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2.
Biochim Biophys Acta ; 1771(2): 139-46, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17234448

RESUMO

9-hydroxystearic acid (9-HSA) belongs to the class of endogenous lipid peroxidation by-products that greatly diminish in tumors, causing as a consequence the loss of one of the control mechanisms on cell division. We have previously shown that 9-HSA controls cell growth and differentiation by inhibiting histone deacetylase 1 (HDAC1) activity. In this paper our attention has not only been focused on HDAC1 inhibition but also on the hyperacetylation of other substrates such as p53, that is involved in inducing cell cycle arrest and/or apoptosis, and whose activity and stability are known to be regulated by posttranslational modifications, particularly by acetylation at the C-terminus region. 9-HSA administration to U2OS, an osteosarcoma cell line p53 wt, induces a growth arrest of the cells in G2/M and apoptosis via a mitochondrial pathway. In particular hyperacetylation of p53 induced by the HDAC1 inhibitory activity of 9-HSA has been demonstrated to increase Bax synthesis both at the transcriptional and the translational level. The subsequent translocation of Bax to the mitochondria is associated to a significant increase in caspase 9 activity. Our data demonstrate that the effects of 9-HSA on U2OS correlate with posttranslational modifications of p53.


Assuntos
Osteossarcoma/metabolismo , Transdução de Sinais , Ácidos Esteáricos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Humanos , Regiões Promotoras Genéticas , Ácidos Esteáricos/toxicidade , Proteína X Associada a bcl-2/genética
3.
Biochem Biophys Res Commun ; 314(1): 138-42, 2004 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-14715257

RESUMO

Growing evidence supports the critical role of lipid peroxidation products in the control of cell proliferation. In previous studies we demonstrated the efficient restriction of the proliferation rate in several cell lines resulting from the in vitro treatment with endogenous lipid polar components of cell membranes. Among these, 9-hydroxystearic acid (9-HSA), a primary intermediate of lipid peroxidation, induced a significant arrest in G0/G1 in HT29 colon cancer cells. In response to 9-HSA treatment of HT29 we observed cell growth arrest and increase in p21(WAF1) expression both at the transcriptional and the translational levels. Growth of p21(WAF1)-deleted HCT116 human colon carcinoma cells was not inhibited by 9-HSA. We present evidence that p21(WAF1) is required for 9-HSA mediated growth arrest in human colon carcinoma cells.


Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ciclinas/metabolismo , Ácidos Esteáricos/metabolismo , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Linhagem Celular Tumoral/patologia , Inibidor de Quinase Dependente de Ciclina p21 , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Ácidos Esteáricos/farmacologia , Regulação para Cima/efeitos dos fármacos
5.
Gene ; 273(2): 173-80, 2001 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-11595163

RESUMO

P21(Waf1/Cip1/Sid1) is a critical component of biomolecular pathways leading to the G(1) arrest evoked in response to DNA damage, growth arrest signals and differentiation commitment. It belongs to the Cip/Kip class of cyclin-dependent kinase inhibitors and is at least partly regulated by p53. P21(Waf1/Cip1/Sid1) functional inactivation possibly resulting from mutations of the gene itself or, more likely, from p53 mutations may be critical for either the cell fate following DNA-damaging insults or clonal evolution toward malignancy. In the study presented here we describe a competitive polymerase chain reaction (PCR) strategy whose sensitivity and reproducibility enable us to attain a precise quantitation of p21(Waf1/Cip1/Sid1) expression levels in hematopoietic progenitors, the cell compartment which mostly suffers from the side effects of genotoxic drugs in use for cancer cure. The strategy was set in the M07 factor-dependent hematopoietic progenitor cell line. We confirmed that its p21(waf1/cip1/sid1) constitutive expression level is very low and up-modulated by DNA-damaging agents: ionizing radiations and ultraviolet light. Gene up-modulation resulted in checkpoint activation and, in particular, in a significant G(1) arrest, required for either the repair of damaged DNA sequences or apoptotic cell death. Our competitive PCR strategy was further validated in CD34(+) purified hematopoietic progenitors from healthy donors mobilized into the peripheral blood by granulocyte colony-stimulating factor and intended for allogeneic bone marrow transplantation. The constitutive p21(WAF1/CIP1/SID1) expression levels, measured in three separate harvests, were very low and no significant differences were apparent. Our results support the use of a competitive PCR strategy as a useful tool for clinical purposes, to assess the individual biomolecular response of early hematopoietic progenitors to antiblastic drugs.


Assuntos
Ciclinas/genética , Células-Tronco Hematopoéticas/metabolismo , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Divisão Celular/genética , Divisão Celular/efeitos da radiação , Inibidor de Quinase Dependente de Ciclina p21 , Reparo do DNA , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos da radiação , Humanos , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
6.
Haematologica ; 86(2): 167-73, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11224486

RESUMO

BACKGROUND AND OBJECTIVES: The chimeric product of the bcr-abl rearranged gene is critical in the pathogenesis of chronic myeloid leukemia (CML), yet its role in the progression of the disease remains unclear. There is some evidence that increased bcr-abl expression levels, possibly due to gene amplification, precede the clonal evolution of CML hematopoietic progenitors toward a fully transformed phenotype and might be involved in their resistance to interferon-alpha or tyrosine kinase inhibitors. DESIGN AND METHODS: To quantify the bcr-abl gene both at the genomic and at the transcriptional levels we developed a competitive polymerase chain reaction (PCR) strategy. The competitive PCR technique is based upon the co-amplification of the sample template (target) together with increasing amounts of a DNA fragment (competitor) sharing with the target the primer recognition sites, but differing in size. We constructed a competitor for the quantification of both b2a2 and b3a2 alternative splicing forms of the bcr-abl chimera and established the accuracy and reproducibility of our competitive strategy in a clone of the murine 32DG hematopoietic cell line (32D LG7), which bears a stable integration of a single copy of p210 bcr-abl fusion gene. We utilized this technique to follow, over a period of 200 days, the fusion gene copy numbers and transcription rates in several p210 bcr-abl-transduced 32D cell clones, an experimental condition mimicking the evolution of CML myeloid progenitors in vivo. RESULTS: Our results are consistent with p210 bcr-abl overexpression but not gene amplification associated with their clonal evolution. Increased p210 bcr-abl transcription rate is associated with the abrogation of radiation-induced apoptotic cell death, suggesting a role for the chimeric gene expression level in cell life expectancy after a genotoxic insult. INTERPRETATION AND CONCLUSIONS: We conclude that the assessment of gene amplification and expression might serve to improve prognostic classification and follow-up of CML patients.


Assuntos
Amplificação de Genes/genética , Genes abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Reação em Cadeia da Polimerase/métodos , Processamento Alternativo , Animais , Linhagem Celular , Transformação Celular Neoplásica/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/etiologia , Camundongos , Células Progenitoras Mieloides/citologia , Reação em Cadeia da Polimerase/normas
7.
Appl Opt ; 37(21): 4656-62, 1998 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-18285922

RESUMO

We present the mechanical and actuator design of an adaptive secondary mirror that matches the optical requirements of the active and adaptive corrections. Conceived for the particular implementation for the 6.5-m conversion of the multiple-mirror telescope, with small variations of the input parameters this study is suitable for applications for telescopes of the same class. We found that a three-layer structure, i.e., a thin deformable shell, a thick reference plate, and a third plate that acts as actuator support and heat sink, is able to provide the required mechanical stability and actuator density. We also found that a simple electromagnetic actuator can be used. This actuator, when optimized, will dissipate a typical power of a few tenths of watts.

9.
Obes Surg ; 3(2): 175-177, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-10757916

RESUMO

Wernicke-Korsakoff disease with sensory-motor neuropathy was diagnosed in three out of a series of 1,663 patients (0.18%), with onset 2, 3 and 5 months after biliopancreatic diversion. Precipitating factors were vomiting, minimal food intake, anorexia, rapid weight loss, and glucose-containing intravenous feeding. Recovery was partial in two and complete in one of the patients. In the early postop, prophylactic thiamine should be given to the patients with excessively limited eating capacity. Larger doses of thiamine should be instituted parenterally either in the case of suspected Wernicke-Korsakoff encephalopathy or before starting feeding for protein malnutrition.

10.
Pathologica ; 83(1085): 351-8, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1923635

RESUMO

The authors have analysed the data of the literature to identify the cases of normotensive hydrocephalus that underwent surgery and then died after the operation; some of these patients died over varying periods of time after the operation and the death was due to accidents. It seems that the anatomopathological lesions are less important in cases that benefited from the operation compared with cases that did not present perceptable clinical variations. The authors report the anatomopathological data of four personal cases which, from the clinical point of view, presented the dementia symptom associated in varying degrees to other neurological symptoms such as disturbances of the gait and of the sphincters functions (Adams' triad). All four subjects presented dilatation of the cerebral ventricles without cortical atrophy. From the histological point of view, there was: exfoliation of the ependyma, subependymal gliosis, demyelination of the white periventricular matter and spongiosis; there were no lesions of the meninges, of the cerebral cortex, no vascular alterations, except for those due to age, or stenosis of the aqueduct. The cause of the ventricular dilatation that was responsible for the clinical symptoms was not clear from the histological examination; the value and the significance of the histopathological data obtained and from the data available from the review of the literature are discussed and they point out the fact that many of the lesions encountered seem to be the consequence rather than the cause of the hydrocephalus.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Encéfalo/patologia , Demência/patologia , Hidrocefalia de Pressão Normal/complicações , Idoso , Demência/etiologia , Humanos , Hidrocefalia de Pressão Normal/patologia
11.
Ital J Neurol Sci ; 11(1): 43-7, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2332325

RESUMO

86 patients suffering from various senile and presenile degenerative diseases were studied using scinticisternography with In111-DTPA. Flow reversal and delayed clearance were observed in 62 of these patients. These alterations, possibly related to the cerebrospinal fluid dynamics, show the aspecificity of the SC picture. The SC picture does not seem to be correlated to the clinical signs.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Demência/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Demência/líquido cefalorraquidiano , Demência/diagnóstico , Humanos , Pessoa de Meia-Idade , Ácido Pentético
12.
Eur Neurol ; 30(4): 186-8, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2209671

RESUMO

Epilepsy is a rare but possible manifestation of thyrotoxicosis. The patient reported here developed recurrent, generalized and focal seizures, as presenting symptoms of a thyrotoxic encephalopathy. Intercritic EEG records showed triphasic waves. Seizures and signs of encephalopathy disappeared and the EEG reverted to normal only after treatment of the thyroid hyperfunction. It is concluded that thyroid function should be evaluated in cases of otherwise unexplained encephalopathy with untreatable seizures and triphasic waves.


Assuntos
Encefalopatias/etiologia , Convulsões/etiologia , Tireotoxicose/complicações , Adulto , Encefalopatias/fisiopatologia , Eletroencefalografia , Humanos , Masculino , Recidiva , Convulsões/fisiopatologia
14.
Ital J Neurol Sci ; 9(4): 369-73, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3220713

RESUMO

To complete our bibliographic review of spinal cord softenings, we now discuss the clinical and pathological findings in the cases of known or probable cause. Comparison of the diagnostic groups yields some differences in respect of sex, age and mode of onset, survival and extent of the anatomical lesion. Further differences, especially in age at onset, clinical pattern and lesion site, emerge from a comparison of these cases of known or probable cause with those whose cause is not apparent.


Assuntos
Doenças da Medula Espinal/patologia , Medula Espinal/patologia , Idoso , Doença das Coronárias/complicações , Doença das Coronárias/patologia , Complicações do Diabetes , Diabetes Mellitus/patologia , Embolia/complicações , Embolia/patologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/patologia , Masculino , Doenças da Medula Espinal/etiologia , Sífilis/complicações , Sífilis/patologia
15.
Eur Neurol ; 28(4): 194-8, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3046947

RESUMO

A case of ischemic myelopathy which was marked by two clinical episodes, separated by a 4-month interval and affecting the same level of the spinal cord, is reported. A wide-ranging search through the literature shows that the recurrent type of ischemic vascular myelopathy is very rare.


Assuntos
Atrofia Muscular Espinal/fisiopatologia , Medula Espinal/patologia , Idoso , Feminino , Humanos , Atrofia Muscular Espinal/patologia , Recidiva , Medula Espinal/irrigação sanguínea
16.
Ital J Neurol Sci ; 8(5): 487-98, 1987 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3323128

RESUMO

311 cases of spinal cord softening, were selected for review. The following points emerged from this study: 1) spinal cord softening is a rare occurrence; 2) while formerly syphilis was the most frequent cause, recently reports of cases secondary to aortic disease or to embolism with diffuse signs of arteriosclerosis and circulatory failure pointing to a different pathogenesis have become more frequent; 3) the site of softening rarely corresponds to the vascular spinal territories as defined by the anatomists, from which it may be argued that often several arterial territories may be involved simultaneously or, alternatively, that the arterial territories are not so rigidly defined as anatomical research has led us to suppose; 4) the few cases of multiple vascular lesions show that, as happens in the brain, the cord may be damaged contemporaneously or successively in several areas.


Assuntos
Isquemia/patologia , Doenças da Medula Espinal/patologia , Medula Espinal/irrigação sanguínea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemorragia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Medula Espinal/patologia , Doenças da Medula Espinal/etiologia
17.
Ital J Neurol Sci ; 8(4): 357-62, 1987 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3679786

RESUMO

An EMG analysis of motor control was performed in 4 patients with unilateral choreic movements of sudden onset, 3 of whom presented CT scan evidence of lacunar infarcts involving the contralateral striatum. The choreic dyskinesias were correlated with EMG bursts of variable duration occurring with a random order of activation. Ballistic elbow flexion movements were performed with a normal triphasic EMG pattern, but both size and duration of the first agonist burst were increased on the affected side. Abnormalities of cerebral somatosensory evoked responses were observed in 3 patients on stimulation of the side with choreic movements.


Assuntos
Transtornos Cerebrovasculares/fisiopatologia , Coreia/fisiopatologia , Eletromiografia , Hipertensão/fisiopatologia , Neurônios Motores/fisiologia , Músculos/inervação , Idoso , Gânglios da Base/fisiopatologia , Infarto Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Eletroencefalografia , Potenciais Somatossensoriais Evocados , Feminino , Humanos , Masculino , Destreza Motora/fisiologia
19.
Riv Neurol ; 57(4): 277-9, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3120293

RESUMO

A case of von Recklinghausen disease with unusual anatomoclinic and genetic aspects. The authors discuss the peculiar evolution of a neurosarcomatosis degeneration.


Assuntos
Neurofibromatose 1 , Neoplasias Cutâneas , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibromatose 1/complicações , Neurofibromatose 1/patologia , Neurofibromatose 1/fisiopatologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/fisiopatologia
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