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1.
J Sex Med ; 14(2): 269-273, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28087356

RESUMO

INTRODUCTION: A cornerstone of treating gender dysphoria for transgender women is gender reassignment surgery (GRS) encompassing vaginoplasty and clitoroplasty. The neoclitoris is harvested as a flap with a neurovascular pedicle from the proximal dorsal part of the glans penis. Few long-term follow-ups exist on postoperative sensation and patient-reported sexual functionality of the neoclitoris. AIM: To examine the sensitivity of the neoclitoris and its relation to orgasm and sexual function at least 1 year after GRS. METHODS: Twenty-two patients were included, with a mean follow-up of 37 months (range = 12-63) after initial surgery. Tactile and vibratory sensitivities were measured with Semmes-Weinstein monofilaments and the Bio-Thesiometer vibratory measurement device, respectively. A questionnaire was provided to the patients, as were interview questions about body image, orgasm, pain, and general satisfaction with the surgery. MAIN OUTCOME MEASURES: Tactile and vibratory sensitivities of the neoclitoris and questionnaire on satisfaction with orgasm, sexual function, and general satisfaction. RESULTS: The average tactile threshold for the clitoris was 12.5 g/mm2 and the average vibratory threshold was 0.3 µm. Most participants (86%) experienced orgasm after surgery, had no or little pain, and were satisfied with the surgery. No statistical correlation was found between better or worse objective pressure and vibratory thresholds and patient answers to questions about the clitoris in the Body Image Scale for Transsexuals questionnaire. CONCLUSION: The neoclitoris derived from the glans penis in GRS provides long-term clitoral sensation that is erogenous. Overall, the vast majority of patients who undergo male-to female GRS experience orgasm and are satisfied with the surgery.


Assuntos
Clitóris/inervação , Clitóris/cirurgia , Orgasmo/fisiologia , Pênis/cirurgia , Transexualidade/cirurgia , Adulto , Imagem Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pênis/inervação , Satisfação Pessoal , Cirurgia de Readequação Sexual/métodos , Comportamento Sexual
2.
Nature ; 451(7177): 460-4, 2008 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-18185516

RESUMO

Stem cell self-renewal implies proliferation under continued maintenance of multipotency. Small changes in numbers of stem cells may lead to large differences in differentiated cell numbers, resulting in significant physiological consequences. Proliferation is typically regulated in the G1 phase, which is associated with differentiation and cell cycle arrest. However, embryonic stem (ES) cells may lack a G1 checkpoint. Regulation of proliferation in the 'DNA damage' S/G2 cell cycle checkpoint pathway is known for its role in the maintenance of chromatin structural integrity. Here we show that autocrine/paracrine gamma-aminobutyric acid (GABA) signalling by means of GABA(A) receptors negatively controls ES cell and peripheral neural crest stem (NCS) cell proliferation, preimplantation embryonic growth and proliferation in the boundary-cap stem cell niche, resulting in an attenuation of neuronal progenies from this stem cell niche. Activation of GABA(A) receptors leads to hyperpolarization, increased cell volume and accumulation of stem cells in S phase, thereby causing a rapid decrease in cell proliferation. GABA(A) receptors signal through S-phase checkpoint kinases of the phosphatidylinositol-3-OH kinase-related kinase family and the histone variant H2AX. This signalling pathway critically regulates proliferation independently of differentiation, apoptosis and overt damage to DNA. These results indicate the presence of a fundamentally different mechanism of proliferation control in these stem cells, in comparison with most somatic cells, involving proteins in the DNA damage checkpoint pathway.


Assuntos
Histonas/metabolismo , Receptores de GABA-A/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Comunicação Autócrina , Blastocisto/citologia , Blastocisto/enzimologia , Blastocisto/metabolismo , Contagem de Células , Ciclo Celular , Linhagem Celular , Proliferação de Células , Tamanho Celular , Dano ao DNA , Agonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-A , Histonas/deficiência , Histonas/genética , Camundongos , Crista Neural/citologia , Crista Neural/metabolismo , Comunicação Parácrina , Técnicas de Patch-Clamp , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Receptores de GABA-A/genética , Células-Tronco/enzimologia , Ácido gama-Aminobutírico/metabolismo
3.
Eur Arch Paediatr Dent ; 25(4): 533-545, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38842758

RESUMO

PURPOSE: The aim of this study was to explore the potential to profile and distinguish varying clinical severity grades of MIH, compared to normal enamel, using proteomics. METHODS: Liquid chromatography-mass spectrometry analyses were conducted on enamel samples of extracted teeth, from 11 children and adolescents, spanning an age range of 6-18 years. Enamel powder samples were collected from extracted, third molars (n = 3) and first permanent molars diagnosed with MIH (n = 8). The MIH tooth samples were categorized into subgroups based on clinical severity grade. The data were statistically analyzed using ANOVA and Welch's t test. RESULTS: Teeth affected by MIH exhibited a diverse array of proteins, each with different functions related to dental enamel, distinguishing them from their normal enamel counterparts. The application of microdissection combined with LC-MS techniques has revealed the potential to discern unique proteomic profiles among MIH-affected teeth, characterized by varying clinical severity grades. Both analyzed MIH groups displayed consistent trends in the presentation of biological processes, including underabundance of proteins primarily associated with cell organization and biogenesis. Furthermore, proteins linked to cell death were overabundant in both MIH groups. CONCLUSION: Proteomics enabled the detection and differentiation of various proteins across different clinical severity grades of MIH.


Assuntos
Esmalte Dentário , Hipomineralização Molar , Proteômica , Adolescente , Criança , Humanos , Esmalte Dentário/patologia , Esmalte Dentário/metabolismo , Técnicas In Vitro , Dente Molar/patologia , Hipomineralização Molar/diagnóstico , Hipomineralização Molar/patologia , Proteômica/métodos , Índice de Gravidade de Doença , Espectrometria de Massa com Cromatografia Líquida
4.
J Craniofac Surg ; 24(1): 134-5, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23348270

RESUMO

Most surgical protocols for head and neck cancer extirpation require concurrent neck lymph node dissection. Hence, the defect involves not only the cancerous anatomical structures but also the neck. The tissue deficiency in the latter region imposes potential problems such as carotid and jugular vein exposure risking blowout, infections and orocutaneous fistulae in the neck, and a cosmetically untoward sunken appearance. The free anterolateral thigh flap (ALT) provides abundant tissue and is often the flap of choice in head and neck reconstruction. To replace the proper amount of postoperative soft tissue deficit in the neck area, we use an oversized ALT flap design. This allows reconstruction of the specific anatomical defects, protection of the important neck structures, and prevention of a sunken appearance. An oversized flap may also provide additional coverage for fixation hardware to prevent its exposure, especially after radiotherapy. In the event of partial flap loss, some viable parts of the oversized flap may be possible to advance or rotate to replace the nonviable part to avoid a repeated free flap procedure or other more complicated reconstructive procedures.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Coxa da Perna/cirurgia , Humanos , Excisão de Linfonodo , Microcirurgia
5.
Br J Cancer ; 106(11): 1807-15, 2012 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-22531632

RESUMO

BACKGROUND: Cellular quiescence is a state of reversible proliferation arrest that is induced by anti-mitogenic signals. The endogenous cardiac glycoside ouabain is a specific ligand of the ubiquitous sodium pump, Na,K-ATPase, also known to regulate cell growth through unknown signalling pathways. METHODS: To investigate the role of ouabain/Na,K-ATPase in uncontrolled neuroblastoma growth we used xenografts, flow cytometry, immunostaining, comet assay, real-time PCR, and electrophysiology after various treatment strategies. RESULTS: The ouabain/Na,K-ATPase complex induced quiescence in malignant neuroblastoma. Tumour growth was reduced by >50% when neuroblastoma cells were xenografted into immune-deficient mice that were fed with ouabain. Ouabain-induced S-G2 phase arrest, activated the DNA-damage response (DDR) pathway marker γH2AX, increased the cell cycle regulator p21(Waf1/Cip1) and upregulated the quiescence-specific transcription factor hairy and enhancer of split1 (HES1), causing neuroblastoma cells to ultimately enter G0. Cells re-entered the cell cycle and resumed proliferation, without showing DNA damage, when ouabain was removed. CONCLUSION: These findings demonstrate a novel action of ouabain/Na,K-ATPase as a regulator of quiescence in neuroblastoma, suggesting that ouabain can be used in chemotherapies to suppress tumour growth and/or arrest cells to increase the therapeutic index in combination therapies.


Assuntos
Histonas/metabolismo , Neuroblastoma/metabolismo , Ouabaína/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaio Cometa , Feminino , Citometria de Fluxo , Humanos , Camundongos , Camundongos Nus , Ouabaína/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Transplante Heterólogo
8.
Clin Exp Allergy ; 40(8): 1276-87, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20545700

RESUMO

BACKGROUND: Dog dander is an important cause of respiratory allergy but its content of allergenic components is still incompletely known. While Can f 1, 2, 3 and 5 have been studied in detail, only fragmentary information is available on the lipocalin Can f 4. OBJECTIVE: To purify, clone and characterize dog dander allergen Can f 4. METHODS: Can f 4 was purified from dog dander extract by size exclusion, ion exchange and reverse phase chromatography. A cDNA encoding Can f 4 was cloned and used to produce recombinant Can f 4 in Escherichia coli. A 23 kDa protein from cow dander, displaying cross-reactivity with Can f 4, was purified and identified by amino acid sequencing and mass spectrometry. IgE antibody binding to dog and cow dander extract and to individual dog allergens among 37 dog allergic subjects and 44 pollen allergic controls was studied using ImmunoCAP. RESULTS: A dog genome segment containing the Can f 4 gene was bioinformatically identified and enabled the cloning of Can f 4 cDNA. Recombinant Can f 4 displayed close immunological and biochemical similarity to purified natural Can f 4 and bound IgE antibodies from 13/37 (35%) sera of dog allergic subjects. Can f 4 reactive sera showed IgE binding to a 23 kDa protein present in cow dander extract, related to a family of odorant-binding proteins. The dog and cow proteins shared 37% sequence identity and their cross-reactivity was demonstrated by IgE inhibition experiments. CONCLUSION: Recombinant Can f 4 brings the panel of available dog allergens closer to completion and will be important in component-resolved diagnostics in allergy to animal epithelial allergens.


Assuntos
Alérgenos/imunologia , Bovinos/imunologia , Cães/imunologia , Hipersensibilidade/imunologia , Adulto , Alérgenos/química , Alérgenos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Cromatografia por Troca Iônica , Reações Cruzadas , Feminino , Humanos , Immunoblotting , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Receptores Odorantes/química , Receptores Odorantes/genética , Receptores Odorantes/imunologia , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Adulto Jovem
9.
Am J Transplant ; 9(12): 2816-24, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19845588

RESUMO

The fate of islets in clinical transplantation is unclear. To elude on this positron emission tomography combined with computed tomography (PET/CT) was performed for 60 min during islet transplantation in five patients receiving six transplants. A fraction of the islets (23%) were labeled with 18F-fluorodeoxyglucose ([(18)F]FDG) and carefully mixed with unlabeled islets just prior to intraportal transplantation. The peak radioactivity concentration in the liver was found at 19 min after start of islet infusion and corresponded to only 75% of what was expected, indicating that islets are lost during the transplantation procedure. No accumulation of radioactivity was found in the lungs. A nonphysiological peak of C-peptide was found in plasma during and immediately after transplantation in all subjects. Distribution in the liver was heterogeneous with wide variations in location and concentration. Islets found in areas with concentrations of >400 IEQ/cc liver tissue varied between 1% and 32% of the graft in different subjects. No side effects attributed to the PET/CT procedure were found. Clinical outcome in all patients was comparable to that previously observed indicating that the [(18)F]FDG labeling procedure did not harm the islets. The technique has potential to be used to assess approaches to enhance islet survival and engraftment in clinical transplantation.


Assuntos
Transplante das Ilhotas Pancreáticas/métodos , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Peptídeo C/sangue , Feminino , Fluordesoxiglucose F18 , Humanos , Inflamação/sangue , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
10.
Mol Oncol ; 13(2): 202-211, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30358081

RESUMO

Bacillus Calmette-Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca2+ (calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca2+ response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca2+ signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.


Assuntos
Sinalização do Cálcio , Citocinas/metabolismo , Mycobacterium bovis/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Cálcio/metabolismo , Linhagem Celular Tumoral , Citosol/metabolismo , Humanos , Interleucina-8/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo
11.
J Cell Biochem ; 104(3): 879-94, 2008 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-18189271

RESUMO

During development neural progenitor cells migrate with extraordinary precision to inhabit tissues and organs far from their initial position. Little is known about the cellular basis for directional guidance by tyrosine kinase receptors (RTKs). RET is a RTK with important functions in guiding the migration of neuronal cells, and RET dysregulation leads to clinical disease such as agangliosis of the colon. We show here that RET migration in neuroepitheliomal and non-neuronal cells is elicited by the activation of specific signaling pathways initiated by the competitive recruitment of the FRS2 adaptor molecule to tyrosine 1062 (Y1062) in RET. FRS2 selectively recruited RET to focal complexes and led to activation of SRC family kinases and focal adhesion kinase (FAK). Activation of SRC depended on its direct interaction with RET at a different intracellular tyrosine (Y981) and activation of molecular signaling from these two separate sites in concert regulated migration. Our data suggest that an important function for FRS2 is to concentrate RET in membrane foci, leading to an engagement of specific signaling complexes localized in these membrane domains.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Membrana Celular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas c-ret/metabolismo , Animais , Células COS , Movimento Celular , Quimiotaxia , Chlorocebus aethiops , Cães , Fibroblastos/metabolismo , Humanos , Camundongos , Transdução de Sinais , Quinases da Família src/metabolismo
12.
Am J Transplant ; 8(2): 458-62, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18093267

RESUMO

A 7-year-old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160,000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C-peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5- and 27-months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C-peptide levels were 0.67 +/- 0.07 and 3.36 +/- 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long-term clinically significant metabolic control.


Assuntos
Transplante das Ilhotas Pancreáticas/métodos , Pancreatectomia , Pancreatite/cirurgia , Transplante Autólogo/métodos , Criança , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Músculo Esquelético , Pancreatite/genética , Fatores de Tempo , Resultado do Tratamento
13.
Gene Expr Patterns ; 8(4): 217-26, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18282814

RESUMO

NEDD9 is a scaffolding protein in the integrin signaling pathway that is involved in cell adhesion dynamics. Little is known of the cellular localization of NEDD9 expression during embryonic development. In the present study, we have analyzed NEDD9 mRNA expression in the mouse and identified new relevant expression sites. In addition, we have characterized NEDD9 protein expression pattern for the first time in mammals. At E9.5-E10.5, high levels of Nedd9 and the neurogenic transcription factor neurogenin-2 (Ngn2) were found to largely overlap in two discrete domains of the trunk neural tube along its dorso-ventral axis, with Nedd9 extending to more ventral regions of the ventricular zone and Ngn2 differentially expressed in neuronally committed progenitors of the intermediate zone. At encephalic and trunk levels of the neural tube, NEDD9 was present in Sox2(+) progenitor cell populations mostly generating Ngn2(+) and/or Nurr1(+) cells. A sharp down-regulation of NEDD9 expression was found in cells upon lineage commitment, as observed in Nurr1(+) and Ngn2(+) mesencephalic dopaminergic and brainstem neuronal progenitors. In other tissues/organs, i.e. prospective heart, retina, olfactory epithelium, gonads, cartilage, gut and pituitary gland, NEDD9 was found to be co-expressed with Sox2, RXR alpha and/or Nurr1-like proteins, suggesting that NEDD9 expression is confined to early progenitors involved in diverse organogenesis and that it may depend on the repertoire and levels of retinoic acid co-receptors expressed by those cells.


Assuntos
Proteínas/metabolismo , Células-Tronco/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Tronco Encefálico/citologia , Tronco Encefálico/embriologia , Tronco Encefálico/metabolismo , Cerebelo/citologia , Cerebelo/embriologia , Cerebelo/metabolismo , Proteínas de Ligação a DNA/análise , Embrião não Mamífero/metabolismo , Expressão Gênica , Proteínas HMGB/análise , Mesencéfalo/citologia , Mesencéfalo/embriologia , Mesencéfalo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Tubo Neural/citologia , Tubo Neural/metabolismo , Proteínas/análise , Proteínas/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição SOXB1 , Fatores de Transcrição/análise
14.
FEBS J ; 275(9): 2055-66, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18355321

RESUMO

Glial cell line-derived neurotrophic factor family ligands act through the receptor tyrosine kinase Ret, which plays important roles during embryonic development for cell differentiation, survival, and migration. Ret signaling is markedly affected by compartmentalization of receptor complexes into membrane subdomains. Ret can propagate biochemical signaling from within concentrates in cholesterol-rich membrane microdomains or lipid rafts, or outside such regions, but the mechanisms for, and consequences of, Ret translocation between these membrane compartments remain largely unclear. Here we investigate the interaction of Shc and Frs2 phosphotyrosine-binding domain-containing adaptor molecules with Ret and their function in redistributing Ret to specialized membrane compartments. We found that engagement of Ret with the Frs2 adaptor results in an enrichment of Ret in lipid rafts and that signal transduction pathways and chemotaxis responses depend on the integrity of such rafts. The competing Shc adaptor did not promote Ret translocation to equivalent domains, and Shc-mediated effects were less affected by disruption of lipid rafts. However, by expressing a chimeric Shc protein that localizes to lipid rafts, we showed that biochemical signaling downstream of Ret resembled that of Ret signaling via Frs2. We have identified a previously unknown mechanism in which phosphotyrosine-binding domain-containing adaptors, by means of relocating Ret receptor complexes to lipid rafts, segregate diverse signaling and cellular functions mediated by Ret. These results reveal the existence of a novel mechanism that could, by subcellular relocation of Ret, work to amplify ligand gradients during chemotaxis.


Assuntos
Membrana Celular/fisiologia , Microdomínios da Membrana/fisiologia , Proteínas Proto-Oncogênicas c-ret/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Compartimento Celular/fisiologia , Fracionamento Celular , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Movimento Celular , Ensaio Cometa , Detergentes/farmacologia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/fisiologia , Proteínas de Fluorescência Verde/metabolismo , Humanos , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/metabolismo , Mutação , Neuroblastoma/patologia , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Adaptadoras da Sinalização Shc , Transdução de Sinais , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Transfecção , beta-Ciclodextrinas/farmacologia
15.
Neurosci Lett ; 435(1): 11-6, 2008 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-18353552

RESUMO

Ret is a receptor tyrosine kinase for the GDNF family of ligands and plays important roles during nervous system development for cell proliferation, cell migration and neurite growth. Signaling initiated from intracellular tyrosine 1062, by recruitment of several different phosphotyrosine binding (PTB) proteins (i.e. Shc, Frs2 and Dok), is important for these biological effects. By a single amino acid substitution in the PTB domain binding sequence of Ret, we have rewired the receptor such that it preferentially recruits Dok (Ret(Dok+)) with little or no remaining interactions with Shc and Frs2. Ret(Dok+) displays a sustained MAP kinase activation and a loss of Akt signaling compared to Ret(WT). We show that early events after ligand stimulation of Ret(Dok+) include massive formation of fine microspikes that are believed to be priming structures for neurite growth from the cell soma. The Ret(Dok+) receptors relocated in the membrane compartment into focal clusters at the tip of the microspikes, which was associated with Cdc42 activation. These results suggest that engagement of different adaptor proteins by Ret results in very different downstream signaling and functions within neurons and that Dok recruitment leads to a rapid receptor relocation and formation of microspikes.


Assuntos
Diferenciação Celular/fisiologia , Extensões da Superfície Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neuritos/metabolismo , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-ret/metabolismo , Proteínas de Ligação a RNA/metabolismo , Células-Tronco/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Substituição de Aminoácidos/genética , Animais , Células COS , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Extensões da Superfície Celular/ultraestrutura , Chlorocebus aethiops , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Humanos , Ligantes , Sistema de Sinalização das MAP Quinases/fisiologia , Mutação/genética , Neuritos/ultraestrutura , Transporte Proteico/fisiologia , Proteínas Proto-Oncogênicas c-ret/química , Proteínas Proto-Oncogênicas c-ret/genética , Transdução de Sinais/fisiologia , Células-Tronco/ultraestrutura , Proteína cdc42 de Ligação ao GTP/metabolismo
16.
Int J Dent Hyg ; 6(4): 371-5, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19138189

RESUMO

BACKGROUND: Reviewing the literature, no study on the rate of regrowth of tongue coatings after tongue cleaning was found. Therefore, the purpose of this study in young adults was to study the rate of reformation of tongue coatings after mechanical removal. MATERIAL AND METHODS: Thirty-five dental students participated in the present study. Following preparatory study instructions, baseline examinations were carried out followed by 3 days of observation. At baseline, tongue coating scores (prescraping) were obtained followed by tongue scrapings and determination of the wet weights of the coatings. A second tongue coating score was then obtained within 5 min of the first score (immediate post-scraping). The subjects returned for repeated tongue coating scores after 1 and 2 days and for final examination after 3 days, which included both tongue coating scores (prescraping and immediate post-scraping) and determination of the wet weights of the coatings. RESULTS: Prior to scraping the tongue at day 0 (baseline), mean tongue coating amounted to a surface extension of 33% of the entire dorsum of the tongue. Scraping the tongue reduced the score to 9%. On average, tongue coating scores had returned to baseline levels on day 2. The mean wet weights of tongue scrapings at days 0 and 3 were similar and amounted to 0.09 +/- 0.07 and 0.09 +/- 0.06 g, respectively. CONCLUSION: If tongue cleaning is to be recommended, the results of this study in dental students indicate that tongue cleaning should be performed on a daily basis.


Assuntos
Biofilmes , Depósitos Dentários/terapia , Língua/microbiologia , Adulto , Depósitos Dentários/química , Depósitos Dentários/microbiologia , Feminino , Humanos , Masculino , Recidiva , Fatores de Tempo , Língua/patologia , Adulto Jovem
17.
Cell Transplant ; 27(11): 1692-1704, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30261751

RESUMO

Adoptive transfer of alloantigen-specific immunomodulatory cells generated ex vivo with anti-CD80/CD86 mAbs (2D10.4/IT2.2) holds promise for operational tolerance after transplantation. However, good manufacturing practice is required to allow widespread clinical application. Belatacept, a clinically approved cytotoxic T-lymphocyte antigen 4-immunoglobulin that also binds CD80/CD86, could be an alternative agent for 2D10.4/IT2.2. With the goal of generating an optimal cell treatment with clinically approved reagents, we evaluated the donor-specific immunomodulatory effects of belatacept- and 2D10.4/IT2.2-generated immunomodulatory cells. Immunomodulatory cells were generated by coculturing responder human peripheral blood mononuclear cells (PBMCs) (50 × 106 cells) with irradiated donor PBMCs (20 × 106 cells) from eight human leukocyte antigen-mismatched responder-donor pairs in the presence of either 2D10.4/IT2.2 (3 µg/106 cells) or belatacept (40 µg/106 cells). After 14 days of coculture, the frequencies of CD4+ T cells, CD8+ T cells, and natural killer cells as well as interferon gamma (IFN-γ) production in the 2D10.4/IT2.2- and belatacept-treated groups were lower than those in the control group. The percentage of CD19+ B cells was higher in the 2D10.4/IT2.2- and belatacept-treated groups than in the control group. The frequency of CD4+CD25+CD127lowFOXP3+ T cells increased from 4.1±1.0% (preculture) to 7.1±2.6% and 7.3±2.6% (day 14) in the 2D10.4/IT2.2- and belatacept-treated groups, respectively (p<0.05). Concurrently, delta-2 FOXP3 mRNA expression increased significantly. Compared with cells derived from the no-antibody treated control group, cells generated from both the 2D10.4/IT2.2- and belatacept-treated groups produced lower IFN-γ and higher interleukin-10 levels in response to donor-antigens, as detected by enzyme-linked immunospot. Most importantly, 2D10.4/IT2.2- and belatacept-generated cells effectively impeded the proliferative responses of freshly isolated responder PBMCs against donor-antigens. Our results indicate that belatacept-generated donor-specific immunomodulatory cells possess comparable phenotypes and immunomodulatory efficacies to those generated with 2D10.4/IT2.2. We suggest that belatacept could be used for ex vivo generation of clinical grade alloantigen-specific immunomodulatory cells for tolerance induction after transplantation.

18.
Plast Reconstr Surg Glob Open ; 5(1): e1210, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28203510

RESUMO

Facial feminization surgery is a term to describe the surgical alteration of a masculine facial appearance to a more feminine appearance, which is most commonly performed for male-to-female transsexual individuals. To alter the midfacial relations, segmentalized osteotomies were performed in selected patients expanding on the established techniques for facial feminization surgery. All patients underwent a preoperative 3D computerized tomography scan and 3D photography before and after the surgery. The inclusion of the midface in surgery was determined based on the relative projection and angle of the zygomatic body compared with the supraorbital region (the supraorbital region was reduced in all patients). Patients were prospectively followed up by 3D surface photography and 3D computerized tomography scans. Rotation and advancement of the zygomatic region was found to be an effective way to further feminize the midfacial appearance in selected male-to-female transsexual patients. No major surgical complications occurred. Although somewhat technically challenging, we suggest that midface surgery should be considered for feminizing purposes in order for the patient to achieve a long-term favorable result compared with other alternative methods.

19.
Eur J Plast Surg ; 40(3): 223-226, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28603386

RESUMO

BACKGROUND: Few studies have examined the long-term quality of life (QoL) of individuals with gender dysphoria, or how it is affected by treatment. Our aim was to examine the QoL of transgender women undergoing gender reassignment surgery (GRS). METHODS: We performed a prospective cohort study on 190 patients undergoing male-to-female GRS at Karolinska University Hospital between 2003 and 2015. We used the Swedish version of the Short Form-36 Health Survey (SF-36), which measures QoL across eight domains. The questionnaire was distributed to patients pre-operatively, as well as 1, 3, and 5 years post-operatively. The results were compared between the different measure points, as well as between the study group and the general population. RESULTS: On most dimensions of the SF-36 questionnaire, transgender women reported a lower QoL than the general population. The scores of SF-36 showed a non-significant trend to be lower 5 years post-GRS compared to pre-operatively, a decline consistent with that of the general population. Self-perceived health compared to 1 year previously rose in the first post-operative year, after which it declined. CONCLUSIONS: To our knowledge, this is the largest prospective study to follow a group of transgender patients with regards to QoL over continuous temporal measure points. Our results show that transgender women generally have a lower QoL compared to the general population. GRS leads to an improvement in general well-being as a trend but over the long-term, QoL decreases slightly in line with that of the comparison group. Level of evidence: Level III, therapeutic study.

20.
J Plast Reconstr Aesthet Surg ; 70(1): 120-126, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27769603

RESUMO

BACKGROUND: Orbitozygomatic fractures often lead to infraorbital nerve (ION) injury, and affected sensibility is a common long-term complaint within this patient group. We present a long-term follow-up study where the validated von Frey filament system was used for testing ION sensibility. Furthermore, we examined the incidence of persistent nerve injury and whether more complex fractures led to more pronounced ION sensibility disturbances. METHODS: Patients treated for facial fractures involving the orbitozygomatic complex were included and the follow-up time was 3 years or more. Depending on the location and severity of the fractures, the patients were divided into 4 groups. The patients answered a questionnaire before ION sensibility testing with von Frey filaments. RESULTS: Eighty-one patients were examined: 65 males (80%) and 16 females (20%). Examinations were conducted between 3.0 and 7.6 years (mean 4.9 years) after injury. Sixteen patients (20%) had affected and 6 patients (7.4%) had severely affected ION sensibility according to von Frey testing. No statistically significant differences were found in terms of questionnaire score between the groups. There was also no statistically significant correlation between questionnaire results and log von Frey values. Although the effect of groups could not be statistically verified using the log von Frey values, a larger proportion of patients with complex fractures had higher log von Frey values than the other groups. CONCLUSIONS: Patients with complex fractures report more permanent sensory disturbance of the ION after surgery than those with isolated orbitozygomatic fractures, although this could not be verified statistically with von Frey filament testing at several locations. Hence, a validated method for testing facial sensibility such as von Frey filaments, although sensitive, is inadequate to determine all aspects of sensory malfunction after orbitozygomatic fractures. This suggests that the patient's experience of long-term sensation after trauma may not be correlated with objective measures.


Assuntos
Fraturas Orbitárias/complicações , Transtornos de Sensação/epidemiologia , Fraturas Zigomáticas/complicações , Feminino , Seguimentos , Humanos , Incidência , Masculino , Fraturas Orbitárias/cirurgia , Estudos Retrospectivos , Transtornos de Sensação/diagnóstico , Fatores de Tempo , Fraturas Zigomáticas/cirurgia
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