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1.
Skeletal Radiol ; 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38466413

RESUMEN

Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign but rare periosteal-originating chondrogenic tumor. It commonly arises from the hands and feet. It is slow-growing and often presents as a painless lump. On imaging, the mass is well-marginated and almost always remains contiguous with the cortical bone. Histologically, the lesion is composed of a disorganized admixture of fibrous tissue, bone, and cartilage with bizarre features. Treatment is surgical and local recurrence is common contiguous with bone. This case report demonstrates an uncommon acromial BPOP with the first reported recurrence not contiguous with the underlying cortex.

2.
J Neuroimmunol ; 390: 578329, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38554665

RESUMEN

We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.


Asunto(s)
Infección por Mycobacterium avium-intracellulare , Humanos , Masculino , Infección por Mycobacterium avium-intracellulare/diagnóstico , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/tratamiento farmacológico , Enfermedades de la Médula Espinal/microbiología , Adulto , Infecciones por VIH/complicaciones
4.
Int J Surg Pathol ; 32(1): 46-57, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37131332

RESUMEN

Background. Lipomas are common superficial soft tissue tumors of mature adipocytes. In contrast, well-differentiated/dedifferentiated liposarcoma typically presents in the retroperitoneum as large masses. We provide clinicopathologic and follow-up details of 9 retroperitoneal/intra-abdominal benign lipomatous tumors (BLT) and discuss the utility of ancillary fluorescence in situ hybridization (FISH) in distinguishing from their malignant counterparts. Design. Clinicopathologic details and histology of 9 intra-abdominal and retroperitoneal lipomas were studied along with ancillary CD10 immunohistochemistry (IHC) and FISH for MDM2 and CDK4 amplification. Results. There were 6 females and 3 males. Median age at diagnosis was 52 years (range 36-81 years). Seven were identified incidentally and 2 presented with primary complaints. On imaging, 7 were considered suspicious for liposarcoma. Grossly, the tumors ranged from 3.4 to 41.2 cm (median 16.5 cm). Histologically, all cases showed well-differentiated BLT, further classified as lipoma (n = 7; 1 with metaplastic ossification, 2 with prominent vessels, and 4 ordinary lipomas) and lipoma-like hibernoma (n = 2)-the latter 2 showed intramuscular lesions with interspersed brown fat. CD10 IHC showed strong staining in the 2 hibernomas, whereas the staining was weak in the remaining. MDM2 and CDK4 amplification were negative by FISH in all. Follow-up (median 18 months) did not show recurrence on clinical or imaging evaluation. Conclusion. Retroperitoneal/intra-abdominal BLT are extremely rare and are indistinguishable clinically and radiographically from liposarcoma. This necessitates molecular confirmation even when the histology is convincingly benign, for a confident diagnosis. Our cohort shows that conservative excision without removal of abutted organs is sufficient in most cases.


Asunto(s)
Lipoma , Liposarcoma , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Hibridación Fluorescente in Situ/métodos , Proteínas Proto-Oncogénicas c-mdm2/genética , Quinasa 4 Dependiente de la Ciclina/genética , Biomarcadores de Tumor , Liposarcoma/diagnóstico , Liposarcoma/genética , Lipoma/diagnóstico , Lipoma/genética , Lipoma/patología
5.
Int J Surg Pathol ; 31(7): 1294-1301, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37796752

RESUMEN

Islet-1 (ISL1) plays key roles in programming the epigenome and facilitating the recruitment of additional regulatory factors. Although it has been used as a marker for pancreatic neuroendocrine tumors (PanNETs), ISL1 reactivity in other tumor types are critically missing. ISL1 immunohistochemistry was performed on 147 neuroendocrine tumors (NET) originated in pancreas, gastrointestinal tract, lung, thyroid, parathyroid, pituitary, adrenal medulla, head/neck, genitourinary tract, and skin; and 110 non-neuroendocrine tumors originated in the pancreas, thymus, lung, thyroid, mesothelium, adrenal cortex, stomach, breast, head/neck, skin, and kidney. ISL1 nuclear staining was observed in normal thymic epithelium, pancreatic islets, adrenal medulla, and pituitary gland cells as well as frequently in tumors of these origins: pancreatic NET (78%), paraganglioma/pheochromocytoma (100%), thymoma (82%), and pituitary NET (50%). ISL1 was also variably expressed in certain non-pancreatic NET such as Merkel cell carcinoma (100%), medullary carcinoma of the thyroid (100%), head/neck NEC (80%), genitourinary NEC (71%), lung small cell carcinoma (46%), lung carcinoids (17%), lower intestinal tract NET (93%) but not in upper gastrointestinal tract NET nor parathyroid adenoma. For other non-NETs, focal ISL1 expression was less frequently detected in gastric adenocarcinoma (40%), mesothelioma (29%), adrenal cortical carcinoma (17%), and squamous carcinoma (24%), but not in others tested. ISL1 is not a pan-NE marker as it is consistently lacking in upper gastrointestinal NET and parathyroid adenoma. It is also differentially expressed in thymoma. ISL1 immunohistochemnistry could help to differentiate PanNET and lower intestinal NET from upper gastrointestinal NET and be used as a marker for thymoma.


Asunto(s)
Neoplasias Gastrointestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias de las Paratiroides , Neoplasias Cutáneas , Timoma , Neoplasias del Timo , Humanos , Biomarcadores de Tumor/metabolismo , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Neoplasias Gastrointestinales/patología , Neoplasias Pancreáticas/patología
6.
Hum Pathol ; 141: 78-89, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37277077

RESUMEN

Pediatric hepatic vascular tumors (HVTs) are rare neoplasms with features distinct from their cutaneous counterparts. Their behavior ranges from benign to malignant, with each subtype having therapeutic differences. Histopathologic descriptions of large cohorts are scarce in the literature. Thirty-three putative HVTs diagnosed from 1970 to 2021 were retrieved. All available clinical and pathologic materials were reviewed. Lesions were reclassified according to the World Health Organization (WHO) classification of pediatric tumors [1] as hepatic congenital hemangioma (HCH; n = 13), hepatic infantile hemangioma (HIH; n = 10), hepatic angiosarcoma (HA; n = 3), and hepatic epithelioid hemangioendothelioma (HEH; n = 1). Vascular malformations (n = 5) or vascular-dominant mesenchymal hamartoma (n = 1) were excluded. HCH frequently showed involutional changes, whereas HIH often had anastomosing channels and pseudopapillae formation. HA had solid areas with epithelioid and/or spindled endothelial morphology, significant atypia, increased mitoses, high proliferation index, and occasionally necrosis. On morphology analysis, a subset of HIH showed features worrisome for progression to HA including solid glomeruloid proliferation, increased mitoses, and epithelioid morphology. The widely metastatic and fatal HEH was observed in a 5-year-old male with multiple liver lesions. Immunohistochemically, HIHs and HA were Glucose transporter isoform 1 (GLUT-1) positive. One HIH patient died from postoperative complications, whereas 3 are alive without disease. Five HCH patients are alive and well. Two of three HA patients died of disease, and 1 is alive without recurrence. To our knowledge, this is the largest series of pediatric HVTs reviewing clinicopathologic features based on current Pediatric WHO nomenclature [1]. We highlight diagnostic challenges and propose inclusion of an intermediate category between HIH and HA which warrants closer follow-up.


Asunto(s)
Hemangioma , Hemangiosarcoma , Neoplasias Hepáticas , Neoplasias de Tejido Vascular , Neoplasias Vasculares , Masculino , Humanos , Niño , Preescolar , Neoplasias Vasculares/patología , Hemangioma/patología , Neoplasias Hepáticas/patología , Hemangiosarcoma/terapia , Hemangiosarcoma/patología
7.
Cureus ; 15(5): e39331, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37351248

RESUMEN

BACKGROUND:  Substance use continues to be on the rise in the United States and has been linked to new onset cardiovascular diseases (CVDs) and cerebrovascular disorders (CeVDs). We aimed to study the association between the types of substance use disorders (SUDs) with specific subtypes of CVDs and CeVDs among hospitalized patients using the National Inpatient Sample (NIS) Database. METHODS:  A retrospective study of the NIS database (2016-2017) using the ICD-10-CM codes was performed. The hospitalizations with a secondary diagnosis of SUDs were identified. Weighted univariate analysis using the Chi-square test and multivariate survey logistic regression analysis was performed to evaluate for the incidence, prevalence, and odds of association between vascular events and SUDs. RESULTS:  There were a total of 58,259,589 hospitalizations, out of which 21.42% had SUDs. SUDs were more common in the younger age group of 18-50, males, and the lower median household income group. We found a significant association of acute ischemic stroke (AIS) with amphetamine dependence (adjusted odds ratio, aOR 1.23, 95% confidence interval, CI 1.14-1.33), cocaine-related disorders (1.17, 1.12-1.23), and nicotine dependence (1.42, 1.40-1.43). There was a significant association between intracerebral hemorrhage with amphetamine dependence (2.58, 2.26-2.93), cocaine-related disorders (1.62, 1.46-1.79), and alcohol-related disorders (1.35, 1.01-1.82). The association of subarachnoid hemorrhage (SAH) was noted to be higher with amphetamine dependence (1.82, 1.48-2.24) and nicotine dependence (1.47, 1.39-1.55). The patients with nicotine dependence had greater odds of having a myocardial infarction (1.85, 1.83-1.87), those with cocaine-related disorders had higher odds of having angina pectoris (2.21, 1.86-2.62), and patients with alcohol-related disorders had higher odds of developing atrial fibrillation (1.14, 1.11-1.17) in comparison to non-SUDs. CONCLUSION:  Our study demonstrates the variability of CVD and CeVD in patients hospitalized for SUD. Findings from our study may help promote increased awareness and early management of these events. Further studies are needed to evaluate the specific effects of frequency and dose on the incidence and prevalence of CVD and CeVD in patients with SUD.

8.
J Surg Case Rep ; 2023(4): rjad226, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37128235

RESUMEN

Metastasis to the supraclavicular lymph nodes usually originate from primary tumours in the head and neck, breast or abdomen. Infradiaphragmatic tumours very rarely metastasise to these nodes. Transitional cell carcinomas (TCCs), also termed urothelial carcinomas, account for ⁓90% of all ureteral cancers; exceptionally few cases have reported such cancers spreading to the supraclavicular fossae. We present the case of a 65-year-old male who was being investigated for gallstones and was subsequently found to have metastatic bony lesions and widespread adenopathy on magnetic resonance cholangiopancreatography. Initially, the primary cancer was an area of contention between clinicians, as radiologists suggested it was of urological origin, but the bladder multidisciplinary team felt the scans did not fulfil this notion. Ultimately, histological analysis confirmed the diagnosis of metastatic TCC.

9.
PLoS One ; 18(5): e0268608, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37163486

RESUMEN

BACKGROUND: Healthcare simulators have been demonstrated to be a valuable resource for training several technical and nontechnical skills. A gap in the fidelity of tissues has been acknowledged as a barrier to application for current simulators; especially for interventional procedures. Inaccurate or unrealistic mechanical response of a simulated tissue to a given surgical tool motion may result in negative training transfer and/or prevents the "suspension of disbelief" necessary for a trainee to engage in the activity. Thus, where it is relevant to training outcomes, there should be an effort to create healthcare simulators with simulated tissue mechanical responses that match or represent those of biological tissues. Historically, this data is most often gathered from preserved (post mortem) tissue; however, there is a concern that the mechanical properties of preserved tissue, that lacks blood flow, may lack adequate accuracy to provide the necessary training efficacy of simulators. METHODS AND FINDINGS: This work explores the effect of the "state" of the tissue testing status on liver and peritoneal tissue by using a customized handheld grasper to measure the mechanical responses of representative porcine (Sus domesticus) tissues in n = 5 animals across five test conditions: in vivo, post mortem (in-situ), ex vivo (immediately removed from fresh porcine cadaver), post-refrigeration, and post-freeze-thaw cycle spanning up to 72 hours after death. No statistically significant difference was observed in the mechanical responses due to grasping between in vivo and post-freeze conditions for porcine liver and peritoneum tissue samples (p = 0.05 for derived stiffness at grasping force values F = 5N and 6.5N). Furthermore, variance between in vivo and post-freeze conditions within each animal, was comparable to the variance of the in vivo condition between animals. CONCLUSIONS: Results of this study further validate the use of preserved tissue in the design of medical simulators via observing tissue mechanical responses of post-freeze tissue comparable to in vivo tissue. Therefore, the use of thawed preserved tissue for the further study and emulation of mechanical perturbation of the liver and peritoneum can be considered. Further work in this area should investigate these trends further, particularly in regard to other tissues and the potential effects varying preservation methods may yield.


Asunto(s)
Abdomen , Fenómenos Mecánicos , Porcinos , Animales , Hígado
10.
J Surg Case Rep ; 2023(5): rjad281, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37251256

RESUMEN

Appendiceal collision tumours are extremely rare, with most reported cases describing tumours consisting of a mucinous component and a neuroendocrine component. Low-grade appendiceal mucinous neoplasms, in some cases, have a tendency to rupture and disseminate their mucin-producing cells throughout the abdominal cavity, leading to a clinical syndrome known as pseudomyxoma peritonei (PMP). We present the case of a 64-year-old male who initially presented with acute appendicitis and was subsequently found to have PMP and appendiceal malignancy. After several years of scans, surgical intervention and histological analysis, it became apparent that the appendiceal malignancy was comprised of distinct cell types. The patient underwent two rounds of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, which resulted in a 2-year disease-free period. Unfortunately, the PMP recurred, having morphological changes consistent with a more aggressive disease process.

11.
Am J Clin Pathol ; 160(1): 106-112, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37026754

RESUMEN

OBJECTIVES: Granular cell tumor (GCT) commonly presents in the subcutaneous tissue and head and neck region, and it is uncommon in the gastrointestinal tract. Experience with esophageal GCTs in the pediatric population is limited, with only 7 cases reported in the literature, 3 with eosinophilic esophagitis (EoE). METHODS: Case information from 11 pediatric patients with GCTs of the esophagus was retrieved. H&E and immunohistochemical slides were reviewed with clinical, endoscopic, and follow-up data from all patients. RESULTS: In total, 7 male and 4 female patients were included, with ages ranging from 3 to 14 years. Indications for esophagogastroduodenoscopy (EGD) included EoE (n = 3), follow-up for Crohn disease, and other nonspecific complaints. Endoscopically, all patients had a single submucosal, firm mass protruding into the lumen, with normal overlying mucosa. The nodules were removed endoscopically in multiple fragments in all cases. Histologically, the tumors showed sheets and trabeculae of cells containing bland nuclei, inconspicuous nucleoli, and abundant pink granular cytoplasm without atypical features. All tumors were immunoreactive for S100, CD68, and SOX10. Follow-up showed that all patients were disease-free (median, 2 years). CONCLUSIONS: We report the largest series of pediatric esophageal GCTs with coincidental association with EoE. These EGD findings are characteristic, and removal by biopsy is both diagnostic and therapeutic.


Asunto(s)
Neoplasias Esofágicas , Tumor de Células Granulares , Humanos , Masculino , Niño , Femenino , Inmunohistoquímica , Tumor de Células Granulares/complicaciones , Tumor de Células Granulares/patología , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/patología , Biopsia
12.
Int J Surg Pathol ; 31(8): 1632-1637, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36898668

RESUMEN

Different authors have recently described a subtype of lipoma characterized by variation of adipocyte size, single cell fat necrosis, and a subset with minimal to mild nuclear atypia, and termed these as anisometric cell/dysplastic lipoma (AC/DL). These lipomas follow a benign course and rarely recur. In 3 examples, AC/DL has occurred in patients with childhood retinoblastoma (RB). We report another such example where multiple AC/DL occurred in the neck and back of a 30-year-old male who had germline RB1 gene deletion and bilateral RB in infancy. On excision, all tumors histologically showed similar morphology of adipocyte anisometry, focal single cell necrosis with surrounding binucleated or multinucleated histiocytes, hyperchromatic and minimally atypical lipocyte nuclei, vacuolated Lockhern change, rare foci of fibromyxoid change, occasional mononuclear cell clusters around capillaries, and loss of RB1 immunostaining. Unequivocal atypical cells, lipoblasts, floret-nucleated or multinucleated giant cells were absent. Molecular analysis of tumor cells showed monoallelic RB1 gene loss without amplification of MDM2 and CDK4 genes. Short-term follow up did not show tumor recurrence. AC/DLs in RB survivors are characterized by multiplicity, unifying histology, and benign course. Their biology appears distinct from ordinary lipomas, spindle cell lipomas, and atypical lipomatous tumors.


Asunto(s)
Lipoma , Liposarcoma , Neoplasias de la Retina , Retinoblastoma , Neoplasias de los Tejidos Blandos , Masculino , Humanos , Niño , Adulto , Retinoblastoma/genética , Neoplasias de los Tejidos Blandos/patología , Biomarcadores de Tumor/análisis , Lipoma/genética , Lipoma/patología , Liposarcoma/patología , Hiperplasia
13.
Pediatr Dev Pathol ; 25(3): 304-315, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35686345

RESUMEN

Background: Cranial fasciitis (CF) is a benign (myo)fibroblastic proliferation of children. Typical presentation consists of a rapidly growing solitary mass on the temporal or parietal cranium in the first 2 years of age. CF is characterized by a rapid growth followed by a relative slowdown and even growth arrest. The finding of somatic USP6 gene rearrangements demonstrating clonality in CF together with its clinical behavior places it in the category of diseases recently termed "transient neoplasia."Methods: Histological, immunohistochemical, and molecular findings of 18 patients with CF were retrospectively studied.Results: The tumor typically presented as a painless rapidly enlarging mass in the temporal region. Sixty-six percent of the cases harbored USP6 gene rearrangement. Nine patients were treated with gross total resection (GTR) and 9 with subtotal tumor resection (STR). Two patients treated with GTR had recurrence. Five patients treated with STR had progression-free disease for at least 10 months after surgery and in four patients the tumor regressed spontaneously a median 16 months after surgery.Conclusions: In this largest series to date, we reported the clinicopathological, immunohistochemical, and molecular findings of 18 pediatric cases of CF with emphasis on the clinical growth pattern of these tumors.


Asunto(s)
Fascitis , Enfermedades Musculares , Neoplasias , Niño , Fascitis/genética , Fascitis/patología , Reordenamiento Génico , Humanos , Enfermedades Musculares/genética , Neoplasias/genética , Estudios Retrospectivos , Ubiquitina Tiolesterasa/genética
14.
J Clin Rheumatol ; 28(2): e401-e406, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33902097

RESUMEN

BACKGROUND/OBJECTIVES: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), first described in December 2019, has infected more than 33 million people and claimed more than 1 million deaths worldwide. Rheumatic diseases are chronic inflammatory diseases, the prevalence and impact of which in COVID-19 patients are poorly known. We performed a pooled analysis of published data intending to summarize clinical presentation and patient outcomes in those with established rheumatic disease diagnosis and concurrent COVID-19. METHODS: PubMed and Google Scholar were searched to identify studies reporting data about rheumatic disease patients who were diagnosed with SARS-CoV-2 infection and published until July 22, 2020. Random-effects models were used to estimate the pooled incidence and rates of hospitalization, intensive care unit admission, and mortality among these patients, and interstudy heterogeneity was identified using I2 statistics with greater than 75% value indicating substantial interstudy variation. RESULTS: Twenty studies were included, giving a total sample size of 49,099 patients positive for SARS-CoV-2. Of 49,099 COVID-19 patients, a total of 1382 were also diagnosed with a rheumatic disease in the past. The random-effects pooled prevalence of COVID-19 among rheumatic disease patients was found to be 0.9%. The rates of hospitalization, intensive care unit admission, and mortality were 70.7%, 11.6%, and 10.2%, respectively. CONCLUSIONS: Although the prevalence of SARS-CoV-2 infection is not dramatically high in rheumatic disease patients, concurrent COVID-19 does seem to play a role in determining disease severity and outcomes to some extent. Further studies are needed to give conclusive evidence about whether this subset of the population is at a higher risk of COVID-19 and related outcomes compared with the population at large.


Asunto(s)
COVID-19 , Enfermedades Reumáticas , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/epidemiología , SARS-CoV-2
15.
Artículo en Inglés | MEDLINE | ID: mdl-34804403

RESUMEN

According to one estimate, zinc supplementation is widely used in the USA by almost 37% of the elderly population above age 71. Zinc has perceived benefits of immune system enhancement without realizing the harmful effects when used in excess. One of its under-recognized side effects is hypocupremia or copper deficiency due to excessive gastrointestinal losses as excessive zinc in the gut competes with copper for absorption. If severe, hypocupremia can cause hematologic changes (anemia, leukopenia/neutropenia, thrombocytopenia, and pancytopenia) with and without neurological deficits. Since zinc-induced hypocupremia is an overlooked entity, there is a lag of 12 months between the onset of symptoms and diagnosis. Most patients usually undergo a series of costly and sometimes invasive tests such as bone marrow biopsies during this lag time. Once diagnosed, the treatment is as simple as discontinuation of zinc and oral copper supplements. Here, we present a case report of zinc-induced hypocupremia and pancytopenia in an 81-year-old lady who was taking zinc supplements for macular degeneration. The patient presented with leukopenia with neutropenia, thrombocytopenia, and moderate anemia. This case report aims to educate clinicians since this is an easily missed entity and likely more prevalent than known due to widely used zinc supplementation.

16.
Neuron ; 109(18): 2847-2863.e11, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34407390

RESUMEN

Asymmetric neuronal expansion is thought to drive evolutionary transitions between lissencephalic and gyrencephalic cerebral cortices. We report that Neurog2 and Ascl1 proneural genes together sustain neurogenic continuity and lissencephaly in rodent cortices. Using transgenic reporter mice and human cerebral organoids, we found that Neurog2 and Ascl1 expression defines a continuum of four lineage-biased neural progenitor cell (NPC) pools. Double+ NPCs, at the hierarchical apex, are least lineage restricted due to Neurog2-Ascl1 cross-repression and display unique features of multipotency (more open chromatin, complex gene regulatory network, G2 pausing). Strikingly, selectively eliminating double+ NPCs by crossing Neurog2-Ascl1 split-Cre mice with diphtheria toxin-dependent "deleter" strains locally disrupts Notch signaling, perturbs neurogenic symmetry, and triggers cortical folding. In support of our discovery that double+ NPCs are Notch-ligand-expressing "niche" cells that control neurogenic periodicity and cortical folding, NEUROG2, ASCL1, and HES1 transcript distribution is modular (adjacent high/low zones) in gyrencephalic macaque cortices, prefiguring future folds.


Asunto(s)
Diferenciación Celular/fisiología , Neocórtex/embriología , Neocórtex/fisiología , Neurogénesis/fisiología , Neuronas/fisiología , Animales , Células Cultivadas , Femenino , Humanos , Macaca fascicularis , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células 3T3 NIH , Neocórtex/citología , Embarazo , Imagen de Lapso de Tiempo/métodos
17.
STAR Protoc ; 2(3): 100670, 2021 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-34382012

RESUMEN

Microglial dynamics and interactions with nearby radial glia can be visualized in real time in embryonic mouse brain tissue using time-lapse imaging in slice culture. This live-cell imaging protocol can be used to study the morphology and activities of a number of cell types across a variety of brain regions and developmental time points. The advantage of this brain slice culture model is that it allows for the visualization of cellular interactions and movements in real time, especially across embryogenesis. For complete details on the use and execution of this protocol, please refer to Rosin et al. (2021).


Asunto(s)
Encéfalo/embriología , Ratones Transgénicos/genética , Microglía , Microscopía Confocal/métodos , Técnicas de Cultivo de Órganos/métodos , Animales , Encéfalo/citología , Dependovirus/genética , Femenino , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Microscopía Confocal/instrumentación , Embarazo , Sefarosa/química , Transducción Genética
18.
Cell Rep ; 34(1): 108587, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33406432

RESUMEN

Despite a growing appreciation for microglial influences on the developing brain, the responsiveness of microglia to insults during gestation remains less well characterized, especially in the embryo when microglia themselves are still maturing. Here, we asked if fetal microglia could coordinate an innate immune response to an exogenous insult. Using time-lapse imaging, we showed that hypothalamic microglia actively surveyed their environment by near-constant "touching" of radial glia projections. However, following an insult (i.e., IUE or AAV transduction), this seemingly passive touching became more intimate and long lasting, ultimately resulting in the retraction of radial glial projections and degeneration into small pieces. Mechanistically, the TAM receptors MERTK and AXL were upregulated in microglia following the insult, and Annexin V treatment inhibited radial glia breakage and engulfment by microglia. These data demonstrate a remarkable responsiveness of embryonic microglia to insults during gestation, a critical window for neurodevelopment.


Asunto(s)
Embrión de Mamíferos/metabolismo , Células Ependimogliales/fisiología , Hipotálamo/embriología , Hipotálamo/fisiología , Microglía/fisiología , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Tirosina Quinasa c-Mer/metabolismo , Animales , Encéfalo/embriología , Desarrollo Embrionario , Regulación del Desarrollo de la Expresión Génica , Inmunidad Innata , Ratones , Ratones Transgénicos , Imagen Óptica/métodos , Tirosina Quinasa del Receptor Axl
19.
Artículo en Inglés | MEDLINE | ID: mdl-32404254

RESUMEN

Osteosarcoma of the jaw (OSJ) is a rare malignancy, accounting for less than 1% of head and neck malignancies. OSJ can arise as a primary malignancy or secondary to locoregional radiation treatment. Radiologically, these tumors show large, destructive growth with periosteal reaction, which can suggest the diagnosis of osteosarcoma (OS). However, histology with demonstration of neoplastic, "lacelike" osteoid is the key to determining the diagnosis. Small tissue samples can complicate the diagnosis, especially in cases of high-grade OS with sheetlike growth and scant areas of immature osteoid formation. We report 3 cases of OSJ, including 1 rare case of epithelioid OS of the mandible, diagnosed at our hospital over a 6-month period: case 1: a 48-year-old male with history of Hodgkin lymphoma, who was treated with radiation and developed osteoblastic OS of the mandible 14 years later; case 2: a 79-year-old female with a history of fibrous dysplasia, who presented with a large destructive maxillary mass, which was diagnosed as histologically fibroblastic OSJ of the maxilla; and case 3: a 70-year-old male with radiation-induced high-grade epithelioid OS, which had been incorrectly diagnosed as poorly differentiated squamous cell carcinoma on a small biopsy specimen; this patient experienced recurrence with multiple neck nodules after treatment, underwent repeat resection, and was finally diagnosed with high-grade OS (epithelioid type).


Asunto(s)
Neoplasias Óseas , Neoplasias de Cabeza y Cuello , Osteosarcoma , Anciano , Femenino , Humanos , Masculino , Maxilar , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/terapia
20.
J Med Virol ; 93(2): 1188-1193, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32975814

RESUMEN

Coronavirus disease 2019 (COVID-19) pandemic is a global health crisis. Very few studies have reported association between obesity and severity of COVID-19. In this meta-analysis, we assessed the association of obesity and outcomes in COVID-19 hospitalized patients. Data from observational studies describing the obesity or body mass index and outcomes of COVID-19 hospitalized patients from December 1, 2019, to August 15, 2020, was extracted following PRISMA guidelines with a consensus of two independent reviewers. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio (OR) and 95% confidence interval (95% CI) were obtained and forest plots were created using random-effects models. A total of 10 studies with 10,233 confirmed COVID-19 patients were included. The overall prevalence of obesity in our study was 33.9% (3473/10,233). In meta-analysis, COVID-19 patient with obesity had higher odds of poor outcomes compared with better outcomes with a pooled OR of 1.88 (95% CI: 1.25-2.80; p = 0.002), with 86% heterogeneity between studies (p < 0.00001). Our study suggests a significant association between obesity and COVID-19 severity and poor outcomes. Our results findings may have important suggestions for the clinical management and future research of obesity and COVID-19.


Asunto(s)
COVID-19/fisiopatología , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Obesidad/complicaciones , Índice de Masa Corporal , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Obesidad/virología , Estudios Observacionales como Asunto , Prevalencia , Respiración Artificial/estadística & datos numéricos
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