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1.
Vasc Endovascular Surg ; 58(5): 505-511, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38258617

ABSTRACT

INTRODUCTION: We sought to examine midterm results and remodeling effect of false-lumen occlusion treatment using AFX VELA in case of chronic dissection repair. MATERIAL AND METHODS: From June 2019 to May 2022, we performed false lumen occlusion treatment using a modified Candy-Plug technique with AFX VELA on 8 chronic aortic dissection patients with a patent false lumen. We collected operative data, short-term clinical outcomes, mid-term clinical outcomes and imaging test results. We conducted follow-up examinations at postoperative, 6-month and 1-, 2- and 3-year intervals, including contrast-enhanced computed tomography to evaluate the diameter, false lumen thrombosis and any events. RESULTS: The average time from the symptom onset to the thoracic endovascular repair was 81.5 (35-155) months. The aorta showed aneurysmal dilation with an average maximum short-axis diameter of 58.9 (41-91) mm. Two cases needed emergency surgery due to rupture and impending rupture. There were no postoperative deaths. Complete thrombosis within the false lumen was achieved in 6 cases (75%), but 2 cases had incomplete thrombosis, requiring additional treatment. The mean maximum diameter showed a significant decrease at 6 months, 1 year and 2 years postoperatively compared to preoperative measurements (P < .05). CONCLUSION: We showed the results of false lumen occlusion treatment using the AFX VELA cuff. We observed favorable clinical outcomes and remodeling effects. While the long-term durability and efficacy of this technique in aortic remodeling will need to be monitored with further observation, the use of this cuff is considered a reliable approach to false lumen occlusion treatment.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Blood Vessel Prosthesis , Endovascular Procedures , Humans , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Aortic Dissection/physiopathology , Male , Middle Aged , Treatment Outcome , Chronic Disease , Aged , Female , Time Factors , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/instrumentation , Endovascular Procedures/adverse effects , Retrospective Studies , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/physiopathology , Prosthesis Design , Stents , Vascular Remodeling
2.
Cureus ; 15(9): e45205, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37842345

ABSTRACT

Anomalous aortic origin of the coronary artery (AAOCA) is a rare congenital cardiac abnormality. Although AAOCA can cause angina, syncope, palpitations, and sudden cardiac death, most patients remain asymptomatic. A 60-year-old woman experienced occasional chest discomfort. A coronary computed tomography (CT) showed that the right coronary artery (RCA) originated from the left sinus of Valsalva, indicating AAORCA. Exercise myocardial scintigraphy revealed ischemia in the inferior wall. Cardiac catheterization showed stenosis in the ostium of the RCA. Therefore, direct reimplantation of the RCA into the right sinus was performed under cardiopulmonary bypass. The patient recovered uneventfully, postoperatively. Postoperative coronary CT showed no evidence of bending or stenosis in the RCA. Moreover, exercise scintigraphy showed no ischemic changes. The patient was discharged on postoperative day 18 after the resolution of chest discomfort and remained healthy for the following one year. AAORCA is a rare congenital abnormality that could lead to sudden cardiac death. Appropriate imaging studies and surgery should be performed in symptomatic patients with AAORCA who have inter-arterial paths between the ascending aorta and pulmonary artery with right coronary ostial stenosis. Reimplantation of the RCA directly into the right coronary sinus with adequate mobilization of the RCA is a simple procedure that can return the anatomic and biophysiologic status of AAORCA patients to normal and resolve most morphologic abnormalities.

3.
Kyobu Geka ; 76(8): 613-617, 2023 Aug.
Article in Japanese | MEDLINE | ID: mdl-37500549

ABSTRACT

A 78-year-old Japanese male with previous gastric cancer and untreated diabetes mellitus was admitted to hospital for persistent fever and leg edema. Blood culture was positive for Streptococcus angino'sus, and echocardiography showed isolated tricuspid valve infective endocarditis. Infection was controlled with intravenous antibiotics, but surgery was indicated because of persistent severe regurgitation and large vegetation of 15 mm in size. As the tricuspid valve anterior leaflet was extensively damaged, he underwent valve replacement using a bioprosthetic valve. The patient was discharged 25 days postoperatively with additional antibiotics, and he has been free from recurrent endocarditis for 6 months.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Male , Humans , Aged , Tricuspid Valve/diagnostic imaging , Tricuspid Valve/surgery , Endocarditis, Bacterial/diagnostic imaging , Endocarditis, Bacterial/surgery , Endocarditis/surgery , Anti-Bacterial Agents , Risk Factors
5.
Ann Thorac Surg ; 111(5): e315-e317, 2021 05.
Article in English | MEDLINE | ID: mdl-33144111

ABSTRACT

Phosphoglycerides are the major lipid component of all cell membranes. Phosphoglyceride crystal deposition disease (PCDD) is defined as the deposition of phosphoglyceride crystals and is considered a lipid metabolic disorder. It predominantly involves injured soft tissues, ultimately forming foreign body granulomas. We present a case of complete resection of PCDD in a 48-year-old woman, in whom the PCDD originated from a myocardial wound created at the time of surgical repair of a ventricular septal defect 40 years ago. We underscore that familiarity with this disease entity will help to stimulate accurate diagnosis and timely treatment.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Glycerophospholipids/metabolism , Granuloma, Foreign-Body/surgery , Heart Ventricles/surgery , Myocardium/metabolism , Postoperative Complications , Female , Granuloma, Foreign-Body/etiology , Granuloma, Foreign-Body/metabolism , Heart Ventricles/diagnostic imaging , Heart Ventricles/metabolism , Humans , Middle Aged , Myocardium/pathology , Reoperation
6.
Gen Thorac Cardiovasc Surg ; 69(3): 610-613, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33068257

ABSTRACT

A 68-year-old woman was referred to our hospital because of ruptured severely calcified thoracic aortic aneurysm on chest computed tomography. She was diagnosed with Takayasu's arteritis ~ 30 years ago and was treated with oral steroids daily. We performed total arch repair using uncalcified ascending aorta with open stent-grafting technique, and additional thoracic endovascular aortic repair immediately after open surgery to avoid type Ib endoleak. Continuous hemodiafiltration was needed owing to postoperative transient acute renal failure, following which the patient recovered. She was referred to another hospital 50 days after surgery. A single-stage hybrid procedure for ruptured severe calcified thoracic aortic aneurysm caused by Takayasu's arteritis was required in this case.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Rupture , Takayasu Arteritis , Aged , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/etiology , Aortic Aneurysm, Thoracic/surgery , Aortic Rupture/diagnostic imaging , Aortic Rupture/etiology , Aortic Rupture/surgery , Female , Humans , Stents , Takayasu Arteritis/complications , Takayasu Arteritis/diagnostic imaging , Takayasu Arteritis/surgery
7.
Sci Adv ; 6(48)2020 11.
Article in English | MEDLINE | ID: mdl-33239290

ABSTRACT

Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (Fbln4-/- ) have disrupted collagen and elastin fibers and die shortly after birth from aortic and diaphragmatic rupture. The function of fibulin-4 in ECM assembly, however, remains elusive. Here, we show that fibulin-4 is required for the activity of lysyl oxidase (LOX), a copper-containing enzyme that catalyzes the covalent cross-linking of elastin and collagen. LOX produced by Fbln4-/- cells had lower activity than LOX produced by wild-type cells due to the absence of lysine tyrosyl quinone (LTQ), a unique cofactor required for LOX activity. Our studies showed that fibulin-4 is required for copper ion transfer from the copper transporter ATP7A to LOX in the trans-Golgi network (TGN), which is a necessary step for LTQ formation. These results uncover a pivotal role for fibulin-4 in the activation of LOX and, hence, in ECM assembly.


Subject(s)
Elastin , Protein-Lysine 6-Oxidase , Animals , Collagen/metabolism , Copper , Elastin/metabolism , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Mice , Protein-Lysine 6-Oxidase/genetics , Protein-Lysine 6-Oxidase/metabolism
8.
iScience ; 19: 559-571, 2019 Sep 27.
Article in English | MEDLINE | ID: mdl-31445376

ABSTRACT

RECK in neural precursor cells (NPCs) was previously found to support Notch-dependent neurogenesis in mice. On the other hand, recent studies implicate RECK in endothelial cells (ECs) in WNT7-triggered canonical WNT signaling essential for brain angiogenesis. Here we report that RECK in NPCs is also critical for brain angiogenesis. When Reck is inactivated in Foxg1-positive NPCs, mice die shortly after birth with hemorrhage in the forebrain, with angiogenic sprouts stalling at the periphery and forming abnormal aggregates reminiscent of those in EC-selective Reck knockout mice and Wnt7a/b-deficient mice. The hemorrhage can be pharmacologically suppressed by lithium chloride. An effect of RECK in WNT7-producing cells to enhance canonical WNT-signaling in reporter cells is detectable in mixed culture but not with conditioned medium. Our findings suggest that NPC-expressed RECK has a non-cell-autonomous function to promote forebrain angiogenesis through contact-dependent enhancement of WNT signaling in ECs, implying possible involvement of RECK in neurovascular coupling.

10.
Cad. Bras. Ter. Ocup ; 26(4): 952-959, Oct.-Dec. 2018.
Article in English | LILACS | ID: biblio-984120

ABSTRACT

Abstract Academic research in social occupational therapy has presented an interface with the theme of Africa, from a cultural diversity perspective to emphasize the need to include new forms of research. This study proposes a panorama of the academic research in Brazil in the context of occupational therapy in different interfaces: human mobility, human rights, religiosity, children's cultures, gender, etc. This multiplicity reveals a perspective of appreciation of African themes. In this context, the concept of cultural diversity is presented as a perspective to expand the discussion of new views, decentralization of technical knowledge and new dialogues required for researchers and professionals. It was proposed to think, experience and produce new forms of research, themes and subjects that cover different ways of life, problems and issues that dialogue with the transformations of the contemporary world, which are also implications of social occupational therapy. Moreover, along with the ethnography and its research tools, one can think of multiple, unique and rich ways to do research. These aspects, in the present work, make interconnections with the diverse productions on Africa and occupational therapy, revealing the potentiality of these elements for the profession.


Resumo A pesquisa acadêmica em terapia ocupacional social tem apresentado interface com a temática da África, numa perspectiva da diversidade cultural, para, então, enfatizar a necessidade de abarcar novas formas de pesquisas. Propomos um panorama da pesquisa acadêmica no Brasil no contexto da terapia ocupacional em diferentes interfaces: mobilidade humana, direitos humanos, religiosidade, culturas infantis, gênero etc. Essa multiplicidade revela uma perspectiva de valorização dos temas africanos. A partir daí, apresentamos o conceito de diversidade cultural enquanto perspectiva para a discussão de novos olhares, descentramentos do saber técnico e produção de novos diálogos necessários aos pesquisadores e profissionais. Propõe-se pensar, vivenciar e produzir novas formas de pesquisas, temáticas e assuntos que abarquem diferentes modos de vida, problemáticas e questões que dialoguem com as transformações do mundo contemporâneo e que também são implicações da terapia ocupacional social. Para tal, com a etnografia e as suas ferramentas de pesquisa, pode-se pensar em modos múltiplos, singulares e enriquecedores de se fazer pesquisa, modos esses que no presente trabalho fazem interconexões com as diversas produções sobre África e terapia ocupacional, revelando a potencialidade desses elementos para a profissão.

11.
Gen Thorac Cardiovasc Surg ; 66(4): 235-238, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28589481

ABSTRACT

We report a case of isolated pulmonary valve endocarditis in a 47-year-old woman without predisposing factors. She had episodes of low-grade fever and non-productive cough and was initially diagnosed with bacterial pneumonia. With antibiotic treatment, her condition improved transiently, but she had repeated respiratory events. Forty days after her first visit, she complained of severe dyspnea. Echocardiography revealed a large vegetation adhering to the pulmonary valve and she was diagnosed with isolated pulmonary valve endocarditis. Surgical treatment was selected because antibiotic treatment was not effective. The main pulmonary artery was transected above the annulus and the infected valve was excised. To avoid contact of the prosthetic valve with the infected pulmonary annulus, a stentless bioprosthesis was interposed between the transected parts of the pulmonary trunk. Two years after the surgery, the patient is stable with no sign of infection.


Subject(s)
Endocarditis, Bacterial/surgery , Heart Valve Diseases/surgery , Pulmonary Valve/surgery , Anti-Bacterial Agents/therapeutic use , Bioprosthesis , Echocardiography , Endocarditis, Bacterial/diagnostic imaging , Female , Heart Valve Diseases/diagnostic imaging , Humans , Middle Aged , Pulmonary Artery/surgery , Pulmonary Valve/diagnostic imaging , Risk Factors
12.
Cad. Ter. Ocup. UFSCar (Impr.) ; 24(4): [859-868], out.-dez. 2016.
Article in Portuguese | LILACS | ID: biblio-832142

ABSTRACT

Discutem-se os exercícios etnográficos − realizados em propostas do Projeto Metuia/USP, entre 2007 e 2013 − como atividade capaz de potencializar o reconhecimento do saber composto, plural e, por vezes, contraditório, mas produzido criativamente no fazer intelectual e social, na interação entre estudantes, terapeutas ocupacionais, pesquisadores e pessoas em situação de rua. Parte-se da necessidade de se desenvolver a compreensão sobre as atividades significativas de artistas que trabalham nos espaços públicos da cidade de São Paulo, pois persiste uma pluralidade de significados que a rua adquire em meio a disputas de interesses e tensões culturais, mas, também, de interconexões e criatividade. A vida itinerante e as características dos espaços de sociabilidade, aliadas às reflexões da antropologia urbana e da pesquisa etnográfica, favoreceram o ensino teórico-prático em ações territoriais dialógicas da terapia ocupacional social. Este artigo é resultado de reflexões construídas a partir da pesquisa Circuitos e práticas religiosas nas trajetórias de vida de adultos em situação de rua na cidade de São Paulo, associado ao projeto de extensão universitária vinculada ao Projeto Metuia/Terapia Ocupacional/USP, denominado Ponto de encontro e cultura: redes sociais, cultura e terapia ocupacional social. Conclui-se, por um lado, que há necessidade da reflexão renovada sobre o lugar do terapeuta ocupacional, considerando as assimetrias das relações na construção do conhecimento. Por outro lado, indica-se que as atividades produzidas em relações dialógicas adquirem sentidos partilhados apenas quando desenhadas na experiência da diferença, em propostas coerentes com sua plasticidade própria e no bojo de contextos sociais e culturais específicos.


Ethnographic exercises are discussed - as proposed by the Metuia Project/ USP between 2007 and 2013 - as an activity able to enhance the recognition of the compound, plural and sometimes contradictory knowledge, but produced creatively in the intellectual and social do, in the interaction among students, occupational therapists, researchers and homeless people. It starts from the need to develop an understanding of the significant activities of artists working in the public spaces in São Paulo, as it persists as a plurality of meanings that the street acquires amid disputes of interests and cultural tensions, but also interconnections and creativity. The itinerant life and social areas' characteristics, combined with reflections of urban anthropology and ethnographic research favored the theoretical and practical teaching in dialogic territorial shares of social occupational therapy. This article is the result of reflections built from the research Circuits and religious practices in life trajectories of adult homeless people in city of São Paulo, associated with university extension project linked to Metuia Project/USP, called Point meeting and culture: social networks, culture and social occupational therapy. In conclusion, on the one hand, there is need for renewed reflection about the occupational therapist's place, considering the asymmetries of the relations in the construction of knowledge. On the other hand, it indicates that the produced activities, necessarily, in dialogical relations, only share meanings when inserted into the experience of the difference in consistent proposals with its own plasticity and in the middle of specific social and cultural contexts.

13.
Sci Rep ; 6: 29174, 2016 07 07.
Article in English | MEDLINE | ID: mdl-27383066

ABSTRACT

The BMAL1 and CLOCK heterodimer in the mammalian circadian transcriptional complex is thought to be repressed by PER2 and CRY1 via direct interactions. We recently reported that PER2 is largely cytosolic in Pml(-/-) cells and did not co-immunoprecipitate (co-IP) with BMAL1 or CLOCK. Here, using multi-color immunofluorescence (IF) staining and co-IP, we observed a nuclear distribution of BMAL1 and a predominately cytosolic distribution of CLOCK in Pml(-/-) MEF. In the presence of WT PML, PER2 co-localized with BMAL1 in the nucleus. In Pml(-/-) MEF transfected with mutant K487R PML, we observed that BMAL1 and PER2 co-localized with K487R PML in the cytosol. Furthermore, cytosolic CLOCK and PER2 displayed a significant non-overlapping IF staining pattern. In Bmal1(-/-) MEF, CLOCK was primarily cytosolic while PML and PER2 were nuclear. Together, our studies suggest that PML mediates the binding of PER2 to BMAL1 in the BMAL1/CLOCK heterodimer and is an important component in the organization of a functional clock complex in the nucleus. Our studies also support that BMAL1 is important for CLOCK nuclear localization.


Subject(s)
ARNTL Transcription Factors/metabolism , CLOCK Proteins/metabolism , Circadian Clocks , Period Circadian Proteins/metabolism , Promyelocytic Leukemia Protein/metabolism , Animals , Cell Nucleus/metabolism , Fluorescent Antibody Technique , Humans , Immunoprecipitation , Mice , Models, Biological , Protein Binding
14.
Ann Vasc Dis ; 9(1): 70-2, 2016.
Article in English | MEDLINE | ID: mdl-27087879

ABSTRACT

Surgical treatment of an infected abdominal aortic aneurysm (IAAA) is difficult and the ideal graft material is a subject of debate. A 60-year-old man with untreated diabetes mellitus was referred to our hospital presenting with fever and left lower abdominal pain. The patient was diagnosed with an IAAA by blood culture and computed tomography. We treated the patient surgically for the IAAA using bilateral reversed superficial femoral veins which were shaped into a bifurcated graft. No signs of recurrent infection or aneurysmal dilation were observed for 3 years after the procedure.

15.
Cad. Ter. Ocup. UFSCar (Impr.) ; 24(1): [91-103], jan.-mar. 2016.
Article in Portuguese | LILACS | ID: biblio-2402

ABSTRACT

O objetivo do presente artigo é problematizar a necessidade de revisão da formação e da ação profissional, no contexto da terapia ocupacional social, diante do fenômeno crescente da migração internacional, particularmente na atual construção da política municipal para populações imigrantes na cidade de São Paulo, SP. Metodologicamente, a discussão articula-se em três eixos complementares de resultados de análise a partir de pesquisa documental acompanhada de estudo de campo, visitas, participação em reuniões, fóruns interinstitucionais, audiências públicas, debates temáticos, além de revisão da literatura. No primeiro eixo de análise, contextualiza-se a legislação vigente no Brasil, a construção da política de migração em âmbito municipal e as articulações da sociedade civil frente à mobilidade humana, compreendida como direito fundamental. No segundo, discutem-se serviços de atenção a pessoas, famílias e grupos em situação migratória no município de São Paulo, SP. Finalmente, no terceiro eixo, discutem-se os desdobramentos da cultura na terapia ocupacional social para a ação profissional e formação no campo da mobilidade humana. Como resultado, observou-se que esse panorama atual coloca novos desafios profissionais, obrigando o terapeuta ocupacional a rever sua posição técnico-política diante novas realidades da contemporaneidade.


This article aims to discuss the need to revise education and professional action, in the context of social occupational therapy, facing the growing phenomenon of international migration, especially in the current construction of the municipal policy for immigrant populations in São Paulo, SP. The discussion is methodologically structured into three complementary lines of analysis results from documentary research accompanied by field study, visits, participations in meetings, inter-institutional forums, public hearings, thematic debates, in addition to literature review. In the first analysis axis, we discuss the current legislation in Brazil, the construction of migration policy at the municipal level and civil society articulations about human mobility, understood as a fundamental right. In the second, we discuss people care services, families and groups in migratory situation in São Paulo, SP. Finally, on the third axis, we discuss the cultural developments in social occupational therapy for professional action and training in the field of human mobility. As a result it was observed that the current panorama poses new professional challenges, forcing the occupational therapist to review its technical-political position face to the new realities of the contemporary world.

16.
Surg Case Rep ; 1(1): 83, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26943412

ABSTRACT

We report the case of a 55-year-old man who initially visited the emergency department of our hospital owing to fever, headache, and neck stiffness. He was diagnosed with meningitis because cerebrospinal fluid culture was positive for Streptococcus pneumoniae. After intravenous antibiotic treatment, the patient's condition returned to normal. On hospital day 20, he complained of lumbar pain with abdominal distension. Because an abdominal computed tomography (CT) scan showed a small sacciform infrarenal abdominal aortic aneurysm, an infected aneurysm was suspected. However, cerebrospinal fluid and blood cultures were negative for S. pneumoniae. Seven days later, a second abdominal CT was performed that showed rapid expansion of the sacciform infrarenal abdominal aortic aneurysm. The patient was diagnosed with an infected abdominal aortic aneurysm and underwent surgery for resection of the aneurysm and in situ reconstruction with a rifampicin-soaked vascular prosthesis. Although blood and aneurysmal tissue cultures were negative for S. pneumoniae, the autolysin (lytA) gene, which is the target gene of S. pneumoniae, was detected in the abdominal aortic wall by using polymerase chain reaction (PCR). Therefore, appropriate molecular diagnostic techniques can be used for the rapid detection of pathogens. An accurate diagnosis can be used to direct postoperative antibiotic therapy.

17.
Nat Commun ; 4: 2444, 2013.
Article in English | MEDLINE | ID: mdl-24051492

ABSTRACT

The mechanistic interconnectivity between circadian regulation and the genotoxic stress response remains poorly understood. Here we show that the expression of Period 2 (Per2), a circadian regulator, is directly regulated by p53 binding to a response element in the Per2 promoter. This p53 response element is evolutionarily conserved and overlaps with the E-Box element critical for BMAL1/CLOCK binding and its transcriptional activation of Per2 expression. Our studies reveal that p53 blocks BMAL1/CLOCK binding to the Per2 promoter, leading to repression of Per2 expression. In the suprachiasmatic nucleus (SCN), p53 expression and its binding to the Per2 promoter are under circadian control. Per2 expression in the SCN is altered by p53 deficiency or stabilization of p53 by Nutlin-3. Behaviourally, p53⁻/⁻ mice have a shorter period length that lacks stability, and they exhibit impaired photo-entrainment to a light pulse under a free-running state. Our studies demonstrate that p53 modulates mouse circadian behaviour.


Subject(s)
Circadian Clocks/genetics , Circadian Rhythm/genetics , Period Circadian Proteins/genetics , Suprachiasmatic Nucleus/physiology , Tumor Suppressor Protein p53/genetics , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Animals , Behavior, Animal , Binding Sites , CLOCK Proteins/genetics , CLOCK Proteins/metabolism , Gene Expression Regulation , Imidazoles/metabolism , Imidazoles/pharmacology , Light , Mice , Mice, Knockout , Period Circadian Proteins/metabolism , Piperazines/metabolism , Piperazines/pharmacology , Promoter Regions, Genetic , Protein Binding , Protein Stability/drug effects , Signal Transduction , Tumor Suppressor Protein p53/deficiency , Visual Perception
18.
J Circadian Rhythms ; 11(1): 9, 2013 Aug 28.
Article in English | MEDLINE | ID: mdl-23984853

ABSTRACT

BACKGROUND: Our recent studies demonstrate that the murine homolog of the human tumor suppressor promyelocytic leukemia (PML) regulates circadian behavior of mice. To further gather insight into PML's contribution to circadian behavior, we generated two strains of mice deficient in one of the two period (Per) genes and the PML gene, with Per1-/-/Pml-/- and Per2-/-/Pml-/- genotypes. RESULTS: Here we report the circadian behavior of these mice based on wheel-running behavioral analysis. In a free-running environment, the Per1-/-/Pml-/- mice maintained circadian rhythm but displayed a significantly shorter period of 22.2 h. In addition, these mice displayed significantly enhanced phase response to a light pulse given at zeitgeber time (ZT) 14 and 22. The Per2-/-/Pml-/- mice lose persistent rhythm when in a free-running environment, as also the case for Per2-/- mice. A transient post-light pulse rhythm seen in the arrhythmic Per2-/- mice was less apparent in Per2-/-/Pml-/- mice. Both the Per1-/-/Pml-/- and Per2-/-/Pml-/- mice displayed a more advanced phase angle of entrainment activity during light-dark cycles than the single gene deficient mice. CONCLUSIONS: Beyond merely regulating PER1 and PER2, the current behavioral studies suggest PML has additional roles in mouse circadian behavior.

19.
EMBO J ; 31(6): 1427-39, 2012 Mar 21.
Article in English | MEDLINE | ID: mdl-22274616

ABSTRACT

Studies have suggested that the clock regulator PER2 is a tumour suppressor. A cancer network involving PER2 raises the possibility that some tumour suppressors are directly involved in the mammalian clock. Here, we show that the tumour suppressor promyelocytic leukaemia (PML) protein is a circadian clock regulator and can physically interact with PER2. In the suprachiasmatic nucleus (SCN), PML expression and PML-PER2 interaction are under clock control. Loss of PML disrupts and dampens the expression of clock regulators Per2, Per1, Cry1, Bmal1 and Npas2. In the presence of PML and PER2, BMAL1/CLOCK-mediated transcription is enhanced. In Pml(-/-) SCN and mouse embryo fibroblast cells, the cellular distribution of PER2 is primarily perinuclear/cytoplasmic. PML is acetylated at K487 and its deacetylation by SIRT1 promotes PML control of PER2 nuclear localization. The circadian period of Pml(-/-) mice displays reduced precision and stability consistent with PML having a role in the mammalian clock mechanism.


Subject(s)
Circadian Clocks/genetics , Circadian Rhythm/genetics , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Period Circadian Proteins/genetics , Period Circadian Proteins/metabolism , Suprachiasmatic Nucleus/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Acetylation , Animals , CLOCK Proteins/genetics , CLOCK Proteins/metabolism , Cell Line , Cell Nucleus/genetics , Cell Nucleus/metabolism , Circadian Clocks/physiology , Cytoplasm/metabolism , Fibroblasts/metabolism , Male , Mice , Promyelocytic Leukemia Protein , Sirtuin 1/metabolism , Transcription, Genetic/genetics
20.
Physiol Genomics ; 43(7): 325-45, 2011 Apr 12.
Article in English | MEDLINE | ID: mdl-21224422

ABSTRACT

There is currently much interest in clinical applications of therapeutic hypothermia. Hypothermia can be a consequence of hypometabolism. We have recently established a procedure for the induction of a reversible deep hypometabolic state in mice using 5'-adenosine monophosphate (5'-AMP) in conjunction with moderate ambient temperature. The current study aims at investigating the impact of this technology at the gene expression level in a major metabolic organ, the liver. Our findings reveal that expression levels of the majority of genes in liver are not significantly altered by deep hypometabolism. However, among those affected by hypometabolism, more genes are differentially upregulated than downregulated both in a deep hypometabolic state and in the early arousal state. These altered gene expression levels during 5'-AMP induced hypometabolism are largely restored to normal levels within 2 days of the treatment. Our data also suggest that temporal control of circadian genes is largely stalled during deep hypometabolism.


Subject(s)
Adenosine Monophosphate/pharmacology , Liver/drug effects , Liver/metabolism , Animals , Female , Hypothermia/chemically induced , Hypothermia/metabolism , Mice , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction , Suprachiasmatic Nucleus/drug effects , Suprachiasmatic Nucleus/metabolism
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