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1.
Pathol Int ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32881200

RESUMO

There are several reports of pleural adenomatoid (microcystic) mesothelioma, but peritoneal adenomatoid mesothelioma is extremely rare. A 64-year-old Japanese woman presented with no symptoms and no asbestos exposure history. An abdominal computed tomography scan revealed multiple hypervascular masses on the liver surface, pelvic cavity and anterior peritoneum. Over 10 pieces of the multiple resected tumors showed numerous microcysts composed of a bland mesothelial cell background with rich capillary vessels. Focally, atypical cells with bizarre nuclei with prominent nucleoli were observed. Adenomatoid mesothelioma was suspected based on histochemical, immunohistochemical and fluorescence in situ hybridization findings. The tumors relapsed 4 years later and metastasized to the lung, but the patient remains alive 7 years after the first tumor resection surgery. Although the prognosis of adenomatoid mesothelioma of pleural origin is poor, the progression of this peritoneal case is slow.

2.
Tissue Eng Part A ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883178

RESUMO

Microtia is a congenital malformation of the auricle. The conventional therapy for microtia is reconstruction of the auricle using the patients' own costal cartilage. Because it is invasive to harvest costal cartilages, less invasive ways for auricular reconstruction need to be established. Recent reports have indicated a new method for the production of cartilaginous particles from human iPS cells. In order to adopt this method to create an auricular-shaped regenerative cartilage, a novel scaffold with the property of a three-dimensional shape memory was created. A scaffold with a three-dimensional shape of auricular frames composed of a helix and antihelix, which was designed to mimic auricular framework carved from autologous costal cartilage and transplanted in auricular reconstruction, was prepared, filled with cartilaginous particles, and subcutaneously transplanted in nude rats. The auricular-shaped regenerative cartilage maintained the given shape and cartilage features in vivo for 1 year. Our findings suggest a novel approach for auricular reconstruction.

3.
J Neurodev Disord ; 12(1): 25, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942984

RESUMO

BACKGROUND: Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. METHODS: To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. RESULTS: Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. CONCLUSIONS: The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ.

4.
Gan To Kagaku Ryoho ; 47(8): 1221-1224, 2020 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-32829359

RESUMO

A 44-year-old woman experienced loss of vision and distorted vision in the right eye. After she visited our hospital, she was diagnosed with a right metastatic choroidal tumor. At the age of 35 years, she had undergone surgery for left breast cancer; as recurrence of the breast cancer was suspected, the patient was referred to our department. A CT scan revealed left axillary lymph node swelling, liver metastasis, and lung metastasis. Lymph node needle biopsy was performed under ultrasound guidance, and the pathological findings revealed recurrence of breast cancer. Combination chemotherapy of bevacizumab( BV)plus paclitaxel(PTX)was administered. After chemotherapy, the metastatic lesion had remarkably shrunk, as observed on a CT scan. Optical coherence tomography(OCT)revealed that the tumor was flattened in her right eye. Choroidal metastasis of breast cancer is rare. BV plus PTX therapy was effective for treating choroidal metastasis of breast cancer, and it should be followed by ophthalmological examination over time.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama , Neoplasias da Coroide , Adulto , Bevacizumab , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Neoplasias da Coroide/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia , Paclitaxel
5.
Neuroimage ; 222: 117241, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32798679

RESUMO

Neuroimaging studies have shown that the brain is functionally organized into several large-scale brain networks. Within these networks are regions that are widely connected to several other regions within and/or outside the network. Regions that connect to several other networks, known as connector hubs, are believed to be crucial for information transfer and between-network communication within the brain. To identify regions with high between-network connectivity at the voxel level, we introduced a novel metric called functional connectivity overlap ratio (FCOR), which quantifies the spatial extent of a region's connection to a given network. Using resting state functional magnetic resonance imaging data, FCOR maps were generated for several well-known large-scale resting state networks (RSNs) and used to examine the relevant associations among different RSNs, identify connector hub regions in the cerebral cortex, and elucidate the hierarchical functional organization of the brain. Constructed FCOR maps revealed a strong association among the core neurocognitive networks (default mode, salience, and executive control) as well as among primary processing networks (sensorimotor, auditory, and visual). Prominent connector hubs were identified in the bilateral middle frontal gyrus, posterior cingulate, lateral parietal, middle temporal, dorsal anterior cingulate, and anterior insula, among others, regions mostly associated with the core neurocognitive networks. Finally, clustering the whole brain using FCOR features yielded a topological organization that arranges brain regions into a hierarchy of information processing systems with the primary processing systems at one end and the heteromodal systems comprising connector hubs at the other end.

6.
Transl Psychiatry ; 10(1): 247, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699248

RESUMO

Schizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the ARHGAP10 gene. ARHGAP10 encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the ARHGAP10 gene is often confused with ARHGAP21, thus, the significance of ARHGAP10 in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in ARHGAP10. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between ARHGAP10 and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare ARHGAP10 variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.

7.
Hum Brain Mapp ; 41(12): 3198-3211, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304267

RESUMO

White matter (WM) fiber bundles change dynamically with age. These changes could be driven by alterations in axonal diameter, axonal density, and myelin content. In this study, we applied a novel fixel-based analysis (FBA) framework to examine these changes throughout the adult lifespan. Using diffusion-weighted images from a cohort of 293 healthy volunteers (89 males/204 females) from ages 21 to 86 years old, we performed FBA to analyze age-related changes in microscopic fiber density (FD) and macroscopic fiber morphology (fiber cross section [FC]). Our results showed significant and widespread age-related alterations in FD and FC across the whole brain. Interestingly, some fiber bundles such as the anterior thalamic radiation, corpus callosum, and superior longitudinal fasciculus only showed significant negative relationship with age in FD values, but not in FC. On the other hand, some segments of the cerebello-thalamo-cortical pathway only showed significant negative relationship with age in FC, but not in FD. Analysis at the tract-level also showed that major fiber tract groups predominantly distributed in the frontal lobe (cingulum, forceps minor) exhibited greater vulnerability to the aging process than the others. Differences in FC and the combined measure of FD and cross section values observed between sexes were mostly driven by differences in brain sizes although male participants tended to exhibit steeper negative linear relationship with age in FD as compared to female participants. Overall, these findings provide further insights into the structural changes the brain's WM undergoes due to the aging process.

8.
Sci Rep ; 10(1): 7137, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32346119

RESUMO

Outbreaks of diarrhea in kindergartens are underreported and frequently go unnoticed in developing countries. To better understand the etiology this study was performed during an outbreak of diarrhea in a kindergarten in Sabah, Malaysia. Outbreak investigation was performed according to the standard procedures. In this outbreak a total of 34 (36.5%) children and 4 (30.8%) teachers suffered from gastroenteritis. Stool samples from seven children and 13 teachers were tested for rotavirus and norovirus. During the investigation stool samples were collected and sent in cold chain to the laboratory. The samples were subjected to rotavirus enzyme linked immunosorbent assay, and reverse transcription PCR for norovirus. All samples were negative for rotavirus but positive for norovirus. To determine the genogroup and genotype of norovirus, nucleotide sequencing of the amplicons was performed. All norovirus from the outbreak was of genotype GII.2[16]. To determine the relatedness of the strains phylogenetic analysis was done using neighbor-joining method. Phylogenetically these strains were highly related to GII.2[P16] noroviruses from China and Japan. This study provided evidence that a diarrheal outbreak in a kindergarten was caused by GII.2[P16] norovirus which is an emerging strain in East Asia and Europe.

9.
Sci Rep ; 10(1): 5820, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32242061

RESUMO

Neuronal migration is necessary in the process of the formation of brain architecture. Recently, we demonstrated that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons exhibit directional migration in vitro. However, it remains unclear how the cell shape is involved in their migration. In this study, we performed live imaging analyses using human iPSC-derived dopaminergic neurons. Our automated method, which can automatically identify the cell body shape and the cell position at specific time points, revealed that healthy iPSC-derived dopaminergic neurons migrate according to their shape. This migration behavior was out of accord in neurons derived from iPSCs carrying an RELN deletion. Our findings provide a novel theory that cell body orientation is related to the stability of movement direction for human dopaminergic neurons, under the regulation of RELN.

10.
Sci Rep ; 10(1): 5425, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214220

RESUMO

HIF-1α, an essential transcription factor under hypoxic condition, is indispensable for chondrocytes during skeletal development but its expression and roles in articular chondrocytes are yet to be revealed. We examined HIF-1α protein expression and the hypoxic condition during mouse osteoarthritis (OA) development using state of the art hypoxic probes and found that its expression decreased as OA progressed, coinciding with the change in hypoxic conditions in articular cartilage. Gain- and loss-of-function of HIF-1α in cell culture experiments showed that HIF-1α suppressed catabolic genes such as Mmp13 and Hif2a. We confirmed these anticatabolic effects by measuring glycosaminoglycan release from wild type and conditional knock-out mice femoral heads cultured ex vivo. We went on to surgically induce OA in mice with chondrocyte-specific deletion of Hif1a and found that the development of OA was exacerbated. Increased expression of catabolic factors and activation of NF-κB signalling was clearly evident in the knock-out mice. By microarray analysis, C1qtnf3 was identified as a downstream molecule of HIF-1α, and experiments showed it exerted anti-catabolic effects through suppression of NF-κB. We conclude that HIF-1α has an anti-catabolic function in the maintenance of articular cartilage through suppression of NF-κB signalling.

11.
Psychiatry Clin Neurosci ; 74(5): 318-327, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32065683

RESUMO

AIM: A Japanese individual with schizophrenia harboring a novel exonic deletion in RELN was recently identified by genome-wide copy-number variation analysis. Thus, the present study aimed to generate and analyze a model mouse to clarify whether Reln deficiency is associated with the pathogenesis of schizophrenia. METHODS: A mouse line with a novel RELN exonic deletion (Reln-del) was established using the CRISPR/Cas9 method to elucidate the underlying molecular mechanism. Subsequently, general behavioral tests and histopathological examinations of the model mice were conducted and phenotypic analysis of the cerebellar granule cell migration was performed. RESULTS: The phenotype of homozygous Reln-del mice was similar to that of reeler mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin. The expression of reelin in heterozygous Reln-del mice was approximately half of that in wild-type mice. Conversely, behavioral analyses in heterozygous Reln-del mice without cerebellar atrophy or dysplasia showed abnormal social novelty in the three-chamber social interaction test. In vitro reaggregation formation and neuronal migration were severely altered in the cerebellar cultures of homozygous Reln-del mice. CONCLUSION: The present results in novel Reln-del mice modeled after our patient with a novel exonic deletion in RELN are expected to contribute to the development of reelin-based therapies for schizophrenia.

12.
Transl Psychiatry ; 10(1): 35, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32066675

RESUMO

The 22q11.2 deletion syndrome (22q11.2DS) is associated with an increased risk for psychiatric disorders. Although most of the 22q11.2DS patients have a 3.0-Mb deletion, existing mouse models only mimic a minor mutation of 22q11.2DS, a 1.5-Mb deletion. The role of the genes existing outside the 1.5-Mb deletion in psychiatric symptoms of 22q11.2DS is unclear. In this study, we generated a mouse model that reproduced the 3.0-Mb deletion of the 22q11.2DS (Del(3.0 Mb)/ +) using the CRISPR/Cas9 system. Ethological and physiological phenotypes of adult male mutants were comprehensively evaluated by visual-evoked potentials, circadian behavioral rhythm, and a series of behavioral tests, such as measurement of locomotor activity, prepulse inhibition, fear-conditioning memory, and visual discrimination learning. As a result, Del(3.0 Mb)/ + mice showed reduction of auditory prepulse inhibition and attenuated cue-dependent fear memory, which is consistent with the phenotypes of existing 22q11.2DS models. In addition, Del(3.0 Mb)/ + mice displayed an impaired early visual processing that is commonly seen in patients with schizophrenia. Meanwhile, unlike the existing models, Del(3.0 Mb)/ + mice exhibited hypoactivity over several behavioral tests, possibly reflecting the fatigability of 22q11.2DS patients. Lastly, Del(3.0 Mb)/ + mice displayed a faster adaptation to experimental jet lag as compared with wild-type mice. Our results support the validity of Del(3.0 Mb)/ + mice as a schizophrenia animal model and suggest that our mouse model is a useful resource to understand pathogenic mechanisms of schizophrenia and other psychiatric disorders associated with 22q11.2DS.

13.
CEN Case Rep ; 9(2): 162-164, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31955390

RESUMO

A 53-year-old man on hemodialysis suffered from short bowel syndrome after subtotal colectomy and partial resection of the small intestine. Laboratory tests showed multiple electrolyte disorders and enlarged sodium and chloride ion (Cl-) gaps despite treatment with large volume of sodium chloride replacement via central venous infusion. Blood gas analysis showed slightly high bicarbonate ion levels and metabolic alkalosis was suspected, which is uncommon in end stage kidney disease. The measurement of electrolytes in feces from ileostomy showed relatively high Cl- excretion. The loss of Cl- to feces may have caused the metabolic alkalosis; thus, additional Cl- replacement may have been necessary.

14.
Soft Matter ; 16(4): 899-906, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31829395

RESUMO

Artificial supramolecular nanostructures showing transient properties have attracted significant attention in recent years. New discoveries in this area may provide insights into a better understanding of the sophisticated organization of complex biomolecular systems. Nevertheless, research concerning such materials is still limited. Better knowledge of the chemical reactivity and corresponding molecular transformations of self-assembling molecules, which guide their assembly/disassembly, may provide an opportunity to construct transient supramolecular nanostructures capable of showing chemical stimulus responsiveness. Herein, we report a short peptide derivative containing a hydrazone bond, which shows transient hydrogel formation (no only sol-to-gel but also gel-to-shrunken gel phase transition) accompanied by continuous transformation and growth of supramolecular nanostructures triggered by hydrazone-oxime exchange reaction in response to hydroxylamine. Such controlled shrinkage behavior of supramolecular hydrogels in response to specific chemical stimuli has rarely been explored compared with conventional polymer hydrogel systems.

15.
Schizophr Res ; 216: 511-515, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31848032

RESUMO

Genetic studies have identified rare RELN variants as risk factors for psychiatric disorders. However, additional genetic factors appear to be necessary for disease onset. Detailed genetic information and the use of patient-derived neuronal cells may thus enable to discover these disease-related additional factors. Here, we performed whole-genome sequencing of a schizophrenia patient with a rare RELN deletion and his healthy mother, and examined the phenotypes of 3D-cultured neuronal cells derived from induced pluripotent stem cells of this patient. Our results revealed that, along with the RELN deletion, neuronal death was promoted in this patient; thus, neuronal death may be a vulnerable factor for schizophrenia.

16.
Arthritis Res Ther ; 21(1): 247, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771658

RESUMO

BACKGROUND: Both loss- and gain-of-function of Wnt/ß-catenin signaling in chondrocytes result in exacerbation of osteoarthritis (OA). Here, we examined the activity and roles of Wnt/ß-catenin signaling in the superficial zone (SFZ) of articular cartilage. METHODS: Wnt/ß-catenin signaling activity was analyzed using TOPGAL mice. We generated Prg4-CreERT2;Ctnnb1fl/fl and Prg4-CreERT2;Ctnnb1-ex3fl/wt mice for loss- and gain-of-function, respectively, of Wnt/ß-catenin signaling in the SFZ. Regulation of Prg4 expression by Wnt/ß-catenin signaling was examined in vitro, as were upstream and downstream factors of Wnt/ß-catenin signaling in SFZ cells. RESULTS: Wnt/ß-catenin signaling activity, as determined by the TOPGAL reporter, was high specifically in the SFZ of mouse adult articular cartilage, where Prg4 is abundantly expressed. In SFZ-specific ß-catenin-knockout mice, OA development was significantly accelerated, which was accompanied by decreased Prg4 expression and SFZ destruction. In contrast, Prg4 expression was enhanced and cartilage degeneration was suppressed in SFZ-specific ß-catenin-stabilized mice. In primary SFZ cells, Prg4 expression was downregulated by ß-catenin knockout, while it was upregulated by ß-catenin stabilization by exon 3 deletion or treatment with CHIR99021. Among Wnt ligands, Wnt5a, Wnt5b, and Wnt9a were highly expressed in SFZ cells, and recombinant human WNT5A and WNT5B stimulated Prg4 expression. Mechanical loading upregulated expression of these ligands and further promoted Prg4 transcription. Moreover, mechanical loading and Wnt/ß-catenin signaling activation increased mRNA levels of Creb1, a potent transcription factor for Prg4. CONCLUSIONS: We demonstrated that Wnt/ß-catenin signaling regulates Prg4 expression in the SFZ of mouse adult articular cartilage, which plays essential roles in the homeostasis of articular cartilage.

17.
Data Brief ; 26: 104445, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31534995

RESUMO

A Mycobacterium tuberculosis strain SBH162 was isolated from a 49-year-old male with pulmonary tuberculosis. GeneXpert MDR/RIF identified the strain as rifampicin-resistant M. tuberculosis. The whole genome sequencing was performed using Illumina HiSeq 4000 system to further investigate and verify the mutation sites of the strain through genetic analyses namely variant calling using bioinformatics tools. The de novo assembly of genome generated 100 contigs with N50 of 156,381bp. The whole genome size was 4,343,911 bp with G + C content of 65.58% and consisted of 4,306 predicted genes. The mutation site, S450L, for rifampicin resistance was detected in the rpoB gene. Based on the phylogenetic analysis using the Maximum Likelihood method, the strain was identified as belonging to the Europe America Africa lineage (Lineage 4). The genome dataset has been deposited at DDBJ/ENA/GenBank under the accession number SMOE00000000.

18.
eNeuro ; 6(5)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31540999

RESUMO

Bipolar disorder (BP) and schizophrenia (SCZ) are major psychiatric disorders, but the molecular mechanisms underlying the complicated pathologies of these disorders remain unclear. It is difficult to establish adequate in vitro models for pathological analysis because of the heterogeneity of these disorders. In the present study, to recapitulate the pathologies of these disorders in vitro, we established in vitro models by differentiating mature neurons from human induced pluripotent stem cells (hiPSCs) derived from BP and SCZ patient with contributive copy number variations, as follows: two BP patients with PCDH15 deletion and one SCZ patient with RELN deletion. Glutamatergic neurons and GABAergic neurons were induced from hiPSCs under optimized conditions. Both types of induced neurons from both hiPSCs exhibited similar phenotypes of MAP2 (microtubule-associated protein 2)-positive dendrite shortening and decreasing synapse numbers. Additionally, we analyzed isogenic PCDH15- or RELN-deleted cells. The dendrite and synapse phenotypes of isogenic neurons were partially similar to those of patient-derived neurons. These results suggest that the observed phenotypes are general phenotypes of psychiatric disorders, and our in vitro models using hiPSC-based technology may be suitable for analysis of the pathologies of psychiatric disorders.


Assuntos
Transtorno Bipolar/patologia , Técnicas de Cultura de Células/métodos , Neurônios/patologia , Células-Tronco Pluripotentes , Esquizofrenia/patologia , Adulto , Transtorno Bipolar/genética , Caderinas/genética , Moléculas de Adesão Celular Neuronais/genética , Células Cultivadas , Variações do Número de Cópias de DNA , Proteínas da Matriz Extracelular/genética , Feminino , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Esquizofrenia/genética , Serina Endopeptidases/genética
19.
J Med Case Rep ; 13(1): 298, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31540583

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis is characterized by partial (segmental) sclerotic lesions in some glomeruli (focal). Primary focal segmental glomerulosclerosis is generally considered resistant to steroid therapy. However, acromegaly is a disease that causes peculiar facial features, body types, and metabolic abnormalities due to the excessive secretion of growth hormone by a pituitary adenoma. Growth hormone has been reported to be involved in glomerular cell growth, mesangial proliferation, and glomerulosclerosis in the kidney. CASE PRESENTATION: We report a case of a Japanese patient with focal segmental glomerulosclerosis in whom decreased urinary protein was observed after surgical treatment for acromegaly. CONCLUSION: The patient's urinary protein improved as the concentration of growth hormone/insulin-like growth factor 1 decreased.


Assuntos
Acromegalia/cirurgia , Glomerulosclerose Segmentar e Focal/terapia , Proteinúria/terapia , Acromegalia/etiologia , Adenoma/complicações , Adenoma/cirurgia , Hormônio do Crescimento/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia
20.
Stem Cell Reports ; 13(3): 530-544, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31402337

RESUMO

A simple induction protocol to differentiate chondrocytes from pluripotent stem cells (PSCs) using small-molecule compounds is beneficial for cartilage regenerative medicine and mechanistic studies of chondrogenesis. Here, we demonstrate that chondrocytes are robustly induced from human PSCs by simple combination of two compounds, CHIR99021, a glycogen synthase kinase 3 inhibitor, and TTNPB, a retinoic acid receptor (RAR) agonist, under serum- and feeder-free conditions within 5-9 days. An excellent differentiation efficiency and potential to form hyaline cartilaginous tissues in vivo were demonstrated. Comprehensive gene expression and open chromatin analyses at each protocol stage revealed step-by-step differentiation toward chondrocytes. Genome-wide analysis of RAR and ß-catenin association with DNA showed that retinoic acid and Wnt/ß-catenin signaling collaboratively regulated the key marker genes at each differentiation stage. This method provides a promising cell source for regenerative medicine and, as an in vitro model, may facilitate elucidation of the molecular mechanisms underlying chondrocyte differentiation.

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