RESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief of British Journal of Anaesthesia. The study is retracted for the following reasons: Statistical analysis suggests that the data may be fabricated. Y Saitoh provided a statement in a personal communication to a member of the editorial board of British Journal of Anaesthesia that the study was not approved by the Institutional Review Board and that no evidence exists to support the study findings. Additionally, the Japanese Society of Anesthesiologists has recommended retraction of this article: http://www.anesth.or.jp/english/pdf/news20170925.pdf.
RESUMO
When used as a photocatalyst under solar light, TiO2 tends to show a low photocatalytic activity. We report here that even TiO2 exhibits a high photocatalytic activity toward the decomposition (mineralization) of aqueous organic contaminants under simulated solar light when used under an Ar atmosphere (Ar flow). The photocatalytic decomposition rate of a cationic dye, crystal violet, and the CO2 evolution rate over TiO2 (P25, mainly composed of anatase and rutile) under Ar flow were substantially higher than those obtained in air and under air, O2, N2 and CO2 flows. Similar positive effects of Ar flow on photocatalytic reactions were observed when another cationic dye, basic violet 4, and TiO2 (anatase) were used, suggesting the versatility of Ar flow for improving photocatalytic activities.
RESUMO
Hallervorden-Spatz syndrome (HSS) (OMIM #234200) is a rare, autosomal recessive neurode-generative disorder with brain iron accumulation as a prominent finding. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals massive iron deposits in the basal ganglia. Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non-haem iron accumulates regionally and is highest in basal ganglia. Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease, Alzheimer's disease and Huntington disease. In order to gain insight into normal and abnormal brain iron transport, metabolism and function, our approach was to map the gene for HSS. A primary genome scan was performed using samples from a large, consanguineous family (HS1) (see Fig. 1). While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage. The HSS gene maps to an interval flanked by D20S906 and D20S116 on chromosome 20p12.3-p13. Linkage was confirmed in nine additional families of diverse ethnic backgrounds.
Assuntos
Cromossomos Humanos Par 20 , Neurodegeneração Associada a Pantotenato-Quinase/genética , Mapeamento Cromossômico , Consanguinidade , Feminino , Ligação Genética , Marcadores Genéticos , Homozigoto , Humanos , Masculino , LinhagemRESUMO
The purpose of this study was to assess the feasibility of polyester mesh culture for the in vitro production of bovine embryos, as polyester mesh is an alternative way for tracking individual embryos throughout culture using time-lapse cinematography (TLC). Bovine embryos were isolated during in vitro culture using sections of three different polyethylene terephthalate (PET) mesh products. In vitro matured and fertilized bovine oocytes were cultured in the 217 × 217, 230 × 230 or 238 × 238-µm openings of PET mesh sections or in simple micro-drops (control) for 7 days under either 20% or 5% O(2) tensions. No difference in embryo developmental rates was found between the culture groups in terms of cleavage, blastocyst formation and blastocyst expansion irrespective of O(2) tension. In contrast, under 20% O(2) tension, blastocysts that developed in PET mesh with 217 × 217-µm opening had significantly higher numbers of total and trophectoderm (TE) cells than control embryos; however, the numbers and proportions of inner cell mass (ICM) cells did not differ. Under 5% O(2) tension, no difference was found among the culture groups in the numbers of total, ICM and TE cells in embryos. All three PET mesh products investigated in this study were proven to be effective to prevent embryo movement. The results demonstrate that bovine embryos can be cultured in PET mesh sections without negative side-effects and suggest that embryo distance determined by the mesh affects embryo quality at atmospheric oxygen tension. Polyethylene terephthalate mesh with 217 × 217-µm openings was found to be the most suitable for further application in TLC.
Assuntos
Blastocisto/fisiologia , Bovinos/embriologia , Técnicas de Cultura Embrionária/veterinária , Oxigênio/química , Oxigênio/farmacologia , Animais , Meios de Cultura/química , Técnicas de Cultura Embrionária/instrumentação , Técnicas de Cultura Embrionária/métodos , Fertilização in vitro/veterináriaRESUMO
BACKGROUND AND STUDY AIMS: Saline as an injection solution for endoscopic resection techniques has several disadvantages such as a short-lasting effect leading to a potentially higher risk of bleeding and perforation. The new substance of photocrosslinkable chitosan hydrogel in a DMEM/F12 medium (PCH) can be converted into an insoluble hydrogel by ultraviolet irradiation for 30 s, and was evaluated in two sets of animal experiments. METHODS: 18 pigs were used in the two parts of the study. First, mucosal resections were done with either PCH or hypertonic saline; the effects of both agents on wound healing were examined endoscopically and histologically. Second, in vivo degradation of PCH was examined using six pig stomachs. RESULT: PCH injection led to a longer-lasting elevation with clearer margins, compared with hypertonic saline, thus enabling precise endoscopic submucosal dissection (ESD) along the margins of the elevated mucosa. The endoscopic appearance after ESD was similar in both groups. PCH biodegradation was completed within 8 weeks according to endoscopic and histologic analyses. CONCLUSION: PCH is a promising agent for submucosal injection prior to various techniques of endoresection. It should be evaluated in clinical trials after biocompatibility testing for PCH is completed.
Assuntos
Materiais Biocompatíveis , Quitosana , Hidrogéis/administração & dosagem , Mucosa Intestinal/cirurgia , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/farmacocinética , Quitosana/farmacocinética , Reagentes de Ligações Cruzadas , Dissecação , Endoscopia , Estudos de Viabilidade , Hidrogéis/farmacocinética , Injeções , Masculino , Modelos Animais , Cloreto de Sódio/administração & dosagem , Suínos , Resultado do TratamentoRESUMO
Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mutations of the dysferlin gene. Although several pairs of homozygous/heterozygous mutations have been reported, few effective treatments of MM are available. We had observed the decreased serum creatine kinase (CK) before and after administration of dantrolene in the elder brother and the increased serum CK before and after discontinuance of the drug on suspicion of drug-induced hepatopathy in the younger sister. We report a novel pair of heterozygous mutations in the 3'-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings, and effective treatment of their MM with dantrolene.
Assuntos
Dantroleno/uso terapêutico , Heterozigoto , Proteínas de Membrana/genética , Proteínas Musculares/genética , Distrofias Musculares/genética , Mutação , Irmãos , Adolescente , Povo Asiático/genética , Disferlina , Feminino , Humanos , Masculino , Doenças Musculares/diagnóstico , Doenças Musculares/tratamento farmacológico , Doenças Musculares/genética , Distrofias Musculares/diagnóstico , Distrofias Musculares/tratamento farmacológico , LinhagemRESUMO
PURPOSE: To review the surgical treatment for metastatic disease of the proximal femur. METHODS: Records of 8 patients who underwent endoprosthetic replacement with tumour resection (group 1) and 8 others who underwent intramedullary nailing without tumour resection (group 2) were reviewed. Treatments were based on the disease progression and patient's condition. RESULTS: In groups 1 and 2, the respective mean survival periods were 16 and 4 months. All patients in group 1 regained preoperative mobility, but only one patient in group 2 was able to walk with crutches. CONCLUSION: This was a retrospective, rather than comparative study of endoprothetic replacement and intramedullary nailing for metastatic disease of the proximal femur. Both procedures are considered palliative, and not curative. The longer survival period in group 1 was mainly due to selection of patients with better preoperative medical status.
Assuntos
Fraturas do Fêmur/cirurgia , Neoplasias Femorais/cirurgia , Fixação Intramedular de Fraturas/métodos , Adulto , Idoso , Pinos Ortopédicos , Feminino , Fraturas do Fêmur/patologia , Neoplasias Femorais/secundário , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In order to conduct non-contact estimation of arterial blood pH after massive haemorrhage, we calculated the arterial pH based on linear-regression analysis of exhaled gas concentrations (CO and CO2) and vital signs (heart rate, respiratory rate, and surface temperature) measured using non-contact methods in hypovolemic animals.
Assuntos
Acidose/diagnóstico , Testes Respiratórios/métodos , Dióxido de Carbono/análise , Monóxido de Carbono/análise , Hemorragia/diagnóstico , Hipovolemia/diagnóstico , Termografia/métodos , Acidose/etiologia , Acidose/fisiopatologia , Animais , Artérias/química , Análise Química do Sangue/métodos , Gasometria/métodos , Diagnóstico por Computador/métodos , Expiração , Estudos de Viabilidade , Hemorragia/complicações , Hemorragia/fisiopatologia , Hipovolemia/etiologia , Hipovolemia/fisiopatologia , Raios Infravermelhos , Masculino , Micro-Ondas , Troca Gasosa Pulmonar , Coelhos , RadarRESUMO
A novel mouse monoclonal anti-fucosylceramide antibody was established by using neutral glycolipids from a human pancreas cancer tissue as the immunogen. Mice were immunized with the neutral glycolipids in the form of liposome-containing lipid A. Mouse monoclonal antibodies were screened with enzyme-linked immunosorbent assay and by thin layer chromatography-immunostaining. The latter technique showed that a mouse monoclonal antibody, designated PC47H, specifically reacts with a ceramide-monoglycoside fraction of the neutral glycolipids. The effects of various monosaccharides on the reactivity of PC47H with the neutral glycolipids were tested, and it was found that only fucose was able to inhibit the binding of PC47H to the neutral glycolipids. We also examined the direct binding activity of PC47H against galactosylceramide, glucosylceramide, fucosylceramide, and ceramide. This showed that the antigen specificity of PC47H was exclusively directed against fucosylceramide. In thin layer chromatography-immunostaining experiments with neutral glycolipids prepared from various human tissues, we observed that fucosylceramide was highly expressed in human colon and gastric cancer tissues. PC47H recognized the human adenocarcinoma cell lines of colon, stomach, pancreas, and lung but did not react with other tumor cells or with several nontumorous human cells.
Assuntos
Anticorpos Monoclonais/imunologia , Cerebrosídeos/imunologia , Glicolipídeos/imunologia , Neoplasias Pancreáticas/imunologia , Animais , Anticorpos Monoclonais/isolamento & purificação , Complexo Antígeno-Anticorpo , Carboidratos , Linhagem Celular , Cerebrosídeos/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Feminino , Glicolipídeos/isolamento & purificação , Humanos , Camundongos , Camundongos Endogâmicos BALB C/imunologia , Neoplasias/química , Neoplasias/imunologia , Neoplasias Pancreáticas/químicaRESUMO
The antigens present in a gastric tumor obtained from a patient of blood group p,O,Le(a-,b+) were studied. The neutral glycolipids were isolated from the cancer tissues and characterized chemically and immunologically. The glycolipid pattern of the tumor was similar to that of the surrounding uninvolved mucosae. The major neutral glycolipids were found to be glucosylceramide, galactosylceramide, lactosylceramide, and the lacto series glycolipids, including the H, Lea, and Leb active fucolipids. The cancer tissues and the uninvolved mucosae did not contain galabiosylceramide, globotriaosylceramide, or globotetraosylceramide after separations by both thin layer chromatography and gas-liquid chromatography. Thin layer chromatography immunostaining was performed to detect incompatible blood group antigens. Immunostaining revealed the presence of globotriaosylceramide, globotetraosylceramide, Forssman glycolipid, and A active glycolipids in the cancer tissues. These incompatible blood group active glycolipids were absent from the uninvolved mucosae. The results indicate that the cancer tissues possess the ability to produce the globo series of glycolipids and the A active antigens but that the surrounding uninvolved mucosae could not synthesize these glycolipids.
Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Glicolipídeos/isolamento & purificação , Neoplasias Gástricas/análise , Idoso , Incompatibilidade de Grupos Sanguíneos , Sequência de Carboidratos , Cromatografia em Camada Fina , Feminino , Glicolipídeos/imunologia , Humanos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgiaRESUMO
The Ca2+ dependent incorporation of [14C]ethanolamine, L-[14C]serine and [14C]choline into phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine, respectively, were investigated in membrane preparations from rat heart. The ethanolamine and serine base-exchange enzyme-catalyzed reactions were associated with the sarcolemma and sarcoplasmic reticulum. There was a 17.2-fold and 6.8-fold enrichment, respectively, of the serine and the ethanolamine base-exchange enzyme activities in the sarcolemma compared to the starting whole homogenate. The sarcoplasmic reticulum was enriched in the ethanolamine and serine base-exchange enzyme activities. The choline base-exchange enzyme activity of all membranes fractions was negligible compared to the ethanolamine or serine base-exchange enzyme activities. The apparent Km for the ethanolamine and serine base-exchange enzyme in sarcolemma was 14 microM and 25 microM, respectively. The pH optimum for these base-exchange activities was 7.5-8.0. There was a dependence upon Ca2+ for these reactions with a 1 or 4 mM concentration required for maximal activity. The properties of the sarcoplasmic reticulum base-exchange enzymes were similar to the sarcolemmal base-exchange enzymes.
Assuntos
Miocárdio/enzimologia , Transferases de Grupos Nitrogenados , Sarcolema/enzimologia , Retículo Sarcoplasmático/enzimologia , Transferases/metabolismo , Animais , Cálcio/farmacologia , Colina/metabolismo , Etanolamina , Etanolaminas/metabolismo , Cinética , Fosfolipídeos/metabolismo , Ratos , Ratos Endogâmicos , Serina/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Distribuição TecidualRESUMO
Plasma membranes were isolated from lactating bovine mammary gland. Two crude membrane fractions; medium/d 1.033 (light membrane) and 1.033/1.053 interfaces (heavy membrane), were obtained by Ficoll density gradient centrifugation of osmotically washed microsomal fraction. Two crude membranes were further purified separately by sucrose density gradient centrifugation. Both light and heavy membranes banded at a sucrose density of 1.14. The purified membranes appeared as heterogeneous smooth membrane vesicles on electron microscopy. The contaminating suborganelles were not detected. The yield of the purified membranes relative to the homogenate was 1.2%. The degree of purity of the membranes was shown by a great increase in the specific activity of 5'-nucleotidase over the homogenate of 20-fold for light membrane and of 16-fold for heavy membrane. The relative activities of Mg2+-ATPase, (Na+ + K+)-ATPase, gamma-glutamyl transpeptidase, phosphodiesterase I, alkaline phosphatase and xanthine oxidase were also high (12-18-times) and nearly 20% of these enzymes was recovered. The activity of marker enzyme for mitochondria, endoplasmic reticulum and Golgi apparatus was very low, while that of acid phosphatase for lysosome was relatively high (5-times). DNA and RNA contents were very low. The major polypeptides rich in other suborganelles were not detected profoundly in the membrane fraction and the polypeptide composition in both light and heavy membranes were similar upon SDS-polyacrylamide gel electorphoresis.
Assuntos
Membrana Celular/ultraestrutura , Lactação , Glândulas Mamárias Animais/ultraestrutura , Animais , Bovinos , Fracionamento Celular/métodos , Centrifugação com Gradiente de Concentração/métodos , Eletroforese em Gel de Poliacrilamida , Feminino , Glândulas Mamárias Animais/fisiologia , Proteínas de Membrana/isolamento & purificação , Microscopia Eletrônica , Peso Molecular , GravidezRESUMO
Glycolipids were isolated from human gastric cancer tissues and normal mucosae. Sulfogalactosylceramide, ganglioside and neutral glycolipid fractions were separated by DEAE-Sephadex and silica gel column chromatography. Sulfogalactosylceramide contents were higher in the cancer tissues than in the normal mucosae. Ganglioside contents showed considerable variations but in the cancer tissues in mole percentage of ganglioside GM3 was higher than in the normal mucosae. The cancer tissues contained more neutral glycolipids than normal tissues. Glycolipids of lacto-series, including fucolipids, were markedly increased in the cancer tissues. Blood group A-active glycolipids were found in the cancer tissues from two patients with blood group O but not found in the uninvolved tissue associated with the cancer tissue.
Assuntos
Sistema ABO de Grupos Sanguíneos , Glicolipídeos/isolamento & purificação , Neoplasias Gástricas/análise , Cromatografia em Camada Fina , Mucosa Gástrica/análise , Glicoesfingolipídeos/análise , Humanos , Imunodifusão , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Glycolipid isolated from normal and cancerous human pancreatic tissues were characterized chemically and immunologically. The major neutral glycolipids in both normal and cancerous tissues were composed of globo-series glycolipids and lacto-series glycolipids. The mole percentage of fucolipids in the total neutral glycolipids of normal tissues was 20-40%, and in general the fucolipids corresponded to blood group glycolipids related to the patient's blood group, however, in cancerous tissues the amount of these fucolipids was decreased. Immunostaining revealed that normal tissues contained only lacto-series (type 1 chain) glycolipids. In contrast, cancerous tissues contained the neolacto-series (type 2 chain) glycolipids as well as the lacto-series glycolipids. Incompatible blood group antigens, A active glycolipids in a blood type O patient and B active glycolipids in a blood type A patient, were also detectable in the neutral glycolipid fractions of the pancreatic cancer tissues.
Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Glicolipídeos/metabolismo , Neoplasias Pancreáticas/metabolismo , Pancreatina/metabolismo , Adenocarcinoma , Adulto , Idoso , Sequência de Carboidratos , Cromatografia em Camada Fina , Feminino , Glicolipídeos/química , Glicolipídeos/imunologia , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
The effects of formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) on the positional distribution of fatty acids in phosphatidylinositol (PI), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were investigated with rabbit neutrophils. The proportion of arachidonate at the C-2 position of PI was 35.0% in resting neutrophils and declined to 30.8% after 5 min stimulation with the peptide at a concentration of 10(-7) M. In contrast, the profiles of the positional distribution of fatty acids in PC and PE were not affected upon stimulation with fMet-Leu-Phe. The phospholipid composition of rabbit neutrophils was examined at different time intervals following the addition of fMet-Leu-Phe. PI and PC, but no other phospholipids, exhibited significant changes in their quantities. The quantity of PC decreased at 5 min with a concurrent increase in that of lysophosphatidylcholine (lysoPC), suggesting a phospholipase A2 action on PC. The quantity of PI, on the other hand, decreased at 1 min with an accompanying increase in phosphatidic acid when the profile of the positional distribution of fatty acids in PI remained unchanged. No lysophosphatidylinositol (lysoPI) was detected. This indicates the enhancement of the PI cycle in the fMet-Leu-Phe-stimulated neutrophils. The augmented PI cycle in response to fMet-Leu-Phe was further supported by the finding that [3H]arachidonyl-diacylglycerol and -phosphatidic acid accumulated at the expense of [3H]arachidonylPI in rabbit neutrophils prelabelled with [3H]arachidonate. Restoration of the content of PI to the higher than the original level at 5 min after stimulation with fMet-Leu-Phe, however, leads to the suggestion that de novo synthesis of PI as well as PI resynthesis along the closed cycle of PI has occurred at 5 min and that this newly synthesized PI, via a de novo pathway with a different pattern of the positional fatty acyl composition, is the cause of the decreased proportion of arachidonate.
Assuntos
Ácidos Graxos/isolamento & purificação , Metionina/análogos & derivados , N-Formilmetionina/análogos & derivados , Neutrófilos/metabolismo , Oligopeptídeos/farmacologia , Fosfatidilinositóis/sangue , Animais , Fenômenos Químicos , Química , Ácidos Graxos/sangue , Técnicas In Vitro , N-Formilmetionina/farmacologia , N-Formilmetionina Leucil-Fenilalanina , CoelhosRESUMO
A cDNA clone encoding ribonuclease inhibitor was isolated from a rat lung cDNA library. The deduced amino acid sequence revealed a high degree of conservation of a repeated structure. The mRNA was detected in all seven tissues of rat examined, the amount being highest in the lung and lowest in the heart.
Assuntos
DNA/genética , RNA Mensageiro/metabolismo , Ribonucleases/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Western Blotting , Clonagem Molecular , Dados de Sequência Molecular , Ratos , Ribonucleases/genética , Homologia de Sequência do Ácido Nucleico , Distribuição TecidualRESUMO
BACKGROUND: Expression of the VLDL receptor, primarily in macrophages, has been confirmed in human and rabbit atherosclerotic lesions. The high binding affinity of the VLDL receptor for remnant particles implicates the VLDL receptor pathway in the foam cell formation mechanism in macrophages. This study investigates the effect of interferon (IFN)-gamma on VLDL receptor expression in phorbol-12-myristate-13-acetate (PMA)-treated THP-1, HL-60 macrophages, and human monocyte-derived macrophages. METHODS AND RESULTS: THP-1 cells were induced to differentiate into macrophages by PMA treatment. IFN-gamma was added to the medium, and expression of the VLDL receptor was determined. (125)I-beta-VLDL degradation study and oil red O staining were examined. In THP-1 macrophages, VLDL receptor protein expression decreased at 2 days after PMA treatment but increased at 3 days and increased up to 5 days. Scavenger receptor proteins, which were not originally present, appeared at 3 days after PMA treatment. IFN-gamma inhibited VLDL receptor expression in a dose-and time-dependent manner in macrophages. However, no inhibitory effect was observed in monocytes. Moreover, IFN-gamma receptor mRNA increased during differentiation to macrophages. (125)I-beta-VLDL degradation study and oil red O staining showed that IFN-gamma significantly inhibited foam cell formation after the uptake of beta-VLDL. LDL receptor-related protein (LRP) and LDL receptor mRNAs were not expressed in macrophages. In PMA-treated HL-60 macrophages and human monocyte-derived macrophages, IFN-gamma also inhibited VLDL receptor expression and foam cell formation by beta-VLDL. CONCLUSIONS: VLDL receptor expression is upregulated during monocyte-macrophage differentiation. IFN-gamma inhibits VLDL receptor expression and foam cell formation only in macrophages. Remnant particles induce macrophage foam cell formation through the VLDL receptor pathway.
Assuntos
Células Espumosas , Interferon gama/farmacologia , Macrófagos/efeitos dos fármacos , Receptores de LDL/fisiologia , Diferenciação Celular/fisiologia , Células Espumosas/fisiologia , Expressão Gênica/efeitos dos fármacos , Células HL-60 , Complexo Antigênico da Nefrite de Heymann , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Glicoproteínas de Membrana/biossíntese , Monócitos/citologia , Receptores de LDL/biossíntese , Células Tumorais CultivadasRESUMO
Angiolipoma of the spine is a rare tumour and no studies have investigated a sufficient number of cases to reach general conclusions. Therefore, as yet, the pathological definition of this entity is not well established. The case of epidural angiolipoma reported here and a review of the literature revealed that this entity is distinct from cutaneous angiolipoma in that the calibre of its predominant vascular component is far greater than that of the fat cells. Therefore, epidural angiolipoma can be regarded as not only topographically, but also histologically, distinct from its subcutaneous counterpart.
Assuntos
Angiolipoma/patologia , Neoplasias Epidurais/patologia , Idoso , Angiolipoma/irrigação sanguínea , Neoplasias Epidurais/irrigação sanguínea , Feminino , Humanos , Neovascularização Patológica/patologia , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/patologiaRESUMO
Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester (CE) from HDL to apolipoprotein (apo) B-containing lipoproteins and plays a crucial role in reverse cholesterol transport, which is a major protective system against atherosclerosis. Genetic CETP deficiency is the most common cause of a marked hyperalphalipoproteinemia (HALP) in the Japanese, and various mutations have been identified in the coding region as well as in the exon/intron boundaries in the CETP gene. In the present study, we identified a novel mutation in the promoter region of the CETP gene. This mutation was a G-to-A substitution at the -69 nucleotide of the promoter region (-69 G-->A), corresponding to the second nucleotide of the PEA3/ETS binding site (CGGAA) located upstream of the putative TATA box. Four (2.0%) of 196 unrelated subjects with a marked HALP (HDL cholesterol >/=2.59 mmol/L=100 mg/dL) were revealed to be heterozygous for the -69 G-->A mutation, and the allelic frequency of the mutant was 0.0102 in the subjects with a marked HALP. The subjects with the -69 G-->A mutation had low plasma CETP levels. Reporter gene assay showed that this mutation markedly reduced the transcriptional activities in HepG2 cells (8% of wild type). These results suggested that this mutation would be dominant negative. In conclusion, a novel -69 G-->A mutation in the CETP gene causes the decreased transcriptional activity leading to HALP.