ; 22(1): 25-32, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36223065

RESUMO

PURPOSE: Acromegaly is characterized by bone changes due to excessive growth hormone (GH) secretion. Hyperostosis frontalis interna (HFI) is described as an overgrowth in the inner plate of the frontal bone. An increased incidence of HFI has been reported in patients with acromegaly. Since the etiology of HFI is poorly understood, we have analyzed whether there is a relationship between the hormonal and metabolic status of patients with acromegaly (with or without hyperprolactinemia) and the pathogenesis of HFI. METHODS: Forty-five patients with acromegaly and two control groups consisting of 25 patients with prolactinoma (group 1) and 47 healthy subjects (group 2) were included in this retrospective study. Baseline hormonal data and cranial imaging were obtained from medical records and analyzed. RESULTS: Mean frontal bone thickness was 6.75 mm in acromegaly, 4.85 mm in group 1, and 5.1 mm in group 2 of controls (p < 0.001). The frequency of HFI was higher in acromegalic patients than in the controls (22%, 0%, and 2.2%, respectively). There was no difference between the HFI positive and negative acromegalic patients in basal GH, IGF-1, and PRL levels, IGF-1 index, diagnosis lag time, and insulin resistance. There was no difference between groups regarding parietal and occipital bone thickness. CONCLUSION: Although the frequency of HFI is 22% in patients with acromegaly, neither excess GH nor hyperprolactinemia plays a role in its etiopathogenesis. Various genetic or epigenetic factors may contribute to its etiology.


Assuntos
Acromegalia , Gigantismo , Hiperostose Frontal Interna , Hiperprolactinemia , Humanos , Hiperostose Frontal Interna/epidemiologia , Hiperostose Frontal Interna/etiologia , Hiperostose Frontal Interna/patologia , Acromegalia/complicações , Acromegalia/patologia , Fator de Crescimento Insulin-Like I , Hiperprolactinemia/complicações , Estudos Retrospectivos , Osso Frontal/patologia
17.
Pituitary ; 26(1): 51-56, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36335516

RESUMO

PURPOSE: We present the results of transsphenoidal microsurgical treatment in 14 patients with gigantism. The influence on the prognosis of factors such as the tumor size and preoperative levels of GH and IGF-1 is also quantified. MATERIALS AND METHODS: The patients, operated between 1982 and 2004, were reviewed retrospectively in June 2022. All patients had complete endocrinological studies in the preoperative period and a postoperative control between 6 days and 3 weeks. Follow-up has been supported with annual check-ups between 3 and 31 years. We have compared the preoperative levels of GH and IGF-1 of these patients with the levels of a series of acromegalic patients operated on in the same Center. RESULTS: In this series there were 4 women and 10 men. The age ranged between 14 and 21 years. In 6 patients, postoperative hormone levels achieved the disease control criteria (42.8%). The CT/MRI studies revealed the existence of invasive tumors in 10 of the patients (71.4%). Postoperative CT/MRI showed no tumor tissue in 3 patients but in 7 patients there were tumor remains. The remaining 4 patients had abnormal images although not considered as tumor. A statistical comparison of preoperative serum GH and IGF-1 levels in patients with gigantism and patients with acromegaly showed a significant elevation in the former. CONCLUSION: Pituitary adenomas that cause gigantism are generally large and invasive, which makes them difficult to cure. High preoperative levels of GH and IGF-1 are also factors that decrease remission.


Assuntos
Acromegalia , Gigantismo , Hormônio do Crescimento Humano , Neoplasias Hipofisárias , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Gigantismo/cirurgia , Acromegalia/cirurgia , Acromegalia/etiologia , Fator de Crescimento Insulin-Like I , Prognóstico , Estudos Retrospectivos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Resultado do Tratamento
18.
Sci Rep ; 12(1): 19689, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36446809

RESUMO

Two of the most-studied ecogeographical rules describe patterns of body size variation within species. Bergmann's rule predicts that individuals have larger body sizes in colder climates (typically at higher latitudes), and the island rule predicts that island populations of small-bodied species average larger in size than their mainland counterparts (insular gigantism). These rules are rarely tested in conjunction or assessed across space and time simultaneously. We investigated these patterns in the Northern Treeshrew (Tupaia belangeri) using museum specimens collected across a wide spatial and temporal range. Contrary to Bergmann's rule, size increases with temperature in T. belangeri, a signal that is highly consistent across space and time. We also show that these rules are intertwined: Bergmann's rule is reversed on the mainland but holds on islands, and therefore the island rule is upheld at higher, but not lower, latitudes. Moreover, we demonstrate a rapid reversal of both rules over time. The mechanism behind these inversions remains unclear, though temperature and precipitation are significant predictors of body size. Ecogeographical rules rely on the assumption of a constant relationship between size and the factors driving its variation. Our results highlight the need to question this assumption and reevaluate these rules in the context of accelerating and uneven climate change.


Assuntos
Mudança Climática , Gigantismo , Humanos , Animais , Tamanho Corporal , Clima Frio , Tupaia
19.
J Med Case Rep ; 16(1): 399, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36316724

RESUMO

BACKGROUND: Pfieffer syndrome is among the syndromes seen in the recognized variant of the FGFR2 gene. There are several conditions related to this variant and a very closely related condition is Crouzon syndrome. This case is important to report because the neonate was a delayed referral from another region, without clear counseling and information on the gravity of situation. We describe additional features , not previously described in Pfieffer or Crouzon syndrome, supernumerary teeth and localized symmetrical gigantism of thumbs and great toes on both sides. That a genetic testing is essential to further manage and counsel to avoid lost opportunities for future births. Several cases are seen in this unit annually, and there is need for a more consolidated and comprehensive counseling and genetic testing. Once early diagnosis is done and the case is recognized to be untreatable, it was avert the need to refer. CASE PRESENTATION: A 2-week-old male African neonate referred from outside the region, presented with massive proptosis soon after delivery, with signs of pan-ophthalmitis and neonatal sepsis. The infant had additional multiple malformations and features initially diagnosed as Crouzon syndrome , but later confirmed after genetic testing to be Type II Pfieffer syndrome. A through clinical evaluation and genetic testing would prevent undue referral to a tertiary center, or if needed, the baby should have been referred much earlier. The uniqueness of this case is the presence of supernumerary teeth. CONCLUSION: A complicated, difficult to remedy case, referred to tertiary center, investigated, and sent back home with no significant intervention. Genetic test confirmed the typical findings of Pfieffer Type II. Presented for describing additional unique features of supernumerary teeth and localized gigantism and ethical challenges in management.


Assuntos
Disostose Craniofacial , Gigantismo , Dente Supranumerário , Humanos , Recém-Nascido , Masculino , Disostose Craniofacial/complicações , Disostose Craniofacial/diagnóstico , Disostose Craniofacial/genética , Erros de Diagnóstico , Testes Genéticos , Síndrome , Dente Supranumerário/etiologia , Dente Supranumerário/genética
20.
BMC Biol ; 20(1): 243, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307800

RESUMO

BACKGROUND: Transposable elements (TEs) have been likened to parasites in the genome that reproduce and move ceaselessly in the host, continuously enlarging the host genome. However, the Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of TE invasion by imposing small-RNA-mediated silencing. Here we compare the TE activity of two grasshopper species with different genome sizes in Acrididae (Locusta migratoria manilensis♀1C = 6.60 pg, Angaracris rhodopa♀1C = 16.36 pg) to ascertain the influence of piRNAs. RESULTS: We discovered that repetitive sequences accounted for 74.56% of the genome in A. rhodopa, more than 56.83% in L. migratoria, and the large-genome grasshopper contained a higher TEs proportions. The comparative analysis revealed that 41 TEs (copy number > 500) were shared in both species. The two species exhibited distinct "landscapes" of TE divergence. The TEs outbreaks in the small-genome grasshopper occurred at more ancient times, while the large-genome grasshopper maintains active transposition events in the recent past. Evolutionary history studies on TEs suggest that TEs may be subject to different dynamics and resistances in these two species. We found that TE transcript abundance was higher in the large-genome grasshopper and the TE-derived piRNAs abundance was lower than in the small-genome grasshopper. In addition, we found that the piRNA methylase HENMT, which is underexpressed in the large-genome grasshopper, impedes the piRNA silencing to a lower level. CONCLUSIONS: Our study revealed that the abundance of piRNAs is lower in the gigantic genome grasshopper than in the small genome grasshopper. In addition, the key gene HENMT in the piRNA biogenesis pathway (Ping-Pong cycle) in the gigantic genome grasshopper is underexpressed. We hypothesize that low-level piRNA silencing unbalances the original positive correlation between TEs and piRNAs, and triggers TEs to proliferate out of control, which may be one of the reasons for the gigantism of grasshopper genomes.


Assuntos
Gigantismo , Gafanhotos , Animais , Elementos de DNA Transponíveis , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Gafanhotos/genética , Gigantismo/genética , Interferência de RNA
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